Log in using OpenID

Join local schools in supporting your Boys & Girls Club!

2010 Annual Meeting
American College of Allergy, Asthma & Immunology
November 11-16, 2010
Section 1 contains all abstracts accepted for presentation
at Concurrent Sessions, Sunday and Monday,
November 14-15, 2010
page A1
Section 2 contains all abstracts accepted for presentation
at Poster Sessions, Saturday and Sunday,
November 13-14, 2010
page A23
Disclosure of Significant Relationships with Relevant Commercial
page A129
Index of Oral and Poster Abstract Authors:
page A135
NOVEMBER 14-15, 2010
PHOENIX convention center
Adverse Food and Drug Reactions, Insect
Reactions, Anaphylaxis
Asthma and Other Lower Airway Disorders
Aerobiology, Allergens/Allergen Extracts,
Pharmacology and Pharmacotherapeutics
Clinical Immunology/Immunodeficiency,
and Other
Rhinitis, Other Upper Airway and
Ocular Disorders
Aerobiology and Food Allergy
Allergy Testing and Immunotherapy
Skin Disorders
R. Borici-Mazi*1, C.G. Wong2, 1. Kingston, ON, Canada; 2. Toronto, ON,
S.L. Grossman, V.P. Hernandez-Trujillo*, B.M. Garcia Pena, M.Y. Linares,
B. Greenberg, Miami, FL.
Rationale: Cold urticaria is a physical urticaria defined by wheal-and-flare
type skin reactions and/or angioedema that occur within minutes of exposure
to cold air, liquids or objects. Manifestations are typically limited to the exposed
skin areas, but extensive cold exposure, such as that which may occur while
swimming, can lead to generalized urticaria and anaphylaxis with respiratory,
gastrointestinal and/or cardiovascular involvement. We report a case of coldinduced anaphylaxis in an elderly woman 12 days after a hymenoptera sting.
Methods: Case report. Results: A previously healthy 68-year-old woman suffered a large local reaction to a hymenoptera sting and 12 days later, developed pruritis of her palms and soles as well as urticaria on her extremities after
swimming for a few minutes in her outdoor pool. Prior to her sting, the patient
had no difficulties while swimming outdoors and her symptoms occurred on
the first swim she took after being stung. When the patient tried swimming
again after her initial reaction, she developed immediate-onset pruritis, then
exited the water and found that she had already developed generalized urticaria,
which was quickly followed by presyncope, vomiting and diarrhea. The patient
treated herself with Benadryl 50mg orally and her symptoms resolved two hours
later. A 5-minute ice cube provocation test was positive. Intradermal skin tests
to five hymenoptera species were positive as well. Other causes of acquired
adult onset cold-induced urticaria were ruled out. She was advised on avoidance of cold stimuli such as air, liquids and swimming. She was asked to follow up in one year and the results will be available for the presentation. Conclusions: Hymenoptera stings can rarely be associated with the development
of cold urticaria / anaphylaxis. Previous reports suggested that cold urticaria
usually develops within 24-48 hours of the initial sting, but our case demonstrates that it may develop more than a week later.
R.L. Campbell*1, S.C. Vukov1, A.R. Kanthala2, W.W. Decker1, J.B. Hagan1,
J.T. Li1, M.F. Bellolio1, V.D. Smith1, 1. Rochester, MN; 2. Gainesville, FL.
Background: Anaphylaxis is a potentially life threatening allergic reaction
commonly managed in the emergency department (ED). The study objective
was to compare the ED presentation and management of anaphylaxis in patients
≥50 years with patients <50 years of age. Methods: A consecutive cohort study
of patients presenting to an academic ED with approximately 80,000 visits per
year was conducted. Patients who met National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network diagnostic criteria for
anaphylaxis from April 2008 to June 2010 were included. IRB approval was
obtained and research authorization was granted by all research subjects. Statistical analysis was performed using JMP 8 software. Results were summarized in odds ratio (OR) with 95% confidence intervals (CI), and p-values represent Chi-square values unless otherwise noted. Results: The study included
211 patients, 123 (58.3%) were female. The median age was 33.5 years
(interquartile range 18.9-49.4). Fifty-one patients (24.2%) were >50 years of
age. The inciting allergen was most commonly unknown (25.5%) for older
patients. Food was the most common cause of anaphylaxis for younger patients
(41.9%) but was much less frequently the cause patients >50 years (13.7%),
OR=0.22, 95% CI 0.09-0.52, p=0.0002. The most common identifiable cause
of anaphylaxis for patients >50 years was medication use in 23.5%. Patients
>50 years were less likely to have a history of asthma (11.8% vs 28.8%,
OR=0.33, 95% CI 0.13-0.83, p=0.014). There were no statistically significant
differences in presenting signs or symptoms across age groups, but older patients
were more likely to have hypotension (15.7% vs 6.9%, p=0.088, two-tail Fisher’s
test). ED management was similar except patients >50 years were less likely
to be dismissed directly home (33.3% vs 55.0%, OR=0.41, 95%CI 0.21-0.79
p=0.007) and less likely to be prescribed self-injectable epinephrine upon their
final dismissal (39.2% vs 65.0%, OR=0.35, 95%CI 0.18-0.66, p=0.001). Referrals to an allergist or subsequent allergist evaluation did not differ significantly.
Conclusions: In ED patients presenting with anaphylaxis, age over 50 is associated with a decreased likelihood of food-induced anaphylaxis, decreased dismissal to home directly from the ED, and fewer prescriptions for self-injectable
OBJECTIVE: To assess how well pediatric emergency medicine (PEM)
physicians are able to recognize and treat anaphylaxis, and to identify predictors of their anaphylaxis knowledge. METHODS: A 21-question survey was
distributed to all U.S. board certified PEM physicians with obtainable email
addresses. Questions included demographics, symptomatology, physicians’
practice preferences in managing anaphylaxis patients, and case vignettes.
RESULTS: 620 (55%) PEM physicians responded to the survey. 580 of the
620 respondents (93.5%) knew that epinephrine is the treatment of choice for
anaphylaxis. Between 601to 608/620 (96% to 98%) knew the obvious symptoms of wheezing, shortness of breath, and hives, and up to 605/620 (97.6%)
correctly recognized and treated the 2 obvious case vignettes of anaphylaxis.
305/620 (49.2%) administered epinephrine to the patient whose presentation of
anaphylaxis was more subtle, and 141/620 (22.7%) gave an intravenous fluid
bolus instead of epinephrine to an anaphylaxis patient who lost consciousness
and was hypotensive.The PEM physicians working at �community hospitals/nonresidency training programs’, those seeing < 5 anaphylaxis patients per year,
and those in practice < 5 years were more likely to administer a medication other
than epinephrine to some of the vignette patients with anaphylaxis. CONCLUSIONS: Obvious cases of anaphylaxis will usually be promptly recognized
and treated by PEM physicians, but the more subtle presentations may be missed.
Optimal patient care in anaphylaxis patients may also be compromised when
the primary presenting symptom is hypotension, in the community hospital/nonresidency training program setting, and with PEM physicians having less experience in treating anaphylaxis.
A.R. Kanthala*, J.B. Hagan, J.T. Li, W.W. Decker, R.L. Campbell, Rochester,
Objective:Anaphylaxis is a potentially life threatening allergic reaction.Anaphylaxis guidelines proposed by the National Institute of Allergy and Infectious
Disease (NIAID) & FoodAllergy andAnaphylaxis Network (FAAN) recommend
that all patients who experience anaphylaxis from an allergen encountered in a
non-medical setting carry self injectable epinephrine and follow up with an allergist. Very little data is available on outcomes of allergy follow up after an emergency department (ED) visit for anaphylaxis. The aim of our study was to determine the outcomes of allergy follow up after an ED visit specifically with regard
to inciting allergen identification. Methods:A retrospective cohort study was conducted in an academic ED setting. Patients presenting to the ED for anaphylaxis
and allergic reactions were screened fromApril 2008 to March 2010 and all patients
who fulfilled NIAID/FAAN criteria for anaphylaxis with research consent were
included. A standardized data abstraction form was used to collect information
on inciting allergen, ED diagnosis, disposition, allergy referrals, and post-ED
allergy follow up and testing. Results: 231 patients constituted the study sample
and were included in the study. The median age was 33(IQR;19-49) years.
136(58.8%) were females and 54 (23.3%) were aged less than 18 years. A total
of 100 patients (43.2 %) followed up with an allergist, of which 76(76%) had
allergy testing. After testing, 55 (72.3%) had an allergen identified. Of the 76
patients who underwent allergy testing, 65 (85.5%) had a specific allergen suspected in the ED and 11(14.4%) had an unknown allergen in the ED. Among the
65 patients with a specific suspected allergen, 49(75.3%) had an allergen identified after testing and 16 (24.6 %) had inconclusive test results. Among the 49
patients with a suspected and confirmed allergen, 38(77.5%) had an identified
allergen which corresponded with the allergen suspected in the ED and 11 (22.4%)
had a different allergen identified. Among the 11 with an unknown allergen in
the ED, 6(54.5%) had an allergen identified after testing. Conclusion: Considerable number of patients had a different allergen identified from the suspected allergen in the ED and most of those with an unknown allergen had an allergen identified.These results suggest that allergy follow-up after an ED visit for anaphylaxis
is useful supporting current anaphylaxis guidelines.
T.M. Nsouli*1, S.T. Nsouli2, C.D. Schluckebier1, E. McSorley-Gerard1,
M. Fakhriyazdi1, 1. Burke, VA; 2. Washington D.C., DC.
R. Steele*, M. Camacho-Halili, B. Rosenthal, L. Fonacier, Mineola, NY.
Background: Patients with NSAID (nonsteroidal anti-inflammatory drug)
intolerance have limited effective alternative pharmacological agents to treat
inflammatory diseases. The safety of meloxicam (MLXC), an anti-inflammatory agent in patients with known NSAID- induced cutaneous hypersensitivity reactions, has not been definitely established and is still open to debate.
MLXC is used in the treatment of arthritis, and is a partial COX-2 inhibitor
with inhibition of COX-1 at a high dose (Prieto et al. J Allergy Clin Immunol
2007;119:960). Objective: We evaluated the tolerability of MLXC in patients
with known NSAID-induced cutaneous hypersensitivity reactions. Method: We
described three patients with cutaneous reactions to naproxen and ibuprofen,
characterized by generalized pruritus and urticaria following ingestion of these
drugs. The first case was a 61-year-old white male with history of osteoarthritis who, 20 minutes after ingestion of 375 mg of naproxen, developed generalized pruritus and urticaria. The second and third cases consisted of a 53 y/o
white female and 38 y/o white female respectively, with a history of osteoarthritis who, 30 minutes after ingestion of 400 mg of ibuprofen, developed pruritus and urticaria. These cutaneous adverse events occurred on at least 3 different occasions in all 3 patients. An oral challenge with 7.5 mg of MLXC was
well tolerated without adverse sequelae by all 3 patients. Discussion: These 3
case reports exemplify NSAID-induced cutaneous hypersensitivity reactions,
and suggest that MLXC could be a safe alternative anti-inflammatory agent.
MLXC is an interesting drug because it preferentially inhibits COX-2 at lower
concentrations (Quaratino D. et al. Ann Allergy Asthma Immunol 2000;84:613),
but its molecular structure allows it to enter the COX-1 enzyme channel at high
concentrations. Results: The 3 study patients with a history of NSAID-induced
cutaneous hypersensitivity reaction were able to well tolerate MLXC at a low
dose (7.5 mg/day) without adverse events. Conclusion: Although these findings suggest that oral low-dose MLXC could be a possible safe alternative in
patients with NSAID-induced cutaneous reactions, it would be prudent to first
conduct a careful challenge in a well-equipped medical setting where clinical
acceptability and tolerability could be safely assessed.
BACKGROUND: Although the identification and management of anaphylaxis in an emergency room (ER) setting has been well studied, our understanding of the independent risk factors for admission in a community-based
hospital is lacking. METHODS: We performed a 5 year retrospective chart
review of all patients seen in the Emergency Department of a community-based
institution, with an ICD-9 code related to anaphylaxis [995.0, 995.6, 989.5].
Only those that met clinical criteria for anaphylaxis as described by The Second Symposium on the definition and management of anaphylaxis (Sampson
et al, J Allergy Clin Immunol 2006) were included into the study. Data collected included involved organ systems, suspected allergen (insect sting vs nonsting allergens such as food and medication) and a history of a previous ER
visit for anaphylaxis. RESULTS: Of the 483 charts with the above ICD-9 codes,
58 visits met inclusion criteria for this study. 55% of patients were adults
(>21yrs), with a median age of 27 years; 53% were male. 34% of the visits
resulted in hospital admission (95% CI: 22% - 48%). Univariate predictors for
admission included (1) the involvement of 2, 3, and 4 organ systems (26%,
55% and 75%, respectively; p<0.02), (2) gastrointestinal involvement vs. no
involvement (59% vs. 24%, p < 0.02), (3) non-sting vs. insect sting allergen
(50% vs. 12.5%, p < 0.005), and (4) a prior history of an ER visit for anaphylaxis (67% vs. 30%, p < 0.05). Multivariate analysis (logistic regression) confirmed non-sting allergens (p < 0.02) and number of organ systems involved
(p < 0.05) as independent predictors of hospitalization. DISCUSSION: In our
study population, the involvement of multiple organ systems, particularly GI
involvement, was more predictive of hospital admission than age, airway compromise, hypotension, and asthma history. A history of prior ER visits for anaphylaxis, and the presence of inciting allergens other than stings demonstrated
higher admission rates. These findings may be explained by a higher incidence of ingested allergens, such as food and medications, causing anaphylaxis
and resulting in increased organ system involvement, including gastrointestinal involvement. These results parallel previous studies, which showed higher
hospitalization rates for food-induced anaphylaxis when compared to insect
sting induced anaphylaxis.
W. Spiegel*, R. Anolik, Blue Bell, PA.
N.U. Swamy*, G. Gross, Dallas, TX.
Introduction: The novel H1N1 epidemic of 2009 brought many challenges
to the allergist, not the least of which, was the administration of an egg vaccine that might contain egg proteins in an egg allergic population. Asthmatics
are at increased risk of complications from influenza including the H1N1 form.
All asthmatics in our practice were actively encouraged to receive the H1N1
vaccine irregardless of food allergy status. The retrospective study relates our
experiences in administrating the vaccine in our egg allergic population. Decription: Our 12 physician single specialty allergy practice has approximately 20,000
active patients. Egg allergic patients were identified and encouraged to receive
the vaccine. At that visit the patient was skin tested using the multitest method
to full strength H1N1 Vaccine, egg (1:20 w/v Greer) and appropriate positive
and negative controls. The skin test was interpreted by the physician to determine a relative risk of administration of the flu vaccine in that egg allergic individual. If the skin test for the H1N1 vaccine approached the size of the egg skin
test, then a desensitization protocol was instituted. This protocol delivered a
full 0.5cc dose of the vaccine in 6 graded steps beginning with 0.05cc of 1:100
dilution. Data: 152 patients ages 1 to 56 were evaluated by this procedure. Egg
testing averaged an 11mm wheal(0-35), and a mean flare of 18mm(3-55). Skin
testing to the H1N1 vaccine demonstrated a mean wheal of 3mm(0-7) and a
mean flare of 7mm(1-27). Physician evaluation of these tests suggested two
patients undergo the desensitization procedure which they did without difficulty. Skin testing in these patients showed equal sensitivity to the vaccine and
egg. Patient “A” had 4mm/9mm to H1N1 and 6mm/8mm to egg. Patient “B”
had 5mm/27mm to H1N1 and 5mm/18mm to egg. 150 patients were given the
H1N1 vaccine in a single dose after testing and observed for a least 20 minutes in our office. There were no allergic reactions in these patients. Conclusion: Our data suggests that with appropriate testing and desensitization, all
egg allergic individuals can safely be given the novel H1N1 Vaccine and therefore can be protected from the influenza itself and the complications arising
from this infection. Egg allergic asthmatics need not avoid this immunization.
Rationale: OTC topical triple antibiotics are a popular preparation used
extensively for wound care at home and in clinical settings. A common reaction is contact dermatitis, however, a growing number of anaphylactic reactions
are being reported. Many physicians are unaware of the potential to cause allergic reactions and continue to use and recommend the drug for its low cost and
presumed high safety profile. Methods: The purpose of this article is to increase
awareness of anaphylaxis as a possible consequence of topical triple antibiotics.
We also report three cases of anaphylaxis secondary to topical triple antibiotic
use. The three patients were seen in an emergency room but the diagnosis was
not made at that time. Upon reviewing the literature, we questioned whether
physicians were conscious of this possible side effect. As a result, we designed
a survey for physicians across different specialties to assess awareness & perception of potential anaphylaxis due to topical antibiotic use. Results: We present three cases of anaphylaxis after topical triple antibiotic use. The aforementioned survey was distributed to physicians of different specialties.
Preliminary results revealed 25% of physicians were cognizant that any adverse
reactions to topical antibiotics existed. Only 16% of physicians were aware that
anaphylaxis is a possible adverse reaction. Conclusion: Anaphylaxis secondary to topical antibiotic ointment is an adverse event of which we present three
cases. Based on the survey, there is a lack of awareness among physicians on
topical triple antibiotic-related anaphylaxis. This study provides allergists with
the opportunity to educate their colleagues in other fields on this systemic
adverse reaction.
S.D. Anderson*1, C.P. Perry1, H. Fox2, B. Charlton2, 1. Camperdown, NSW,
Australia; 2. Sydney, NSW, Australia.
BACKGROUND: Mannitol dry powder for inhalation (ARIDOLв„ў/OSMOHALEв„ў) is approved in 18 countries as a bronchial provocation test to assess bronchial hyperresponsiveness. It is available as a standardized kit with different doses of mannitol prepacked in capsules to enable
convenient and easy administration. As with all bronchial provocation tests
there is the potential for large falls (≥30%) in FEV1 to occur following challenge. AIM: To report the time taken to perform a positive bronchial provocation test with mannitol and to show maximum FEV1 fall in the same patients.
METHODS: The mannitol is delivered using a dry powder inhaler. The FEV1
is measured 60 seconds after each dose of mannitol (0, 5, 10, 20, 40, 80, 160,
160, 160 mg). The doses of 80 and 160 are given as two 40 mg and four 40 mg
capsules. The subject is asked to exhale before taking a controlled deep inspiration from the device and to hold their breath for 5 seconds. A positive test is
a 15% fall in FEV1 from 0 mg capsule or a 10% fall in FEV1 between consecutive doses. The time to perform the test, and the fall in FEV1 after a positive mannitol test were analyzed from two IRB approved Phase III multi centre studies in subjects with asthma and suspected asthma who gave written
consent to testing. RESULTS: The results are summarised in the Table below.
There were few large falls in FEV1 in the two studies. In study A301 the comparator was hypertonic saline 4.5%. The mean maximum fall in FEV1 was 21%
for both mannitol and saline with falls of ≥30% occurring in 4.9% & 2.0% of
subjects respectively. No subjects had falls ≥50%. Time to perform positive
challenge was similar for mannitol and saline at 17.3 min В± (7.1) & 15.0 min
± (9.1) respectively. In study A305 falls of ≥30% and ≥50% occurred in 0.7%
& 0% after mannitol, 6.2% & 0.7% of subjects after exercise, & 12.1% & 1.4%
after methacholine. In the same study the time to perform a positive mannitol
test was significantly shorter than a positive methacholine test by approximately
25 min (19.9 min В± 8.2 vs 44.5 min В± 14.7 respectively). CONCLUSION: The
standardized kit enables efficient administration while the dose response protocol and 15% positive cut off point mean that falls in FEV1 ≥ 30% after mannitol testing are uncommon and less frequent than with exercise or methacholine
testing in the same subjects.
Results: Time to perform positive challenge and maximum FEV1 fall
L.R. Forbes*, C. Koziol-White, M. Fehrenbach, B. Ducka, A. Haczku,
Philadelphia, PA.
CD11c/MHC-II/CD86 positive bronchoalveolar lavage (BAL) dendritic cells
from mice sensitized and challenged with the allergen Aspergillus fumigatus
(Af). By FACS analysis 100% of RAW264.7 cells and >85% of mature dendritic cells from the culture were SIRP-О± positive. Dendritic cells from the BAL
showed a time dependent SIRP-О± expression after Af challenge of sensitized
mice peaking at 24 hours. These results indicate that allergen challenge elicits
a rapid influx of mature myeloid dendritic cells into the airways of mice and
that mature, but not immature, dendritic cells maybe susceptible for an inhibitory
effect by SP-D because of high levels of SIRPО± expression. To study this further we analyzed the (CD11c+/CD11b+) BAL dendritic cells of wild-type (WT)
and SP-D-/- C57BL/6 mice, by FACS for the presence of SP-D on the cell surface, expression of SIRP-О± and maturation/activation markers. SP-D was present on the WT and absent on the SP-D-/- dendritic cell surface. Furthermore,
there was an increase in TNF-О±, MHC-II and CD86 as well as CD91 expression in the SP-D-/-, as compared to the WT BAL cells. Both populations showed
equal SIRP-α expression indicating that SIRP-α ligation by SP-D, may be necessary for suppressing the inflammatory phenotype. Whereas, in it’s absence,
there is a skewing towards a pro-inflammatory state. These results suggest that
co-expression of SP-D and SIRP-О± is associated with immunoprotection in
myeloid dendritic cells in the lung. Thus, presence of SP-D is important to
prevent constitutive innate immune cell activation and to protect from development of chronic inflammatory changes in the lung.
S. Kapoor*1, S. Patel2, M. Dave2, D. Axelrod2, E. Capitle2, P. Rameshwar2,
1. Bloomfield, NJ; 2. Newark, NJ.
Mesenchymal Stem Cells(MSCs) show bimodal immune responses: suppressor and enhancer functions; are safe for human application; can be delivered across allogeneic barriers; are easy to expand and have minimum ethical
concerns. MSCs also show clinical benefit for tissue regeneration and as antiinflammatory cell therapy. With this knowledge, we studied the effects of MSCs
on dustmite allergic asthma(AA), a disease entity marked by bronchial inflammation that can progress to fibrosis in severe cases. We explored a role for
MSCs as an anti-inflammatory therapy and also in the induction of tolerance
to dustmite antigen. To this end, we hypothesize that allogeneic MSCs suppress
the proliferation of peripheral blood mononuclear cells(PBMCs) in patients
with dustmite AA, when challenged with the antigen. We also hypothesize that
MSCs can induce anergy in the PBMCs that are challenged with multiple small
doses of dustmite antigen. Blood samples were collected from non-asthmatic
controls(N=2) and dustmite allergic asthmatics(N=3) and the PBMCs were
stimulated for 5 days with dustmite antigen(5 Вµg/106 PBMCs), in the presence and absence of MSCs. Anergy was induced with introduction of low dose
dustmite antigen at 2-day intervals over the course of 7 days, in the presence
and absence of MSCs. After this, the PBMCs were washed and then studied
for proliferation in the presence of dustmite(5 Вµg/106 PBMCs). Cell proliferation was determined by tritiated thymidine uptake. In all the patients with dustmite AA, MSCs showed significant(p<0.05) decreases in the stimulation
indices(S.I.) as compared to parallel studies with normal subjects. When the
PBMCs exposed to low dose dustmite antigen were subjected to re-challenge
with higher concentrations of the antigen, they were refractory to stimulation,
demonstrating a non-significant proliferation(p>0.05) over PBMCs from the
same patients that were not subjected to the low-dose challenges. The studies
show that MSCs not only suppress the inflammatory responses in dustmite AA,
but they also induce tolerance to dustmite antigen. These findings are a part of
our ongoing studies to examine the mechanism by which MSCs can attenuate
the inflammatory responses to allergic triggers in asthma patients in hopes of
translating these studies to `off the shelf ’ MSCs.
Myeloid (bone-marrow derived) dendritic cells are important in promoting the allergic airway response. SP-D plays a potent protective role in the airways and may regulate the function of myeloid dendritic cells. Ligation of SIRPО±, an inhibitory membrane receptor, has been implicated in inhibition of
macrophage function. We previously showed that SP-D suppressed autocrine
TNF-О± production by bone marrow derived dendritic cells in vitro. We hypothesized that SP-D exerts its inhibitory effect through binding SIRP-О± on the dendritic cell surface. To study expression of SIRP-О±, we assessed RAW264.7 cells
(a monocyte/macrophage cell line), bone marrow derived dendritic cells and
C.O. Prys-Picard*1, R. Niven2, N. Thomson3, P. Corris4, R. Olivenstein5,
H. Siersted6, I. Pavord7, G. Cox8, D. McCormack9, A. Rubin10,
M. Laviolette11, 1. Campbell River, BC, Canada; 2. Manchester, United
Kingdom; 3. Glasgow, United Kingdom; 4. Newcastle-upon-Tyne, United
Kingdom; 5. Montreal, QC, Canada; 6. Odense, Denmark; 7. Leicester,
United Kingdom; 8. Hamilton, ON, Canada; 9. Ontario, ON, Canada;
10. Porto Alegre, Brazil; 11. Laval, QC, Canada.
Introduction: Bronchial thermoplasty (BT), is a novel bronchoscopic procedure designed to improve asthma control by reducing excessive airway smooth
muscle mass. The effectiveness of BT in moderate to severe asthma patients
managed on inhaled corticosteroids (ICS) alone after withdrawal of long-acting beta agonists (LABA) was studied in the randomized, controlled Asthma
Intervention Research (AIR) Trial (Cox et al. N Engl J Med 2007 356:132737). Methods: Patients enrolled were on ICS ≥200µg beclomethasone or equivalent + LABA, with pre-BD FEV1 ≥60% and ≤85% predicted, and demonstrated worsening of asthma on LABA withdrawal for two weeks at baseline.
A two week LABA withdrawal was repeated at 12 weeks after treatment and
various asthma control measures were evaluated in BT (n=55; BT and
ICS+LABA) and Control (CON: n=54; ICS+LABA) groups. Approval was
obtained from all IRB’s at participating centers and written informed consent
obtained from all research subjects. Results: Mean inhaled corticosteroid dose
(beclomethasone equivalent) at study entry was 1305В±880 mcg (median dose
1000 mcg). At baseline there was no difference between the BT and CON groups
in the change in AQLQ and ACQ scores, and pre- and post-BD FEV1 after a
2 week LABA withdrawal period. At 12 weeks post-BT, LABA withdrawal for
2 weeks resulted in worsening of AQLQ and ACQ scores in the CON, but not
the BT group. There was no difference between groups in the change in preand post-BD FEV1 at 12 weeks post-BT. Additionally, following a 2 week
LABA withdrawal (ICS alone) at 12 weeks, the proportion of AQLQ responders (AQLQ score change ≥0.5) was 72% in the BT group and 39% in the CON
group. Conclusions: In patients with moderate to severe asthma, the improvements in asthma control and asthma related quality of life following BT were
maintained with patients on controller medication alone following withdrawal
of LABA therapy.
S. Raj, V.P. Kailasnath, J.L. Sublett*, Louisville, KY.
Background: The Ohio River Valley, including the Commonwealth of Kentucky, is among the top areas in the U.S with very high prevalence of environmental allergens. Mouse allergen (MA) exposure is a well known risk factor
for allergic sensitization and implicated in the pathogenesis of pediatric asthma.
It is best assessed by using skin prick testing. Though previous studies report
high prevalence of MA sensitization in inner city asthmatic children, no data
exists on its comparison with either suburban or rural children with asthma.
Methods: Our retrospective cohort study by chart review was approved by the
institutional review board and informed consent was obtained from the research
participants. All pediatric patients (≤ 18 years age) who underwent allergy testing during 6 month period (July 2009 – December 2009) in a tertiary care referral center were included. Patients were geographically divided into Suburban,
Rural and Inner City groups based on their zip codes. MA was tested using the
standard allergy test panel by skin prick/puncture. Positive skin test reactivity
was defined as wheal diameter ≥ 3mm and erythema ≥ 5mm. Results: A total
of 989 patients underwent allergy testing (Table 1). Mean age of patients with
MA testing was 13.5 years (SD В± 3.04). Among 35% patients who were tested
for MA (n=349), the overall positivity rate was 18.6% (65/349). In children
with asthma (mean age 12.8 years, SD В± 3.19) who had MA testing (n=166),
the rate of positive skin test reactivity was 18% (n=33). Inner city asthmatic
children had significantly greater MA sensitization compared to either suburban or rural children. Conclusions: MA sensitization is highly prevalent among
children with asthma, especially in inner city population but also among suburban and rural children. Though most allergists do not routinely test for MA
sensitization during the initial evaluation, it may be useful to include it in the
allergy testing for children with asthma.
Table 1: Demographics of patients and their MA skin test reactivity
M.J. Siegel*, C.J. Siegel, L.H. Stekoll, Kansas City, MO.
Background: Studies have questioned swimming, especially total hours
swam in a life time (THS), and swimming in indoor chlorinated pools (ICP),
to the development or worsening of asthma (A), based on chlorine chemical
exposure. This study explored the frequency of active asthma (AA) among
swimmers(S)based on:(1) THS;(2)and the frequency of AA versus THS of S
using ICP compared to chlorinated outdoor (OCP) pool facilities. Methods:
IRB approval was obtained from Children’s Mercy Hospital in Kansas City.
1500 surveys were distributed by coaches to the parents of S ages 5-18y/o
participating in a variety of Kansas City competitive swimming programs.
Responses were collected by the study investigators. Each survey queried THS
in ICP and OCP. Estimations of swimming hours spent in swim venues were
given. THS were categorized as follows. 0-99(A);100-249(B);250-499(C);500999(D);1000-1499(E);>1500(F) for each type of facility. Queried was whether
S have health care provider diagnosed A and if A meds were used in the last
year (criteria for AA). S gender and age were also noted. S were age bracketed by std USA swimming divisions. Results: An independent samples t test
was used. For AA, there was a marginal difference overall between S in groups
(grp) A-F t=1.73 (301), p=.085, and S in ICP in groups A-F t=1.68(209),
p=.094. There was a sig differences between S in OCP grp A-F t=2.48(287),
p=.014. There was no difference of AA between male S in ICP, OPC or overall in grp A-F. In female S, AA was significant in hours spend in OCP
t=2.45(139), p=.016 and ICP t=2.15(104), p=.034. AA frequency by age
bracket had a significant correlation between 9-10 y/o S in OCP t=2.039(69),
p=.045 (primarily driven by females at this age), and 11-12 y/o in OPC
t=2.55(60), p=.013. No differences in AA noted between age groups for A-F
overall and ICP. Conclusion: Our study supports the notion that increased
hours of swimming may contribute to the persistence of AA in both ICP and
OCP and female S may be more at risk for persistence of AA than males as
THS increases.S ages 9-12y/o appeared to have an increased frequency of AA,
particularly in females. Although the results are interesting,as swimmingisoften
recommended as a sport for AA, further results are needed to validate the
above conclusions. This study is ongoing. The specific role of inhaled chlorine products being responsible for the persistence of AA in S is yet to be
S.A. Thobani*1, E. Hu2, T. Morphew2, M. Li2, P. Huynh2, L. Scott2, 1. Porter
Ranch, CA; 2. Los Angeles, CA.
BACKGROUND: 2007 National Asthma Education and Prevention Program Expert Panel Report 3 focuses on asthma control as goals of therapy, with
specific components(symptoms, functional limitation, and risks of untoward
events) defining levels of asthma control. Assessment of control provides guidance to medical management. OBJECTIVE: To evaluate which defining components of asthma control most often contribute to uncontrolled asthma, as
defined by risk and impairment components. METHODS: Retrospective analysis of 1,299 pediatric asthmatic patients(4,098 follow up visits) enrolled in an
inner-city pediatric asthma disease management progra (ages, 3-18), was performed to evaluate components of asthma control as defined by the 2007 NAEPP
Expert Panel 3(symptoms, functional limitation, and risks of untoward events)
that contributed to uncontrolled asthma(Not Well Controlled or Very Poorly
Controlled). RESULTS: Patients exhibited uncontrolled asthma at 27.4% of
follow up visits(1,125/4,098) Table 1 illustrates the most frequent contributing
components for uncontrolled asthma. Limitation of activity, defined as interference with exercise usually or always, accounted for 15% of uncontrolled
asthma at follow up visits. Combination of persistent daytime symptoms, nighttime symptoms and beta agonist use accounted for 13% of uncontrolled asthma
at follow up visits. Persistent daytime symptoms(alone or in combination with
other components) were a contributing factor in 52% of uncontrolled asthma
follow up visits. Nighttime symptoms alone occurred as a factor 3% of time.
CONCLUSION: Daytime symptoms, occurring alone or in combination with
other symptoms accounts for the majority of uncontrolled asthma at follow up
visits. Asthma symptoms occurring at night has been reported as indicators of
worsening asthma control. This study demonstrated nighttime symptoms rarely
occur alone, and may represent other disease processes such as obstructive sleep
apnea, GERD or obesity. The inclusion of interference with daily activities in
the new guidelines imposes stricter parameters in assessing asthma control.
The high percentage of follow up visits (15%) rated as uncontrolled solely due
to limitations with exercise may include a proportion of patients with exercise
induced asthma. The inclusion of risk (ED visits, hospitalizations, steroid burst)
contributed minimally as a reason for uncontrolled asthma.
guidelines for assessing asthma control in children. Lung function testing is
often limited in use in the primary care setting. Objective: To assess the importance of lung function tests in defining guideline-based control of asthmatic
children age 5-18. Methods: A retrospective analysis of 2009 data for 453 pediatric patients (886 follow-up visits) enrolled in an asthma disease-specific management program was performed. Initial analysis defined asthma control by
2007 NAEPP/NHLBI guidelines, excluding lung function. Secondary analysis defined asthma control with the inclusion of lung function. The impact of
lung function in defining asthma control was assessed between the two analyses. Results: Patients were predominantly inner-city, male (61.1%), and Hispanic (83.2%). Baseline disease severity: Intermittent (29.4%), mild persistent (21.4%), moderate persistent (24.5%), and severe persistent (34.7%).
Excluding lung function, patients exhibited well controlled asthma in 594/886
(67%) follow-up visits. Overall, the inclusion of lung function resulted in reclassification of patients’ asthma at follow-up visits from well controlled to not
well controlled (9.1%), from well controlled to very poorly controlled (1.6%),
and from not well controlled to very poorly controlled (1.8%). Reclassification occurred less in patients 5-7 years old compared with 8-11 and 12-18 years
of age (6.3%, 13.2%, and 9.2%, respectively, p = .041). The influence of female
gender and severe baseline severity on asthma control reclassification was
significant for children 12-18 years (p < .05). Conclusions: This study provides
support for evaluating lung function to properly assess asthma control. Exclusion of lung function in asthma control assessment could result in underestimation of control level and possibly under treating the disease, particularly for
12-18 year old females with severe persistent baseline severity. The inclusion
of lung function testing in kids 5-7 resulted in less reclassification compared
to other age groups; however, a small percentage of asthma control for this
group was underestimated. These findings suggest that lung function testing
is important to assess asthma control for children who can coordinate performing the tests.
Reasons Asthma Uncontrolled
E. Egea*, D.L. Mendoza, S. Saavedra, G. Garavito de Egea, Barranquilla,
Atlantico, Colombia.
D= day symptoms >2d/week
N=Nigt Sx >2nt/month
B=SABA(not excercise)>2day/week
S= steroid burst>1
H=ED visits/hospitalizations
A=School Absenteeism >5dD= day symptoms >2d/week
E.K. Hu*, S. Thobani, T. Morphew, P. Huynh, M. Li, L. Scott, Los
Angeles, CA.
Background: Lung function testing is a component of the 2007 National
Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3
The use of nanotechnology in is a useful tool in biomedicine. Chiken IgY
has a comparatives advantages in regard the serum IgG because of its low and
simplicity cost in its production and its ionic stability. IgY does not present
cross-reactivity with human rheumatoid factors. The combination of these antibodies with colloidal gold nanoparticles is an innovation that has been using
in many immune assays. The purpose of this study was to produce and evaluate a novel inmunocongugate IgY antibody anti dust mite allergens conjugated with colloidal gold nanoparticles obtained by immunization of Hi Line
Brown hens with synthetic oligopeptides from the dust mite group 1 allergens
in the detection of Dust mite allergens. The synthesis of colloidal gold nanoparticles (“GNPs”) was performed by reducing HAuCL4 by boiling trisodium
citrate at 1%. The HAuCl4 concentration was standardized as well as the reaction time of the colloid. GNPs were conjugated with the IgY-anti cisteinprotease at room temperature incubation. Its stability was determined through pH
ranges between 6.5 and 8.0 and at different antibody concentrations of flocculation testing with NaCl 2M. The nanoparticles and immune-conjugates were
characterized by UV-visible spectroscopy. The capacity of the immune-conjugates to detect and bind to the allergens of the species Dermatophagoides farinae was demonstrated by Dot-Blot using a somatic proteins extract from whole
body of the mites. The synthesized GNPs from 0.03% and 0.04% concentrations of HAuCl4 showed a maximum absorption peak at 520 nm, corresponding to the visible range where oscillations are radicals on their plasmon sur-
face. The best nucleation time was 15 minutes. The best efficiency pH for the
conjugation was 7.5 with a concentration of 0.25 mg/mL of IgY anti-cysteine
protease. The Dot-blot experiments shows evidence of this immune-conjugate
bind to allergens present in the D-Farinae mite whole body extract (detection
limit: 1.5 µg total protein). A novel conjugate hen IgY –conjugated to colloidal gold nanoparticles was produced and this gold labeled IgY antibody is
able to recognizes allergens from D.farinae representing a new tool for detection and control of mites allergens that could be used in the control of these
allergens and could benefit sensitized atopic patients to mites, who daily are
exposed to pollution from indoor spaces.
Figure 1: Dot-Blot with IgY-Nanogold Immune-conjugates: Lanes 1 – 2 Df
allergens extracts incubated with 0.02% of IgY-nanogold. Lanes 3 - 4 D F
allergens incubated with 0.03% of IgY-nanogold. Lanes 5 - 6 D F allergens
incubated with 0.04% of IgY-nanogold.
B.K. Graham*, M. Dhar, C. Barnes, J. Portnoy, Kansas City, MO.
Introduction: High concentrations of airborne tree pollen occur every spring
in the midwestern United States. Tree pollen production may be dependent on
several climate related factors including temperature, precipitation and sunlight. To determine the impact these factors have on total seasonal tree pollen
collected, we conducted the following study. Methods: A Hurst style spore
trap was positioned atop a 5-story hospital building in the urban core of Kansas
City. The collector operated from February to November from 1997 to 2010.
Slides were stained with Calberlas stain and pollen grains were counted microscopically at 400X. Pollen counters were certified by the National Allergy
Bureau. Weather parameters were recorded by an Automated Weather Service
station located adjacent to the collector. Pollen counts were generated daily and
recorded in an Access database. The database was queried for total tree pollen
grains collected per day and summed to produce a count of tree pollen collected
per year. Daily rainfall was displayed and summed to produce total inches of
rainfall for the year. Results: Tree pollen grains collected annually varied from
7043 in 1997 to 63,397 in 2010. Total yearly rainfall varied from 25 inches in
2002 to 54 inches in 2008. The mean yearly tree pollen was 26,326 with a
deviation of 16,099 and the mean yearly rainfall was 40.04 inches with a deviation of 10.3 inches. There has been a continuous yearly increase in total tree
pollen collected for the 14 years of records (corr = 0.84). For weather parameters, total yearly pollen collection correlated best with the sum of rainfall for
the previous two years (corr = 0.67). Conclusion: These results indicate a trend
to larger tree pollen collections for subsequent years from 1997 to 2010 in the
midwestern United States. Total tree pollen production tends to correlate with
area rainfall for the subsequent two years.
A. MacGinnitie*1, W.E. Pullman2, P.T. Horn2, 1. Pittsburgh, PA; 2. Cambridge, MA.
Rationale: Hereditary angioedema (HAE) is characterized by unpredictable,
acute swelling attacks at varied locations. Ecallantide, a novel plasma kallikrein
inhibitor, is an effective therapy for acute HAE attacks. To supplement a previous analysis by overall primary attack location, we report the efficacy of
ecallantide versus placebo by individual symptom severity and attack site. Methods: Integrated data from 2 double-blind, placebo-controlled trials of ecallantide (EDEMA3 and EDEMA4) were analyzed by symptom severity rating (mild,
moderate, or severe) and anatomical site (based on 5 symptom complexes: internal head/neck [laryngeal], stomach/gastrointestinal [abdominal], cutaneous,
genital/buttocks, and external head/neck). Patients may have had >1 attack site.
Efficacy endpoints include 2 validated, HAE-specific, patient-reported outcome measures: Mean Symptom Complex Severity (MSCS) score and Treatment Outcome Score (TOS). IRB approval was obtained at each site and written informed consent was obtained from each research subject. Results: 143
total treatments (70 ecallantide, 73 placebo) were analyzed. Ecallantide was
effective for both severe and moderate symptoms with TOS (out of 100) of 45.8
and 57.1, respectively, vs 14.7 (P=0.14) and 22.7 (P<0.01) for placebo, and
MSCS score improvement of -1.38 and -0.92, respectively, vs -0.65 and -0.49
for placebo (P<0.05 for both). Relatively few mild symptoms were treated (16
in each group); TOS for ecallantide was 50.0 vs 28.6 (P=NS) for placebo while
MSCS score was -0.07 vs 0.00 (P=NS). The safety profile was similar for all
attack severities. Ecallantide was effective for treatment of laryngeal and abdominal symptoms with improvements in MSCS score of -1.15 and -1.27, respectively, vs -0.33 (P=0.04) and -0.54 (P<0.01) for placebo, and TOS of 65.4 and
66.7 vs 12.5 (P=0.06) and 29.3 (P=0.01) for placebo. Ecallantide was significantly efficacious for cutaneous symptoms based on TOS (51.0 vs 14.1 for
placebo, P<0.01) but not change in MSCS score (-0.79 vs -0.47 for placebo,
P=NS). Despite small samples, ecallantide showed some improvement in external head/neck and genital/buttocks symptoms. Conclusions: Ecallantide
appeared effective for treatment of acute HAE attacks at all anatomic sites.
Ecallantide was well tolerated and showed efficacy for moderate and severe
M.A. Kausar*, V.K. Vijayan, S.K. Bansal, M. Vermani, W.A. Siddiqui,
M.K. Agarwal, New Delhi, India.
Introduction: In an earlier study, we have reported the identification, isolation and purification of a 24 kd major allergenic protein of crude mosquito
(Culex quinquefasciatus; Cq) extract1. We further characterized the 24 kd allergen by matrix assisted laser desorption-ionization-time of flight mass spectrometry (MALDI-TOF-MS) analysis. Methods: The 24 kd protein was reduced,
alkylated and digested using trypsin. Mass spectrometry was performed using
a MALDI-TOF mass spectrometer. The digested peptide fragments were
searched in the NCBI non-redundant protein database using the Mascot program from Matrix Science ( By comparison
with the established database, a protein score ≥50 was considered to be significant for identification. Results: In the peptide mass fingerprint analysis,
the masses obtained from the 24 kd protein band showed the highest correlation with conserved domains of glutathione s-transferase (23.2 kd, score 84),
Ferritin subunit precursor (Ferritin heavy chain-like protein; AeFer(H); 23.8
kd, score 84) and calcium-binding protein, putative (22.1 kd, score 70) from
Aedes aegypti. Conclusion: Peptide mass fingerprinting revealed that the fragments of 24 kd major allergenic protein of Cq showed homology with three
proteins of another common species of mosquito, Aedes aegypti. Reference:
1. Kausar MA, Vijayan VK, Bansal SK, Vermani M and Agarwal MK. Isolation and purification of a 24 kd major allergen of Culex quinquefasciatus whole
body extract. Annals of Allergy, Asthma and Immunology 2009;102:23.
B.P. Davis*, J.K. Picard, J.P. Cooper, S. Zheng, L.S. Levin, J.A. Bernstein,
Cincinnati, OH.
M. Riedl*, Los Angeles, CA.
Rationale: Non-allergic rhinitis (NAR) affects millions of Americans, but
the mechanism(s) remains unknown. Transient receptor potential vanilloid-1
receptor may be involved, as single dose intranasal capsaicin studies have
demonstrated reduced nasal congestion in NAR subjects. This study investigated the efficacy and safety of treatment with an intranasal capsaicin and eucalyptol preparation (ICX72 or Sinus Busterв„ў) compared to a placebo when
administered continuously over two weeks in subjects with a significant component of NAR. Methods: Forty-two informed consented patients with a significant component of NAR were randomized to receive ICX72 (n=20) or a
filtered water control (n=22) administered 1-2 puffs in each nostril twice daily
over 2-weeks. The primary endpoint was change in total nasal symptom scores
(TNSS) from baseline to end of study. Secondary endpoints included changes
in individual symptom scores (nasal congestion, sinus pain, sinus pressure,
headache) over two weeks and average time to first relief. Mean TNSS and individual symptom scores were also recorded after single dosing with ICX72 vs.
placebo at 5, 10, 15, 30 and 60 minute intervals. Rhinitis quality-of-life domains
at end of study and safety endpoints were also analyzed. All data was analyzed
by SAS. Results: Statistically significant differences in changes from baseline
to end of study between the ICX72 and placebo groups were observed for TNSS
and each individual symptom (p<.01). The average time to first relief for ICX72
subjects was 52.6 seconds which was significantly less than placebo (p<.01).
For ICX72 subjects, nasal congestion, sinus pain, sinus pressure and headache
was improved at 5, 10, 15, 30, which persisted up until 60 minutes for nasal
congestion and sinus pain (p<.05). ICX72 patients also experienced significant
improvement in each quality of life domain at end of study (p<.05). No significant difference between groups in adverse events or rescue medication
was observed. ICX72 subjects experienced no rebound congestion but did have
improvement in olfaction versus placebo at end of study. Conclusion: This is
the first controlled trial to demonstrate that ICX72 provides safe, rapid onset
and sustained relief for subjects with a NAR component over the course of a
two week treatment period.
S. Nsouli*, Danville, CA.
Previously we have shown that the combination of a Nasal Corticosteroid
Mometasone with an oral antibiotic may be more efficacious than monotherapy with an oral antibiotic in the treatment of serous otitis media in children.
Since chronic inflammation is the histopathologic landmark of otitis media
with effusion, clinical observations have led us to believe that the combination
of a Nasal Antihistamine Olopatadine with an oral antibiotic may be more effective than monotherapy with an oral antibiotic in the treatment of serous otitis
media. We studied forty pediatric patients( age 6 years to 11 years) in a randomized open labeled 2-week trial to compare the efficacy of the combination
nasal Olopatadine 665 mcg/nostril twice daily with an oral antibiotic Amoxicillin/Clavulanate potassium( 90mg/kg/day in 2 divided doses every 12 hours)
for the treatment of otitis media with effusion. The efficacy of the treatment
options was assessed using pneumatic otoscopy, impedance tympanometry, and
audiometry to monitor the clinical course of the middle ear effusion in both
treatment groups. In the combination group nasal Olopatadine and oral antibiotic a resolution of otitis media with effusion occurred at the 7th day. In contrast in the group treated with monotherapy with the oral antibiotic the resolution of otitis media with effusion occurred on the 14th day. In conclusion, the
combination of nasal antihistamine Olopatadine plus an oral antibiotic is more
effective than monotherapy with an oral antibiotic. The combination nasal antihistamine Olopatadine plus an oral antibiotic may be a safer and shorter therapy given the safety issues with long term use of systemic antibiotics.
Introduction: Icatibant, a selective bradykinin B2-receptor antagonist, is
a novel treatment for acute attacks of hereditary angioedema (HAE). Icatibant
is an investigational treatment in the US. The efficacy and safety of icatibant
was assessed in patients with acute laryngeal HAE attack during the controlled
and open-label extension (OLE) phases of the FAST (For Angioedema Subcutaneous Treatment)-1 Phase III trial. Methods: During the controlled phase,
patients with a laryngeal HAE attack (first attack) received 1 subcutaneous
injection of open-label icatibant (30 mg). In the OLE phase, subsequent laryngeal attacks were each treated with up to 3 injections (≥6 h apart) of openlabel icatibant, with repeat dosing possible if symptoms worsened within 48 h.
Efficacy was assessed using patient and physician assessments. Approval was
obtained from the independent ethics committee for each center. All participants gave written informed consent. Results: 26 patients experienced 45 laryngeal attacks (controlled n=8; OLE n=37). 69% (31/45) of attacks were assessed
as moderate-to-very severe in intensity. Rapid improvement in symptom severity was observed, with mild-to-absent symptoms for most attacks achieved
within 4 h of icatibant administration (controlled phase, 100%; OLE phase,
84%), irrespective of attack severity. All symptoms resolved by 24 h. Patientreported median time to symptom regression was 0.6 h during the controlled
phase and between 0.3 and 1.2 h during the OLE phase. Investigator-reported
median time to �observable regression of symptoms’ (start of improvement)
and �overall patient improvement’ were 1.0 and 0.8 h, respectively. Approximately 86.5% of attacks resolved following 1 injection, 10.8% following 2
injections, and 2.7% following 3 injections. All patients experienced generally
mild transient injection-site reactions (erythema, swelling, itching, burning,
and pain) which resolved spontaneously without intervention. No drug-related
serious adverse events or safety issues were observed. Conclusions: Icatibant
was effective and generally well tolerated, providing rapid regression of symptoms associated with acute laryngeal HAE attacks.
L.A. Wiens*, Tulsa, OK.
Studies demonstrate the impact pharmacists have on improving outcomes
of ARD(rhinitis, asthma, sinusitis). Utilization of pharmacists has practical and
cultural barriers to effective collaboration. This survey is designed to gather
opinions on the collabaration between pharmacists and healthcare providers in
the treatment of ARD. Access to the survey was provided by Oklahoma Pharmacy Association website and letters sent to Oklahoma Society of HealthSystem Pharmacists. Responses were tabulated and reported as a percentage
of the total. 93 pharmacists started and 57(61.3%)completed the entire survey.
46% had been in pharmacy practice for > 20 yrs with an equal mix of independent, academic, rural, and urban settings. 73.1% do not routinely monitor
refills of ARD medications, and only 2% believe this is an effective service
provided to prescribers. The most common reason for interaction with the prescriber’s office was prescription refill authorization(50%). 95% are familiar
with medication therapy management(MTM)and 57.3% participate in MTM
programs. The most common concern of pharmacists regarding the care of
ARD was efficacy (drug selection, side effects, improper dose), followed by
compliance, proper use of inhalers, and drug interactions/adverse events. Inappropriate asthma control was a concern in 7.9%. Adjusting existing therapy
for inadequately controlled ARD with documentation sent to the provider’s
office was acceptable practice in 82.2%. Greater than 90% of pharmacists
believed their role in MTM for ARD should increase because of their expertise in drug management, accessibility to patients, and improved outcomes. They
would like additional training in asthma(61.7%), allergy shots(59.6%), and
chronic rhinosinusitis (48.9%). They preferred to receive training in a local
community setting or in their own pharmacy. Most pharmacists would like to
have a greater role in MTM for ARD. While the majority of pharmacy interaction with the prescriber’s office was for refill authorization, most pharmacists do not routinely monitor prescription refills and do not believe this is an
important service for prescribers. This suggests an opportunity for education
and collaboration between pharmacists and prescribers in the care of ARD. The
preferred venue for such activity is a local community event or the individual
pharmacy store.
Pharmacist Response to ARD Survey
events occurred, and no viral infections arose during the study. Conclusions:
C1-INH concentrate at a single dose of 20 U/kg provides rapid and safe relief
from the symptoms of acute peripheral skin swellings in patients with HAE.
J. Baker*1, M. Riedl2, A. Banerji3, D. Hurewitz4, R. Levy5, T. Craig6,
I. Kalfus7, 1. Lake Oswego, OR; 2. Los Angeles, CA; 3. Boston, MA; 4.
Tulsa, OK; 5. Atlanta, GA; 6. Hershey, PA; 7. New York, NY.
T.J. Craig*1, R.L. Wasserman2, R.J. Levy3, A.K. Bewtra4, L. Schneider5,
F. Packer6, W.H. Yang7, H.O. Keinecke8, P.C. Kiessling8, 1. Hershey, PA;
2. Dallas, TX; 3. Atlanta, GA; 4. Omaha, NE; 5. Boston, MA; 6. Idaho
Falls, ID; 7. Ottawa, ON, Canada; 8. Marburg, Hessen, Germany.
Rationale: Hereditary angioedema (HAE) is a rare disorder characterized
by functional deficiency of C1 inhibitor (C1-INH), resulting in periodic attacks
of acute edema that can be life-threatening if they occur in the laryngeal region.
We conducted a prospective study of the efficacy and safety of C1-INH concentrate in the emergency treatment of acute laryngeal HAE attacks. Methods:
Each laryngeal attack was treated with a single dose (20 U/kg body weight) of
purified human C1-INH concentrate (Berinert). Efficacy was assessed as time
to onset of symptom relief and time to complete resolution of all symptoms,
based on the patients’ assessments. Safety was assessed in terms of adverse
events and viral markers. Results: C1-INH concentrate was used to treat 48
laryngeal attacks in 16 patients, in all cases successfully. The median time to
onset of symptom relief was 15 minutes. The median time to complete resolution of all symptoms was 8.4 hours. No serious adverse events occurred and
the treatment was well tolerated. Administration of C1-INH concentrate was
not associated with infections of human immunodeficiency virus, hepatitis
virus, or parvovirus B19. Conclusions: C1-INH concentrate is an effective
and safe emergency treatment for providing reliable and rapid relief from the
potentially life-threatening symptoms of laryngeal HAE attacks.
R.J. Levy*1, A.K. Bewtra2, D. Hurewitz3, R.L. Wasserman4, T.J. Craig5,
J.N. Moy6, G. Janss7, F. Packer8, H.O. Keinecke9, P.C. Kiessling9, 1. Atlanta,
GA; 2. Omaha, NE; 3. Tulsa, OK; 4. Dallas, TX; 5. Hershey, PA; 6. Chicago,
IL; 7. Rapid City, SD; 8. Idaho Falls, ID; 9. Marburg, Hessen, Germany.
Rationale: Acute peripheral subcutaneous edema is a frequent symptom of
C1-inhibitor (C1-INH) deficiency in patients with hereditary angioedema
(HAE). Although often not treated, these peripheral attacks can be sufficiently
painful to impact the ability to work and undertake other daily activities. Clinical studies on their treatment with C1-INH concentrate are rare. The objective
of our prospective study was to investigate the benefit of using C1-INH concentrate in the treatment of acute peripheral HAE attacks. Methods: Each peripheral attack was treated with a single intravenous dose (20 U/kg body weight)
of purified C1-INH concentrate (Berinert). The efficacy endpoints were time
to onset of symptom relief and time to complete resolution of all symptoms,
based on the patients’ assessments. Safety was assessed as adverse events and
markers for viral infection. Results: C1-INH concentrate was used to treat 235
peripheral attacks in 30 patients. The median time to onset of symptom relief
was 30 minutes in the by-attack analysis. Within 1 hour after the start of treatment, onset of relief had been reported in at least 90% of all attacks. The median
time to complete resolution of all symptoms was 23.5 hours. No serious adverse
Introduction: Pregnancy has been associated with an increased number
of HAE attacks. Attenuated androgens are often prescribed for prophylaxis of
HAE attacks, but are contraindicated in pregnancy (Category X) due to the
potential for adverse events including virilization of the female fetus. Presented
here are reports of Cinryze use in pregnant subjects from Cinryze open-label
studies. Methods: Pregnancy was not an exclusion criterion in two open label
studies investigating the use of Cinryze for the treatment of acute attacks and
for prophylaxis of HAE attacks. In these studies Cinryze 1000 U IV was administered for either acute attacks (followed by another injection 60 minutes later
if needed) or routine prophylaxis (every 3-7 days). Pregnancy outcome data
were collected retrospectively. Approval was obtained from WIRB and informed
consent obtained from all subjects. Results: Fourteen pregnant women were
treated with Cinryze in the studies; one subject who was treated in both studies delivered a healthy neonate. Of the 13 remaining subjects, 3 subjects enrolled
in the acute treatment study. One received 8 doses and 2 subjects received a
single dose of Cinryze at delivery only. All 3 subjects delivered healthy neonates.
Ten subjects in the prophylaxis study received a median of 34 doses (range: 2
to 85) during their pregnancy and reported the following outcomes: 7 subjects
delivered 8 healthy neonates (1 set of twins), 1 subject (45yr old) with a history of miscarriage and ectopic pregnancy had a spontaneous abortion (reported
as possible ectopic pregnancy), and 1 subject delivered a stillborn neonate with
multiple congenital anomalies. This subject was first exposed to Cinryze in the
second trimester. One subject had an unknown outcome. Conclusion: In this
limited sample of pregnant women, Cinryze had a favorable risk/benefit profile for management of HAE.
B. Zuraw*1, W. Lumry2, J. Baker3, R. Levy4, D. Hurewitz5, M. White6,
T. Craig7, M. Riedl8, P. Busse9, L. Bielory10, J.A. Grant11, I. Kalfus9, 1. La
Jolla, CA; 2. Dallas, TX; 3. Lake Oswego, OR; 4. Atlanta, GA; 5. Tulsa,
OK; 6. Wheaton, MD; 7. Hershey, PA; 8. Los Angeles, CA; 9. New York,
NY; 10. Newark, NJ; 11. Galveston, TX.
Background: Cinryze is approved in the US for routine prophylaxis against
angioedema attacks in adolescent and adult patients with HAE. This study evaluated the efficacy and safety of repeat use of Cinryze for the treatment of
HAE attacks. Methods: This open-label, multicenter (29 sites) study enrolled
113 subjects with a diagnosis of HAE. Approval was obtained from WIRB
and informed consent obtained from all subjects. Subjects were eligible to
receive Cinryze 1000U IV for attacks of angioedema at any anatomic location. Subjects could receive a second dose of Cinryze 1000U if they had not
improved by 60 minutes. Documentation of attack occurred every 15 minutes
by diary card. The presence of three consecutive assessments of improvement
constituted relief. Safety was monitored by recording AEs, vital signs, virology (HBV, HCV, HIV) and anti-C1 inhibitor antibody. Results: Of the 113 subjects (aged 2-80 years) in this study, 101 received Cinryze for an acute attack,
and were included in the efficacy analysis. Twelve received Cinryze for shortterm prophylaxis only. A total of 609 attacks in 101 subjects were treated.
Median time to beginning of relief of the first attack was 45 minutes. Of 84
laryngeal attacks, none required intubation after receipt of Cinryze. No difference was observed in subject response between children and adults. In subjects
treated for >1 attack the efficacy of Cinryze was not reduced; of 15 subjects
who had ≥ 10 attacks, the median time to beginning of relief of their 10th attack
was 30 minutes. Adverse events were reported in 41% (46/113) of subjects.
The majority (87%) were of mild or moderate intensity. The most common
(3%-5% of subjects) were sinusitis, nasopharyngitis, streptococcal pharyngi-
tis, HAE, constipation, cough, rash, and bronchitis. There were no severe hypersensitivity reactions, including anaphylaxis, related to Cinryze. HBV, HCV, and
HIV testing revealed no evidence of viral transmission. There was no evidence
of development of clinically relevant anti-C1 INH antibodies. Conclusion: Cinryze was safe and effective for the treatment of all HAE attacks. For subjects
with >1 attack, the efficacy of Cinryze for the treatment of HAE did not diminish with subsequent repeated administration.
K.Y. Kwong*1, P. Minoo2, V. Rehan1, 1. Torrance, CA; 2. Los Angeles, CA.
Persistent inflammation plays a pivotal role in development of bronchopulmonary dysplasia (BPD). CD74 (invariant chain of MHC2) has been
shown to facilitate chronic inflammation in gastro-intestinal epithelial cells
after binding infectious and inflammatory signals. In this pilot study we endeavor
to demonstrate expression of CD74 in lung inflammatory cells from preterm
infants at risk of developing BPD. Lung inflammatory cells in tracheal aspirates (TAs) obtained by routine clinical care (suctioning to clear secretions)
from preterm infants between 28 and 32 weeks gestations. Samples were taken
during the first 4 days of life then at subsequent 4 day intervals. After washing
to remove mucous cytosins were made comprising of 250,000 cells. A commercially available anti-CD74 antibody was used to detect CD74 via immunoflorescence. Lung inflammatory cells obtained from 5 preterm newborns consisted of predominantly neutrophils and mononuclear cells. CD74 was
undetectable on lung inflammatory cells in all 5 newborns during the first 4
days of life. CD74 was expressed on lung inflammatory cells by 16 to 20 days
of life in 2 infants (Figure 1) and by days 24 to 28 days of life all patients
expressed CD74 on lung inflammatory cells. Results of this pilot study show
that CD74 is expressed on lung inflammatory cells from premature infants 2832 weeks gestation who are at risk for development of BPD. Expression of
CD74 in these infants may be developmentally regulated and may contribute
towards chronic airway inflammation in these patients.
behavior and actual change at one month. This was a quality improvement project conducted by the ACAAI and did not require IRB approval. Results 848
learners participated in the symposia assessments and 157 in the workshop
assessments. 44 workshop participants completed the one month post evaluation. In the workshops, the mean baseline competency score was 58% which
increased to 71% (p<0.001) immediately post workshop. The increase was sustained one month post workshop at 73% (p=0.0014). After the workshops, 66%
of the participants indicated an intent to change their behavior, and at one month
40% reported an actual change in practice based on the workshop (p=0.003).
In the symposia activities, the mean baseline competency was 45% which
increased to 61% (p<0.001) after the activity. Conclusions ACAAI workshops
activities increased learner competence and maintained it over time. The workshops also led to a change in the practice behavior of nearly half the participants. ACAAI symposia activities also increased learner competence.
D.M. Robertson*, J.L. Baldwin, M.J. Greenhawt, Ann Arbor, MI.
Objective: Allergic disease is increasing in prevalence and is a common
reason for specialist referral. Health beliefs about allergic disease among nonallergist physicians and patients have been only minimally studied. Methods:
With IRB approval and after informed consent was obtained, a 35-item survey
was administered to University-based non-allergy physicians, practicing allergist members of a state allergy society, and patients of a university-based allergy
clinic. Response concordance within and between the groups was measured
using chi-square. Results: Twenty-two allergists, 109 patients, and 149 nonallergist physicians completed the survey. Allergists agreed on 85.7% of items,
but showed discordance on food testing for non-classic symptom presentation, delayed introduction of allergenic foods to children, the role of food allergy
in atopic dermatitis, non-antibiotic sulfa drug avoidance in sulfa allergic patients,
and skin testing for drug allergy. Opinions among non-allergy physicians were
concordant on 35% of items, and among patients on 14%. For these specific
items both groups were agreement with allergists’ opinions. Non-allergist physicians demonstrated varied opinions on allergy testing, food allergy, eczema,
and chemical or drug sensitivity. Allergist and non-allergy physicians were in
significant disagreement on 16/35 (45.7%) of items, but non-allergy physicians
who either completed an allergy elective during their training or had a personal history of an atopic condition had significantly greater agreement on an
additional 5.7% of items, respectively. Non-allergists and patients disagreed
significantly on 29/35 (82.8%) of items. The median answer for patients on all
items was �no opinion,’ suggesting a knowledge deficit despite being actively
treated by an allergist. Conclusions: Patients and non-allergist physicians have
strongly discordant beliefs from those of practicing allergists and amongst themselves. However, either prior allergy education or a history of personal atopy
significantly improved concordance with allergists among non-allergist physicians. In addition to a lack of concordance on allergy opinions, patient responses
suggested poor awareness of allergic disease. Continued allergy education is
needed among allergy patients and non-allergy physicians, as well as practicing allergists.
S.V. Montandon1, M. Thorsen2, T. Le*3, 1. Louisville, KY; 2. Arlington
Heights, IL; 3. Elizabethtown, KY.
Background The American College of Allergy Asthma and Immunology
(ACAAI) is a major provider of allergy, asthma and immunology education
for healthcare professionals. However, learning outcomes have not been well
documented for ACAAI Annual Meeting educational activities. Methods Participants in six workshops and seven symposia activities at the 2009 ACAAI
Annual Meeting were asked to complete case-based multiple-choice questions developed by the symposia and workshop faculty. The questions were
administered prior to the start and at the conclusion of each activity. In addition, a one month post-test was electronically submitted to the attendees of the
workshops. Workshop participants were also surveyed on their intent to change
R.I. Siles*, F.H. Hsieh, Cleveland, OH.
Introduction: Mast cells play an important role in the pathogenesis of
urticaria. Mastocytosis is a heterogeneous disorder characterized by the abnormal proliferation and activation of mast cells in various organs of the body,
including the skin. We sought to determine if subjects with mastocytosis presented with symptoms of chronic urticaria, defined as having recurrent hives
lasting for more than six weeks. Methods: We performed a retrospective chart
review of patients with biopsy-proven systemic and cutaneous mastocytosis
who were seen at our institution from 2004-2009. Demographic, clinical, and
laboratory data were analyzed. Results: We identified 29 cases of systemic mastocytosis meeting World Health Organization diagnostic criteria. The mean age
was 56.9 years old with a 1:1.2 male:female ratio; 87% of the subjects were
Caucasian. The mean tryptase level was 190.0 ug/L (normal <13.5 ug/L). No
subject had chronic urticaria. One subject reported sporadic episodes of acute
urticaria. Seventy nine percent of the subjects had dermatological symptoms
including pruritis, flushing and/or biopsy-proven cutaneous mastocytosis
lesions. Common presenting symptoms included gastrointestinal symptoms
(72%), hematological manifestations (55%) and B symptoms (27%). Thirty
subjects were found to have isolated cutaneous mastocytosis with a mean age
of 26.3 years old and a 1.5:1 male:female ratio. The mean tryptase level was
16.2 ug/L. In this group, 70% had urticaria pigmentosa, 20% telangiectasia
macularis eruptiva perstans and 10% had a solitary mastocytoma. Three subjects had urticaria, with one subject presenting with chronic urticaria and coexisting cutaneous mast cell disease. The other two patients reported isolated
episodes of acute urticaria. Conclusions: Chronic urticaria is not a common
presenting symptom for either systemic or cutaneous mastocytosis. Elevated
serum tryptase was not a marker for the presence of urticaria in mastocytosis
subjects. The recognized cutaneous manifestations of mastocytosis are distinct from the syndrome of chronic urticaria.
E. El-Hassan*1, N. Pasch2, N. Achilles1, R. Moesges1, 1. Cologne, Germany; 2. Aachen, Germany.
Rationale: The purpose of this investigation was to visualize the 3-D spatial distribution of mucosal swelling in the nasal cavity and to demonstrate the
prophylactic effect of treatment with an antihistamine (levocetirizine) on exposure to allergens. Methods: A suitable test subject with a history of allergic
rhinitis proven by skin prick and nasal challenge tests was identified during the
symptom-free interval after the pollen season when she showed signs of “minimal persistent inflammation” . The test subject developed significant symptoms of allergic rhinitis (nasal congestion, rhinorrhea, sneezing attacks, and
itching) after provocation with birch pollen. This subject underwent nasal allergen challenge before and after two and five weeks of treatment with levocetirizine 5 mg OD at night. High resolution MR imaging was used to capture,
visualize, and process the geometrical data of the nasal cavity immediately
before and after the challenge tests. Based upon the MRI data collected, we calculated the nasal airflow with the help of computational fluid dynamics models [CFD]. The surface of the nasal cavity mucosa was extracted from MRI data
by using the so-called reconstruction pipeline. First, the three-dimensional MRI
data was pre-processed. Then, the region of interest was extracted using segmentation methods and contouring methods to generate a surface in the reconstruction step. This surface was subsequently optimized for flow simulations.
State-of-the-art nasal flow diagnostics such as rhinomanometry, acoustic rhinometry, and 24 hr rhinometry were used to validate the results. Results and
Conclusions: After 36 days of treatment with levocetirizine, a 33% reduction
of the nasal symptom score and a 37% improvement in the nasal flow were documented as compared to the allergen challenge of the untreated case. The spatial distribution of nasal swelling before and after allergen challenge was visualized in 3-D [Fig. 1, Unsmooth surface].
A.K. Ellis*1, J.D. Ratz1, S.J. Tebbutt2, D.J. Adamko3, J.H. Day1, 1. Kingston,
ON, Canada; 2. Vancouver, BC, Canada; 3. Edmonton, AB, Canada.
Background: The Environmental Exposure Unit (EEU) is an internationally recognized and validated model of allergic rhinitis (AR) that utilizes controlled allergen challenge to generate symptoms in allergic individuals. To date,
study participants have not been formally phenotyped to determine what proportion of subjects exhibit an isolated early phase response (EPR) versus a dual
response (DR; EPR + late phase). Objective: To characterize a cohort of AR
subjects exposed to pollen in the EEU in order to identify subjects with isolated EPR and DR for genomic and metabolomic analysis. Methods: After providing written informed consent, healthy, allergic subjects underwent skin prick
testing (SPT) to short ragweed and selected aeroallergens, recording late phase
SPT responses at home. Eligible subjects returned for exposure to ragweed
pollen in the EEU (3 h) and assessed individual rhinoconjunctivitis symptoms
and Peak Nasal Inspiratory Flow (PNIF) q30min. All subjects were discharged
with diary cards and asked to continue recording symptoms and PNIF q1h from
hours 6 to 12 after pollen exposure ended. Total Symptom Scores (TSS) and
Total Nasal Symptom Scores (TNSS) were calculated and subjects classified
as follows: isolated EPR - TSS/TNSS decreased by 50% or more by hour 6/7
and did not increase; protracted EPR - TSS/TNSS had not decreased by 50%
by hour 6/7 and never returned to baseline; DR - a 50% decrease in TSS/TNSS
by hour 6/7 followed by a clear and sustained increase. IRB approval was
obtained from the Queen’s University REB. Results: Of 57 subjects screened,
44 subjects remained eligible and attended the 3 h pollen exposure visit. 19
(43.2%) subjects had an isolated EPR, 17 (38.6%) subjects had a protracted
EPR and 6 (13.6%) subjects had a DR. Two subjects (4.6%) could not be reliably phenotyped. In general, there was a good correlation between ratings of
nasal congestion and PNIF, but PNIF on its own could not reliably distinguish
between EPR versus DR. Five out of the 6 subjects (83.3%) that exhibited a
late phase AR response following pollen exposure in the EEU also reported a
late phase SPT response at screening. Conclusions: 13.6% of subjects demonstrated a dual AR response to ragweed allergen challenge in the EEU. The
EEU is a useful model to phenotype AR subjects for clinical research purposes.
J.S. Lee, D. Wilson, N. Camuso, D. Patel, A. Salapatek*, Mississauga,
ON, Canada.
Background: Dust mite allergens cause allergic sensitization and asthma
worldwide. One of the major dust mite species responsible for allergic reactions in N. America is Dermatophagoides pteronyssinus (Der p). This study
assessed the symptoms induced using aerosolized Der p allergen in an Environmental Exposure Chamber (EEC) model. Method: Thirty patients with positive SPT to Der p and/or Dermatophagoides farinae were exposed to 10120ng/m3 aerosolized Der p allergens for 3 hrs in an EEC over 4 consecutive
days(V2-V5). Allergic Rhinoconjunctivitis symptoms were assessed using diary
cards [nasal congestion, rhinorrhea, sneezing, itchy nose (TNSS:Total Nasal
Symptoms Score), itchy eyes, watery eyes, red eyes and itchy ear/palate
(TNNSS:Total Non-nasal Symptom Score) - scale of 0-3] at pre-EEC and 10,
20, 30, 45, 60, 90, 120, 150, and 180 min. Sufficient symptoms were considered to have been met if patients had pre-defined criteria of ≥10/24 for Total
Symptom Score (TSS:TNSS+TNNSS) and ≥6/12 for TNSS. Written informed
consent from all subjects and IRB approval were obtained. Results: There were
significant increases in both nasal and non-nasal symptom scores in 80% of
patients. Responses over the 4 visits were reproducible with some carry-over
effect as pre-EEC scores were higher on V3-V5 compared to V2. In V2, preEEC TSS was 0.5В±0.18 units with max TSS of 13.2В±0.90 (2.5 hr). During V3V5, pre-EEC TSS ranged between 2.5 to 3.8 with max TSS of 12.8В±0.99(V3),
14.1В±0.89(V4), and 14.0В±0.74(V5) units all at 2.5 hr of each visit. Similarly,
pre-EEC TNSS at V2 was 0.3В±0.11 units with max TNSS of 7.0В±0.45 units at
2.5 hours. The max TNSS was 6.6В±0.50(V3) at 2 hr with max TNSS of
7.1В±0.59(V4) and 7.4В±0.45(V5) units at 2.5 hr. Pre-EEC scores ranged from
1.5 to 2.3 units. The TNNSS were similar to TNSS but slightly lower. Pre-EEC
TNNSS were 0.2В±0.09 at V2 and ranged from 1.0 to 1.5 on subsequent days.
Maximum TNNSS were approximately 6.3 units(V2), 6.5В±0.52(V3),
7.0В±0.41(V4), and 6.6В±0.44(V5) at 2.5 hr. Conclusion: Dust Mite EEC clinical model is effective in evoking significant, reproducible levels of both nasal
and non-nasal symptoms in patients. The EEC model is a safe, well-controlled
environment which provides a robust clinical model to reliably and safely test
anti-perennial allergy therapeutics.
of TOSS reported at all timepoints was statistically significant compared to
baseline. The HNV did not respond to the NARC triggers. Conclusions: Ozone
induces greater ocular symptoms than CDA, suggesting air pollution is a significant trigger in environmental irritant induced NARC. The NARC EEC clinical model is effective in evoking significant ocular and nasal symptoms in
NARC patients but not HNV, and provides a safe, well-controlled environment in which to test putative NARC therapeutics.
N.W. Wilson*, V. Wong, K. Peele, S. Budhecha, V. Loffredo, M. Hogan,
Reno, NV.
H. Shirasaki*, E. Kanaizumi, N. Seki, T. Himi, Sapporo, Hokkaido, Japan.
Introduction: Currently, there is little data evaluating the use of a Water’s
View Sinus film in the diagnosis and treatment of chronic cough in children.
Furthermore, there is no data assessing the accuracy of interpretation of a film
by a pediatric allergy/immunology clinician versus a radiologist. Methods:
Patients aging 2 to 18 years were evaluated for chronic cough lasting over 3
weeks. All patients received a Water’s View Sinus film. Data of physical exam,
sinus film results, and clinical outcomes were categorized and all Fisher’s exact
tests and Chi-squared analyses were calculated using software.
The study was IRB exempt per institutional guidlelines. Results: 110 patients
met inclusion criteria with the clinician finding 68.2% had a positive Water’s
View film and the radiologist finding that 67.3% positive. There was no significant difference between the clinician’s reading of the Water’s View film and
the radiologist’s report. There were significant associations between patients
who had post-tussive emesis (p=0.0139) and additionally those with boggy
nasal exams (p=0.0262) and a positive film. Out of the 86 patients who followed up after treatment, 68.6% had no symptoms and/or Water’s View film
improvement or resolution. 72% of patients received antibiotics, and 61.3% of
these patients had resolution of symptoms and/or film improvement. Conclusions: A Water’s View Sinus film is necessary for the diagnosis and treatment
of chronic sinusitis in children age 2-18 years. Post-tussive emesis and boggy
nasal exams may help diagnose chronic sinusitis clinically. In this population,
pediatric allergy/immunology clinicians read Water’s View Sinus films as accurately as radiologists.
J.S. Lee*1, D. Wilson1, D. Patel1, P. D’Angelo1, J. Liu1, Y. Song1,
J.A. Bernstein2, D. Tsitoura3, R. Murdoch3, A. Salapatek1, 1. Mississauga,
ON, Canada; 2. Cincinnati, OH; 3. Stevenage, United Kingdom.
Background: While the NAR EEC clinical model has been previously
shown to evoke significant nasal symptoms, its effect on ocular symptoms is
unknown. The purpose of this study was to objectively assess ocular symptoms
evoked by Cold Dry Air (CDA)/simulated weather change and Ozone/simulated
environmental irritant in the NARC EEC. Method: Pure NARC patients with
≥1 yr history of NAR were exposed to CDA at Visit 2 (V2-60 min) and Ozone
at Visit 3 (V3-90 min) in the NARC EEC. At each visit, ocular symptoms [red,
itchy, watery eyes] were reported on diary cards using a 5-point scale (0-4:max
of 12) and Total Ocular Symptom Score (TOSS) [average of both eyes] collected. Patients with change from baseline of ≥4/12 in Total Nasal Symptom
Score [congestion, rhinorrhea, post-nasal drip] during V2 or V3 returned for
Visit 4 (V4) using the trigger which induced the greatest response (n=26/trigger).
Symptom scores were also collected from 10 Healthy Normal Volunteers (HNV)
at V2 and V3. Written informed consent from all subjects and IRB approval
were obtained. Results: Significant ocular symptoms were evoked by both
CDA and Ozone. Qualifying patients from V2 reported Mean Change from
Baseline (MCFB)В±SE of TOSS of 1.2В±0.30 at 10 min with 2.6В±0.42 and
3.1В±0.44 units at 30(mid) and 60(post) min, respectively. Repeat exposure to
CDA at V4 showed MCFB of TOSS of 0.8В±0.19(10 min), 2.0В±0.34(30 min)
and 2.7В±0.46(60 min) units. Greater TOSS response was observed with Ozone
during V3 with MCFB of 1.8В±0.40 at 20 min with increase to 3.0В±0.47 at 45
min(mid) and 4.3В±0.53 at 90 min(post). During V4 with Ozone, the MCFB of
TOSS was 1.1В±0.22 at 20 min, 2.8В±0.38 at 45 min(mid), and 3.6В±0.53 at 90
min(post). For both triggers, symptoms were slightly less during V4 than V2
or V3 which may reflect patient accommodation to repeat exposures. The MCFB
BACKGROUND: The cysteinyl leukotrienes (CysLT) are lipid mediators
that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate two classes of receptors named CysLT1
and CysLT2 receptor exist. The former is sensitive to the CysLT1R antagonist
currently used to treat asthma and allergic rhinitis. We have previously reported
the localization of CysLT1R by using immunohistochemistry and in situ
hybridization (Shirasaki et al. Clin Exp Allergy 32:1007-1012, 2002).Recent
studies have begun to uncover receptors selective for LTE4:P2Y12, an adenosine diphosphate receptor, and CysLTER, which was observed functionally in
skin of mice lacking the CysLT1R and CysLT2R. OBJECTIVE: To clarify the
expression of P2Y12 receptor in human nasal mucosa, we investigated P2Y12
receptor protein localization in human nasal mucosa by immunohistochemistry. METHODS: Human turbinates were obtained after turbinectomy from 6
patients with nasal obstruction refractory to medical therapy. To identify the
cells expressing P2Y12 receptor protein, immunostaining was performed using
anti-human P2Y12 receptor antibody. RESULTS: The immunohistochemical
studies revealed that anti-P2Y12 receptor antibody mainly labeled epithelial
cells and submucosal glands. CONCLUSIONS: The results suggest a primary
role for P2Y12 receptor as the LTE4 mediated-secretory responses in upper
respiratory tract.
M. Blaiss*1, J. Maloney2, H. Nolte2, S. Gawchik3, D. Skoner4, 1. Memphis,
TN; 2. Kenilworth, NJ; 3. Upland, PA; 4. Pittsburgh, PA.
Background: A number of immunological changes have been previously
reported in subjects undergoing specific immunotherapy, particularly changes
in allergen specific antibody responses. A phase 3, randomized trial was conducted to investigate the efficacy and tolerability of a new grass allergy
immunotherapy tablet (AIT) and its effects on IgG4 levels and IgE blocking
factor in North American children. Methods: IRB approval was obtained at all
sites and written informed consent obtained from subjects/legal guardians. 345
children (5-17 yrs) with grass pollen-induced allergic rhinoconjunctivitis were
randomized 1:1 to once-daily 2800 BAU grass AIT (oral lyophilisate, Phleum
pratense) or placebo (PBO) beginning approximately 16 weeks before and continuing through the 2009 grass pollen season (GPS). The primary efficacy endpoint was the total combined daily symptom and medication score (TCS).
Secondary endpoints were daily symptom score (DSS), daily medication score
(DMS), and the Pediatric or Adolescent Rhinoconjunctivitis Quality of Life
Questionnaires (RQLQ). Specific IgG4 levels and IgE-blocking factor were
measured before, during, and at the end of GPS. Safety was assessed by adverse
events (AEs). Results: The mean GPS lasted 43 days (mean grass pollen count
28 grains/m3). 89% of subjects were multisensitized. AIT treatment yielded
significant improvements relative to PBO in TCS (26%, P=0.001), DSS (25%,
P=0.004), DMS (66%, P=0.006), and RQLQ (18%, P=0.028). The effect of
grass AIT on IgG4 levels was significantly greater compared with PBO at peak
season (P<0.001) and increased through the end of GPS (P<0.001). Similarly,
the effect of grass AIT on IgE blocking factor was significantly greater compared with PBO at peak season (P<0.001) and was sustained through the end
of GPS. The majority of treatment-related AEs were local, application site reactions. Conclusions: We report the first successful phase III pediatric grass AIT
trial in North America. Once-daily administration of grass AIT is effective and
well-tolerated, representing a new therapeutic modality for children with grass
pollen–induced allergy. The effect of treatment on the immune system was confirmed by the changes in immunologic parameters, specifically increases in
specific IgG4 and IgE blocking factor.
H. Nolte*1, H. Nelson2, S. Durham3, M. Blaiss4, A. Bufe5, R. Dahl6,
1. Kenilworth, NJ; 2. Denver, CO; 3. London, United Kingdom; 4. Memphis, TN; 5. Bochum, Germany; 6. Aarhus, Denmark.
Background: The safety of sublingual allergen immunotherapy is of primary importance for its widespread use in clinical practice. Methods: Pooled
analyses of data from subjects with allergic rhinoconjunctivitis enrolled in 7
randomized, double-blind, placebo (PBO)-controlled trials (5 phase 2/3 adult;
2 phase 3 pediatric [aged 5–17y]) were conducted to evaluate the safety of oncedaily Timothy grass allergy immunotherapy tablet (AIT) (oral lyophilisate,
Phleum pratense, 2800 BAU). Data from adult and pediatric trials were pooled
separately. IRB approval and written informed consent from subjects or their
legal representation were obtained. Adverse events (AE) were monitored in all
trials. Results: In adult trials, 742/1060 (70%) of AIT subjects and 236/1036
(23%) of PBO subjects reported a treatment-related (TR) AE. In pediatric trials, 188/302 (62%) of AIT subjects and 80/296 (27%) of PBO subjects reported
TRAEs. The majority of TRAEs (≥96%) were mild or moderate. The most common TRAEs were oral pruritus, throat irritation, and ear pruritus in adults and
oral pruritus, throat irritation, and stomatitis (mild erythema) in children (Table).
TRAEs were generally transient local application site reactions. Local oropharynx AEs rarely led to premature discontinuation. The median days of onset for
local AEs were 1–5 days for adults and 1–7.5 days for children. The median
number of days local AEs were reported was 3.5–29.5 days for adults and
1.5–16.5 days for children. In adults, there were 5 investigator-assessed likely
systemic allergic reactions (4 mild, 1 moderate) to AIT treatment (0.01
events/subject-treatment year) and 1 AIT-related sponsor-assessed possible systemic reaction (severe diarrhea and mild hives under the tongue). In children,
there were no events diagnosed by investigators as likely systemic allergic reactions, but 4 AIT-related possible systemic reactions were observed based on
sponsor assessment (moderate dyspnea and swollen tongue; moderate urticaria;
moderate dyspnea with mild pruritus; mild flushing with moderate vomiting).
Conclusion: A pooled safety review of >2000 subjects in 7 trials supports the
overall good safety profile of daily Timothy grass AIT in adults and children
and did not reveal any new or unexpected safety concerns.
est tree pollination peaks to be shifted to a later time in 2009 versus 1999.The greatest peak concentrations of tree pollen 10 years ago were observed between April
16 and 19, a week before the peak days in 2009. Peak pollination for Birch was from
April 16 to 20 in 1999; for hornbeam was April 18 to 20; for oak was April 16 to
17; for ash was April 17 to 20; and for elm was April 13 to 17, while the greatest
peaks of pollination for each of these trees in 2009 were April 21 to 25. The shift
to later pollen peaks was exemplified well by hornbeam which had a first peak of
pollen from April 15 to 21 in 1999 versus April 21 to 28 in 2010. In general there
is more intense pollination seen in 2009 and 2010 versus 1999 and 2000.An exception to later pollination was maple which had peak pollination April 16 to 17 and
28 to 29 in 1999 versusApril 7, 18, and 20 to 21, in 2009 with reduction in the length
of the maple pollen season. This was also seen with alder which had peak pollination on April 13 and 23 with pollen seen throughout all May in 1999 versus peak
pollination on March 26, with high level concentrations of pollen rapidly seen with
conclusion of the pollen season by April, 15 2010. Conclusions: Over the past ten
years most trees have seen peak pollination shift to about 1 week later than in 2000
with a general trend towards more intense pollen seasons. Earlier pollination occurs
however for maple and alder. Tree pollen allergic symptoms may begin to occur
earlier and persist longer into the spring in Ukraine in the future likely related to
global climate changes.
A. Beigelman*, R.C. Strunk, M.W. Jaenicke, J.S. Stein, L.B. Bacharier,
St. Louis, MO.
AE=adverse event; AIT=allergy immunotherapy tablet
*Blanks indicated the AE was experienced in <5% of subjects.
Indicates mild erythema, not lesions or infection.
Introduction: Clinical guidelines recommend that children with FSIgE
≤2KIU/L to milk, egg, or peanut, or ≤5KIU/L to peanut without history of clinical reaction are appropriate candidates for an OFC to document oral tolerance to these foods. These cutoffs values have been shown to have a prediction
power of approximately 50% for a negative OFC. We aimed to validate these
cutoffs by determining the proportion of negative OFCs done in our clinics
based on these values, and to investigate whether demographics and atopic characteristics differ between children who had negative and positive OFCs. Methods: Retrospective chart review of all graded OFC done in our clinics over the
past 6 years. The same data were collected prospectively from patients enrolled
after April 2010. OFCs were performed when oral tolerance was suspected
based on lack of any clinical reaction to the suspected food within the preceding 12 months, and once the child’s FSIgE values met the above cutoff criteria. We excluded non graded OFCs, and OFCs in which the FSIgE was not done
by the ImmunoCAP method. If a child had multiple OFCs to the same food,
we evaluated only the first OFC. Washington University IRB approved the
study. Results: We collected data on 592 OFCs. 444 OFCs met entry criteria
for the study: 76 to milk, 170 to egg, and 198 to peanut. Median age at time of
OFC was 51 months. Sixty six percent of participants were males and 76%
were Caucasian. The proportions of negative OFCs were: 58% to milk, 42%
to egg, and 63% to peanut. Median FSIgE levels [KIU/L] were lower among
children who had negative challenges compared to children with positive challenges: milk: 0.49 vs. 0.8, p=0.019; egg: 0.17 vs. 0.88, p<0.001; peanut: 0.17
vs. 0.61, p=0.02. In addition, history of consumption of egg as an ingredient
(p<0.001) and non-white race (p=0.02) were more common in children with
negative vs. positive egg challenge. Conclusions: Selection of candidates for
OFC based on milk/egg/peanut FSIgE values of ≤2KIU/L (or ≤5KIU/L to peanut
without history of clinical reaction) identifies children with approximately 50%
probability demonstrating oral tolerance to these foods. Lower FSIgE values
(all foods), non white race (egg) and consumption of egg as an ingredient were
more common among children with negative OFC.
Table. Treatment-Related AEs Reported by ≥5% of Subjects in 7 Clinical
V. Rodinkova*1, O. Bilous1, L. Kremenska1, O. Palamarchuk1,
L.M. DuBuske2, 1. Vinnitsa, Ukraine; 2. Gardner, MA.
Background: The kinetics of tree pollination from 1999-2000 to 2009-2010
could provide insight into climate change in Ukraine, predicting future trends in
allergic respiratory diseases. Methods: Pollen counts from 1999-2000 years were
obtained by gravimetric sampling. Pollen collection in 2009 employed volumetric
methods using a Hurst Burkard trap. The 2009 study was conducted at Vinnitsa
National Pirogov Memorial Medical University in conjunction with the European
Aeroallergen Network (EAN). Results:There was a general tendency for the great-
T. Lupoli*, P. Dowling, J.M. Portnoy, C. Barnes, Kansas City, MO.
Over 7 million persons in the United States are allergic to shellfish including shrimp, crab and lobster. The most commonly recognized protein allergen
in these animals is tropomyosin. Many shellfish sensitive persons report symptoms in areas where shellfish is being cooked. To test for airborne shellfish protein the following studies were conducted. Common brown shrimp, Penaeus
aztecus, were obtained from a local food store. An enzyme immunoassay for
crustacean tropomyosin was obtained from bio Merieux. An Omni 3000 airborne sampler was obtained from Evogen Inc. Shrimp were prepared either
by boiling in water or frying in oil for periods up to 20 minutes in a well ventilated room. Airborne samples were taken for 10 minutes at 300 liters of air
per minute immediately adjacent to the cooking shrimp and 1 meter away from
the cooking shrimp. Airborne tropomyosin was measured to be 156 nanograms
per cubic meter immediately adjacent to boiling shrimp while samples 1 meter
away from boiling shrimp had airborne tropomyosin levels below 20 nanograms
per cubic meter. Airborne tropomyosin levels were also below 20 nanograms
per cubic meter when measured adjacent to frying shrimp and 1 meter distant
from frying shrimp. Water from boiling shrimp contained tropomyosin levels
greater than 500 nanograms per milliliter and oil remaining after frying shrimp
contained tropomyosin levels of 2.6 micrograms per milliliter. We conclude
that boiling shrimp releases shrimp tropomyosin into the air at measurable
concentrations. Airborne exposure to shrimp tropomyosin will vary with the
ventilation of the cooking area and the volume of air the cooking vapors diffuse into.
R. Johnson*, C. Barnes, P. Dowling, Kansas City, MO.
Introduction: Food allergy to peanut is a significant health problem and is
becoming more frequently discussed in the news media. Many patients and
families report allergic reactions to peanut despite not eating or having physical contact with peanuts. It is presumed that an allergic reaction may have
occurred from inhalation of airborne peanut allergens, but there is a paucity of
evidence to quantify the amount of airborne peanut proteins. Objective: The
purpose of this study is to detect the concentrations of airborne peanut proteins for various preparations and during specific uses. Methods: Separate Ara
h 1 and Ara h 2 monoclonal ELISA assays (Indoor Biotechnologies, Inc.), and
a polyclonal sandwich enzyme immunoassay (RIDASCREENВ®) for peanut
(R-Biopharm Inc.) were used to detect the amount of airborne peanut protein
collected using a Spincon 3000 air collector under different peanut preparation methods and situations. The different peanut preparations included: raw
peanuts, shelled roasted peanuts, unshelled roasted peanuts, an open jar of
peanut butter, refined peanut oil, unrefined peanut oil, and peanut flour. In addition, air was sampled under various situations to simulate real-life circumstances that included: boiling peanuts, removing roasted peanuts from their
shells, spreading peanut butter onto a slice of bread, and pouring peanut flour.
Positive controls were prepared using 100mg of roasted peanut flour in 10ml
of distilled water. Positive controls specific for the RIDASCREEN polyclonal
immunoassay were also prepared per its protocol. Air samples were measured
for each peanut preparation and scenario directly adjacent to the air collector
and at 1 meter from the air collector. Air sample controls were also performed
prior to each measurement sample. Results: Significant concentrations of Ara
h 1 and polyclonal peanut protein were detected when removing the shells of
roasted peanut. No Ara h 1, Ara h 2, or polyclonal peanut protein was measured above the lower limit of detection in all other peanut preparation samples.
Conclusion: Small amounts of airborne peanut proteins and very small amounts
of airborne Ara h 1 protein can be detected but was only measureable in the
circumstance of removing the shells from roasted peanut. Although, allergenic
peanut protein was able to be detected, the concentration of airborne peanut
protein that is necessary to elicit a clinical allergic reaction is unknown.
tionship of airborne Basidiospore concentrations and rainfall we conducted the
following studies. Methods: Airborne spores were collected daily from February to November for the years 1997 through 2009 using a Hirst style spore trap
located in the midst of the Kansas City metropolitan area. The collector was
mounted atop a 5 story building according to National Allergy Bureau guidelines. Slides containing spore collections were mounted in glycerin jelly containing 1% Calberlas stain for contrast. Slides were evaluated microscopically
every 4 hours for the presence of total Basidiospores. Basidiospores were not
differentiated into individual taxa. Spore counts were stored in an Access database and weather data was recorded on an Automated Weather Station. The
database was queried for the relationship between airborne basidiospores and
rainfall on the day of collection and rainfall on up to 20 days preceding collection. Analysis of nearly 4800 data points throughout the preceding 13 years
indicated a positive but weak correlation (.04) between basidiospore levels
and daily rainfall. When the correlation was extended to include rainfall for the
preceding 5 days the correlation increased (0.15). The correlation was best for
basidiospore levels and rainfall for the preceeding 15 days (0.30). Conclusion:
Airborne basidiospore levels in the Midwestern US are strongly correlated with
rainfall over an extended period of time.
J. Lieberman*, H.A. Sampson, New York, NY.
Introduction: Double-blind, placebo-controlled oral food challenges remain
the gold standard for diagnosis of food allergy. Since this procedure is costly,
time consuming and typically requires specialized centers and support staff, it
is not commonly used in outpatient practices. While the open food challenge
can produce false positive reactions, a negative challenge is considered to definitively rule-out allergy to the food administered. However there are little data
in the literature on open food challenge to support these contentions. Thus we
present our results on data obtained from the Jaffe Food Allergy Institute outpatient clinic. METHODS: We performed a retrospective medical records review
of all open oral food challenges performed in our outpatient center from January 1, 2009 through December 31, 2009. RESULTS: We performed 334 challenges on 276 patients. Median age was 5.5 years (8 months – 21.3 years) and
61.9% were male. Foods administered included peanut (19.5%), egg (18.3%),
tree nuts (12.3%), soy (9.05%), milk (8.1%), fish (7.2%), shellfish (5.1%),
wheat (4.5%), and others. Serum IgE levels ranged from <0.35 – 29.3 kUA/L
and mean skin prick test wheal diameters ranged from 0 – 12 mm. The majority of challenges, 253 (76%), were negative, while 73 (22%) were positive,
and 8 (2%) were indeterminate. Challenges to milk showed the highest rate of
reactivity with 37.0% of milk challenges resulting in a reaction, while shellfish had the lowest rate of reactivity (11.8%). Of the 184 challenges done on
patients with positive skin tests (mean wheal diameter 3 mm greater than saline
control), 136 (73.9%) were negative. Reactions were generally localized and
mild and treated with oral antihistamines. 7.2% of challenged patients experienced generalized hives, 1.5% experienced vomiting, and 0.9% experienced
wheezing. A total of 3 (0.9%) challenges resulted in the administration of epinephrine. CONCLUSIONS: The open food challenge is a safe and effective
diagnostic tool, which can be of great value in ruling out food allergy in patients
in the typical outpatient setting.
D.D. Crocker*1, D. Ownby1, S. Havstad2, 1. Augusta GA; 3. Detroit, MI.
S. Stanga*, C. Barnes, Kansas City, MO.
Rationale: The presence of airborne Basidiospores have been strongly linked
with asthma related Emergency Department visits. Elevations of airborne
Basidiospores also appear to be linked to rainfall events. To study the rela-
Background: Previous studies have shown that between 14%-84% of patients
sensitized to food allergens actually experience clinical symptoms when the
food is ingested. Most of these studies have been performed in selected populations from allergy clinics where there is a high suspicion for food allergy. The
percentage of patients sensitized to a food allergen that experience clinical
symptoms with food ingestion may be much lower in an unselected population-based sample. Objective: Evaluate relationship between food sensitization
and self-reported clinical symptoms to ingested foods in an unselected general
population. Methods: Adolescents who had been enrolled in the Detroit Childhood Allergy Study (CAS) birth cohort in 1987-1989 were contacted at age 18
years. Serum total and allergen-specific IgE levels to 4 common food allergens
(shrimp, egg, peanut, mild) were measured at age 18 years. Atopy was defined
as any specific IgE level >/=0.35 kU/L. Annual interview data at age 18 years
were used to determine self-reported food-related illness. Results: We obtained
specific IgE results and interviews on 428 of the 835 original CAS adolescents.
Three (3.7%) of the 81 adolescents sensitized to shrimp reported shrimp-related
illness, one (1.1%) of the 91 adolescents sensitized to peanut reported peanutrelated illness, zero (0%) of the 61 adolescents sensitized to egg reported eggrelated illness, and zero (0%) of the 86 adolescents sensitized to milk reported
milk-related illness. The odds of having a food-related illness in sensitized individuals were highest for shrimp [OR: 12.2 (1.3, 119.2)] followed by peanut
[OR: 5.3 (0.3, 84.8)]. The odds of food-related illness in those sensitized to egg
and milk were not calculable since no one reported food-related illness to these
foods. Conclusions: In an unselected population of adolescents, few individuals sensitized to foods reported actual food-related illnesses to those foods.
Individuals sensitized to shrimp and peanut had much higher odds of experiencing clinical symptoms that individuals sensitized to milk and eggs. Specific
IgEs should only be obtained when clinical suspicion for food allergy is high
and always correlated with clinical symptoms to avoid false positive results.
T.L. Hostetler*, S.G. Hostetler, B.L. Martin, Columbus, OH.
Introduction: Peanuts and tree nuts are common food allergens and are the
leading cause of fatalities from food-induced anaphylaxis. Dietary avoidance
is the primary management of these allergies and requires the ability to identify peanuts and/or tree nuts. This study investigated the ability of adults and
children to visually identify peanuts and tree nuts in common forms. Methods:
We obtained approval from the Behavioral/Social Sciences IRB and verbal
informed consent from all research subjects. A nut display was assembled that
held peanuts and 9 tree nuts in a total of 19 different forms. Persons 6 years or
older completed a worksheet to name the items. Responses were analyzed based
on demographics, presence or absence of food allergies, and occupational history. Results: 1105 subjects completed the study. The mean number of peanuts
and tree nuts identified by all subjects was 8.4 (44.2%) out of a possible 19.
The mean for children ages 6-18 was 4.6 (24.2%) compared with 11.1 (58.4%)
for adults older than 18 (p<0.001). Twenty-one (1.9%) correctly identified all
19 items. The most commonly identified items were peanut in the shell (94.7%)
and without the shell (80.5%). The least identified was hazelnut (filbert) in the
shell (16.1%) and without the shell (16.7%). Twenty-seven subjects (2.4%)
identified themselves as having a peanut or tree nut allergy; their mean number correct was 9.4 compared with 8.4 for those without such allergy (p=0.465).
Fifty percent of subjects with a peanut or tree nut allergy correctly identified
all forms of peanuts and/or tree nuts to which they are allergic. Twenty subjects were parents of children with a peanut or tree nut allergy. These parents’
mean number correct was 14 compared with 12 for parents of children without such allergy (p=0.081), and 73.3% of them correctly identified all forms
of peanuts and/or tree nuts to which their children are allergic. The mean number correct for subjects who have ever worked in childcare, food service, and
the medical field were 11, 11, and 12, respectively. Conclusion: Overall, both
children and adults are unreliable at visually identifying most nuts. This is independent of their peanut or tree nut allergy status or occupational history. Treatment of nut allergies with dietary avoidance should include education for both
adults and children on identification of peanuts and tree nuts.
C.A. Esteban*, R.B. Klein, S.K. Kopel, E.L. McQuaid, D. Koinis-Mitchell,
R. Seifer, A. Vasconcellos, G.K. Fritz, Providence, RI.
Introduction: Blomia tropicalis (BT) has been studied in island Puerto Rico,
but sensitization patterns of Puerto Rican children living in mainland US are
largely unknown. Even less is known about BT sensitization among Dominicans. Method: 604 children in Puerto Rico and Rhode Island between 7-16
years old, underwent skin prick testing for BT as part of a clinical evaluation
for asthma in a larger study. The sample was composed of 311 island Puerto
Ricans, 86 RI-Puerto Ricans (RI-PR), 105 RI-Dominicans (RI-DR), and 102
RI-Non-Latino Whites (RI-NLW). Results: More Island Puerto Ricans skintested positive for BT (51%) compared to RI-PR (35%), RI-DR (38%), and
RI-NLW (27%), П‡2= 21.8, p<.001. There were no significant differences among
the 3 groups in RI. Most children in the RI sample were born in the US (RIPR 85%, RI-DR 73%, and RI-NLW 99%). The proportions of US-born RIPR and RI-DR children were not significantly different. A positive BT skin
test result was not significantly associated with child’s country of birth, caregiver’s country of birth, or country where caregiver grew up. Both RI-PR and
RI-DR participants reported traveling outside the US mainland more often
than RI-NLWs (F=13.7, p<.001). There was a significant interaction between
frequency of travel outside the mainland US and BT positive skin test (F=4.6,
p<.05). Among RI-DR, BT positive participants reported more travel than
BT negative participants. The RI-PR sample had the opposite pattern: BT negative participants reported more travel compared to BT positive participants.
Conclusion: A surprising number of children in RI tested positive for BT,
despite the colder and drier climate in RI. Potential reasons for this finding
are: (1) cross-reactivity with other dust mites; (2) presence of BT in RI; and
(3) other travel within the US to areas where BT counts are higher (e.g., Florida,
Texas). Although participant recall of travel details was limited, our finding
regarding BT sensitization and travel among RI-PR was unexpected and
deserves further study. Prospective data of migratory patterns among Puerto
Ricans between island and mainland Puerto Rico are needed to determine time
of sensitization.
S.J. Fox*, M. Park, Rochester, MN.
Rationale: Penicillin skin testing (PST) has been shown in several large
studies to be an effective tool to determine penicillin allergy. Penicillin skin
test patterns have been described in adults indicating that a combination of the
major and minor determinants of penicillin will detect a majority of penicillin (PCN) allergic patients. We describe our clinical experience with penicillin skin test patterns in children. Methods: 778 children (less than 18 years)
with a history of PCN allergy were evaluated for PCN allergy by PST. Charts
were reviewed for basic demographic data and PST results. The PST skin test
panel included benzylpenicillin polylysine (PPL), penicillin G, and benzylpenicilloate. 685 of the 778 children were also tested with amoxicillin.
The concentration of amoxicillin used was 10-2M. Using the Fisher’s exact
test, we compared the differences in the proportion of children and adults positive to the various determinants of penicillin skin testing. P value ≤ 0.05 was
considered statistically significant. The IRB approved the study and all subjects signed a written informed consent. Results: 778 children underwent PST
and 367 (47.1%) were females. 703 (90.4%) of 778 patients had a negative
PST, 66 (8.5%) had a positive PST, and 9 (1.1%) had an equivocal PST. 31
(47%) of the 66 children that had a positive PST were positive to the PPL, 19
(29%) were positive to penicillin G, and 23 (35%) were positive to benzylpenicilloate. 62 of the 66 children with a positive PST were tested to amoxicillin, and 21 (34%) of these children were positive. Children were more likely
to be positive to amoxicillin (P=0.0441) compared to adults [9 (14%) of 64]
if they were also positive to another determinant. Children were also more
likely to be positive solely to amoxicillin (P=0.0326) when compared with
the adult population [2 (3%) of 64]. None of the other determinants were found
to be significantly different when comparing children and adults. Conclusions:
Children are more likely to be positive to amoxicillin on PST compared to
adults. Amoxicillin should be considered as part of the penicillin skin test
panel when testing children, and if included, there may be a better chance of
detecting penicillin allergy in this group.
Z.D. Jacobs*, H. Dai, C. Dinakar, Kansas City, MO.
INTRODUCTION: There have been no population studies quantifying total
IgE since the late 1970s. To gauge the temporal trend of age-related total IgE,
we analyzed a large cross-sectional United States population database, the
National Health and Nutrition Examination Survey (NHANES). We then compared the results to those of the Tucson Epidemiological Study (TES) (Barbee
et al. J Allergy Clin Immunol.1980;68:106-111), the most recent large-sample
analysis prior to this. METHODS: This analysis was IRB-exempt (public database; no personal identifiers). We analyzed continuous NHANES data for 20052006 from the public web-site. Since total IgE was heavily right skewed a logarithmic transformation was applied and summary statistics including geometric
mean, standard deviation, and 95% confidence interval were calculated. The
means of each group were compared using an unpaired t-test. RESULTS: A
total of 7398 NHANES and 2743 TES subjects were analyzed. The demographic
data are as follows (NHANES; TES): males (49%; 55%); 6-14 yrs (22%; 9%),
15-24 yrs (23%; 17%), 25-34 yrs (12%; 14%), 35-44 yrs (10%; 9%), 45-54
yrs (10%; 12%), 55-64 yrs (8%; 15%), 65-74 yrs (7%; 17%), over 75 yrs (both
7%) respectively. The total IgE for the population in the age-related groups
were as follows (NHANES; TES): 6-14 yrs (63.1 ku/L; 79.5 ku/L), 15-24 yrs
(66.1 ku/L: 53.1 ku/L), 25-34 yrs (47.9 ku/L: 36.4 ku/L), 35-44 yrs (51.3 ku/L:
34.1 ku/L), 45-54 yrs (46.8 ku/L: 28.2 ku/L), 55-64 yrs (53.7 ku/L: 21.6 ku/L),
65-74 yrs (S 47.9 ku/L: 20.8 ku/L) and 75+ yrs (S 39.9 ku/L: 17.1 ku/L) (see
figure). The two groups were well-matched for age and gender. While TES
initially had higher IgE, the NHANES IgE had a later peak and declined much
less with age. A comparison of the mean IgE between the two studies revealed
a highly statistically significant difference for each age group (p<0 .0001).
The same trends (p <0 .0001) were seen when male and female subgroups were
analyzed. CONCLUSION: The average IgE in both males and females has risen
significantly in the United States population compared to current reports in
standard reference texts. Particularly noteworthy is the doubling of IgE levels
in individuals over 55 years, and the more gradual decline in levels with increasing age. Possible reasons include increased allergic sensitization in our population or methodological changes in laboratory assessments of IgE.
M.L. Johnson*1, C.M. Webber2, E.G. Gonzalez-Reyes1, 1. Lackland AFB,
TX; 2. US Air Force Academy, CO.
INTRODUCTION: Allergy skin prick tests (SPT) are one of the primary
tools used by Allergists to confirm IgE-mediated sensitization. Interpretation
of results can vary depending on the skill of the reader, and subsequent visualization of SPT is not possible once wheal and flare formation resolves. This
study compares SPT results read by digital photography with those made by
direct visualization (used as the gold standard) and assesses consistency of
interpretation between interpreter groups. METHODS: An IRB-approved
prospective comparative study enrolled patients who were allergy skin tested
using a 49-allergen panel. SPT were assessed by direct visualization using a
semi-quantitative scoring method, with a positive test defined as a wheal ≥3mm
with surrounding flare. Digital photographs of the SPT were forwarded electronically to physicians in blinded fashion for interpretation using the same
scoring method. Photograph scores were compared with those from direct visualization and inter-rater reliability was analyzed using П‡2 test and Kappa statistic. RESULTS: A total of 258 individual skin prick digital data-point readings were performed and compared with the gold-standard. Positive and negative
score conversion was assessed and reported as sensitivity and specificity. Overall sensitivity of the digital photograph scoring was 77.3% and specificity was
89.6%. Interpreter group-specific readings for sensitivity was 90.9%, 54.5%,
and 86.4% for 1st-year fellows, 2nd-year fellows and staff, respectively while
specificities were 87.5%, 95.3% and 85.9% for 1st-year fellows, 2nd-year fellows, and staff, respectively. A significant difference in sensitivity was found
comparing 2nd- year fellows with 1st-year fellows and staff (p<0.007 and
p<0.02, respectively), but no significant difference was noted in specificity
among groups. Interrater reliability for the groups was found to be Kappa=0.69.
CONCLUSIONS: This study represents the first prospective evaluation of photographic allergy skin testing assessment. Preliminary findings suggest digital photographic interpretation may provide a reliable and objective means of
assessing aeroallergen skin testing with a high specificity, as well as permanent documentation of such results. Ongoing data collection and analysis will
further assess the validity of digital photographic interpretation of allergy skin
S.R. Durham*1, W. Emminger2, J.S. Andersen3, B. Riis3, H. Nolte4, R. Dahl5,
1. London, United Kingdom; 2. Vienna, Austria; 3. Horsholm, Denmark;
4. Kenilworth, NJ; 5. Aarhus, Denmark.
Background: The sustained efficacy 2 years after completion of 3 years
of treatment with the fast-dissolving SQ-standardized grass allergy immunotherapy tablet (AIT), Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU, ALK,
Denmark) was investigated in a randomized, double-blind, placebo-controlled
Phase III trial in Europe. The trial included adult subjects, with a history of
moderate to severe grass pollen allergy inadequately controlled by symptomatic medications. Methods: The analyses are based on the full analysis set
(with no imputation of missing data). 238 subjects completed 5 years of the
trial. Approval was obtained from the local ethics committees and written
informed consent was obtained from all subjects. Predefined secondary endpoints included 2 combined rhinoconjunctivitis symptom and medication scores:
1) weighted symptoms according to medication use and 2) sum of scores.
Results: The efficacy was sustained 2 years after end of treatment for both
combined scores. The treatment effect (reduction in combined score relative
to placebo) was significant (all p<0.001) and similar during the 3 treatment
years and 2 follow-up years (i.e. p=0.60 and p=0.15 for treatment*year interaction for weighted and sum combined score, respectively). The average treatment effect for all 5 years was 35% (CI [28%; 42%]) for the weighted and
33% (CI [27%; 39%]) for the sum combined score (Figure 1). The average
pollen seasons lasted 58-77 days over the 5 years. The small fluctuations in
treatment effect on the weighted combined score from year to year was highly
correlated to the cumulative pollen exposure at the beginning of the season (i.e.
the first 20 days) (r2=0.98). A sustained treatment effect was also found for
the immunological parameters. AIT was well-tolerated and no treatment-related
serious adverse events were reported over the entire 5 years of the trial. Conclusion: 2 years after completing a 3-year treatment period with the SQ-standardized grass AIT, a sustained, significant, disease-modifying effect was
observed. Over the 5 years of the trial, an average effect of 35% (CI [28%;
42%]) for the weighted and 33% (CI [27%; 39%]) for the sum combined score
was found. The trial was the first large-scale, placebo-controlled trial showing
long-term disease modification after grass AIT treatment.
Figure 1: Efficacy of grass AIT; weighted (б­№) and sum (б­є) combined scores
for treatment years (TY), follow-up years (FY) and all years together (All)
C. Santos*, N. Reshamwala, S. Vissamsetti, J. Galant, R. Swami, K. Nadeau,
Palo Alto, CA.
BACKGROUND: Allergic rhinoconjunctivitis (AR) is a prevalent disease
with significant morbidity. Most AR treatment provides symptomatic relief,
while allergy immunotherapy effectively modulates disease course. Sublingual
immunotherapy (SLIT) decreases symptom scores and medication use. Most
SLIT studies have investigated the use of one allergen. We sought to evaluate
the safety of dual allergen SLIT in patients with Dermatophagoides farinae
(DF) and Timothy Grass (TG) sensitivity. METHODS: This is a randomized
double-blind placebo-controlled study in subjects with DF and TG allergy based
on skin prick test. At the preliminary dosing visit subjects received escalating
doses of SLIT to a maximum dose (2,800 DF AU; 28,000 TG BAU). During
the treatment course this dose was self-administered daily for 1 year, with follow up every 3 months. Adverse events were documented using the National
Institute of Allergy and Infectious Diseases Grading Scales and were assigned
event severity and relationship to study drug. RESULTS: Thirty subjects, age
5-57 years, were enrolled. During the preliminary dosing visit, 16/30 (53%)
subjects experienced adverse events, most commonly mild-moderate
mouth/throat itching in 14/30 (47%) subjects and mild itchy nose/rhinorrhea
in 8/30 (27%) subjects. One subject experienced uvula swelling that resolved
with Benadryl and epinephrine, and he withdrew from the study. In the treatment course, 16/30 (53%) subjects had adverse events, most commonly mildmoderate mouth/throat itching in 7/30 (23%) subjects. One subject, after tolerating 3 months of daily doses, had an episode of dyspnea and hypotension
12 hours after her last dose. The event was concluded less likely related to the
study drug. She continued to receive daily SLIT with no reactions. DISCUSSION: Preliminary data on subjects who received placebo or SLIT shows that
most tolerated treatment well, as most reactions were mild-moderate site-related
events. One event was a severe local reaction but was not systemic in nature.
The other was deemed less likely related to the study drug given that the subject tolerated subsequent doses with no untoward events. We will further stratify our results once subjects are divided into placebo and active treatment groups.
To date, our data reveals that dual allergen SLIT therapy is a safe modality of
treatment for AR.
W. Smits*1, J.T. Inglefield2, R.V. Maples1, R.K. Holley1, J.A. Hamm1, 1.
Fort Wayne, IN; 2. Hickory, NC.
Conventional immunotherapy is effective in the treatment of allergic rhinitis, allergic asthma, and chronic rhinosinusitus. Rapid desensitization (rush
immunotherapy, rapid allergen vaccination) offers advantages of faster efficacy, improved compliance, and cost effectiveness. While premedication with
corticosteroids and antihistamines substantially reduces the incidence of systemic reactions, safety remains the primary concern for this procedure. Two
separate half-day schedules with minor differences were used to rapidly desensitize 2804 patients in two outpatient settings equipped to treat anaphylaxis.
Of these patients 1146 were male (41%) and 1658 were female (59%) with
age ranging from 1.7 to 77 years. All patients exhibited positive subcutaneous
skin tests to perennial and/or seasonal allergens. 1708 patients were premedicated with prednisone (60 mg daily for adults, 2 mg/kg daily for children) and
H1 antihistamine, cetirizine, fexofenadine, or loratidine, for three days. 1103
patients received a three day premedication regimen of prednisone, identical
H1 medication, but also utilizing the H2 antagonists ranitidine, famotidine, or
cimetidine. The final dose of both protocols ranged from 0.1 to 0.5 cc of a
1:1000 dilution of extracts manufactured by ALK and Greer Laboratories.
Patients then continued onto higher doses by resuming a conventional schedule. Diagnoses included allergic rhinitis (2688/95.9%), allergic asthma
(1397/49.8%), and chronic rhinosinusitus (1393/49.7%). All patients were
offered traditional immunotherapy and signed consent forms noting potential
risks prior to the procedure under IRB approval. Seventy patients (2.5%) experienced a mild systemic reaction. One patient (<.001%) experienced true anaphylaxis. This is an improvement over previously reported reaction rates. All
patients responded to subcutaneous epinephrine and/or nebulized albuterol and
were sent home after an observation period. Our experience with rapid desensitization confirms that maintenance immunotherapy can be reached quickly,
safely, and effectively under careful supervision. However, caution must be
exercised when using this procedure as anaphylaxis does occur. Finally, systemic reactions with rapid desensitization occur less frequently than previously
described in the literature when using premedication combined with a lower
targeted final dose.
M.A. Rank*, J.H. Butterfield, Rochester, MN.
Introduction: New strategies for preventing systemic reactions to subcutaneous allergen immunotherapy (SCIT) could improve the safety profile of an
effective, underutilized therapy. Methods: We performed a pilot study that
prospectively enrolled patients with systemic and large local reactions (SRs
and LLRs) to SCIT. A serum sample and 24 hour urine sample was obtained
for each patient beginning immediately after the SR or LLR and 4-6 weeks later
when the patients were asymptomatic (convalescent sample). Serum tryptase
and urine N-methylhistamine, 11-ОІ-prostaglandin F2-О±, and LTE4 levels were
measured and compared between acute and convalescent samples. Approval
was obtained from the IRB and written informed consent obtained from all
patients enrolled in the study. Results: A total of 8 patients were enrolled (5
with SR and 3 with LLR). Serum tryptase and 24 hour urine collections for Nmethylhistamine were within normal limits for all patients except for 1 SR
patient, who had an elevated level in both acute and convalescent samples. Urine
collections for 11-ОІ-prostaglandin F2-О± were elevated in 3/5 patients with acute
SRs and 1/5 of convalescent samples from these same patients (mean levels
767 pg/mg creatinine versus 579 pg/mg creatinine). LTE4 was detected in 2/5
acute SR samples and 3/5 of convalescent samples from these same patients,
with mean levels (of those detected) 71 pg/mg creatinine and 59 pg/mg creatinine, respectively. One patient with an acute LLR had an elevated 11-ОІprostaglandin F2-О±; all other mediators tested in patients with LLR were within
normal limits. Conclusions: Prostaglandins may play an important role in mediating symptoms of systemic reactions to allergen immunotherapy. Future studies are recommended to determine if baseline prostaglandin levels can predict
SRs or if interventions that block prostaglandin formation can prevent SRs to
J. Wisniewski*, P. Heymann, J. Woodfolk, Charlottesville, VA.
Rationale: We and others have reported expansion of circulating CD25hi
T cells in the blood of highly atopic patients with severe AD; however, it remains
unclear whether these cells constitute effector or regulatory T cells, or else a
mixture of both cell types. The objective was to examine the relationship between
specific IgE and T cell proliferative responses to an array of allergens, and to
assess the phenotype of responding cells in severe disease. Methods: PBMCs
were isolated from an 11 year old boy with severe recalcitrant early-onset atopic
dermatitis (AD)(SCORAD=84, total IgE=34,241). Cells were stimulated with
different allergens (20µg/well) selected according to the patient’s sensitization
profile and clinical history of reactivity on exposure. Allergens tested included
egg (Gal d 1), peanut (Ara h 2), shrimp (tropomyosin), dust mite (Der p 1),
and grass pollen (Phl p 2). Proliferation was measured by [3H] thymidine incorporation and cells were analyzed for expression of surface markers (CD25,
CD45RO, CCR4 and CLA) by flow cytometry (day 7). Results: Maximal proliferative responses were observed for PBMCs stimulated with Ara h 2 (stimulation index (SI)=35Г—103) while Gal d 1 induced the weakest response
(SI=5Г—103). Interestingly, specific IgE ab titers for these two allergens were
markedly discordant (Table 1). Proliferative responses were also readily detected
for Der p 1, Phl p 2 and shrimp tropomyosin (SI=5Г—103, 10Г—103 and 7Г—103,
respectively)(Table 1). The frequency of Ara h 2-stimulated CD4+ T cells that
were CD25hiCCR4+ was 20% as compared with ≤10% for all other allergens .
Regardless of the type of allergen, CD25hiCCR4+ T cells, but not
CD25negCCR4neg T cells, maintained high expression of the skin-homing marker
CLA, and CD45RO. These findings coincided with successful introduction of
egg into the patient’s diet. Conclusion: The capacity for allergen to expand
CD25hiCCR4+ T cells with skin-homing capabilities may be linked to atopic
status. These findings support the view that allergen exposure contributes to T
cell-driven inflammation in the skin of AD patients.
S. Boos Regan*, D. Khan, Dallas, TX.
Rationale: Chronic urticaria (CU) causes significant morbidity. Many
patients do not achieve adequate control with conventional antihistamine therapy; others require long term corticosteroids, with significant adverse effects.
Numerous alternatives have been used including calcineurin inhibitors, primarily cyclosporine. We sought to determine the safety and effectiveness of the
calcineurin inhibitor tacrolimus. Methods: A retrospective chart review was
conducted of adult CU patients who were treated with tacrolimus in our allergy
clinic. Laboratory values and clinical evidence for toxicity were abstracted as
well as physician reports of efficacy. Results: Twenty-four adults with CU treated
with tacrolimus were identified. All patients were refractory to both 1st and
2nd generation antihistamines, and 54% were on daily prednisone (mean dose
of 23mg/day). Eighty-three percent had failed alternative medications, including montelukast, sulfasalazine, dapsone, hydroxychloroquine, colchicine and
thyroxine. Mean duration of symptoms prior to starting tacrolimus was approximately 6 years. Tacrolimus dosing ranged from 1mg-8mg/day. Nineteen patients
(79%) improved with tacrolimus, most within 1 month. Sixty-two percent were
able to discontinue daily prednisone, and 23% were able to decrease Prednisone
dose by >50%. Fourteen of twenty-four reported adverse effects, most commonly gastrointestinal symptoms or dysesthesias. Three had elevated creatinine levels. Three discontinued tacrolimus because of adverse effects. Three
patients required a second course of tacrolimus due to recurrent CU, and 2
achieved remission with this second course. Conclusions: Tacrolimus appears
to be an effective alternative agent for management of refractory chronic
urticaria patients. While adverse effects were common, most were benign and
dose related.
G.N. Drannik*1, A.I. Kurchenko1, L.T. Aliyeva1, L.M. DuBuske2, 1. Kiev,
Ukraine; 2. Gardner, MA.
Background: Psoriasis is a chronic dermatologic with skin lesions infiltrated by activated T-cells. Staphylococcal superantigens from the oral cavity
of periodontitis patients may influence T-cell activation in psoriasis patients.
Methods: Venous blood was obtained from 10 patients with psoriasis and generalized periodontitis, from 5 patients with generalized periodontitis and from
5 healthy subjects. Staphylococcal toxin was used to induce cytokine (IFN-Оі,
TGF-ОІ, IL-10) release after 24 hours of peripheral blood mononuclear cell
(PBMC) culture. IFN-Оі, TGF-ОІ and IL-10 in the culture supernatants were
determined by ELISA. As a positive control the effects of the polyclonal lymphocyte stimulator FGA was assessed on cytokine production in PBMC cultures. Results: The greatest amount of IFN-Оі, TGF-ОІ and IL-10 was induced
by Staphylococcal toxin in PBMC cultures of patients with both psoriasis and
generalized periodontitis (IFN-Оі = 192В±20; TGF-ОІ = 149В±31; and IL-10 =
255В±63) compared with healthy controls (IFN-Оі = 40В±3; TGF-ОІ = 62В±5; and
IL-10 = 53В±7) while PBMC cultures from patients with generalized periodontitis
alone had intermediate levels of these cytokines (IFN-Оі = 107В±12; TGF-ОІ =
104В±14; and IL-10 = 82В±16). Conclusion: Staphylococcal infection in the oral
cavity may be a factor in the pathogenesis of psoriasis related to stimulation of
inflammatory cells by Staphylococcal superantigens.
Table 1: Serum IgE, T cell surface marker frequency, and proliferation results
in response to specific allergen stimulation. %CLA and %CD45RO denote
frequencies of CLA+ and CD45RO+ cells within the CD4+ CD25hi CCR4+
M. Eisenfeld*, A. Rubinstein, Bronx, NY.
Introduction: Chronic urticaria (CU) is defined as the presence of hives
for longer than 6 weeks. To differentiate between idiopathic and autoimmune
causes, a CU Index may be performed. If elevated on exposure of the patient’s
serum to donor basophils, it signifies the presence of an autoantibody directed
against IgE, FcОµRI, or FcОµRII (CD23), or the presence of histamine releasing
factors. When an autoimmune basis has been established, successful treatment
with first-line agents such as antihistamines and corticosteroids often proves
to be a challenge. Methods: We followed a 20-year-old patient with severe
chronic autoimmune urticaria (CAU) over a period of 4 years. Results: The
patient had a 4 year history of debilitating CAU, occurring 4 to 5 times per
week, which was unresponsive to multiple antihistamines and low-dose corticosteroids. Labwork revealed a CU Index of 12.7 (Reference Range <10), CRP
elevation to 4.1 mg/dL, and an IgE of 299 kU/L. An autologous serum skin
test could not be performed due to daily antihistamine use. He was placed on
hydroxychloroquine 200 mg twice a day with little benefit. A trial of 4 doses
of intravenous gammaglobulin, 500 mg/kg, was infused every 3 weeks, which
resulted in a 4-6 day asymptomatic period following each infusion. The patient
had improvement in pruritis but had persistent urticaria for the 3 months following the last infusion, and still required low-dose prednisone, hydroxychloroquine, and multiple daily antihistamines. Urticarial vasculitis was
excluded by a punch biopsy, which demonstrated numerous eosinophils consistent with autoimmune urticaria. The CU Index was repeated, and remained
elevated to 13.7. The patient eventually received 300 mg of omalizumab, the
humanized monoclonal anti-IgE antibody, and within 3 days post-injection, he
became free of hives. The effect lasted for 3 months, without the concomitant
use of any other medications. He then received a second dose of omalizumab
and an identical response was noted, with the symptom-free interval lasting 7
weeks off of all other medications. Conclusion: Omalizumab decreases the level
of circulating IgE and also down-regulates FcОµRI expression on basophils. It
may be an optimal alternative treatment for CAU because it can prevent basophil
histamine release by decreasing available binding sites for autoantibodies against
ure). Tonsils were visible and small lymph nodes were palpable. Lungs were
clear to auscultation and heart sounds were normal. Our initial diagnosis was
tinea corporis, and griseofulvin was prescribed. Laboratory studies revealed
normal CBC, electrolytes, liver enzymes, and IgE level (11 IU/mL). He had
positive ANA, anti-Ro, anti-La, and anti-Sm antibodies, but negative antidsDNA, anti-Scl 70, anti-RNP, RPR, and RF. Neonatal lupus erythematosus
was considered and treatment with griseofulvin was discontinued after 2 days.
EKG was normal. Though the mother had no symptoms or signs suggestive of
SLE, her serum showed positive ANA, RF, anti-Ro and anti-La antibodies, but
negative anti-Sm, anti-dsDNA, anti-RNP, and anti-Scl 70. She was referred to
rheumatology, particularly since her sister has SLE. We believe the infant probably has cutaneous lupus secondary to transplacental transfer of maternal IgG
antibodies. While the mother is being evaluated, the course of the infant’s rash
and lab tests are being followed. Conclusion: Neonatal lupus occurs in about
half of newborns of mothers with SLE, and can be associated with systemic
manifestations, including heart block in up to 10% of cases. When limited to
the skin, the rash can be misdiagnosed, particularly in the absence of maternal
symptoms of SLE. With the decline in the antibody level, the rash usually disappears within 6-8 months.
G. Gurka*, Arlington, MA.
There are many causes of chronic urticaria. Viral illness and vaccination to
viral antigens have both been associated with acute hives/angioedema and may
play a role in chronic urticaria. Our staff noticed an increase in demand for
allergy evaluation for hives during the past influenza season. The 2009-2010
influenza season was complicated by the discovery of a new novel H1N1
influenza virus which originated in mexico. During this season, our new patient
volume experienced a 30% increase in requests for allergy evaluation regarding chronic hives (daily hives for at least 6 weeks). We evaluated 135 patients
with these complaints in a six month period. Several of these patients (seven)
noted a temporal association between their hives and vaccination with the novel
H1N1 virus preparation. In our referral network over 10,000 vaccinations for
the novel H1N1 virus were administered. Later in the season, several other
patients (three) presented who had experienced hives which began following
the clinical diagnosis of active influenza due to the novel H1N1 virus. Approval
was obtained from the hospital IRB and oral consent was obtained from all
research subjects. Allergy evaluation of these individuals found no atopy.
Immunologic evaluation in selected subjects revealed the presence of expanded
CD56 NkT cells (in five) and Influenza A specific high titre IgG (in six). Paired
controls seen for non-hive related complaints did not have these findings. In
these subjects, their chronic hives responded partially to oral antihistamines;
and oral steroids were not needed. Over several months (8 to 25 weeks), each
individual had resolution of their symptoms, and none need treatment for hives
at this time. repeat immune studies in a subgroup of these patients at the time
of follow-up revealed return of blood levels to normal. The novel H1N1 virus
and the vaccination for this virus can cotribute to the development of chronic
urticaria. Immunologic, rather than atopic etiologies can play a role in these
episodes of hives.
A. Kounavis*1, M. Tan2, S.L. Bahna1, 1. Shreveport, LA; 2. Alexandria, LA.
Introduction: Rashes in the neonatal period are usually benign, but occasionally may be a sign of serious disease. We present an infant with an unusual
rash. Case description: A 3-month-old African-American male was referred to
our clinic for a rash since 2 weeks of age. It started as small annular lesions
that continued to enlarge despite hydrocortisone 2.5% ointment. He was the
product of a normal full-term pregnancy and delivery. His mother was 28-yearsold with asthma, eczema, and possible food allergy. On physical examination,
the infant was playful and normally active. There was a scaly erythematous
annular rash on his trunk in patches 5-13 cm, with active serrated edges (Fig-
J. Posthumus*1, A. TiГ±ana2, J. Mozena1, J. Steinke1, L. Borish1, 1. Charlottesville, VA; 2. Galveston, TX.
Introduction: A significant proportion of CIU patients are believed to have
auto-antibodies that induce mast cell degranulation. Using a novel immortalized
human connective tissue mast cell line displaying high concentrations of FcОµRI
(LUVA cells), we proposed that 1) serum derived from patients with CIU would
activate the LUVA cells to produce prostaglandin D2 (PgD2) and 2) this activation
would correlate with autoimmune markers, including the autologous serum skin
test (ASST), anti-FcεRIα antibodies and Hashimoto’s thyroiditis. Methods: CIU
subjects (n=16) and controls with no history of hives (n=16) were enrolled and written informed consent was obtained under a protocol approved by the University of
Virginia IRB. Subjects were diagnosed with CIU based on the presence of urticaria
of greater than 6 weeks duration and with hives present at least 3 days per week.
Serum was assayed for anti-thyroid antibodies, FcОµRIО± antibodies, and the ASST
was performed. LUVA cells were incubated with sera and PgD2, cysteinyl
leukotrienes (CysLTs), and histamine levels were measured by enzyme-linked
immunoassay. Sera from both groups were also directly assayed for PgD2, CysLTs,
and histamine without incubation with the LUVA cells. Results: PgD2 secretion
was significantly increased after incubation of serum with LUVA cells in the CIU
group (363.3 pg/mLВ±33.6 N=14), but not in the controls (243.5 pg/mLВ±25.2 N=14;
p=0.008). Further increases in PgD2 were seen after overnight incubation of the
LUVA cells with IgE, reflecting upregulation of the IgE receptor. Surprisingly, there
was no association between the capacity of serum to induce PgD2 and the presence
of either a positive ASST (p= 0.699); or the anti-FcОµRIО± antibodies (p= 0.839); or
thyroid antibodies (p=0.949). Serum without LUVA cell incubation was devoid of
histamine and PgD2 but demonstrated expression of CysLTs, which did correlate
to theASST (p=0.03) and anti-FcОµRIО± antibodies (p=0.04). Conclusion:The serum
of CIU but not control patients increased prostaglandin D2 production by LUVA
cells. The LUVA cell activation and production of PgD2 by CIU sera was not correlated with the presence of anti-thyroid antibodies, FcОµRIО± antibody, or a positive
ASST. In contrast, serum CysLTs were correlated with the ASST and anti-FcОµRIО±
antibodies suggestive of basophil activation.
S. Spector4, S. Saini1, K.E. Rosen2, H. Hsieh2, M. Parsey2, D. Wong2,
E. Connor2, A. Kaplan*3, M. Maurer5, 1. Baltimore, MD; 2. San Francisco,
CA; 3. Charleston, SC; 4. Los Angeles, CA; 5. Berlin, Germany.
Introduction: Omalizumab (OMA) binds to IgE and is indicated in the US
for patients ≥12 years with moderate to severe persistent allergic asthma. Patients
with chronic idiopathic urticaria (CIU) who remain symptomatic despite H1
antihistamine therapy were treated with either placebo (PBO) or OMA. Methods: Ninety patients in the US (12-75 years) or Germany (18-75 years), with
a weekly urticaria activity score (UAS7) ≥12 despite concomitant H1 antihistamine therapy were enrolled. The UAS7 is a composite score including both
itch severity (0-3 point scale) and number of hives (0-3 point scale) that is
recorded daily for 1 week (max score = 42). PBO or a single 75, 300, or 600mg
dose of OMA was added to existing H1 antihistamine in a 1:1:1:1 ratio. The
primary endpoint was mean change from baseline in UAS7 score at week 4.
Key secondary endpoints included mean change from baseline in weekly itch
and hive scores. Written informed consent was obtained for all participants
after ethics committee approvals. Results: Mean (SD) UAS7 scores at baseline
were: 28.2 (7.5), weekly itch: 13.2 (3.7) and weekly hives: 15.0 (5.1). Patients
required 4.9 (6.4) daily doses of H1 antihistamine and mean (SD) pre-dose
IgE levels were 215.3 (431.6 IU/mL). Ninety percent of patients completed 4
weeks on the study. At week 4, the OMA 300-mg (n=25) and 600-mg groups
(n=21) showed significantly greater improvement than PBO (n=21) in UAS7;
the differences were statistically significant at P = 0.0003 and P = 0.0473 respectively. Similar results were seen for weekly hive and itch scores. No correlation was found between efficacy and baseline serum IgE or patients’ body
weight. A rapid onset of effect was seen, with the OMA 300-mg group having
a 13.2 point (mean) decrease from baseline in UAS7 at week 1. The rate of
AEs across groups was similar and no serious AEs were observed in any group
during the first 4 weeks of the study. Conclusions: A single dose of OMA 300
or 600mg was well tolerated and significantly reduced the UAS7 score at week
4 in patients with CIU who remain symptomatic despite concomitant H1 antihistamine therapy. A rapid onset of effect was observed with OMA therapy and
efficacy did not appear to correlate with baseline IgE or body weight.
NOVEMBER 13-14, 2010
PHOENIX convention center
Adverse Food and Drug Reactions
Aerobiology, Allergens, Allergen Extracts
Allergy Testing, Clinical Laboratory Immunology
Asthma & Other Lower Airway Disorders
Basic Science Allergy and Immunology
Clinical Case Reports
Clinical Immunology, Immunodeficiency
Food Allergy
Immunotherapy, Immunizations
Pharmacology and Pharmacotherapeutics
Rhinitis, Other Upper Airway and
Ocular Disorders
Skin Disorders
R. Arora*, C. Maddox, El Paso, TX.
A. Gaye1, M. Girdhar*2, 1. Chicago, IL; 2. Maywood, IL.
Background: Exanthemous rashes are the most frequent of all cutaneous
drug reactions. Despite being a common manifestation of drug reactions, exanthems due to acetaminophen are rarely reported. Methods: A 30-year-old female
presented for an evaluation for possible acetaminophen allergy. The patient
reported having two episodes of an urticarial-sounding rash developing several
hours after taking oral acetaminophen in childhood. She had strictly avoided
acetaminophen since childhood. The patient tolerated non-steroidal anti-inflammatory drugs. She was actively trying to become pregnant and desired to have
acetaminophen as a pain medication option. Results: The patient was given
acetaminophen orally every 30 minutes at the following doses (in mg): 50, 100,
200, 325 and 650. She was monitored for one hour after the final dose and had
no evidence of an immediate systemic reaction. However, about 3 hours after
the last dose, the patient noted the onset of a non-urticarial, erythematous, maculopapular eruption that was symmetric, well-demarcated and present on the
bilateral breasts only in regions of skin contact with her bra. She had no evidence of anaphylaxis. The following day, the rash on her breasts was unchanged
but she had developed a similar eruption in the anterior pelvic region at her
panty-line. This was also only present in the area of skin contact with her undergarment. The rash resolved within 4 days with topical steroid and oral antihistamine therapy. To confirm that the eruption was truly from acetaminophen,
the open oral drug challenge was repeated 4 weeks later. The same maculopapular exanthem on the bilateral breasts underlying the bra developed 20
minutes after the 325mg dose. The challenge was stopped at this point. The
patient did not develop any other symptoms. The following day, she had the
same symmetric eruption involving the bilateral breasts and anterior pelvis only
in regions covered by her undergarments. A punch biopsy was obtained from
the right breast and tissue examination revealed spongiotic dermatitis and
perivascular lymphocytic infiltrates with eosinophils consistent with an exanthemous drug eruption. Conclusion: We report an unusual case of a drug induced
exanthem due to acetaminophen and speculate that the exanthem had a pressure-induced component, occurring only in thinner skinned areas which had
pressure applied from the patient’s undergarments.
W. Chin*, A.A. White, D.D. Stevenson, San Diego, CA.
Approximately 15% of patients that undergo aspirin desensitization have
no reaction during the procedure; what would be considered a negative challenge. These patients have been instructed to try aspirin therapy for 1-3 months
to see if they would benefit from treatment. A number of patients in this situation report that aspirin therapy has been successful. These patients would
represent “silent desensitizations”. We report such a case of “silent desensitization”. Methods: The patient underwent two desensitization procedures 18
months apart. Both protocols were identical in that they were initiated by a
nasal ketorolac challenge followed by a modified aspirin challenge with doses
of 60mg, 60mg, 150mg and 325mg. Both desensitizations were pretreated identically, including the use of montelukast. Data A 37 year old male with nasal
polyposis, chronic sinusitis, and asthma, presented after a classical reaction to
Excedrin. Aspirin desensitization was performed in January 2009, during which
he had absolutely no symptoms. This was interpreted as a negative challenge/desensitization. He remained on daily aspirin and on two follow up visits reporting benefits from aspirin therapy; improved sense of smell, decreased
nasal congestion, and was able to taper his prednisone dose to 10mg every three
days. Subsequently, the patient underwent sinus surgery and was instructed to
stop his aspirin therapy in January 2010. Several months later the patient took
400mg of Aleve and within an hour developed progressive asthma symptoms
requiring hospitalization and intubation for 3 days. During his second aspirin
desensitization, he developed a classical reaction with nasal ocular reactions
and a 27% drop in FEV1 after nasal ketorolac. After treatment he successfully
completed the aspirin desensitization protocol without further adverse reactions. Conclusion There has been a suspicion that silent desensitization to aspirin
can occur. This is an important consideration in a patient with a strong history
of reactions to multiple cyclo-oxygenase 1 inhibitors who had no reaction during desensitization. These patients may obtain benefit from continued ASA
therapy. Also, in rare cases such as the patient described above, cessation of
aspirin therapy followed by re-challenge could lead to another reaction.
Rationale: Raising awareness of adverse reaction to egg-based folk remedies Methods: Report of a case and review of the literature Results: A 2 y/o
atopic boy presented to the emergency room (ED) with respiratory distress
and generalized urticaria. First and second degree burns on his forearm involved
1.5% of his body surface. Mother stated that he had spilled her cup of hot tea
while playing in the kitchen. She had quickly applied fresh egg white on his
burn, a customary practice in her family. He soon developed a full body rash
and began to have difficulty breathing. She administered Epi-pen and took him
to the ED. She reported that although he was kept on a diet free of egg products for his known allergy, she did not realize that he could react to their skin
contact. Children ages 5 and younger sustain the majority of the 120,000 pediatric burn injuries requiring emergency care and treatment each year in the
USA. The prevalence of food allergies is estimated at 6% in children under the
age of 3 years, and of egg allergy at near 2.6% in the general pediatric population. Five major proteins of hen egg are recognized as responsible for IgEmediated reactions. Most of these proteins are found in raw egg white: ovomucoid, ovalbumin, ovotransferrin, lysozyme, and ovomucin. Ovomucoid is
the most allergenic protein, and ovalbumin is the most abundant. Most children allergic to egg react within 30 minutes of ingestion with cutaneous (85%),
gastrointestinal (60%), and respiratory (40%) symptoms. A similar generalized
reaction may result from a rapid absorption of intact dietary allergen trough a
disrupted and inflamed skin barrier. Applying a kitchen staple such as fresh
egg white as a “natural” first aid treatment for minor burns is a traditional
remedy in conservative cultures. The practice is becoming more common, as
recommended in many home-remedy manuals and promoted by many blogs
and websites. Conclusions: Ingestion of a dietary allergen is the most common cause of a severe reaction. Given that egg allergy is common in the pediatric population, that most burns affecting children happen in the kitchen, and
that care takers may receive erroneous information from various sources, it
behooves the pediatrician and the allergist of an egg-sensitive child to review
with the family the proper handling of burns, stressing abstaining from using
egg white as a remedy, as the practice may induce anaphylaxis.
A. Gaye*1, R. Shah2, 1. Chicago, IL; 2. Maywood, IL.
Rationale: Raising awareness of adverse reactions to herbal remedies and
their allergen cross-reactivity Methods: Report of a case and review of the literature Results: In his home kitchen, a 23 month old atopic boy watched his
father choose, then helped him grind, a mix of fennel seeds, chamomile flowers, marshmallow roots, and peppermint leaves, to prepare a medicinal decoction-infusion for gastro-intestinal discomfort. The child was helped pour the
dry mix in boiling water and hence inhaled the first vapors over the stove. Within
a few minutes he developed bronchospasm and required diphenhydramine
and epinephrine in the emergency room. We performed skin tests (Prick and
Patch) and measured specific serum IgE to the medicinal plants and to their
known cross-reacting major pollens and various fruits and vegetables. The allergens of medicinal plants may be heat-stable (chamomile), heat-labile (marshmallow) or revealed by warm moisture (fennel). A T cell-mediated reaction to
peppermint was confirmed. The prevalence of food allergies is estimated at 6%
in children under the age of 3 years. Ingestion of a dietary allergen is the most
common cause of an immediate severe reaction but a similar generalized reaction may result from rapid absorption, via the respiratory mucosa, of crossreacting airborne allergens. The simultaneous inhalation of chamomile allergens while sensitized to cucumber, zucchini and ragweed on one hand, and of
fennel allergens while sensitized to celery and mugwort on the other, was likely
the trigger of anaphylaxis, by the respiratory route, for this child affected by a
combination of two pollen-food syndromes. In conservative cultures, the transmission of the knowledge in traditional home-remedy preparation is an important part of the children’s education in respectful reliance on nature. Treating
minor ailments with tisanes and other herbal beverages is enjoying a renewed
interest, as promoted by many self-help manuals, blogs and websites. Conclusions: We report the first case of a child anaphylacting after inhalation of allergens cross-reacting over two pollen-food syndromes. It behooves the pediatrician and the allergist of an atopic child to review with the family the proper
handling of medicinal herbs and plant extracts, stressing their potent allergenicity and potential cross-reactivity with dietary and airborne proteins, as
the practice may induce anaphylaxis.
M.S. Georgy*, B. Sabin, A. Ditto, Chicago, IL.
Background: Beer allergy is very rare, but has been reported. Barley is usually the culprit. This is a case report of a patient who reacted to home brewed
beer. Case Presentation: A 41 year-old male presented to the
Allergy/Immunology clinic with the complaint of chest tightness, wheeze,
oral pruritus, sneeze, and nasal congestion after consumption of different beers
and wine, including home brewed beer. His peak flow decreased from a personal best of 710 L/min to 510 L/min with these episodes, and symptoms
resolved within 30 minutes after either albuterol therapy or drinking water and
relaxing. His beer was brewed from yeast, water, barley, hops, and occasionally wheat. Skin testing to barley, hops, and grapes were negative (skin testing
to mold and yeast were previously done and he was positive to mold, but negative to yeast). He was prescribed a proton pump inhibitor (PPI) which greatly
improved his symptoms and he reported being able to drink several bottles of
a microbrew beer that previously gave him symptoms. However, he still had
some symptoms after consuming home brewed beer. Skin testing was performed
and was positive to his home brewed beer, but negative to a commercial beer
which also caused symptoms. Given his inconsistent history and improvement
with PPI, GERD causing bronchospasm was thought to be the most likely cause
and he was challenged to his home brewed beer. He had no symptoms 30 minutes after consuming 2 ounces of beer. An additional 10 ounces were given
and 15 minutes later, he developed nasal congestion, sneezing, and slight chest
tightness. On physical exam he was noted to have conjunctival injection, patchy
erythema on his chest and wheezing. His vital signs were stable and he was in
no acute distress, but his FEV1 decreased from 4.85 L to 1.94 L. Epinephrine
and diphenhydramine were administered and his symptoms resolved within
15 minutes; FEV1 also increased to 4.73 L. Conclusion: This is a case of report
of patient who reacted to a beer challenge. A potential mechanism for his reactions to home brewed beer is yeast content (particular yeast and/or amount of
yeast since this beer is not filtered). VMR plus GERD provoking bronchospasm
may be potential etiologies or contributors. Further testing with different beers
and ingredients is necessary to ascertain whether this is a true beer allergy versus another etiology.
subjects experiencing anaphylaxis from a variety of triggers, including foods.
A variety of drugs of different classes are associated with anaphylaxis and elevated post-event serum tryptase. Additional studies with larger numbers of subjects should be considered to see if food anaphylaxis occurs in the absence of
elevated serum tryptase.
R.M. Harris*, Beverly Hills, CA.
This is a case report of a 34 year old male who presented to the ER with
severe periorbital edema, facial angioedema and respiratory complaints. he was
treated and referred to our office for evaluation. He had no prior history or family history of angioedema, no lip,tongue,laryngeal,hand,foot or scrotal swelling
nor any recent or ongoing GI complaints.There were no new oral medications,foods,herbal-vitamin supplements. The only new item was recent use of
Restasis eye drops for “dry eyes”. Restasis eyed drops contain castor oil and,
although people often think of castor beans they are actually castor seeds. Prick
puncture testing was done for all nuts and seeds due to previously reported
cross reactivity between these groups. Tests were 3+ to 4+ skin test positive to
many nuts and seeds, testing to castor oil was negative. We obtained a packet
of castor seeds and both soaked them in saline for testing and scraped the center directly and skin tested the patient. Testing with castor seed, both as fresh
food and in solution showed 3+ to 4+ reactivity. It is recommended that patients
be asked if they have nut or seed allergies prior to prescribing this eye drop.
And that if they do have nut or seed allergy they be tested for castor seed prior
to the use of Restasis eye drop solution.
R. Gutta*, R. Siles, F.H. Hsieh, Cleveland, OH.
INTRODUCTION: Serum tryptase testing has been demonstrated to have
clinical utility in confirming the diagnosis of anaphylaxis. However, foodinduced anaphylaxis has been suggested to occur without concomitant elevations in serum tryptase. We sought to confirm that food anaphylaxis was not
associated with elevated post-event serum tryptase and catalog the antigens
associated with anaphylaxis with elevated serum tryptase. METHODS: Patient
records from a tertiary care institution over an eight year period were reviewed
retrospectively. Twenty-three subjects who experienced anaphylaxis and had a
serum tryptase value drawn within 24 hours after the onset of anaphylaxis were
included in the study. Anaphylaxis was diagnosed based on the 2005 Joint
Task Force Practice Parameters on the Diagnosis and Treatment of Anaphylaxis. Demographic information, clinical and treatment data, laboratory studies including serial tryptase levels, and outcomes were reviewed. RESULTS:
Of the 23 subjects identified, 20 were adult (mean age 58.9 years old) and 3
were pediatric (mean age 14.3 years old) subjects. 21 subjects were Caucasian;
2 were African-American. 44% were atopic (10/23); 13% had a history of previous anaphylaxis (3/23). 61% of subjects experienced hypotension during initial presentation (14/23); 65% required intubation (15/23); mean doses of epinephrine required for resuscitation was 2.13 doses. 65% of subjects had a serum
tryptase drawn within 6 hours of the onset of anaphylaxis (15/23). The mean
event tryptase was 53.1 ug/L. In 87% of the subjects (20/23) the antigen triggering anaphylaxis could be identified – these included drugs (15), insect venom
(2), foods (1), latex (1) and radiocontrast media (1). The identified drugs
included ceftriaxone, cefazolin, cefuroxime, ketorolac, metronidazole, vancomycin, vitamin K and succinylcholine. 22/23 subjects survived the anaphylactic event. CONCLUSIONS: Elevated serum tryptase can be identified in
Castor Seeds
K.K. McKinney*, Washington, DC.
Introduction: Drug Rash with Eosinophilia and Systemic Symptoms
(DRESS) is a potentially life-threatening drug hypersensitivity reaction involving rash, fever, and multi organ failure. Drugs that have been implicated most
commonly in DRESS include antiepileptics and minocycline. Reports of other
antibiotics as causes are rare. A patient who developed severe DRESS after
brief exposure to four antibiotics is presented. The patient was also found to
have HHV-6 reactivation. Case Presentation: A 20-year-old previously healthy
man was treated for tenosynovitis following a car accident. He received one
dose of Ceftriaxone, two days of Doxycycline, one pre-op dose of Vancomycin
and ten days of Septra. Two weeks after completing the course of Septra, he
developed upper respiratory symptoms and a rash. Three weeks later (five weeks
after the last exposure to any antibiotic) he became severely ill with added fever,
myalgias, transaminitis and renal failure. He was hospitalized in the ICU and
treated for presumed septic shock. During his one month hospital course, he
developed respiratory failure, DIC, splenic infarct, lymphadenopathy, leuko-
cytosis (WBC 50,000/uL), atypical lymphocytosis (7%) and eosinophilia (27%,
AEC 10719). He was exposed to multiple antibiotics during his hospitalization, including Vancomycin and Doxycycline. The rash progressed from erythroderma to total body desquamation and was accompanied by generalized
swelling. Results: Infectious and other etiologies were ruled out; a comprehensive evaluation including lumbar puncture, serologies and imaging, failed
to identify a definitive cause. One month after his initial presentation, DRESS
was diagnosed. All antibiotics were discontinued, a skin biopsy was done and
additional testing for HHV-6 was performed. The skin biopsy showed spongiotic and lichenoid dermatitis consistent with a drug-related eruption. The
HHV-6 IgG titer was elevated at 1:5120 then dropped to 1:320 over a few
months suggesting HHV-6 reactivation. High dose systemic steroids were
initiated and the patient improved clinically with his lab abnormalities returning to normal over two months. Conclusions: This patient had severe DRESS
associated with HHV-6 reactivation likely caused by one of four rarely
described antibiotics. This case emphasizes the need for increased awareness
amongst medical providers of DRESS and the need for diagnostic tests to confirm the causative drug.
J. Mendiola*, B.E. Del Rio, M.A. Rosas, Mexico City, Mexico.
Introduction: The adverse drug reactions are unexpected adverse events
caused by drug intake not responding to its pharmacological effects are unpredictable and medicine in small quantities involved. Almost virtually all
chemotherapeutic agents have the potential to initiate a hypersensitivity reaction. Most occur in the first hours after administration and almost all are associated with oral rather than parenteral use. We report a case of male 8 years old
who has a diagnosis of M4 acute myeloid leukemia in remission after the first
cycle of chemotherapy and a history of adverse reaction to cytarabine pruritic
erythematous rash characterized by starting immediately after its administration, Despite premedication with antihistamine and intravenous steroid. Presents bone marrow relapse in March 2010 it was decided to restart chemotherapy regimen with cytarabine, etoposide and doxorubicin. Resubmitted reaction
to cytarabine maculopapular rash characterized by pruritic erythematous papular start immediately after application. It was decided readministration of new
cycle with premedication 13, 7 and 1 hour before the start based desensitization protocol for carboplatin as amended, which was held in intensive care unit,
with the following schedule.(table1) Total dose was 100mg per day for 5 days.
Day 1: We used protocol schedule in 24hours. Day 2-5: Continuous infusion
in 24hours . Results: Adequate tolerance readministration of cytarabine with
carboplatin desensitization protocol for modified without showing skin or
systemic reactions. Adverse drug reactions have held positions as a producer
of pathologies in recent decades. In patients with suspected hypersensitivity
reaction to any medications, you should stop and get a second management
option. In the case of chemotherapy such as cytarabine, which is the cornerstone of treatment of myeloid leukemias, premedication may be tried, in case
of failing conservative management should be attempted desensitization, which
gives you the opportunity to receive best medication for severe illness, which
threatens the life of the patient.
Schedule of dosification
K. Miro*, C.W. Bassett, U. Kaza, W. Mak, E. Rothstein, C. Smith-Ricks,
B. Modi, New York, NY.
gested an increased prevalence in non-Asian populations, this has not been
widely studied. METHODS: A random survey involving 16 patients was conducted to identify patients that experience flushing with alcohol. RESULTS:
A total of 16 patients responded to the survey. Ages ranged from 22-59; 7/16
(44%) patients were aged 30-39 and 4/16 (25%) patients were aged 20-29 years
old. We included 11/16 Asian patients (69%) and 5/16 non-Asian patients (31%).
Seventy five percent (12/16) of the participants had flushing after consumption of one alcoholic beverage. Sixty percent (3/5) of the non-Asian patients
also had flushing with consumption of only one alcoholic beverage. Thirty
one percent (5/16) of patients, all of whom were Asian, had a feeling which
they described as “intoxication” with only one to two alcoholic beverages,
whereas non-Asian patients required an average of approximately four alcoholic beverages. The survey was also used to determine the clinical reactions
patients have had after consuming alcohol. In addition to flushing, patients
experienced vomiting, “lightheadedness” or “dizziness”, and “facial swelling”.
Forty four percent (7/16) of patients described feeling “lightheaded” or “dizzy”,
nineteen percent (3/16) had vomiting, and thirteen percent (2/16) had “facial
swelling”. Twenty percent (1/5) non-Asian patients had all of the symptoms
described whereas eighty percent (4/5) only had flushing. Thirty one percent
(5/16) of patients stopped alcohol use as a result of this reaction, two of whom
were non-Asian. CONCLUSION: Flushing after alcohol consumption, as seen
in our survey and previous studies, is prevalent in both Asian and non-Asian
populations. In addition to flushing, some patients may also experience “dizziness”, vomiting, “facial swelling” and a feeling of being “intoxicated” with
small amounts of alcohol ingestion. Flushing in response to alcohol is a phenomenon that occurs not only in Asian patients but in non-Asian populations
as well, though has been studied less in non-Asian populations and therefore
warrants further study in this group.
K. Miro*, B.A. Feigenbaum, A. Mathew, J.N. Weinfeld, New York, NY.
INTRODUCTION: Oxaliplatin is part of the chemotherapy regimen FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin), used in the treatment of colorectal cancer. Various protocols described as oxaliplatin “hypersensitivity”
protocols have been reported in the literature. Failure of one oxaliplatin hypersensitivity protocol may lead the clinician to abandon the drug permanently,
potentially resulting in suboptimal treatment of the cancer. METHODS: Case
report of a patient with a previous hypersensitivity reaction to oxaliplatin, who
failed one hypersensitivity protocol and then was successfully treated with
oxaliplatin utilizing an acute drug desensitization protocol from the Allergy literature. RESULTS: A 73 year old female with metastatic colon cancer developed a hypersensitivity reaction, including flushing, chest tightness and shortness of breath, during oxaliplatin infusion. The infusion was terminated and
the full dose was not delivered. Approximately two weeks later, oxaliplatin was
infused using a hypersensitivity protocol. The patient received dexamethasone
20 mg IV, diphenhydramine 25 mg IV and famotidine 20 mg IV as pre-medication. Oxaliplatin 132 mg was then ordered as follows: oxaliplatin 1 mg in
100cc D5W over 1 hour; oxaliplatin 5 mg in 100cc D5W over 1 hour; oxaliplatin 10 mg in 100cc D5W over 1 hour; the remaining oxaliplatin 116 mg in
250cc D5W over 2 hours. After receiving approximately 50 mg of oxaliplatin,
she experienced flushing, chest tightness, and shortness of breath. The infusion was terminated and the full dose was not delivered. After referral to Allergy,
oxaliplatin 132 mg was infused without reaction, utilizing the 12-step rapid
desensitization protocol including pre-medications as described by Castells.
(Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to
chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J
Allergy Clin Immunol 2008; 122(3): 574-580.) Two weeks later, oxaliplatin
132 mg was infused again, without reaction, utilizing the same protocol as
described by Castells. CONCLUSION: Infusion of oxaliplatin or other
chemotherapy utilizing this 12-step protocol, or similar acute drug desensitization protocol, may be successful even if a patient has failed a hypersensitivity protocol.
INTRODUCTION: Flushing after alcohol ingestion is a common phenomenon recognized in the Asian population. Though some studies have sug-
Omalizumab Desensitization Protocol
M.B. Morales*, Norfolk, VA.
Heiner’s syndrome is a rare delayed food hypersensitivity (non IgE mediated) pulmonary disease caused by cow’s milk. This is a case of a child who
initially presented at 14 months old with respiratory issues of recurrent cough
and wheeze associated with hypoxia with partial response to bronchodilators
and antiinflammatory medications including systemic steroids. Her respiratory
symptoms progressed requiring several hospital admissions. With later findings of CMV pneumonitis on bronchoscopy, she was also worked up for primary immune deficiency which all came back normal. She had equivocal initial bronchoscopies showing numerous neutrophils,RBC, eosinophils with few
hemosiderin laden macrophages. Incidentally she also had anemia on her initial CBC.With her history having an onset around the time her soy formula was
switched to regular milk at 12 months, a milk precipitin panel was ordered showing positivity to casein and cow’s milk. After eliminating cow’s milk from her
diet for a few months her respiratory symptoms have resolved without any further therapy. She is currently 5 years old doing well off of inhaled steroids and
has not needed albuterol in a while. This syndrome is a non IgE mediated hypersensitivity to cow’s milk characterized by recurrent episodes of pneumonia, pulmonary infiltrates, hemosiderosis and anemia. Key to diagnosis is positive milk
precipitin panel and resolution of symptoms after elimination of cow’s milk.
G. Owens*, A. Petrov, Pittsburgh, PA.
Introduction: Omalizumab has been successfully utilized for the treatment of moderate to severe allergic asthma. Omalizumab has been shown to
decrease inhaled corticosteroid use, asthma exacerbations, and asthma emergency room visits. Although rare, 0.1-0.2% of patients experience anaphylaxis with omalizumab use. The mechanism of anaphylaxis in these patients
appears to be IgE mediated. Methods: A pubmed search for previous omalizumab desensitizations revealed only one desensitization performed by
Dreyfus and Randolph in a 32 yo female with asthma who developed serum
sickness after desensitization. We created a novel 9-10 step omalizumab
desensitization protocol for two patients seen in the University AllergyImmunology Clinic (Table 1). Results: Patient X is a 32 yo female with severe
persistent steroid dependent asthma and paradoxical vocal cord dysfunction.
She developed anaphylaxis (pruritus, swelling, and asthma exacerbation)
twice after omalizumab administration (1.5 years into therapy, < 3 hours after
injection). She had skin testing to omalizumab performed which was negative. Patient Y is a 21 yo female with severe steroid dependent asthma. She
developed anaphylaxis (facial and oropharyngeal swelling) after omalizumab
administration (3 months into therapy, <30 minutes after injection). Both
patients received antihistamines, steroids, and epinephrine for treatment of
their anaphylaxis. The protocol designed for both patients was the same
except for the final doses which differed based on patients individual dose.
The final biweekly dose (chosen based on the omalizumab package insert
instructions) was divided in half with a plan for weekly infusions after desensitization. Both patients had transient difficulties during desensitization.
Patient X developed a vocal cord dysfunction flare (visualized by laryngoscopy) which resolved with breathing exercises and patient Y developed
pruritus which also resolved spontaneously. They have tolerated subsequent
weekly omalizumab injections. Conclusions: Hypersensitivity reactions to
omalizumab have presented a serious challenge in treating severe asthma
patients who require omalizumab therapy. We report a novel protocol for
omalizumab desensitization providing physicians with an option to continue
treatment in patients who benefited from omalizumab therapy prior to their
allergic reaction.
Protocol for patient X. Patient Y’s protocol was similar only differing in the
final steps to achieve a different goal dose.
K.M. Patchan*, M. Singla, Baltimore, MD.
Introduction: Mustard seed is an under-recognized, yet increasingly important allergen, in foodstuffs. The 1st case report describing anaphylactic shock
following mustard ingestion was reported in 1980. Additional case reports have
been published, almost exclusively in France and Spain. This led the European
Union, in 2003, to require manufacturers to label food products containing
more than 25% mustard as potential allergens. In contrast, the United States
does not have a similar mandate. Our case report describes a 2-year old Caucasian male who recently developed urticaria after eating a small portion of
mustard at a fast food restaurant. Description: The patient has a past medical
history significant for poorly-controlled asthma, moderately severe allergic
rhinitis, and atopic dermatitis. He experiences frequent nocturnal cough and
dry cough exacerbated by URI and exercise. Additionally, his mother reported
reactivity to a number of food products including peanut butter (wheezing),
chocolate (cough, emesis), Cheeze-It crackers (wheezing), and green peas
(angioedema). There is no evidence of anaphylaxis among 1st degree relatives. Methods & results In June 2010, a standard skin prick test (SPT) was
conducted, along with dilutions of products believed to be allergens (see attached
table). Among routinely tested allergens, the patient tested positive only to
peanuts. Additionally, his results showed mild reactivity to powered donuts and
Cheeze-It crackers, moderate reactivity to green peas, and severe reactivity to
mustard. He was asked to avoid mustard-containing products and was restarted
on Flonase (44mcg 2 puffs BID) and begun on Singular 4mg PO QHS for better asthma control. Conclusion Our case study, as well as prior case reviews
and prospective studies, relate the potential harm that can occur from ingestion of mustard, the most serious being anaphylactic shock. Further, mustard
is often not labeled as an ingredient in food packaging, making it a hidden
condiment that can be ingested without knowledge. Further research and clinical investigation is required to discern potential allergens in mustard, clinical
characteristics, and environmental precipitants.
Table: Immunologic responses to SPT
A.E. Perez-Mercado*, F. LГёopez-Malpica, S. Nazario, San Juan, Puerto
Introduction: Anaphylaxis is a severe and potentially life threatening type
I hypersensitivity reaction. Few studies have examined the frequency of this
condition amongst Puerto Rican patients or attempted to characterize its impact
on their well-being. We sought to assess patient awareness of this condition and
evaluate whether disparities in the triggers or treatment of anaphylaxis exist
between patients insured by private health insurance (PHI) companies and those
insured by the Puerto Rico government-sponsored health care system (GHI).
Methods: We distributed a validated survey among several offices and clinics
of adult primary-care physicians in the Puerto Rico Metropolitan area. These
surveys sought to evaluate the frequency of anaphylaxis, the triggers for these
episodes, and the associated morbidity. The surveys were voluntarily self-administered by patients. This study was carried out with the approval and under the
supervision of the University of Puerto Rico: Medical Sciences Campus IRB.
Results: 50% of patients with GHI reported symptoms consistent with anaphylaxis compared with 24% of those with PHI. Insects were the most common trigger identified affecting 22% of GHI and 33% of PHI patients, followed
by milk (12%), eggs (12%), and fish(12%) in the GHI group; and crustaceans
(25%), medications (25%), peanuts (17%), and nuts (17%) in the PHI group.
17% of patients with anaphylaxis in the GHI group could not recognize a trigger for their symptoms and 56% reported having received a diagnosis of severe
allergy or anaphylaxis, compared with 0% and 100% respectively in the PHI
group. 28% of patients in the GHI group reported having been prescribed epinephrine injectors compared with 17% of the PHI group. 22% of anaphylaxis
patients in the GHI group reported having been evaluated by an allergist compared to 66% of those with PHI. Discussion: A greater proportion of patients
in the GHI group reported symptoms of anaphylaxis. Discrepancies were noted
in the triggers, the proportion of patients requiring medications for treatment,
allergist evaluation, and the use of epinephrine injector among the groups. GHI
patients were more likely to be under-diagnosed and to suffer more severe
episodes. Further studies are needed to determine the cause of these disparities and to devise clinical interventions to address them.
two cases of anaphylaxis induced by cumin in mainland China. Methods:
A 25 year old girl presented with 2 episodes of acute onset generalized
itching, hoarseness, shortness of breath and syncope in the last year. Both
episodes started 5 to 10 minutes after meal and symptoms progressed rapidly. The first case was after eating fried lamb with cumins, the second case
fried chicken with cumins. She also suffered cramping abdominal pain and
diarrhea before falling unconsciously. Past medical history included seasonal rhinitis in the past three autumn, oral tinnitus and facial edema after
eating mango and longan. The second case was a 16 year old girl. She
consulted to the clinic because of generalized urticaria, dyspnea and loss
of consciousness which started 15 minutes after eating stir-fried lamb with
cumins. She also recalled two similar incidents in the past two years. One
developed several minutes after eating potato and eggplant, the other after
eating longan. She had seasonal rhinitis from July to September for years.
Skin prick tests with cumin exact and fresh fruit juice, a panel of intradermal inhalant allergen skin test and serum specific IgE test were carried
out to identify the culprit allergens. Results: In both patients, skin prick
test demonstrated positive reactions to cumin extract and longan juice. In
the first patient, inhalant allergen skin test showed positive reaction to mugwort. Serum specific IgE for mugwort was 43.5 Kua/l, for Mango 1.73Kua/l,
for litchi 0.69kua/l. In the second patient, serum IgE test for mugwort was
98.3kua/l, for silver birch was 24.6kua/l. In both cases, because of the risk
of anaphylaxis, challenge tests were not performed. Conclusion: For the
first time in China, we demonstrate that cumin could induce life threatening anaphylaxis in sensitized people. Both patients in the report have pollen
induced allergic rhinitis and allergic reaction to other food like longan. In
vitro ELISA and RAST inhibition test will be carried out to further investigate the mechanism underlying the two patients.
T.W. Pun*, C. Kalicinsky, Winnipeg, MB, Canada.
Introduction: There is a pervasive myth in the medical community that shellfish allergy precludes the use of radiocontrast media in diagnostic procedures.
A study by Beaty et al. in 2006 in the US demonstrated that 37.2% of polled
radiologists and 50% interventional cardiologists share this perception. We
sought to determine the strength and or existence of this myth in Canada. Methods: We distributed Dr. Beaty’s survey to radiologists and interventional cardiologists (staff and residents) based at teaching hospitals across Canada. The
survey consisted of 8 yes/no questions, with 2 questions of interest embedded
amongst 6 distractors. Results: 146 radiologists and 42 interventional cardiologists responded. 68% and 71% of responding radiologists and interventional
cardiologists, respectively, indicated that they or someone on their behalf inquire
about shellfish allergy prior to the administration of contrast. 12.5 % and 43%
of responding radiologists and interventional cardiologists, respectively, claimed
they would withhold radiocontrast media or recommend premedication if the
patient had a positive history of shellfish allergy. Conclusion: The myth associating IgE mediated shellfish allergy and nonimmunologic anaphylactoid reactions to radiocontrast media is present in Canada. While Canadian radiologists
are less likely to alter their management based on a history of shellfish allergy,
Canadian interventional cardiologists report similar perceptions to their American counterparts. More education in this area is required.
M. Qing*, P.L. Wen, Beijing, China.
Background: Cumin is the dried seed of the herb Cuminum cyminum,
a member of the Apiaceae family. It is often used as a seasoning in Chinese food to improve the taste of meat. Here for the first time, we report
D. Seth*, M. Pansare, Detroit, MI.
Introduction: Photosensitivity reactions are uncommon but can masquerade serious dermatitis. We report a case of voriconazole-induced photosensitivity . Method: A 17-year-old Caucasian female with CVID and pulmonary
Aspergillosis was admitted for Stevens- Johnson syndrome. She initially developed erythematous rash on her face followed by her arms and legs. Patient had
been out on the beach 5 days prior to the rash. Subsequently, she developed
swelling of her face and arms with mild pain, cheilitis and seven small blisters
on the dorsum of her hands. She denied any swallowing difficulties, eye or
other mucosal involvement. Past Medical History-She was diagnosed with
CVID at 3 years and received intravenous immunoglobulin (IVIG) every 4
weeks. She was diagnosed with pulmonary aspergillosis a month ago for which
voriconazole was initiated. The dose of Voriconazole was increased ten days
before hospital admission. Clinical examination-Erythematous rash with mild
edema on face, arms and legs. No involvement of chest or abdomen. Absent
Nikolsky sign. Laboratory results: Non detectable PCR for viruses and
mycoplasma. Skin biopsy showed mild vacuolar interface dermatitis with
necrotic keratinocytes and superficial vessel involvement consistent with photosensitivity reactions. Clinical course: The rash improved gradually with topical application of Triamcinolone 0.1% and photo protection. Voriconazole was
discontinued at admission. Discussion: Voriconazole is second generation triazole antifungal agent. Mild dermatologic reactions occur in less than 10% of
treated patients which include cheilitis, xerosis, facial erythema, and photosensitivity. Stevens-Johnson syndrome and toxic epidermal necrolysis has been
rarely reported. In contrast to the other azole antifungal agents, photosensitivity is more common with voriconazole, most often after prolonged treatment
(5 weeks to 14 months).The etiology is unclear either idiosyncratic, direct phototoxic or indirect retinoid effect. Photosensitivity reaction with voriconazole
has been reported in patients with B and T cell immunodeficiency. Drug discontinuation is not always required. Appropriate photo protection is recommended Conclusions: Allergists should be aware of photosensitivity reactions
with voriconazole as this drug is likely to be used in immuno-compromised
ment of a fixed, pruritic, erythematous, papular rash on his torso and arms.
There was no evidence of desquamation, blistering, or urticaria. The patient
was also receiving enoxaprin for a recently discovered deep vein thrombosis.
While a variety of hypersensitivity reactions occur, that drug almost never causes
a generalized eruption similar to what this patient developed. Therefore, we
believed that his presentation was due to a delayed hypersensitivity reaction to
daptomycin. Both medications were stopped and the patient was treated with
3 days of corticosteroids resulting in near resolution of the rash. Due to the
nature of his LVAD infection, limited antibiotic susceptibility, and significant
known adverse reactions to other antibiotic options, reintroduction of daptomycin was considered a necessity. To avoid a serious drug eruption, he was
reintroduced to intravenous daptomycin slowly over 5 days in the inpatient
setting. The desired final dose of daptomycin was 400mg/d. After Day 5, he
received daptomycin daily with no change in physical exam, but continued pruritus that was controlled with oral antihistamines. At Day 12, the patient’s pruritus continued to improve with decreased medication requirements and no evidence of rash. Conclusion: Delayed hypersensitivity reaction to daptomycin
and successful reintroduction have not been reported in the literature. We believe
this is an example of a safe and successful reintroduction of an essential new
K. Weiss*1, J. Wachs2, E. Jerschow2, 1. New York, NY; 2. Bronx, NY.
Erythematous rash on face with cheilitis
R. Shah*, P.A. Greenberger, L.C. Grammer, Chicago, IL.
Introduction: There are no reported cases of delayed cutaneous reactions
to daptomycin or report of generalized delayed dermatitis to enoxaparin. Circumstances occur when a drug causes a cutaneous reaction and the suspected
drug is considered essential to the care of the patient. Methods: We report successful test challenge of daptomycin in a patient with delayed onset dermatitis due to daptomycin and a review of the literature. Case: A 62 year old male
with heart failure requiring a left ventricular assist device (LVAD), developed
a vancomycin resistant Enterococcus faecium (VRE) bacteremia. VRE was susceptible to linezolid and daptomycin. Since bacteremia was due to infection of
the LVAD, long term antibiotics were required. He was treated with linezolid
for 4 weeks, and then switched to daptomycin due to concern for cytopenia
with linezolid. Two weeks later, he was admitted to the hospital for manage-
Introduction - Administration of mesna usually accompanies the use of
cyclophosphamide in order to prevent hemorrhagic cystitis, which may result
from the use of cyclophosphamide. Case reports have shown adverse reactions from mesna including cutaneous reactions, described as macular-papular rash, urticarial rash, or fixed drug eruption (FDE). In the reported cases the
appearance of the FDE lesions occurred immediately after the administration
of mesna and prior to cyclophosphamide administration facilitating the diagnosis of mesna-induced FDE. We report a case of FDE where the diagnosis was
complicated by the fact that the lesions appeared during the cyclophosphamide
infusion. Case Report - A 41 year old female, employed as a police officer at
World Trade Center site after its destruction in 2001, was diagnosed with interstitial lung disease in 2004. She was treated with several cycles of cyclophosphamide and mesna showing a good clinical response. However after the 5th
cyclophosphamide infusion, she complained of skin burning and with subsequent treatments she developed sharply demarcated itchy erythematous plaques
on her face, chest, back, and upper arms. After each treatment, these hyperpigemtented lesions would recur within one to several hours at the same sites
and numerous new sites. A diagnosis of generalized FDE was made with the
suspicion that cyclophosphamide was the causative agent. She was referred to
the allergy clinic for possible desensitization to cyclophosphamide. She underwent intradermal testing as well as patch testing at both the previously affected
skin area and a control site. Her skin tests were positive at the previously affected
sites. It was concluded that the patient’s FDE was due to mesna. She underwent
a graded challenge test with cyclophosphamide with aggressive hydration, without mesna, which she tolerated well with no adverse reactions. Discussion Mesna is widely used for prophylaxis of hemorrhagic cystitis resulting from
cyclophosphamide administration. Despite its wide use, it is rarely associated
with cutaneous or systemic hypersensitivity reactions. Diagnosing mesna-
induced reactions could be challenging if another medication is also involved
such as cyclophosphamide. However, it is important to consider mesna-induced
reaction, as failure to do so may prevent patients from receiving an optimal
INTRODUCTION: Allergies to macrolide antibiotics are very rare (0.4%
- 3). Here we report a pediatric patient with multiple drug allergies successfully desensitized to clarithromycin. CASE PRESENTATION: A 7-year-old
girl with asthma presented to the clinic with one week history of cough, fever
and wheezing. She had been on oral prednisone and loratidine. On exam, she
had low grade fever, erythematous oro-pharynx, purulent rhinorrhea, end-expiratory wheezing and crackles on the right lower zone. She was diagnosed with
pneumonia and asthma exacerbation. About two months ago, she developed
streptococcal pharyngitis. She was started on amoxicillin, however within one
hour of taking the first dose she developed hives, rhinorrhea and wheezing. The
antibiotic was changed to azithromycin, after the second dose of azithromycin,
she developed hives and severe nasal congestion. Then, she was placed on clindamycin to which she again had a reaction with generalized hives and cough.
She also has a history of hives, nausea and vomiting after taking sulfa drugs,
and hives after taking erythromycin. Patient was admitted for drug challenge
with clarithromycin, she did not have a history of reaction to this drug. The procedure went uneventful. However, within 20 min of the second dose (given 10
hours after the challenge), she developed urticaria on the neck and trunk and
generalized itching. Her symptoms improved with oral Benadryl. Later, she
underwent induction of tolerance procedure using a protocol which is modified from a previously published protocol (Table). She tolerated the procedure
with no reaction and was subsequently begun on clarithromycin 15 mg/kg/d
twice daily. She tolerated following 2 full doses, her fever improved within 24
hours, and she was sent home on oral clarithromycin which she continued to
tolerate throughout the course of the treatment. CONCLUSION: Although
cross-reactivity has not been studied thoroughly, it is generally believed that
macrolide antibiotics are unlikely to cross react with other macrolide antibiotics. However, our patient had systemic reactions to azithromycin, erythromycin and clarithromycin. After induction of tolerance, she continued to tolerate clarithromycin during the course of treatment of her pneumonia. To our
knowledge, this is the first published pediatric patient who was successfully
desensitized to clarithromycin.
L. Wen*, J. Liu, Beijing, China.
Rationale: Many hay fever patients are complicated by food allergy, especially fruit, vegetable and tree nuts. To our knowledge, anaphylaxis caused by
yacon in hay fever patients has never been reported in China. Here we report
a case of anaphylaxis induced by yacon in a pollenosis patient. Method: The
clinical data was collected. Skin test and serum Unicap IgE test were performed.
Prick skin test with fresh fruit juice was also performed.Result: A 28 years old
male was referred to us with chief complains of urticaria, dyspnea and hypertension after intaking yacon, a recently introduced fruit in China. One month
before, he developed slight itches in mouth and throat after having a piece of
yacon (about 25g) to which he ignored. This was his first exposure of this
fruit. Several days later he had more of this fruit, about 250g this time, and
was immediately attacked by generalized itchy rashes, severe dyspnea, palpitation, dizziness, perspiration, abdominal pain and diarrhea. He felt weakness
and lost consciousness several minutes later. He was sent to ER and recovered
soon after adrenaline and antihistamine therapy. Four years ago he developed
itchy eyes, watery nose and sniff, with seasonal recurrence during spring and
autumn (April to May, August to September). Night cough and chest tightness
was also noticed without obvious wheezing in last autumn. He had itchy or
burning sense in mouth and throat tightness while having fruits such as peach,
apple and jujube. He had similar symptoms after eating peanuts, walnuts and
hazelnuts. He has no episode of anaphylaxis ever before. He could tolerance
pear, mango, banana, watermelon and most vegetables fairy well. Intradermal
skin test and Unicap IgE test revealed that he was allergic to mugwort (7.93
Ku/L), birch pollen (3.88 Ku/L), oak pollen (2.66 Ku/L), apple (4.29 Ku/L),
peanuts (1.38 Ku/L) were positive. Prick test of fresh juice of apple, peach,
yacon was positive with the most severe reaction in yacon. Pear prick test was
negative. Conclusion: Yacon is a potential food allergen in hay fever patients.
S. Nanda*, Y. Yilmaz Demirdag, Morgantown, WV.
Induction of tolerace protocol for clarithromycin.
Modified from NE Holmes, et al. Report of oral clarithromycin desensitization. Br J of Clin Pharm,2008,66(2):323-4.
I. Kriunis*1, P. Pendino2, C. AgГјero3, P. Cavagnero2, K. Lopez2, G. BandГ­n2,
E. Mindel2, G. Arnolt2, P. Sarraquigne2, M. Gervasoni2, B. Menendez2,
H. Bottai2, M. Leiva2, 1. San Lorenzo, Argentina; 2. Rosario, Argentina;
3. San NicolГЎs, Argentina.
T.J. Grier*, D.M. LeFevre, E.A. Duncan, K.N. Whitaker, R.E. Esch,
T.C. Coyne, Lenoir, NC.
Aim To determine the prevalence of skin reactivity to pollens (trees, grasses,
weeds) in pediatric patients with diagnosis of allergic rhinitis. Materials and
method 281 patients of both sexes from 1 to 10 years of age with diagnosis of
persistent allergic rhinitis according to ARIA criteria were included. All patients
had total serum IgE >100 U/ml, positive atopic family history and previous
positive prick test to house dust mites. Prick tests were performed to all patients
using commercial extracts of common pollens in our area, according to previous studies. Seventy patients were included for each group, except group four
(71). Results From 281 patients tested, 29 (10.3%) had positive skin tests to
any extracts of pollen studied. Of these 29 patients with positive skin test, 23
were positive to only one extract (79.5%), 5 were positive with two pollen extract
(17.4%) and one patient shows positive skin test with three pollen extract (3.5%).
Overall, 36 skin prick test was positive. Ligustrum lucidum was positive in 10
oportunities (27.7%) followed by Cynodon dactylon in 7 (19.4%), Poa annua
in 3 (8.3%), Sorghum vulgare in 3 (8.3%), Platanus acerifolia in 3 (8.3%), Fraxinus excelsior in 3 (8.3%), Morus alba in 3 (8.3%), Ambrosia elatior in 3 (8.3%),
and Zea mayz in 1 (2.7%). Discriminating by age, patients from group 1 shows
2 prick test positive (5.5%), group 2 shows 6 prick test positive (16.7%), group
3 account for 11 test positive (30.5%) and group 4 had 17 test positive (47.3%).
Trees account for 44.4% from total positive prick test (16 positivity). Weeds
are responsible for 8.3 % (3 positivity) and grasses account for 47.3% (17 positivity). Conclusion Our study shows that from 281 rhinitis allergic patients,
10.3% were sensitive to pollens and sensitiveness increases with age. Trees and
grasses were responsible for 91.7 % of total sensitization. Ligustrum lucidum
was the most allergenic pollen. Based on these results and previous studies,
we suggests that patients with allergic rhinitis whose symptoms worse or begin
in spring or summer should be tested with pollens.
G. Plunkett*, M. Schell, Round Rock, TX.
Introduction. Allergen extract concentrate vials are labeled with expiration
dates, and when standardized the dating is verified by potency testing. Only a
few studies have been performed to determine the stability of these extracts
once they are diluted for use in immunotherapy (IT). Previous studies have
shown that adding a protein carrier to the diluting solution may improve the stability, but these studies are limited due to the lack of sensitive analytical methods. This study investigates stability of dilute extracts using in vitro allergen
potency methods. Methods. Standardized dust mite, Timothy grass, Cat Hair,
and non-standardized Birch and English plantain extracts were tested for total
protein by Brandford type Coomassie Plus assay. The extracts were diluted to
1 microgram per mL of protein. Dilutions were prepared using saline-phenol
diluent (NSP) supplemented with human serum albumin (HSA) at concentrations ranging from 0 to 300Вµg/mL. The diluted extract solutions were stored at
2-8В°C for 7 days and up to 3 months. Extracts were also diluted in NSP to 1 to
100 Вµg/mL total protein. Potency was measured using major allergen ELISAs
developed by ALK-AbellГі. IgE binding assays and SDS-PAGE were also used
to assess stability. Results. The extracts were diluted in 5mL glass serum vials.
Extract dilutions were between 1:100v/v and 1:2500v/v. Each allergen extract
maintained expected major allergen content in 300 and 100 Вµg/mL HSA. However, after just 6 days each extract lost allergen protein in a dose dependent manner in 33, 11, 4, 1 and 0 Вµg/mL HSA. For example, English plantain lost 66%
Pla l 1 in 11 Вµg/mL HSA. Similar protein-dependent loss of allergen was seen
when the extracts were diluted 3 fold serially from 100 Вµg/mL to 1 Вµg/mL. Timothy grass Phl p 5 decreased 50% when diluted 1:200v/v. The loss of major
allergens was confirmed with electrophoresis and IgE binding titration. Glycerin at 10% or 50% did not prevent the loss of allergens in the low protein solutions. Conclusions. Extracts diluted as typically done for IT lose allergen content when the protein level drops below about 4 to 30 Вµg/mL. Use of diluent
containing HSA can prevent this loss of in vitro allergenic activity.
Introduction: Glycerinated allergenic extracts are utilized by allergy clinics with increasing frequency because of their enhanced physical and biochemical stabilities relative to aqueous products. Phenolated extract mixtures
containing 50% glycerin are often employed as stock concentrates for testing
and treatment, or as patient-specific formulations. For many common extract
mixtures, the stabilities of allergens present in these solutions during typical
storage or daily-use conditions have not been investigated. Methods: The compatibilities of various phenolated (0.2%), glycerinated (50%) extracts were
determined after mixing with high-protease (fungal, insect) and/or low-protease (pollen, animal, dust mite) glycerinated products and storage for up to
13 months at refrigeration (2-8 deg C) or ambient (20-25 deg C) temperatures.
Test mixtures and single-extract controls were analyzed by quantitative human
IgE ELISA inhibition and radial immunodiffusion assays, the methods established by FDA for extract standardization in the United States. Results: Glycerinated dust mite, cat and dog extracts displayed near-complete recoveries of
allergenic activities (70-130% of controls) after mixing with all other glycerinated extracts examined in this study after up to 13 months at either 2-8 deg C
or 20-25 deg C. Glycerinated short ragweed pollen extracts were highly compatible with all products tested except Penicillium at 20-25 deg C (57-65%
recovery after 6-12 months). Glycerinated grass pollen extracts (Timothy,
meadow fescue) were destabilized by mixing with insect (cockroach) and several fungal extracts (Penicillium, Aspergillus, Cladosporium) at 2-8 deg C
(32-49% recovery after 4-13 months), but were compatible with other glycerinated fungal, pollen and dust mite extracts under these conditions. Conclusions:
Grass pollen allergens were degraded by fungal or insect proteases in 50% glycerin solutions stored for 6-12 months at 2-8 deg C or for 3-12 months at 20-25
deg C. Separation of grass extracts from these (and other) high-protease products stabilized grass allergen potencies in glycerinated extract mixtures. All
other glycerinated extracts tested retained moderate to high levels of allergenic activity after mixing with high-protease or low-protease glycerinated
extracts and storage for up to 12 months at 2-8 deg C or 20-25 deg C.
A.A. Velasco Medina*, G. CortГ©s-Morales, A. Barreto, G. VelГЎzquezSГЎmano, Mexico City, Mexico.
During the last decade there has been an increase in allergic diseases. In
Mexico, there is an incidence of 6% in allergic diseases. Aeroallergens, such
as pollens are implicated in its physiopathology. There are some allergens that
are not considered as important causes of allergic diseases, although in other
locations it has been demonstrated its relevance as aeroallergens. Pollinosis
studies at Mexico City have found an important amount of pollen from Casuarina equisetifolia and Pinus spp, but its clinical relevance has not been studied.
Materials and methods: we performed a prospective, clinical, observational
research to determine the prevalence of sensitization to pollen produced by
Casuarina equisetifolia and Pinus spp. Our ethical and investigation committee approved it. Every patient included in this research signed an informed consent before skin prick testing. We included patients with a clinical diagnosis of
asthma, allergic conjunctivitis and allergic rhinitis. They all had a complete
clinical evaluation and laboratory tests including complete blood count, nasal
cytology, spirometry, serum total IgE and skin prick tests. Results: We included
142 patients 3 to 50 years old who attended our clinic between may and june
2010. It included 44 children (36% females, 64% males) and 98 adults (73%
females, 27% males). We found that 8 (18.18%) of the children and 35 (35.7%)
of the adults had a positive skin prick test to Casuarina equisetifolia. None of
the patients included in the study had a positive skin prick test to Pinus spp.
We found a high prevalence of sensitization to Quercus and Alnus in those
patients with a positive result to Casuarina equisetifolia. Conclusions: In our
country, we don’t have large trials studying the prevalence of sensitization to
Casuarina equisetifolia and Pinus spp. Casuarina species are found all around
our city and can be a major source of pollen. In other countries, it has been
demonstrated its importance as aeroallergens. We concluded it should be tested
in our routine skin tests. More studies need to be done to determine the proteins involved in the cross reactivity to Quercus and Alnus. Pinus spp has tra-
ditionally been considered as non-allergic, despite some reports of their role
as important aeroallergens in other countries. We couldn’t demonstrate its role
as an important aeroallergen in our population.
K. Kowal*1, I.V. DuBuske1, P. Bielecki1, P.S. Skov2, L.M. DuBuske1,
1. Gardner, MA; 2. Copenhagen, Denmark.
Background: New biologic agents which are candidate molecules for clinical development need to be carefully assessed for their ability to induce anaphylaxis perhaps using histamine release from peripheral blood basophils as a
means of screening for anaphylactic potential. Methods: The glass fiber based
whole blood basophil histamine release test (Histareader, Copenhagen, DK)
was performed in 62 allergic rhinitis/asthma patients sensitized to perennial
allergens as demonstrated by positive skin prick tests and elevated serum specific IgE levels. The tests were performed with and without pre-treatment with
interleukin 3 (IL-3) and dilutions of candidate biologicals. Total histamine content was determined by evaluation of histamine concentration in lysates of the
whole blood samples. The results are expressed as the fraction of total histamine content. Areas under the curve were calculated for each dilution of the
studied formulation or control anti-IgE antibody. The study was performed in
triplicates and the mean values were used for calculations. Results: Subjects
demonstrated an average Total IgE of 177 and average kU/L of allergen Specific IgE of 4.70 for M1; 1.25 for M3; 3.81 for M6; 10.57 for D1; 13.27;15.92
for E1; 10.02 for E5; and 2.21 for I6. The positive control (polyclonal antihuman IgE) maximum histamine release in the presence of IL-3 was 37.71%
and without IL-3 was 31.42%.The AUC of histamine release with the presence of IL-3 was 37.83% and without IL-3 was 23.82%. The negative control
(isotype control antibody) maximum histamine release with the presence of
IL-3 was 2.59% and without IL-3 was 2.395%.The AUC of histamine release
with IL-3 was 0.944% and without IL-3 was 0.755%. There was no difference
between basophil histamine release induced by any of the studied biologic
agents and that induced by isotype control negative antibodies. Addition of specific allergen induced histamine release comparable to the positive control
and was nit impacted by the investigated biologic. Conclusion: Assessment of
histamine release from peripheral blood human basophils may be a safe means
of rapidly screening new biologic agents for anaphylactic potential with rapid
screening of anaphylactic safety of candidate biologic agents.
specificity of assessment of overall mold sensitization (Aspergillus sensitization and Alternaria alternate) was 83.95%. Conclusion: FastCheckPOC (2nd
generation) is a significant advance in the rapid assessment for the presence of
allergen sensitization and can be run at any point of care as it is easy to perform and requires only a few drops of blood or sera. The over-all diagnostic
efficiency and specificity of the FastCheckPOC indicates excellent assay performance for the presence of perennial inhalant aeroallergen sensitization.
A. Gaye*, M. Callaghan, Chicago, IL.
Rationale: To determine if measuring the specific poly-isotype IgG to basic
dietary proteins is helpful in designing an individualized avoidance diet for
non-allergic children with confirmed eosinophilic esophagitis (EE) Methods:
Report of a case series and review of the literature Results: EE is a chronic disease of unclear etiology with a suspected allergic component. A significant proportion of children with EE do not have the customary IgE or T cell-mediated
markers of dietary sensitivity which could guide their diet. Six (4 boys, 2 girls)
non-atopic immunocompetent children (mean 8y 8mo, range 4-14y) with
unequivocal EE, on no medical or dietary management by the time of testing,
and unwilling or unable to adhere to an elemental or empirically wide-ranging
elimination diet, followed an elimination regime tailored after the specific
IgG to the major dietary proteins consumed at the time of the initial consultation. One, two, or three, items were eliminated from their diet, chosen for the
IgG levels highest above the 2 standard deviation limit of the reference population of normal healthy individuals. Strict adherence to the diet was encouraged for a minimum of 3 months. The clinical progress was assessed by a noninvasive symptom scoring tool (EOSIN) designed in our service, at 6 week
interval for up to a mean of 9 months (range 5-20). The subjective improvement is the impetus to maintaining the diet. By the time of this report, the children are still following their diet and have not needed medication or further
invasive investigation. Conclusions: While waiting for precise genetic etiology and scientific explanations of the pathophysiology of EE, we propose to
identify a few proteins to be removed from the child’s diet by using the readily available method of measuring specific dietary poly-isotype IgG from a reputable laboratory. The interpretation of the IgG level against established normal ranges should be left to the allergy expert and the child’s parents with the
guidance of a dietician, for relevance, feasibility, and best continued adherence
to the diet. Controlling the symptoms of the children affected by EE and providing a diet that allows for their adequate growth and development are the
most important aspects of their treatment.
I.V. DuBuske1, A. Babakhin1,Y.A. Bisyuk1, N. Beaupre1, L. Von Olleschik2,
L.M. DuBuske*1, 1. Gardner, MA; 2. Schwerin, Germany.
Background: FastCheckPOC (2nd generation), has been developed as a
new generation easy to use point of contact assay for assessment of sensitization to common inhalant allergens. This test uses a diagnostics platform combining microfluidic liquid handling with lateral and transversal flow in a novel
device. Methods: Subjects with suspected respiratory allergic disease were identified based on symptoms of respiratory allergy. 108 allergen specific IgE determinations were performed using the FastCheckPOC assessing patient serum
employing a 30 minute assay protocol. Results of FastCheckPOC assessing
for presence of allergen specific IgE consistent with sensitization to common
allergens including house dust mites, common molds and dog dander were compared to results of Phadia UniCAP allergen specific IgE using >3.5 KU/L as
true positives which were clinically significant. The FASTCheckPOC results
were evaluated using two reference bands for comparison with 5 semi-quantitative levels determined including: Level 0 : negative; Level 1 : between CAP
classes I and II; Level 2 : border line between CAP classes II and III; Level 3
: between low CAP class III and top line CAP class V; and Level 4 : at or above
top line of CAP class V. Results: Sensitivity for detection of allergen-specific
IgE directed towards house dust mites (D. pteronissinus – d1 and D. farinae –
d2) was 88.23 %. Specificity for assessment of mold sensitization for Aspergillus
fumigatus – m3 was 86.66 %. Specificity for assessment of mold sensitization
for Alternaria alternata was 81.25 %. The Mean value of specificity for both
molds was 83.95 %. For dog dander sensitization specificity was 100 %. The
Objectives: The purpose of this study was to describe nonirritant skin test
concentrations as well as describe the frequency of immediate irritant skin reactions and delayed irritant reactions to military significant vaccines such as
anthrax, japanese encephalitis, meningococcal, and typhoid. Methods: This
study was approved by the Wilford Hall Medical Center IRB and written
informed consent was obtained from all research subjects. Seventeen subjects,
who met safety screening standards, were enrolled to have skin prick testing
at full strength concentration for the anthrax, japanese encephalitis, meningococcal, and typhoid vaccines. In addition, intradermal skin testing to 1:100,
1:10 and full strength concentrations were performed to all 4 vaccines. Patients
were monitored for immediate reactions as well as for any delayed reactions at
24-72 hours and 7 days post-procedure. Results: None of the subjects experienced irritant dose reactions to skin prick testing with anthrax, japanese
encephalitis, meningococcal, and typhoid vaccines. Immediate irritant dose
reactions were only seen in full strength vaccine intradermal testing, no reactions developed at the 1:100 and 1:10 concentrations for any of the vaccines
tested. Numerous delayed reactions did occurred after 24 hours post-procedure
and usually lasted over 7 days in duration but resolved within 21 days. The
delayed reactions were associated with findings of erythema and induration.
Residual hyperpigmentation took several days to fade completely. None of the
delayed reactions caused any permanent skin injury. Conclusions: Allergists
can feel confident in skin prick testing for anthrax, japanese encephalitis,
meningococcal, and typhoid vaccines at full strength concentration and should
K.S. Johnson*, C.W. Calabria, San Antonio, TX.
not expect results to be confounded by an irritant dose reaction. As well, intradermal skin testing to these same vaccines at the 1:100 and 1:10 concentrations
are not associated with generating an immediate irritant dose response thus
making the interpretation of these skin tests easier since rarely false positive
results are encountered. Allergists should interpret a positive intradermal at the
full strength concentration with care as 8-25% of the time an irritant dose
reaction was encountered. Delayed reactions are common and patients undergoing this type of testing should be warned of this phenomenon.
G.F. Pavon*, M. Gonzalez, M. Garcia, L. Teran, Mexico City, Mexico.
quent, while very few patients showed sIgE to Gal d 3 (6/46, 13.0%) or Gal d
5 (2/46, 4.3%). Using the FCT results as the reference parameter, sIgE to Bos
d 8 and Gal d 1 had the highest AUC. Use of 95% clinical decision points for
sIgE to Bos d 8 and Gal d 1 resulted in negative predictive values (78 and 79,
respectively) higher than those obtained with sIgE measured with the ImmunoCAP. Conclusion: in patients with sIgE allergy to CM or to HE, the microarray allergen test appears to have a good clinical performance in predicting the
outcome of the FCT. In a clinical application perspective the microarray could
be used as a second level assay, if the ImmunoCAP sIgE is <95% CDP. This
approach would lead to a decrease in the number of the FCT to be performed,
as well as of positive FCTs with a subsequent decrease in severe reactions
INTRODUCTION: Allergic diseases are a public health concern, 20% of
the world’s population suffers at least one of them, all of which represent a number of chronic and recurrent diseases most frequent in the world. Skin testsarediagnostic toolsable to identify patients with clinical history suggestive of
atopia to a given allergen. The description of the results published in different
studies in other countries about skin test cannot be extrapolated to our population, due todifferent conditions in factors such as age, race, occupation, geography or weather. MATERIALS AND METHODS: A cross-sectional studyin
patients withallergy was performedbetween 2007-2010.A positive skin test
(considered > 5 mm wheal) was carried out with a set ALK-AbellГі. The population was stratified by groupage, gender and allergic diseases, and we calculated frequencies with X2, with SPSS 16 software. RESULTS: We analyzed
data on 965 patients with positive skin tests,49.6%men, aged from 16 to 78
years. The most common allergens were Dermatophagoides pt. (Dpt) 25.5%,
Quercus sp.11%, Ligustrum vulgare 8.6%, Periplaneta Americana 8.0% and
Fraxinus excelsior 5.5%. The frequencies were: Rhinitis 41.8%, Asthma 37.9%,
Aspirin Exacerbated Asthma 8.4%, Allergic conjunctivitis 2.5%, Atopic Dermatitis 2.2.%,Urticaria1.2%. The frequencies of positive skin tests were higher
in men under 19 years to Dpt and Periplaneta, (p <0.05); after this age is more
common in women with positive Dpt, Fraxinus and Ulmus (p <0.05).Rhinitis
and Asthma had the same trend in the different age groups and gender (p <0.08).
The patients older than 6 years old with Asthma and Rhinitis had a higher positivity test to Dermatophagoides pt,Quercus and Ligustrum.( p <0.05). CONCLUSIONS: The number of positive skin test reported in our Institute have a
frequency of allergens and allergic diseases stratified by age and sex similar
to other published papers and shows positive change in adult women. The skin
test are safe and quick method to detect a patient’s sensitization to specific allergens, allowing better environmental control, and developing specific
immunotherapy to change the clinical course of allergic disease. Knowing the
frequency of most common sensitizing allergens in the Mexican population
will contribute to implementing health programs. PavГіn G,GonzГЎlez M,JuГЎrez
L,Garcìa M,Terán L.
Introduction: To determine the rate of atopy in patients with AERD (aspirinexacerbated respiratory disease) and to determine whether atopy affects the
response to aspirin desensitization. Methods: Inclusion criteria include patients
18 years or older with a clinical diagnosis of AERD who presented for aspirin
desensitization. Subjects on omalizumab, with a history of allergen immunotherapy, or with a negative histamine control were excluded. Subjects underwent
8 skin prick tests to a total of 33 common aeroallergens. Results: From our initial patient population who presented for aspirin desensitization (n=22), 8 of
them were found to be atopic. Interestingly, the most common causative allergens were found to be grass pollen, cat and dust mite. In addition to those with
positive skin tests, if patients who are currently or were previously on
immunotherapy are included in our study, the total number of patients would
increase to 30. Of those, 15 are likely to be atopic (50%). Finally, if we include
patients with positive skin test, history or current IT and currently on xolair,
our presumed rate of atopy would be 16 of 31 (52%). Conclusion: Although
included as a secondary data set in other studies, our study is the first prospective evaluation of the prevalence of atopy in patients with AERD. In this preliminary evaluation of the data, the rate of atopy appears to be approximately
52 %. This includes patients who are either skin positive or have been given
specific allergen treatment in the form of immunotherapy or omalizumab at
some time point. Intradermal testing was not performed. Intradermal testing
likely would have detected more sensitized patients, but with decreased certainty as to the clinical relevance. Further study should clarify the rate of atopy
in the AERD population. Atopy and AERD frequently co-exist. It is likely that
a treatment plan which does not include aggressive management of allergic disease will be less effective.
D.A. Swender*, L. Chernin, T. Sher, H. Tcheurekdjian, R. Hostoffer, Cleveland, OH.
G. Cavagni*, L. D’Urbano, K. Pellegrino, R. Luciano, S. Mancini,
C. Riccardi, A. Tozzi, L. RavГ , F. De Benedetti, Roma, Italy.
Background: the diagnosis of food allergy is based on allergen-specific history, skin prick test, the measurement of seric allergen-specific IgE (sIgE) and
the food challenge test (FCT). Although cut-off values of sIgE levels have been
proposed, the FCT still represents the diagnostic gold standard. The aim of
this study was to compare the performance of the measurement of sIgE with a
component-based allergen microarray (ISACв„ў version CRD89) and that of
the standard ImmunoCAP System™ in children with allergy to cow’s milk
(CM) or hen’s egg (HE) proteins that underwent FCT. Method: we enrolled 104
children, with clinically suspected diagnosis of allergy to CM (58) and HE (46).
In these patients we performed sIgE measurement with the CAPв„ў and ISACв„ў
and FCT. The performance of IgE reactivity to each component of microarray,
of the ImmunoCAP was evaluated by ROC analysis. Sensitivity, specificity,
positive predictive value (PPV) and negative predictive value (NPV) of the
two methods for sIgE measurement were evaluated as predictors of a positive
diagnostic FCT performed in all patients. Result: FCT was positive in 32/58
(55%) patients with suspected CM allergy and in 22/46 (44%) with suspected
HE allergy. IgE reactivities to Bos d 8 (27/58, 46.5%) and Bos d 4 (16/58,
27.6%) were more frequent, while very few patients showed sIgE to Bos d 7
(6/58, 10.3%) or lactoferrin (6/58, 10.3%). IgE reactivities to Gal d 1 (18/46,
39.1%), Gal d 2 (24/46, 52.1%) and Gal d 4 (17/46, 36.9%) were more fre-
S.S. Shah*, A.A. White, San Diego, CA.
Background: Skin prick testing (SPT) is considered a relatively safe method
for testing IgE-mediated allergic responses to various allergens. However, previous studies have described rates of systemic reactions, ranging from 0.02%
to 3.6%. Previous chart reviews and surveys of physician providers describe a
broad range of rates of systemic reactions. The current study was developed to
review a large number of patient charts over a broad period of time to better
describe the rate of systemic reactions to skin prick testing. Methods: We evaluated patient encounters where SPT was performed in an allergy/immunology
clinic. This retrospective chart review utilized billing and coding records during the time period from January 1997 to June 2010 to flag potential encounters where systemic reactions or anaphylaxis developed from SPT. Charts with
codes for epinephrine, intramuscular steroid or antihistamine administration
were reviewed when associated with SPT encounters. Results: We reviewed
28,907 patient encounters where SPT was performed. Of these, four patients
(0.02%) developed systemic reactions. All received epinephrine. There were
no fatalities. Average number of positive SPTs per patient was 36 (range 2647) (mean number positive tests to food, 21; mean number positive tests to
inhalants, 15). Conclusion: Skin prick testing is a relatively safe procedure,
with a rate of anaphylaxis of 0.02% in our population. This is the largest chartbased review of SPT-related systemic reactions to date and covers the longest
period of time. Further studies are needed to better characterize risks for developing systemic reactions during skin testing.
D. Wilson*, J. Lee, N. Camuso, D. Patel, A. Salapatek, Mississauga, ON,
statewide program with the collaboration of government agencies and a nonprofit organization to increase community awareness. Attack on Asthma
Nebraska should serve as a model for combining both asthma education and
treatment in our schools, to increase awareness in children, parents, teachers,
and the health care community alike.
S. Abu Hussein1, M. Wafaa*2, 1. Tanta, GHR., Egypt; 2. Cairo, Egypt.
Background:There are 2 major DM species, Der p and Der f, in N. America, however the extent to which patients respond to each of these or the degree
of cross-reactivity/sensitivity in an allergen challenge model is unknown. The
goal was to examine symptoms developed during exposure to Der p in an EEC
model. Methods:Approval was obtained from IRB with written consent for
30 DMA patients who were SPT positive for Der p and/or Der f. Patients were
exposed to 10-120ng/m3 airborne Der p for 3 hours over 4 consecutive days
(V2-V5). Total Nasal Symptom Scores (TNSS), sum of 4 individual nasal symptoms (NS) of congestion, rhinorrhea, sneezing and pruritis were measured (scale
of 0-3;possible maximum of 12) and collected prior to and
10,20,30,45,60,90,120,150 and 180 min post-EEC entry. Results:Seventy percent of patients were SPT positive to both allergens while 10% were positive
to Der p only and 20% to Der f only. The Der p only group had the highest mean
TNSS [5.3(V2),6.9(V3),7.3(V4),7.0(V5)] and AUC [1173(V2),1323(V3),
1551(V4),1398(V5)] during all EEC visits. Mean TNSS was less for Der f only
[3.4(V2),4.4(V3),4.4(V4),4.7(V5)] and Der p/Der f positive groups
[3.7(V2),4.0(V3),4.2(V4),4.6(V5)] as was mean AUC for Der f only
[749(V2),904(V3),882(V4),909(V5)] and both Der p/Der f [822(V2),809(V3),
876(V4),941(V5)]. Der p only group showed the highest pre-EEC carryover
from one visit to the next with mean TNSS of 0.0(V2),5.0(V3),3.0(V4), and
3.3(V5) compared to Der f only [0.3(V2),1.0(V3),1.5(V4),3.3(V5)] or both Der
p/Der f positive [0.2(V2),1.0(V3),1.0(V4),1.6(V5)]. Conclusions:Most patients
were SPT positive to both Der p and Der f, responding to controlled airborne
Der p exposure in the EEC with significant and reproducible NS, supporting
the molecular evidence that there should be cross-reactivity/sensitivity to DM
allergens. Exclusive Der p sensitive patients had highest TNSS suggesting these
patients are most responsive to Der p exposure in the EEC. Subtle differences
in symptom responses to inter-species allergens shows the DMA EEC model
is a sensitive and effective clinical model to better understand the etiology of
perennial allergens like DM and to study putative anti-allergy therapeutics.
Introduction: Hemopoietic cytokines play a crucial role in the activation
and survival of cells involved in asthmatic inflammation. Stem cell factor (SCF)the c-kit ligand, although initially was described as a mast cell growth factor
appeared to be a pleiotropic cytokine exerting its role at the first stages of
bone marrow stem cells development, inducing eosinophil activation and
basophil chemotaxis and survival. As mast cells and eosinophils are key cells
in the inflammatory process ongoing in the airways of patients with asthma
the role of SCF in this disease has been studied. Aim of the Study: The aim
of the study is to assess if the concentration of SCF and its soluble receptor ckit in peripheral blood is increased in patients with asthma and if it correlates
with disease severity and asthma phenotype. Methods: The study involved 51
patients with bronchial asthma, well characterized with respect to severity and
7 healthy controls. SCF assessed in 29 patients with bronchial asthma (severe
– non-severe), and soluble c-kit was evaluated in 22 asthmatic patients also
according to severity. Concentration of SCF and sc-kit in the patients’ serum
were measured by ELISA method. Results: Mean serum SCF level in the group
of asthmatics (n= 29) was significantly higher as compared to healthy controls.
The level of SCF was higher in patients with severe asthma as compared to
patients with non-severe asthma. The mean sc-kit serum level (n= 22) did not
differ between asthmatic patients and healthy controls; however the level of
sc-kit in non-severe asthmatics was significantly higher as compared to patients
with severe asthma and healthy controls. The level of sc-kit correlated positively with FEV1% predicted value. Conclusion: Serum levels of SCF and its
soluble receptor c-kit increased according to asthma severity and this indicates the role for these molecules in asthmatic inflammation.
T. Lee*1, C.L. Chang2, J.J. Stephenson2, S. Sajjan3, E.M. Maiese3, F. AllenRamey3, 1. Chicago, IL; 2. Wilmington, DE; 3. West Point, PA.
T. Nguyen*, K. Murphy, A. Holka, R. Hopp, Omaha, NE.
Introduction: Asthma is a major cause of morbidity in children. In response
to this issue in 1998, the Emergency Response to Life-Threatening Asthma or
Systemic Allergic Reactions (Anaphylaxis) Protocol was designed and evaluated in 78 Omaha public schools and, based on its success, led to adoption of
a revised protocol for all Nebraska schools, public and private in 2004 (Murphy et al, Ann Allergy Asthma Immunol. 2006;96:398-405). It also led to the
establishment of Attack on Asthma Nebraska, a nonprofit organization that
partnered with the Nebraska Department of Education to mandate this protocol, ensure proper education and training, to support collaborative partnerships,
and to promote asthma and allergy education and awareness in the community. Methods: Nurses and school staff were trained in an emergency protocol,
which requires administration of nebulized albuterol and intramuscular epinephrine in concordance with the emergency response procedure (911). Outcomes were measured by improvement in acute care in school and individual
survival, which are reported from 2004-2010 for all 1513 Nebraska schools
(grades K-12). Results: Based on the incident reports generated by the protocol from May 2004 through June 2010, 282 individuals were successfully
treated. 72% received both albuterol and epinephrine, 19% received albuterol
only and 9% received epinephrine only. 911 was called in 82% of incidents.
CPR was not performed in any incident and no deaths were reported. Of 192
individuals treated who had history of asthma, 93 had asthma action plans
(AAP). Of the 99 students who did not have an AAP, 42 returned subsequently
with an AAP. Of the 27 individuals treated who had history of anaphylaxis, 13
had an anaphylaxis action plan and 14 did not. 7 of those 14 returned with an
anaphylaxis action plan. Conclusions: This school-based treatment protocol for
asthma and anaphylaxis was effectively implemented and expanded into a
Introduction: Several options for asthma controller therapy currently exist.
Differences in medication adherence may impact asthma-related resource use
and costs for various regimens. Methods: A retrospective analysis of a US managed care claims database was conducted to examine asthma-related resource
use and costs among adults (18-56 years) who initiated asthma controller therapy between Jan 2005 and Mar 2008. Patients had 2 years continuous enrollment and >1 medical claim for asthma (ICD9: 493.xx) between Jan 2004 and
Mar 2009. Asthma exacerbations, short-acting β-agonist (SABA) fills, adherence to controller therapy (MPR ≥ 80%) and asthma-related costs were assessed
for 1 year after initial asthma controller medication claim. Separate logistic and
negative binomial regression models for monotherapy and combination regimens were developed to assess the impact of controller therapy on outcomes
while controlling for patient characteristics, asthma risk, year, season, region
and type of care providers. Results: A total of 28,074 patients [inhaled corticosteroids (ICS) (26.3%), leukotriene modifiers (LM) (23.2%), ICS+long acting ОІ-agonist (LABA) (48.5%), ICS+LM (2%)] were included. LM patients
had lower odds of >6 SABA fills (ORadj = 0.83, 95% CI: 0.73-0.96) and lower
rate of asthma exacerbations (RRadj= 0.82, 0.75-0.89) compared to ICS patients.
For combination therapy, odds of ≥6 SABA fills were similar for ICS+LM vs.
ICS+LABA patients (ORadj=1.3, 0.96-1.76) while the rate of asthma exacerbations was greater for ICS+LM patients compared to ICS+LABA patients
(ORadj=1.4, 1.2-1.6). Odds of treatment adherence were significantly greater
for LM patients compared to ICS (ORadj =11.7, 9.5,14.4). The odds of adherence were similar for ICS+LABA and ICS+LM patients. LM patients had higher
unadjusted pharmacy costs, but lower medical costs compared to ICS patients.
For combination therapy, ICS+LM patients had higher unadjusted mean medical and pharmacy costs compared to ICS+LABA patients. Higher adjusted
mean total costs in the post-index period were observed for LM vs. ICS patients
($837 vs. $684) and for ICS+LM vs. ICS+LABA patients ($1,223 vs. $873).
Conclusion: In monotherapy patients, LM was associated with better asthma
control than ICS as evident by a lower exacerbation rate and fewer SABA fills
than ICS. Greater adherence among LM patients influenced the higher total
costs observed.
Determinants of Air Trapping in Asthma (Table 1).
E. AL-Selahi*, C. Kalicinsky, A. Becker, Winnipeg, MB, Canada.
Background: In 2003 pediatric allergists and nurse educators at Winnipeg’s
Children’s Hospital Pediatric Allergy Department identified children deemed
to be high risk asthmatics. Inclusion criteria includes: admission to pediatric
intensive care unit (PICU), repeated admissions (>1/yr), admission/ER visit
for anaphylaxis, repeated ER visits (> 1/yr), use of >1 beta-agonist inhaler canister in a month, frequent missed clinic appointments and adolescents at risk
for anaphylaxis. A nurse educator was assigned to follow each family closely
between clinic visits. Each child in this group is reviewed during monthly high
risk asthmatic cohort round. Objective: To determine whether there are characteristics common to children in a high risk asthma cohort in addition to the
criteria used to define them as high risk asthmatics at Children’s Hospital in
Winnipeg. Methods: Charts of asthmatic children ages 5-17 who met the criteria for inclusion in the high risk asthma cohort from 2003-2010 were reviewed.
Results: Total of 102 charts were reviewed. 74% (73/99) were male and 26%
(26/99) were female. 29% (29/100) had PICU admission. Mean age was
(10.5В±4.2) years. Mean BMI was 19.8, mean BMIz score was (0.6В±1.1). 41/97
had allergic rhinitis, 40/97 had eczema, 38/98 had food allergy (14/38 egg, 8/38
milk, 24/28 peanut, 13/38 fish, 7/38 other). 74/94 were skin test positive to
environmental allergens (57/74 cat, 46/74 mold, 25/74 other). 21% (6/29) of
PICU admitted children had food allergy, and 78% (21/27) had environmental
allergy. 54/73 males were < 14 years of age (prepubertal), 19/73 were ≥ 14 years
of age. 17/26 females < 13 years of age (prepubertal), 9/26 ≥ 13 years of age.
77% (64/83) had mild obstruction (FEV1≥80%), 22% (18/83) had moderate
and 1% (1/83) had severe obstruction. 62% (41/66) of males had normal BMI
Z score compared to 68% (17/25) of the females. Household income was determined based on postal code, majority of the families in this cohort are low
income. Conclusion: In addition to the criteria which define this cohort, variables such as skin test positivist to environmental allergens (cat, mold), food
allergy, allergic rhinitis, eczema, and lower household income are common to
this group. The very atopic male, < 14 year old asthmatic with food allergy,
whose family is in the lower income bracket should be given close attention
based on the analysis of this cohort.
M. Blumberg*, D. Ko, S. Jeffrey, T. Rickey, Richmond, VA.
A retrospective chart review was done of all patients (151) seen in an outpatient allergy and asthma practice between May 2007 and June 2010 and evaluated with methacholine challenge for symptoms consistent with asthma, but
without significant FEV-1 reversibility. Demographic factors were analyzed
to evaluate which would predict challenge results. Accuracy of prior asthma
diagnosis was assessed. Information obtained included patient age, gender,
race, occupation, atopic status, family and smoking history, BMI, time with
symptoms, recent diagnosis, medications and challenge results. A challenge
was positive if FEV-1 decreased ≥20% at ≤8mg/ml methacholine. Average age
of patients 40В±20 years, 72% female, 83% caucasian and 15% african-american. Symptoms were present 43В±72 months. Thirty-six percent of patients had
a current diagnosis of asthma and 42% had chronic cough. Thirty-two percent
were on combination ICS/LABA, 25% ICS and 7% LTRA. Fifteen percent had
≥10 pack-year smoking history, 42% GERD, 20% a parent with asthma and
67% a positive prick skin test. Forty-three patients(28%) had a positive methacholine challenge. The only predictor of a positive challenge was a prior diagnosis of asthma. Twenty-four of the 43 patients(56%) with a positive challenge had a prior asthma diagnosis while 30 of 54(56%) with a prior asthma
diagnosis had a negative challenge. Parental history, race, gender, skin tests and
BMI were not associated with a positive challenge. Only 13 of 64 patients(20%)
with chronic cough had a positive challenge. Most patients treated for years
with ICS/LABA or ICS alone did not have a positive challenge. Chronic cough
without FEV-1 reversibility was usually not a symptom of asthma.
M.H. Bashir*, F.H. Bashir, A.N. Escobar, J. Joseph, Fresno, CA.
N.S. Brady*, Colorado Springs, CO.
Purpose: Asthma is characterized by reversible airway obstruction in presence of an appropriate clinical history. Air trapping is mostly thought to be
associated with Severe Asthma. However, the prevalence and the determinants
of air trapping in a stable population of subjects with asthma are unknown.
Therefore, we estimated the prevalence of air trapping and factors affecting
RV/TLC ratio in a population of asthmatics Methods: We retrospectively evaluated 286 patients with diagnosis of asthma who had a pulmonary function test
done in 2008 and 2009. Patients with COPD were excluded from the study. The
determinants considered for air trapping in our cohort were age, gender, ethnicity, BMI, smoking history, FEV1, FEF 25%—75% and % Change in FEV1.
A quartile distribution of RV/TLC ratio was used to categorize patients into
mild, moderate and severe air trapping. For logistic regression analysis, subjects with RV/TLC ratio of >35 were classified as having significant air trapping (Fig 1). Results: Of 286 patients 88 (31%) were male and 198 (69%)
were females. The mean age was 48 years and BMI 33. The ethnicity was Caucasians 140 (49%), African Americans 29(10%), Hispanics 111 (39%) and
Asians 6 (2%) . One hundred thirty-four (47%) were smokers. Air trapping was
absent in about 83 (29%) and mild air trapping was observed in 79 (28%) moderate in 64 (22%) and severe in 60 (21%). Table 1 shows the results of logistic
regression analysis. Conclusion: Significant air trapping was present in 61%
of asthmatics. Age and FEV1 had a positive correlation to air trapping. There
was no association between smoking and FEV1 reversibility to the presence
of air trapping. Further, a significant negative correlation between BMI and
air trapping has not been observed in asthmatics and the significance of this
finding needs further investigation.
INTRODUCTION Asthma is a common respiratory disease process in children. Osteopathic manipulative therapy (OMT) includes manipulation of the
musculoskeletal and lymphatic systems. We developed a study to determine if
osteopathic therapy would have an effect on children with asthma. METHODS
Children 4 to 17 years old with moderate persistent asthma were eligible and
block randomized to two groups. Approval was obtained from University Hospitals, Cleveland. RESULTS The treatment group showed no improvement in
FEV1 with a change of 0.001L, while the control FEV1 decreased by 0.075L.
Analysis showed no significant improvement in FEV1 in either the treatment
(p=0.982) or the controls (p=0.081). Analysis of the change in FEF25-75,
showed no improvement in either the treatment (p=0.532) or the controls
(p=0.401). Comparing subjective scores, there was a nonsignificant improvement in the treatment group (p=0.331), but no improvement in symptom score
with the controls. DISCUSSION Our findings showed no significant difference between the treatment and control groups. The increase in FEV1 in the
treatment group of 0.001L is not clinically significant. The control group average FEV1 decreased by 0.075L. While clinically measurable, it did not meet
statistical significance. Similar results were seen in FEF25-75, with an increase
in the treatment group of 0.069L and a more impressive but not statistically
significant increase of 0.442L in the controls. The subjective asthma symptoms
showed no difference between treatment and control groups. The treatment
group had an average starting score of 4.83 with improvement to 4.9 (p=0.331).
The control group had the same average pre and post treatment score of 4.9.
There are limitations that may have affected the results. Primarily, the study
was limited in size. Another limitation was the study was not double blinded.
The treating physician was aware of which patient was receiving targeted treatment versus those in the control group. Finally, the measurements of symptomatology and FEV1 were patient dependent. CONCLUSIONS A specific OMT
protocol did not significantly improve pulmonary function or subjective asthma
symptoms, in pediatric patients with moderate persistent asthma. Further studies would be warranted in this field.
Asthma Questionnaire
was dog (n= 30) and the least frequent was roach (n = 13). Mean measured dust
allergen levels to pets and pests were Fel d1=80 ng/g, Der f1 and Der p1=532
ng/g, Can f1=388 ng/g, Mus m1=196 ng/g, and Bla g2=112 ng/g. Mean measured allergen levels to mold were cladosporium=9.03 ug/g, alternaria=5.19
ug/g, aspergillus=5.24 ng/g, and penicillium=6.07 ng/g. Mean airborne total
spore levels were 2618/m3 of air with mean cladosporium levels of 176/m3
and mean aspergillus/penicillium levels of 1389/m3. Among atopic subjects,
asthma severity positively correlated to dust allergen levels of Fel d1, Can f1,
and Mus m1 regardless of specific sensitization. Conclusion: Although mean
house dust allergen levels in our cohort are lower than levels published for other
urban areas, we found a positive correlation of dust levels of pet and pest allergen and asthma severity.
H. Chung*, M. Ju, J. Shin, Taegu, Korea, Republic of.
Mycoplasma pneumoniae (M. pneumoniae) is a common cause of pneumonia in children and a link between chronic asthma has been suggested. However, it has not been well studied whether the children’s immune response during M. pneumoniae pneumonia is affected by the presence of atopic asthma.
In the present study, seventy-five children, 6-12 years of age, admitted with
M. pneumoniae pneumonia were enrolled. Two patient groups were defined;
atopic, asthmatic patients (N=36) and. non-atopic, non-asthmatic patients
(N=39). Interleukin (IL)-18 and selected chemokines, IL-8, CXCL9, CXCL10,
and regulation upon activation normal T-cell expressed and secreted (RANTES)
were measured by means of ELISA in the plasma samples collected on admission. We also studied the values of these mediators in relation to the severity
of pneumonia. The severity score ≥ 3 was defined as severe pneumonia and ≤
2 as non-severe pneumonia. Plasma levels of IL-18 and the chemokines
increased significantly in the patients with acute M. pneumoniae pneumonia
compared to non-infected, age-matched controls (N=20) (P<0.01). However,
asthmatic patients showed significantly decreased IL-18 and CXCL10 levels
(P<0.01, <0.05, respectively), and had higher severity score (P<0.01) compared
with non-asthmatic patients. IL-18 was significantly lower in severe pneumonia group than in non-severe group (P<0.05). Our study suggests that IL-18
and the chemokines are importantly involved in the pathogenesis of M. pneumoniae pneumonia. It also indicates that some patients with atopic asthma have
significantly deficient IL-18 response, which might be associated with more
severe pneumonia observed in this group of patients.
C.E. Ciaccio*, F. Pacheco, K. Kennedy, L.C. Gard, R. Allenbrand,
J.M. Portnoy, C.S. Barnes, Kansas City, MO.
Introduction: Children with asthma have a high prevalence of allergic sensitization to indoor environmental allergens. These allergens are frequently
found in the homes of asthmatic children during environmental home assessment. In 2008, the Kansas City Safe and Healthy Homes Program (KCSHHP)
began enrollment of children with chronic illness in order to evaluate the effect
of living conditions and targeted intervention on asthma severity. This study
attempts to characterize the indoor allergens collected from the homes of this
cohort, and their impact on asthma severity. Methods: This study was approved
by our Institutional Review Board and written informed permission/assent was
obtained from each family. Charts of the first 200 families enrolled in the
KCSHHP were reviewed. Vacuum dust and airborne fungal spores collected
from the enrolled child’s bedroom were available from the homes of 100 families. Dust allergen levels were measured by enzyme immunoassay. Airborne
fungal spores were collected onto a silicon-grease coated glass slide and counted
using light microscopy. Asthma severity was assigned a number on a scale of
1 to 6 depending upon reported symptoms, medical utilization and medication
use. Subjects were tested for specific IgE to cat, dog, dustmite, cockroach,
alternaria, aspergillus, cladosporium and penicillium by ImmunoCAP technology. Results: Of the 100 subjects, 75 were asthmatic and 60 were sensitized
to at least one indoor allergen. The most frequent sensitizing indoor allergen
M. Cohen*, A. Kivelowitz, R. Brehm, Brooklyn, NY.
Introduction One of the hallmark effects of reactive airway disease is poor
sleep quality. Because air pollutants worsen symptoms in these patients, a logical intervention to improve sleep quality may be air filtration. The PureNight
Air Filtration is a novel system that delivers pre-filtered air around the head of
a sleeping person and may improve sleep quality by decreasing exposure to
noxious triggers. We hypothesized that subjects would have improved sleep
quality while using PureNight than during no filtration. Methods One method
to measure sleep quality is 24-hour actigraphy. The actigraph is a device that
contains an accelerometer that measures wrist movement. Algorithms interpret
movement on an epoch-by-epoch basis and identify sleep/wake states and circadian rhythm cycles from activity counts. In a cross-over double-blind randomized trial, measurements were taken at baseline and then during treatment
with PureNight and with “sham” filtration in random sequence. Sleep quality,
circadian rhythm and sleep quality-of-life (Pittsburgh Sleep Quality Index
[PSQI]) were compared between test conditions. Approval was obtained from
VA, NYHHCS IRB; written informed consent was obtained from all subjects.
Results 13 men and 4 women with self-reported sleep disturbance due to respiratory symptoms completed testing. All subjects had obstructive disease by
spirometry; 11 subjects had significant response to a bronchodilator. Actigraphy-defined sleep fragmentation and wake bouts were significantly better during PureNight filtration than during baseline or sham. Baseline PSQI scores
were high (>75% of scores >5); total scores and reported sleep duration
improved during PureNight over sham and baseline. Inter-day stability (circadian rhythm) favored PureNight over baseline but not sham. In sub-group analysis, only those with bronchodilator response had significantly less sleep fragmentation and wake bouts and lower (better) PSQI scores. Conclusion PureNight
air filtration significantly improved objective sleep maintenance and subjective sleep quality in a small cohort of subjects with obstructive airway disease,
predominantly in those with bronchodilator response. Results suggest that a
meaningful improvement in sleep quality with PureNight air filtration is likely
in patients with symptomatic reactive airways disease.
Comparison of Sleep Measures
n=17, *p<0.05, **p<0.01; sd= standard deviation
V.N. Tsibulkina*1, N.N. Mazitova1, A.A. Saveliev1, L.M. DuBuske2, 1.
Kazan, Russian Federation; 2. Gardner, MA.
Background: The pathogenesis of the inflammatory response in COPD may
be associated with inflammatory cytokine responses among workers exposed
to silica. Methods: 88 male foundry workers with silica dust exposure includ-
ing 33 with occupational bronchitis, 36 with occupational COPD and a control group of 11 healthy foundry workers were studied. 8 patients with cigarette induced COPD formed a second control group. Levels of interleukin (IL)1ОІ, IL-6, IL-8, tumor necrosis factor-О±, interferon (IFN)-Оі, О±1-antitrypsin
(AAT) were analyzed. Spirometry was performed. Diagnosis of COPD was
determined by GOLD criteria. Results: The greatest levels of cytokines were
found in patients with occupational COPD, followed by occupational bronchitis, with lower levels were found in cigarette induced COPD and healthy controls, differences being greatest for IL-1ОІ, IL-8 and IFN-Оі. A logistic regression analysis model showed increasing the level of IL-1 increases the probability
of occupational COPD development. In a logistic probability model for occupational COPD, significant variables were occupational quartz exposure (pvalue = 0.03; z-value = 2.167) and years of exposure (p-value = 0.02; z-value
= 2.228), both also being significant determinants for the expression of inflammatory cytokine responses. Conclusion: Both smoking and exposure to silica
dust impact on the development of occupational COPD. IL-1 may serve as a
biomarker of inflammatory responses in occupational COPD.
A. Emelyanov*1, I. Tsukanova1, G. Fedoseev1, G. Sergeeva1, N. Lisitsyna1,
L. Bakanina1, E. Nikitina1, L.M. DuBuske2, 1. St. Petersburg, Russian Federation; 2. Gardner, MA.
Background: This study was performed to assess the changes in diagnosis
and treatment of asthma over 7 years in primary health care facilities in Saint
Petersburg, the second largest city in Russia. Methods: Case record forms (CRF)
of 1248 outpatients 18 to 89 years old with asthma were reviewed in 13 outpatient departments in 7 residential areas in Saint Petersburg in 1998, 2002 and
2005 (253, 579 and 416 CRFs respectively). Completeness of CRF’s was determined by the presence of documented assessments for allergic history, spirometry with reversibility, and results of skin prick tests or measurement of allergen specific IgE. Results: Complete diagnostic evaluation of asthma was noted
in 8.4 % of CRF from 2005, versus 14.9% of CRF from 2002 and only 0.4%
of CRF from 1998 (p<0.001). Inhaled corticosteroids (ICS) were most often
prescribed for persistent asthma patients in 2005 (88%) versus 63% in 2002
and 46% in 1998 (p<0.01). Oral steroids were more frequently used in 1998
(32%) and 2002 (28%) versus 14.9% in 2005 (p<0.001). The use of short-acting beta(2)-agonists increased from 64.4% in 1998 to 77.7 in 2002 and to 89.9%
in 2005 (p<0.001). Fixed combinations of budesonide/formoterol and fluticasone/salmeterol were not used in 1998 while their prescriptions were increased
from 0.9% in 2002 to 34.9% in 2005 (p<0.001). Conclusion: There were
improvements in the quality of asthma diagnostic assessments from 1998 to
2002 but no further improvements were seen by 2005. The overall quality of
asthma diagnostic assessments was low, with 85% to 90% of cases having inadequate assessment of asthma especially related to the presence of allergic disease and use of spirometry. Asthma treatment, however, has shown dramatic
increases in the use of inhaled corticosteroids and combination inhaled corticosteroid/ long acting beta agonist products with a reduction in oral steroid
use over this same time period consistent with a significant impact of global
asthma treatment guidelines on asthma treatment in Russia.
T.Z. Kralimarkova1, V.D. Dimitrov1, L.M. DuBuske2, T.A. Popov*1, 1. Sofia,
Bulgaria; 2. Gardner, MA.
Background: Measurement of exhaled breath temperature (EBT) may be
useful as a surrogate biomarker of airway inflammation. A portable user-friendly
device with a high level of precision and reliability has allowed for easy assessment of EBT in adult subjects. This study assesses the utility of this device for
measurement of EBT in children. Methods: EBT was evaluated in 39 consecutive patients (29 boys and 10 girls, age range 3 and 17 years) referred to the
outpatient pediatric department of the Clinic of Allergy & Asthma in Sofia.
Measurements of EBT were done by means of a hand-held device (X-halo,
Delmedica Investments Ltd, Singapore) as part of the regular objective assessments, following an informed consent of the children’s parents / guardians.
Children and their accompanying persons were briefly instructed on how to use
the X-halo device. Diagnoses of the children were based on the overall judgment of the consulting physician without consideration of the EBT values.
Results: All children, irrespective of their age and gender, were able to provide
meaningful values of EBT. There was no correlation between the EBT and the
routinely measured otic temperature. Younger children tended to have lower
EBT. The patients had a broad spectrum of diagnoses including asthma (8
children), allergic rhinitis (14 children), chronic cough (6 children), viral upper
airway infection (8 children), and skin allergic diseases (3 children). EBT was
higher in children with upper and lower airway diseases including asthma, allergic rhinitis and viral respiratory infections. The widest range of EBT values
was among the children with chronic cough. Conclusions: EBT measurement
with the X-halo device is non-invasive, easily applied method in an outpatient
pediatric clinical setting. EBT may be impacted by age. EBT is independent
of otic temperature and may provide an indication of the presence of inflammatory upper or lower respiratory tract diseases.
S. Fitzpatrick*, R. Joks, W. Shaikh, A. Schneider, J. Silverberg, Brooklyn,
Rationale: Asthma is reaching epidemic levels in the United States, where
8% of the total and 10% of the African-American populations suffer from this
disease. Obesity rates are also increasing, where 33.8% of the population suffers from obesity. However, the relationship of obesity and asthma is not well
defined. Methods: We conducted a retrospective practice-based cohort study
of an adult allergy/asthma clinic (n=107). Height and weight were used to calculate body mass index (BMI). Logistic regression was used to determine the
association between BMI and asthma. BMI was modeled as a continuous variable and as an ordinal variable for normal weight (normal BMI (<25), overweight (25-30), obese (30-35) and super obese (>35). Results: Ninety subjects
(84.4%) were Afro-American/Caribbean and 83 (77.5%) were female, with
mean age 43.7 yrs В± 15.4 yrs. Mean BMI was 30 В± 7.7. 41 (38.3%) subjects
were diagnosed with asthma. BMI, modeled as a continuous variable, was significantly associated with asthma (odds ratio (OR) =1.174, 95% confidence
interval (CI) =1.09-1.27). Obesity (n=24) and super obesity (n=23) were significantly associated with asthma when compared to normal weight subjects
(obesity: OR=5.3, 95% CI=1.4-19.9, P=0.0138; super obesity: OR 17.7, 95%
CI=4.3-72.3, P<0.0001). Overweight (n=31) was not significantly associated
with asthma (OR=2.6, 95% CI=0.7-9.5, P=0.1602). In contrast, there was no
association of age or gender with asthma (P=0.63 and P=0.26, respectively).
Conclusion: Our findings suggest a strong link between increasing obesity
and asthma, which may potentiate one another. Aggressive interventions for
weight loss may be an important adjunctive strategy for the treatment of asthma.
G. Colice*1, T. Craig2, J. Parsons3, M.L. Hayden4, S. Stoloff5, N. Eid6,
N. Ostrom7, 1. Silver Spring, MD; 2. Hershey, PA; 3. Columbus, OH; 4.
Reston, VA; 5. Carson City, NV; 6. Louisville, KY; 7. San Diego, CA.
Introduction: Although EPR-3 treatment guidelines recommend the use of
short-acting beta agonists (SABAs) prior to exercise in patients with exerciseinduced bronchospasm (EIB), there are limited data on how well these recommendations are being followed. Objective: To assess physical activity, exercise-related respiratory symptoms, and use of SABAs in adults with asthma.
Methods: The EIB Landmark Survey is the first comprehensive study focusing on exercise-related respiratory symptoms in the United States. This national
cross-sectional survey was conducted in adults (≥18 years) with asthma or
taking medications for asthma in the prior year. Parameters assessed included
exercise-related respiratory symptoms, activity levels, and SABA utilization.
Results: Survey responses from 1001 adults with asthma were obtained. Exercise (30.9%) was the most commonly reported asthma trigger in respondents.
Although 8 of 10 adults experienced at least 1 of 6 exercise-related respiratory
symptoms (coughing, shortness of breath, chest tightness, wheezing, noisy
breathing, trouble getting a deep breath), only 30.6% reported being diagnosed
with EIB. A majority of all respondents (76.3%) “strongly agree” or “somewhat agree” that exercise is more beneficial than harmful for persons with
asthma. 45.6% of adults avoid activities because of their symptoms. 41.2% of
respondents reported that asthma limits them “a lot” or “some” in going to the
gym or exercising. 2.6% of respondents reported never playing sports or exercising. Of those who reported exercise-related respiratory symptoms, 54.6%
said their symptoms last ≥10 minutes; 8.1% said their symptoms last >30 minutes; 15.6% said their symptoms last until they use their SABAs. Despite symptoms, 44.4% of individuals continued exercising “always” or “most of the time.”
Only 22.2% of respondents took their SABAs before exercise “always” or “most
of the time”; 36.3% took their rescue medications after or during exercise. Conclusions: Although exercise-related respiratory symptoms are prevalent, EIB
is often underdiagnosed. While many subjects stated that their asthma symptoms limit their physical activity, less than 25% adhered to treatment guidelines by utilizing SABAs prior to exercising. Patient education is needed to
support proper use of SABAs in optimizing the management of EIB.
N. Eid*1, N. Ostrom2, M.L. Hayden3, T. Craig4, J. Parsons5, S. Stoloff6,
G. Colice7, 1. Louisville, KY; 2. San Diego, CA; 3. Reston, VA; 4. Hershey,
PA; 5. Columbus, OH; 6. Carson City, NV; 7. Silver Spring, MD.
Introduction: Use of short-acting beta agonists (SABAs) prior to exercise
is recommended in patients with exercise-induced bronchospasm (EIB). Objective: To assess physical activity, exercise-related respiratory symptoms, and use
of SABAs in children. Methods: The EIB Landmark Survey is the first comprehensive study focusing on exercise-related respiratory symptoms. This survey was conducted with parents of school-aged children (4-17 years) with
asthma or taking medications for asthma in the prior year. Parameters assessed
included exercise-related respiratory symptoms, activity levels, and SABA utilization. Results: Exercise was the asthma trigger most commonly reported by
parents (N=516) in this population; almost half (45.6%) of all children have
experienced at least 4 of 6 exercise-related respiratory symptoms (coughing,
shortness of breath, chest tightness, wheezing, noisy breathing, trouble getting
a deep breath). 80% of respondents “strongly agree” or “somewhat agree” that
exercise is more beneficial than harmful for persons with asthma. Parents
reported that their child’s health limits their ability to participate in sports in
school: 12.5% of children aged 13-17 and 6.5% of children aged 4-12 are limited “a lot.” Adolescents were also more likely to avoid activities because of
EIB symptoms compared with younger children (31.8% vs 22.2%, respectively). Furthermore, 46.9% of children continue exercising with symptoms
“sometimes,” “only rarely,” or “never.” Of those with exercise-related respiratory symptoms, 41.6% had symptoms that last ≤10 minutes; 9.8% had symptoms that last >30 minutes; 21.9% had symptoms that last until a SABA is used.
23.1% of children with asthma took bronchodilators such as albuterol “always”
or “most of the time” before exercise; 27.7% took them after exercise. Conclusions: EIB interferes with the ability of children to participate in exercise
and physical activity. Many children and adolescents with EIB experience symptoms with exercise, which may contribute to their avoidance of physical activity. Therefore, SABAs should be utilized before exercise as recommended by
treatment guidelines. Further analyses are planned to assess whether there is a
correlation between BMI and uncontrolled exercise-related symptoms in this
3mm wheal with flare reaction to a common aeroallergen by the prick method
with appropriate skin test controls. There was a seasonal increase in sputum
eosinophilia during the Spring, Summer and Fall (mean value 14.4; median
[IQR] 3 [0-18.25] with a nadir of sputum eosinophils during the winter months
December, January, and February, (mean value 4.11; median [IQR] 1 [0-4] ),
p value 0.003. Eosinophil percentages peaked in the months of August and
October (mean values 16.6, 22.2; medians [IQRs] 5.5, 4 [1.75-24, 0-45] ), p
values <0.001, 0.0197, respectively and were significantly increased compared
to the winter season. These findings occurred despite significant inhaled (57.8%)
and oral (13%) corticosteroid use. CONCLUSIONS: Sputum eosinophilia in
atopic asthmatics appears to exhibit seasonal variation. Prospective studies
are needed to confirm these preliminary findings. Validation of seasonal periodicity in sputum eosinophilia could have profound implications regarding
the importance of allergy assessments and treatment options in atopic asthmatics.
J.B. Hales*1, M.E. Wechsler2, R. Niven3, C. Prys-Picard3, M. Castro4,
G. Cox5, 1. Arlington, VA; 2. Boston, MA; 3. Manchester, United Kingdom;
4. St. Louis, MO; 5. Hamilton, ON, Canada.
Introduction: BT is a procedure that improves asthma control by reducing
excessive airway smooth muscle mass. Three randomized controlled trials evaluating the effect of BT with the AlairВ® System in patients with varying asthma
severity supported the approval of BT by FDA in April 2010. Review of inclusion and exclusion criteria from these studies helps identify the appropriate
patient selection for BT. Methods: Patient selection criteria for the AIR, RISA,
and AIR2 trials were related to respiratory-related hospitalizations following
BT. Patients in all 3 trials were managed on ICS+LABA at baseline. According to NAEPP guidelines, AIR patients were moderate to severe, RISA patients
were severe refractory, and AIR2 patients were severe. Treatment period (1st
procedure to 6 wks after last procedure) respiratory-related hospitalizations
were compared across studies. Results: Hospitalizations in the Treatment Period
were more frequent in RISA (15.6%) compared to AIR (3.7%). Patient factors
that were potentially related to increased hospitalization risk after BT included:
Post-bronchodilator FEV1 < 65% predicted; Use of OCS > 10 mg/day for
asthma; ≥ 3 hospitalizations for asthma in past 12 months; ≥ 4 LRTI in the
past 12 months; ≥ 4 pulses of OCS for asthma in the past 12 months Avoiding
these factors likely contributed to the reduced the rate of hospitalization in AIR2
(3.4%) to a rate similar to AIR. Conclusions: BT is a procedure-based treatment for patients with severe asthma not controlled with conventional therapy.
To reduce the potential risk of hospitalization around the time of treatment,
patients should be stable with respect to asthma status for at least 2 weeks before
BT. Patient selection criteria developed in AIR2 may have reduced the periprocedure risk of hospitalization and should be considered when scheduling
patients for BT. Patients with higher risk for hospitalization may be treated but
warrant appropriate observation and post-procedure care, including extended
recovery time. Previously presented data suggests that such patients likely benefit in the long term from BT so should still be considered for treatment.
J.B. Hagan*, H. Kita, Rochester, MN.
INTRODUCTION: Metaanalysis has shown that sputum eosinophil assessments may be used to guide optimal antiinflammatory asthmatic treatment.
Aeroallergens as well as immediate skin test reactions exhibit seasonal variation. However, the seasonal variability of sputum eosinophilia is not known.
We sought to evaluate seasonal variation of sputum eosinophil percentages in
atopic asthmatics. METHODS: We performed a retrospective review of subjects undergoing sputum evaluation predominately for asthma at a tertiary
care referral center in accordance with the institutional review board guidelines. RESULTS: From November 2000 to December 2008, 204 successful sputum inductions for eosinophils were performed in 176 individual atopic asthmatic subjects (male 78, female 126, median age 49.5, 4% current/ 25% former
smokers, and mean FEV1 83%). Atopy was defined by a minimum 3mm x
R.T. Manley*1, M.D. Wong1, W. Chen2, S. Bowlin2, L.M. Salmun2, 1. Liberty Lake, WA; 2. Franklin Lakes, NJ.
Introduction: Despite the lack of evidence or guideline endorsement, inhaled
corticosteroid and long-acting beta agonist (ICS/LABA) combination products
are likely used in patients with mild persistent asthma. The potential costs and
benefits of this deviation from guideline recommended care have not been quan-
tified. Objective: To compare medical and pharmacy costs and clinical outcomes of mild asthma patients taking single-entity ICS therapy vs. ICS/LABA
combination therapy across different prescriber specialties in a large pharmacy
benefit population. Methods: Medical and pharmacy claims for patients with
mild asthma who received single-entity ICS or ICS/LABA combination therapy between July 1 – December 31, 2008 were analyzed to determine cost
(adjusted for age, gender, and baseline clinical characteristics) and clinical outcomes during 1 year of follow-up. Results: 27,336 patients treated for mild
asthma (17,898 ICS/LABA, 9,438 single-entity ICS) were identified. The rate
of ICS/LABA combination therapy use was highest among individuals 18 years
of age and older (<12 years 25.3%; 12-17 years 60.3%; 18-49 years 74.7%;
>49 years 72.9%). Treatment with ICS/LABA combination therapy was associated with significantly higher asthma-related drug costs vs. single-entity ICS
therapy ($1,173.27 vs. $981.65, p<0.001), while asthma-related medical costs,
number of oral steroid claims per patient, and time to pulmonary-related emergency department visit or hospitalization remained similar between treatment
groups. Total asthma-related healthcare costs were higher in the ICS/LABA
combination group ($1,612.26 vs. $1,376.84, p<0.001). Pediatricians were least
likely and family practice/primary care physicians were most likely to prescribe
ICS/LABA combination products in mild asthma patients. Conclusions: Findings confirm that ICS/LABA combination use is prevalent in mild asthma
patients and is associated with increased asthma-related pharmacy and total
healthcare costs with no observed clinical benefit.
Risk factors to ever asthma according age group and gender
A. Ibarra*1, B. Del Rio2, A. Berber2, J. Sienra-Monge2, U. Chavez2, 1.
Guadalajara, Jalisco, Mexico; 2. Mexico City, Mexico.
The ISAAC was done in order to know the prevalence and severity of asthma
and allergies in children, but also was focused in monitoring trends and risk
factors of these diseases. Mexico City -who was included in Phase IIIb of
ISAAC- is one of the biggest cities in the world with a population of 20 millions inhabitants. We describe risk factors related to the prevalence and severity of asthma in two groups of 6-7 years and 13-14 years to seek possible risk
factors from the north and center area of Mexico City. With an urgent need in
the investigation of them. Transversal study with school children from Mexico
City was done. Data from the group were analyzed together and separately for
the 6-7 year age group and the 13-14 year age group. Description and logistic
regression were used to analized risk factors. SPSS 9.0 package and the Spanish version of the ISAAC questionnaire was used. Sample size according to
ISAAC specifications was of 3000 for the group of 6-7 years and for the 1314 years with an expected drop-out rate of 20%. The list of schools were obtained
from Secretaria de Educacion Publica which is the organ in charge of education in Mexico, schools were randomly selected from each district. Children
of 6-7 years of age and their parents were invited to participate. The group of
13-14 years had their parents consent although they were required to fill in the
qiestionnaires by themselves. Conclusions Rhinitis represented a major risk for
current wheezing and wheezing ever in life. The use of antibiotics and paracetamol were significant risk factors for current wheezing. Traffic near house
was a risk factor to current and wheezing ever. Maternal cigarrete smoking was
a major risk in the group of 6-7 years with current wheezing. Watching TV
(for more than 3 hours) represented a risk factor in teenagers for current wheezing. Being obtained by cesarean represented a risk factor in the group of 6-7
years for wheezing ever in life. Low birth weight ( < 1,500 g.) was also a risk
factor for wheezing ever in the group of 6-7 years of age. A higher mother
education represented a protectective factor for current wheezing in the group
of teenagers.
General Characteristics of participants
Y. Klebanova*, S.M. Meltzer, N. Pitts, K. Willis, Long Beach, CA.
Introduction: Inhaled corticosteroid and long acting beta-agonist (ICSLABA) combination MDI therapy has been used successfully for the treatment
of moderate to severe persistent asthma in children over the age of 4. Little data
exists for ICS-LABA in children under the age of 4. We evaluated the efficacy
of fluticasone proprionate-salmeterol (FP-SA) fixed combination MDI therapy in children under 4 years of age with uncontrolled asthma on medium-high
ICS monotherapy. Methods: A retrospective chart review was performed on
children under 4 years of age with uncontrolled asthma on medium-dose ICS
that were started on FP-SA MDI therapy between April 2007 and January 2009
in a community practice. Data was collected for 6 months before and after the
start of FP-SA MDI therapy. The primary outcomes were frequency of ER visits, hospitalizations and prednisone bursts. The asthma predictive index was
calculated for all patients. Wilcoxon signed-rank test was used for statistical
analysis. Results: Twenty-two patients (7 male, 15 female) fulfilled the inclusion criteria with age range 9-48 months (mean=30.5 months) at the start of
combination treatment. After the combination therapy ER visits decreased from
16 to 0 (p<0.01), mean ER visits per patient before and after combination
therapy were 0.73 and 0 respectively. Hospitalizations decreased from 15 to 0
(p<0.01), mean hospitalizations per patient before and after combination therapy were 0.68 and 0 respectively. Prednisone bursts decreased from 28 to 5
(p<0.01), mean prednisone bursts per patient before and after combination therapy were 1.27 and 0.23 respectively. Out of 22 patients, 20 (91%) had a positive asthma predictive index for future development of asthma. Conclusion: In
22 patients under the age of 4, fixed dose FP-SA MDI was an effective treatment for asthma in children less than 4 years of age with reduction in the most
severe asthma symptoms requiring ER visits, hospitalizations, and exposure
to systemic steroids.
J.A. Luna-Pech*1, B.M. Torres-Mendoza1, A.M. Elizalde-Lozano2,
M.S. Navarrete-Navarro1, C.Y. Garcia-Cobas1, M.C. Fausto-Brito1, 1.
Guadalajara, Jalisco, Mexico; 2. Colima, Mexico.
Introduction: Nutritional assessment focused on weight loss has been shown
to be effective in improving pulmonary function in obese asthmatic adults. Nevertheless, slimming strategies are not usually indicated in adolescence, as this
is a period of unsteady and rapid growth rate. A good choice for treating obese
adolescents without severe energy restriction is an energy-balanced normocaloric diet (EB-ND). The actual impact of such nutritional strategy on clinical indicators of disease control and asthma related quality of life in obese adolescents with asthma remains poorly studied. Methods: Sixty-six adolescents
(aged 12-15 yr.) with obesity (BMI >95 Centile) and moderate persistent asthma
were randomly assigned to control (n=33) and EB-ND (n=33) groups. The main
features of the nutritional assessment were: energy intake according to expected
body weight for height (normocaloric), with carbohydrate intake ranging from
54–60%, protein intake from 12–14%, and cholesterol intake less than 100
mg/1000 calorie. Diet was adjusted on the basis of dietary habits of the families and children and was assessed twice a month for an 18 week period. Spirometry was performed at baseline and at the end of the follow-up period. Daily
doses of inhaled steroids and the standardized Pediatric Asthma Quality of Life
Questionnaire (PAQLQ[S]) scores were also recorded. Results: The drop-out
rate was (15%) in the EB-ND group and (19%) in the control group. The EBND program was associated with significant improvements in spirometric variables (P<0.05); in contrast, no significant changes were found in controls. In
addition, the nutritional assessment was related to a significant improvement
in PAQLQ[S] scores compared with the controls. Total score (p<0.04) as well
as all domain scores (activity, p<0.05; symptom, p<0.04; emotional function,
p<0.04) improved in the EB-ND group compared with the controls. Daily doses
of inhaled steroids were reduced in EB-ND patients (67%), but they remained
unchanged or increased in controls (70.6%) (p=0.09). Conclusion: Supervised
nutritional assessment might be associated with beneficial effects on disease
control and quality of life in obese asthmatic adolescents. Further research is
needed to develop, implement, and evaluate interventions to promote specific
nutritional strategies within this specific population.
I. Malinow*1, C. Acantilado1, M. Alvarez1, C. Lopez-Almodovar1,
G. Ramos1, A. Rivera1, R. Rodriguez1, V. Velazquez2, R. Zaragoza1,
A. Torres-Palacios1, S. Nazario1, F. Lopez-Malpica1, 1. San Juan, Puerto
Rico; 2. Ponce, Puerto Rico.
Introduction: Puerto Ricans have a high asthma prevalence and morbidity
and yet there has been no validation tests done for instruments to assess asthma
control. The Asthma Control Test (ACT) questionnaire has been widely used
and validated in other ethnic groups, showing an adequate correlation with
physician assessment of asthma control. We sought to evaluate measures of
asthma control in the ambulatory setting among Puerto Ricans to determine
which measure is more accurate for our population. Methods: A retrospective
study of the data collected in Ambulatory Health Screen Clinics conducted on
August 2008 in three cities in Puerto Rico was done. After signing a consent
form, the participants filled a survey consisting of 8 questions related to asthma
and rhinitis. Self-reported asthmatics answered the Spanish version of the ACT.
Peak flow was measured on three consecutive times using the Wright portable
peak flow meter. Subjects were skin tested for the common aeroallergens. The
study was approved by the IRB of the University of Puerto Rico. Results: We
evaluated data from 316 subjects aged 5-86. 36% reported a history of asthma,
29% reported to still have asthma, 76% reported rhinitis. 64% of the subjects
were sensitized to at least one antigen. There was no difference in the ACT
among patients sensitized to the common aeroallergens. Among patients with
self-reported current asthma, the mean ACT was 17.8, compared with 21 among
those with a past history of asthma (p=0.068). Among patients with self-reported
current asthma, the mean PEF was 86% compared with 89% among those
with a past history of asthma (p=0.464). There was no correlation between ACT
score and PEF. (R2=0.035,p=0.07) Discussion: A trend was noted between ACT
score and current asthma suggesting it was a better measure of asthma control
than PEF. The accessibility, cost effectiveness, and ease of use support the utilization of the ACT in the determination of asthma control among Puerto Ricans.
A prospective study could be done comparing ACT with other measures of
asthma control.
B.A. Massare, M. Lunn*, T.B. Fausnight, Hershey, PA.
Introduction: Asthma is the leading serious chronic illness of children
in the United States. In 2008, 7 million children under the age of 18 had been
diagnosed with asthma. The highest prevalence rate was seen in those 5-17
years of age (106.3 per 1,000 population), with rates decreasing with age.
Since children are in school for most of the day, it is important that they have
albuterol available at school. Our goal is to establish what percentage of children have albuterol available at school and determine potential barriers to
availability. Methods: After IRB approval, a patient list of children aged 512 was compiled by ICD-9 codes for asthma (493.xx). All patients were
treated by Allergists. The parents/guardians were mailed a questionnaire.
Consent was implied with a returned questionnaire. Questions focused on
the availability of albuterol in the school setting, school nurse awareness of
an asthma diagnosis, and barriers to albuterol availability. Results: Two hundred and thirty seven questionnaires were mailed, 22 returned to sender. Forty
five (21%) completed surveys were received (age range 5-12). Eighty two
percent of respondents reported having albuterol available at school. Of the
seven with no albuterol in school, four (9.3%) reported never being asked
by a physician about having albuterol for school use, two reported not needing albuterol in school, and one reported not being allowed to have albuterol
at school. The nurse was aware of an asthma diagnosis in 36 (80%). Of those
students, only three did not have albuterol at school. Of those with albuterol
at school, the school nurse held 97% of inhalers. Conclusion: In this study,
the majority of respondents had albuterol available at school. Of those without albuterol available, the most reported limitation was never being asked
by a physician. Our findings stress the importance of asthma education. It
is the Allergist’s responsibility to treat a patient and educate patients and
families about how to best manage their illness. During asthma maintenance visits, physicians should discuss the availability of albuterol in the
school setting. Physicians also need to encourage families to make sure the
school is aware of their child’s asthma diagnosis, and that albuterol is available. Future research could determine additional limitations, such as questioning school nurses and surveying students followed by primary care
S. Mela*, Denver, CO.
A 10-year-old boy was brought for evaluation after two episodes of suspected anaphylaxis resulting in significant respiratory compromise. The second episode was a near fatal reaction requiring CPR, intubation and PICU
admission. The first episode occurred at the racetrack an hour after he ate a
piece of chicken and drank Gatorade. His initial symptoms were upset stomach and diaphoresis followed by chest tightness that was unresponsive to
Albuterol. He was taken to the ER and received epinephrine. The second
episode occurred 2 weeks later while he was watching TV and drinking
Gatorade. His symptoms consisted of GI upset and diaphoresis followed by
difficulty breathing. He used his Albuterol MDI with Aerochamber without
a significant response and lost consciousness. His Mother did CPR until the
paramedics arrived and intubated him on the scene. He was hospitalized in
the PICU for 5 days. His mother denied any new food exposures, medications
or recreational drug use. An MRI of the brain, EKG and echo were all within
normal limits. His past medical history includes recurrent wheezing associated with viral illnesses until 5 years of age. He does not have any known EIB
or food allergies. Food challenges to chicken and Gatorade were both negative, as well as an exercise challenge after consuming both chicken and
Gatorade. He was also monitored with twice-daily spirometry. His FEV-1
prior to starting maintenance therapy with Fluticasone 220 mcg ranged from
73 to 80% of predicted. His exercise challenge pre-bronchodilator therapy
FEV-1 was 75% of predicted and afterwards was 54% of predicted, documenting exercise-induced bronchospasm and suggesting that he would benefit from pretreatment with a bronchodilator prior to exercise. At National
Jewish, his FEV-1 dropped to 69% of predicted; although he was asymptomatic at that time. This was an indication that his asthma was very labile and
that he had poor symptom recognition. He was placed on Advair HFA with
Aerochamber. Upon discharge, his FEV-1 ranged from 93 to 100% of predicted. Follow-up one year later showed an FEV-1 of 96% of predicted and
his Advair was continued. He has not had any subsequent episodes and is
leading an active lifestyle. Further evaluation and better characterization of
the severity of his asthma and level of bronchial hyperresponsiveness was
revealed which suggested he had poor symptom recognition with highly labile
J. Mendiola*, B.E. Del RГ­o, D. Pietropaolo, A. Ibarra, Mexico City, Mexico.
Introduction: Obesity is a mayor health issue in all the world.It is asociated with a range of adverse consequences and its prevalence appears to
be increasing among children and adolescents.The effects of ventilatory
function have been widely studied in adults but there are scarce studies in
children and even more, in specific population as in morbid obese adolescents.Knowledge of early complications on the lung by pulmonary function tests allow the development of new management strategies aimed at
the sporting activity in patients with morbid obesity. Methods Study Design:
transversal prospectiveopen,in a group of morbidly obese,not morbid and
eutrophic adolescents. We included morbid obese,obese and eutrophic adolescents attending to the the Hospital Infantil de Mexico Federico Gomez,
aged between 11-17 years and divided into 3 groups: 1) Eutrophic adolescents(BMI <p85). 2) Adolescents with no morbid obesity (BMI> p95 and
<99). 3) Adolescents with morbid obesity (BMI> 35 or BMI> P99).
Approval was obtained from the parents and (oral or written) informed consent obtained from all research subjects. All patients included in the study
underwent complete medical history, anthropometric measurements and
pulmonary function tests (plethysmography) using a Sensor Medics VMAX
plethysmograph. Results: We used descriptive stadistics, measurment of
standar deviation,standar error, confidence interval95%, we analized in
groups using analysis of variance (ANOVA)with a Tukey post hoc analysis.Significance was taken as p< 0.05 for all tests. The results show that
Funtional Residual Capacity (FRC) and Expiratory Reserve Volume (ERV)
decrease sharply comparing the three groups:FRC p<.032 eutrophic vs
obese and p<.031 eutrophic vs morbid obeses ERV p<.001 eutrophic vs
obese and p<.003 eutrophic vs morbid obese. We also found a decrease in
FEV1 comparing the three groups with a p<.011 morbid vs eutrophic and
p<.049 morbid vs obese. Our results confirm the findings of others, who
have shown that lung volumes especially FRC and ERV decrease as body
weight increases.Obese patients have a combination of mechanical and
inflammatory effects that result in pulmonary disability.
E. Navarro*, S. Jimenez, B.E. Del Rio, D.Y. Lopez, J.L. Jimenez, L. Orozco,
Mexico City, Mexico.
Introduction. Is well documented that single nucleotide polymorphisms
(SNPs) in genes that encode molecules involved in immune and inflammatory
response contribute to the development of asthma. For participation in these
mechanisms, signal transducers and activators of transcription (STAT) are candidate genes whose SNPs can also contribute to its etiology. Objective. To determine whether SNPs in the STAT1 gene are associated with development of
asthma in children in Mexico. Method. We conducted a case-control study in
86 pediatric patients with asthma (diagnosed clinically) and 179 controls without asthma and atopy. Genotyping of SNPs (rs2280234, rs2280232, rs13395505,
rs3088307, rs1467199, rs13005843) was performed by TaqMan. Data analysis included evaluation of Hardy-Weinberg equilibrium (HWE), haplotype construction and determination of the statistical significance of the results using
the Finetti program, and EPIINFO HAPLOVIEW (X2 test), respectively.
Results. The comparative analysis between both groups showed statistically
significant differences in the distribution of the alleles of SNP rs1467199 and
the G allele showed a greater frequency in controls than in cases (12.6% vs
6.5%, respectively), giving an OR of 0.48 (95% CI 0.23-1.0, p = 0.0356). The
haplotype analysis revealed the presence of 11 common haplotypes (frequency>
1%), but none showed statistically significant differences. Conclusions. The
results suggest that the SNP rs1467199 G allele confers protection to asthma.
This is the first study that demonstrates the possible involvement of STAT1
gene SNPs in the etiology of the disease.
E. Navarro*1, L. Hernandez1, A. Barraza1, M.G. MuГ±oz1, C. Escamilla1,
B.E. Del Rio1, J.J. Sienra1, F. Holguin1, I. Romieu2, 1. Mexico City, Mexico;
2. Cuernavaca, Macao.
Abstract Body Rationale. Both obesity and asthma are common conditions,
and both are characterized by the presence of inflammation. The effects of
weight loss on lung function and inflammation are not well known. Objective:
To identify the effect of weight-loss induced by nutritional intervention on lung
function and inflammatory response in obese adolescents with and without
asthma Methods: 52 asthmatics and 88 non-asthmatics adolescents age 9 to 18
years, were followed monhtly during a weigh-loss intervention program. and
anthropometry, lung functions (spirometry) and exhaled nitric oxide (eNO)
were measured. Data were analyzed among adolescents that reduce weight during the follow up using GEE models controlling for gender, age and basal BMI.
Results: At baseline, Inflammatory marker (feNO) was higher among asthmatics(54.7 vs 35.3 in non asthmatic, p<0.05); however not difference were
observed for FEV1, FVC and FEF2575 between asthmatic and non asthmatics. Mean BMI (kg/m2) decreased from 30.2(SD=5.5) to 28.1 (SD=5.6) after
5 months average of follow up . FEV 1 and FVC increased 79.9 (95% CI:23.0,
136.8)ml and 69.4 (95% CI:-19.2,0.158.0) ml respectively, and fef2575
increased 131.0(IC95%:12.9,149.2) ml/sec. feNO decreased by 7 % (3.3 ppb)
although not significantly, p=0.17). There were no significant difference between
asthmatic and on-asthmatics. Conclusion, The weight reduction in obese adolescents is associated with an improvement of lung function and reduction of
airway inflamation . The mechanisms underlying the effects of weight loss on
asthma in severe obese subjects would require further studies.
E. Navarro*, S. Jimenez, B.E. Del Rio, D.Y. Lopez, J.L. Jimenez, L. Orozco,
Mexico City, Mexico.
Introduction. Is well documented that single nucleotide polymorphisms
(SNPs) in genes that encode molecules involved in immune and inflammatory
response contribute to the development of asthma. For participation in these
mechanisms, signal transducers and activators of transcription (STAT) are candidate genes whose SNPs can also contribute to its etiology. Objective. To determine whether SNPs in the STAT1 gene are associated with development of
asthma in children in Mexico. Method. We conducted a case-control study in
86 pediatric patients with asthma (diagnosed clinically) and 179 controls without asthma and atopy. Genotyping of SNPs (rs2280234, rs2280232, rs13395505,
rs3088307, rs1467199, rs13005843) was performed by TaqMan. Data analysis included evaluation of Hardy-Weinberg equilibrium (HWE), haplotype construction and determination of the statistical significance of the results using
the Finetti program, and EPIINFO HAPLOVIEW (X2 test), respectively.
Results. The comparative analysis between both groups showed statistically
significant differences in the distribution of the alleles of SNP rs1467199 and
the G allele showed a greater frequency in controls than in cases (12.6% vs
6.5%, respectively), giving an OR of 0.48 (95% CI 0.23-1.0, p = 0.0356). The
haplotype analysis revealed the presence of 11 common haplotypes (frequency>
1%), but none showed statistically significant differences. Conclusions. The
results suggest that the SNP rs1467199 G allele confers protection to asthma.
This is the first study that demonstrates the possible involvement of STAT1
gene SNPs in the etiology of the disease.
J. Mercado*1, A. Baez2, J. Mercado1, B. Rivera2, S. Nazario2, 1. Carolina,
Puerto Rico; 2. San Juan, Puerto Rico.
Introduction: Puerto Ricans suffer a high asthma severity, elevated rate
of Emergency Department (ED) visits due to asthma, unresponsiveness to
conventional treatment, and high hospitalization rate compared to other ethnic groups. The increased severity is likely to be multifactorial. One of
factors considered are variations in the response to ОІ-agonist bronchodilators. Polymorphism in the ОІ-2 adrenoreceptor (ADRB2) gene receptor at
position 16 has significant effects in modulating responses to ОІ-agonist agonist drugs in the acute setting. We propose to evaluate the clinical significance of ADRB2 polymorphisms in Puerto Ricans by comparing the
response to albuterol in children with an acute asthma exacerbation arriving to the Emergency Department. Methods: We conducted a pilot study to
enroll Puerto Rican asthmatic children 6-20 years of age arriving to ED
from July, 2009 until February, 2010. Children received standard asthma
treatment, Pediatric Asthma Severity Score (PASS) for severity of exacerbation, answered an asthma control questionnaire (ACQ) and provided saliva
samples for genotyping. Peak expiratory flow, pulse oximetry, and clinical
markers were measured at baseline and one hour after treatment. The study
was approved by the IRB of the University of Puerto Rico. Results: Twenty
children were enrolled with a mean age of 10 years. All participants were
insured by the government sponsored health care plan. Their asthma was
uncontrolled as reflected by an ACQ score of 3. PASS showed mild to moderate asthma exacerbation. ADRB2 genotype showed that 11% were ArgArg, 61% were Arg-Gly and 28% were Gly-Gly homozygotes. Arg Arg
homozygotes had a mean peak flow improvement of 72 L/min, heterozygotes had a 30 L/min improvement and Gly-Gly homozygotes had a 9 L/min
improvement. There was a trend for a difference between the ADRB2 genotype and the response to albuterol treatment as measured by peak flow measures one hour after initiation of treatment (p=0.075). Conclusions: ADRB2
polymorphism could explain the variable responses to acute asthma treatment among Puerto Ricans. The study underscores the need to identify
ADRB2 polymorphism in order to diminish treatment failures, avoid unnecessary medications, and provide cost-effective treatment in the ED.
M. Castro*1, S. Mathur2, F. Hargreave3, F. Xie4, J. Young5, H.J. Wilkins4,
T. Henkel4, P. Nair3, 1. St. Louis, MO; 2. Madison, WI; 3. Hamilton, ON,
Canada; 4. Frazer, PA; 5. Ann Arbor, MI.
Background: Eosinophilic asthma is a subtype of severe asthma characterized by persistence of eosinophils in the lung and sputum. IL-5 is involved
in the maturation, recruitment, and activation of eosinophils. Objective: To eval-
uate the effect of the humanized antibody to IL-5, reslizumab, on asthma symptoms in patients with asthma and eosinophilic airway inflammation. Methods:
Patients with poorly controlled asthma on high dose inhaled corticosteroids
and ≥3% sputum eosinophils were randomly assigned to receive infusions of
reslizumab 3.0 mg/kg or placebo at weeks 0, 4, 8, and 12 with stratification by
baseline Asthma Control Questionnaire (ACQ) score ≤2 or >2. The study had
IRB approval, and patients provided informed consent. The primary endpoint
was change from baseline to week 15 in ACQ score. Secondary endpoints were
measures of lung function and number of clinical asthma exacerbations (CAEs).
A CAE was defined as a ≥20% decrease from baseline in FEV1, emergency
treatment or hospitalization for asthma, or oral corticosteroids for ≥3 days.
Results: 106 subjects (mean age 45.4 years) with poorly controlled (mean ACQ
2.7), eosinophilic-predominant asthma (median sputum eosinophils 10%) were
enrolled. 8% had aspirin sensitivity, 14% had atopic dermatitis, 29% had chronic
sinusitis, and 80% had allergic rhinitis. Baseline characteristics were balanced
between the groups. Overall, there was a trend toward improvement in asthma
control associated with a significant improvement in lung function and a
decrease in airway eosinophilia (Table). 8% of patients in the reslizumab group
and 19% in the placebo group had a CAE (p=0.0833). Significantly greater
improvements in ACQ score were observed with reslizumab versus placebo in
patients with nasal polyps. The most common adverse events (AEs) with
reslizumab (≥3 patients) were nasopharyngitis, fatigue, and pharyngolaryngeal
pain. The AE profile of reslizumab and placebo were similar, and no drugrelated serious AEs were observed. Conclusion: In patients with severe, poorly
controlled eosinophilic asthma, reslizumab improved lung function and airway
eosinophilia with a trend towards improved asthma control that was not statistically significant. In a subgroup with nasal polyps, reslizumab demonstrated
an even greater improvement in asthma control. Reslizumab was generally well
Efficacy outcomes: changes from baseline to end of therapy (week 15)
Values are mean (standard deviation) changes from baseline to week 15
unless otherwise indicated.
S. Nsouli*, Danville, CA.
For persistent asthmatics that remain symptomatic on a low dose of an
inhaled corticosteroid (Fluticasone propionate; 88-264 mcg, Beclomethasone
dipropionate;160-480 mcg, Budesonide flexhaler; 90-180 mcg) the addition of
Formoterol a long acting inhaled beta 2-adrenergic receptor agonist 12 mcg
twice daily, may provide an alternative to increasing corticosteroid therapy. In
this open labeled 12 week trial, 30 patients with symptomatic asthma currently using a low dose inhaled corticosteroid where randomized to receive
either: a double dose of their current inhaled corticosteroid or inhaled Formoterol 12 mcg twice daily, in addition to a low dose inhaled corticosteroid.
The endpoints of the trial include: FEV1, PEF (am), exacerbations, nocturnal
awakenings and sputum eosinophilia. Mean efficacy measurements at 12 weeks
revealed significant difference in FEV1, Exacerbations, Nocturnal awakenings,
PEF (am) and reduction in sputum eosinophilia. In conclusion, the addition of
Formoterol inhaled to a low dose inhaled corticosteroid is as effective and
may be a safer alternative in controlling symptomatic persistent asthma as compared to doubling the dose of inhaled corticosteroids. This study may suggest
that Formoterol may have a more beneficial action than only bronchodilator.
Formoterol inhaled may inhibit inflammation in the airways more than inhaled
corticosteroid used alone.
J.A. Olvera*, N.H. Segura, R. Mondragon, G. Vargas, N.I. Rodriguez,
Mexico City, Mexico.
Asthma and obesity are public health problems in Mexico and worldwide.
An estimated 300 million people worldwide suffer from asthma, and at least
400 million people over 15 are obese. The global mortality rate for asthma is
3.73 / 100,000 inhabitants, and 80% occur in developing countries. Mexico and
Uruguay have the higher mortality rates in Latin America. Each BMI unit
increases the risk of asthma by 10%. Obesity increases the prevalence and incidence of asthma, reduces its control, and is considered a risk factor for asthma
exacerbations. Both pathologies have a chronic systemic inflammatory base.
The accumulation of abdominal visceral adipose tissue produces alterations in
ventilatory function, and works as an endocrine organ producing adipokines,
which enhance the inflammatory state. JUSTIFICATION. Asthma and obesity
are chronic diseases with high prevalence and growing trend, diminish the quality of life, the years of healthy and productive life, and generate high economic and social cost. Currently there is little information on the relationship
between BMI, severity of asthma, concentrations of adipokines considering the
quality of life, and the impact of a Maneuver to reduce the BMI on them. METHODS. Determine the relationship between BMI, severity of asthma and serum
concentrations of adipokines, evaluating quality of life in obese asthmatic
patients. We pretend a 10% BMI reduction maneuver in these patients. Quality of life will be determined with the Asthma Quality of Life Questionnaire
validated in Spanish for Mexico. It was reviewed and approved by the local
ethics committee, and informed consent was obtained from patients. Currently
the study is being conducted at the Specialty Hospital of the National Medical
Center, XXI Century of the Social Security Mexican Institute. We believe that
this relationship can be modified by reducing the BMI and thus improve asthma
control and quality of life.
Body Mass Index, Asthma Severity and Serum Adipokines, In Asthmatic
Obese Adults
J.M. Pantoja Alcantar*, N.H. Segura Mendez, Mexico City, Mexico.
It is well known, the association that exists in obesity and asthma, but no
data exist in the international literature that relates metabolic syndrome with
asthma, both are important health problems worldwide and inflamatory diseases. It should be noted that much of our asthmatic patients are obese which
is a risk factor of metabolic syndrome, but there is little information on the
prevalence of this pathology in asthma, as well as the association between
both entities because are inflammatory processes that may be related
E. Pascual*, B. Del Rio Navarro, J. Sienra Monge, Mexico City, Mexico.
Obesity and asthma are chronic diseases affecting millions of individuals
around the world. In the last two decades there has been an increase in the prevalence of asthma and obesity worldwide. Because obesity is a public health problem that has been superimposed on other diseases such as asthma is a common
management challenge that can bring benefit to lung function (FEV1,
FEV1/FVC) and the metabolic status. In addition to the major alterations in
lung function in obese asthmatic inherent complications of obesity are observed:
In addition to taking account of cardiovascular complications is necessary to
emphasize that obesity per se increases the intensity of asthma and leads to
increased use of medications. A therapeutic alternative to reduce triglyceride
levels is omega-3 supplementation has proven effective in the lipid profile in
adults. There are conflicting results in asthma, and not yet experienced the effect
of the administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA) in hypertriglyceridemic adolescents suffering from obesity and asthma
at the same time. This will assess the effect of omega-3 supplementation in
this group with a local inflammatory disease in the lungs such as asthma and
systemic low-grade and obesity. METHODOLOGY. Experimental, longitudinal, comparative, prospective study whose design corresponds to controlled,
randomized, parallel in two groups of obese asthmatics and not asthmatic with
hypertriglyceridemia, group one received three grams of omega 3, group two
received gellatin. Results. We used paired simple statistics, T de students, and
we had 31 adolescents; in the group receiving gellatin we found a decrease in
level of triglycerides in visit 1(p≤0.005), the group receiving omega3 showed
loss weight in visita 1 vs visita 2,3,4 (p ≤0.00)and a diminution in body mass
index in visita 1 vs V2,4(p ≤0.01)
A. Grullon*1, B. Akinsola1, R. Vega1, M. Reddy1, R. Neugabauer2, 1. Bronx,
NY; 2. New York, NY.
Introduction: The 2007 NAEPP Guidelines recommend initiating inhaled
corticosteroids (ICS) for patients with persistent asthma at discharge from the
emergency department (ED). This study surveyed inner city pediatric ED physicians’ knowledge, attitudes and prescribing practices regarding initiating ICS
therapy, including barriers to ICS initiation. Methods: This cross-sectional
study gathered data using self-administered surveys mailed to physicians at
seven inner city EDs. The survey instrument used was obtained from Scarfone
and colleagues who published results of a similar study (2006) conducted prior
to the 2007 update of the practice guidelines. Data obtained were analyzed
(SPSS) and compared to the results of the 2006 study. Approval was obtained
from Bronx-Lebanon Hospital Center’s IRB and written informed consent
was obtained from all research subjects. Results: 48% (58/120) of mailed surveys were returned, compared to 50% (391/782) in 2006. While both studies
had similarly low response rates, a comparison of the two data sets can be warranted since both pertain to physicians who are cooperative in terms of responding to surveys. Among respondents, 18.4% were board-certified or board-eligible in both Pediatrics and Pediatric Emergency Medicine and 26% completed
residency in the past decade. Compared to 20% in 2006, 35% (p<0.03) of
respondents indicated that more than half of their patients were already using
an ICS at the time of the ED visit. About 99% of respondents stated that they
believed that ICS use could reduce ED visits or hospitalizations, but only about
30% prescribe them at ED discharge. Although this represents significantly
more physicians (p<0.04) than in 2006 (20%), the most common reasons for
not prescribing an ICS at ED discharge continue to be the belief that prescribing an ICS is the role of the primary care physician (PCP) (54.7%) and longterm management is not part of ED practice (9.4%). Conclusion: It appears
that rates for initiating ICS therapy at ED discharge have improved since 2006.
However, the vast majority of physicians still believe that prescribing an ICS
is the role of the PCP, not the ED provider. Therefore, ED providers should be
encouraged to integrate this NAEPP recommendation into their routine practice in an effort to bridge the gap between emergency and primary care, particularly for at-risk populations.
L. Brown, C. Leeds, M. Reddy*, L. Heuring, D. Strom, Bronx, NY.
INTRODUCTION: The Asthma Literacy Project (ALP) was designed to
address the issue of health literacy in asthma self-management. As physicians
and other health providers often lack adequate time to educate their asthma
patients, ALP was designed to bridge the patient-provider communication gap
while encouraging community volunteerism. With the primary goal of empow-
ering caregivers with the asthma-specific literacy skills needed to better manage their children’s asthma, ALP trains community volunteers to provide skillsbased asthma education to parents and caregivers of children with asthma.
METHODS: Volunteers were recruited from the community, trained in health
literacy basics, and taught to deliver three skills-based modules: I) Using a
Spacer, II) Understanding Asthma Medications and III) Using an Asthma Diary.
To evaluate the efficacy of the education provided, volunteers completed retrospective pre- and post-evaluations for each module taught, assessing caregivers’ skills before and after the intervention. Approval was obtained from
Bronx-Lebanon Hospital Center’s IRB and an informed consent waiver was
obtained for use of an anonymous evaluation survey tool. RESULTS: Between
December 2008 and May 2009, Asthma Literacy Advocates taught 407 modules to 157 caregivers in the pediatric emergency department and in-patient
unit. Before the educational intervention, 30% of caregivers could fully demonstrate the proper technique for how to use a spacer (Module I), compared with
97% post-intervention. 10% of caregivers could describe the different types of
asthma medication (Module II) before the intervention, compared to 94% postintervention. Lastly, before the intervention 14% of caregivers could state what
an asthma diary is and why it is helpful (Module III), compared to 97% postintervention. CONCLUSION: Enlisting community volunteers is an inexpensive way to promote skills-based asthma education among caregivers in an
urban pediatric ED and in-patient unit. A secondary study evaluating skill retention and asthma-related hospital use post-education is currently being conducted to assess the long-term impact of the educational intervention on health
outcomes, asthma control and caregiver confidence in managing asthma.
S.L. Spector*1, U.J. Martin2, T. Uryniak2, C.D. O’Brien2, 1. Los Angeles,
CA; 2. Wilmington, DE.
Introduction: Use of long-acting ОІ2-adrenergic agonists in black patients
with asthma is an area of debate (Chest. 2006;129:15–26). The effect of budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler (pMDI) and
BUD dry powder inhaler (DPI) on asthma control in black patients with inhaled
corticosteroid (ICS)-dependent asthma was assessed. Methods: This 12-week,
randomized, double-blind, double-dummy, multicenter phase 4 study
(NCT00702325) included black (self-reported) patients aged ≥12 years with
moderate to severe persistent asthma previously treated with a medium- or highdose ICS. Patients who were symptomatic after 2 weeks on BUD DPI 90 Вµg Г—2
inhalations twice daily (bid) were randomized to BUD/FM pMDI 160/4.5 Вµg
Г—2 inhalations bid or BUD DPI 180 Вµg Г—2 inhalations bid. Assessments included
asthma symptom indices, rescue medication use, predefined events of asthma
worsening, and withdrawals due to predefined events. Approval was obtained
from each site’s IRB, and written informed consent was obtained from all
patients. Results: The overall efficacy analysis included 153 and 148 patients
in the BUD/FM and BUD groups, respectively. Reductions (improvements)
from baseline in mean daily asthma symptom score and mean total daily rescue medication use were statistically significantly greater with BUD/FM pMDI
compared with BUD DPI (Table). Improvements in the percentage of symptom-free days, rescue medication–free days, awakening-free nights, and asthma
control days were numerically greater with BUD/FM pMDI compared with
BUD DPI; however, differences between treatment groups were not statistically
significant. The percentage of patients who experienced a predefined event of
asthma worsening or were withdrawn from the study due to these events was
numerically lower with BUD/FM pMDI versus BUD DPI (P=.189 and P=.097,
respectively). The safety profile of BUD/FM pMDI was similar to that of BUD
DPI. Conclusions: Black adolescents aged ≥12 years and adults with moderate
to severe persistent asthma achieved greater improvements in asthma control
with BUD/FM pMDI than with BUD DPI. These findings are consistent with
those of a similarly designed study in predominately (78%) white patients with
moderate to severe asthma (Drugs. 2006;66:2235–2254).
Asthma Control and Predefined Asthma Events
Baseline defined as the mean of all run-in data excluding days with missing
Mean of daytime and nighttime scores; cP=.039; dno symptoms or nighttime
awakenings; eP=.029; fP=.054; gno symptoms, nighttime awakenings, or rescue medication use.
S.L. Spector*1, C.D. O’Brien2, T. Uryniak2, U.J. Martin2, 1. Los Angeles,
CA; 2. Wilmington, DE.
Introduction: Response to asthma treatments may differ in black patients
versus non-black patients (Chest. 2006;129:15). Two studies assessed treatment
with budesonide/formoterol (BUD/FM) pressurized metered-dose inhaler
(pMDI); study I included predominantly non-black patients and study II included
only black patients. Methods: Two 12-week, randomized, double-blind, multicenter studies included patients aged ≥12 years with moderate to severe asthma
previously treated with inhaled corticosteroids. Study I patients received 1 of
5 treatments, previously described. (NCT00652002; Drugs. 2006;66:2235).
Data from non-black patients (Caucasian, Asian, or other) taking twice-daily
BUD/FM pMDI 320/9Вµg or BUD pMDI 320 Вµg are presented (n=198). In study
II (NCT00702325), 311 self-reported black patients were randomized to receive
twice-daily BUD/FM pMDI 320/9Вµg or BUD DPI 360Вµg. The study protocols were approved by institutional review boards, and written informed consent was obtained from all patients. Results: Mean body mass index was higher
for the black patients in study II versus patients in study I (32.6 vs 29.0 kg/m2).
In study I, the percentages of non-black men in the BUD/FM and BUD groups
were the same (37.4%). In study II, there was a lower percentage of men in the
BUD/FM versus BUD group (28.8% vs 41.2%). In both studies, improvement
in FEV1 and reduction in total rescue medication use from baseline to the treatment mean were significantly greater with BUD/FM versus BUD (P<.05; Table).
Lung function results were similar between men and women for non-black
patients in study I and black patients in study II. In both studies, most adverse
events (AEs) were mild or moderate, and headache was most common. Low
percentages of patients in the BUD/FM and BUD groups experienced serious
AEs, discontinuations due to AEs, or treatment-related AEs. These AE categories occurred less frequently in study II than in the non-black subgroup in
study I; however, the studies were relatively small. No deaths occurred in either
study. Conclusions: Budesonide/formoterol pMDI produced similar tolerability and significantly greater improvements in predose FEV1 and rescue medication use compared with budesonide in black patients with asthma, consistent with results in non-black patients with asthma of similar severity.
Mean Changes From Baseline,a to the Mean During the Randomized Treatment
Period in Predose FEV1 and Rescue Medication Use and Percentage of Patients
With AEs
For FEV1, baseline obtained on the day of randomization in both studies; for
rescue use, baseline defined as the mean of all run-in data excluding day of
randomization (study I) or missing days (study II).
Study I: BUD/FM pMDI, n=99, BUD pMDI, n=91; Study II: BUD/FM
pMDI, n=150, BUD DPI, n=143.
P≤.05 vs BUD.
Study I: BUD/FM pMDI, n=103; Study II: BUD/FM pMDI, n=150, BUD
DPI, n=144.
R.H. Stanford*1, M. Shah2, A. D’Souza2, 1. Research Triangle Park, NC;
2. Palm Harbor, FL.
INTRODUCTION Short-acting beta-agonist (SABA) use has been shown
to be a predictor of future asthma-related events in adults but not as well established in pediatrics. The objective was to assess the effect of increasing SABA
use and risk of future asthma events, to identify the optimal number of SABA
canisters and optimal assessment period that is most predictive of future asthma
events in peds (4-17 years) and adults (>=18 years). METHODS Patients
with an asthma diagnosis (ICD-9, 493.xx) and >=1 dispensing of any asthma
medication during January 1, 2004-June 30, 2006 using administrative medical and pharmacy claims from a large managed care database were identified.
Following the date of first asthma medication (index date), a 3, 6, and 12 month
period was used to assess SABA use and to assess asthma-related outcomes
(hospitalization/emergency department (IP/ED) and oral corticosteroids (OCS)
use). Receiver operating characteristic (ROC) curves were used to determine
the number of optimal SABA canisters and assessment period that best predicts future outcomes. The critical cutoff and assessment period was evaluated
with logistic regression adjusting for SABA and ICS use in the follow-up
period. RESULTS A total of 101,437 patients were identified: 41,753 peds
and 59,684 adults. A higher cutoff value and assessment period were identified for the peds compared to adults (≥3 canisters in 12 months vs. ≥2 canisters in 6 months, respectively). Patients having SABA use at or above the identified cutoff values in both cohorts had a two-fold increase in the risk of a
IP/ED visit [odds ratio (95% CI):2.228 (1.943-2.555) and 2.481 (2.154-2.857)],
and ~50% increase in OCS dispensing events [1.606 (1.446-1.784) and 1.506
(1.419-1.597)] compared to those below the cutoff. In addition, each SABA
canister dispensed during these time periods resulted in a 13% and 18% higher
risk of a IP/ED visit and a 10% and 11% higher risk of an OCS dispensing
event in the subsequent year for adults and peds respectively. CONCLUSION
. A 50% increase in risk of asthma related events is associated with ≥ 3 canisters of SABA in 12 months and ≥ 2 in 6 months for peds and adults respectively. In addition, each SABA canister dispensed is associated with an incremental risk increase. Care should be taken to limit the amount of SABA with
adequate controller therapy. (ADA112607; GSK-funded)
R.H. Stanford*1, M. Shah2, A. D’Souza2, 1. Research Triangle Park, NC;
2. Palm Harbor, FL.
INTRODUCTION Prior research has shown controller-to-total asthma medication ratio [ratio] to significantly predict future asthma events in adults. This
study assessed the incremental change in asthma event risk associated with various ratio numbers and identifed an optimal cutoff that best predicts future
events in peds (4-17 years) and adults (>18 years). METHODS Subjects with
an asthma diagnosis and > 1 dispensing event of an asthma medication were
identified during January 1, 2004-June 30, 2006 using administrative medical
and pharmacy claims from a large managed care database. Following the date
of first asthma medication (index date), the ratio was computed during a 3, 6,
and 12-month period. Asthma outcomes (hospitalization/emergency department visit [IP/ED] and oral corticosteroid [OCS] dispensings) were measured
in a subsequent 3, 6, and 12-month period. Receiver operating characteristic
[ROC] curves determined the optimal cutoff and assessment period. The risk
of outcomes on the incremental increase in ratio was evaluated with logistic
regression. RESULTS A total of 101,437 patients met the final study criteria
of which ~59% were defined as persistent asthma. In this at risk population,
the mean ratio was lower in pediatrics compared to adults (mean [SD]: 0.63
[0.26] vs. 0.70 [0.29]). Each unit (0.1) increase in the ratio resulted in a 56%
(OR 0.438 95% CI 0.326-0.590) and 60% (OR 0.398 95%CI 0.321-0.495)
decrease in the risk of IP/ED visit in the peds and adults respectively. The ratio
value of >0.5 in a 6-month assessment period was identified as optimal in
both pediatrics and adults. The risk reduction in subsequent asthma-related
IP/ED visits in patients with a ratio of ≥0.5 vs. <0.5 was higher in the adults
(OR 0.522 95% CI 0.452 -0.603) compared to the peds (OR 0.670 95% CI
0.563 -0.797). Ratio markers were only significant predictors of OCS dispensing
for adults with a ratio of ≥0.5 vs. <0.5 in a 1-year follow-up period (OR 0.814
95%CI 0.756–0.876). CONCLUSION Risk reduction in asthma events was
associated with ratios ≥0.5 in adults and peds. In addition, improvements in the
ratio by 0.1 increments reduces the risk of subsequent asthma events, disease
management programs that increase ratios may improve asthma outcomes.
(ADA112607; GSK-funded)
R.H. Stanford*1, M. Shah2, S. Chaudhari2, 1. Research Triangle Park, NC;
2. Palm Harbor, FL.
Objective: To compare asthma-related exacerbations (emergency department (ED) or inpatient (IP) visit) and related cost in pediatric patients aged 411 years that received either fluticasone propionate 44 mcg (FP44) or montelukast (MON). Methods: Retrospective observational study utilizing a large
managed care database with linked pharmacy and medical claims. Patients with
≥ 1 pharmacy claim FP44 or MON between January 1, 2000 through June 30,
2008 (4-11 years old at time of index) with ≥ 1 diagnosis for asthma (ICD-9
493.xx) in the pre-index period and continuously eligible to receive healthcare
services for 1-year pre-index and at least 60 days post-index. Patients were
excluded if they had ≥ 1 Rx claim for any asthma controller in the pre-index
period. MON subjects were propensity score matched 2:1 to FP44 based on
age, gender, region, season of index, specialist (y/n), rhinitis diagnosis, ED/IP
visits, mean albuterol and/or OCS use. Exacerbations (ED/IP visits) were compared across the cohorts and cox proportional hazards regression analysis compared time to asthma related event. Predicted monthly total asthma costs were
estimated using a generalized linear model with a gamma distribution and log
link. All statistical models adjusted for age, pre-period mean SABA canisters,
mean OCS use, and costs. Results: 19,178 subjects were identified (2,294 FP44
and 16,884 MON). After matching, there were 6636 children (34.6%) with
2212 FP44 and 4424 MON use. Mean age was 7.2 (В±2.2) years and 40.6%
female for both cohorts. Asthma-related ED/IP visits, 7.8% vs 8.4%, and mean
albuterol canisters, 1.29 (1.15) vs 1.21 (1.61), were similar at baseline for FP44
and MON respectively. The use of low dose FP44 was associated with a 29%
lower risk of having an asthma-related ED event (HR 0.706, 95% CI 0.5190.961) and 25% lower risk of having an asthma-related ED/IP visit (HR 0.751,
95% CI 0.565 – 0.999). In addition, FP44 was associated with $28 (-$27, $29) lower predicted monthly asthma related costs compared to MON. Conclusion: In asthma patients aged 4-11 years, the use of FP44 was associated
with lower risk of asthma related events and lower costs compared to the use
of MON in a managed care population.(ADA112608; GSK-funded)
may predispose individuals to both conditions. Temporality could not be
established due to the cross-sectional nature of the study. Future research
with cohort designs is needed to further elucidate this association.
R.H. Stanford*, J. White, Research Triangle Park, NC.
Objective: Treatment of asthma in the emergency department (ED) or hospital accounts for a significant portion of total treatment costs. The purpose of
this study was to estimate the type and amount of resources consumed for an
asthma event requiring ED visit and/or hospitalization. Methods: Cross sectional retrospective observational study of patients admitted to the ED or hospital for asthma between January 1, 2008 and December 31, 2008. Eligible
patients from 411 hospitals (bed size range 22-1,836, urban: 76.9%; teaching:
27.0%) from Premier’s Perspective Comparative Database with a discharge
diagnosis of asthma (493.xx) were identified. Costs and length of stay (LOS)
were calculated for three cohorts: 1) patients treated and discharged from the
ED only, 2) patients seen in the ED but then subsequently admitted to the hospital (ED + IP) and 3) patients evaluated in a non-ED setting and subsequently
admitted as an inpatient (IP). Results: A total of 149,319 patients with events
(age ≥1 year) were identified, with 108,569 (72.7%) ED only, 30,829 (20.6%)
ED + IP and 9,921 (6.6%) IPonly. For those that visited the ED only, the average cost was $391.56 (В±280.18). For ED + IP patients, the average LOS was
3.76 days (В±3.57) with a cost of $5,911.34 (В±7,538.04) while IP only patients
had a LOS of 3.56 days (В±3.02) and costs of $5,039.97 (В±6,188.42). Nursing
care was the primary source of hospital costs for asthma (51.9%-56.5%), followed by medications (11.8%-12.2%), and respiratory therapy (9.7%-10.6%).
Conclusion: For asthma patients requiring an ED visit or hospitalization, the
total cost is high and resources consumed are unavoidable. Thus, a continuum
of care aimed at appropriate asthma management, could result in substantial
cost savings by reducing ED and inpatient utilization. (ADA112608; GSKfunded)
D.R. Sun1, B.R. Ward2, J.K. Harris3, C. Xu*1, 1. Glen Allen, VA; 2. Richmond, VA; 3. St. Louis, MO.
Introduction: Asthma and arthritis/rheumatism (A/R) are associated with
chronic inflammation mediated by different immune responses; Th2 vs.
Th1, respectively. A secondary analysis was conducted to determine the
strength and direction of the association between the prevalence of these
two diseases. Method: Data was taken from a Missouri Department of Health
and Senior Services IRB approved cross-sectional study. It was a 2007 statistical sampling of 51,144 Missourians via random-digit-dial telephone
interviews. Informed consent was obtained at the time of interview. A binary
logistic regression was run using SAS version 9.2. An overall type 1 error
rate of 5% was observed. Result: A/R as the greatest impairment to one’s
health was the dependent variable. The independent variable of interest was
asthma. The model controlled for demographic and comorbidity variables.
Non-significant variables included race (p=0.2325), martial status
(p=0.2291), number of household children under 5 (p=0.8473), between 5
and 12 (p=0.5858), between 13 and 17 (p=0.4047), health insurance status
(p=0.3488), hypercholesterolemia (p=0.8897), and diabetes (p=0.4332).
Significant confounders included age (OR 1.068, 95% CI 1.057–1.080),
gender (OR 0.678, 95% CI 0.552–0.833), education (OR 0.515 thru 0.718),
employment (OR 0.094 thru 0.257), annual household income (OR 2.153
thru 6.173), hypertension (OR 1.313, 95% CI 1.079–1.597), and BMI (OR
1.074, 95% CI 1.061–1.087). The model showed asthma to be significantly
associated with A/R (OR 1.506, 95% CI 1.202–1.886). Other notable associations include: Men had lower likelihood of A/R than women. Higher education attainment was associated with higher likelihood of A/R. Compared
to those unable to work, self-employed participants had the lowest likelihood of A/R whereas students had the highest likelihood of A/R. Higher
annual household income was associated with a decline in the likelihood
of A/R until the $25k–$35k level. Income above this level was associated
with an incline in the likelihood of A/R. Conclusion: A significant association exists between asthma and A/R. Hence, an inflammatory phenotype
H.W. Kelly*1, W. Lincourt2, K. Kral2, D. Stempel2, 1. Albuquerque, NM;
2. Research Triangle Park, NC.
Introduction: There is debate regarding the effectiveness of inhaled asthma
treatment to optimally target both large and small airways. The therapeutic relevance of deposition characteristics into small airways is poorly understood
and is difficult to directly assess. It has been suggested that FEF25-75% may
provide some information on small airways function while FEV1 is thought to
be a measure of larger airway function. The purpose of this analysis was to
examine the relationship between FEV1 and FEF25-75%. Methods: Data from 6
randomized double-blind clinical studies comparing fluticasone propionate
(FP), FP/salmeterol via Diskus (FSC), placebo (PLA) or montelukast (MON)
were included in this analysis. Spearman correlations (r) were generated to
compare the change from baseline FEF25-75% and FEV1 results within study and
treatment group. The difference in mean change from baseline for FEF25-75%
and FEV1 between treatment groups within a study was generated and testing
was based on analysis of covariance controlling for baseline results and investigator site. Results: see Table Conclusion: These data show that both FP and
FSC significantly improve FEV1 and FEF25-75% to a greater extent than either
PLA or MON. The relationship between FEV1 and FEF25-75% for FP and FSC
is significantly greater than 0.50 (r≥0.77 and r≥0.82, respectively) suggesting
these measures are highly correlated. If FEF25-75% is a marker for small airway
function then FP and FSC demonstrated clinical effectiveness in the small airways that was significantly predictive of improvements in FEV1.(GSK-funded)
FEF25-75% and FEV1: Mean change from baseline to endpoint and associated correlation between the pulmonary function tests
R.A. Nathan*1, M. Blaiss2, S. Stoloff3, K. Murphy4, E.O. Meltzer5, 1. Colorado Springs, CO; 2. Memphis, TN; 3. Reno, NV; 4. Boys Town, NE; 5.
San Diego, CA.
Introduction: The Asthma Insight and Management (AIM) survey comprehensively assessed the state of asthma care in the United States in 2009
via interviews of large and nationally representative samples of asthma
patients and physicians. Since effective communication between patients
and physicians is necessary to optimize asthma care, we investigated whether
terms frequently used to describe asthma deterioration conveyed the same
meaning to these groups. Methods: National samples of 2500 patients with
asthma (≥12y of age), 101 family practitioners, 104 allergists, 54 pulmonologists, and 50 internists were interviewed. Results: When asked what
terms they normally used when discussing asthma deterioration with patients,
most physicians (≥69%, by specialty group) reported using “asthma exacerbation,” as opposed to “asthma flare-up” or “asthma attack.” However,
only 24% of asthma patients were familiar with “asthma exacerbation.”
Almost all asthma patients (97%) were familiar with “asthma attack,” and
most (71%) were familiar with “asthma flare-up.” For patients familiar with
both “flare-up” and “exacerbation,” only 38% said that they thought flareups and exacerbations were the same thing, 50% said they were not, and
12% said that they did not know. More than half of patients aware of “flareup” or “exacerbation” would consider them to have the same meaning as
“asthma symptom worsening” (57% and 52%, respectively). For patients
familiar with “asthma attack,” 36% said that “asthma attack” had the same
meaning as “flare-up” or “exacerbation,” 38% said they were not the same
thing, and 26% said that they did not know. A total of 49% of patients aware
of “asthma attack” would not consider the term to be the same as “asthma
symptom worsening.” Among patients who reported that an “asthma attack”
was not the same thing as a “flare-up” or “exacerbation,” 18% said that
attacks were more sudden, 17% said attacks were more severe, 14% said
attacks required medical attention (eg, acute care, hospitalization), 12% said
attacks required more rescue medication, and 10% said attacks were more
serious. Conclusion: The understanding of the terminology used to describe
asthma deterioration (ie, asthma exacerbation, attack, flare-up) differs
between patients and physicians, which may result in miscommunication
about asthma, asthma symptom magnitude, and asthma care.
R.A. Nathan*1, S.F. Weinstein2, H. Nolte3, 1. Colorado Springs, CO; 2.
Huntington Beach, CA; 3. Kenilworth, NJ.
Introduction: Asthma guidelines recommend measurement of forced expiratory volume in 1 second (FEV1) in asthma patients, which can indicate airway obstruction that patients may not perceive. Two multicenter, phase III, double-blind trials (P04334 and P04431) evaluated the efficacy and safety of a new
combination of mometasone furoate and formoterol (MF/F) administered via
a pressurized, metered-dose inhaler in subjects with persistent asthma not well
controlled on inhaled corticosteroids. This analysis evaluated MF/F effects on
FEV1 to determine whether improvements occurred early in therapy and were
sustained over time. Methods: Approval was obtained from institutional review
boards; informed consent was obtained from all subjects or their guardians.
Subjects in P04334 (n=781; aged ≥12y; 2−3wk twice daily [BID] MF 200µg
run-in [no washout]) were randomized to 26 weeks of BID treatment with MF/F
200/10Вµg, MF 200Вµg, F 10Вµg, or placebo (PBO). Subjects in P04431 (n=718;
aged ≥12y; 2−3wk BID MF 400µg run-in [no washout]) were randomized to
12 weeks of BID treatment with MF/F 200/10Вµg, MF/F 400/10Вµg, or MF 400Вµg.
A primary endpoint in both trials was change from baseline in FEV1 area under
the curve from 0–12h postdose (FEV1 AUC0−12h) at week 12 for MF/F vs MF.
Change from baseline in FEV1 AUC0в€’12h at day 1 and wks 1, 12, and 26 (P04334
only) was a secondary endpoint. FEV1 AUC0в€’12h values were converted to standardized FEV1 values averaged over time by applying a constant divisor of 12.
Results: In the MF/F 200/10Вµg trial (P04334), MF/F significantly increased
FEV1 AUC0в€’12h (3.11 LГ—h) vs MF 200Вµg (1.30 LГ—h) at wk 12; P<0.001, while
in study P04431, MF/F 200/10 and 400/10Вµg significantly increased FEV1
AUC0в€’12h (3.59 LГ—h and 4.19 LГ—h, respectively) vs MF 400Вµg (2.04 LГ—h) at
wk 12; P<0.001. Increases in FEV1 AUC0в€’12h with MF/F were significantly
greater than increases with MF (by approximately 2–3 fold; all P<0.001) at all
evaluated visits in both trials, and also vs PBO (2–8 fold; all P<0.001) in P04334
(Table). In both studies, significant improvements in FEV1 in subjects receiving MF/F vs MF were observed day 1 and sustained through the end of treatment. Conclusions: MF/F provided significantly greater improvement in FEV1
vs MF and PBO throughout the investigated treatment periods. There was no
evidence to suggest tachyphylaxis.
Table. Changes From Baseline in Standardized FEV1
M. Blaiss*1, E.O. Meltzer2, K. Murphy3, R.A. Nathan4, S. Stoloff5, 1. Memphis, TN; 2. San Diego, CA; 3. Boys Town, NE; 4. Colorado Springs, CO;
5. Carson City, NV.
BID=twice daily; BL=baseline; FEV1=forced expiratory volume in 1 sec;
MF=mometasone furoate; MFF=mometasone furoate/formoterol; NA=not
applicable (study P04431 included a 12-week treatment period);
*P<0.001 vs MF 200 Вµg BID.
P<0.001 vs PBO BID.
P=0.017 vs F 10 Вµg BID.
P<0.001 vs MF 400 Вµg BID.
W. Berger*1, M. Noonan2, A. Teper3, J. Moreno-Cantu3, P. Stryszak3,
E.O. Meltzer4, 1. Mission Viejo, CA; 2. Portland, OR; 3. Kenilworth, NJ;
4. San Diego, CA.
Introduction: Anecdotal reports of patients uncontrolled on a given inhaled
corticosteroid (ICS) who, when switched to a different ICS, achieve control,
suggest that differences in ICS molecules and/or delivery devices may yield
clinically relevant effects. We report findings from an analysis of lung function changes in patients switched from their prescribed ICS to mometasone
furoate administered via a dry-powder inhaler (MF-DPI). Methods: Data from
3 randomized, double-blind, placebo (PBO)-controlled, 12-week, multicenter
trials (C97-300, C97-380, & P01431) investigating the efficacy and safety of
several doses of MF-DPI in children with persistent asthma (4–11y) were analyzed. The percentage predicted FEV1 (%FEV1) after MF-DPI treatment (endpoint) and the %FEV1 reported when subjects were on their previous ICS (pICS;
baseline) were compared. All children were on ICS therapy for >30 days and
at stable doses for ≥2 weeks at baseline; trials had no washout periods. MFDPI treatments were: 100µg once daily in the evening (QD PM; approved dose),
MF-DPI 100Вµg once daily in the morning (QD AM), 200Вµg QD AM; 100Вµg
twice daily. ANOVA compared the effect of pICS dose on pooled %FEV1 results
at endpoint. Subjects were grouped in low, medium, and high pICS groups
according to recommended pediatric doses. Results: Subjects were on one of
the following pICS: beclomethasone, budesonide, flunisolide, or fluticasone
propionate (FP). Overall, improvements for pooled MF-DPI were 7.7% for lowdose pICS (–0.3% for PBO) subjects and 3.8% for medium/high-dose pICS
(–0.8% for PBO) subjects. The effect of MF-DPI vs PBO was also evaluated
for the fluticasone subgroup (n=282). In subjects switched from previous lowand medium/high-dose FP to MF-DPI, %FEV1 improved 5.3% and 2.3%,
respectively. In pooled subjects switched from low-dose FP and medium/highdose FP to PBO, %FEV1 decreased approximately 2.7% and 1.6%, respectively.
Conclusions: Evidence from this post hoc analysis suggests that for some
patients, switching from pICS therapy may further improve lung function. More
analyses, including crossover studies, are needed to clarify the role of the delivery device and the ICS molecule in improving lung function and to identify
those patients who are most likely to benefit from a switch in ICS therapy.
Introduction: The impact of new asthma treatments and management guidelines on asthma care in the US has not been recently elucidated. We completed
a comprehensive asthma survey designed to assess patient and physician
insights, attitudes, and perceptions of asthma burden and treatment in the US.
Methods: The Asthma Insight and Management (AIM) survey comprised 3 separate surveys, each based on telephone interviews with national probability
samples of 3 populations: asthma patients aged ≥12y; adults without current
asthma (general population; to compare with adult asthma sample); and healthcare providers. Asthma patients were recruited from a national random sample
of 60,682 households, while general population adults were recruited from a
national random sample of 5975 households. Survey questions evaluated aspects
of asthma burden, control, and management, as well as overall health status.
Results: 2500 asthma patients were interviewed (В±2.0% sampling error, 95%
confidence interval). General population characteristics were assessed via a
national sample of 1090 adults aged ≥18y (1004 without current asthma; ±3.1%
sampling error). Healthcare community perceptions were assessed via responses
from 309 healthcare providers (104 allergists, 101 family practitioners, 54
pulmonologists, 50 internists; ±5.7% sampling error). Asthma patient and general population samples were US-representative cross-sections. Most respondents in the asthma patient sample were female (69%, n=1732), aged ≥35y
(73%, n=1819), and had “Not Well Controlled” or “Very Poorly Controlled”
asthma (71%; control categorization based on national asthma guidelines and
patients’ survey responses). Of the overall adult general population (n=1090),
8% had current asthma (ie, patients had symptoms or clinically judged deterioration in past year or were currently taking asthma medication). Another 6%
were diagnosed with asthma in the past but had not experienced symptoms or
clinically judged deterioration in the past year and were not taking medication. Additionally, 31% of the adult general population reported that other family members had asthma. Conclusions: Results of the AIM survey provide a
comprehensive depiction of the current state of asthma burden and care in the
US and suggest that asthma continues to play an important role in the health
of the American public.
M. White*1, E.O. Meltzer2, R.A. Nathan3, H. Nolte4, 1. Wheaton, MD; 2.
San Diego, CA; 3. Colorado Springs, CO; 4. Kenilworth, NJ.
Introduction: Optimizing asthma control is an important goal of asthma
therapy. The efficacy and safety of a new combination of mometasone furoate
and formoterol (MF/F), a recently approved asthma treatment, were evaluated
in 2 phase III trials (P04334 [n=781] and P04431 [n=728]) in subjects with persistent asthma uncontrolled on inhaled corticosteroids. We describe findings
from an analysis conducted to evaluate the effects of MF/F on asthma control
as measured by the Asthma Control Questionnaire (ACQ). Methods: Subjects
(≥12 y of age) were randomized to twice-daily (BID): MF/F 200/10µg, MF
200Вµg, F 10Вµg, or placebo (26 wks), following 2в€’3 wks BID MF 200Вµg runin treatment in study P04334; MF/F 200/10Вµg, MF/F 400/10Вµg, or MF 400Вµg
(12 wks), following 2в€’3 wks BID MF 400Вµg run-in treatment in study P04431.
All subjects provided written informed consent, and institutional review boards
approved all protocols. The ACQ, a validated patient-reported measure of asthma
control, includes 7 questions (Q): 5 major symptoms, FEV1 % predicted, daily
rescue bronchodilator use; each scored from 0 (totally controlled) to 6 (severely
uncontrolled). Percentage changes from baseline to endpoint in ACQ scores
were assessed. Results: In P04334, change from baseline in overall ACQ score
was significantly better for MF/F 200/10µg (–22.0%) compared with MF 200µg
(–8.0%; P=0.026), F 10µg (21.2%; P<0.001), and placebo (30.3%; P<0.001;
Table). In P04431, change from baseline in overall ACQ score was significantly
better for MF/F 200/10µg (–25.4%) and MF/F 400/10µg (–20.4%) compared
with MF 400µg (–4.8%; P≤0.008; Table). In both studies, MF/F had the greatest positive impact (baseline to endpoint) on “waking” (Q1): MF/F 200/10µg,
-53.6% [P04334] and -47.7% [P04431]; MF/F 400/10Вµg, -35.4% [P04431])
and “daily SABA puffs” (Q6): MF/F 200/10µg, -57.5% [P04334] and -38.1%
[P04431] and MF/F 400/10Вµg, -41.1% [P04431]). In both studies, subjects
receiving MF/F reported improvements reaching the ACQ minimal importance
difference of ≥0.5 (vs placebo in study P04334; changes from baseline to endpoint in study P04431). Conclusions: Changes from baseline in overall ACQ
score were significantly greater in the MF/F groups than in corresponding
MF, F, or placebo groups. Improvements in the waking and SABA use domains
were important drivers behind the reported ACQ score improvements.
that maintenance treatment should be taken daily, only 41% of the 241 patients
administering prescription maintenance treatment in the past year did so on a
daily basis; 40% of all asthma patients “somewhat” or “strongly” agreed that
maintenance medication was not necessary when asthma symptoms were not
experienced regularly. Conclusions: Asthma burden remains high in the US.
Despite the availability of asthma management guidelines and effective asthma
treatments, asthma care is suboptimal, underscoring the need for improved
patient education and utilization of written action plans.
Table. Changes From Baseline in Asthma Control Questionnaire Scores
K. Murphy*1, E.O. Meltzer2, R.A. Nathan3, M. Blaiss4, S. Stoloff5, 1. Boys
Town, NE; 2. San Diego, CA; 3. Colorado Springs, CO; 4. Memphis, TN;
5. Reno, NV.
ACQ=Asthma Control Questionnaire; BID=twice daily; BL=baseline;
EP=change from baseline at endpoint; F=formoterol; FEV1=forced expiratory volume in 1 sec; MF=mometasone furoate; MF/F=mometasone
furoate/formoterol; PBO=placebo; Q=question; SABA=short-acting ОІ2-agonist; SOB=shortness of breath.
*P≤0.018 vs PBO.
P≤0.004 vs F 10 µg BID.
P≤0.035 vs MF 200 µg BID.
P≤0.034 vs MF 400 µg BID.
E.O. Meltzer*1, R.A. Nathan2, M. Blaiss3, S. Stoloff4, K. Murphy5, 1. San
Diego, CA; 2. Colorado Springs, CO; 3. Memphis, TN; 4. Reno, NV; 5.
Boys Town, NE.
Introduction: Results of the recently completed Asthma Insight and Management telephone survey (the largest and most comprehensive US-based
asthma survey in the past 10y) provide a unique and timely opportunity to
assess current patient asthma burden and treatment practice in the US. Methods: Geographically stratified screening of 60,682 households provided a
national sample of 2500 patients with current asthma (2186 adults aged ≥18y,
314 adolescents aged 12–17y). A national sample of 1004 adults without current asthma (general population) was interviewed for comparison with the
adult asthma population. Results: Compared with the general population, asthmatic adults more frequently reported fair, poor, or very poor overall health
(13% vs 26%, respectively) and health-related activity limitation (23% vs 57%,
respectively). In the total asthma population, 73% of patients experienced
asthma symptoms or an asthma attack in the past 12 months, 63% were affected
by asthma throughout the year, and 41% felt that their asthma was interfering
with their life “some” or “a lot.” Almost all asthma patients (94%) reported
prescription medication use for the management of asthma symptoms; however, only 32% reported having a written action plan for asthma treatment.
Prescription reliever/rescue medication use was reported by 81% of asthma
patients, and 67% “somewhat” or “strongly” agreed that rescue medication
could be used every day if needed. Among patients prescribed asthma medication for asthma maintenance therapy, only 51% (n=241) reported prescription medication use in the past year. Of these 241 patients, 26% used
rescue medication as maintenance treatment, while 59% used controller medication. While 74% of all asthma patients “somewhat” or “strongly” agreed
Introduction: Achievement and maintenance of asthma control is an essential aspect of asthma management. We evaluated results from the recently
completed Asthma Insight and Management (AIM) survey to characterize
the current state of asthma control in adults and adolescents with asthma in
the US. Methods: A cross-sectional sample of 2500 patients with current
asthma were recruited from a national random sample of 60,682 households.
Interviews were conducted via telephone (from July 29, 2009в€’September
10, 2009) with 2186 adults with asthma and with parents of 314 adolescents (aged 12–17y) with asthma. Interviewees were asked questions regarding the frequency of asthma symptoms and the control and management of
asthma in the preceding 4-week period. Results: As many as 42% of asthma
patients surveyed were poorly or not well controlled and reported experiencing symptoms “daily” (16%), “most days per week” (11%), or “≥2 days
per week” (15%). Similarly, 32% of asthma patients reported experiencing
asthma symptoms during exercise, play, or physical exertion “daily” (11%),
“most days per week” (9%), or “≥2 days per week” (12%). Although 71%
of patients self-reported that their asthma was “completely controlled” or
“well controlled,” only 29% of asthma patients would be categorized as having “well controlled asthma” according to the objective classification of
asthma control used by the National Asthma Education and Prevention Program asthma management guidelines. The majority of asthma patients considered their asthma well managed based on having: only 2 urgent doctor
visits per year (67%); ≥2 months between exacerbations (64%); only 3–4
exacerbations per year (63%); only 1 emergency room visit for asthma per
year (61%), and asthma that was bothersome less than half the time during
exercise (64%). A substantial percentage of asthma patients also considered asthma well managed if daytime symptoms occurred only 3 days per
week (46%) and reliever medicine was required only 3 times per week (46%).
Conclusions: In spite of continued advances in asthma management and the
availability of effective treatments, findings from the AIM survey demonstrate that asthma remains poorly controlled in the US. Many asthma patients
overestimate their real level of asthma control and/or have inappropriately
low expectations for asthma control.
A. Nayak*1, C. LaForce2, R.A. Nathan3, H. Nolte4, S.F. Weinstein5, 1. Normal, IL; 2. Raleigh, NC; 3. Colorado Springs, CO; 4. Kenilworth, NJ; 5.
Huntington Beach, CA.
Introduction: Reducing short-acting β2-agonist (SABA) rescue medication use to ≤2 d/wk is an important objective of therapy in patients with persistent asthma. Two phase III studies assessed the efficacy and safety of combined mometasone furoate and formoterol (MF/F) in subjects with
moderate/severe persistent asthma previously not well controlled on inhaled
corticosteroids (ICS); the use of SABA rescue medication during treatment
was assessed in both studies. Methods: Proportions of SABA-free days, nights,
and days & nights combined following treatment were secondary efficacy endpoints in 2 multicenter, double-blind studies: P04334 (n=781, 26wk, placebo
[PBO]-controlled study comparing MF/F 200/10Вµg twice daily [BID] vs MF
200Вµg BID and F 10Вµg BID) and P04431 (n=728; 12wk study comparing
MF/F 200/10Вµg BID and MF/F 400/10Вµg BID vs MF 400Вµg BID). Institutional review board approval was obtained for each study center; written
informed consent was obtained from all subjects (≥12y of age) or their parents/legal guardians. Immediately after 2−3-wk run-in treatment with MF
200Вµg (P04334) or 400Вµg (P04431), subjects were randomized to MF/F
200/10Вµg, MF 200Вµg, F 10Вµg, or PBO BID in P04334 and to MF/F 400/10Вµg,
MF/F 200/10Вµg, or MF 400Вµg BID in P04431. Results: In study P04334, the
proportion of SABA-free days increased significantly from baseline with MF/F
200/10Вµg vs MF 200Вµg (P=0.035), F 10Вµg (P=0.003), and PBO (P<0.001);
SABA-free nights also increased significantly with MF/F 200/10Вµg vs F 10Вµg
(P<0.005) and PBO (P<0.001; Table). Overall, SABA-free days & nights
increased significantly with MF/F 200/10Вµg vs MF 200Вµg (P=0.033), F 10Вµg
(P<0.001) and PBO (P<0.001; Table); increases were >2-fold greater for MF/F
200/10Вµg vs MF 200Вµg. In study P04431, proportions of SABA-free days,
nights, and days & nights increased significantly from baseline with MF/F
400/10Вµg and MF/F 200/10Вµg vs MF 400Вµg (P<0.001; Table). Increases in
SABA-free days and/or nights were 1.2–2.0-fold greater with MF/F doses
compared with MF 400Вµg. Conclusions: Treatment with MF/F 200/10Вµg or
400/10Вµg BID in persistent asthma subjects previously not well controlled on
ICSs significantly increased the proportion of days, nights, and days & nights
that were SABA-free compared with MF (200Вµg or 400Вµg BID), F 10Вµg BID,
and/or PBO BID.
(P≤0.005) or F 10µg (P≤0.024; Table). Clinically meaningful improvements in total AQLQ(S) from baseline to wk26 were observed in patients
receiving MF/F 200/10Вµg (0.61). In P04431 (n=728), subjects receiving
MF/F 200/10Вµg experienced significant improvements in total score and
the Symptoms and Activity Limitation domain scores of the AQLQ(S) at
endpoint vs those who received MF 400µg (P≤0.017; Table). Clinically
meaningful improvements in total AQLQ(S) from baseline to wk12 occurred
in patients receiving MF/F 200/10Вµg (0.61), MF/F 400/10Вµg (0.51), or MF
400Вµg (0.5). Conclusions: Patients with persistent asthma receiving MF/F
had statistically significant, clinically meaningful improvements in QoL in
2 phase III studies. These data suggest that MF/F combination therapy
improves the health-related QoL of patients with persistent asthma who are
inadequately controlled on medium- or high-dose ICS.
Table. Changes From Baseline in AQLQ(S)* Total and Individual Domain
Table. Changes From Baseline in Proportion of SABA-Free Days, Nights, and
Combined Days & Nights
MF/F=mometasone furoate/formoterol; PBO=placebo.
*All sample sizes represent values for SABA-free days and nights analyses.
P≤0.024 vs PBO BID.
P≤0.005 vs F 10µg BID.
P≤0.035 vs MF 200µg BID.
P<0.001 vs MF 400Вµg BID.
K. Murphy*1, E.O. Meltzer2, R.A. Nathan3, H. Nolte4, 1. Boys Town, NE;
2. San Diego, CA; 3. Colorado Springs, CO; 4. Kenilworth, NJ.
Introduction: A major goal of asthma treatment is to improve patients’
health-related quality of life (QoL). Mometasone furoate/formoterol (MF/F)
combination therapy was recently approved for the treatment of persistent
asthma. The objective of this analysis was to examine the effect of MF/F
on health-related QoL at the approved doses. Methods: Data from 2 phase
III studies investigating the effects of MF/F 200/10Вµg (study P04334) and
MF/F 400/10µg (study P04431) were included. All subjects were ≥12y and
not well controlled on medium-dose (P04334) or high-dose (P04431)
inhaled corticosteroid (ICS). After 2-3wks of run-in on twice-daily (BID)
MF 200Вµg (P04334) or 400Вµg (P04431), subjects were randomized to
26wks of BID MF/F 200/10Вµg, MF 200Вµg, F 10Вµg, or placebo (PBO) in
P04334; or 12wks of BID MF/F 200/10Вµg, MF/F 400/10Вµg, or MF 400Вµg
in P04431. The Asthma Quality of Life Questionnaire with Standardized
Activities (AQLQ[S]), consisting of 4 domains (Table), was used to assess
QoL. AQLQ(S) score changes from baseline were assessed; a difference
≥0.5 was considered clinically meaningful. Study protocols were approved
by IRBs; written informed consent was provided by all subjects or a parent/guardian. Results: In P04334 (n=781), subjects receiving MF/F
200/10Вµg experienced significant improvements in total score and the
Symptoms, Activity Limitation, Emotional Function, and Environmental
Stimuli domain scores of the AQLQ(S) at endpoint vs those receiving PBO
AQLQ(S)=Asthma Quality of Life Questionnaire With Standardized
Activities; BID=twice daily; BL=baseline; EP=mean percentage change at
MF=mometasone furoate; PBO=placebo.
*The AQLQ(S) included 32 questions categorized into 4 domains (Symptoms,
Activity Limitation, Emotional, and Environmental Stimuli); responses were
scored from 1 (worst) to 7 (best).
P≤0.005 vs PBO BID.
P≤0.024 vs F 10 µg BID.
P≤0.017 vs MF 400 µg BID.
S.F. Weinstein*1, R.A. Nathan2, H. Nolte3, 1. Huntington Beach, CA; 2.
Colorado Springs, CO; 3. Kenilworth, NJ.
Introduction: Two clinical trials (P04334, P04431) evaluated combined
mometasone furoate and formoterol (MF/F) treatment in subjects previously
uncontrolled on medium- or high-dose inhaled corticosteroids (ICS). We
present data from an analysis performed to examine the effects of MF/F
200/10Вµg and 400/10Вµg treatments on asthma deterioration (ie, severe
asthma exacerbation) relative to the effects of individual MF/F monocomponent treatments and/or placebo (PBO). Methods: Patients (≥12y) received
2в€’3-week run-in treatment of twice daily (BID) MF 200Вµg (P04334) or MF
400Вµg (P04431) before randomization to: MF/F 200/10Вµg, MF 200Вµg, F
10Вµg, or PBO for 26 weeks (all BID; study P04334); MF/F 200/10Вµg, MF/F
400/10Вµg, or MF 400Вµg for 12 weeks (all BID; study P04431). There was
no washout period between run-in ICS monotherapy and randomized treatment. The effect of MF/F on asthma deteriorations was evaluated by comparing reductions in lung function and clinically judged deteriorations across
treatment arms as defined in the Table. In both studies, all subjects provided
written informed consent; institutional review boards approved all protocols. Results: Significant reductions in asthma deteriorations were consistently observed for both MF/F doses investigated. In study P04334 (n=781),
fewer patients receiving MF/F 200/10Вµg reported asthma deteriorations
(30%) compared with those receiving F 10Вµg (54%; P<0.001) or PBO (56%;
P<0.001), while 34% of patients receiving MF 200Вµg reported an asthma
deterioration (Table). Similarly, in study P04431 (n=728), fewer patients
receiving MF/F 200/10Вµg or MF/F 400/10Вµg reported an asthma deterioration (12%, both doses) compared with patients receiving MF 400Вµg (18%;
P=0.038 for MF/F 200/10Вµg vs MF 400Вµg; Table). Clinically judged deteriorations were infrequent, and were reduced with MF/F treatment, as determined by 1) the need for systemic corticosteroids (P04334: MF/F 200/10Вµg,
1%; MF 200Вµg, 2%; F 10Вµg, 8%; PBO, 4%; P04431: MF/F 200/10Вµg, 2%;
MF/F 400/10Вµg, 3%; MF 400Вµg, 5%; Table) and 2) the need for emergency treatment (P04334: MF/F 200/10Вµg, 0%; MF 200Вµg, <1%; F 10Вµg,
2%; PBO, <1%; P04431: MF/F 200/10Вµg, 1%; MF/F 400/10Вµg, <1%; MF
400Вµg, <1%; Table). Conclusions: MF/F reduced asthma deteriorations in
patients previously uncontrolled on medium or high-dose ICS.
Table. Asthma Deteriorations
translates to $419/month and $5023/year per patient if purchased at retail prices.
There was an association between higher medication cost per patient and severity of persistent asthma (mild=$32/month, moderate=$74/month,
severe=$176/month, p<0.001). A statistically significant association (p=0.03)
existed between elevated IgE (>99 IU/mL) and increased asthma medication
cost. CONCLUSION: Severity of asthma defined by NAEPP criteria and elevated IgE may help identify asthmatics that require a higher cost to treat. The
growing burden of asthma cost might be improved by targeting and treating
these patients early, as well as employing other strategies. Additional treatments
include aggressive patient education, omalizumab, allergen immunotherapy,
and management of co-morbid conditions that impact asthma. Finally, future
studies with additional power are needed to further assess the baseline characteristics of asthmatics and their association with medication cost.
A.G. Weinstein*, J.P. Laurenceau, Newark, DE.
BID=twice daily; FEV1=forced expiratory volume in 1 second;
furoate/formoterol; PEF=peak expiratory flow.
*Includes only the first event day for each patient. Patients could have experienced >1 event criterion.
**Decrease in absolute FEV1 below the treatment period stability limit
(defined as 80% of the average of the 2 predose FEV1 measurements taken 30
minutes and immediately prior to the first dose of randomized trial medication).
Decrease in AM or PM PEF on ≥2 consecutive days below the treatment period stability limit (defined as 70% of the AM or PM PEF obtained over the last
7 days of the run-in period).
Fifty-four patients received systemic corticosteroids; 1 patient received F via
dry powder inhaler in the F 10 Вµg group; 1 patient received albuterol in the
MF/F 400/10 Вµg group.
P<0.001 vs F 10 Вµg BID and PBO BID.
P=0.038 vs MF 400 Вµg BID.
P. Verma*, W. Klaustermeyer, Los Angeles, CA.
INTRODUCTION: Asthma is a chronic medical condition affecting over
20 million people in the United States and over 300 million people worldwide.
Both GINA and NAEPP guidelines emphasize stepwise management based
on disease severity. Controller medications used to treat asthma are often expensive, which can be a barrier to optimal control. Additionally, poor baseline
asthma control often results in higher healthcare cost due to exacerbations. The
primary objective of this study was to perform a cost analysis of medication
use in well-controlled, persistent asthmatics over a 2 month period at a tertiary
care center. Secondary objectives were to determine baseline characteristics
of patients associated with higher cost of asthma medications. METHODS:
Using our clinical database, we retrospectively studied 112 patients (mean age
62 yr) with persistent asthma defined by NAEPP criteria from July – August
2009 (mild=11, moderate=39, severe=62). Chi-squared, Fischer exact test, and
regression analyses were used to determine associations between medication
cost and baseline characteristics. ED/Office visits and hospitalizations were
excluded from the cost analysis. Patients receiving omalizumab or allergen
immunotherapy were also excluded. RESULTS: The average cost of medications for persistent asthmatics in our tertiary care clinic was $126/month and
$1512/year per patient based on wholesale cost through our formulary. This
Rationale: Identifying patient adherence status and reasons for non-adherence (NA) is an important component of asthma management. GINA 2008
Guidelines have identified risk-factors associated with poor adherence. Methods: 518 adults (79.5% female; 68.9% Caucasian; mean age 41 yrs.) with intermittent and persistent asthma completed the AsthmaPACT, a 96-item asthma
survey hosted by the Asthma and Allergy Foundation of America website. The
AsthmaPACT identifies barriers to treatment recommendations as well as medication use. The asthma surveys were completed from August thru June 2010.
Results: Descriptive statistics indicated that 350 (67.6%) of the sample reported
taking one or more anti-inflammatory medication. Of these, 106 (32.5%) were
diagnosed as NA, operationalized as whether an individual reported taking at
least one anti-inflammatory “less than prescribed by their physician”. During
the 4 weeks prior to completing the survey, 48.3% reported having daily symptoms and 37.7% were using albuterol MDI daily. In this cross-sectional data
set, links between self-reported NA and items intended to assess risk factors
to NA were examined using chi square (П‡2) statistics. Individuals who reported
taking anti-inflammatory medication less than prescribed were more likely to
report: 1) symptoms during distressing emotional states (Angry:
П‡2(df=2)=11.695, p=.003; upset: П‡2(df=2)=6.756, p=.034; frustration:
П‡2(df=2)=8.611, p=.013); 2) Lack of comprehension of care instructions (Uncertain when to use which medication: П‡2(df=1) =11.665, p=.001; Not understanding how to use their prescribed medication: П‡2(df=1)=9.716, p=.002; Not
understanding how to use a peak flow meter: П‡2(df=1)= 10.883, p=.001); 3)
quality of life disruption affecting sleep: П‡2(df=2) =19.971, p< .001; and 4)
poorer family support (Lack of agreement by significant other with the treatment plan: П‡2(df=2)=9.878, p=.007). Conclusions: The AsthmaPACT provides
an assessment of 1) risk-factors for non-adherence and 2) patient self-report
of adherence, and is readily available as a tool to individuals with asthma who
have access to the Internet. Findings in this study are consistent with GINA
2008 Guidelines regarding common barriers to adherence. The AsthmaPACT
might be considered for symptomatic patients to identify barriers to treatment
and adherence status.
S.A. Whyte*1, P.F. Detjen2, P.H. Sheridan3, K.P. Malamut1, S.H. Samuelson1,
1. Chicago, IL; 2. Kenilworth, IL; 3. Evanston, IL.
INTRODUCTION: Asthma remains a difficult to control problem for urban
school children as evidenced by continued high utilization of emergency departments (ED). Several mobile van intervention programs have demonstrated
significant improvement in asthma control in these patients. School children
with incompletely controlled moderate to severe allergic asthma, despite combination therapy were evaluated. The setting is a specialty allergy asthma van
providing screening procedures for an entire school population by a physician
including diagnosis, comprehensive asthma management, validated screening
tool, allergen skin testing, spirometry, individualized education, environmental control, allergen avoidance measures, pharmacological therapy, scheduled
mobile clinic visits, and 24-hour physician on-call access. METHODS:
Immunoglobulin (Ig) E levels of patients with incompletely controlled moderate to severe allergic asthma, defined by rescue albuterol use ≥2 times per
week, awakening ≥2 times per month from asthma or recurring urgent visits
for exacerbations, despite compliance with regimen, were evaluated in consideration for omalizumab therapy. Written informed consent was obtained
from all research subjects and parents. Four patients had IgE levels outside the
dosing criteria, 44 were identified for enrollment, 32 declined, and eight were
enrolled in the trial. All patients were on combination therapy with daily inhaled
corticosteroid (ICS), long-acting beta-agonists (LABA) and daily leukotriene
modifier. Subcutaneous omalizumab was administered monthly for six months.
Primary outcome measures were albuterol use ≤2 times per week, the absence
of ED treatment, and decreased ICS requirement. RESULTS: The mean IgE
level was 314 kU/L and mean FEV1 93.5% of predicted. One patient discontinued; six patients were weaned off daily ICS and LABA therapy. All patients
had decreased albuterol use ≤2 times per week. Six patients did not require
ED treatment while on omalizumab therapy. CONCLUSION: Omalizumab
therapy improves the quality of asthma control in poorly controlled moderate
to severe pediatric asthma patients, while decreasing the ICS and LABA requirements in a school-based mobile van specialty-oriented clinic program.
K.W. Wyrwich*1, A.M. Ireland1, P. Navaratnam2, H. Nolte2, D. Gates2, 1.
Bethesda, MD; 2. Kenilworth, NJ.
Introduction: The Asthma Quality of Life Questionnaire with Standardized
Activities (AQLQ12+) was developed for adolescents age 12 to 17 years old,
as well as persons 18+ years old. This study investigated: 1) the psychometric
properties of the AQLQ12+ in moderate persistent asthma patients treated with
a combination inhaled glucocorticoid and long acting beta2-agonist; and 2)
factors associated with important treatment-related improvements on the
AQLQ12+. Methods: The psychometric properties of the AQLQ12+ were
assessed through post-hoc analysis of two large Phase III randomized placebocontrolled efficacy studies of mometasone furoate/formoterol fumarate (MF/F)
combination compared with monotherapy in subjects 12 years old or older
with moderate persistent asthma previously treated with either low-dose or
medium-dose inhaled glucocorticoids. The trial protocol was approved by
numerous IRBs and written informed consent and assent (adolescents only)
were obtained from all trial participants. Intra-class correlation coefficients
(ICC) evaluated reliability, and Pearson correlations of both ACQ baseline and
change scores with other relevant measures of asthma-related health examined construct validity and the ability to detect change. Results: In the lowand medium-dose studies, blinded trial data demonstrated excellent reproducibility (ICC ≥0.76) and moderate-to-strong construct validity with other
clinical and self-reported measures of asthma health at baseline and over time
for the AQLQ12+. A greater percentage of the MF/F treatment group (44%)
achieved an important change at 26 weeks on the AQLQ12+ compared with
formoterol fumarate (F, 23%) and placebo (18%) treatment groups in the
low-dose study (p<0.001), and the medium-dose study (50% (MF/F) vs. 34%
(F) and 23% (placebo); p<0.001). Using multiple logistic regression to explore
the factors associated with an important AQLQ12+ improvement, pre-randomization nighttime awakenings and rescue medication use emerged as significant predictors of this outcome. Conclusions: These findings provide strong
support for the measurement properties of the AQLQ12+ among moderate
persistent asthma patients, and confidence in the AQLQ12+ improvements
demonstrated by the MF/F treatment group.
K.W. Wyrwich*1, A.M. Ireland1, P. Navaratnam2, H. Nolte2, D. Gates2, 1.
Bethesda, MD; 2. Kenilworth, NJ.
Introduction: This study: 1) investigated the psychometric properties of the
Asthma Control Questionnaire (ACQ) in moderate persistent asthma patients
ages 12 years or older treated with a combination inhaled glucocorticoid and
long-acting beta2-agonist; and 2) explored factors associated with important
improvements in asthma control. Methods: Data from patients in two large
Phase III randomized placebo-controlled studies of mometasone
furoate/formoterol fumarate (MF/F) combination compared with monotherapies in subjects with uncontrolled moderate persistent asthma previously treated
with either: 1) low-dose, or 2) medium-dose inhaled glucocorticoids were used
to evaluate the ACQ psychometric properties and predictors of achieving important improvements in asthma control, defined as an ACQ score decline from
baseline of 0.5 or more at the end of treatment. The study protocol was approved
by numerous IRBs and written informed consent and assent (adolescents only)
were obtained from all trial participants. Intra-class correlation coefficients
(ICC) were used to evaluate reliability, while Pearson correlations of both ACQ
baseline and change scores with other relevant measures of asthma-related
health examined construct validity and the ability to detect change. Multiple
logistic regression techniques explored the factors associated with improvement. Results: The ACQ yielded acceptable reliability (ICC ≥ 0.75), and baseline and change scores demonstrated moderate to strong correlations with other
baseline measures and change scores in other clinical and self-reported measures of asthma-related health. More MF/F treatment group patients (40%)
achieved an important ACQ change at 26 weeks compared with formoterol
fumarate (F, 29%) and placebo (18%) treatment groups in the low-dose study
(p<0.03), and with all other treatments in the medium-dose study (48% (MF/F)
vs. 32% (MF), 26% (F) and 19% (placebo); p<0.001). Exploratory analyses
demonstrated that rescue medication use before randomization was a significant predictor of important ACQ improvement in both studies. Conclusions:
These findings support the psychometric properties of the ACQ to measure
asthma control among moderate persistent asthma patients, and provide confidence in the improvements in asthma control demonstrated by the MF/F treatment group.
L.Yang*1, M. Weinstein2, M. Kanuga2, D. Axelrod2, P. Fitzgerald-Bocarsly2,
1. Montclair, NJ; 2. Newark, NJ.
Rationale Patients with allergic asthma demonstrate immune reactions
shifted toward a Type 2 Helper T-cell (Th2) mediated response. Plasmacytoid
dendritic cells (PDCs) are increasingly recognized as having an important role
in the differentiation of naГЇve T-cells into Th2 cells. Methods A review of the
literature was performed to examine the role of PDCs in Th2 differentiation
and the development of allergic asthma via Pubmed and MEDLINE searchs
of “plasmacytoid dendritic cells” and “asthma”. Eleven relevant articles were
identified. Results Dendritic cells play a key role in innate immunity by secreting type 1 interferons in response to binding of antigenic molecular patterns
to intracellular and cell surface receptors such as Toll-like receptors (TLRs)
and C-type lectins. PDCs play a key role in antiviral immunity, mainly via secretion of proinflammatory cytokines in response to microbial nucleic acid binding to intracellular TLRs 7 and 9. One study demonstrated that, in vitro, asthmatic patients showed increased expression of high-affinity IgE receptors on
the surface of PDCs and impaired immune response after TLR9 stimulation.
PDCs in asthmatic patients appear to produce less interferon alpha and induce
greater Th2 response by signalling through CD40 and IL-3. A study of PDCs
in bronchoalveolar lavage fluid and peripheral blood after allergen challenge
in asthmatic subjects demonstrated that plasmacytoid dendritic cells accumulate in the airway lumen with reduction in peripheral blood. Conclusions In
the immune cascade, PDCs not only initiate but also modulate immune response.
By making use of the role of PDCs, more targeted therapeutic interventions in
asthmatic diseases may be developed.
R. Khanferyan*1, N. Milchenko1, Y. Dorofeeva1, L.M. DuBuske2, 1.
Krasnodar, Russian Federation; 2. Gardner, MA.
Background: Dual histamine H3/H4 receptor antagonists may modulate
IgE synthesis by PBMC from healthy donors and allergic subjects. This IgEmodulatory effect is not dependent on the structure of antagonists, but highly
dependent on the potency and affinity of these agents. This study assesses the
influence of H3/H4 receptor antagonists on IgE regulatory cytokines. Methods: Peripheral blood mononuclear cell (PBMC) cultures from healthy donors
and ragweed sensitive patients were incubated for 14 days with both low (10-
8 M) and high (10-5 M) concentrations of the H3/H4 antagonist Imoproxifan
(IMP). Cell supernatants were assessed for IL-4, IL-10, IL13 and ОіIFN levels
by ELISA (Diaclon) and were assessed for total IgE by ImmunoCAP FEIA
methods (Phadia). Results: The highly specific H3/H4 histamine receptor antagonist IMP in a concentration-dependent manner increased IL-4 and IL-10 production both in healthy donors and allergic subjects. PBMC from ragweed allergic patients showed increased IgE synthesis when assessed during the pollen
season but decreased synthesis during clinical remission (p<0.05). IMP modulated the IgE stimulatory effects of histamine decreasing the level of total IgE.
IMP induced a co-stimulatory effect together with histamine on IL-10 production in healthy donors and allergic subjects during the pollen season. High
concentrations of IMP (10-5 M) increased the effects of histamine in suppressing
IFNОі while low concentrations of IMP (10-8 M) increased IFNОі production.
Neither high nor low concentrations of IMP had an effect on IL13 production.
Conclusion: H3/H4 histamine receptor antagonists modulate IgE synthesis in
healthy donors and allergic subjects mainly via an impact on IL4 and IL10 production and a concentration dependent effect on IFNОі without influencing IL13
production. H3/H4 blockade thus can modulate the effects of histamine on synthesis of IgE and select cytokines which regulate IgE production.
M. Dzhindzhikhashvili1, M. Frieri*1, M. Samih1, H. Liu1, A. Aljada2,
M. Goeller2, S. Rubinstein1, L. Balsam1, 1. East Meadow, NY; 2.
Brookville, NY.
Introduction: In the lupus mouse model and systemic lupus erythematosus
(SLE) patients, DNA fragments isolated from plasma may mimic microbial
DNA and trigger Toll-like receptor 9 (TLR9) signalling, leading to the production of autoantibodies against these DNA fragments and nucleosomes. Vascular endothelial growth factor (VEGF) is a tightly regulated angiogenic
cytokine in the kidney. The present study investigates glomerular and tubulointerstitial expression of both TLR9 and VEGF in biopsies from human subjects with lupus nephritis (LN) and normal controls. Methods: Immunohistochemistry was performed using the Vector Vectastain Elite ABC method. Slides
were incubated with antibodies against VEGF and TLR9 at 4C overnight. Slides
were stained with hematoxylin and eosin, mounted and microscopically scored
at 10x and 20x. Statistical significance was analyzed by the two tailed t-test.
Results: Kidney biopsies from study subjects with LN (n=10) and normal controls (n=10) were evaluated for the expression of TLR9 and VEGF. LN samples demonstrated class III, IV and V histopathological changes. Degree of kidney damage was analyzed according to International Society of Nephrology/
Renal Pathology Society (ISN/RPS) classification of LN (2003). We observed
statistically significant intense staining of glomeruli as well as tubules for TLR9
up to 3+ of samples obtained from patients with LN versus negative controls,
(p=0.006) for glomeruli and (p=0.018) for tubules. Samples from LN subjects
showed 3+ staining of glomeruli but only up to 2+ in tubules for VEGF
(p=0.005) and ( p=0.012), respectively. There was no significant staining in
glomeruli, tubules or interstitium for TLR9 not for VEGF noted in control slides
obtained from healthy subjects. There was no correlation observed between LN
class severity and intensity of staining for TLR9 or VEGF. Conclusion: This is
the first study that investigated expression of TLR9 in human samples as well
as combined expression of TLR9 and VEGF. Our finding could be an important tool for understanding the role of TLR9 and VEGF in renal disease, as it
gives insight into the early detection and targeted treatment of LN.
Immunohistochemistry staining for TLR9 and VEGF in lupus nephritis kidney tissue sections
A. Fishbein*, K.A. Erickson, C. Szychlinski, D. Wang, R. Fuleihan, Chicago,
Introduction Egg allergy is the second most common food allergy in childhood, with 1-2% of the population affected. Most egg allergic children develop
tolerance prior to adulthood. Data is lacking about how the immune system differentiates along the T-cell pathway and induces tolerance to egg protein. Methods Using strict clinical and laboratory criteria, blood was drawn from patients
who were: egg allergic, not allergic (control) or tolerant (n= 7, 8, 6, respectively). Approval was obtained from the Children’s Memorial Hospital IRB and
written informed consent obtained from all research subjects. Peripheral blood
mononuclear cells were isolated and stimulated in vitro with a non-specific tcell stimulator (anti CD3/CD28) or (ovalbumin) at 0, 1, 10, 50 and 100 Вµg/mL
concentrations. After incubation, several cytokines which are known be part
of the Th1, Th2, Th17 or T-regulatory cell pathways, were measured. Results
Allergic patients’ cytokine profiles were best characterized by TH-2 (IL-4,IL5,IL-9, IL-13). Tolerant patients were best characterized by a T-reg response
(IL-10). At 100 Вµg /mL ovalbumin stimulation, median IL-10 concentrations
were 554 pg/mL, 804 and 1027 (control, allergic, tolerant, respectively). In a
linear mixed model analysis, individuals who were tolerant had the highest
responses of IL-10 to increasing doses of ova, with intermediate responses in
allergic and lowest responses in non-allergic (F(10, 18) interaction =3.20,
p=0.015). Tolerant patients were noted to produce the most IL-10 in response
to ova. Allergic patients had a significantly greater production of IL-4, IL-5,
IL-9 and IL-13. Conclusions Egg tolerant patients who have overcome an allergy
had a predominantly T-regulatory response. IL-10 appears to have a role in
inducing tolerance to egg protein. Further investigation is underway to explore
this mechanism. IL-10 could serve as a clinical marker of tolerance as well.
S. Kapoor*1, L. Geng2, H. Jyonouchi2, 1. Bloomfield, NJ; 2. Newark, NJ.
Although the percentage of children with severe asthma is small, this group
consumes a large proportion of the available medical resources. A major setback
is that current treatments are not effective in controlling exacerbations or disease
progression with severe asthma. Moreover, our understanding about the pathogenesis for progression to a severe, resistant asthma phenotype is lacking which is
critical for developing more effective treatments. In our pediatric practice we find
that patients with severe asthma present more often with recurrent infections than
with atopy, without any significant T cell defects. In this study, we hypothesized
that the dysregulation of innate immune responses results in the severe asthma phenotype encountered in the pediatric population. To test our hypothesis, we tested
responses to Toll like receptor(TLR) agonists in children diagnosed with severe
asthma. Our study subjects include children with severe asthma(N=15) as well as
controls, including healthy non-asthmatic children(N=26) and children with mild
to moderate asthma(N=25). We tested the production of pro-inflammatory(TNFО±, IL-6, IL-1ОІ and IL-12) and counter-regulatory(IL-10, TGF-ОІ, and sTNFRII)
cytokines after peripheral blood mononuclear cells(PBMCs) were stimulated
overnight with agonists for TLR 2/6, TLR3, TLR4, TLR7/8 and TLR9. Subsequently, we used ELISA to measure the cytokine expression. The most notable
results were found with the TLR4 agonist. Those patients with severe asthma
revealed a significantly higher production of IL-6, IL-1ОІ, IL-10 andTGF-ОІ(p<0.02).
Also, they demonstrated a greater production of IL-1ОІ and TGF-ОІ with agonists
of TLR2/6 and TLR7/8(p<0.02). Interestingly, TGF-ОІ production was higher in
severe asthma even when compared with mild to moderate asthma controls(p<0.05).
In contrast, we did not find significant changes in the production of any of these
cytokines in patients with mild to moderate asthma as compared to normal controls. To our knowledge, this is the first report of altered immune responses to
TLR agonists in children with severe asthma. This was most significant among
severe asthmatics in the presence of TLR4 agonist, endotoxin. Also, the data suggests that elevated TGF-ОІ levels may contribute to the development of fibrosis
and may play a role in the pathogenesis for severe refractory asthma.
18hours, 49% at 40hours). But caspase 3 inhibitor supressed CD30 induced
eosinophil apoptosis. The apoptosis rate decreased to 27.8% at 18
hours(P=0.012) and to 48.4% at 40 hours(P=0.029), respectively, which were
similar to that of eosinophils pretreated with Ig G1. Caspase 9 inhibitor also
suppress the CD30 induced eosinophil apoptosis from 72.8% to 47.8% at 40
hours incubation, which was similar to that of IgG1. In the western blot, procaspase 3 protein expression extracted from the eosinophils cultured with caspase 3 inhibitor in BerH8 pretreated wells was more marked than that of
extracted from the eosinophils cultured in the BerH8 pretreated wells without
the inhibitor. Additionally, we also detect the marked expression of procaspase
9 with the addition of caspase 9 inhibitor. Conclusion : This study showes that
caspase 3 and 9 have pivotal roles in CD30 induced eosinophil apoptosis.
B.V. Kim*, I. Voloshyna, M. Littlefield, L. Fonacier, A.B. Reiss, Mineola,
F.A. Placeres*, R. GonzГЎlez de Alfonzo, M. Alfonzo, I. Lippo de Becemberg, Caracas, Distrito Capital, Venezuela.
Introduction: The cyclooxygenase(COX)-2 inhibitor, celecoxib is an antiinflammatory and analgesic, while omalizumab is a monoclonal anti-IgE antibody used to treat allergic asthma. Published studies indicate that celecoxib and
possibly omalizumab increase risk of myocardial infarction and stroke. We previously reported that COX-2 inhibitors reduce expression of the anti-atherogenic reverse cholesterol transport (RCT) proteins, cholesterol 27-hydroxylase
(27-OHase) and ATP binding cassette transporter A1 (ABCA1). These proteins
are crucial for efficient cholesterol efflux, a process that prevents foam cell formation and protects against atherosclerosis. In this study, we investigated the
effect of omalizumab on the expression of these RCT proteins as well as on
scavenger receptor CD36 (promotes cholesterol influx) in THP-1 human monocytes and compared its effect to celecoxib. Methods: THP-1 human monocytes/macrophages (10^6 cells/ml), an established model of atherosclerosis,
were incubated (20hrs, 37В°C, 5%CO2) В± omalizumab(500Вµg/ml, 1000Вµg/ml),
and В± celecoxib(10ВµM). Expression of ABCA1, 27-OHase and CD36 message
was evaluated by quantitative PCR as well as protein translation evaluated by
Western blot analysis. Results: In cultured THP-1 monocytes, omalizumab
had a modest impact on ABCA1 and 27-OHase mRNA, but had no effect on
the expression of CD36 mRNA, while celecoxib significantly changed expression of each of these proteins in an atherogenic manner. Following celecoxib
exposure, 27-OHase and ABCA1 mRNAs decreased by 43.9В±5.6% and
34.8В±3.55% respectively, while CD36 increased by 45.5В±3.91%, p<0.001. Omalizumab treatment decreased message for the 27-OHase and ABCA1 by
28.6В±3.77% and 27.6В±3.68%(p<0.05), respectively, while CD36 expression
did not change significantly. Celecoxib treatment promoted foam cell formation to 52.4В±4.75 vs. 19.4В±2.17 for untreated cells, p<0.001, while omalizumab
treatment had no significant effect on the foam cell formation. Conclusions:
COX-2 inhibition may contribute to the pathological process of atherosclerosis by promoting lipid overload through effects on genes involved in cholesterol transport, while omalizumab does not substantially affect these pathways.
If reported cardiovascular and cerebrovascular risks are confirmed with omalizumab, the effect is likely by an alternate mechanism.
Asthma is a chronic inflammatory lung disease characterized by airway
hyperactivity that results in intermittent airway obstruction. The cAMP and
cGMP are important regulators of smooth muscle relaxation. Soluble guanylyl cyclase (sGC) is an enzyme highly expressed in the lung that generates
cGMP contributing to airway smooth muscle relaxation. Lungs of asthmatic
patients and animals, in which an asthma like response has been triggered,
express high levels of inducible NO synthase (iNOS). However, despite the
presence of ample amounts of NO that could activate sGC in the airway
smooth muscle cells (ASMC) and cause relaxation, airway tone is significantly elevated in asthma. This observation may be consistent with reduced
expression and/or responsiveness of signaling macromolecules downstream
of NO synthase. To determine whether the bronchoconstriction observed in
asthma is accompanied by changes in sGC activity, which a relevant member in this signal cascade, we used a well-established murine model of allergic asthma. Rats Sprague-Dawley were sensitized with ovalbumin (OVA),
by intraperitoneal injection and subsequent sprays. The ASMC were isolated
for digestion the smooth muscle using collagenase II and dispase. The sGC
enzyme activity were determined measuring the production of cGMP in
ASMC isolated from tracheal rat. All cells were pre-incubated for 15 min
with IBMX 100 uM (an inhibitor of PDEs). In both study groups GC activity was assayed in cells in the presence of 100ВµM SNP and carbamylcholine
(Cch 1x10-5M) and in both conditions, ODQ was tested. We found that all
cultures cells exposed to Cch and SNP increased cGMP, which were inhibited by 100 nM ODQ, suggesting that sGC was involved. However, OVAASMC showed lower GC activity compared to control ASMC. In addition,
SNP and Cch stimulation in OVA-ASMC were more lower than control
ASMC. Both cGMP rise in OVA-sensitive-ASMC for SNP and Cch were
inhibited to ODQ. Analyzed in PAGE (12%) showed bands (PM: 72-, 82,65- and 76-kDa), were identified by Western blotting as subunit alpha1, 2
and beta 1, 2; we found that all bands showed lower expression in compare
to ASMC-OVA vs ASMC-CONTROL . We conclude that sGC activity is
reduced in experimental asthma, which may contribute to airway hyperreactivity presents in asthma.
H. Lee*1, J.T. Kim2, 1. Uijongbusi, Korea, Republic of; 2. Seoul, Korea,
Republic of.
K.M. Shah*1, J.B. Hagan2, K. Bachman2, D. Squillace2, H. Kita2, 1.
Mankato, MN; 2. Rochester, MN.
Introduction: It has been known that expression of CD30 on eosinophil is
increasing in a time dependent manner and ligation of CD30 can accelerate
the eosinophil apoptosis. We evaluated the signaling pathways of the CD30
induced eosinophil apoptosis. Approval was obtained from the Uijongbu St
Mary’s hospital IRB and ( written) informed consent obtained from all research
subjects Methods : We drew 90mL of peripheral blood from healthy donors,
and purified eosinophils using MACS system at Uijeongbu St. Mary’s Hospital. Purified eosinophils were cultured in pretreated wells with anti-CD30 Ab
(BerH8) and IgG1 Ab. Aliquots of eosinophils were incubated with addition
of 100ВµM caspase 3 and 9 inhibitor in pretreated wells with BerH8, respectively. We analyzed eosinophil apoptosis using flow cytometry. We measured
the expressions of caspase 3 and caspase 9 protein by western blot. Results:
Stimulation of CD30 by BerH8 increased eosinophil apoptosis to 59.8% at 18
hours, 72.8% at 40 hrs, compared with that of IgG1 Ab in solution(25% at
Introduction: Soluble ST2 (sST2) acts as a decoy receptor binding directly
to IL 33 inhibiting binding to membrane bound ST2. Soluble ST2 may help
attenuate innate and adaptive immune responses. The aim of our study was to
quantitate the sST2 levels in patients with asthma and compare them to allergic patients and non-atopic controls. Methods: We obtained serum and induced
sputum samples from 10 patients with asthma, 10 with allergic rhinitis and 10
normal controls. The asthma group was based on prior pulmonary function testing and physician diagnosed asthma. The allergic rhinitis group had a clinical
diagnosis of allergic rhinitis or positive skin prick testing. Patients with AR had
no history or symptoms of chronic rhinosinusitis (CRS) or asthma. The normal controls are individuals with no history of allergy, asthma or sinus disease. The absolute value of sST2 in serum and induced sputum supernatants
were determined using an ELISA commercial kit (MBL Wolburn, MA). The
differences were analyzed by Mann-Whitney U test and Spearman correla-
tion, using InStat. The Institutional Review Board at the Mayo Clinic approved
the study prior to initiation. Results: We studied 30 patients with an age range
of 19-63 years old and average age of 44.8 years. There were 12 males and 18
females. Comparisons between the sST2 levels in the serum and sputum of the
various groups showed no statistical significance. Allergic rhinitis compared
with normal controls serum had p value of 0.53 and sputum p value of 0.15.
Looking at serum asthmatics compared with normal controls showed p values
of 0.81 and 0.38 for serum and sputum respectively. Comparing the serum and
sputum sST2 levels in asthmatics to allergic rhinitis resulted in p values of 0.77
and 0.43. We also found no correlation between sST2 in the sputum supernatant
and the eosinophil and neutrophil counts in the sputum cell pellets. Sputum
eosinophils and neutrophils to sST2 had r values of -0.04 and -0.13 respectively
with a p value of 0.479. Conclusions: Serum and sputum sST2 may not be
excellent biomarkers for asthma, likely because they are implicated in many
other inflammatory processes. There may be a trend toward increased sputum
sST2 in allergic rhinitis and asthma compared to normal controls, however in
our study this was not found to be statistically significant. These results do not
exclude the effects of medications.
S. Wu*, J.I. Silverberg, S. Kohlhoff, H.G. Durkin, R. Joks, T.A. SmithNorowitz, Brooklyn, NY.
Background: Green tea is known for its anti-oxidant and other beneficial
properties. Previous studies have shown the main antioxidant epigallocatechin
gallate(EGCG) to inhibit mast cell degranulation, neutrophil chemotaxis, and
type IV allergic responses. Previous studies in our lab have showed suppression of IgE production by green tea extract (GTE) in U266 cells, however the
effects of GTE on IgE production by human peripheral blood mononuclear
cells (PBMC) have not been studied. Methods: PBMC (1.5 x 106) obtained
from serum IgE+ (734-2491 IU/mL) allergic asthmatic, rhinoconjunctivitis
patients were cultured with anti-CD40 monoclonal antibody and recombinant
human interleukin-4 in the presence or absence of GTE (Topix) (1-100 ng/mL).
IgE levels in supernatants were then determined on day 10 (ELISA). Approval
was obtained from the SUNY-Downstate Institutional Review Board and written informed consent was obtained from all research subjects. Results. High
IgE levels were detected in supernatants of the PBMC cultures on day 10 (8.267.0 IU). When GTE was included in culture, IgE production by PBMC was
strongly suppressed in dose-dependent fashion on day 10 (21%-98% with 1100 ng). Conclusion: These results suggest that there may be therapeutic benefits for allergic asthma patients from GTE, in part as a result of suppression
of IgE production.
D. Alle*, L.G. Wild, M. Lopez, New Orleans, LA.
Rationale: Epstein-Barr virus (EBV) is the cause of heterophile positive
infectious mononucleosis (IM) typically characterized by fever, sore throat,
lymphadenopathy and atypical lymphocytosis. Periorbital edema is reported in
up to 33% of patients with IM, but rarely occurs as the initial manifestation of
the disease. Therefore, it may often be mistaken for angioedema or other etiologies. We report a 16 year old girl with periorbital edema as the initial manifestation of IM. Methods: Case report of a 16 year old girl who developed nonpruritic periorbital edema which improved with gravity nearly two weeks prior
to the presentation of acute pharyngitis, lymphadenopathy, and fever. She was
initially referred for a possible allergic reaction, but was subsequently diagnosed with EBV infection. Results: During the initial visit, physical exam
revealed non-pruritic bilateral periorbital edema. CBC revealed normal WBC,
hemoglobin, hematocrit, a decreased platelet count of 131 K/ВµL (150-350
K/ВµL), and normal differential. CMP revealed elevated total bilirubin of 2.3
mg/dL (0.1-1.0 mg/dL) with normal transaminases. Total IgE, C3, and C4 levels were normal. During a follow-up visit, exam revealed pharnygitis with lymphadenopathy. Monospot test returned positive, and CBC showed elevated WBC
of 17 K/ВµL (4.5-13 K/ВµL) with normal differential. Conclusions: Periorbital
edema rarely occurs as the initial manifestation of IM. We suggest that IM
should be included among the initial differential diagnoses of periorbital edema
as it is often initially mistaken by practitioners for angioedema, cellulitis,
nephrotic syndrome, or thyroid disease.
M.L. Alvares*1, I. Warrier2, 1. Irving, TX; 2. Dallas, TX.
INTRODUCTION: Pneumococcal vaccines are often given to patients with
Systemic juvenile idiopathic arthritis on Anakinra, a recombinant IL-1 receptor antagonist, as there is the concern for serious pneumococcal infections. This
case report offers a situation where pneumococcal vaccination should be
delayed. CASE REPORT: A.B. is a 2 year old male who initially presented with
fever, cough, vomiting and decreased urine output in the setting of elevated
ESR, CRP. On day two of admission he was noted to have dullness to his tympanic membranes, a diffuse rash described as maculopapular, erythematous
with some areas being serpiginous, and an erythematous pharynx. As a result,
he was started on antibiotics. An echocardiogram revealed an ectatic right coronary artery without evidence of aneurysm. In the incomplete Kawasaki algorithm, he fulfilled three of the laboratory criteria (WBC, platelets, albumin) in
addition to the fever and elevated CRP. As a result, it was decided to treat for
Kawasaki’s and he was given IVIG (2g/Kg) and ASA times 2 doses in total.
However, he did not respond as expected with persistent fevers. Rheumatology was consulted and felt his story was consistent with systemic onset juvenile idiopathic arthritis – due to his fever pattern,and rash. After the completion of a negative infectious workup, Rheumatology started Anakinra and he
quickly became afebrile. At this time, he was given the Pneumococcal vaccine
(23 valent) and shortly thereafter developed a fever and rash at the injection
site which progressed. His rash soon included urticarial plaques to his chest
and back, purpuric plaques to dorsal feet bilaterally, and scattered purpuric
plaques to his legs. The Allergy/Immunology service was then consulted who
believed that the large doses of IVIG followed by antigen (vaccine) triggered
the precipitation of antibody/antigen complexes which produced the skin rash
as well as other systemic symptoms such as fever and the peripheral purpura
(serum sickness). Complement levels C3 and C4 were sent and seen to be low.
C3D level was sent and was elevated. CONCLUSION: Currently there are
recommendations for timing of vaccinations after IVIG for measles and varicella vaccines – 11 months after treatment. However, since the IVIG provides
protective antibody titers to common pathogens and the half life is approximately 30 days, other vaccinations after IVIG should be delayed.
W.C. Anderson*, D. Stukus, Pittsburgh, PA.
Background: Gelatin is ubiquitously encountered in foods, medications,
vaccines, and cosmetics. While there have been published reports of both IgEand non-IgE-mediated allergic reactions to gelatin, most have been documented
occurring with vaccinations. IgE-mediated allergic reactions to gelatin in food
have been reported rarely in the literature, especially in the pediatric population. Here we present a case of a 9-year-old patient with a likely IgE-mediated
reaction to gelatin in gummy candy. Case History: The patient is a 9-year-old
male with a history of well-controlled asthma who presented with two episodes,
separated by six months, of generalized urticaria, pruritus, and facial
angioedema of the eyes and lips occurring fifteen minutes after the ingestion
of Target brand gummy worms and bears. Both episodes resolved rapidly in the
emergency department following administration of diphenhydramine and intramuscular corticosteroids without the use of epinephrine. The patient had previously tolerated other gelatin containing products including Jell-o, marshmallows, and MMR and DTaP vaccinations. Results: A physician supervised
oral challenge was performed to the exact same products that the patient reacted
to previously. Within sixty minutes of consuming two servings of gummy bears
and one serving of gummy worms in a dose-graded fashion, the patient developed lip angioedema and generalized urticaria of his face, neck, trunk, and
extremities. The patient had no associated shortness of breath, wheezing, dysphagia, or emesis. His reaction reversed within twenty minutes of administration of diphenhydramine. After this reaction, RAST testing was performed
which revealed elevated results for both bovine and porcine gelatin at 2.1 and
0.94 kU/L, respectively. Conclusion: IgE-mediated gelatin allergies in food are
rare secondary to gelatin’s processing, which may alter its allergenicity. Other
ingredients in the consumed candy included basic sugars, natural and artificial flavorings, and food coloring. The patient has tolerated multiple other
candies with these same ingredients, except gelatin, without adverse reaction.
This case represents a likely IgE-mediated reaction to gelatin in gummy can-
dies confirmed both by oral challenge and RAST testing, which is a rarity in
the general population and especially in pediatrics.
W.C. Anderson*, A. Petrov, Pittsburgh, PA.
Background: Intravenous immunoglobulin (IVIG) is a well-established
treatment for patients with common variable immunodeficiency (CVID), but
severe anaphylactoid reactions to IVIG have been documented. Subcutaneous
immunoglobulin (SCIG) has been reported as a safe alternative therapy in these
patients. A PubMed search revealed that these reports used a 16% concentration of SCIG (Vivaglobin or Subcuvia). Here we present the case of a patient
with CVID with a delayed anaphylactoid reaction following IVIG who was
then successfully treated with a 20% concentration of SCIG (Hizentra). Case
History: The patient is a 50-year-old female with a history of juvenile rheumatoid arthritis on chronic steroids who presented for evaluation of chronic bronchitis, recurrent sinusitis, and hypogammaglobulinemia. She was subsequently
diagnosed with CVID and started on IVIG. The patient tolerated the first infusion well with mild chest tightness, headache, and arthralgias. Within twelve
hours of her second infusion, she developed similar symptoms with the addition of fever, rigors, diffuse erythematous rash, altered mental status, and witnessed syncope. The patient was found by EMS to be hypoxic and hypotensive
requiring fluid resuscitation. Results: Six weeks after the patient’s anaphylactoid reaction, she was admitted to the ICU for initiation of Hizentra. She received
ten grams over three hours at three separate sites without an adverse reaction.
The patient did not require pretreatment or symptomatic care. She was monitored for a total of eighteen hours, with six in the ICU, prior to discharge. One
week later the patient’s second 20% concentration SCIG infusion was administered at home over two hours, followed by weekly hourly infusions at three
separate sites, all without a reaction. Conclusion: An infusion of 16% concentration of SCIG has been used as an effective alternative therapy for patients
with prior anaphylactoid reaction to IVIG. This patient with a delayed anaphylactoid reaction to IVIG was successfully challenged without premedication to a 20% concentration of SCIG in the ICU with subsequent tolerance of
infusions at home. A higher concentration, more rapidly administered form of
SCIG may be used safely in patients with a prior anaphylactoid reaction to
A.M. Arseneau*1, S.D. Rubenstein2, H.F. Otto2, M.S. Tankersley1, 1. San
Antonio, TX; 2. Dayton, OH.
Introduction: A 27 year old male with poorly controlled, severe persistent
asthma on omalizumab was evaluated for rush immunotherapy (RIT). He had
persistent seasonal and environmental allergic triggers which continued to exacerbate his asthma despite maximal medical therapy. Though not on omalizumab
at the time, he previously experienced anaphylaxis to his initial injection of
aeroallergen IT six years prior requiring emergent intubation and ICU admission. As he had now been on omalizumab for three years, RIT was selected given
his previous severe IT reaction. Methods: The patient continued use of omalizumab, fluticasone/salmeterol 500/50 mcg bid, beclomethasone 80 mcg bid
and montelukast 10 mg once daily with prn albuterol MDI. He was started on
prednisone 20 mg two weeks prior then increased to 40 mg two days prior to
planned RIT due to a FEV1 of 72% in order to achieve a FEV1 ≥ 80% predicted.
In addition, he was started on ranitidine 150 mg bid and zileutin 1200 mg bid.
A four day RIT was designed (Table 1), and he was admitted to the ICU for the
duration. Results: The patient tolerated his four day RIT. He had two minor
pruritic events treated successfully with intravenous diphenhydramine. His predetermined maintenance IT dose (yellow vial, 1:10 v/v 0.05 mL) was given prior
to discharge, and he has continued IT without systemic reaction. At three month
follow-up, he continued to tolerate IT and had no further asthma exacerbations
or steroid requirement. Conclusions: This case demonstrates a successful
approach to RIT in a patient on omalizumab with refractory, severe persistent
asthma and a previous severe systemic reaction to aeroallergen IT. To our best
knowledge this is the first reported case of an RIT protocol, emphasizing the
improved safety with the use of pretreatment consisting of omalizumab, prednisone, ranitidine and zileutin.
S. Axelrod*, M.A. Davis-Lorton, Mineola, NY.
BACKGROUND: Bullous Pemphigoid is a well-described autoimmune
blistering disease of the elderly. Early manifestations can be urticarial, pruritic,
erythematous lesions that subsequently form bullae. The histology of bullous
pemphigoid has much in common with that of erythema multiforme. Both
exhibit necrosis of the roof of the blister, have similar acantholysis, intracellular edema, and spongiosis. We report a case of a 72 year old female who presented clinically with a erythema multiforme, and subsequently diagnosed with
drug-induced bullous pemphigoid by biopsy and immunofluorescence. CASE
REPORT: A 72 year old female with a new history of gout, treated with Allopurinol and Colchicine for 3 weeks prior to admission presented with a 3 day
history of fevers (104В° F) and rash. The rash started on her arms, spread to the
trunk and face and was mildly pruritic. She developed erythematous lesions
with central clearing, raised border with a targetoid appearance (one lesion with
4 distinct rings) that coalesced, producing polycyclic configurations. (Image
1) The patient previously reported fluid-filled “blisters”, although none were
observed at the time of examination. The oral and ocular mucosa were clear.
RESULTS: She had a positive HSV I/II IgG (45.4) and IgM I/II (2.54).
Mycoplasma and monospot tests were negative. H&E staining of skin biopsy
revealed a superficial perivascular and interstitial infiltrate and Direct Immunofluorescence showed 1+ linear deposition of C3 at the basement membrane
zone, compatible with bullous pemphigoid – likely drug-induced. A salt-split
skin preparation revealed focal C3 deposition on the roof of the artifactually
induced vesicle, yielding the diagnosis of bullous pemphigoid. DISCUSSION:
This is the first case report of drug-induced bullous pemphigoid mimicking
erythema multiforme without bullous lesions. The following clinical features
resembled erythema multiforme: extensor surfaces of extremities were most
frequently affected, the individual erythematous plaques increased in size centrifugally with targetoid appearance. However, immunohistologically, a linear
C3 deposition at the basement membrane zone on direct immunofluorescence,
consistent with bullous pemphigoid. The patient was treated with the discontinuation of Allopurinol and Colchicine, as well as a slow taper of intravenous
followed by oral corticosteroids with near complete recovery.
spray/swallow technique over a 3 month period. C. Results One year after clinical improvement following topical CS treatment, the patient developed oral
herpetic lesions accompanied by severe odynophagia. Endoscopy revealed diffuse caseous exudative mucosal lesions throughout the esophagus. Histopathologic examination of the lesions revealed evidence of rare eosinophilic infiltration within the squamous epithelium, but striking pathognomonic findings
of herpetic infection confirmed by an elevated anti-HSV-1 IgM titer of >1:160
(nl< 1:10) and an IgG titer of 1.22 (nl<1.1) D. Conclusions This case report
raises several interesting questions: 1) Does EE predispose to the development of HSV infection? 2) Can oral HSV infection progress to esophageal
infection? 3) Does treatment of EE with topical corticosteroids predispose to
subsequent esophageal HSV infection? The results of this study favor the possibility that EE creates a conducive environment, similar to that seen with atopic
dermatitis, for susceptibility to HSV infection. The predilection for HSV by
prior CS therapy seems less likely because of the temporal delay between infection and CS treatment. Nonetheless, the case study illustrates the importance
of careful surveillance by the allergist-immunologist during EE treatment of
complicating infections which may accompany CS therapy.
C.S. Bauer*, E. Shakir, M. Vasudev, L. Goodman, J. Fink, Milwaukee, WI.
INTRODUCTION: Loeffler first identified an association between pulmonary infiltrates and eosinophilia in 1932. To date, this heterogenous group
of conditions has remained difficult to classify, with etiologies ranging from
drug-induced to tropical infections. A consistent underlying feature in these
disorders is a striking clinical, lab, and radiographic disease remission in
response to steroids. In a subset of patients, this response is transient and disease recurrence occurs with steroid tapering. METHODS: A 67 y/o male with
intermittent asthma presented with 2 months of non-productive cough. Spirometry revealed FEV1 2.77L (84%) and FVC 3.7L (91% ). On CBC, white blood
cell count was 16.7 K/ВµL with eosinophilia (8,800 cells/ВµL). Chest CT revealed
peripheral and upper lobe ground-glass opacities and enlarged mediastinal
and hilar lymph nodes. Other causes of eosinophilia such as Aspergillus and
parasitic infections were excluded and a course of oral steroids was initiated.
After 3 weeks of Prednisone 60 mg/day, the patient had drastic clinical, radiographic, and laboratory improvement. Prednisone was then tapered over the
next 2 months. Upon reaching 10mg/day, the patient’s symptoms returned. Follow up chest CT showed mediastinal lymph nodes and two new focal infiltrates
in the right apex and his eosinophil count was 24,000 cells/ВµL. This prompted
further evaluation. RESULTS: Bone marrow biopsy revealed tri-lineage
hematopoiesis and mild eosinophilia; FISH was negative for FIP1/L1-PDGFRA,
bcr-abl, and CHIC2. There was no monoclonality on T-cell rearrangement.
Colonoscopy, endoscopy, and echocardiography were without abnormalities.
Over the next seven months, he failed steroid wean repeatedly. Nine months
later, he developed a DVT. Favoring a dual diagnosis of chronic eosinophilic
pneumonia and presumed idiopathic hypereosinophilic syndrome, non-steroid
treatment options were considered—mepolizumab, cyclosporine, suplatast tosilate, and interferon-alpha. To date, on week 6 of interferon, the patient has
weaned to Prednisone 10 mg/day. He is asymptomatic and with a normal
eosinophil count, but has suffered a TIA. CONCLUSION: As illustrated here,
the cause of peripheral eosinophilia with respiratory symptoms is often challenging. The long-term treatment options are controversial and complicated
by high costs, difficult access, and side effects.
Y.H. Pung*1, K.P. Bull-Henry1, A.V. Manoukian2, J.A. Bellanti1, 1. Washington, DC; 2. New Brunswick, NJ.
A. Introduction This case study describes a patient with a novel presentation of esophageal herpes simplex viral (HSV) infection occurring one year
after successful topical corticosteroid (CS) treatment for eosinophilic esophagitis (EE) B. Methods After establishing the diagnosis of EE by histopathologic
demonstration of >25 eosinophils/hpf, the patient was treated by food elimination, allergen immunotherapy and oral fluticasone administered by a
S. Benouni*, W. Klaustermeyer, Los Angeles, CA.
The loss of taste often does not receive the medical attention it deserves
which may have serious implications for patients’ quality of life. More than 2
million Americans have some type of chemosensory disorder. We report a
case of a patient with a history of allergic rhinitis presenting with loss of taste
who was found to have pernicious anemia. A 64-year-old male with a history
of allergic rhinosinusitis presented with diminished gustation to sweet flavors
for one year. He denied any decreased sense of smell. On prior visits this loss
of taste was attributed to his allergic rhinitis. He denied heartburn, head trauma,
surgical procedures or radiation treatment. Past medical history was significant for hyperlipidemia and glaucoma. His medications included cetirizine,
mometasone nasal spray, simvastatin, and travoprost eye drops. His exam was
significant for a beefy tongue. There were no thyromegaly or parotid masses.
His neurologic exam was unremarkable. No polyps or nasopharyngeal masses
were seen on rhinoscopy. Significant labs included zinc=548 ug/L (normal>600ug/L), vitamin B12=146pg/mL (160-911pg/ml), homocyteine=19.47
umol/L (5-13.9 umol/L), methylmalonic acid=0.78 umol/L (<0.40 umol/L),
and intrinsic factor antibody was detected. CBC did not reveal macrocytosis.
The diagnosis of pernicious anemia was made. The patient was begun on vitamin B12 replacement therapy with improvement of his taste sensation. With
the exclusion of nasal and sinus diseases, the common causes for gustatory dysfunction are viral and oral infection, aging, neoplasia, trauma, and middle ear
surgery and disease. In addition, metabolic diseases such as diabetes or hypothyroidism, vitamin B12 or zinc deficiency, medication side effects, or irradiation can be the source of neural injuries. Rarely, central neural factors result in
loss of taste. No standardized tests are presently available for workup of taste.
Evaluation should include thorough oral pharyngeal and neurologic exam as
well as workup for metabolic or endocrine disease. If no abnormality is found,
fiberoptic evaluation should be performed. Additional evaluation with CT or
MR of the head is further indicated to rule out an intracranial or peripheral
nerve abnormality. Loss of taste, to sweets in particular, is often overlooked as
a result of loss of smell. Allergists should be aware of the evaluation for loss
of taste, keeping in mind a broad differential diagnosis.
S. Benouni*, A. Rafi, W. Klaustermeyer, Los Angeles, CA.
We are reporting the first case of a patient with CVID that experienced a
systemic hypersensitivity reaction to subcutaneous VivaglobinВ®. A 63-yearold female with a history of CVID with recurrent sinus infections and pneumonias experienced urticaria and anaphylaxis to Vivaglobin subcutaneous infusion (SQIg). During the course of her first two infusions, she developed localized
urticaria within twenty minutes. During her third infusion, not only were her
reactions around her infusion sites larger but she developed generalized swelling
of her face as well as asthmatic symptoms. No symptoms of throat or tongue
swelling occurred. All three episodes resolved with oral diphenhydramine. Previously, after receiving GammagardВ® infusions uneventfully for one year, she
developed urticaria and transient hypoxia. She is currently on GamunexВ® and
tolerating it well. She has additional allergies including urticaria with penicillin, erythromycin and tetanus vaccine. Past medical history is significant
for colitis, asthma, CAD, von Willebrand deficiency and B12 deficiency. She
has normal IgA levels. Laboratory testing for IgG-IgA antibodies and hypersensitivity testing to Vivaglobin is pending. The mainstay of therapy for primary antibody immunodeficiency remains Ig replacement therapy either by IV
infusion or SQIg. Immediate adverse events arise from an inflammatory
response to elements within IgG products such as IgG complexes and chemical substances used in purification and excipients. IgG infusions may lead to
acute complement activation with production of anaphylatoxins C3a and C5a.
Low molecular weight polypeptides and compounds activating plasminogen
pro-activator also produce harmful effects thru fibrinolysis. Foreign IgG may
increase IgE leading to an allergic reaction. Lastly, IgA in IgG preparations can
elicit anti-IgA antibodies leading to an anaphylactic reaction. Although, a retrospective study has shown that even in the presence of anti-IgA antibodies,
patients who had reported serious adverse events with previous IVIg tolerated
treatment with SQIg. Vivaglobin and Hizentra™ are the only two SQIg available. One hypothesis for our patient’s reaction is she may have developed IgG
to IgA given the high content of IgA, up to 1170mcg/mL, in Vivaglobin. However, this does not explain her previous reaction to Gammagard which has the
least amount of IgA (<2.2ug/mL).
K. Bhat*, R. Bonds, Galveston, TX.
Introduction: There is little information regarding the allergenicity of newer
insulin analogues such as detemir. Case reports of Type I, III and IV hypersensitivity reactions to detemir have been described, mostly consisting of local
cutaneous reactions at the injection site. One case of anaphylaxis to detemir
has been reported in the literature to date. We present a second case of anaphylaxis following detemir injection. Case: A 43 year old female with Type 2
diabetes mellitus presented with an anaphylactic reaction seconds after subcutaneous injection of detemir. The medication was initially tolerated for several months without any adverse effects. One month prior to anaphylaxis, localized erythema and edema at injection site was intermittently noted after
administration. During treatment in the emergency department for the initial
anaphylactic event, she developed a second episode of anaphylaxis, with documented hypotension, upon receiving regular insulin. Further evaluation of
insulin allergy was requested. Skin prick testing using 1:10 dilutions and full
strength detemir, aspart, glargine and HSA diluent with phenol was negative.
Histamine and saline were used for positive and negative controls. Immunocap testing (IBT) did not detect significant levels of human insulin IgE. Graded
dose challenges to glargine and aspart were performed at a subsequent visit to
establish possible alternatives to detemir. Incremental doses of intradermal followed by subcutaneous injections were tolerated without reactions. Discussion:
The prevalence of insulin allergy in patients receiving human insulin is <1%.
Reactions may occur due to the insulin compound or the inactive ingredients.
Cross reactivity between human insulin and insulin analogues has been described
but is difficult to evaluate. In this case, sensitization to additives such as zinc
and cresol is less likely given tolerance to glargine and aspart, which also contain these substances. Furthermore, tolerance to the two analogues suggests
there may be limited cross-reactivity amongst these insulin compounds compared to that of detemir and regular insulin. Conclusion: Anaphylaxis is a rare
but potentially fatal reaction that can occur with insulin and insulin analogues.
When possible, therapeutic alternatives including oral hypoglycemic agents
should be used. Further testing or desensitization to other insulin formulations
should be performed when appropriate.
hirsutism, and hepatotoxicity. Danazol is a Category X drug for pregnancy, contraindicated secondary to the risk of virilization of female fetuses, especially
after the 8th week of pregnancy, when androgen receptor sensitivity begins. A
lesser known side effect of danazol is suppression of ovulation. Case: A 23 year
old female who was diagnosed at age 20 with HAE decided to attempt to conceive a second child. The patient started treatment with danazol in January 2008
after an episode of throat edema following a dental procedure. Since August
2008, the patient’s symptoms have been well-controlled on danazol 200 mg
alternating with 400 mg daily. The patient’s IUD was removed in hopes of
becoming pregnant in January 2010. Plans were made to transition her from
danazol to nanofiltered C1 inhibitor concentrate in the event that she became
pregnant. She was unable to become pregnant, however, during her treatment
with danazol. Her insurance company was then petitioned to allow her to start
her C1 inhibitor treatment while trying to conceive, and C1 inhibitor was ultimately approved. Conclusions: While danazol is generally well-tolerated, it
does have known complications. One of these complications is its properties
as a potent contraceptive agent. It was studied as a contraceptive in the 1970s
and found to be quite effective at the dosage of 200 mg, less than our patient’s
average daily dose. With the availability of nanofiltered C1 inhibitor concentrate, patients who require prophylaxis for HAE have more therapeutic options,
but this agent requires twice weekly intravenous dosing and is extremely expensive. Given the current economic climate, the evolving state of health care,
and limited resources, the potential advantages of this therapy must be weighed
against its cost.
S.I. Breitbart*1, L. Bielory2, 1. Englewood, NJ; 2. New Brunswick, NJ.
Background: HAE is a life-threatening autosomal dominant condition
that results in acute attacks of facial, laryngeal, genital, or peripheral swelling
associated with a deficiency or malfunctioning form of the C1-esterase
inhibitor (C1-INH). Treatment includes anabolic steroids, C1-INH replacement (C1-INHr), or bradykinin-receptor-antagonists (О±ОІ2R). We report
the spontaneous resolution of a Type II HAE after a 36-pound weight loss
in a 63-year-old Caucasian male. He was diagnosed in 1994 and treated with
methyltestosterone (1994-2008), where he was symptom-free from the late
1990s through 2006. He subsequently began C1-INHr (10/08-9/09), where
he averaged one HAE exacerbation/month on C1-INHr. In 9/09 the patient
ceased C1-INHr and enrolled in a О±ОІ2R trial but never commenced treatment. At the time that therapy was discontinued, the patient had concurrently been involved in a demanding exercise program, where he recorded
daily weights. Objective: To report of spontaneous resolution of HAE
attacks/symptoms (despite absence of therapy) while on a stringent 11-month
weight-loss regimen. Methods: C1-INH (total and functional) was obtained
from 3/06-4/10. The patient’s labs are compared before and after weight loss
was achieved. Results: A weight loss of 36 pounds was recorded between
June 2009 and April 2010 (see Table 1). Before weight loss: Functional
C1-INH was normal (>68%). After weight loss: Testosterone was normal
(457 ng/dL), and total C1-INH was elevated (31 mg/dL) while functional
C1-INH was low (14%). Conclusion: This is the first reported case of
improvement of C1-INH that may be related to weight loss and associated
with increased testosterone. We believe that reduced HAE symptoms are
due to an increased androgen release.
A. Boyd*1, J. Bonner2, G.W. Bates2, 1. Vestavia Hills, AL; 2. Birmingham,
Introduction: Hereditary angioedema (HAE) is a rare autosomal dominant
disorder which leads to recurrent angioedema secondary to a deficiency of C1
inhibitor. Patients who have experienced severe attacks in the past are often
placed on prophylactic therapy with impeded androgens such as danazol. There
is good data to support the use of danazol for prophylactic treatment of HAE,
but the drug has concerning side effects including weight gain, dyslipidemia,
Table 1: Weights and Associated Values of C1-Esterase Inhibitor
M. Camacho-Halili*, M. Davis-Lorton, Mineola, NY.
A 36-pound weight loss was achieved between June 2009 and April 2010.
A. Butt*, D. Ledford, Tampa, FL.
Background: Cryoglobulinemia (CG) is associated with a leukocytoclastic vasculitis primarily affecting the kidneys, vasa nervorum and skin. Urticaria,
but not usually angioedema, is a potential presentation for CG. Cryoglobulins
are associated with a variety of conditions which include infectious, autoimmune and lymphoproliferative disorders. Hence, treatment options of CG are
varied. We report a male with corticosteroid (CS)-dependent urticaria and
angioedema (U/AE) who discontinued CS therapy following initiation of weekly
oral methotrexate (MTX). Results: 57-year- old Caucasian male presented with
a seven month history of recurring symptoms of generalized urticaria and facial
angioedema. The symmetrical rash initially developed after a dental procedure requiring penicillin therapy. The findings were attributed to penicillin, but
persistence of the rash prompted a skin biopsy diagnosing a leukocytoclastic
vasculitis. Prednisone, 10 mg twice daily, resulted in minimal improvement of
the rash, but arthritic pain in the hands and knees developed. An immunologic
and rheumatologic evaluation showed type 3 mixed CG without monoclonal
protein, 2+ urinary protein, decreased C3 (50 mg/dL) and CH50 (13 U/mL).
Negative studies included serum rheumatoid factor, hepatitis antibodies, antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA) and
CT scan of the abdomen. Treatment with daily doxepin (100 mg), meloxicam
(7.5 mg), hydroxycloroquine (400 mg) as well as prednisone (20 mg) was
ineffective for the U/AE, with exacerbations occurring when the dose of prednisone was reduced. Oral MTX (25 mg weekly) facilitated a prednisone taper,
which was discontinued completely within 6 months without U/AE exacerbation. The cryoglobulin quantification was unchanged. Conclusion: The differential diagnosis of U/AE includes a variety of less common immunologic conditions. The mechanism of action of weekly, oral MTX is not completely defined.
Suppression of cell replication is probably not the primary mechanism of action.
Weekly MTX is a minimally immunosuppressive therapy that may be effective for U/AE associated with CG. Evaluation for CG should be considered in
subjects with U/AE requiring chronic CS therapy or with features of leukocytoclastic vasculitis.
BACKGROUND: Rituximab is an anti-CD20 monoclonal antibody used
with significant efficacy in the treatment of Non-Hodgkin’s B cell lymphoma,
chronic lymphocytic leukemia and rheumatoid arthritis. B cell depletion often
results for six to nine months after therapy, though may persist for years following treatment with associated immunoglobulin suppression. Literature to
date has described rituximab associated hypogammaglobulinemia in the context of bone marrow transplantation and adjuvant chemotherapy, but most
authors cite an absence of associated infections. We report a series of patients
referred to our center for recurrent, severe infections, found to be hypogammaglobulinemic in the context of previous rituximab administration. CASE
REPORTS: Four patients are described in Table 1, all of whom had no previous history of recurrent infections but developed significant sinopulmonary
illnesses after rituximab therapy for malignancy. Age, gender, oncologic history, prior chemotherapeutics, and presenting infections are reviewed in detail.
RESULTS: All four patients were found to be hypogammaglobulinemic with
absent B cells on laboratory evaluation. Replacement immunoglobulin therapy
was begun for each patient, given their histories of recurrent, non-neutropenic
sinopulmonary infections. Symptoms resolved with immunoglobulin replacement. Mean duration of follow-up was 20 months post-rituximab therapy; however, all patients continued to have persistent immunoglobulin suppression and
B cell depletion beyond the typical six to nine month period. DISCUSSION:
The advent of monoclonal antibodies that target specific cellular markers are
highly effective in combating specific diseases, but are not without complication. Although previous case series have reported a paucity of severe infections
in the setting of acquired hypogammaglobulinemia post-rituximab therapy, serious infections can develop which merits close follow up of such patients. Assessment of immunoglobulin levels and lymphocyte panels may be warranted prior
to the start of therapy.
Table 1. Patient Characteristics and Subsequent Immunologic Workup
E. Chang*, S.P. Jariwala, J. Collins, G. Hudes, D. Rosenstreich, Bronx, NY.
Introduction: Mastocytic enterocolitis is a recently reported entity characterized by chronic diarrhea, abdominal pain, and bloating caused by the localized increase of intestinal mast cells. This condition is confirmed by the presence of greater than 20 mastocytes/hpf with immunohistochemical staining for
mast cell tryptase or c-kit (CD117). We describe a case of mastocytic enterocolitis in an adult with chronic diarrhea and abdominal bloating, all of which
resolved following treatment with loratadine. Our case is only the third to be
reported in the English literature. Methods: Case description; literature review
Results: A 62-year-old female presented to our Allergy Clinic with two years
of diarrhea and bloating. Past history was significant for hypothyroidism, osteoporosis, and depression. Physical exam and vital signs were unremarkable, and
skin testing was negative. Serum blood count, chemistries, liver function testing, thyroid function and stool studies were within normal range. Colonoscopy
performed one year prior was unremarkable. The patient was tested for tryptase,
immunoglobulins, SPEP, HIV, RAST, C3, C4, IGE, ANA, anti-Sm, anti-RNP,
RF, anti-CCP, CRP, ESR, Lyme, and EBV, which all returned negative. In light
of the negative laboratory evaluation and chronic symptoms, repeat staining for
mast cell tryptase on colonoscopy samples was requested in order to evaluate
for mastocytic enterocolitis. Histologic samples demonstrated greater than 20
mast cells/hpf with c-kit immunostaining, and the patient was diagnosed with
mastocytic enterocolitis. A trial of oral cromolyn was initiated and subsequently
stopped due to decreased appetite and bloating. The patient was started on loratadine with symptom resolution. Conclusion: Mastocytic enterocolitis is thought
to result from the paracrine effects of histamine released by increased mast cells
in the intestines. Mast cell stabilizers and H1 and H2 receptor antagonists are
considered therapeutic. As this condition may be misdiagnosed as irritable bowel
syndrome, clinicians must maintain a high index of suspicion in any patient that
presents with chronic functional diarrhea of unclear etiology.
N.M. Chase*, J.T. Casper, J. Verbsky, J.M. Routes, Milwaukee, WI.
Introduction: The complement system is an evolutionarily conserved group
of proteins that interact with the innate and adaptive immune systems. Activation of complement proteins occurs through a proteolytic cascade, generating
fragments that serve to opsonize and induce inflammation; initial proteolysis
is triggered by one of three pathways (i.e., classical, alternative, mannose-binding lectin). The unifying complement component is C3, which serves a critical role in amplification of the complement cascade in all three pathways of
activation. Deficiencies in C3 are exceedingly rare, and have been associated
with severe, recurrent infections and immune complex-mediated disease, often
presenting in early childhood. Case Description: A previously healthy 18year-old male was hospitalized after developing fever, chills, and hypotension; blood and cerebrospinal cultures were later positive for N. meningitidis,
serotype Y. Upon discharge, he was referred to a clinical immunologist, as he
had previously received a meningococcal polysaccharide vaccine three years
prior. Antibody titers to meningococcal serotypes A, C, and Y were low, while
titers to serotype W135 were protective. Screening of his total hemolytic classical complement pathway (CH50) was abnormally low (<10 U/mL; normal =
31-66 U/mL). Further workup revealed an undetectable C3 level (<6 mg/dL;
normal 70-206 mg/dL), a total alternative complement pathway (AH50) level
of 0 U/mL (normal = 77-159 U/mL), and a normal Factor B level (237.5
mcg/mL; normal = 127.6-278.3 mcg/mL), consistent with a primary C3 deficiency. Molecular screening of the patient’s C3 gene is in progress. The patient
is currently doing well, and carries antibiotics for immediate initiation if he
develops symptoms of illness. Discussion: C3 deficiencies are extremely rare
defects that affect the functionality of all three complement activation pathways. While C3 deficiencies are often diagnosed in young children on the basis
of infection, this case illustrates the potential for the development of infection
later in life. Additionally, despite the association of meningococcal meningitis
with defects in late complement components, infection can result from deficiencies in other early complement proteins.
L. Chernin*, D. Swender, R. Hostoffer, H. Tcheurekdjian, Cleveland, OH.
Introduction: Hairy cell leukemia is a mature B-cell neoplasm characterized by leukemic infiltration of the bone marrow, liver and spleen. Vasculitis
is a rare presenting sign of hairy cell leukemia. We present a patient with the
longest reported history of cutaneous vasculitis as the presenting manifestation of hairy cell leukemia. Method: Retrospective chart review. Results: A 43
year old female with a history of allergic rhinoconjunctivitis and recurrent
sinusitis presented to our Allergy Immunology practice with a recurrent nonpruritic purpuric rash. The rash first presented 2.5 years prior and was suc-
cessfully treated with a 21 day course of prednisone. In the ensuing 2.5 years
the patient had occasional self-limited purpuric lesions. At our initial evaluation the patient was noted to have painful erythematous nodules and purpura
on her extremities and buttocks. The initial diagnosis was cutaneous vasculitis and the patient was treated with oral steroids. Lab findings were significant
for an elevated CRP, ANA 1:80, and mild pancytopenia. Skin biopsy revealed
a superficial and deep perivascular and, to a lesser extent, interstitial lymphocytic inflammatory cell infiltrate suggesting a possible urticarial vasculitis. The
symptoms improved with steroids; however, a week after the steroids were
discontinued the rash returned. Due to the persistent vasculitis and pancytopenia,
peripheral lymphocyte phenotyping was performed which revealed 0.9% of
lymphocytes being CD103+, Kappa+ B cells consistent with hairy cell leukemia.
Bone marrow biopsy demonstrated leukemic infiltrates occupying approximately 90% of the marrow space. No hairy cells were observed in the peripheral blood. Conclusion: To our knowledge this case reports the longest history
of cutaneous vasculitis as the presenting symptom of hairy cell leukemia. This
case reinforces the importance of evaluating and monitoring patients who present with cutaneous vasculitis for malignancy.
K. Garg*, L. Chernin, D. Swender, H. Tcheurekdjian, R. Hostoffer, Cleveland, OH.
Background: Behcet’s syndrome is an autoimmune disease associated with
chronic relapsing vasculitis that leads to recurrent orogenital ulcers, ocular disease, gastrointestinal disease and skin disease. Therapy typically involves
immunosuppression aimed at dampening the autoimmune response to the disease. The current case report describes the first patient diagnosed with Behcet’s
syndrome and Common Variable Immunodeficiency (CVID) who failed
immunosuppressive therapies for Behcet’s syndrome but was successfully
treated with immunomodulatory doses of intravenous immunoglobulin (IVIG).
Methods: Retrospective chart review. Results: A 53-year-old female with past
medical history of Behcet’s syndrome unresponsive to multiple immunosuppressive medications presented to our Allergy/Immunology practice in December 2008 for further evaluation of her frequent sinopulmonary and skin infections. Immune workup was initiated and the patient was diagnosed with common
variable immunodeficiency with low levels of IgG (level = 315mg/dL) and IgM
(level = 30mg/dL) and no response to pneumococcal immunization. The patient
was subsequently started on IVIG infusions in January 2009 at immunomodulatory doses (1g/kg) every 3 weeks. Since beginning IVIG therapy, the patient
reports a decreased number of sinopulmonary and skin infections as well as a
dramatic decrease in the amount of her oral aphthous ulcers. Conclusions: This
case report demonstrates the first successful use of immunomodulatory doses
of IVIG treatment in a patient with Behcet’s syndrome and common variable
C.B. Cho*, A.M. Patterson, P.U. Ogbogu, Columbus, OH.
Rationale: TNF-О± inhibitors are used to treat chronic inflammatory conditions. While agents such as infliximab and etanercept have been linked to allergic reactions and angioedema, adalimumab has been proposed to be less
immunogenic due to its fully humanized structure. We report a 29-year old
female with Crohns disease with angioedema secondary to adalimumab. Methods: Description of clinical presentation, and laboratory studies including
total IgE, C4, C1 esterase inhibitor antigen and function, and serum C1q binding assay. Results: A 29-year old female with a 13-year history of Crohns disease presented with acute lower lip swelling of 5 hours duration. Her medication list included lansoprazole, clonidine, dextroamphetamine, ibuprofen, and
adalimumab. She was unable to identify any triggers that preceded the onset
of swelling, including foods, insect sting, stressful event, or exercise. Her last
dose of adalimumab was 30 hours prior to onset of lip swelling. She had been
treated with adalimumab for 1.5 years prior to this event. Her physical exam
was significant for marked angioedema isolated to the lower lip, with no other
associated features such as urticaria, rash, or mucous membrane involvement.
Her laboratory evaluation was remarkable for a normal IgE, C4, C1 esterase
inhibitor antigen, and serum C1q binding assay. She was treated with epi-
nephrine, IV corticosteroids, and H1 and H2 antihistamines which resulted in
resolution of her lip angioedema. Adalimumab was discontinued, and she has
had no further recurrence of angioedema. Conclusions: Adalimumab is a fully
humanized recombinant IgG1 monoclonal antibody that binds specifically to
TNF-О±. The mechanism of angioedema in this case is unknown, but is less
likely to be mast-cell mediated due to lack of urticaria, and may be driven by
the bradykinin pathway. Recent case reports have identified adalimumabinduced angioedema in 3 young women with Crohns disease. Our case demonstrates the need to consider adalimumab in the differential diagnosis of
angioedema in young women with Crohns disease, regardless of treatment duration. This case also illustrates the need to further investigate the mechanism of
adalimumab-induced angioedema in this unique group of patients.
E. Clarke*, D.A. Khan, Dallas, TX.
Abstract Rationale: Treatment of AAE with C1INH concentrate as longterm and short-term prophylaxis has not been well described. Methods: A 65
year-old man with multiple medical problems including monoclonal gammopathy of undetermined significance and AAE presented with episodic
angioedema every 4 months while on danazol 200 mg three times a day. Previously he had multiple angioedema attacks triggered by surgeries. Given that
his attacks of angioedema involved his upper airway and severe abdominal
attacks requiring hospital treatment, C1INH concentrate was added at a dose
of 1000 units three times a week in attempt to further reduce the frequency of
his angioedema episodes and to be used as short-term prophylaxis prior to
procedures in this patient. Results: During the first 3 months of C1INH therapy, he noticed an increase in the frequency of his angioedema attacks from
every 4 months to every 2 weeks. His dose was decreased to 1000 units once
a week. After 5 months, he had no episodes of angioedema. He also received
C1INH concentrate on two separate occasions as short-term prophylaxis for
procedures. He was administered 2000 U the night prior to an EGD with no
angioedema. 10 days later he received 2000 U the night prior to right ear tympanoplasty. Three hours after discharge from day surgery he developed lip
swelling and shortness of breath which was treated successfully with C1INH
concentrate 1000 U at home. Conclusions: C1 inhibitor concentrate can be used
for long-term prophylaxis in acquired C1 esterase inhibitor deficiency, but dose
adjustment may be necessary in patients who experience a paradoxical increase
in angioedema episodes. Also, C1 inhibitor concentrate may have a role in shortterm prophylaxis in AAE.
F.C. Cogen*1, M. Ku2, L. Japko3, 1. Meadowbrook, PA; 2. Haddonfield,
NJ; 3. Newark, DE.
Allergic Bronchopulmonary Mycosis (ABPM) due to the dematiaceous
fungi Curvularia has been rarely reported. The diagnosis of ABPM is based on
well-defined clinical criteria; lung biopsy is seldom required. We present a case
of ABPCu in an atopic asthmatic patient originally diagnosed with fungal pneumonia who underwent lung biopsy. H.W., a non-smoking 35 yr. old teacher,
developed allergic rhinitis and asthma by age 7. At age 31 he experienced wheezing, cough and pleuritic chest pain. Asthma therapy with Advair and albuterol
was ineffective. Four months later he was admitted with a lingular infiltrate,
cough and wheeze. WBC was 11,900 with 15% eosinophiles. A large mucoid
plug was removed via bronchoscope from the lingular bronchus. Both the plug
and BAL fluid were positive for Curvularia lunata on culture. H.W. improved
on a brief course of Voriconizole but continued to report bronchospasm with
rare production of grayish mucoid plugs. Chest CT revealed proximal bronchiectasis. He was hospitalized again 11 months later with bronchospasm, chest pain,
hemoptysis, moderate eosinophilia, and a new left upper lobe infiltrate. Total
IgE was elevated at 514 KU/L (mean=13.2 KU/L). Repeat bronchoscopy and
bacterial/ fungal sputum cultures were negative. Infectious disease and pulmonary specialists suspected fungal pneumonia. Left upper lobe pneumonectomy for tissue diagnosis revealed necrotizing granulomas with rare degenerating hyphal fragments within them. Fungal culture of the biopsy was negative.
Allergy evaluation post-discharge revealed positive skin prick tests to Curvularia, Helminthosporium, &Alternaria. Aspergillus skin tests were negative.
Late phase skin reactivity was absent, and IgG precipitins were not available.
Two cases published in 1985 and 1991 meet the diagnostic criteria for ABPM
caused exclusively by Curvularia. This appears to be the third well-defined case
of ABPCu and the second in which a lung biopsy was performed. Histopathology from H.W.’s pulmonary infiltrate revealed a granulomatous inflammatory
reaction with a paucity of fungal forms consistent with the few prior reports of
lung pathology in ABPM. Allergists and physicians consulting on asthmatic
patients with pulmonary infiltration and eosinophilia should be cognizant of
Curvularia in the differential of ABPM.
G.M. Cowan*, Phoenix, AZ.
Chronic granulomatous disease is a primary immunodeficiency disorder
that is usually diagnosed in early childhood. Affected patients are at risk for
severe, life-threatening infections. Advances in antimicrobial therapy have
improved the prognosis in these patients and may have contributed to the delayed
recognition of the disease in infants. We describe the case of a child with recurrent fevers, adenopathy and liver abscesses who was diagnosed with CGD at
only 3 months of age.
G. Dapul-Hidalgo*, W. Li, J. Moallem, Brooklyn, NY.
INTRODUCTION: Macrophage Activation Syndrome is due to activation
and uncontrolled proliferation of Th1 CD4+ T cells and macrophages and overproduction of proinflammatory cytokines. It is characterized by sudden onset
of nonremitting high fever, hepatosplenomegaly (HSM), and lymphadenopathy (LN), cytopenia, abnormal liver functions tests, coagulopathy, hypoalbuminemia, hypertriglyceridemia, and hyperferritinemia. CASE HISTORY: 7 year
old African American girl with 2-3 day history of sore throat was treated with
amoxicillin by her PCP. On day 5, she developed a swollen right knee and pruritic maculopapular rash on her face, hands, thigh, legs and feet. Amoxicillin
was discontinued and, despite treatment with ibuprofen, her symptoms persisted for several days. She was admitted to a local hospital, treated with prednisone and diphenhydramine for serum sickness. At home, she developed fever
spikes to 104В°F and her rash intensified. She was readmitted for fever of
unknown origin with no HSM or LN with negative cultures, chest x-ray, echocardiogram, and CT of the chest, abdomen and pelvis. Despite treatment with IVIG
and high dose aspirin for presumed atypical Kawasaki disease, her fever, arthralgia, and rash persisted. Labs included serum LDH 726 U/L (H), CK 591 U/L
(H), D-dimer 3.14 mg/L (H), serum ferritin 5399 U/L (H), ESR 11 mm/hr and
CRP 4.00 mg/dL (H). WBC, platelets, and triglycerides were normal. Hgb
was 9.6 g/dL (L), AST 183 U/L (H), ALT 68 U/L (H), PT 11.8 sec and albumin 2.4 g/dL (L). Rheumatologic work-up (ANA, anti-dS DNA, anti-Smith,
SSA, SSB, RF, P-ANCA, C-ANCA) was negative. Patient was treated for possible Macrophage Activation Syndrome with IV methylprednisolone and
cyclosporine A and defervesced. Her inflammatory markers also started to
decrease, and she was discharged on prednisone and cyclosporine. In followup visits, she had no complaints of fever, joint pain or rash. Ferritin decreased
and LDH, PT, CRP, and albumin have normalized. She is doing well on
J.P. DeMore*, Lansing, MI.
Introduction: Hypersensitivity pneumonitis (HSP) is an immunologically
mediated lung disease triggered by an inhaled antigen. Bird fancier’s lung, a
type of hypersensitivity pneumonitis, was first observed with exposure to pigeon
droppings. This case reports HSP triggered by a pet cockatiel. Methods: A 54
year old woman presented to the clinic as a referral for worsening asthma. She
was newly diagnosed with asthma 3 years prior and continued to have worsening difficulty breathing and frequent coughing. Even with minimal exercise
of walking to her apartment mailbox, she would be short of breath. She had
been prescribed increasing doses of inhaled corticosteroids with long-acting
beta-agonist without improvement in her symptoms. She also noted significant
fatigue, headaches and lack of energy. She had moved into a new apartment 3
years ago and acquired her first pet cockatiel. Since then, she has acquired 3
more cockatiels. Results: Chest x-ray demonstrated several old granulomas
noted in both perihilar regions. Pulmonary function tests revealed reduced lung
volumes with forced vital capacity 47%, forced expiratory volume in 1 second
54%, total lung capacity 81%, and carbon monoxide diffusing capacity 38%
predicted. Skin prick testing was done to parakeet which was negative. Blood
tests for hypersensitivity pneumonitis panel confirmed positive pigeon serum
antibodies. IgE to feather mix and parakeet were negative <0.05 kU/L. High
resolution CT scan of chest displayed inter and intraseptal thickening of the
interstitial tissues. Conclusion: This case illustrates the importance of evaluating all possible triggers of airway disease, especially individuals with late-onset
asthma. With removal of the cockatiels and treatment, the patient will be monitored for symptom improvement.
V. Dimov*1, S. Randhawa2, T. Hamieh3, M. Sandhu1, A. Bewtra1, 1. Omaha,
NE; 2. Shreveport, LA; 3. Minneapolis, MN.
BACKGROUND: Statins are commonly used to lower plasma cholesterol
level and are often distributed to physician offices as samples by representatives of pharmaceutical companies. Hypersensitivity reactions to statins are not
commonly reported. Unilateral angioedema is a rare manifestation of drug
hypersensitivity with a only few cases reported in the literature, mainly related
to ACE inhibitors. OBJECTIVE: To report a novel case of unilateral periorbital
angioedema related to inadvertent intake of expired atorvastatin. CASE
REPORT: A 37-year-old man with a history of hyperlipidemia was provided
with samples of atorvastatin by his primary care physician over the course of
12 months. The medication samples were supplied on a regular basis by the
representatives of the manufacturing pharmaceutical company and had expiration dates in the range of 4-6 months. His other medications included a daily
dose of fish oil, flaxseed oil and vitamin C. After 11 months of therapy with
atorvastatin, the patient noticed left periorbital angioedema which was worse
in the morning. After a week, he made an appointment with our clinic and his
symptoms were confirmed. The rest of the physical examination was normal.
After inspection of his medication supplies, it was revealed that his atorvastatin samples were 10 months past their expiration date. The patient was unware
of the expiration date for the sample. He stopped all his prescribed and over
the counter medications and the angioedema resolved within 2 days. The patient
declined incremental oral challenge with atorvastatin and a challenge with the
expired atorvastatin sample was deemed unethical. Over the course of 4 weeks,
he was able to restart his over the counter medication and another statin (simvastatin) without a recurrence of angioedema. He was followed for 4 months
and continued to be asymptomatic. CONCLUSION: To the best of our knowledge, this is the first reported case of unilateral periorbital edema following
inadvertent intake of expired atorvastatin. The samples provided to patients are
transported in the vehicles of pharmaceutical company representatives where
they are often exposed to higher temperatures which may shorten their shelf
life. Physicians and patients should be aware that the inadvertent intake of
expired pharmaceutical samples may lead to hypersensitivity reactions.
O.C. Dokmeci*, C.K. Woo, A. Casillas, Shreveport, LA.
Introduction: X-linked lymphoproliferative disease (XLP), also known as
Duncan’s disease, is a disorder of immune regulation that was first described
by Purtilo et al. Its characteristic features are lymphoproliferative disease including fulminant infectious mononucleosis and lymphoma in affected males. Case:
A 7 month old African American male referred to our allergy and immunology clinic for evaluation after his older brother died at age 4 with complications of fatal infectious mononucleosis. He had a maternal cousin who died at
a similar age with bone marrow failure, hepatic necrosis, meningo-encephalitis and aquired hemophagocytic lymphohisticytosis after a fulminant EpsteinBarr virus (EBV) infection. Prior to our evaluation, the patient had a prenatal
genetic work up via amniocentesis that showed a mutation on SH2D1A gene
confirming the diagnosis of XLP. He was otherwise a healthy toddler with
normal growth and development parameters, normal complete physical examination and a normal review of systems. His evaluation showed no current EBV
infection and his flow cytometry for all cell lines studied were within normal.
He had low IgG level however, a common finding in XLP cases. Discussion:
XLP is a rare disorder characterized by severe dysregulation of the immune
system, usually in response to EBV infection. Both cellular and humoral immunity are affected. XLP type 1 is caused by mutations in the SLAM-associated
protein (SAP) gene and XLP type 2 is caused by mutations in the gene encoding the X-linked inhibitor of apoptosis (XIAP). The most common clinical manifestations observed are fulminant infectious mononucleosis, lymphoma and
dysgammaglobulinemia. Average age at presentation is 2.5 years. Affected individuals have no apparent disease prior to presentation. Management of XLP
focuses upon three aspects: treatment of disease manifestations, prevention of
further sequelae and curative treatment through bone marrow transplantation.
Conclusion: Patients with a family history of early mortality with lymphomas,
severe infectious mononucleosis or XLP should be screened for the presence
of SAP protein. If negative, further testing to reveal mutations on SH2D1A or
XIAP should be done to confirm the diagnosis of XLP. Patients diagnosed as
CVID with a similar history to above mentioned, should have further work up
to rule out this fatal disease.
A. Emmert*, H.J. Wedner, St Louis, MO.
Introduction: Eosinophilic pneumonia is a rare disorder which manifests
as a protracted respiratory illness often accompanied by systemic symptoms.
This disorder typically presents in individuals older than 45 years and comprises 2.5 % of cases of interstitial lung disease. The majority of patients are
female, and 50 to 67% of patients have concomitant diagnosis of asthma. Case
Presentation: The patient is a 62 year old Caucasian man with a history of
severe-persistent asthma, and recurrent sinopulmonary infections who presented to our clinic for evaluation of immunodeficiency. He had 6 episodes of
pneumonia in the 5 years prior to his presentation and had been hospitalized
on one occasion, requiring intravenous antibiotics. At the time of presentation
he complained of a cough productive of yellow-green sputum, headaches, and
shortness of breath. He required oral corticosteroids in order to control his
asthma. His pulmonary function testing revealed an obstructive pattern with a
FEV1/FVC of 61%. The immunodeficiency work-up was remarkable for an
IgM of 28.7 mg/dl. His total IgG, immune competence panel, tetanus, pneumococcal, and diphtheria titers were normal. At one month follow-up, the patient
reported severe shortness of breath, fever, chills, weight loss of 12 pound and
hypoxemia. Upon hospital admission for these symptoms, his absolute
eosinophil count was 7800. Chest computed tomography revealed peripheral
consolidation with predominant involvement of the upper lobes with enlarged
mediastinal lymph nodes. Broncheoalveolar lavage demonstrated a cell count
of 672 cells, of which 72% were eosinophils. Transbronchial biopsy showed
an interstitial, alveolar and perivascular infiltrate of eosinophils with bronchiolitis obliterans. The patient was started on oral corticosteroids, resulting in a
rapid reduction in circulating eosinophil count to 300 and a corresponding
decrease in his respiratory symptomatology. During subsequent followup, his
corticosteroid dose was slowly decreased and he continues to do well. Conclusion: Chronic eosinophilic pneumonia should be in the differential of patients
presenting with persistent respiratory symptoms and pneumonias who have
failed conventional therapies.
D.P. Erstein*, M. Demede, M. Butnariu, E. Porosnicu, R. Joks, Brooklyn,
INTRODUCTION: Actinomycosis is an indolent, slowly progressive infection caused by anaerobic Gram-positive bacilli that usually colonize the mouth,
colon and genitalia. The pulmonary form of actinomycosis constitutes 15% of
the total burden of disease and has not been associated with asthma. The atypical presentation makes pulmonary actinomycosis a major diagnostic and treatment challenge. CASE HISTORY: A 42 year old African American woman with
oral steroid-dependent, severe persistent allergic asthma, treated with omalizumab (anti-IgE) for three years presented with intermittent fever, 20lb weight
loss and a persistent right middle lobe infiltrate which did not respond to both
oral and IV antibiotics. She had no history of tobacco use or tuberculosis exposure (PPD negative). Prednisone dose was stable at 10 mg daily. Lab results
included a total WBC of 25,000/Вµl and an absolute eosinophil count of
10,000/Вµl. Initial bronchoscopy showed squamous metaplasia. Considering her
constitutional symptoms and concern for malignancy, she underwent an elective RML lobectomy. Histology showed branching filamentous gram positive
bacilli consistent with actinomycosis. Post operative course consisted of six
months of doxycycline with improvement in constitutional symptoms and resolution of eosinophilia. Eosinophil counts later increased from normal levels
to 1900/Вµl when the subject was non-adherent to a six month course of doxycycline. This is the first reported pulmonary actinomycosis case in a severe
asthmatic who developed hypereosinophilia in the setting of anti-IgE therapy.
Although there have been reports of a selectivity of eosinophilic migration
and degranulation patterns in vitro elicited by different bacterial species, there
is currently no known association between actinomycosis and eosinophilia.
These findings suggest a Th2 mediated inflammatory response to actinomycosis when associated with anti-IgE therapy.
D. Esham*, M. Nasir, J.A. Grant, Galveston, TX.
Introduction: Local heat urticaria is a rare type of physical urticaria. It presents as well defined pruritic erythematous wheals limited to areas exposed to
heat. Common triggers are hot baths, sunlight, hot mugs, or oven steam. There
have been few cases of local heat urticaria that also reported oral symptoms
due to heat exposure. Case: A 56 year old Caucasian female presented with a
3 month history of erythema and finely demarcated pruritic wheals after bathing
in hot water or holding a hot mug. Patient would initially notice burning, tingling and itching in any area exposed to heat. A few minutes later she developed redness and a well defined area of swelling which would last 30 minutes
to 1 hour after exposure. Patient experienced a sensation of a lump in her throat
after drinking hot soup. She denied any difficulty breathing or abdominal
pain. Physical exertion or sweating did not induce urticaria. Results: To confirm the diagnosis of local heat urticaria, the patient’s arm was immersed in a
41В°C water bath for 4 minutes. The patient quickly developed a band of erythema which burned, itched and became a large well demarcated plaque wheal
within 2-3 minutes. Patient denied any systemic symptoms. Conclusion: Local
heat urticaria with oral symptoms, but without systemic symptoms is an atypical presentation of this already rare disease. The possible therapies for this disease are heat avoidance, H1 and H2 blockers or repeat heat exposure inducing
tolerance. Because our patient had symptoms with ingestion of hot foods avoidance was very difficult. Our patient was treated with H1 and H2 blockers and
a leukotriene receptor antagonist. She reports that she occasionally develops
erythema and mild tingling but without wheal or severe pruritis.
Right forearm following heat challenge
F. Farrahi*, J. Kelso, San Diego, CA.
Introduction: Although typically used to treat allergic contact dermatitis
(ACD), topical corticosteroids causing ACD is an increasingly common phenomenon and they are now included in the North American Contact Dermatitis Group (NACDG) standard panel for patch testing. Some drugs capable of
causing a local ACD by topical exposure are also capable of causing generalized skin reactions by systemic exposure. However reports of systemic corticosteroids causing generalized skin reactions are rare. Methods: We report
the case of a 67 year old woman who developed so called “systemic contact
dermatitis” (SCD) after ingestion of budesonide (Entocort EC) for treatment
of microscopic lymphocytic colitis. Although Entocort EC acts locally in the
gut, the budesonide is also absorbed. Results: The patient developed a generalized erythematous pruritic rash about 8 to 12 hours after ingestion of the
first dose of budesonide (9 mg). After taking another dose the next day, the rash
worsened and she developed swelling of the face, hands, feet and legs and some
cracking of the skin. The rash lasted about 2 weeks. More than forty years ago,
the patient recalled having a similar reaction to a corticosteroid injection, probably triamcinolone (Kenalog). Patch tests with 6 different corticosteroids from
the NACDG 65 antigen series were performed and read at 48 hours, 96 hours
and one week. Her tests were clearly positive to budesonide (3+) and triamcinolone acetonide (2+) (both group B), the two drugs to which she had reacted
clinically. Patch tests were negative to tixocortol-21-pivalate (group A) and clobetasol-17-propionate (group D1) and possibly positive to desoximetasone (1+)
(group C) and hydrocortisone-17-butyrate (1+) (group D2). She was advised
to avoid steroids in groups B, C and D2. Subsequently, she was treated with
oral prednisone (group A) without any reaction. Conclusion: Corticosteroids
can cause delayed type hypersensitivity reactions. In sensitized patients, systemic exposure can cause generalized cutaneous reactions or “systemic contact dermatitis”. Patch tests can be helpful in demonstrating the mechanism and
causative agent. Since cross-reactions can occur within and between groups, it
is useful to test to a representative steroid from each group to aid in guiding
L. Ford*, A. Nowak-Wezgryn, New York, NY.
Introduction: Citrus fruits are not a common cause of food-induced anaphylaxis. There may be different allergens in the citrus pulp and citrus seeds.
Methods: We present a 15-year-old male with life-threatening anaphylaxis to
tangerine seeds. Results: Our patient’s reaction occurred during a soccer match
in late Spring. After eating a honey Murcott tangerine during half time, he raced
back onto the field chewing the seeds, which he had not done before. Fifteen
minutes later pruritus developed in his groin and feet, which rapidly spread and
intensified. He took diphenhydramine, then developed conjunctival redness
and breathing difficulties, and felt faint. He proceeded to the ED, where he
lost consciousness. BP was 70/30. He received two doses of epinephrine, steroids
and diphenhydramine and stayed overnight in the ICU. Prior to the reaction he
ate peanut, sesame, mustard, and an unrestricted range of fruits and vegetables.
Following the reaction, he precautionarily avoided all citrus. He continued to
play soccer and exercise vigorously without any allergic reactions. He has strictly
avoided tree nuts since age 2, and had convincing immediate allergic reactions
to cashew, pistachio and walnut between the ages of 2 and 10, but had never
been prescribed epinephrine. In addition to food allergy, the medical history
also includes Springtime allergies. His parents are both atopic, including a
history in the father of several episodes of exercise-induced anaphylaxis during Spring. Testing showed normal spirometry, and elevated serum-specific IgE
to mandarin orange (3.94 kIU/L), grass and tree pollens, peanut and tree nuts.
Prick-prick testing was positive to seeds from many citrus fruit but mostly negative to the pulp from the same varieties. He therefore reintroduced citrus juices
and flesh, while continuing to avoid the seeds. Conclusion: Citrus seed allergy
may occur in patients who are tolerant to citrus pulp. The putative allergens in
citrus fruit might be cross-reactive with tree nuts but not with peanut or other
seeds. Factors that may have increased the severity of our patient’s reaction
include concurrent exercise, delay in treatment, and co-existence of seasonal
C.D. Freccia*, V.B. Reddy, M.C. Tobin, Chicago, IL.
Introduction: The differential diagnosis for skin rash at birth can be extensive. Methods: An infant female presented with with an unusual rash on
abdomen on day of life 1. By day of life 2, the rash spread to multiple areas of
her body including forehead, anterior scalp, abdomen, inguinal folds, hands
and feet. Consultation was requested to evaluate for vasculitic etiology of rash,
specifically neonatal lupus. The baby was born at term by normal spontaneous
vaginal delivery to a mother of non-advanced maternal age with history of Factor V Leiden deficiency on enoxaparin during pregnancy. The pregnancy was
uncomplicated, and routine maternal serologic screening was unremarkable.
On initial consultation (day of life 2) there was a large, central, coarse, ecchymotic plaque without scaling on the baby’s forehead, and another similar plaque
extended posteriorly from the anterior scalp line. Rash on the abdomen and
inguinal folds was well demarcated, erythematous, and also plaque-like. Dorsa
of hands and feet had erythematous, scaly, eczematous patches. A Darier’s sign
was not elicited, and the rash was non-blanching. Other than the described
skin findings, the baby was generally well. An initial complete blood count was
remarkable only for mild thrombocytopenia of 122,000, which resolved. Results:
Punch biopsy of an abdominal plaque showed dense, upper dermal infiltrate
of monomorphous mononuclear cells that obscured the dermoepidermal junction. The histologic differential diagnosis included Langerhans’ cell histiocytosis and mastocytosis. By immunohistochemistry, the cells were positive for
mast cell tryptase and CD117 but negative for S-100 protein and CD1a which
supported a diagnosis of cutaneous mastocytosis. The baby showed no convincing evidence for systemic involvement of mastocytosis. The skin has been
treated with emollients and topical steroid ointment. Conclusion: Cutaneous
mastocytosis should be included in the differential diagnosis for neonatal rash
at birth.
An abdominal plaque (pre-biopsy) is seen here on the left abdomen.
(Courtesy of B.K. Bonish)
thyroid nodules with benign histology on fine needle aspiration. Joint examination revealed limited range of motion, warmth and tenderness of affected
joints which was consistent with an inflammatory arthritis. Examination of
the skin revealed urticaria and angioedema and subsequent skin biopsy demonstrated histologic changes consistent with urticaria without evidence of underlying vasculitis. Radiographic examination of involved joints only revealed evidence of mild degenerative changes. Arthrocentesis showed no evidence of
crystalline arthropathy. An extensive workup for infectious disease, autoimmunity and malignancy failed to reveal an underlying cause of her symptoms.
Her arthritis resolved after a short course of oral steroids and is currently in
remission. Although she continues to have episodes of urticaria and angioedema,
she is much improved with on H1 and H2 blockers. Conclusions: Our patient’s
presentation is consistent with previous reports of the AHA Syndrome. The
diagnosis of AHA syndrome should be considered when inflammatory joint
manifestations accompany hives and angioedema in the absence of an identifiable cause.
A. Gaye*, M. Callaghan, Chicago, IL.
Rationale: Need for a non-invasive alternative to follow the progress of children with eosinophilic esophagitis (EE) Methods: Description of the scoring
tool and review of the literature Results: To follow the progress of EE, a chronic
inflammatory disease of multifactorial etiology, and its response to medical
and dietary management, repeated endoscopies and biopsies remain the best
objective approach, yet are not devoid of risks. We designed a simple scoring
system (EOSIN) that measures symptoms of children and adolescents with EE,
and correlates with the known histopathology of the disease, along 5 categories
of attributes, or domains. Two points maximum are given to each domain for
a possible total score of 10, at the initial consultation and each return visit. It
maintains consistency of record, provides the physician with an assessment of
the progress and a subjective threshold for change in the medical or dietary
care or for surgical intervention, and gives the family an incentive for adhering to the suggested management. - E (esophageal) - mechanical domain dysphagia (1), or food impaction (2) - O (oral) - GERD-like domain - pyrosis
and/or nausea (1), or regurgitation and/or emesis (2) - S (social) - social domain
- nocturnal awakening and/or irritability and/or school absenteeism and/or
decreased physical activity and/or social maladjustment from chronic pain or
listlessness (1) or (2) for severity - I (inflammatory) - long term effects of inflammation domain - anorexia and/or early satiety and/or feeding aversion and/or
failure to thrive (1), or weight loss (2) - N (noxious) - general referred discomfort domain - abdominal pain (1) or (2) for severity All the children followed for EE are presented with the EOSIN score sheet at the initial and each
subsequent visit. With the help of their parents they reminisce on the gastrointestinal and other manifestations of EE since their previous visit. An adjustment of their diet and medical management is ideally addressed by a team
consisting of a gastro-enterologist, a nutritionist, and an allergo-immunologist.
Conclusions: To follow the children’s subjective progress, we advocate using
a non-invasive symptom scoring tool and suggest EOSIN. The proper assessment of their symptoms is of utmost importance in the management of this
chronic disease, which affects their quality of life, growth, and development.
S.M. Gada*, P.J. Papadopoulos, E.L. Spillane, S.W. Peng, M.R. Nelson,
Washington, DC.
Introduction: The triad of arthritis, hives and angioedema has been associated with infectious and autoimmune disease. Based on a case series of patients
with arthritis, hives and angioedema in the absence of underlying disease,
McNeil and colleagues coined the Arthritis, Hives and Angioedema (AHA)
Syndrome. We describe a case of AHA Syndrome in an adult female who presented to our institution. Case Report: A 58-year old African-American female
was referred for evaluation of inflammatory arthritis with concurrent urticaria
and angioedema. She initially presented with daily urticaria and angioedema
of one month’s duration, followed by the development of inflammatory arthritis of the ankle, wrist, and knee. Past medical history was significant for
osteoarthritis of the knees and ankles, type II diabetes mellitus and two cold
S. Ghazan-shahi, A.K. Ellis*, Kingston, ON, Canada.
Background: Angioedema is the result of swelling of cutaneous and/or
mucosal tissue due to vascular leakage. The rate of idiopathic angioedema is
reported to be up to 41% in previous clinical surveys. Most cases of idiopathic
recurrent angioedema respond to a regimen of H1 and H2 receptor antagonists
and/or corticosteroids and epinephrine. Case Presentation: We report the case
of a 19 year old female with recurrent idiopathic angioedema limited to tongue,
throat swelling and hoarse voice (presumably laryngeal edema); never any
wheeze or dyspnea nor decrease in SaO2 but aware of sensation of throat closure and inability to breath normally. She had no hives, loss of consciousness
or GI manifestations (including GERD). Past history was significant for controlled asthma. Her symptoms were escalatory, requiring multiple and higher
doses of epinephrine and corticosteroids to control recurrences, ultimately culminating in a protracted hospital admission as only parenteral corticosteroids
could be administered due to severe oropharyngeal angioedema. She was inves-
tigated extensively (See Table 1) with the only clue to its underlying etiology
being a positive ANA (1:640), but anti-dsDNA was negative. A trial of hydroxychloroquine with immunomodulatory IVIG produced seizures and required
discontinuation of both. Dapsone was initiated and led to both methemoglobinemia and hemolytic anemia, despite a normal G6PD screen. An open tracheostomy was placed at the patient’s request to allow corticosteroid tapering
with a secure airway. Ultimately Rituximab was initiated at a dose of 560 mg
weekly for 4 weeks, and produced significant reduction of symptomatology
after the 3rd and 4th infusion; this medication was used with written informed
consent from the patient that it was experimental and off-label, and with the
approval from the hospital’s pharmacy and therapeutics committee. Conclusion: We present a case of severe, steroid-dependent recurrent idiopathic/autoimmune angioedema intolerant of usual corticosteroid sparing agents
that ultimately had an excellent response to Rituximab.
Table - 1. Investigations performed aimed at determining the etiology of
K.A. Gonzaga*, J.F. Southern, J.M. Routes, J.W. Verbsky, Milwaukee, WI.
INTRODUCTION: X-linked agammaglobulinemia (XLA) is a primary
humoral immunodeficiency characterized by severe pan hypogammaglobulinemia, near absence of B cells, an increased susceptibility to sinopulmonary
infections by encapsulated organisms and atypical bacteria, gastrointestinal
tract infections, and enteroviral infections. XLA is due to defects in the Bruton’s tyrosine kinase (Btk) gene located on the long arm of the X chromosome
and is involved in B cell receptor signaling. CASE DESCRIPTION: A 20 month
old boy with a history of left thigh abscess presented after his three year old
brother died suddenly from pseudomonas septicemia with multiorgan system
dysfunction. On postmortem analysis, his brother had lymphoid depletion of
his spleen, lymph nodes, and thymus. Based on this finding, our patient was
encouraged to seek further immune evaluation. He had undetectable serum IgG
and IgA. His IgM was depressed at 21mg/dL (27-111). His ANC was normal
at 1500K/uL(1100-1600). B lymphocyte enumeration by flow cytometry
revealed a significantly decreased count of CD19+ B cells (94/mm3, 2%).
Monocyte Btk expression also detected by flow cytometry was within normal
limits. Btk gene sequencing revealed a novel variant resulting in a single base
pair substitution in codon 365 of Btk (exon 12; g.63,158; c.1227C>G; p.N365K).
The substitution resulted in a change in the amino acid at position 365 from
asparagine (N) to lysine (K). Carrier analysis of his mother (heterozygous)
and maternal grandmother (homozygous) by genomic DNA sequencing confirmed carrier status. DISCUSSION: The diagnosis of XLA is usually suspected based on a combination of family history, clinical presentation, and
physical exam findings. This case was unusual in that it was detected by the
astute finding of a pathologist who communicated these findings to the patient’s
family for work up of an infection not typically associated with XLA. Also,
this is the first description of this mutation causing XLA. Previous reports have
documented XLA in a patient with a missense mutation in residue 365. This
suggests that the residue 365 is structurally important for Btk function. In addition, the Btk protein was detectable in our patient. Therefore, it is likely that
this mutation resulted in abrogate function. The cornerstone of treatment for
XLA is replacement therapy with immune globulin.
R. Gutta*, H.M. Bhatti, C. Radojicic, D. Lang, Cleveland, OH.
Introduction: Good syndrome is an atypical combination of thymoma and
immune deficiency characterized by adult onset hypogammaglobulinemia, low
to absent B cells, and T cell defects. Good syndrome is comprised of an array
of features distinct from CVID, despite being categorized as a subset of the
latter. Early recognition and treatment are critical due to the significant mortality in these patients. We present two cases of thymoma and immunodeficiency with review of their clinical and immunologic findings. Case 1: A 70
year old man presented with history of hypothyroidism, status post thymectomy for enlargement. Work up for recalcitrant CMV revealed hypogammaglobulinemia (IgG 400 mg/dL, IgA 60 mg/dL, IgM 92 mg/dL), low peripheral
B cells (15/ВµL), CD4 472/ВµL, inverted CD4:CD8 ratio of 0.59, and low titers
after Pneumococcal vaccination (30% response). He was started on monthly
intravenous immunoglobulin (IVIG) and antiviral therapy with improvement.
Case 2: A 70 year old woman presented with history of red blood cell aplasia,
status post thymectomy and recurrent sinopulmonary infections. Work up
revealed hypogammaglobulinemia (IgG 93 mg/dL, IgA <6.2 mg/dL, IgM <4.2
mg/dL), low Peripheral B cells (<1/ВµL), CD4 1058/ВµL, CD4:CD8 ratio of 1.84,
and extremely low titers after Pneumococcal vaccination (no response). She
was started on monthly IVIG, and weekly subcutaneous immunoglobulin with
improvement. Discussion: Good syndrome diverges from CVID in its late age
of onset and the profound decrease or absence of peripheral B cells with
increased susceptibility to infections. These infections and concurrent immunosuppressive treatment for underlying autoimmune disease may predict an ominous prognosis in contrast to CVID. Thymoma may precede immune deficiency
in 42% of patients, but thymectomy does not resolve immune deficiency. Proposed mechanisms of pathogenesis in Good syndrome suggest autoimmune
destruction of B cells and loss of naГЇve or memory T cells. Analysis of
immunoglobulin level and functional response can help ascertain if IVIG will
be beneficial. IVIG should be administered if there is humoral immune deficiency to decrease mortality from life-threatening infections.
A.S. Haque*, S.J. McGeady, Wilmington, DE.
Introduction: A 17-year-old African American female with history of recurrent gonococcal arthritis and MRSA skin infections presented to the Emergency Department with a 2 day history of fever, chills, and sore throat Initial
Evaluation: Physical Examination revealed cervical adneopathy, erythematous
pharynx, and skin pustules over extremities. Results: A rapid strep screen was
negative. Skin, throat, urine, and blood cultures were negative as were HIV
PCR and Hepatitis B and C serologies. CBC demonstrated leukocytosis with
a left shift. Clinical Course: The patient had progression of skin lesions after
2 days of Bactrim therapy and was therefore given 7 days of ceftriaxone treatment with complete resolution of her illness. A CH50 was found to be markedly
reduced and the patient was found to be deficient in complement C5 upon further testing. Conclusion: The C5 cleavage product C5a serves as a potent phagocyte chemoattractant and C5b is an anchor for the complement membrane attack
complex formation. This case illustrates features suggestive of both defects in
host defense and may emphasize the importance of C5 in susceptibility to
both invasive Neisserial and pyogenic infections.
A. Harish*, M. Hartz, Rochester, MN.
Introduction: Hyper-IgE syndrome (HIES) is a rare multisystem immunodeficiency characterized by eczema, recurrent skin abscesses, pneumonia,
eosinophilia, and elevated serum IgE levels. Affected individuals typically present with infections caused by Staphylococcus aureus, Candida Sp., and even
Aspergillus. Pneumocystis jiroveci infection is not associated with HIES, but
rather with T-cell immunodeficiency. We present a 3-month old boy in whom
Pneumocystis jiroveci pneumonia (PJP) was an initial sign of HIES. Methods:
The patient’s electronic medical record was reviewed and the medical literature searched. Results: A 2 month old infant presented for evaluation of
eosinophilia and rash. He was delivered at full term with a diffuse vesiculopapular rash. CBC revealed an absolute eosinophil count of 2835/L. Newborn screening, HIV test and TORCH screen were all negative. Skin biopsy
was consistent with neonatal pustular melanosis. There was no family history
of skin disease or primary immunodeficiency. The patient appeared to improve
over the next two months, but then developed a flare of his body rash. Peripheral eosinophil count was 6,700/L. Skin cultures were positive for methicillin
sensitive staphylococcus. Work-up for causes of eosinophilia was negative,
including bone marrow biopsy, leukemia and lymphoma phenotyping, and Tcell gene rearrangement. The IgE level was elevated at 721 mg/dL. Quantita-
tive T and B cells and other immunoglobulins were within normal limits. There
was no history of prior pneumonias, and no facial, dental, or skeletal features
of HIES. The patient was started on 2 mg/kg of prednisone to prevent end-organ
complications of eosinophilia. The patient’s skin and eosinophil count improved
and prednisone was tapered. Toward the end of the taper (4 weeks), the patient
developed cold symptoms and rapidly deteriorated. Chest x-ray showed right
pulmonary infiltrates which was confirmed as PJP by bronchoscopy. The infant
was treated with trimethoprim-sulfamethoxazole and recovered. Gene testing
for the STAT3 was promptly sent and confirmed positive for the R382Q missense mutation. Conclusion: Early recognition of HIES can be difficult in infants
since many features of HIES, do not occur until later in the disease course.
While PJP is typically associated with T-cell immunodeficiency, it may be the
presenting indication of underlying HIES.
In 2010, the patient had two more pneumonias. During this time, she had an
asymptomatic CMV viremia. Laboratory values are in table 1. She was started
on monthly IVIg, daily Bactrim and weekly Azithromycin. Conclusion: The
underlying immunological defect in GS is not known. Although their immune
evaluations varied, both A and B presented similarly. Like our patients, most
GS patients have fewer infections when placed on monthly IVIg and prophylactic antibiotics chosen based upon their CD4 counts. Despite therapy, GS
patients have a poorer five and ten year survival rate then patients with CVID,
(70% and 33% vs 100% and 95% respectively). Interestingly, both of our
patients manifested GS around the time they were diagnosed with metastatic
disease. Of the approximately 250 reported cases of GS, fewer than five had
metastatic disease. Overall, Good’s Syndrome remains a rare disease, but it
should be considered in patients with adult onset immunodeficiency.
Table 1 - Lab Values
A. Mehta*, J.E. Yu, J. Sher, R. Herzog, New York, NY.
Introduction: Thymic transplantation carries the best prognosis for
patients with complete DiGeorge Syndrome. However, patients often do not
survive infections while awaiting transplantation. Methods: We describe a
5 month old boy with complete DiGeorge syndrome (DGS) whose course
was complicated by cytomegalovirus (CMV) viremia not responsive to Ganciclovir, CMV immunoglobulin and intravenous immunoglobulin. This case
demonstrates the importance of early recognition of CMV resistance in
patients with complete DGS. Results: Our patient was a full term boy of an
uncomplicated pregnancy who initially presented with left sided focal seizures
on the first day of life. Initial evaluation revealed hypocalcemia, undetectable
parathyroid hormone (PTH) level, absent thymus, and truncus arteriosus.
Laboratory testing revealed lymphopenia with an absolute lymphocyte count
of 1,200/mm3 (normal 3610-8840), completely absent T cells (0 CD3 T cells,
0 CD4 T cells, 0 CD8 T cells), 759/mm3 (62%) CD19 B cells, and normal
NK cells. Fluorescence in situ hybridization (FISH) confirmed chromosome
22q11.2 deletion, and the patient was enlisted for thymic transplantation. At
2 months of age, the patient developed CMV viremia and was treated with
ganciclovir, CMV immunoglobulin, and intravenous immunoglobulin for several months but was noted to have an increased viral load despite treatment.
The patient clinically deteriorated secondary to the overwhelming CMV infection, and foscarnet was started. A UL97 mutation M460M/V was later detected
by PCR which is known to confer ganciclovir resistance. A UL97 mutation
C603C/S was detected as well. However, the patient eventually succumbed to
the CMV viremia and pneumonitis prior to transplantation. Conclusions: Early
empirical treatment with foscarnet may be indicated in complete DGS patients
with increasing CMV viremia not responsive to ganciclovir and immunoglobulin. In addition, an early survey of the CMV genetic resistance panel may
help facilitate more targeted intervention and thus prevent clinical deterioration of the patient while awaiting transplantation.
S.M. Hollander*, S.S. Joo, H.J. Wedner, St. Louis, MO.
Background: The estimated incidence of thymoma in the general population is 0.15 cases per 100,000 of which 6-11% have hypogammaglobulinemia. The combination of thymoma and adult-onset immunodeficiency was
first reported by Dr. Robert Good in 1955 and is now referred to as Good’s
Syndrome (GS). GS is characterized by hypogammaglobulinemia, low B cells
and variable defects in cell-mediated immunity, although, there is significant
variability. Case Presentations: Patient A is a 63 year old African American
male with metastatic thymoma and myasthenia gravis, both diagnosed in 1993.
He underwent a thymectomy and chemotherapy and was in remission until
2009 when a lung metastasis was found. This was treated with surgery and
radiation therapy. During 2009, he had three pneumonias and was found to
have an asymptomatic CMV viremia. In 2010, he had another pneumonia
and his CMV viremia progressed to retinitis and meningitis leading to blindness and persistent decreased mental status. Laboratory values are in table 1.
He was started on monthly IVIg and daily Bactrim. Patient B is a 49 year old
African American female with metastatic thymoma and myasthenia gravis
diagnosed in 1990. She underwent a thymectomy and radiation therapy in
2000, but had a metastatic lesion found in her lung in 2004. She then underwent resection and chemotherapy. The patient did well until 2009 when she
developed a pneumonia, Enterococcus bacteremia, and Serratia bacteremia.
J.C. Hong*, T. Jordan, J. Temprano, A. Dixit, A. Katta, R.G. Slavin, St.
Louis, MO.
Introduction: Hypersensitivity pneumonitis(HP) is an immune mediated
lung disease that occurs in response to repeated inhalation of a variety of inhaled
antigens. These antigens can be from animal proteins, fungi, amebas, bacteria,
medications, or chemicals. It can present as an acute, subacute, or chronic interstitial pneumonitis and can lead to chronic end stage lung disease. A high index
of suspicion is necessary to make the diagnosis. Identifying the causative antigen is of paramount importance as exposure avoidance is the mainstay of therapy. Methods: Serum precipitating antibodies, pulmonary function testing, chest
radiography, chest computed tomography, bronchoalveolar lavage, open lung
biopsy, and a home survey for possible causative antigens were performed.
Case History: A 53 year old white male with history of HIV (CD4+=352) presented with a two year history of increasing dyspnea, decreased exercise tolerance, dry cough, and chest discomfort. He was initially diagnosed with PCP
and treated with prednisone and Septra with no improvement. Chest exam was
significant for diffuse crackles bilaterally. Chest CT showed bilateral fine reticulonodular infiltrates predominantly in the bases. PFTs demonstrated a restrictive pattern and a decreased DLCO. An open lung biopsy showed widespread
uniform interstitial granulomas without evidence of necrosis and an interstitial lymphocytic infiltrate with mature plasma cells. Stains and cultures of the
lung biopsy were negative. An HP panel was performed in a university lab and
was positive for Thermoactinomyces sacchari(TS). A home visit was performed
to identify a causative antigen. A black mold was found growing on a limestone painted basement wall near the home ventilation system. Samples were
collected from the home and were positive for TS. On further questioning it
was discovered that two years ago the patient had mechanically cleaned the
walls with a wire brush for several days and subsequently developed the above
symptoms. Conclusion: Prior reports implicating TS as a cause of HP have been
in sugar cane workers(Bagassosis). This report of HP due to TS exposure in an
urban, household setting is supported by the clinical, laboratory, radiographic,
and pathologic findings. This case illustrates the importance of a home survey
to confirm the source of antigen exposure in patients with HP for future avoidance measures.
F.L. Hoyte*, O.P. Patel, T. Wine, R.K. Katial, Denver, CO.
Introduction: Cicatricial pemphigoid is an autoimmune blistering disease
that is a rare cause of supraglottic stenosis. We report a case of a woman presenting with progressive respiratory difficulties, ultimately found to have cicatricial pemphigoid with multi-system involvement. Case: A 39-year old woman
presented with a 5-year history of progressive dyspnea, chest tightness, and
difficulty with both inspiration and expiration. Review of systems was remarkable for dysphagia, fluctuating visual acuity, painful oral ulcers, and fragility
of the skin with occasional blistering that scarred upon healing. Past history
included a clinical diagnosis of asthma, allergic rhinoconjunctivitis, and frequent acute sinusitis episodes, for which she had undergone two sinus surgeries. Several years prior, she had been prescribed prednisone for a questionable
diagnosis of Wegener’s Granulomatosis, improving her visual, sinus, and respiratory symptoms, which recurred upon steroid discontinuation. Physical exam
on presentation was remarkable for dysphonia, loss of nasal architecture with
scarring, inspiratory stridor, and scattered hyperpigmented skin lesions. Results:
Sinus CT showed mild sinusitis and cicatrix formation in the bilateral nasal
cavities. Chest CT demonstrated mild bronchial wall thickening and air trapping. Neck MRI showed narrowing of the retropalatal airway, and a swallow
study was severely abnormal. Laboratory results included an IgE of
231kU/L(nl<100), CRP of 0.59mg/dL(nl<0.4), and ESR of 33mm/hr(nl<20).
PFTs demonstrated flattening of both inspiratory and expiratory loops. Following a positive methacholine challenge, rhinolaryngoscopy showed nasal,
nasopharyngeal, and supraglottic stenosis due to significant cicatrix formation (fig 1). Her IgG BP 180 and BP 230 antibodies were elevated, and biopsy
of a blistering skin lesion showed linear IgG deposition along the basement
membrane of the epidermis and hair follicles, consistent with a diagnosis of
cicatricial pemphigoid. Cyclophosphamide therapy was initiated with a plan
for surgery by otolaryngology. Conclusion: We report a case of cicatricial pemphigoid with multi-system involvement presenting as progressive respiratory
difficulty. This case highlights the broad differential diagnosis of respiratory
symptoms mimicking asthma and the importance of a thorough evaluation for
glottic and periglottic disease in such cases.
and throat pain, but rarely has it been reported to be associated with sinusitis.
In a review of MEDLINE files back to 1966, we found only two cases of subacute thyroiditis associated with bacterial sinusitis: one was associated with
acute bacterial sinusitis, the other with chronic bacterial sinusitis. We present
a 54-year-old woman with asthma and eczema who presented for evaluation
of six weeks of low-grade fever, rhinorrhea, sore throat, sinus congestion, and
ear fullness refractory to over thirty days of antibiotics. Exam was notable for
boggy inferior turbinates and tender unilateral thyromegaly. Computed tomography of the sinuses demonstrated mild to moderate mucosal thickening of bilateral maxillary, ethmoid, and sphenoid sinuses. TSH was low, T3 and free T4
were high, antithyroglobulin and thyroid peroxidase antibodies were negative,
and ultrasound of the thyroid revealed a diffusely enlarged and heterogenous
right thyroid lobe. To our knowledge, this is only the second reported case of
subacute thyroiditis associated with chronic rhinosinusitis. This case highlights
the fact that the differential diagnosis of chronic rhinosinusitis refractory to
antibiotics should always include atypical presentations of other diseases such
as subacute thyroiditis.
K.S. Hsu Blatman*1, A.M. Ditto2, 1. Brookline, MA; 2. Chicago, IL.
Introduction: Chronic idiopathic urticaria and angioedema can be a debilitating disease. Systemic steroids are often used to induce remission. When
steroids cannot be tapered or are ineffective, alternative agents such as azathioprine, cyclosporine or mycophenolate mofetil can be used. Case reports
suggest that omalizumab, a monoclonal anti-IgE antibody used for asthma, may
be effective in those patients who poorly respond to more standard treatments.
Case report: A 31-year-old female with a 3-year history of severe chronic idiopathic urticaria and angioedema presents to our clinic after seeing six other
specialists. She had no history of asthma, allergic rhinitis or atopic dermatitis.
At an outside institution, a biopsy ruled out urticarial vasculitis. Thyroid peroxidase antibodies, antinuclear antibody, H. pylori antibodies and 24-hour urine
N-methyl histamine were within normal. Lab work at our institution, including cbc with differential, thyroid stimulating hormone, T3 uptake and IgE (74
IU/L), was within normal limits. She had responded to prednisone with doses
as high as 80mg/day in conjunction with antihistamines, zileuton, doxepin
150 mg with an improvement but not resolution of her urticaria. Due to her disease, the patient had to quit her job and moved into her parents’ home. In our
clinic, therapy with colchicine, hydroxychloroquine, sulfasalazine, dapsone
and azathioprine in conjunction with steroids were all without benefit. Mycophenolate mofetil was employed, but she developed hypertension and tachycardia
during the one month she was taking it without benefit, so it was discontinued.
Cyclosporine was not attempted because of the hypertension she had experienced on mycophenolate mofetil. Using asthma dosing guidelines, the patient
was treated with omalizumab 300mg subcutaneously every four weeks. She
was not on systemic steroids during this time. Results: After her first injection, her hives improved. After the fourth injection, her symptoms completely
resolved for the first time in four years and she remains hive free. Doxepin,
fexofenadine and cetirizine were able to be discontinued. Conclusion: Although
the pathophysiology of chronic idiopathic urticaria is still unknown, omalizumab should be considered for treatment, particularly in refractory cases
regardless of serum IgE level. The role of IgE in chronic idiopathic urticaria
and angioedema needs further investigation.
A. Ibarra*1, B. Del Rio2, J. Mendiola2, J. Sienra2, 1. Guadalajara, Jalisco,
Mexico; 2. Mexico City, Mexico.
Figure 1. Supraglottic stenosis due to cicatrix formation.
J. Hsu*, S. Bealert, A.T. Peters, Chicago, IL.
Subacute thyroiditis is an inflammatory, self-limited condition thought to
be caused by an antecedent viral illness. Common symptoms include fever
Advderse reactions to medications are the most frequent complications
derived from the clinical practice, 10 to 20% of hospitalized patients, 6% are
dangerous, 80% are predictable associated to the metabilism of the drug and
only 6 to 10% are immunological. In the case where the clinical history offeres
doubtful data the medication cannot be replaced and there is not therapeutic
option and it`s indicated that a diagnosis study be carried out in order to offer
therapeutic options which could be possibly more safe to the patient. Male
12y without any family background of atopy. With high respiratory repetitive
infections. At 4m life and 48h after the administration of penicilin, shows general exantematic pimply signs and fever. At 2y the patient gets eritromicine and
after 2h he shows rashes and angiodema. At 4y immediately after the adminsitration of TMP/SMX presents generalized macula. After 6y amoxaciline is
administered after 1h presents transitory exantema. We obtaining the written
consent of the parents. Prick test to Penicillin, Amoxaciline, TMP/SMX and
eritormicina. As positive control histamine was used and negative control of
saline solution, induration ≥ 3mm was considered a positive proof. The proof
of the parch only to penicillin with lectures of 48 to 72 hours positive lecture
in accordance with the european classification of contact dermatitis. In case
of the negative reaction to the antibiotics we did the intrademoreaction, in
dose of 0.02mg to concentrations of 1:1000 and 1:100 with lectures every 20
minutes. It is positve whenenever the induration ≥5mm. Only in the case of
the two proofs to be negtive it was considered the controlled administration of
antibiotics con icreased dosages until reaching the therapeutic dosis under the
strict medical supervision. Presented prik test of amoxaciline 5mm. Penicillin
3.5 mm, TMP/SMX 4mm and eritomicine negative. The parch test was done
for penicillin with a positive lecture after 48 and 72 hours later. The prik test
to eritomicine was in both concentrations negative. Further on the controlled
administration of eritromicine in increasiong dosages under the strict medical
supervision. There was no adverse reactions during this procedure. Eritromicine
constitutes a therapeutic option safe for this patient.
Controlled administration of increasing doses of erythromycin
No reactions during the procedure
Patch test was applied to penicillin with positive reading at 72 hrs + + +
K.B. Jacobson*, K. Paris, R.U. Sorensen, New Orleans, LA.
Hyper IgE Syndrome (HIES) is an immunodeficiency disorder with both
autosomal dominant and recessive inheritance. The autosomal dominant HIES
is associated with many specific phenotypic characteristics due to dominantnegative mutations of the STAT3 gene. Patients with HIES are susceptible to
pulmonary infections with pneumatocele formation. Superinfection with
Pseudomonas and Aspergillus fumigates can cause significant morbidity and
mortality. Case: The patient is a 10 year old African American male first evaluated at 2 years of age for recurrent pneumonias, empyema formation and right
apical pneumatoceles requiring upper and middle lobectomies. He had eczema
and furunculosis, two prior skeletal fractures and scoliosis and retention of
primary teeth. Total IgE was 5,462 IU/mL and eosinophils were 1630/mm3.
Total leukocytes were normal. He was diagnosed with Hyper IgE Syndrome.
Subsequently, a STAT3 mutation was confirmed. During the Influenza A (H1N1)
pandemic of 2009, the patient developed influenza with marked enlargement
of a recently developed left apical pneumatocele, with subsequent empyema
formation in the cavity. A viral respiratory culture was positive for Influenza
A, and cultures from bronchoscopy grew Methacillin-resistant Staphylococcus
aureus and Pesudomonas aeruginosa. He was treated with a 5-day course of
oseltamivir, a prolonged course of antibiotics, and drainage of the empyema.
Therapy with with 1,25[OH]2D3 was initiated with marked, persistent improvement. Discussion: Patients with HIES are not only at increased risk for influenzaassociated complications but are also at high risk for life-threatening invasive
infections. In this case, development of H1N1 infection immediately preceded
the development of empyema in a newly enlarged pneumatocele. The STAT3
mutation leads to impaired differentiation of TH17, resulting in decreased
production of IL-17, IL-21, and IL-22, which are crucial in host defense against
extracellular pathogens and in the generation of regulatory T cells (Treg). The
relationship between vitamin D deficiency and increased sinopulmonary infections has been shown to be statistically significant. Therapy with 1,25[OH]2D3
not only increases number and function of Treg, but may also increase antimicrobial peptides in the innate immune response against infections.
A.M. Jongco*, L. Katz, S. Schuval, Great Neck, NY.
RATIONALE: Secondary antibiotic prophylaxis is recommended for
patients with acute rheumatic fever (ARF). Although penicillin is the drug of
choice, the American Academy of Pediatrics recommends sulfadiazine or sulfisoxazole as alternatives. We describe a child with ARF who developed StevensJohnson syndrome (SJS) and cholestatic hepatitis secondary to sulfadiazine.
METHODS: A 10 year old male was diagnosed with ARF after presenting with
chorea and valvular insufficiency following a streptococcal infection. Aspirin
and penicillin VK were started but penicillin was discontinued 9 days later,
after the child developed a diffuse maculopapular rash with fever, nausea, and
vomiting. The rash resolved completely and sulfadiazine was begun for secondary ARF prophylaxis. One week later, sulfadiazine and aspirin were both
stopped due to high fever. However, the fever persisted and the child required
hospitalization 3 days later for conjunctival erythema, cracked lips, facial
swelling and elevated liver function tests (AST 5983 U/L; ALT 3236 U/L).
Abdominal ultrasound showed a normal liver with pericholecystic hepatic
edema. Overnight, the patient deteriorated with development of hemorrhagic
crusting of the lips, increased conjunctival injection, urethral irritation, and rectal erythema with mild skin blistering. Skin biopsy showed prominent dyskeratotic cells under a hyperkeratotic cornified layer, scattered necrotic keratinocytes in the basal epidermis, and sparse lymphocytic infiltrate, consistent
with SJS. Methylprednisolone (1 mg/kg IV every 8 hours) was started and one
dose of IVIG (1g/kg) was given. Although the extent of the blistering increased
over the next 24 hours, the blisters remained superficial, and the patient had a
mild clinical course. RESULTS: The patient did well with complete healing of
skin and normalization of liver function tests 18 days later. Penicillin skin testing was negative; he subsequently tolerated oral penicillin, on which he remains
for secondary rheumatic fever prophylaxis. CONCLUSIONS: Sulfadiazine
most likely caused SJS/hepatitis in this patient although aspirin cannot be ruled
out as a potential cause. Multiple studies have shown that use of anti-infective
sulfonamides is strongly associated with subsequent development of SJS, with
odds ratios greater than 40. This case highlights the risks associated with sulfa
drug administration in the setting of ARF.
R.K. Kado*, J. El-Dahr, New Orleans, LA.
A 14 year old white male presents with a 2 month history of weight loss,
vomiting, fevers, abdominal pain and oral ulcers. Previous diagnostic testing
and biopsies of the esophagus and colon for possible underlying GI etiologies
were inconclusive but significant for ulceration in the esophagus and friability
in the colon. Over the past month he has also began to develop aphthous ulcers
and fevers with a generalized lacy rash lasting for a couple of minutes between
the hours of 11pm-2am. Observation and a full work up for a possible rheumatological disorder during hospitalization for the above symptoms identified the
patient as an atypical presentation of systemic JRA. Resolution of symptoms
was noted once appropriate treatment for the disorder was initiated.
T.A. Kamdar*, B. Sabin, P. Avila, Chicago, IL.
Case Presentation: A 32 year old male with history of allergic rhinitis and
GERD presented to the emergency department (ED) with facial pruritus, flushing, rhinorrhea, hand edema, urticaria, presyncope and hypotension 30 minutes after his breakfast. For breakfast, he ate cheerios, bananas, and milk. In
addition, he took omeprazole, fluticasone nasal spray and 2 tablets of Tylenol
Cold TM (each containing acetaminophen 325mg, dextromethorphan 10mg,
guaifenesin 200mg, and phenylephrine 5mg). He was in a taxi on his way to
work when he noticed rapid onset of the aforementioned symptoms, diverting
his way to the ED. The night before, he had taken 1 tablet of Aleve TM. In the
ED, his BP was 80/50. He was treated with epinephrine 0.3mg x1, IV fluids,
and parenteral diphenhydramine, famotidine, and solumedrol. Symptoms
resolved within 1 hour. He avoided all possible culprit foods and medications
until follow up. In the clinic, we excluded mastocytosis as serum tryptase was
normal. Food allergy was excluded with negative skin pricks to banana (including fresh extract), wheat, oat, almond, peanut, pecan, pistachio, cashew, barley, and multigrain cheerios along with negative oral challenges to cheerios and
banana. Skin testing to medications, including fluticasone nasal spray, visine,
Tylenol Cold TM and graded dose challenges to naproxen and omeprazole on
separate visits were all well tolerated. Graded dose oral challenge to Tylenol
Cold TM provoked erythematous patches over his face similar to those he experienced during the anaphylactic episode. On follow up, skin prick testing was
negative to the individual components of Tylenol Cold TM and graded dose
oral challenges to acetaminophen, dextromethorphan and phenylephrine were
all negative. During a graded dose challenge to guaifenesin, the patient tolerated 4mg, 16mg, 20mg and 40mg without symptoms. Ten minutes after ingesting the 120mg dose (cumulative dose 200mg), the patient experienced erythema/warmth of face and ears as well as bilateral hand edema. Thus, guaifenesin
was confirmed as the etiology of his anaphylaxis Discussion: While other cough
expectorants have been described in the literature as causing anaphylaxis, this
is the first report of urticaria, angioedema or anaphylaxis to guaifenesin. Skin
testing was not helpful in the diagnosis, suggesting that guaifenesin haptens
may have induced IgE-mediated reactions in this case.
L.U. Karkhanis*, J.S. Kuriakose, D.J. Resnick, New York, NY.
Introduction: Angioedema refers to abrupt, nonpitting and short-lived
swelling of the skin, mucous membranes, or both. Hereditary angioedema
(HAE) is usually without hives, unlike idiopathic acquired angioedema. We
present a case of angioedema and rash in a young woman with normal C1
inhibitor level and function, who was unresponsive to antihistamines and corticosteroids, and improved only after C1 inhibitor infusion. Case report: An 18
year old girl with a history of asthma, vocal cord dysfunction, anxiety and celiac
disease was transferred from an outside institution with recurrent sudden onset
tongue and facial swelling and a non pruritic rash. She had failed oral and intravenous antihistamines, corticosteroids and epinephrine. On admission, the
patient had evidence of laryngeal edema and severe abdominal distension. No
hives were noted, but a transient blanching erythema of the extremities was
seen. She did not respond to diphenhydramine, cetirizine, doxepin, ranitidine,
montelukast and high dose intravenous methylprednisolone. Specific
immunoglobulin E (IgE) testing for an extensive panel of triggers, including
foods and latex, was negative. Her C1 inhibitor level and function were normal on two separate occasions. Complement 2 and C1Q levels were normal,
Complement 4 was minimally decreased. Tryptase, total IgE levels and a chronic
urticaria index were normal. An autoimmune workup, which included rheumatoid factor, anti-nuclear antibody (Ab), anti-double stranded DNA Ab, and thyroid antibodies, was unrevealing. Biopsy of the skin lesions was non diagnostic. Computed tomography of the abdomen did not show bowel wall edema. The
patient was empirically started on C1 inhibitor infusions and her episodes subsided. She has since been maintained on C1 inhibitor infusions. Conclusion:
HAE is associated with a mutation in the gene for the plasma protein C1 inhibitor.
HAE type 3, a variant seen in women, has no association with C1 inhibitor deficiency, but is linked to mutations in the factor XII gene. This case highlights
an atypical presentation of angioedema that is not consistent with traditional
HAE classification. It is difficult to make a definitive diagnosis as the diagnostic criteria for HAE type 3 are not established. However, the response to C1
inhibitor infusion suggests an HAE variant. It is imperative for clinicians to be
aware of variant types of HAE and potential management strategies.
L. Katz Buglino*1, S. Esterow2, B. Kaplan1, 1. Great Neck, NY; 2. New
Hyde Park, NY.
Rationale: Rituximab is used to treat various B cell dyscrasias and autoimmune conditions. Low immunoglobulin levels after Rituximab therapy have
been reported. However, studies have shown that B-cells usually recover within
six months after discontinuation of therapy and normalize at 1 year. Combining Rituximab with other chemotherapeutic agents has been reported to cause
more significant immunosuppression. Methods: We describe 3 patients who
received Rituximab and had persistently low immunoglobulin levels despite
normal B cell numbers. Patient A is a 2-year-old female with hemolytic anemia. Patient B is a 15-year-old male with Burkitt’s lymphoma. Patient C is a
58-year-old female with non-Hodgkin’s lymphoma. Results: Patient A required
multiple hospitalizations for pneumonias after treatment with one dose of Rituximab. Patient B had a history of frequent sinus infections with normal immune
evaluation at baseline. However, after receiving Rituximab along with
chemotherapy, he continued to have recurrent sinus infections and developed
new onset hypogammaglobulinemia. Patient C developed increased frequency
of sinus infections and bronchitis one year after completing treatment with Rituximab, along with chemotherapy and stem cell transplant. B cell numbers had
normalized in all patients by 8, 16, and 12 months after completion of treatment with Rituximab, respectively. However, due to hypogammaglobulinemia,
all three patients remain on immunoglobulin replacement at 28, 22, and 14
months after completing Rituximab treatment. Conclusion: These three patients
had recurrent infections and persistently low immunoglobulin levels despite
normalization of B cell numbers. They continue to require immunoglobulin
replacement more than one year after completion of therapy with Rituximab.
Undiagnosed immune deficiency prior to starting a Rituximab containing regimen may be a reason for the significant and persistent hypogammaglobulinemia. Another possibility is that there are some patients who develop more profound and persistent immunosuppression after receiving Rituximab. This finding
underscores the importance of obtaining baseline immunoglobulin levels prior
to starting therapy with Rituximab and monitoring them if clinically relevant.
R. Khianey*, E. Capitle, A. Wolff, Newark, NJ.
Rationale: We report a patient with recurring angioedema who was discovered to have systemic lupus erythematosis with lupus related cardiac tamponade and anti-phospholipid antibody syndrome. Methods: A review of the
medical record was done followed by a literature search. Case: A 20 y/o female
presented to our clinic with a two-week history of bilateral eyelid swelling. She
was previously hospitalized with fevers, fatigue, wrist/ankle pain, and leukopenia attributed to an infection with cytomegalovirus. There was a history of painless oral ulcers but not of photosensitivity, alopecia, rash, swelling of her
tongue/airway, urticaria, or difficulty swallowing. Review of her labs from the
previous hospitalization showed an ANA of 1:640, a C4 <5 (NL 17-52) and
C3 of 30 (NL 90-205). We entertained a diagnosis of complement deficiency
related angioedema secondary to autoimmune disease and prescribed prednisone but she never followed up. Nine months later, she returned to our emergency room with angioedema of her lips, eyes and extremities associated with
severe dyspnea and abdominal distension. She was treated for a pericardial
effusion with tamponade, and diagnosed with a subsegmental pulmonary artery
embolism. Her diagnosis of lupus with anti-phospholipid antibody syndrome
was confirmed with serology. The diagnosis of hypocomplementemic-acquired
angioedema was supported with persistently low C3 and C4, normal C1 INH
antigenic level, C1q 6.5 (NL 11.8 to 24.4), C1q antibody of 15.5 (NL up to 11),
and normal C2. She was treated with high dose steroids, anticoagulation, and
cytoxan with improvement. Discussion: This is an unusual case of lupus presenting with angioedema. Angioedema has been associated with autoimmune
disease, but usually in cases in which the diagnosis is well established. These
patients often demonstrate complement consumption, supported by a low C3
and C4, as seen in our patient. In addition, this patient developed complications of cardiac tamponade and anti-phospholipid syndrome. Conclusion:
Although uncommon, angioedema has been associated with lupus. To our knowledge, this is a rare case of lupus presenting with angioedema and the first case
of acquired angioedema with lupus manifesting with cardiac tamponade and
anti-phospholipid syndrome. The clinician should be aware of the association
of angioedema and autoimmune diseases and of their various presentations.
Hispanic girl presented with cough and shortness of breath, one month later
developed hypertension and nausea and vomiting. Lab results included: hemoglobin 3.1 g/dl, BUN 119 mg/dl, creatinine 12.1 mg/dl, p-ANCA 768 U/ml
(high), and negative c-ANCA. She was started on hemodialysis. Renal biopsy
showed crescenteric glomerulonephritis without presence of granulomas or
immune complex deposition. A chest CT lacked granulomas but showed nonspecific scattered, centrilobular, patchy areas of ground glass opacities consistent with vasculitis and associated hemorrhage consistent with MPA. She was
treated with plasmapheresis, pulse steroids, cyclophosphamide, and continued
on prednisone. RESULTS: Both patients were treated with prednisone and
cyclophosphamide. CaseA’s course was complicated by acute renal failure requiring dialysis and generalized clonic tonic seizures several months after her diagnosis despite treatment. Both patients remain dialysis dependent, currently on
transplant waiting list. CONCLUSION: ANCA positive vasculitis is uncommon but can occur in children. Presentation may vary, but given the poor prognosis without early treatment, it is imperative to think of it in the differential
diagnosis early on when relevant, evaluate appropriately, and treat aggressively.
Even with current treatment however, there is significant mortality and morbidity from end organ failure, especially the kidneys, as seen in our patients.
Comparison of Case A and B
R. Khianey*, E. Capitle, A. Wolff, Newark, NJ.
Rationale: Drug-induced hypersensitivity syndrome (DIHS) is a non-IgE
mediated syndrome, which usually presents weeks after exposure to an inciting viral or pharmacological agent. Classically it presents with rash, fever, and
multi-organ failure. We report a patient with DIHS who developed the atypical manifestation of tracheitis. Methods: A review of the medical record was
done followed by a literature search. Case: Our case involved a 69 y/o female
admitted with dilantin toxicity 3 weeks after starting the medication for seizures.
She presented with generalized weakness and fatigue. Within 48 hours of admission, she developed fevers, hypotension, lymphadenopathy, generalized erythroderma, anemia, thrombocytopenia and acute hepatitis. Like more than
half the cases of DIHS, she did not demonstrate eosinophilia. Despite initial
treatment with Solumedrol 60mg and IV Immunglobulin (2mg/kg), her symptoms progressed with refractory hypotension, ST segment depressions on her
EKG with mildly elevated cardiac enzymes, wheezing, dyspnea, cough and
hypoxemia. A transthoracic echocardiogram showed no abnormalities. Chest
x-ray demonstrated mucous plugging without pneumonia. Twenty-fours hours
later, she developed stridor and an endoscopy showed narrowing of the trachea with erythema and edema, compatible with tracheitis. Solumedrol was
increased to 100mg IV and the next morning the rash improved, the fevers
resolved, liver function tests returned to baseline, and a repeat endoscopy demonstrated resolution of the tracheitis. Conclusion: DIHS is well documented to
be precipitated by anticonvulsant agents such as dilantin. To our knowledge,
this is the first case of DIHS manifesting with tracheitis in addition to the
other classical symptoms that have been previously described. This case also
exemplifies the necessity for high dose systemic corticosteroids and early administration of immunglobulin to terminate the disease progression and to prevent
further morbidity and mortality.
M. Kim*, W. Li, J. Moallem, Brooklyn, NY.
INTRODUCTION: ANCA positive vasculitis is rarely reported in children. It includes a spectrum of vasculitides including Wegener’s Granulomatosis (WG), Microscopic Polyangeitis (MPA), and Churg Strauss Syndrome. We
report two cases diagnosed in adolescents with WG and MPA. PRESENTATION: Case A: 15 year old African American girl presented with erythema
and swelling of the left foot that initially was treated with PO antibiotics for cellulitis. One week later, she developed swelling and erythema of the eyelid and
worsening of left foot swelling. She was treated for episcleritis with a topical
ophthalmic steroid and PO indomethacin for arthritis. One month later, she developed cough and hemoptysis. Chest CT showed multiple lung densities consistent with granulomas. Lab results included: hemoglobin 11.6 g/dl, platelet count
510 x 103/uL, normal creatinine (0.8 mg/dl), ESR 71 mm/hr, c-ANCA 77 U/ml
(high), and negative p-ANCA, all consistent with WG. Case B: 14 year old
J.Y. Kim*, L. Katz, B. Kaplan, Great Neck, NY.
RATIONALE: Obesity is associated with increased morbidity and mortality through its multi-systemic effects on the human body. A complex interplay
of neuroendocrine peptides and adipokines associated with adipose tissue metabolism may be responsible for increased total leukocyte counts, poor antibody
responses, decreased mitogen proliferation and overall increased risk for infection seen in obese patients. Various autoimmune disorders are associated with
Common Variable Immunodeficiency (CVID) with many symptoms improving after starting replacement immunoglobulin therapy. METHODS: We
describe a 59-year-old obese female (BMI: 48) who presented with persistent
asthma and recurrent pulmonary infections. Immunologic evaluation revealed
an IgG of 549mg/dL (694-1618), IgM of 152mg/dL (40-230), IgA of 72mg/dL
(68-378). She had protective titers to Tetanus and Diphtheria, but made a suboptimal response to Pneumovax. Lymphocyte subsets were normal and she had
appropriate responses to Candida, Tetanus, PHA, Pokeweed Mitogen, but a
diminished response to Con-A. There was no family history of immune deficiency or autoimmune disease. The patient was diagnosed with CVID and
treated with Vivaglobin. RESULTS: One year after her CVID diagnosis, the
patient underwent gastric bypass surgery. After losing 56kg over 8 months postoperatively, she was given a trial off immunoglobulin replacement. Her
immunoglobulin levels remained within normal ranges (IgG: 724-799mg/dL,
IgM: 83-101mg/dL, IgA: 160-180mg/dL) for 9 months with no inter-current
infections, but she still failed to make adequate responses to Pneumovax and
Prevnar. Concurrently, the patient developed keratoconjunctivitis sicca, xerostomia, and increased dental caries. Rheumatologic evaluation revealed an elevated ANA with salivary gland biopsy consistent with Sjogren’s. Given a slow
trending decline in IgG levels to < 550 mg/dL, re-initiation of subcutaneous
IVIG was begun at month 11. CONCLUSIONS: This case demonstrates the
transient but potential benefit of weight loss in obese CVID patients. Her case
is further highlighted by her Sjogren’s presentation which may have been masked
by the anti-inflammatory properties of immunoglobulin replacement therapy.
Further research is needed regarding immune deficiency associated with obesity and the effects of immunoglobulin therapy in autoimmune disorders.
M.J. Ku*1, N. Kim2, H.R. Peterman3, 1. Haddonfield, NJ; 2. Camden, NJ;
3. Philadelphia, PA.
Chronic cough is frequently seen in the allergist’s office. The differential
diagnosis can be extensive. We present a challenging case of chronic cough,
which demonstrates the importance of high clinical suspicion and thorough
evaluations to make the correct diagnosis and to implement appropriate treatment. A 51-year-old African American woman presented with chronic cough
for nine months. She was unresponsive to treatments for asthma and gastroesophageal disease. Even after she underwent surgery for documented sinus disease and was treated aggressively with medications, her cough persisted. Culture of surgical specimen, which was positive for Aspergillus, and elevated
IgE level of 1366 kU/L led to suspicion of allergic fungal sinusitis (AFS) and
allergic bronchopulmonary aspergillosis (ABPA), but skin test and precipitins
to multiple molds were negative. A CT scan of the lungs revealed bronchiectasis and several nodules suggestive of a mycobacterium avium-intracellulare
(MAI), however, bronchioalveolar lavage, lung biopsy and sputum culture were
negative. Multiple studies for immunodeficiency, infection and autoimmunity
were negative: ANA, ds-ANA, c-ANCA, p-ANCA, ACE, PPD panel, hypersensitivity pneumonitis panel, HIV, ESR, CBC, IgG, IgM, IgA, IgG subclasses,
CH50, C2, C3, C4, pneumococcal antibody titers, serum protein electrophoresis
and genetic testing for cystic fibrosis. The patient’s condition deteriorated and
she eventually developed severe pneumonia, leading to acute respiratory failure requiring intubation. The diagnosis of primary ciliary dyskinesia (PCK)
was originally thought to be less likely because of her history of uneventful and
successful pregnancy. But electron microscopy of nasal biopsy ultimately confirmed that PCK was the correct diagnosis, showing abnormalities in 98.7%
of ciliary profiles. This case challenges physicians to understand the nuances
in diagnosing the causes of chronic cough. One must understand the diagnostic criteria in conditions such as MAI, ABPA and AFS. It is also important to
remember that, though primary ciliary dyskinesia has been classically associated with infertility, one cannot rule out the diagnosis in a fertile patient. It is
imperative that the correct diagnosis be made in patients with chronic cough
so that proper treatments can be implemented to prevent the potential damaging effects of these conditions.
plement also contained proteases. Once again, the patient experienced a life
threatening anaphylactic reaction. Thankfully, she recovered after appropriate
treatments. The patient’s skin prick test was strongly positive to diluted extracts
of all 3 supplement enzymes, but were negative on a non-atopic control subject. This is the first case report of a patient with papaya allergy who had anaphylaxis to proteases derived from fungus. It is important to understand that a
cross-reactivity may exist between papain and fungus derived proteases. In
addition, allergists should be aware that digestive aids and other over-the-counter
supplements may cause anaphylaxis in papaya allergic patients.
A. Kung*, H. Mawhinney, Los Angeles, CA.
Introduction: Erythropoeitin is a glycoprotein hormone produced by the kidney to promote red blood cell production. The human recombinant form (hrEPO)
is widely used in chronic anemia associated with renal failure. Although allergic reactions are rare, we present a case of a woman who experienced recurrent
facial edema and whole body pruritus with hrEPO who underwent successful
desensitization with no further occurrence of symptoms with continued hrEPO
administration. History:A 47 year old woman with history of chronic kidney disease, status post transplant and dialysis dependent, experienced recurrent periorbital/facial swelling and severe diffuse pruritus approximately 8-12 hours after
weekly hrEPO injections. These symptoms would gradually improve over the
week, but would recur with her next dose of hrEPO. She denied any history of
skin rash, hives, flushing, desquamation, lip/tongue swelling, throat constriction,
or respiratory distress. Her past medical history was significant for allergic rhinitis, but negative for asthma, urticaria, or angioedema. Different brands of hrEPO
(Epogen®, Procrit®, and Aranesp®) all produced similar symptoms. Discontinuation of hrEPO resulted in resolution of symptoms, but the patient’s requirement for blood transfusion increased. The patient was admitted for inpatient
desensitization to hrEPO similar to a previously reported protocol (Ruano FJ et
al.,Allergy 2009). Results: The patient received increasing doses of hrEPO given
subcutaneously over a 2 day period. She was pre-treated with cetirizine, famotidine, and prednisone, with continued daily dosing throughout hospitalization.
During desensitization, the patient experienced some mild itching which was
relieved with oral diphenhydramine. She showed no evidence of facial edema
during hospitalization and completed the desensitization without complication.
The patient was discharged home to continue on hrEPO 4000 units subcutaneously 3 times per week. To date, the patient has had no further recurrence of
her previously reported symptoms. Conclusion: This is the first reported case of
successful desensitization to hrEPO for allergic symptoms. Although a similar
protocol has been previously published (Ruano) with success in treating acute
exanthematous pustulosis following hrEPO administration, we believe this protocol can be used to treat allergic-type symptoms with hrEPO.
Table 1: Epoetin alfa desensitization regimen
M.J. Ku*1, N. Kim2, F.C. Cogen1, 1. Haddonfield, NJ; 2. Camden, NJ.
Papain, a protease derived from papaya, has been known to cause anaphylaxis in non-occupational settings. Papaya is known to be cross-reactive with
latex. In 2008, the FDA warned against the manufacture of topical papain products because of reports of anaphylaxis in latex allergic patients. This created
the impetus in enzyme producing companies to start manufacturing proteases
from a different source, particularly from the fungus. There have been no reports
of cross-reactivity between papain and fungus derived protease (FDP). We present the first case report of anaphylaxis in a papaya allergic patient exposed to
FDP. A 44-year-old woman with history of asthma and allergic rhinitis experienced hives around her face after receiving a facial with papaya. Radioallergosorbent test was positive for papaya (2.07 kU/L) and papain (3.24 kU/L).
One week after the facial, the patient took AFP-Peptizyde and Zyme Prime,
both of which are digestive enzymes derived from fungus and neither product
contains papain. Within 40 minutes, the patient developed severe skin, respiratory and gastrointestinal symptoms consistent with life threatening anaphylaxis. She was treated appropriately and recovered without sequelae. Three
months later, she felt the onset of a respiratory infection and took ViraStop, a
supplement touted to be an “immune stimulator.” Unbeknownst to her, this sup-
J. Kuryan*1, K.D. Jhaveri2, X. Wang2, C. Colter2, D.W. Rosenthal1, 1. Great
Neck, NY; 2. Manhasset, NY.
Introduction: While HIV-associated nephropathy is the most common renal
disease in HIV+ patients, a wide variety of renal pathology has been noted in
this population. This includes several forms of immune complex (IC) disease.
C1q nephropathy (C1qN) is an uncommon podocytopathy with two subsets;
one with features of minimal change disease or focal segmental glomerulosclerosis, and another with features typical of IC disease. To our knowledge,
this is the first report of C1qN in an HIV+ patient. Methods: We report the case
of a 20-year-old male with perinatally acquired HIV and schizophrenia who
presented with hematuria, proteinuria and declining renal function over nine
months. The patient had progressively worsening nephrotic range proteinuria
(peak 10g) and increasing serum creatinine (Cr, 1.4 to 2.0 mg/dL). During this
time, CD4 count improved (124 to 294/ВµL) and HIV viral load (VL) remained
undetectable while being treated with ritonavir, darunavir, etravirine, sulfamethoxazole/trimethoprim (TMP-SMX), fluoxetine, haloperidol, and benztropine mesylate. Serologies for SLE and ANCA vasculitis were negative
and serum C3 and C4 levels were normal. Renal biopsy demonstrated IC mediated glomerulonephritis with mesangial and capillary wall staining for C1q(+2),
IgG(+2), Оє(+2) and О»(+2) chains, with no IgA, IgM or C3 deposits by immunofluorescence. Electron microscopy showed many discrete electron dense
deposits predominantly in the mesangium. Acute allergic interstitial nephritis
was also noted. Results: TMP-SMX was discontinued. The patient was treated
with prednisone 60mg for 3 months, as well as lisinopril and fluvastatin with
interval improvement of renal function (Cr=2.0 to 1.6 mg/dL) and modest
improvement of proteinuria (nadir 5.4g). CD4 improved (488/mL) and VL
remained undetectable. Conclusion: This case describes unique renal pathology in a patient with HIV. The chronic presentation of hematuria, renal dysfunction and nephrotic syndrome along with co-dominant C1q staining in a
predominantly mesangial distribution is most consistent with a diagnosis of
C1qN. Treatment of IC disease with high dose corticosteroids in patients with
secondary immunodeficiency with T-cell lymphopenia provides a therapeutic
challenge, yet this patient responded well. Further understanding of IC formation in HIV+ patients will provide additional insight into the pathogenesis
of both diseases.
M.N. Le*, S. Gierer, D. Stechschulte, M. Altrich, Kansas City, KS.
The patient is a 66 y.o. male with allergic rhinitis, DMII, CAD, HTN, OSA,
and dyslipidemia. His medications include nitroglycerin, rosuvastatin, niacin,
fish oil, carvedilol, hydrochlorothiazide, sitagliptin, insulin glargine and aspart,
ranitidine, aspirin, and nasal fluticasone. He has a history of clopidrogrel induced
rash. In 03/2009, he had unstable angina and occlusive coronary disease upon
catheterization. He was subsequently desensitized to clopidrogrel and returned
for coronary artery stent placement. He, then, began having severe urticaria
and was referred to our allergy clinic. On physical exam, he was found to have
urticaria. RAST testing to foods and common aero-allergens were negative,
except for mild reactions to two molds. His IgE level was elevated at 199 kU/L.
Autoimmune studies and a hepatitis panel were negative. CXR and CT of the
abdomen/pelvis were negative. Clopidrogrel was deemed the offending agent
as the onset of urticaria coincided with its initiation. In 05/2009, Cetirizine,
Ranitidine, Montelukast, Azathioprine 50 mg twice daily and Prednisone 10
mg daily were started and the urticaria abated. However, alternatives were
sought. Prasugrel, a novel thienopyridine that inhibits the platelet adenosine
diphosphate receptor, was approved in 07/2009 for patients with unstable angina
or myocardial infarction that undergo percutaneous stent placement. Clopidrogrel was discontinued; the patient was initiated on the standard dose of Prasugrel and was doing well, having been tapered off prednisone. However, return
of his urticaria was noted two weeks after cessation of Azathioprine and one
month after Prednisone was discontinued. Restarting prior medications alleviated symptoms. He was eventually weaned off all medications in 12/2009 while
continuing Prasugrel. He had another stent placed in 03/2010 and Prasugrel
was continued. He has tolerated this treatment without any immunomodulation. Basophil activation, T-cell lymphocyte proliferation, and cross reactivity
studies with these drugs are pending. Cross reactivity is not well established.
However, this experience suggests patients that are intolerant to Clopidrogrel
may also be intolerant to Prasugrel, especially if they fail desensitization efforts.
J. Lee*1, J. Lee2, A. Jang1, D. Kim1, 1. Bucheonsi, Kyeonggido, Korea,
Republic of; 2. Houston, TX.
30-year-old women presented with cough that aggravated at night for 10
days. She had an ulcerative colitis and underwent a left hemi-colectomy with
colostomy 7 weeks ago. She had received a mesalazine suspension(1g/day)
for 3 weeks after operation. There was no abnormal finding in common blood
test or blood chemistry analysis. Tests for 7 respiratory associated virus and
novel H1N1 virus were all negative.Chest X-ray showed peripheral patchy consolidative lesions in both mid and lower lung zone and HRCT showed peripheral patchy consolidations with interlobular septal thickening in both lungs,
that suspicious a intersititial lung disease. The lung biopsies demonstrated that
patchy interstitial and intraalveolar histiocytic infiltration admixed with many
eosinophils and some neutrophils, and foci of organizing fibrosis, suggestive
of chronic eosinophilic pneumonia with foci of organizing pneumonia. She was
recovered after discontinueing Mesalazin suspension and using systemic steroid.
J.S. Lee*, H. Lehman, Buffalo, NY.
Introduction: Hereditary periodic fever syndromes are a group of rare inherited disorders characterized by recurrent episodes of fever with localized sites
of inflammation. The recurrent fever syndromes are sometimes referred to as
autoinflammatory disorders because they manifest episodic inflammation without high-titer autoantibodies or antigen specific T lymphocytes. Methods: A
case report. Results: A 3-year-old male presented with recurrent fever since 2
years of age, up to Tmax of 104В°F. These fever episodes lasted for 7 days, occuring every 2-3 weeks. Fevers resolved with acetaminophen and ibuprofen. Initially he did not have any other associated symptoms during the time of fever.
At 3 years of age, he started to have oral ulcers and abdominal pain during fever
episodes. Short courses of oral steroids during acute febrile episodes led to resolution of symptoms. Infectious history was unremarkable with only 2-3 lifetime episodes of acute otitis media, and no history of pneumonia, sinus infections, or skin infections. Laboratory results were within normal limits for the
following during afebrile period: CBC with differential, complete metabolic
panel, complement levels, ESR, UA, S. cerevisae titers, P and C-ANCA,
immunoglobulin G/M/A, pneumococcal titers, and T and B cell subsets. During acute febrile periods, labs were notable for elevated CRP, but normal ESR
and ferritin. Genetic analysis for autoinflammatory diseases showed heterogeneous R92Q mutation in TNFRSF1A gene. Other genetic tests were negative
for CIA1S, MEFV, and MVK gene mutations. The patient is now clinically
improved on etanercept therapy. Conclusion: Our patient was diagnosed with
TNF Receptor Associated Periodic Fever Syndrome (TRAPS), which is an autosomal dominantly inherited disease that has clinical manifestation of fever,
abdominal pain, rash and joint pain. Typically, TRAPS patients will demonstrate a global acute phase response during a febrile attack with elevated CRP,
ESR, haptoglobin, fibrinogen, and ferritin. Interestingly our patient only had
elevated CRP, with normal ESR and ferritin during acute attack. This case illustrates that it’s important to consider this diagnosis even if not all the acute phase
reactants are elevated.
E. Leechawengwongs*, P. Shroff, Y. Ogawa, Houston, TX.
Introduction: Hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by eczema, recurrent skin and sinopulmonary
infections, elevated serum IgE and eosinophilia. A subgroup of autosomal dominant HIES (AD-HIES) is caused by mutations in STAT3, which lead to impaired
Th17 function. Autoimmunity has been reported in sporadic and autosomal
recessive HIES (AR-HIES) cases although the association has not been well
described. Method: We describe a case report of a 19 year old female with HIES
and immune-complex glomerulonephritis. Results: Patient is a 19 year old
African American female with eczema, recurrent Staphylococcal abscesses,
right lung abscess and pneumatocele status post lobectomy at age 12 who presented with renal disease. She has non-immunologic characteristics of ADHIES including facial features, retained primary teeth, scoliosis and Chiari malformation. She continues to have recurrent skin abscesses and has been started
on sulfamethoxazole-trimethoprim for prophylaxis. Her IgE level was highest
at 20,000 mg/dl. NIH score for HIES was 47 consistent with probably affected
HIES. At the time of presentation, her IgE level was 947.2 mg/dl with a white
blood cell count of 7.7 k/ul and absolute eosinophil count of 847 (11%). Creatinine was 2.1 mg/dl with marked proteinuria 6.4g/day and hematuria. Renal
biopsy revealed immune-complex mediated proliferative and necrotizing
glomerulonephritis (IgG, IgM) that could be compatible with lupus nephritis
(class IV), and focal intracapillary hyaline thrombi. However her ANA, antidsDNA, antiphospholipid antibodies, hepatitis serology and cryoglobulin were
all negative. She had normal serum IgG, IgM, IgA and complement levels.
Patient was started on mycophenolate, hydroxychloroquine, prednisone and
ramipril with mild improvement of her renal function. Conclusion: We report
a case of atypical HIES with immune-complex glomerulonephritis. Our patient
most likely has STAT3 mutation based on her clinical characteristics. STAT3
mutation is associated with impairment of Th17 differentiation, therefore we
would expect to find less autoimmunity.
and B cell receptor (О»5, IgО±, IgОІ), or the scaffold protein BLNK account
for approximately 90% of patients with defects in early B cell development.
This patient’s personal and family history support a diagnosis of X-linked
Agammaglobulinemia, however commercial gene testing for the BTK mutation showed no sequence variance. In addition his CD19 count is higher
than expected in XLA. In this setting it is important to consider a broader
differential and more specialized testing. If only exons were sequenced when
utilizing commercial molecular genetic testing a mutation may have been
missed. When molecular genetics testing is unsuccessful, detection of BTK
protein by immunofluorescence or western blot may help confirm the diagnosis.
S. Leibel*, G.R. Bloomberg, Saint Louis, MO.
Background: Children with chronic cough can be misdiagnosed as coughvariant asthma. We present a case of tic-induced chronic cough in a child receiving stimulant medication given for Attention Deficit Hyperactivity Disorder.
Case Presentation: An 8-year-old African-American girl was referred by her
pediatrician for chronic cough of seven months’ duration. There was no history
of wheeze, exercise intolerance, or nocturnal cough. There was no family history of allergic disease. Previous treatments included use of bronchodilator,
oral prednisolone, and azithromycin with the consideration that her condition
represented cough variant asthma or atypical pneumonia. There was no change
in symptoms. Physical exam was unremarkable except for repetitive eye blinking and face rubbing. Evaluation included testing for pertussis, aeroallergen
sensitization, chest radiograph, and airway hyperreactivity, all with normal
results. Additional history revealed that the patient’s cough had started shortly
after initiating dextroamphetamine for ADHD. She did not have motor or phonetic tics prior to the initiation of this medication. We discontinued the medication and requested a return visit in 4 weeks. All symptoms of cough resolved
within 24-48 hours of discontinuing the medication. Furthermore she had no
further repetitive behavior. She was prescribed a different stimulant medication with no relapse of cough. Discussion: Increasingly, many children are being
diagnosed with ADHD and are placed on stimulant medication. The labeling
information does make it known that symptoms of Tourette’s syndrome may
become apparent but does not specify the presence of chronic cough. Primary
care pediatricians and allergists need to be aware of this complication of stimulant therapy. Additional personal and social history may bring this information to light when considering the diagnosis of a chronic cough, especially when
unaccompanied by symptoms consistent with allergic rhinitis, sinus disease,
or lower respiratory symptoms of wheeze or exercise intolerance. We bring
attention to a unique case of chronic cough in children that is associated with
co-morbidity of Attention Deficit Hyperactivity Disorder and subsequent treatment with stimulant medications.
S. Leibel*, C. Horner, Saint Louis, MO.
Introduction: We present an atypical case of B-cell Lymphopenia in a
patient with a positive family history of immunodeficiency. Case: The patient
is a 5 year old male who presented for evaluation of chronic cough and
recurrent pneumonia. His past medical history was significant for respiratory failure with pertussis at 7 months of age and subsequent pseudomonas
line bacteremia. His family history revealed a half brother who was evaluated for “CVID”. On examination the patient had mucoid discharge from
his left eye and mild clear rhinorrhea with crusting bilaterally. On chest
exam he had crackles in upper lobes bilaterally, no wheeze. Of note, the
patient also had digital clubbing present and facial impetigo. His chest radiograph showed a left lower lobe infiltrate. Further laboratory investigation
revealed a IgG<60mg/dl, IgA<7mg/dl, IgM 2.3mg dl, IgE 0.1 IU/ml. His
lymphocyte subpopulations were significant for a CD19 count of 71/cumm
(3%). His CD 20 was 62/cumm (4%) His tetanus, Hib and Strep. Pneumonia titers were low. His lymphocyte proliferations to mitogens were normal.
We evaluated BTK sequencing and no sequence variants were detected. Further investigation revealed that the patient’s half brother also has B-cell
Lymphopenia, Hypogammaglobulinemia and normal BTK gene sequencing. The patient received IV antibiotics and is currently clinically stable on
IVIG therapy. We will attempt to further evaluate BTK by flow cytometry
to look for the intracellular protein in macrophages. Other diagnostic considerations include Hyper IgM syndrome, NEMO, BLNK or B-Cell Receptor defects. Discussion: Mutations in BTK, components of the pre-B cell
E. Lewis*, R. Hopp, S. Kunnath, Omaha, NE.
Introduction: Eosinophils are found in the gastrointestinal tract with the
exception of the esophagus. Their location allows access to defend against
parasitic infections. Upon activation, eosinophils release granules/cellular products to kill parasites to large for phagocytosis. Eosinophilic esophagitis (EE)
clinically results in heartburn, abdominal pain and vomiting, and most children
with EE are atopic. Diagnosis is supported by an esophageal biopsy findings
of > 15 eosinphils/hpf. Enterobius vermicularis infection is characteristically
mild with symptoms of perianal pruritis secondary to egg deposition. Peripheral eosinophilia is an uncommon feature. There are case reports of eosinophilic
ileocolitis, gastroenteritis and appendicitis secondary to pinworm infestation.
However, there are no case reports of EE associated with pinworm infestation.
Case Discussion: A 12 year old male presented with recurrent abdominal pain
for 2 years. A sledding accident resulted in a CT scan, showing thickening of
the colon. A CBC revealed 21% eosinophils. A esophagogastroduodenoscopy
and colonic endoscopy with biopsies revealed 20 eosinophils/hpf in the esophagus, chronic gastritis with eosinophils, and chronic duodenal inflammation
with eosinophils. Pinworms were visualized during colonoscopy. Stools testing for other parasites and celiac testing were negative. Skin testing was positive to milk, egg, peanut and beef. Patient was treated for pinworms, started on
Budesonide 500mcg swallowed twice daily, food restriction based on positive
skin testing, and Prevacid 15mg twice daily. Repeat biopsy 3 months later on
therapy was negative for eosinophils in all biopsy specimens, and the lower
endoscopy was negative visually for pinworms. Eosinophils 2% on repeat CBC.
Discussion: Elimination of pinworms and proper treatment for EE has resulted
in both clinical and pathological improvement. The question remains as to
whether pinworms can elicit an eosinophilic-based immune response in the
esophagus. Since the lifecycle of Enterobius vermicularis involves the entire
GI tract (eggs ingested travel to bowel where they hatch, grow and deposit new
eggs around anus), it is logically to conclude that certain individuals could have
an eosinophil response in the esophagus to the ingested eggs. Removal of the
offending allergen would then result in resolution of EE.
A. Leyton*, J. Baldwin, Ann Arbor, MI.
L. Lu*, J. Leung, P. Ponda, Great Neck, NY.
INTRODUCTION: “Blended” reactions (BRs) to ASA are characterized
by both cutaneous (urticaria and/or angioedema) and respiratory adverse effects.
BRs to ASA are less common and less well characterized mechanistically than
pure AERD reactions (1). Additionally these patients are generally more challenging to fully desensitize. We describe a case supporting COX-1 inhibition
as the shared mechanism responsible for both components of the BR and
describe a successful desensitization in a patient with a BR. METHODS:
ASA/NSAID desensitization in a patient with BRs to ASA/NSAIDs utilizing
a modified AERD practice paper (2) approach. DATA: A 38 year old male with
a history of BR’s to ASA and NSAIDs was successfully desensitized to
ASA/NSAIDs. Despite initial successful desensitization of the respiratory component, the cutaneous component persisted using standard practice paper desensitization approach. Cutaneous component desensitization was achieved and
maintained only after the addition of zileuton. Withdrawal of zileuton resulted
in rapid recurrence of urticaria which was abrogated with the reinitiation of
zilueton. CONCLUSION: ASA/NSAID desensitization per practice paper
guidelines for pure AERD patients may need augmentation with the 5-LO
inhibitor zileuton for successful complete desensitization to occur in patients
with BRs to ASA/NSAIDS. References: 1. Stevenson DD, et al: Sensitivity to
aspirin and nonsteroidal anitiinflammatory drugs. In: Adkinson NF et al (eds):
Allergy Principles and Practice 6th edition; (Mosby, 2003):1695-6. 2. Macy E
et al. Aspirin challenge and desensitization for aspirin exacerbated respiratory
disease: a practice paper. Allergy Asthma Immunology 2007;98:172-174.
B.D. Liu*, M.B. Fasano, Iowa City, IA.
X-Linked Agammaglobulinemia (XLA) is typically characterized by absent
or markedly diminished serum immunoglobulins and B cells and a paucity of
lymphoid tissue. Infectious complications occur by 9-18 mo of age, coinciding
with the disappearance of maternal antibodies. However, there have been
reported cases of atypical XLA, which may lead to delayed or misdiagnosis. In
a family of 4 affected males with the same BTK mutation, we report atypical
and common features associated with XLA. Chart review of clinical notes,
laboratory and imaging data was conducted on 4 males (proband, identical twin
brothers and a maternal cousin) between 2008 and the present. Pt 1 (proband)
presented at 5 yo for evaluation of a facial cellulitis responsive to oral antibiotics. PMH included multiple episodes of otitis media, 2 episodes of sinusitis
and adenoidectomy at age 3. There was no history of serious invasive disease.
He had detectable IgE to cat and grass pollen. Testing demonstrated decreased
IgG and IgM with normal IgA and IgE and protective titers to prior immunizations. However, CD19+ cells were <1% and he had no response to the PneumovaxВ® 23 vaccine. He was found to have a R28H mutation in the BTK gene;
mother was identified as a carrier. Pt 2, the maternal cousin of Pt 1, presented
at 13 yo with Pneumocystis jeroveci pneumonia. PMH included 4 episodes of
pneumonia and crescentic glomerulonephritis treated with cyclophosphamide
and prednisone. Testing showed decreased IgG and IgM with normal IgA and
IgE and protective titers to prior immunizations. CD19+ cells were 3%. He
was found to have a R28H mutation in the BTK gene. Mother was identified
as a carrier. Pts 3 & 4 are identical twin siblings of Pt 1 born at 32 weeks gestation. As expected, both had detectable, but diminished IgG, undetectable IgA
and IgM, CD19+ cells <1%. Pt 4 had CD3-CD56+ cells < 1% with improvement seen at age 3 mo. This case series highlights both common and atypical
presentations of XLA within 1 family with the same R28H BTK gene mutation. Pts 1 & 2 had normal IgA and IgE, protective antibody titers to selected
vaccines and visible lymphoid tissue. Pt. 4 had undetectable NK cells initially.
This report illustrates features that may result in delayed or misdiagnosis of
XLA. Recognition of atypical features in XLA is critical for prompt diagnosis,
therapeutic intervention and family counseling.
Introduction: Caramel colors have been widely used in foods and beverages including soda. It has been reported that histamine levels are significantly elevated after drinking a caramel colored carbonated beverage among
asthmatic children. However, allergy or anaphylaxis caused by drinking sodas
has rarely been seen. We report a case of allergic reaction to caramel containing sodas. Case Description: A 14-year-old female presented with a recurrent
burning sensation and pruritis of her lips for 6 months when drinking canned
soda (Coca Cola, Pepsi or Dr. Pepper). On 2 occasions she developed generalized urticaria, facial erythema and lip swelling. However, Sunkist Orange soda
and Mountain Dew were tolerated. No wheezing, difficulty in breathing, dysphagia or gastrointestinal discomfort were noted. Her symptoms were relieved
by antihistamines. Physical examination revealed erythema on bilateral axillary folds, rough and dry skin on eyelids, and occasional vocal and musculoskeletal tics. The patient’s past medical history is significant for Tourette Syndrome and accomodative spasms of her left eye. Skin prick testing was reactive
to Dermatophagoides pteroyssinus. A double-blind placebo-controlled food
challenge was done and was positive for Dr. Pepper (urticaria “burning sensation” on her neck, flushing and anxiety). Symptoms were again relieved with
antihistamines. Dr. Pepper, Pepsi and Coca Cola all contain caramel color.
Avoidance of caramel color containing sodas was recommended. Discussion:
This case is an unusual manifestation of a food allergy to a food product that
contains caramel color. Caramel colors often contain soluble food dyes and
caramelized sugar. They are commonly used in commercial soda products.
Although the exact ingredients are proprietary, the manufacturers confirm
that these drinks contain caramel colors approved by the FDA. Thus, a higher
level of awareness of these potential allergic reactions to commonly consumed
beverages is warranted.
T. Mainardi*, J. Kuriakose, S. Canfield, New York City, NY.
Introduction: Hypereosinophilic syndrome (HES) represents a group of disorders that consist of a pathological increase in the numbers of circulating and
tissue bound eosinophils with resultant end organ damage. In myeloproliferative HES (M-HES), a subset of patients bearing the FIP1L1/PDGFRA (F/P)
fusion protein respond well to oral Imatinib therapy. Here we report a case of
myeloproliferative HES negative for the F/P fusion with a dramatic response
to Imatinib therapy. Case Report: A 40 year old male with a history of hypertension, type 2 diabetes and end-stage renal disease on dialysis, was admitted
to the hospital for worsening shortness of breath and rash. Physical exam
revealed splenomegaly and an erythematous maculopapular eruption. Laboratory examination revealed an absolute eosinophil count of 15,000, thrombocytopenia and anemia, an elevated tryptase and normal vitamin B12. Echocardiography revealed right ventricular dilation; endomyocardial biopsy revealed
fibrosis and eosinophilic thrombi. Evaluation revealed no evidence of helminth
infection; normal karyotype; no monoclonal Ig or TCR rearrangement; no
evidence of the F/P -fusion protein, nor of the V617F JAK2 mutation. The
patient was started on prednisone (1 mg/kg), but eosinophil counts remained
high, reaching 43,000 nearly one month into treatment. The patient was then
started on Imatinib 400 mg daily by mouth with eosinophil counts dropping to
1900. Conclusion: HES is defined as a persistent elevation of
eosinophils>1500/mm for six months without secondary cause, and with end
organ involvement. The myeloproliferative variant is strongly associated with
a mutation encoding a novel fusion between FIP1L1 and the PDGFRa polypeptides. This mutation was discovered in a subset of M-HES patients who
responded to the tyrosine kinase inhibitor Imatinib. In patients with the F/P+
M-HES variant, Imatinib therapy yields remission rates at one month near
100%. Imatinib’s mechanism of action involves binding at the evolutionarily
conserved ATPase region of target kinases, explaining imatinib’s utility in diseases mediated by tyrosine kinases as well as the loss of response to Imatinib
in patients who have developed secondary mutations. In patients such as the
one described, the target of Imatinib has not been identified but is likely to
represent a mutant tyrosine kinase with unregulated activity.
S.K. Mane*, A. Casillas, Shreveport, LA.
Introduction: Among other erythrodermic conditions such as Toxic Epidermal Necrolysis (TEN), Erythema Multiforme (EM), vancomycin-induced
Red Man Syndrome (RMS), and adult Kawasaki Disease (KD), the rapid recognition and treatment of Drug Rash with Eosinophilia and Systemic Symptoms
(DRESS) Syndrome and Stevens-Johnson Syndrome (SJS) is crucial for a favorable outcome. DRESS Syndrome and SJS are both acute severe skin conditions
that can result in significant morbidity and mortality. We present three cases
of DRESS in combination with SJS that demonstrate the need for systemic
steroids and high-dose intravenous immunoglobin (IVIG) for successful management of these patients. Case presentations: The first patient is a 35 year-old
African American female who presented with a subarachnoid hemorrhage from
a ruptured basilar artery aneurysm. Post neurosurgical clipping, the patient was
placed on Phenytoin and developed a rash ten days later. Her liver function tests
peaked eight days later. At that time, she had mucosal lesions and was placed
on corticosteroids and high dose IVIG. A skin biopsy confirmed SJS. She
improved clinically and liver function tests normalized. The second case is a
3.5 year-old Indian female with no significant past medical history who was
diagnosed with a febrile seizure and placed on Phenobarbital. Twelve days later,
she developed a rash. She was admitted four days later with mucosal lesions
at which time high dose IVIG was initiated. Her liver function tests peaked the
following day, and corticosteroids were started. She improved clinically and
her liver function tests normalized. The third case is a 38 year-old male who
was placed on Phenytoin for four weeks after a subarachnoid hemorrhage.
Two weeks later, he developed a rash, mucosal lesions, and increased liver function tests. Corticosteroids were initiated immediately; however, despite strong
recommendation, initiating IVIG was delayed and the patient suffered significant epidermal sloughing requiring transfer to the burn unit. Improvement was
noted two days after initiating IVIG. Conclusion: These cases demonstrate the
need for early recognition and treatment of DRESS and SJS in order to prevent significantly morbidity and mortality.
Mucosal findings in a 3.5 year-old Indian female admitted for dehydration.
This image was taken prior to the initiation of corticosteroids and high dose
The high risk populations are the atopic individuals, health workers and children with spina bifida or multiple surgeries. Reactions occur in a short period
after exposure (mucosal vasodilation, severe bronchospasm and increased permeability with edema and cardiovascular collapse). Diagnostic methods for latex
allergy include skin test with 65-96% sensitivity and 88-94% specificity, glove
tests with low sensibility and specificity, rubbing test, determination of specific IgE to latex, and most recently a diagnostic method with nasal challenge
to latex. CASE PRESENTATION A Mexican 7 year old girl, with a history of
asthma since age 5, treated with Salmeterol/Fluticasone BID and Salbutamol
as needed. When she touches balloons, she notes itching in the oral cavity, lips
edema, dyspnea, wheezing, coughing, conjunctival erythema, so does eating
kiwi, banana and avocado. In the glove test refers mild local itching and examination reveals erythema. The skin tests included avocado, kiwi, banana, potato,
apple, apricot, grapes, wheat, tomato and latex; only with the last one she presented erythema of 30 and wheal of 17 mm with a histamine control of 10 and
5 mm respectively. The nasal challenge started with instillation of Latex Sol with
0.9% saline, a nasal flow of 408 ml/s, then latex was instilled with increasing
doses until the end of 50 mcg in Latex at which the nasal flow decreases significantly because she couldn’t perform rhinomanometry due to nasal obstruction symptoms (sneezing, moderate rhinorrhea and nasal obstruction) that precluded the test. Specific IgE was reported in 3.51-17.5 kU/l (normal ≤ 0.35
kU/l). We start specific latex immunotherapy, and recommend eliminating from
the diet: avocado, kiwi, bananas, potatoes, apricots, grapes, wheat and tomato.
DISCUSSION: Latex allergy is rare, so we present a case in which various diagnostic tests were performed to corroborate the usefulness of nasal challenge to
support a diagnosis of latex allergy and to give immunotherapy and dietary
support. It is noteworthy that the patient is currently with maintenance SLIT
with specific latex vaccine and successful immunotherapy outcomes.
M. Martucci*, R. Katial, Denver, CO.
INTRODUCTION: Vocal cord dysfunction is a condition where the larynx
exhibits paradoxical vocal cord adduction during inspiration, resulting in wheezing, cough, and SOB. We present a case of a woman originally diagnosed with
severe persistent asthma requiring high dose oral steroids and intubation. CASE
PRESENTATION: 47 yo female with previous diagnosis of severe persistent
asthma presented with continued asthma exacerbations despite high dose inhaled
steroids, long acting beta agonists, and oral steroids. Symptoms included dysphonia, wheezing, cough and SOB. Triggers were cinnamon odors, smoke inhalation and oral cinnamon. She required use of an EpiPen ten times over past 2
years. PMH included anxiety, HTN and migraines. Medications included Advair,
QVAR, Zyrtec, Claritin, oral albuterol, Singular, Aciphex, ProAir, Benadryl,
hydroxyzine, Zantac, lorazepam and an EpiPen. ROS was negative. Physical
exam at time of presentation was within normal limits. RESULTS: A through
evaluation was performed for her worsening respiratory symptoms. CT sinus
was negative. CT chest was normal. PFTs demonstrated no airflow limitation
and no response to bronchodilator. Lab workup was unremarkable. During cinnamon skin testing, she began to experience cough and SOB. A laryngescope
was inserted demonstrating severe vocal cord dysfunction. She was given Heliox
and relaxation techniques and her symptoms subsided. Vocal cord exercises were
initiated, but she was unable to perform secondary to anxiety. We referred her
to a physician who specializes in hypnosis for severe vocal cord dysfunction.
Through several sessions she was able to develop techniques to avoid any further exacerbations. Her asthma medications including inhaled steroids, LABAs,
oral steroids, antihistamines and albuterol were discontinued. She is currently
tolerating both oral and inhalation cinnamon. Plan is for her to continue with
hypnosis and relaxation techniques. CONCLUSION: We report a case of severe
vocal cord dysfunction presenting as refractory asthma. It highlights the importance of reevaluating the diagnosis when patients fail to respond to standard
treatment. Extensive morbidity and possible mortality may result from incorrect diagnoses and treatment decisions. The differential is broad in conditions
that mimic asthma; therefore a thorough evaluation is warranted in all patients.
L.L. JuГЎrez-MartГ­nez*, G.F. PavГіn-Romero, M.R. GonzГЎlez-Galarza,
F. RamГ­rez-JimГ©nez, L.M. TerГЎn-JuГЎrez, M.L. GarcГ­a-Cruz, Mexico City,
INTRODUCTION: It is a hypersensitivity reaction predominantly type I,
sometimes type IV hypersensitivity caused specifically by the proteins in latex.
Alpha1-Antitrypsin Deficency Phenotypes
N.A. Mazer*, A. Rubinstein, Bronx, NY.
Introduction: Haptoglobin is an acute phase protein that is synthesized primarily by liver cells in response to IL-6. A main role of haptoglobin is the binding of free hemoglobin during hemolysis; in doing so, it prevents oxidative tissue damage. Haptoglobin has also been reported to have involvement in major
inflammatory disorders, autoimmune disease, and immune modulation. We
describe a patient with chronic, unexplained inflammatory and autoimmune
manifestations who was found to have haptoglobin deficiency in the absence
of hemolysis. Methods: We evaluated a 26-year old woman with a complex
medical history who was found to have persistent haptoglobin deficiency in
the absence of hemolytic anemia. Results: The patient was referred for evaluation of possible immunodeficiency. As a young child she suffered from frequent otitis media, strep throat, pneumonia, and febrile seizures. Her school
years were uneventful but at age 18 her health deteriorated, with chronic and
progressive fatigue, headaches, myalgias, bruising, and Raynaud-like symptoms of the hands. She was also treated for hypothyroidism and adrenal insufficiency. Family history was remarkable for a grandmother with Addison’s
disease. Immune evaluation revealed marginally low serum IgA at 68 mg/dL,
low serum IgM at 42 mg/dL, and low IgG2 at 204 mg/dL. She had normal protective antibodies to pneumococcal serotypes. Other findings were a leucopenia of 3.1 x103/mcL, and low CD19+ B cells at 3%. She was incidentally found
to have a persistently low haptoglobin. Conclusion: Persistently low or absent
haptoglobin in the absence of hemolysis was an incidental finding during evaluation for a possible hemolytic process. Haptoglobin has been shown to play
a part in counteracting potentially harmful oxidative and Nitric Oxide-scavenging effects associated with circulating hemoglobin, and elicits an anti-inflammatory response. Haptoglobin deficiency in this patient may be the key to her
autoimmune and inflammatory conditions.
T.L. Mertz*, Hershey, PA.
Introduction Alpha1-antitrypsin deficiency (О±1ATD) is a genetic disorder
caused by a mutation in Alpha1-antitrypsin, an inhibitor of human neutrophil
elastase. Mutations lead to decreased levels or function of О±1AT. Genotype
screening evaluates for the presence of the S or Z. The normal genotype is the
MM, which is associated with normal amounts of the enzyme. The ZZ genotype occurs at a frequency of 1/2500 and is associated with a marked reduction of О±1AT levels resulting in disease in the lung, liver and sometimes skin.
The F-Null phenotype is a rare and poorly characterized form of О±1ATD. The
case presented is a patient with F-Null phenotype with a review of the literature on this topic. Methods OVID and Pub Med were searched with the following terms: Alpha1-antitrypsin deficiency (О±1ATD), Chronic Obstructive
Pulmonary Disease (COPD) and phenotype. Case Report A 64 year-old male
with a long standing diagnosis of О±1ATD presented for evaluation of recurrent urticarial rash and chronic dyspnea that was resistant to standard treatment.
He quit smoking at the time of his О±1ATD diagnosis about 15 years prior, but
had never been treated with augmentation. Evaluation revealed non-reversible
obstructive lung disease on pulmonary function tests (PFTs) and a skin biopsy
was consistent with neutrophilic urticaria. The О±1AT level was 93 mg/dl (normal 100-190) and the genotype was MM. Given the discordance with the low
normal level and his clinical picture, a phenotype was checked and revealed Fnull phenotype. The patient was placed on О±1AT replacement therapy with
hopeful improvement of his lung and skin symptoms. Results Literature review
revealed limited information about the rare variant phenotype of F-Null. Lab
studies have shown decreased activity of the F protein in vivo. Case reports
have been published of patients with FZ phenotype and obstructive lung disease. No case reports have documented skin and lung disease in the F-null
subset. Conclusion Clinicians should be aware that there are several rare mutations which can lead to clinical О±1AT disease. Genotype screening tests assess
only for the most common mutations; S and Z. Therefore, phenotyping for
patients with a normal genotype whose clinical history strongly suggests О±1AT
deficiency is recommended.
American Thoracic Society, Am Rev Respir Dis 1989; 140:1494.
S. Mithani*1, S. Farzan1, M. Frieri2, V. Bonagura1, 1. Great Neck, NY; 2.
New Hyde Park, NY.
Background: Mannose-binding lectin (MBL) plays an important role in the
host immune response and binds to pathogen-associated molecular patterns
typically expressed on microbial surfaces. This leads to opsonization of microbes
containing repeating mannose motifs, recruitment of phagocytic cells, and complement activation with microbial lysis. MBL deficiency has been implicated
in the increased susceptibility to infections in man. In addition, selective IgA
deficiency is one of the most common primary immunodeficiency disorders,
and patients may have increased respiratory and gastrointestinal infections, or
be asymptomatic. Severe infections may be more common in patients with combined IgA and MBL deficiency. Methods: We describe a 31-year-old male, former IV drug abuser, with a history of recurrent infections. For the past year,
he has had recurrent skin abscesses on his upper and lower extremities which
have occurred at sites where IV lines have been placed but have also occurred
spontaneously. Wound cultures have been positive for Streptococcus,
Corynebacterium, Enterococcus, Staphylococcus aureus, Bacteroides ovatus,
and Klebsiella oxytoca. Past medical history is significant for beta thalassemia,
ADHD, allergic rhinitis, recurrent viral upper respiratory tract infections, two
pneumonias, and multiple urinary tract infections. Family history is significant
for a mother with multiple sclerosis, father, paternal cousin, and a nephew all
with IgA deficiency. Physical examination was significant for resolving
abscesses on his arms and wrists. Results: Low IgA level = <7 mg/dl (70-312
mg/dl) Low mannose binding lectin = <5 ng/ml (> 5 ng/ml) Positive Anti-IgA
IgG = 100.4 U (< 52 U) Conclusions: This is a case of a patient with concurrent MBL deficiency and IgA deficiency with recurrent skin, respiratory, and
genitourinary infections. He is IgA deficient and has evidence of IgG anti-IgA
antibodies, and thus is unable to receive fresh frozen plasma or serum purified
MBL as a form of MBL protein replacement, because of the risk of developing an anaphylactoid reaction to IgA contamination of these serum products.
Although not yet available in the USA and currently in clinical trials, replacement therapy with recombinant MBL would be ideal along with appropriate
antibiotics to treat serious or life threatening infections in patients with MBP
and severe IgA deficiency with autoantibodies.
M. Nasir*, J.A. Grant, Galveston, TX.
Introduction: Urticarial vasculitis (UV) is a disorder characterized by
histopathologic evidence of leukocytoclastic vasculitis in addition to episodes
of urticaria. Common skin findings include urticarial papules and plaques,
annular erythema and dermographism. Here we present a case of UV presenting in a patient with angioedema and erythema multiforme, a rare cutaneous
manifestation of this disease. Case: A 32 year-old female with a history of intermittent asthma presented to our allergy/immunology clinic with complaints of
angioedema and a painful, burning rash for 8 weeks. She was being treated
with anti-histamines and montelukast without improvement. Intramuscular
steroid injections and oral steroids provided temporary relief. In our clinic physical examination was remarkable for erythematous, raised target lesions with
central clearing. These were present on her abdomen and back. Additionally
she had some purplish, hyperpigmented lesions on her inner thighs. She reported
that these were target lesions that had been resolving for three days. Results:
A punch biopsy of a target lesion revealed dermal edema and a prominent
perivascular infiltrate composed of neutrophils and occasional eosinophils.
Infiltration of vessel walls, leukocytoclasia and extravasated blood cells were
also noted. These findings were consistent with urticarial vasculitis. Laboratory tests revealed a normal basic metabolic panel, thyroid function tests, hepatic
function panel and urinalysis. A complete blood count was notable for a mildly
elevated white blood cell count of 11.4. Once results of the biopsy were available a further work-up was performed. Testing revealed normal serum cryoglobulins, tryptase, erythrocyte sedimentation rate, rheumatoid factor, hepatitis B and C antibodies, anti-nuclear antibody, C3, C4, C1q and C1 inhibitor
function. Initiation of treatment with hydroxychloroquine resulted in resolution of her symptoms. Conclusion: Erythema multiforme is a rare cutaneous
manifestation of UV. Biopsy of skin lesions is necessary for diagnosis. Hydroxychloroquine is a safe and effective steroid-sparing agent for these patients.
concentration, and intradermal testing was done with 1:100 and 1:10 dilutions of
factor IX concentrate, which were all negative. Histamine and saline served as positive and negative controls.The patient received IV factor IX at 0.01u/kg with doses
doubled at 10-min intervals with a cumulative test dose total of 1843 units. The
patient tolerated the modified Jamieson desensitization protocol well, with no
immediate reaction. However, the patient’s PTT remained elevated >300 following treatment with Factor IX, suggesting presence autoantibodies. Patient would
need mixing studies for clinical correlation Conclusion: This patient’s successful
response to Factor IX desensitization demonstrates that a similar approach can be
applied to hemophilia A patients with hypersensitivity. Furthermore, it shows the
important role of the allergist in the management of hospitalized patients with
hypersensitivity to drugs or biological agents.
Factor IX Desensitization Protocol
T. Nguyen*, V. Dimov, A. Bewtra, Omaha, NE.
Introduction: Allergic disorders, such as allergic rhinitis and asthma, have
a profound impact on quality of life, but conditions that worsen with sexual
intercourse are infrequent yet strongly affect the emotional well-being of both
partners and affect their family planning. Methods: We present a series of
patients evaluated in our clinic to illustrate the challenges of semen allergy
and other allergic disorders triggered by intimate relations. Results: Patient 1
is a 27yo woman with allergic rhinitis who presented with history of peri-vaginal itching, burning and erythema only after unprotected intercourse with her
husband. She even used a topical lidocaine spray to make symptoms bearable.
Skin prick test to her husband’s semen was positive. Symptoms resolved with
condoms. Patient 2 is a 28yo woman who presented with similar history and
positive skin prick testing to semen. Her symptoms are proportional to the
amount of ejaculate released. She and her husband did not want to use condoms but did want to conceive. We prescribed prophylaxis with cetirizine and
prednisone prior to intercourse. Patient 3 is a 27yo woman who developed postcoital perineal pruritus and rash 1 year after normal sexual relations with her
husband; however, symptoms occurred prior to ejaculation and even with condoms. For her diagnosis of vibratory urticaria, we prescribed fexofenadine
and recommended less vigorous intercourse. Patient 4 was a 36yo woman who
had 3 courses of pneumonia unresponsive to antibiotics but responsive to
steroids. Needle biopsy showed neutrophilic vasculitis with complement
involvement. She had no constitutional symptoms and immunologic work-up
was negative. All episodes correlated with sexual activity, confirmed with
skin testing to semen: she had both an immediate and Arthus reaction. She had
an immune complex disease to glycoproteins in the seminal fluid. Symptoms
resolved with condoms. Conclusion: This case series reinforces the importance
of obtaining an accurate patient history, especially when sensitive issues of intimacy are involved. Women with semen allergy may be desensitized, but daily
unprotected sexual intercourse is required to maintain this state, which then
involves discussing contraception. Alternatively, prophylaxis with steroids and
antihistamines may allow intercourse to be tolerated to allow for successful
pregnancy, occurring in two of the above cases.
M. Nguyen*, N.O. Ekeke, Oakland, CA.
A Useful Approach to Achieve Hemostasis: Factor IX Desensitization for
Hemophilia B Introduction: Hemophilia B is the less common of the inherited
bleeding disorders. Factor IX infusions remain first line therapies during a bleeding crisis. Hypersensitivity to this compound severely restricts treatment options
for affected patients. Currently, there is little research showing the utility of desensitization with factor IX in such a setting, for its future use as an acute therapy. How
does an allergist proceed to offer such a treatment to a Hemophilia B patient with
this allergy? Case: The patient is a 19 yo man with Hemophilia B, and a documented allergy to factors VIII and IX. At age 2, he had an episode of urticaria,
hypotension, and loss of consciousness with exposure to factor IX. Since then, he
has been receiving factor VII with generalized pruritus with each treatment. The
limited availability and cost of factor VII made it a less desirable mode of treatment. The patient had been admitted earlier this year for a severe hemarthrosis of
the R arm. During this recent admission, he was admitted the ICU for inpatient factor IX desensitization. His prior PTT was > 300, H/H was 12.9/38.3. He had no
bleeding episodes at that time. Methods: Skin prick testing was done at full strength
M. Nguyen, N.O. Ekeke*, Oakland, CA.
Introduction: Antibiotic hypersensitivity is common to patients with a history of frequent hospitalizations or infections. Often, penicillin is the offending agent. This limitation in antibiotic therapy need not impede proper treatment when other non-penicillin agents are equally effective. But, if a
Cephalosporin or Carbapenem is the preferred drug, how does an Allergist manage the infection? Case: The patient is a 62 yo woman with small cell lung
cancer and past medical history of penicillin allergy, who developed urticaria
and severe angioedema during outpatient Augmentin therapy for chronic sinusitis. She was admitted with neutropenia, and was treated with antihistamines
and high-dose steroids. She later developed pneumonia and septic shock, blood
cultures positive for Pseudomonas. ANC on admission was 1.1, WBC -0.6,
Hgb-10.6, Hct-30.8. Per ID recommendations, Meropenem was an appropriate treatment based on bacterial culture and sensitivities. Skin prick test to penicillin was equivocal. Methods: The patient was treated using the 12-step protocol for drug desensitization designed by Maria Castells. Three separate 250ml
solutions are prepared containing the antibiotic at different concentrations 0.011 mg/ml, 0.114 mg/ml, 1.131 mg/ml respectively. Initial rate for solution
#1 is 2ml/h, with increases at 15 min intervals for a total of one hour (2.5x, 2x,
2x). This technique is applied for the second and third solutions, with initial
rates of 5ml/h and 10ml/h respectively. The final infusion occurs over 174
min. The patient had no adverse reaction to the medication during the procedure. Conclusions: Patients with deficient innate immunity from chemotherapy, are vulnerable to Type I hypersensitivity reaction- due to the separate cellular pathway of this immune response. The rapid drug desensitization protocol
is useful for patients with drug allergy in need of antibiotics, and the allergist
should direct the protocol’s implementation as a standard of practice.
C.J. Ocampo*, R. Shah, C. Saltoun, Chicago, IL.
G. Owens*, T. Green, Pittsburgh, PA.
Individuals with common variable immunodeficiency (CVID) have
markedly reduced levels of circulating immunoglobulins and a minimal or
absent response to immunization. Hence, they are prone to recurrent infections,
malignancies, and other disorders. Up to 20% of CVID patients have autoimmune conditions such as idiopathic thrombocytopenia purpura (ITP), autoimmune hemolytic anemia, and granulomatous disease. Interestingly, in the majority of cases, autoimmune disease is the initial presenting condition, with CVID
diagnosed afterwards. We describe a 22-year old female 34 weeks pregnant
with a history of ITP seen for evaluation of immunodeficiency. Over the preceding 12 months she had five infections (bronchitis, UTI, 2 URIs, and a diarrheal illness) requiring antibiotics. She did not have frequent infections previously, nor as a child. Her history is significant for ITP, diagnosed 1 year earlier,
requiring steroids and platelet transfusions. Six months later she developed
pleuritic chest pain and was found to have mediastinal and abdominal lymphadenopathy, and splenomegaly, raising suspicion for sarcoidosis or lymphoma. At the same time she discovered she was pregnant, and further diagnostic testing was postponed. Additional workup confirmed the diagnosis of
CVID with quantitative IgG = 198 mg/dL (normal 750-1700 mg/dL), IgA =
14 mg/dL (normal 82-400 mg/dL), and IgM = 58 mg/dL (normal 46-304
mg/dL). She had absent specific IgG antibodies to 13 of 14 Streptococcus pneumoniae serotypes tested. Treatment of CVID in pregnancy is essential for protecting the fetus from neonatal infection and providing subsequent passive
immunity. She received 3 IVIG infusions (400mg/kg) 2 weeks apart prior to
delivery with no adverse reactions and no additional infections. It is important
to characterize the degree of passive transfer of immunoglobulins to the newborn, which has been reported. Also, bronchoscopy and transbronchial biopsy
are planned to evaluate the lymphadenopathy postpartum. The pathogenesis of
autoimmunity in CVID is unknown. Theories postulate that autoimmune B cells
are not efficiently eliminated in CVID because of abnormal B cell receptor signaling pathways. This case is an informative example of the complex pathology seen in an individual with CVID and the challenges posed by pregnancy
during treatment of this disease.
K. Otsu*1, S.C. Dreskin2, 1. Denver, CO; 2. Aurora, CO.
INTRODUCTION: Intraoperative anaphylaxis is a potential life-threatening immediate-hypersensitivity reaction that occurs due to the release of preformed and newly synthesized mediators from basophils and mast cells. CASE
PRESENTATION: This is a 54 year old male with no history of previous allergic diseases who has had four previous surgeries with general anesthesia. One
month prior to being evaluated at the University of Colorado Hospital Allergy
Asthma and Immunology Practice, he underwent an elective laparoscopic cholecystectomy. Within minutes of receiving midazolam, lidocaine, propofol, succinylcholine and cefoxitin he became hypotensive to 103/66. Volume expanders
(Plasma-lyte and HextendВ®) were given through a peripheral IV and his blood
pressure normalized. Over the next 10 minutes, he was given vecuronium,
fentanyl and propofol and a surgical incision was made. Immediately thereafter, he appeared to jerk and flushing was noted on the face and upper chest.
His blood pressure dropped to 63/37 with sinus bradycardia between 30 and
40 bpm. He then progressed to asystole. Cardiopulmonary resuscitation was
successful with full recovery. The tryptase level in serum obtained 1 hour after
the event was 91ng/ml (total) and 36ng/ml (mature) and increased to 132ng/ml
(total) and 37nl/ml (mature) at four hours. Two months after the event, skin testing was conducted to test for possible allergy to vecuronium, succinylcholine,
propofol, cefoxitin, lidocaine, bupivicaine, fentanyl, HextendВ®, and Plasmalyte. All tests were negative except for a positive intradermal skin test with full
strength HextendВ®. This same material gave a negative skin test in two controls (KO and SCD). CONCLUSIONS: Elevated levels of tryptase immediately following this episode demonstrates that this was intraoperative anaphylaxis. The results of the skin tests strongly suggest that this was an IgE-mediated
hypersensitivity reaction to HextendВ®.
Introduction: Common Variable Immune Deficiency (CVID) is a primary
immunodeficiency associated with a spectrum of disorders including recurrent
infections, autoimmune and gastrointestinal diseases, and malignancy. As symptoms typically develop over years, the diagnosis of CVID is commonly made 5
to 7 years after onset of symptoms. We present a patient with acute gastrointestinal symptoms, severe weight loss, and respiratory failure who was found to be
agammaglobulinemic and diagnosed with CVID. Case: Our case involves a previously healthy female with an infectious history limited to two to three episodes
of otitis media per year. At age 18 years she acutely experienced diarrhea, loss of
appetite, and weight loss of 30 pounds (from 110 to 80 lbs) over 2 weeks followed closely by the development of fever and cough. She was diagnosed with
bilateral pneumonia, admitted to the ICU, and intubated for increasing respiratory distress. She was found to have no measurable IgA, IgG, or IgM. Endoscopy
with biopsies was performed revealing crypt abscesses, increased intraepithelial
lymphocytes, and villous atrophy consistent with an autoimmune enteropathy.
She was later found to have a positive giardia serology and started on metronidazole although this was not thought to explain her endoscopy findings. Her IgG
level stabilized after IVIG administration indicating her agammaglobulinemia
was not secondary to GI loss. She was also found to be anemic, neutropenic, lymphopenic and have slightly decreased B cells. Proliferative responses to mitogens
were normal and she had negative serologies for tetanus, diphtheria, and pneumococcus. Discussion: While complete agammaglobulinemia and pancytopenia
are sometimes features of CVID, the dramatic nature of this patient’s presentation is unusual given the severe, concurrent infectious and autoimmune manifestations in the face of a relatively benign past medical history. Conclusion: CVID
may present acutely and dramatically and it should be considered in the differential of similar patients. (Our patient is currently being evaluated by the National
Institutes of Health to help identify her B cell maturation defect. We expect to be
able to report findings by the 2010 meeting.)
P. Paranjpe*, D. Khan, Dallas, TX.
Introduction: Aspirin (ASA) and non-steroidal anti-inflammatory drugs
(NSAIDs) can cause a variety of hypersensitivity reactions. Successful challenge-desensitizations have been reported in aspirin exacerbated respiratory
disease and ASA-induced urticaria/angioedema without underlying chronic
urticaria. We report a failed challenge-desensitization in a patient with ASAinduced urticaria/angioedema. Methods: A 52 year old female with history of
hypertension and coronary artery disease presented with unstable angina. Cardiac catheterization with possible coronary stent placement was recommended.
However 25 years prior, the patient had an episode of aspirin hypersensitivity.
Per our patient, she had taken aspirin previously without adverse reaction. She
received the first dose of aspirin without symptoms. One hour later, a second
dose was given. Thirty minutes following the second dose, she developed tongue
swelling and generalized urticaria. No dyspnea, wheezing, nausea, or hypotension was noted. It was unclear if any treatment was given or how long her symptoms persisted. She has since avoided aspirin and NSAIDs. Results: Due to this
history, the patient was transferred to the ICU. Prior to the rapid oral challengedesensitization, vitals were pulse of 67, blood pressure of 130/81 mmHg, and
oxygen saturation of 97% on room air. The protocol administered ASA doses
every 15 minutes: 0.1 mg, 0.3 mg, 1 mg, 3 mg, 10 mg, 30 mg, 40 mg, 81 mg,
162 mg, and 325 mg. She complained of sweating after the 40 mg dose, and
her blood pressure had been decreasing over the preceding 105 minutes. The
protocol was aborted when mean arterial pressure (MAP) fell to 40 mmHg
following the 81 mg dose. Dyspnea, angioedema, and urticaria were not documented. She received intravenous fluids and oral anti-histamines but not epinephrine. She continued to have low MAPs (51-65 mmHg) over the next few
hours. Tryptase obtained during the prolonged hypotension was 6.9Вµg/L.
Twenty-four hours later, blood pressure had returned to normal. No other etiology for her hypotension was discovered. Subsequently, her angina was managed with a medical regimen, and cardiac catheterization was not pursued. Conclusion: This failed desensitization to aspirin highlights the risk in undertaking
procedures to induce drug tolerance in which the mechanism of the drug reaction is unknown.
D. Park*1, N.P. Tran2, J.M. Duncan2, D.B. Lew2, 1. Cordova, TN; 2. Memphis, TN.
F. Valaie*, S.R. Patel, Los Angeles, CA.
Background: Momordica charantia (bitter melon) is popular in systems
of traditional medicine to treat diabetes, viral infections, immune disorders,
and AD. Its bioactivity in AD may be linked to induction of IFN-Оі and TGF-ОІ,
and stimulation of epidermal barrier homeostasis. While there is growing community interest in using crude preparations of bitter melon topically, there are
no clinical studies looking at its use for AD. Case Report: A 6 year-old female
presented with four years of refractory AD symptoms. Medical history was significant for allergic rhinitis, multiple food allergies, and family history of AD.
Previous therapies had included moisturizers, antihistamines, high potency topical corticosteroids, and four courses of oral steroids in the last year. On physical exam, the patient had severe AD on her arms, legs, hands, and feet with
skin atrophy and tightness and a SCORAD of 72.8. The AD limited range of
motion by 30В° in both knees and index fingers. Labs showed negative ANA
and anti-Scl 70, elevated total IgE 1,750 IU/ml, eosinophil count 700/mm3, and
nasal culture with heavy growth of Staphylococcus aureus. Skin tests were positive for multiple food and inhalant allergens. The patient was started on moisturizers, antihistamines, specific allergen avoidance, antistaphylococcal therapy, and pimecrolimus 1% cream twice daily to lesions on the right side of her
body (total use: 100 grams in one month) and a trial of topical bitter melon
three times daily to lesions on the left side of her body. The patient’s mother
prepared the bitter melon at home by boiling it, then pureeing it to a paste consistency. In one month, the patient returned significantly better, with equal
improvement on the pimecrolimus treated side as compared to the bitter melon
treated side. She now had full range of motion in both knees and a SCORAD
of 44.6. There was no phytodermatitis from using the bitter melon. Conclusions: Topical bitter melon may be a beneficial steroid- and pimecrolimus-sparing herbal medicine for severe AD in some patients. Further studies are needed
to isolate the phytocomponents that mediate its effects and to determine what
bearing they have on AD.
J.H. Park*, C. Cunningham-Rundles, New York, NY.
Introduction: Initially regarded as a pure deficiency of cellular immunity
from T cell defects, DiGeorge syndrome now represents a chromosomal disorder with highly variable phenotypic expression and immunologic defects. In
addition to characteristic T cell abnormalities, humoral abnormalities and
autoimmune disease have been described in recent years in some patients with
DiGeorge syndrome. Here we present a case of a young man with DiGeorge
syndrome who later developed hypogammaglobulinemia and massive
splenomegaly. Case: JD is a 20 year old male diagnosed with DiGeorge syndrome in infancy by FISH. He underwent cardiac repair in infancy and was
started on calcium for hypocalcemia early on. At age 5, he developed hypogammaglobulinemia (IgG=17 mg/dL, undetectable IgA) in the setting of frequent
respiratory infections, along with poor antibody response. A concern for common variable immunodeficiency was raised, and he was started on intravenous
immunoglobulin with a good clinical response. At age 10, he developed
splenomegaly with a marked increase in its size over the past 2-3 years, currently his spleen tip reaching the right lower quadrant of his abdomen. The
splenomegaly has been refractory to multiple doses of steroid and Remicade.
He subsequently developed thrombocytopenia, with platelet count ranging
around 50K. Around the same time, he also developed generalized lymphadenopathy (about 1.5-2.0cm in size) with biopsy demonstrating non-caseating granuloma. More recently, in the past 2 years, he developed hypercalcemia
(iCa 1.78 mmol/L) off calcium supplement responsive to steroid, and a markedly
increased level of IgM (3220 mg/dL) in the setting of normal expression of
CD40L by flow cytometry. Calcium dysregulation is a persistent problem now
with episodes of hypocalcemia (iCa 0.93 mmol/L) after steroid and bisphosphonate administration. Conclusion: JD represents a case of DiGeorge syndrome with unusual clinical features, including hypogammaglobulinemia now
with a markedly increased IgM, massive splenomegaly, granuloma, and calcium dysregulation. Although the question remains as to how to best tie all
these features to the underlying DiGeorge syndrome, the case still demonstrates
the highly variable phenotypic expression and immunologic defects of this syndrome. The biggest challenge now is how to formulate the best treatment option
in this complicated case.
Introduction: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and
cervical adenitis) is a chronic disease of the unknown etiology, characterized
by abrupt onset of cyclic episodes of high fever associated with aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy. Patients are asymptomatic in-between episodes. PFAPA first was described on 1987; however there
still are many unknown facts about it. It is probably the least known amongst
the periodic fever syndromes. This syndrome has been usually described in
patients less than 5 years. Currently just a few cases of this syndrome in adolescents have been described, and to the best of our knowledge, none have
been associated with menstruation. Case: A fourteen year old Hispanic female
with a two year history of recurrent monthly fevers (up to 40.5 C), chills,
throat pain, swollen red tonsils, and aphthus ulcers. These episodes occurred
around the time of her menstruation. Her episodes were 5-7 days long, and she
was well in between. Her work up included evaluations for immunodeficiency,
collagen vascular disease, allergies, and multiple infectious causes. All of which
was negative. Adeno-tonsillectomy at age 13, did not alleviate her symptoms.
She was empirically treated with oral steroids, which aborted her episodes. Discussion: Compared to multiple previously published case reports and case series
our patient showed some different characteristics and can be reported as a unique
case of PFAPA, which potentially can broaden the diagnostic criteria: Ethnicity: Our patient is Hispanic. Previous reports showed mainly a Mediterranean
predilection. Pade et al, on 1999 reported a series of 28 patients, all of whom
originated from Mediterranean or nearby countries. Age of onset: Multiple
reports indicate the syndrome usually begins around age 4, however in our
patient the age of onset was 12Y. Effectiveness of surgery: Tonsillectomy is
considered therapeutic for these patients. Overall effectiveness of tonsillectomy
alone and tonsillectomy with adenoidectomy is reported 75% and 86%, respectively; however our patient shoed only a minimal improvement. Association
with body rhythms: To our knowledge no report showed any association with
other body rhythms. Our patient is the first reported case of definite association with menstruation.
N.S. Patel*1, S.M. Fung2, A. Zanichelli3, M. Cicardi3, J.R. Cohn2, 1. Wilmington, DE; 2. Philadelphia, PA; 3. Milano, Italy.
Introduction: Acquired deficiency of C1 inhibitor (C1-INH) can be caused
by auto antibodies to C1-INH rapidly catabolizing the protein. The resulting
deficiency exposes to angioedema recurrences (Acquired angioedema, AAE)
mediated by bradykinin released upon contact system activation. Replacement with C1-INH and specific inhibition of the bradykinin releasing enzyme
plasma kallikrein with ecallantide, a potent kallikrein inhibitor, have been successful in the treatment of angioedema due to hereditary C1-INH deficiency.
C1-INH has been used in the treatment of AAE, but due to the rapid catabolism, some patients do not respond. Therefore we evaluated ecallantide as alternative treatment for AAE and here we report three patients successfully treated
with ecallantide, a total of 13 times. Objective: To assess ecallantide for treatment of attacks in AAE. Methods: Written informed consent and IRB approval
were obtained for administration of ecallantide for an acute AAE exacerbation.
Three patients with a diagnosis of AAE and autoantibodies to C1-INH were
treated and clinical responses were recorded. Results: Patient 1, a 47 year old
female, presented with an acute abdominal attack and was treated with 30 mg
of ecallantide subcutaneously. Ten additional episodes of acute abdominal
attacks were similarly treated, resulting in resolution of symptoms within 4-8
hours of drug administration. Patients 2 and 3, 47 and 66 year old males, presented with acute lip swelling. Patient 3 had a well documented history of resistance to replacement therapy with C1-INH. They were treated with 80mg of
intravenous ecallantide. Lip swelling resolved within 4 and 2 hours respectively
after drug administration. In both patients angioedema relapsed after 8 hours,
but it was mild and resolved spontaneously. Ecallantide was well tolerated,
and no adverse effects were observed. Conclusion: Inhibition of kallikrein with
ecallantide appears to be a suitable approach to the treatment of AAE and may
represent an important alternative for those patients who are resistant to C1INH replacement therapy.
C.S. Patel*1, K.L. Marks1, R.W. Hostoffer2, 1. Philadelphia, PA; 2. Cleveland, OH.
Rationale: Data are inconclusive regarding the clinical relevance of mannose-binding lectin (MBL) deficiency; however, mounting evidence points to
an association with poorer outcomes. MBL replacement may offer a therapeutic
option in select cases to prevent severe complications. Methods: Case Review
Results: 50 year old non-smoking male with allergic rhinosinusitis, mild asthma
and allergic bronchopulmonary aspergillosis (ABPA) presented with recurrent fungal pneumonia complicated by chronic necrotizing pulmonary
aspergillosis (CNPA) resulting in left upper lobectomy followed by 1 month of
amphotericin B and itraconazole for tissue and sputum culture positive
Aspergillus fumigatus. No history of abscesses, eczema or any other recurrent
infections and PPD negative. Cough recurred 1 week after antibiotics stopped
and sputum and bronchoalveolar fluid cultures positive for Scopulariopsis and
Aspergillus, respectively. Treated with 6 months of caspofungin and prednisone
20mg then maintained on prednisone 10mg qOD and advair 500/50 BID. Workup revealed an undetectable MBL level (<25ng/mL) without other immune
defects: normal nitroblue tetrazolium test, quantitative and specific
immunoglobulins (to pneumococcus and tetanus), CH50, CD16/56+ cells and
T-cell proliferation to Candida. Absolute CD3+ and CD19+ cells were initially
decreased at 613 (range 710-4,180) and 25 (range 70-910), respectively; however, fraction of CD3+ cells were normal at 73% (range 59-87%), consistent
with acute infection with normalization after antibiotic course: CD3+ 1,349
(67%) and CD19+ 141 (7%). IgE 1,449 (range 3-48) and eosinophils 1,832
(range 0-450), consistent with ABPA. Conclusions: MBL-deficiency in the setting of an underlying infectious burden, e.g. ABPA, can lead to worse outcomes,
e.g. CNPA. This case supports the hypothesis that MBL plays an important role
in modulation of the severity of certain infections. In vitro studies have shown
strong MBL binding to Aspergillus and retrospective analyses have found
patients with CNPA to have low levels of MBL vs controls. Additionally, murine
models have shown MBL replacement increases host defense and survival
against invasive Aspergillus. Taken together, MBL-deficiency may be clinically
relevant in certain populations and replacement may confer resistance to invasive fungal infections.
trol at 10 weeks which was presumed to have no effect because eosinophils
continued to decline with 768 eosinophils by 15 weeks and normalized to 200
at 30 weeks. CONCLUSION: This case likely represents hypersensitivity syndrome due to celecoxib. It also illustrates the prompt clinical improvement yet
much slower resolution of eosinophilia and other enzyme abnormalities.
A.M. Patterson*, R.A. Friedman, Columbus, OH.
Introduction: Influenza vaccines (seasonal and H1N1), cultured in chick
embryoblasts, are generally contraindicated in egg-allergic patients, as well as
in those who have experienced severe adverse reaction to other vaccine components. Some theorize that egg-allergic patients who tolerate influenza vaccine once will likely tolerate it again. We present two cases of adverse reaction
to H1N1 influenza (H1N1) vaccine after tolerating seasonal influenza (SI)
immunization. Methods: Patients were seen in clinic, and follow-up reports
obtained by review of medical record, telephone and e-mail. Results: Case 1
was a previously egg-allergic adult male, who currently tolerates eating some
egg, presenting for influenza vaccination. Skin-prick testing to egg was negative, and he tolerated SI vaccine well. Three weeks later, he received H1N1 vaccine, and within 4 hours had itchy, swollen throat, runny nose, and limited shortness of breath. Case 2 is a non-egg-allergic, 8 year old female who has tolerated
seasonal flu shots yearly since infancy. 2 hours after SI vaccine this year, she
developed itchy, erythematous, macular rash. Patient was dealing with chronic
rash at the time, so it was initially unclear if the new eruption was exacerbation of ongoing rash or reaction to vaccine. She later received H1N1 vaccine
and developed similar rash. Specific IgE testing revealed sensitivity to both
beef and porcine gelatin. Subsequently, we held a flu vaccine clinic for eggallergic patients, where several patients tested positive (skin prick or intradermal) to one, but not both, of either SI or H1N1. Conclusions: Influenza vaccine lots (SI and H1N1) may vary in amount of allergenic components, making
it unsafe to assume tolerance between lots. We suggest that any egg- or gelatin-allergic patient or anyone with history of severe reaction to any type of
influenza vaccine should be tested to the specific vaccine lot number they will
be given prior to immunization or graded drug-challenge. Do not assume that
egg- or gelatin-allergic patients who have tolerated influenza vaccine in the
past will tolerate it again.
M.O. Paterniti*, B.S. Bochner, S.S. Saini, Baltimore, MD.
RATIONALE: Hypersensitivity syndrome, also known as Drug Rash with
Eosinophilia and Systemic Symptoms (DRESS), is a severe multi-organ iatrogenic reaction. Several drugs have been implicated in this syndrome. We report
a case of a previously healthy 59 year-old male who we suspect experienced
this reaction due to celecoxib. METHODS: This patient was evaluated for potential causes of eosinophilia and followed clinically without treatment other than
discontinuation of suspected drugs. RESULTS: Celecoxib, amlodipine and
benazepril were started on the same day, the latter two replacing hydrochlorothiazide to improve control of hypertension. This otherwise healthy 59 y/o male
was on no other medications. One week later he noted fever and myalgias.
One week after symptom onset, laboratory evaluation showed WBC of 45,000
with 6,300 eosinophils, Alk phos 539, AST 32 and ALT 95 prompting hospitalization. Celecoxib, amlodipine and benazepril were stopped. WBC peaked
5 days after the initial evaluation at 86,000 with 34,000 eosinophils and a nonblanching, macular rash developed. Tryptase, FIP1L1, TCR rearrangement and
clonal studies were normal. IgE was elevated at 1220 kU/L and B12 was >2000
pg/mL. CT abdomen/pelvis showed mild hepatosplenomegaly and subcentimeter abdominal lymph nodes. MRI of the brain, echo, PFTs, stool, urine and
blood cultures were all normal. Bone marrow biopsy was consistent with reactive eosinophilia. Skin biopsy showed neutrophilic and eosinophilic perivascular and interstitial infiltrates. Rash and other signs and symptoms resolved
3 weeks after stopping suspected medications, as did the Alk phos, AST and
ALT. After 9 weeks WBC decreased to 8,500 with 1,200 eosinophils. Patch
testing to celecoxib, amlodipine and benazepril at that time was negative. Leukocyte toxicity assay, which exposes lymphocytes in vitro to drug metabolites,
showed 18% toxicity to celecoxib, 2% to benazepril and 5% to amlodipine with
a normal value being 12.5%. Benazepril was restarted for blood pressure con-
Y. Persaud*1, M. Abraham2, R. Ramdeo2, P. Parsi1, 1. Bronx, NY; 2. New
York, NY.
Etanercept, a biologic modifier, is a TNF-О± soluble receptor fused to the
Fc fragment of IgG. It is used for symptomatic treatment of Juvenile and Adult
Rheumatoid Arthritis, Psoriatic Arthritis, Reactive Arthritis, and Ankylosing
spondylitis. However, many patients discontinue treatment due to intolerable
adverse effects, which includes serious infections such as the reactivation of
latent tuberculosis, invasive fungal infections and other opportunistic pathogens.
Another side effect is hypersensitivity reactions which can occur via CD4+ T
lymphocytes or IgE mediated reactions. Although data tends to favor the IgE
mediated mechanism, these reactions typically exhibit themselves as skin lesions
such as injection site reactions (ISRs) that can lead to urticarial eruptions, erythema, pain, pruritis, edema, plaques, eosinopilic cellulitis and even recall reactions at prior sites. The ISRs appear within the first 2 months of treatment and
tend to diminish in frequency over time. Other adverse reactions include
angioedema and anaphylaxis. We present a patient who was successfully desensitized and was able to resume etanercept treatment despite having severe hyper-
sensitivity reactions. We present a 53 year old male with a history of HepC,
DM, Angina and unbearable Rheumatoid Arthritis. His medication history
included severe hypersensitivity reactions to methotrexate, infliximab, adalimumab, leflunomide, and sulfazine. While being treated with etanercept, he
developed unbearable itching, diffuse urticaria and shortness of breath. However, the symptoms of rheumatoid arthritis only improved with etanercept. After
a careful review of risk vs. benefits, it was decided to initiate a desensitization
procedure to etanercept to induce immunologic tolerance. He was able to tolerate a total of 12.5 mg during his first session, and an additional 12.5 mg during his second session after a week. He was observed for 30 minutes after each
dose and 1 hour after each session, without incident. Since his arthritis symptoms were not controlled, he was put on 25 mg twice a week with only mild
urticarial reactions. Desensitization to etanercept has not been widely performed. Care must be taken during the procedure to avoid any serious complications. In patients with intolerable hypersensitivity reactions to etanercept,
desensitization is still a treatment option. However, risk vs benefits must be
addressed in each case.
Desensitization Protocol
N. Poliak*, J.S. Orange, P.F. Weiss, Philadelphia, PA.
Introduction: Eosinophilic fasciitis (EF) is a rare disorder that typically
presents with symmetric swelling, pain, and stiffness of extremities associated
with eosinophilia. The hands and feet are usually spared. The mean age at diagnosis is 40 to 50 years. Due to rarity and varying symptoms, diagnosing EF can
be challenging, especially in pediatric population. We report an interesting pediatric case of EF that initially presented with diffuse edema of the face, hands,
and feet. Methods: Case report Case report : A 5-year-old previously healthy
male developed acute, diffuse edema and erythema of the face, abdomen, and
extremities including the hands and feet. His white blood count was
12,600cell/uL with 51% eosinophils (absolute eosinophil count (AEC) of 6426
cells/uL). Based on his symptoms, he was initially diagnosed with angioedema
and treated with antihistamines and oral steroids. When the symptoms reoccurred and eosinophilia persisted, he underwent extensive evaluation. Infections, malignancy, immunodeficiency, and drug reaction were ruled out. A thorough family history revealed a cousin diagnosed with EF. Patient’s MRI of lower
extremities showed thickened and increased signal in the fascia surrounding
the muscles. Full thickness skin biopsy showed fascia and adjacent adipose tissue with a perivascular infiltrates of eosinophils and eosinophils present in a
deep dermal perivascular pattern consistent with EF. Our patient was initially
treated with oral steroids and oral methotrexate but continued to have progressive subcutaneous induration. He also developed peau d’orange changes
of all extremities. Subsequently his therapy was escalated to weekly intravenous
methylprednisolone, oral steroids, methotrexate, and infliximab (10 mg/kg)
with gradual improvement. In response to therapy his range of motion has
improved and AEC has dropped to 159cells/uL. Conclusion: EF has various
clinical presentations making diagnosis challenging. When pediatric patient
presents with recurrent edema of the extremities and peripheral eosinophilia,
it should not be confused with angioedema and EF should be considered. Some
patients with EF are resistant to steroids and methotrexate. Thus, other therapeutic options e.g. infliximab should be considered. Family history might be a
risk factor and a helpful diagnostic clue. Early diagnosis and intervention are
associated with better prognosis.
N. Poliak*, J.S. Orange, P.F. Weiss, Philadelphia, PA.
Introduction: Eosinophilic fasciitis (EF) is a rare disorder that typically
presents with symmetric swelling, pain, and stiffness of extremities associated
with eosinophilia. The hands and feet are typically spared. The mean age at
diagnosis is 40 to 50 years. Due to rarity and varying symptoms, diagnosing
EF can be challenging, especially in pediatric population. We report an unusual
pediatric case of EF that presented with diffuse edema of the face, hands, and
feet, thus suggesting the need to extend the differential of angioedema-like
findings. Methods: Case report Case report : A 5-year-old previously healthy
male developed acute, diffuse edema and erythema of the face, abdomen, and
extremities including the hands and feet. His white blood count was
12,600cell/uL with 51% eosinophils (absolute eosinophil count (AEC) of 6426
cells/uL). Based on his symptoms, he was initially diagnosed with angioedema
and treated with antihistamines and oral steroids. When the symptoms reoccurred and eosinophilia persisted, he underwent extensive evaluation. Infections, malignancy, immunodeficiency, and drug reaction were excluded. A thorough family history revealed a cousin diagnosed with EF. Lower extremity MRI
showed thickened and increased signal in the fascia surrounding the muscles.
Full thickness skin biopsy showed fascia and adjacent adipose tissue with a
perivascular infiltrates of eosinophils and eosinophils present in a deep dermal perivascular pattern consistent with EF. Our patient was initially treated
with oral steroids and oral methotrexate but continued to have progressive
subcutaneous induration. He also developed peau d’orange changes of all
extremities. Subsequently his therapy was escalated to weekly intravenous
methylprednisolone, oral steroids, methotrexate, and infliximab (10 mg/kg)
with gradual improvement. In response to therapy his range of motion has
improved and AEC has dropped to 159cells/uL. Conclusion: EF has various
clinical presentations making diagnosis challenging. When pediatric patients
present with recurrent edema of the extremities with peripheral eosinophilia,
typical considerations of angioedema should be extended to include EF. Furthermore, some patients with EF are resistant to steroids and methotrexate.
Thus, other therapeutic options e.g. infliximab should be considered. Family
history might be a risk factor and a helpful diagnostic clue.
P. Poowuttikul*, E. Secord, P. Britto-Williams, Detroit, MI.
Introduction: Acquired Angioedema associated with Lymphoproliferative
disorders is well established. Most cases are associated with an acquired decrease
in C1 inhibitor quantitative or qualitative secondary to lymphoproliferative conditions. We report a patient with recurrent Angioedema of the face and neck
requiring multiple intubations as an early manifestation of a low grade B-cell
lymphoma and with normal quantitative and qualitative (functional) C1 inhibitor
levels whose diagnosis was delayed because the Angioedema was falsely attributed to ACE inhibitor. Methods: A 59 yr old man with a past medical history
significant for hypertension, Hepatitis C, recurrent DVT’s, ESRD on Hemodialysis for 16 years, s/p renal transplant with acute rejection 4 years prior now on
Peritoneal dialysis for the past 3 months presented to the ER with worsening
Angioedema of the face and neck for the past 5 days. Results: He was recently
started on an ACE inhibitor (Lisinopril) about 10 days ago and 5 days prior to
the current presentation when he started noticing swelling of his face he discontinued it. Initially the Angioedema was attributed to the delayed clearance
secondary to the ESRD of the ACE inhibitor which had a half life of 12 hours.
The patient required intubation and then discharged 2 days later when edema
subsided. However the patient returned again a week later with recurrent
Angioedema of the face requiring intubation again. C1 esterase inhibitor level
was 49 (21-39) mg/dl and the C1 functional was 116385 (75672-190932)
Units/mL. Serum electrophoresis was normal. CT of the chest showed mediastinal lymph nodes. CT of the abdomen showed splenomegaly, calcified granulomata of the liver and a small amount of ascitis. Biopsy and Flow cytometric analysis of a supraclavicular node revealed a lambda monotypic population
with expression of CD 19, CD 20, CD 23 and co-expression of CD 5. FMC 7
was not expressed. The morphologic and immunophenotypic findings were
consistent with a Low-grade B-cell lymphoma, consistent with Chronic Lymphocytic Leukemia. The patient was referred for chemotherapy and the
Angioedema subsided with the treatment for the lymphoma. Conclusion: Late
onset recurrent Angioedema in older adults and especially in the elderly, should
prompt physicians to initiate work-up for lymphoproliferative disorders.
immunocompromised state is not already present. Although chronic diarrhea
can be seen in IgA Deficiency, a stool culture should be considered in these
patients especially when symptoms worsen.
C. Prasad*, Rochester, MN.
T.R. Prematta*, F. Ishmael, T. Craig, Hershey, PA.
INTRODUCTION: Good syndrome is the combination of thymoma and
adult-onset primary immunodeficiency characterized by a profound deficiency
in B cells and hypogammaglobulinemia. Despite its fairly classic presentation, its rare incidence can cause diagnostic delays and thereby significant morbidity and mortality. CASE: A 66-year-old man presented for evaluation of a
1-year history of cough and recurrent sinusitis despite multiple courses of antibiotics. Physical exam was remarkable for mucopurulent post-nasal drainage,
tenderness to palpation over the frontal and maxillary sinuses, and faint crackles in the left lung base. A chest x-ray revealed an anterior mediastinal mass
and findings consistent with prior coronary artery bypass grafting. Biopsy
was consistent with an encapsulated thymoma. Thymectomy was not pursued
given its small size and history of sternotomy. The patient initially responded
well to a prolonged course of antibiotics for chronic sinusitis but went on to
develop worsening productive cough. Physical exam revealed pronounced crackles in the left lung base as well as egophony, whispered pectoriloquy, and dullness to percussion. Chest x-ray showed a left lower lobe infiltrate. Sputum gram
stain revealed gram positive cocci in chains and Streptococcus pneumoniae
antigens were found in the urine. CBC was normal. Testing for HIV was negative. Flow cytometry showed normal numbers of T-cells but a complete absence
of B-cells. IgA, IgM, and IgG levels were all profoundly low. The combined
presence of thymoma with adult-onset immunodeficiency was consistent with
the diagnosis of Good syndrome. After antibiotic therapy, monthly immunoglobulin replacement was initiated and the patient has continued to avoid any infections. The thymoma is being followed and has not progressed. CONCLUSION:
This case illustrates the classic presentation of Good syndrome. Patients present with an anterior mediastinal mass and recurrent sinopulmonary infections
caused by encapsulated bacteria. Clinical and laboratory findings include thymoma, hypogammaglobulinemia and a deficiency or complete absence of B
cells. Recognition of Good syndrome and distinguishing it from solitary thymoma without immunodeficiency is crucial as the severe deficit in cell-mediated immunity is an important cause of morbidity and mortality in this disorder. Once recognized, it is easily treatable with immunoglobulin replacement.
Introduction Hyperimmunoglobulin-D syndrome (HIDS) is an autoinflammatory disorder presenting with periodic fevers. It is caused by mutations
in the mevalonate kinase (MVK) gene and is characterized by elevated IgD levels. We present a case, and a review of the literature, of a patient with atypical
HIDS who responded to montelukast. Methods Ovid and PubMed were searched
with the following terms: HyperIgD, HIDS, mevalonate kinase deficiency, treatment, management, montelukast and Singulairв„ў. Case Report A 15 year old
female with a history of allergic rhinitis (AR) and exercise-induced bronchospasm (EIB), presented for evaluation of recurrent fever. Episodes occurred
every 2-4 weeks for 2 years and lasted 3-4 days, regardless of antibiotics. Symptoms included temperature to 103В°F, lymphadenopathy, splenomegaly, arthralgias and headache. In between episodes, she felt well. Labs reviewed at presentation revealed intermittent leukocytosis and elevated ESR. Extensive immune
assessment was normal except IgD level was elevated (491 mg/L (NL <140))
on 3 separate occasions. She was treated with oral corticosteroids for one episode
with resolution of symptoms in about 1 day. For her EIB and AR she was placed
on montelukast. A few weeks after starting montelukast, febrile episodes essentially resolved. Over the last year, she has only had 3 additional episodes of
fever, with milder symptoms, less severe fever (T max 101В°F) and shorter duration of fever (1-3 days). Results Literature review revealed a number of proposed treatments for HIDS including NSAIDs, corticosteroids, statins, etanercept, thalidomide and anakinra; several of which have mixed results. No
studies have looked at the effectiveness of leukotriene antagonists for HIDS.
Conclusion This is the first known reported case of a patient with atypical HIDS
who responded to montelukast. Controlled studies are needed to prove the efficacy of montelukast. However, given the safety profile of this drug, montelukast
may be a reasonable treatment option to try for patients with HIDS.
E.T. Pratt*, K. Paris, New Orleans, LA.
Introduction: Patients with selective IgA deficiency are at increased risk
for gastrointestinal disorders including celiac disease, milk intolerance/allergy,
inflammatory bowel disease and infections. They are known to have increased
incidence of diarrhea caused by common viral, bacterial, and giardia species,
but generally not by more invasive and unusual pathogens. Plesiomonas shigelloides (formerly known as C27 and Aeromonas shigelloides) is an oxidativepositive, facultatively anaerobic gram-negative bacillus found in both soil and
fresh or brackish water. It typically causes self-limited watery or secretory diarrhea especially after ingestion of raw seafood or exposure to reptiles and tropical fish. A prolonged course can occur. Extraintestinal manifestations, including skin, CNS, lung and blood infections, have been documented in acquired
immunodeficiencies, particularly HIV or liver disease, and can be fatal. There
are no documented cases of P. shigelloides infections in patients with Selective IgA deficiency. Case Description: An 18 month old male presented for
evaluation of food hypersensitivity due to a history of loose stools since infancy.
Family history was significant only for gluten sensitivity enteropathy. Evaluation revealed an IgA of less than 6.3mg/dl, and further investigation showed a
normal Anti-Gliadin IgG level which did not support a diagnosis of celiac disease. He continued to have chronic diarrhea and was treated empirically with
metronidazole as patients with IgA deficiency are susceptible to enteric infections. Subsequently he was evaluated for worsening, persistent watery diarrhea.
A stool culture was positive for the unusual bacteria Plesiomonas shigelloides.
He was treated with Bactrim and symptoms improved after 3-4 days. Discussion: Recognizing rare or unusual bacteria found in the gut in the appropriate
clinical setting should prompt measurement of immunoglobulins if a known
B.T. Prince*1, H. Tcheurekdjian2, 1. Cleveland Heights, OH; 2. Cleveland, OH.
Introduction: Tumefactive multiple sclerosis is a rare form of multiple sclerosis in which patients acutely develop large ring enhancing areas of demyelination in the central nervous system. Some tumefactive lesions are refractive
to standard therapies, but effective second-line therapeutic options have not
been established. Herein, we describe a case of rapidly progressive, treatmentresistant tumefactive multiple sclerosis that improved rapidly with the initiation of intravenous immunoglobulin therapy. Methods: Retrospective chart
review Results: A 38 year old with a history of biopsy proven tumefactive
multiple sclerosis that previously remitted during pregnancy was found to have
a new left frontal tumefactive lesion after presenting with worsening fatigue,
paresthesias, and forgetfulness. Over a four-month period, treatment with high
dose, intravenous glucocorticoids, glatiramer acetate, and plasmapheresis
showed no improvement in symptoms. Furthermore, during these treatments,
there was approximately a 1.5cm increase in the original tumor size with the
development of a second, right temporal lesion approximately 1.5cm in diameter. Intravenous immunoglobulin (IVIG) therapy was started with a loading
dose of 0.4g/kg daily for 4 days, followed by monthly infusions of 0.4g/kg. One
month after beginning IVIG therapy, the patient reported a significant improvement in symptoms. Three months after beginning IVIG therapy, serial MRIs
have documented a decrease in the original tumor size by approximately 1.5cm
and the complete resolution of the right temporal lesion with the persistence
of symptom improvement. Conclusion: IVIG may be an effective treatment
option for patients with treatment-resistant tumefactive multiple sclerosis.
M.T. Provido*, M.T. Patrimonio, Iloilo City, Philippines.
Objectives: 1.To report a case of cerebral venous thrombosis in a postpartum with Protein S Deficiency. 2.To review Protein S deficiency, its etiology,
pathogenesis, clinical manifestations, complications and managements. Setting: Iloilo Mission Hospital, Jaro, Iloilo City, Philippines Case Summary: Protein S deficiency is a genetic trait that predisposes one to the formation of
venous thrombosis. It is rare in the healthy population and occurs in about 1 in
20,000 people (1). Less than half develop thrombosis, usually between the ages
of 20 and 30 (2). Of all the inherited thrombophilic condition, it remains the
most difficult to diagnose. We present a case of a 30-year old G4P1(1-0-2-1)
patient at 36 5/7 weeks age of gestation, a known asthmatic with history of
recurrent rhinosinusitis since childhood. She was worked up and found negative for lupus anticoagulant and anticardiolipin antibody testing despite recurrent fetal losses. She delivered a live, full term baby boy via a primary low
transverse cesarean section with bilateral tubal ligation. Postpartum, she had
catastrophic thrombotic phenomenons with evidences of different organ involvements simultaneously occurring thereafter. She had episodes of chest discomfort with an electrocardiogram revealing 2nd degree AV block, Mobitz I with
anteroseptal wall ischemia. She complained of sudden blurring of vision and
had episodes of generalized seizure two days after. Plain cranial CT scan revealed
biparietal and left cerebellar parenchymal hypodensities. Brain MRI with MRA
and venogram revealed multiple infarcts bilateral and bioccipitoparietal areas.
There was narrowing of the M2 segment of the left middle cerebral artery. She
underwent effective anticoagulation with intravenous heparin and after the 14th
hospital day was discharged improved. Keywords: Protein S deficiency, pregnancy, venous thrombosis ________________ (1) Schafer AI. Thrombotic disorders: hypercoagulable states. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 182. (2) Makris
et al, “Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis
in families with inherited deficiencies of Protein S”, Blood, Vol 95, No 6, 2000,
daily, which reduced her symptoms to only infrequent urticarial lesions that
improved with additional doses of cetirizine 10mg. Conclusion: To our knowledge, there are no reports in the literature about infertility treatment; specifically IVF, induced urticaria and angioedema and the treatment modality for
this subgroup of patients. There are reports of progesterone desensitization as
treatment for patients with progesterone induced urticaria and angioedema,
specifically APD. For patients who are receiving progesterone as part of treatment for infertility, including IVF, and during pregnancy, desensitization is contraindicated in all but the most life-threatening situations. In our patients cetirizine 10mg daily (class B medication for pregnancy) seemed to alleviate most
of their symptoms.
J. Rajan*, D. Khan, Dallas, TX.
Introduction: DRESS is a drug-allergic syndrome noted to occur several
weeks after starting a medication characterized by exanthems, fever, peripheral eosinophilia, and multi-organ involvement. While systemic corticosteroids
are typically recommended, data on their efficacy is limited. Methods: A retrospective chart review of patients seen by our Allergy & Immunology Division for DRESS was performed. Data on clinical characteristics, causative
drugs, treatment and outcomes was collected. Results: Four patients were identified as having DRESS. The mean age was 29 (range, 10-56 yr) and 3/4 were
female. All had fever and maculopapular or morbilliform exanthems, 3/4 had
lymphadenopathy, 2/4 had facial edema, all had hepatitits (one with abnormal
liver function), and all had eosinophilia with mean peak eosinophilia of 2244
cells/mm3 (range, 936-4490). One patient had acute renal failure and liver failure and was considered for liver transplant. Causative drugs included antibiotics in 3 and allopurinol in one case. All 4 were treated with systemic corticosteroids with a mean initial dose of 63mg (range, 40-80) of prednisone
equivalents. Average duration of prednisone therapy was 4 weeks (range, 1.56). All patients had complete resolution of their symptoms and laboratory abnormalities with prednisone with the exception of one patient with persistent mild
elevation in AST. One patient developed diabetes following prednisone therapy. Conclusion: This case series of 4 patients with DRESS of varying severity and causes all had resolution of their reaction with systemic steroids. While
controlled studies are lacking, systemic corticosteroids should be strongly considered as first-line agents in the treatment of DRESS.
A.C. Ramsey*, S.S. Mustafa, Rochester, NY.
V. Rahimian*, M.E. Weinstein, Newark, NJ.
Introduction: Progesterone induced urticaria and angioedema have been
discussed in the literature as the trigger for autoimmune progesterone dermatitis
(APD), which is characterized by cyclic skin eruptions 10 to 14 days prior to
onset of menses. We present 2 pregnant patients who presented with urticaria
and/or angioedema after in vitro fertilization (IVF) and exogenous progesterone
supplementation. Unlike APD, these patients did not have any prior history of
cyclic urticaria nor angioedema. Methods: A review of the medical record and
relevant literature. Results: The first patient is a 32 year old female with a history of hypothyroidism who presented with urticaria and angioedema. Her
history was negative for allergies. Laboratory studies of C3, C4, CH50, C1
esterase inhibitor (total and functional), ESR, antinuclear antibodies, rheumatoid factor, complete blood count with differential, and thyroid antibodies were
all negative supporting chronic idiopathic urticaria. Her symptoms were well
controlled with cetirizine 10mg daily and remitted within 1 year. She now presents 3 years later with urticaria and angioedema after she was started on progesterone as part of her IVF treatment. The second patient is a 48 year old, 5
weeks pregnant by IVF, female who presents with diffuse urticaria and pruritic
angioedema of arms and face. Her symptoms started 3 weeks after she was
started on intramuscular (IM) progesterone injections and there was no improvement when switched to suppository form. She was started on cetirizine 10mg
RATIONALE: Eosinophilic tissue infiltration, including myocarditis, without peripheral eosinophilia is rare. There are few case reports on this condition.
METHODS: Case report. RESULTS: The patient is a 24 year old healthy female
who developed persistent palpitations at age 17, leading to a diagnosis of SVT
at age 19. She had AVNRT ablation at age 21. At age 22, she had a possible
cardiac contusion after a car accident. Troponin = 2.2 and angiography was normal. The patient was treated with NSAIDs for possible pericarditis soon after
the accident. Ongoing chest pain, palpitations, and a syncopal event prompted
a cardiac MRI, which showed a hypokinetic RV and a hypokinetic, dilated LV.
Another syncopal event with negative troponins resulted in an echo (EF of 4550%) and a negative repeat EP study. Cardiac MRI 6 months later showed
subepicardial enhancement in a uniform and well-defined distribution suggestive of myocarditis. Given the patient’s ongoing symptoms and arrhythmias,
she was fitted with a life vest and had AICD placement and an unsuccessful
ablation of ventricular tachycardia. A repeat syncopal event with troponin =
15.22 prompted repeat cardiac angiography, which was normal, but EF was
decreased to 35%. An endomyocardial biopsy was done, showing focal
myocarditis consistent with eosinophilic myocarditis. Allergy/immunology was
consulted, recommending therapy with high dose steroids and further laboratory testing (Table 1). There was no evidence of peripheral eosinophilia on 21
CBCs dating back to 2006. Surrogate markers of eosinophil activation (ECP,
GM-CSF, IL-5) were within normal limits. A bone marrow biopsy showed no
evidence of FIP1L1/PDGFR fusion protein. The patient reported profound
improvement in symptoms on steroids. EF improved to 55%. Steroids were
tapered over 3 months and discontinued. The patient’s cardiac regimen was sim-
plified and she was maintained on low dose carvedilol with continued normal
EF. A repeat endomyocardial biopsy showed no eosinophilic infiltration and
no fibrosis. Currently, the patient has intermittent chest pain but otherwise feels
well. Her echo remains normal. She has not had any further evidence of myocardial damage as evidenced by elevated troponins. CONCLUSIONS: Our case
is one of the few reports of eosinophilic myocarditis without peripheral
eosinophilia. As in previous reports, our patient demonstrated a striking response
to steroids.
Table 1 - Laboratory Results
of recurrent swelling. Life threatening episodes can occur when swelling
involves the larynx making the correct diagnosis essential. Current guidelines
recommend obtaining a C4 level to screen for HAE. A normal C4 level is considered sufficient to exclude Type I and II HAE. Methods: A PubMed search
including HAE patients with normal C4 levels reported only case reports with
isolated decrease in C1-INH protein. To our knowledge, this is the first case of
HAE associated with isolated decrease in C1-INH activity. Results: A 50 year
old female with no known family history of HAE presented with recurrent
episodes of swelling involving her face and hands with increasing frequency
over the past year. She was treated with prednisone leading to incomplete control of her symptoms. Ultimately, she presented to the emergency department
for abdominal pain associated with nonbloody diarrhea. A CT scan of the
abdomen and pelvis revealed circumferential wall thickening of multiple distal small bowel loops without evidence of obstruction. A detailed chart review
uncovered a normal C4 level of 27 (16-38 mg/dL), C1-INH quantity of 20
(11-26 mg/dL), C1q level of 6.9 (5-8.6 mg/dL), and low C1-INH activity at
18% (>68%). Repeat levels in our office confirmed these findings. Additional
testing included tryptase, anti-IgE receptor antibody, ESR, CRP, and ANA all
of which were unremarkable. She was diagnosed with HAE and started on
Danazol 200 mg three times daily. Following 2 months of therapy her C1-INH
activity normalized to >100%. She has been tolerating Danazol and her
angioedema episodes have resolved. Her daughter was screened and found to
have a normal C4 level and decreased C1-INH level and activity. Conclusions:
Our patient with HAE had normal C4 levels during acute flares and decreased
C1-INH activity. This is the first report of a patient diagnosed with HAE with
normal C4 level, normal C1-INH level, and decreased C1-INH activity. Given
high rates of morbidity and mortality in patients with HAE, it is crucial to
exclude HAE as a potential cause of swelling. Therefore, we recommend obtaining C1-INH quantity and activity in addition to C4 levels in the initial screening for HAE.
C.C. Randolph*, Waterbury,CT.
Introduction: IgE mediated sensitivity to Januvia has not been documented
systemically in the literature. Rationale: We present a possible case of Januvia
IgE mediated sensitivity documented by intradermal skin testing. Methods: A
case report Results: A 62 year old white female administrative secretary with
diabetes and asthma presented with a generalized pruritic,flat and blistering
exanthem x 14 months beginning with the introduction of Januvia. .Dermal
biopsy suggested drug hypersensitivity nonspecific contact dermatitis.She had
been on Metformin prior to the onset of the rash and Lantus was introduced
one year into the exanthem.She was given Eucerin bid and topical steroids per
dermatology but her exanthem resolved temporarily when she was given prednisone for “bronchitis”or exacerbation of asthma but recurred after completion
of the oral steroid.She was referred by her endocrinologist.On exam she had a
maculopapular exanthem with a insect bite configuration on the flexor and
extensor areas of the arms,legs,abdomen and lower extremities below the
knees.Skin testing to inhalants was negative,However prick skin testing to full
strength metformin and Januvia were negative but intradermal skin testing
toJanuvia 100mg dissolved in saline 1/100 was negative but 1/10 was positive
5mm wheal/10mm flare+2,full strength neat was 10mm/20mm(+)3while metformin was negative at all concentrations and Januvia was negative by intradermal to the author as control.Histamine was 5mm/10mm +2 and saline was
negative.Discontinuation of Januvia resulted in resolution of the rash within 2
weeks without recurrence. Conclusion:Though serious reactions including
Stevens -Johnson,erythema multiforme and exfolative rashes have been
reported(1) we report a possible IgE mediated reaction to Januvia.Reference:1
Rev Prescrire 2008;28(302):907
B.D. Robertson*, M.R. Nelson, S. Laubach, Washington, DC.
Introduction: The medical literature regarding poultry meat anaphylaxis is
limited to a few case reports, and concomitant eosinophilic esophagitis (EE)
is limited to one case series. We present two patients with poultry meat anaphylaxis and EE. Cases: Patient 1: A 10-year-old male presented with a history of poultry meat allergy consisting of a perioral rash within minutes of
ingestion in 2007 and was later diagnosed with EE in 2009 . His 2007 evaluation for food allergy included a positive skin prick test to chicken and recommendation for poultry avoidance. Repeat skin prick testing with commercial
extracts in 2009 was positive for turkey, but was twice negative for chicken.
He then underwent a chicken challenge and within five minutes of a 3g dose
developed anaphylaxis consisting of hives, hypotension, rhinorrhea, nausea and
diarrhea. A subsequent chicken-specific IgE level was elevated (2.55 kU/L),
and repeat skin testing with fresh chicken was positive. Patient 2: A 57-yearold female patient presented with EE diagnosed in 2007 and a history of recurrent anaphylaxis to poultry starting in childhood. Skin testing in 2009 with
commercial extract was negative to chicken, but her chicken meat-specific
IgE level was elevated (0.62 kU/L). Conclusions: These cases support the possible association between poultry food allergy and subsequent development of
EE. Interestingly, skin prick testing with commercial chicken extract was negative during the evaluation of these two patients. These cases demonstrate the
limitations of percutaneous skin testing for chicken meat sensitization and support the findings of Sicherer et al. that skin prick testing for food allergies may
not be as sensitive as ImmunoCAP testing in detecting some food allergies.
Poultry meat allergy preceding EE requires further study, to include identification of the epitopes in poultry meat that are responsible for the food allergy.
Reference: Sicherer SH, Wood RA, Stablein D, et al. Immunologic features of
infants with milk or egg allergy enrolled in an observational study (Consortium of Food Allergy Research) of food allergy. J All Clin Immunol.
C.K. Rao*, A.A. Petrov, Pittsburgh, PA.
Introduction: Hereditary angioedema (HAE) is a rare autosomal dominant
disease caused by a deficiency or dysfunction in C1-esterase inhibitor (C1INH) resulting in uncontrolled activation of the classical pathway with episodes
R.G. Robison*, M.R. O’Gorman, M.A. Proytcheva, R.L. Fuleihan, Chicago,
Introduction: Hyper IgM syndromes are primary immunodeficiency disorders due to defects in class switch recombination with or without defects in
somatic hypermutation. The most common form of hyper IgM is CD40 ligand
deficiency with X-linked inheritance. Other defined causes of autosomal recessive hyper IgM include deficiencies in CD40, activation-induced cytidine deaminase (AID) and uracil DNA-glycosylase (UNG). Methods: Case report; literature review. Results: A 13 year old male presented for evaluation of an
asymptomatic left supraclavicular mass present for 2 to 3 months. Medical history was significant for laproscopic appendectomy at age 10 and a tonsillectomy/adenoidectomy with myringotomy tube placement at age 12. Family history was notable for a mother with gastric cancer. On examination, he had a
mobile, left clavicular mass, 2-3 cm in diameter that was non-tender/non-fluctuant and without erythema. Submandibular and anterior neck lymphadenopathy
was also noted. Chest X-ray showed hilar adenopathy with suggestion of a bilateral reticulonodular infiltrate. Biopsy revealed moderate follicular hyperplasia, microabscesses, mononuclear inflammatory infiltrates with intranuclear
and intracytoplasmic inclusions. Immunohistochemistry was positive for
cytomegalovirus (CMV). A diagnosis of CMV adenitis/pneumonitis was made.
The patient re-presented 1 month later with development of enlarged submandibular nodes. CMV IgG and IgM were negative. Further evaluation of
immune function revealed IgA and IgG below detection with a normal IgM.
Tetanus antibody was below detection, pneumococcal antibody titers were inadequate and he had normal T cell proliferation to antigens. Both expression of
CD40 on B cells and expression of in vitro induced CD40 ligand on T helper
cells (assessed by both monoclonal antibody and binding of chimeric CD40/Ig
molecule) were consistent with normal. AID gene sequencing showed no mutations. Discussion: We describe a teenage male with newly diagnosed autosomal recessive hyper IgM. This case illustrates an important point that not all
patients with immunodeficiency present with serious recurrent infections.
The patient has not yet been tested for a deficiency of uracil DNA-glycosylase
or postmeiotic segregation increased 2(PMS2). If no mutation is found in either
gene, our patient may have an undefined form of hyper IgM syndrome not
previously described.
B.R. Sabin*, D. Conley, A.M. Ditto, Chicago, IL.
Introduction: Nasal foreign bodies are often considered in the differential
diagnosis of purulent, fetid unilateral discharge in children, but in the absence
of appropriate history are rarely considered in adults. Case Presentation: A 36
year old male was referred to our allergy clinic for chronic rhinosinusitis (CRS).
He noted nasal congestion and clear rhinorrhea in the spring since childhood,
however in the past 2 years he developed constant nasal congestion and intermittent green mucoid drainage. In the past 3 months he described frequent
bloody noses, pain in his left upper molars, decreased olfaction, and fatigue.
Symptoms continued despite treatment with azithromycin for 5 days and moxifloxacin for 14 days including increased drainage from his left nare and pain
behind his left ear with reported swelling. His medical history included Multiple Endocrine Neoplasia I manifested by hyperparathyroidism, and zollingerellison syndrome. He had a benign pituitary adenoma resected transsphenoidally
6 years prior and subsequent gamma knife treatment. Physical exam revealed
his turbinates were 1+ boggy, erythematous bilaterally, with a synechiae from
the right inferior turbinate to the nasal septum, and purulent drainage from the
left nostril. The prominent unilateral symptoms were concerning for mechanical obstruction and referral to otolaryngology was made. Rhinoscopy confirmed mucoid drainage and identified a nasal obstruction inferior to the middle turbinate. CT scan of the sinuses showed a 1cm calcified structure at the
level of the nasal obstruction, and under endoscopic visualization a 1.5 x 1.5
cm foreign body was extracted. Visual inspection confirmed this to be hydroxyapatite cement (HAC) used as a bone graft substitute during his pituitary
adenoma resection 6 years prior that was anteriorly displaced in the nose. Discussion: HAC can be molded intraoperatively to form an accurate contour of
bone making it useful to repair cranial defects. In a ten year experience of using
HAC for temporal bone surgery including 102 patients, 2 grafts were resorbed
but none were dislodged. In another 55 patients who had HAC bone recon-
struction after transsphenoidal tumor removal, no graft dislodgement was
described. This is the first description of a transsphenoidal pituitary tumor
resection followed by a HAC graft complicated by graft dislodgement and CRS
due to a nasal foreign body.
M.S. Sandhu*1, A.K. Sandhu2, V. Dimov3, A. Bewtra3, 1. Surrey, BC,
Canada; 2. Vancouver, BC, Canada; 3. Omaha, NE.
Autoimmune progesterone dermatitis (APD) is a rare disorder characterized by recurrent skin manifestations starting during the luteal phase of a
woman’s menstrual cycle. The clinical symptoms of APD (eczema, urticaria,
angioedema, etc.) usually begin approximately 7 days prior to the onset of menstrual flow, and end 1–2 days into menses. Severity of symptoms can vary from
nearly undetectable to anaphylactic in nature, and symptoms can be progressive. We describe a case of progesterone sensitivity in a 31 year old female
nurse. The patient presented to our office with a 1 year history of episodic
generalized pruritis followed by urticaria, eyelid angioedema and occasional
throat tightness. Initially it was believed that the symptoms were secondary to
ibuprofen which she took for migraine treatment. An open oral challenge to
ibuprofen refuted this as the cause. Since the patient’s symptoms were cyclic
and begin approximately 1 week prior to menses and abated shortly after the
initiation of menses, a diagnosis of progesterone allergy was entertained. Skin
prick testing (SPT) was performed with a 50mg/ml progesterone suspension
(histamine 5x6; 10x12mm, progesterone 2x3; 6x5mm). Intradermal(ID) testing was done with a 10fold dilution 5mg/ml ( histamine 8x6;15x20mm, progesterone 8x9;30x30mm). Both SPT and ID concentrations of progesterone were
tested in our clinic and confirmed to be non-irritating doses. The patient’s symptoms did not respond to antihistamines and was requiring frequent prednisone
courses. Treatment with the GnRH agonist leuprolide 11.25mg IM every
3months was initiated to suppress ovulation. The patient has been on leuprolide for 3months and has remained symptom free.
O.J. Saucedo-RamГ­rez*, B.E. Del RГ­o-Navarro, M.L. Avila-CastaГ±Гіn,
M.A. Rosas-Vargas, Mexico City, Mexico.
Introduction: Allergic bronchopulmonary aspergillosis is a lung disease that
is caused by a hypersensitivity to Aspergillus fumigatus, characterized by chronic
asthma, recurrent pulmonary infiltrates and bronchiectasis. The literature report
an incidence of 1% to 2% in asthmatic patients and 2% to 15% in patients with
cystic fibrosis. Case: It is a male aged 16, from the State of Mexico, with the
following history of importance: family history of parent with asthma; medical history of chickenpox and hepatitis in the school years. Comes in February 2000, referring condition of three years of evolution with continuous nasal
obstruction, nasal itching, sneezing, runny nose, without seasonal predominance, night cough four times a week, shortness of breath and wheezing on
three occasions per year. Physical examination with oral respiration and hyaline rhinorrhea. He joined the diagnosis of mild persistent rhinitis, moderate
persistent asthma, giving treatment with topical nasal steroid and inhaled with
short-acting ОІ2 agonist necessary grounds. Extension studies were performed
with skin test sensitization to molds (Aspergillus fumigatus), intra-refuges allergens and food, so we give him mite immunotherapy treatment. In partial response
to immunotherapy. Losing track, performing in 2007 with nasal and bronchial
symptoms compatible with allergic rhinitis moderate persistent and severe persistent asthma; extension studies were conducted, finding multisensitization
to fungi (Aspergillus fumigatus, Candida albicans, Cladosporium herbarum ),
intra-allergens and food. We suspected allergic bronchopulmonary aspergillosis, total IgE of 1250UI/mL, specific IgG positive for Aspergillus fumigatus
and Aspergillus niger, computed tomography with central bronchiectasis, peripheral eosinophilia of 6%, confirming the diagnosis. Currently being treated with
prednisone with poor response to treatment. Discussion: In a recent systematic review and meta-analysis reported an incidence of allergic bronchopulmonary aspergillosis in asthmatic patients 12.9% and 40% in patients with
asthma and sensitization to Aspergillus. So we can say that allergic bronchopulmonary aspergillosis is a disease with high incidence in reference centers, being forced to rule out this condition in all patients with asthma and sensitization to Aspergillus, as exemplified by the case reported.
Laboratory studies
N.A. Sharif*, J. Fagin, Great Neck, NY.
D.R. Scott*, G. Allada, A. Montanaro, Portland, OR.
Introduction: Although intermittent dyspnea, wheezing and nocturnal cough
are hallmarks of asthma, diligent clinical evaluation and open-minded reassessment following treatment occasionally reveal an uncommon etiology for these
common symptoms. We report the case of a woman presenting with symptoms suggestive of asthma who instead was found to have a unique constellation of findings, including markedly elevated IgE, eosinophilia and pulmonary
hypertension. Case Report: A 57-year-old Cambodian woman with a history
of seasonal allergies presented with three weeks of rhinorrhea, watery eyes and
chest symptoms characterized by nocturnal cough, intermittent dyspnea and
wheezing. Nasal and ocular symptoms were unresponsive to antihistamines.
Chest symptoms were minimally responsive to inhaled beta-adrenergic agonist, but markedly improved with systemic prednisone. Her exam revealed a
healthy appearing woman with mild tachypnea and normal oxygenation without wheezes, rales or clubbing. Pulmonary function tests indicated mild restriction without evidence of obstruction and decreased DLCO. A CXR revealed
prominent pulmonary arteries. Chest CT further suggested pulmonary hypertension and also revealed mild basilar ground glass attenuation concerning for
interstitial lung disease (ILD). A transthoracic echocardiogram measured an
elevated pulmonary artery systolic pressure of 68 mmHg. Further serologic
testing demonstrated a total IgE of 14,379 IU/mL and an eosinophil count of
1100 per ml (19%). Stool returned strongly positive for strongyloides. Autoimmune serologies were negative. Discussion: Although our patient initially presented with symptoms suggestive of straightforward asthma, her poor response
to bronchodilator therapy and unexpected PFT’s led to further investigation and
the discovery of a rare combination of findings, including pulmonary hypertension, markedly elevated IgE levels, eosinophilia and potentially, ILD. Few
conditions are known that could singularly account for this constellation of
abnormalities. Pulmonary Strongyloidiasis, which is a rare cause of ILD and
a difficult condition to diagnose, was thought to potentially account for her
symptoms. A course of antiparasitic medication was initiated. Other possible
explanations of her rare constellation of findings are discussed, such as hypersensitivity pneumonitis and other types of ILD and parasitic infection.
Basilar ground glass opacification and dilation of pulmonary arteries noted
on chest CT.
Introduction: Autoinflammatory disorders are a group of illnesses characterized by recurrent episodes of fever and systemic inflammation starting in
early childhood. Dysregulation of inflammatory mediators, such as interleukins,
has been documented in some of these disorders. We describe one such case
with overlapping features of several autoinflammatory syndromes. Methods:
This patient is a 2-year-old girl, who was in good health until 12 months of age
when she was hospitalized with fever, rash, diarrhea and mental status changes
one week after an MMR vaccine. She had five subsequent hospitalizations,
including one following varicella and dTAP vaccination. Presentation prior to
each hospitalization was marked by fever and a combination of rash, mental
status changes, unsteady gait, seizures, vomiting, diarrhea and/or upper respiratory symptoms. ESR and CRP were markedly elevated during each episode.
No specific diagnoses were confirmed during any of these admissions, although
atypical Kawasaki disease was considered a possibility. During each hospitalization, she was given IVIG with rapid and dramatic clinical improvement and
resolution of most laboratory abnormalities. She was started on Anakinra at
32 months of age. Since then she has remained asymptomatic. Results: Genetic
testing was negative for the CIAS1 mutation (Muckle-Wells/NOMID/CAIS).
She is heterozygous for a p46L mutation in the TNFRSF1A gene (TRAPS),
though this may represent a benign polymorphism. CBC, immunoglobulin levels (including IgD), complement studies, ANA, serum chemistries, thyroid studies, CSF studies and lipid prolife were all within normal limits. Liver biopsy,
bone marrow aspiration and brain CT were normal. An MRI/MRA demonstrated non-specific vasculitis. Discussion: We report a 2-year-old female with
an autoinflammatory syndrome complicated by overlapping clinical features.
Her dramatic response to Anakinra (IL-1 receptor antagonist) suggests IL-1
involvement in the pathophysiology of her disease. Parental genotyping is in
progress to determine the relevance of the p46L mutation. This case illustrates
the difficulty frequently encountered in making a specific diagnosis in patients
presenting with an autoinflammatory syndrome and highlights the need to consider empiric treatment with biologic agents.
A.P. Sharma*1, T. Prematta2, J. Rosch2, F. Ishmael2, 1. Hummelstown, PA;
2. Hershey, PA.
Sharma, Ashika MD, Prematta,Tracy MD, Rosch, J MD, Ishmael, F
MD/PhD. Hershey Medical Center- Penn State University Hershey, PA Introduction: Rubinstein Taybi Syndrome (RTS) is a rare condition characterized
by broad toes and thumbs, facial dysmorphisms, and mental retardation. Children with RTS have recurrent upper respiratory tract infections which have predominantly been attributed to structural abnormalities, microaspiration and
gastroesophageal reflux. Few studies have attempted to define the immunological status of these patients. We present a case and results of a literature
search illustrating patients with RTS and immunodeficiency. Methods: Ovid
and PubMed were searched with these key terms: Rubinstein-Taybi, immunodeficiency, recurrent infections. Case Report: A 19 year female with known
RTS was evaluated for recurrent otitis media and sinus infections. She was
treated with antibiotics every other month and would respond quickly, but after
discontinuation symptoms would recur within a few days. Allergy testing was
negative. She was screened for immunodeficiency and found to have IgA level
of 4 mg/dL (NL >10), IgG2 179mg/dL (NL 241-700) and IgG4 of 3.9mg/dL
(NL 4-86). She had an inadequate response to Pneumovax with protective antibody levels to 4 out of 14 serotypes. Total IgG, IgM, IgG1 and IgG3 were normal and she had a protective Tetanus antibody level of 3.94 IU/mL. She was
started on prophylactic amoxicillin 6 months ago and since starting, has not
had any symptoms consistent with OM or sinusitis. Results: Literature review
revealed the first documented case association of RTS with immunodeficiency
in a 4 year old boy with RTS and B and T cell defects who responded well to
IVIG. Another study identified 3 patients with RTS and inadequate response
to polysaccharide vaccine. One Japanese study documented a 20 month boy
with RTS and thymic hypoplasia on autopsy. Our patient with RTS has IgA
deficiency with IgG2 subclass deficiency and inadequate response to polysaccharide vaccine. Conclusion: We present a case of a patient with RTS and
immunodeficiency; review of the literature showed 5 other documented cases
of RTS with immunodeficiency. Thus, it appears that immunodeficiency may
be a feature of this syndrome that may be under recognized. For patients with
RTS and history of recurrent infections, immune evaluation should be considered.
J.M. Sturm*, J. Temprano, St. Louis, MO.
Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS)
is a severe drug reaction resulting in skin rash, fever, eosinophilia, lymphadenopathy, and multiorgan involvement. DRESS usually occurs 2-8 weeks
following the start of a medication. Affected patients develop diffuse maculopapular skin lesions along with systemic involvement. The most common
causes of DRESS are aromatic anticonvulsants, sulfonamides, antibiotics, and
non-steroidal anti-inflammatory drugs. Treatment involves discontinuing the
offending medication. Many single case studies are present in literature. Few
studies report multiple cases. Methods: A retrospective study of all patients
with DRESS syndrome seen in consultation at a university hospital between
1997 and 2010. Cases were evaluated for patient demographics along with clinical and laboratory findings. Results: The study reviewed 7 cases of DRESS
syndrome (4 female and 3 male). Age of patients ranged from 25 to 67. Days
between the start of drug treatment and development of DRESS syndrome
ranged from 21 to 39 days. The most common skin lesions described were maculopapular lesions present diffusely throughout the chest, arms, and legs. Three
patients had documented lymphadenopathy. Six patients had documented fevers.
Elevated liver enzymes were seen in 4 patients. Renal involvement was present in 5 patients. All patients developed eosinophilia or atypical lymphocytosis. Anticonvulsants were the leading cause of DRESS in our study with 2 cases
of phenytoin and one case with levetiracetam. Sulfasalazine was attributed to
one case. Three cases involving the use of multiple antibiotics (vancomycin,
ceftriaxone, ampicillin, fluconazole, and piperacillin/tazobactam) were categorized as undetermined. All patients treated with anticonvulsants and sulfasalazine developed elevated liver enzymes. Symptoms improved in all patients
on withdrawal of the offending agent and treatment with corticosteroids. Conclusion: In our study, anticonvulsants were the most common etiology of
DRESS, but antimicrobials were also a common cause. Physicians should be
aware of DRESS syndrome in patients who develop fever, rash, and systemic
symptoms. Importantly, all patients in this series improved upon withdrawal
of the offending drug and treatment with systemic steroids.
J. Toh*, S. Jariwala, G. de Vos, New York, NY.
Introduction: Eosinophilic gastroenteritis (EG) is a rare inflammatory disease characterized by distinct gastrointestinal symptoms and eosinophilic infiltration of the bowel wall. Although food allergy is commonly associated with
the disease in children, there are fewer studies supporting an association in
adults. We describe a case of EG in an atopic patient with primary biliary cirrhosis (PBC) and Sjogren’s syndrome. Methods: Case description Results: A
48-year-old female with PBC, Sjogren’s syndrome and mild asthma presented
to the emergency room with watery, non-bloody diarrhea for 3 weeks, generalized abdominal pain for 3 days and anasarca with a 40-lb weight gain over
the last 3 months. CT abdomen revealed pancolitis with sparing of sigmoid
colon and rectum. Labs were significant for hypoalbuminemia (0.8 g/dL), elevated ESR (120 mm/hr), and increased total IgE (712 IU/ml). The peripheral
eosinophil count was normal but increased transiently up to 1740/ul (25%)
during her hospital stay. Stool studies were unremarkable. Endoscopy showed
significant eosinophilic infiltration of the duodenum and mild non-specific
inflammation of the colon. Despite negative parasitic work-up, the patient was
given Ivermectin empirically. At the same time, high dose IV corticosteroids
were started and her symptoms improved rapidly. However, while on a tapering dose of oral steroids after discharge, her diarrhea returned after ingesting
milk and eggs. Allergen specific serum IgE revealed milk 0.998 kIU/L, egg 1.19
kIU/L, mugwort 11.5 kIU/L, shrimp 11.7 kIU/L, wheat 0.186 kIU/L and fish
0.204 kIU/L (DPC Immulite 2000). She was then encouraged to eliminate milk,
egg, wheat, seafood and potentially cross-reactive mugwort-associated food
from her diet. She currently remains symptom-free while maintained on low
dose prednisone, and consistently avoiding milk, egg and shellfish. Conclusion:
Food allergy associated EG should be suspected in any patient with gastrointestinal symptoms associated with eosinophilic infiltration of the gastrointestinal mucosa. There is also a known association between PBC and peripheral
eosinophilia, but there are currently no published cases of EG in this disease
population. All suspected patients, including adults, should have a complete
allergy evaluation as food elimination may be an important part of treatment.
T. Moncrief*, B. Uygungil, L. Zuo, Cincinnati, OH.
Objective: Hereditary Angioedema (HAE) is a disorder characterized by a
quantitative or functional deficiency of C1 inhibitor affecting up to 1 in 100,
000 in the general population. It is characterized by stress-induced soft tissue
edema due to the inability to breakdown bradykinin, a potent vasodilator. Due
to the significant morbidity and potential mortality associated with HAE, agents
are needed to decrease the risk of attacks associated with triggers, including
surgical procedures. Methods and Results: We report here a case of a 3-yearold boy with serologic testing consistent with Type I HAE (low C1 Inhibitor
7.8 mg/dL, low C4 <6.3 mg/dL and a maternal history of HAE. He had a history of recurrent abdominal discomfort, but no other signs of angioedema. A
tonsillectomy and adenoidectomy was scheduled due to sleep apnea so pre-procedure prophylaxis was required. We elected to use purified C1 inhibitor at 20
units/kg IV as recommended by the manufacturer. He tolerated the drug with
no adverse effects and no evidence of angioedema post-operatively. He was
monitored in the ICU for a total of 48 hours post-procedure reporting only minimal vague abdominal pain that self-resolved. His C1 inhibitor level increased
to 14.9 mg/dL providing evidence for an increased serum level. Discussion:
Short term prophylaxis of HAE attacks was historically achieved with fresh
frozen plasma (FFP), which contains C1 inhibitor, but now is less favorable
given the risk of worsening attacks and potential infectious exposure. Newer
purified C1 inhibitor commercial formulations offer detectable increased plasma
C1 inhibitor levels following infusion. One formulation has been approved for
treatment of acute attacks, while the other has been approved for both acute
attacks and prophylaxis in adolescents and adults. Although this commercial
purified C1 inhibitor has been approved for use in adolescents and adults for
acute attacks, it is not approved for the purpose of pre-procedure prophylaxis.
Conclusion: This is the first case to our knowledge reporting the successful use
of purified C1 inhibitor in a child with HAE for pre-procedure prophylaxis.
Purified C1 inhibitor can be considered for use in pediatric patients with HAE
undergoing a surgical procedure as an alternative to FFP. Optimal pediatric dosing, safety, and efficacy warrant further investigation.
N. Madhok, N. Vernon*, A. Rubinstein, Bronx, NY.
Introduction: In the majority of cases, EBV latently infects B cells without
any persisting immunological aberrations. There have been no reported cases
to date of patients with prolonged lymphopenia following acute EBV infection.
Methods: Chart review was performed on three patients presenting for evaluation of lymphopenia with recent EBV infections. Results: Patient A is a 21 yo
man with acute EBV infection demonstrated by an elevated IgM. Following
infection, he developed lymphopenia. CD4+ cells were 246 with reversed
CD4/CD8 ratio and CD19+ cells were 11% with absolute count of 61. Currently, 5 yrs after infection, his CD4+ counts are trending towards normal,417,
with normal B cells. Patient B is a 22 yo girl with acute EBV infection demonstrated by elevated IgM. She subsequently had a decrease in CD4+ counts to
12% with normal absolute count of 705 and CD19+ of 1%, absolute count 60.
Now, 2 yrs after EBV infection, her T and B cells counts have normalized. Patient
C is an 18 yo girl with history of clinical EBV infection. Subsequently, she had
6 episodes of tonsillitis and sinusitis. She was found to have lymphopenia,
550, with normal percentage of CD19+ cells, 10%, but low count of 55. Normal CD4+ count. Conclusion: Most EBV infections are self limited and latent
infection is established for life without any further manifestations or immune
aberrations. This case series demonstrates the possibility of developing prolonged, but transient, T and B cell abnormalities following acute infection.
S. Wang*1, O.P. Patel1, S.C. Dreskin2, 1. Denver, CO; 2. Aurora, CO.
C.K. Woo*, S.L. Bahna, Shreveport, LA.
INTRODUCTION: Hypersensitivity reactions to trimethoprim-sulfamethoxazole (TMP-SMX) are common. Oral desensitization to TMP-SMX
is relatively safe in patients with HIV, lung transplantation, and in other selected
patients with careful consideration of the risk of severe reactions, such as StevenJohnson syndrome. We previously reported successful rapid IV desensitization
to TMP-SMX in a single intubated patient who was s/p lung transplantation
(Mann R., et al., Chest, 1997; 111:1147). In 2008, we again successfully performed rapid IV desensitization to TMP-SMX in an immunocompromised,
intubated patient with HIV. However, rapid IV desensitization to TMP-SMX
has not been reported in a non-immunocompromised patient. CASE REPORT:
This 62 year old female with a history of CF since childhood, was admitted due
to CF exacerbation and was empirically treated with Meropenem, Aztreonam
and Levaquin. Her sputum culture was positive for B. Cepacia, which was sensitive only to TMP-SMX and Levaquin. As her symptoms were worsening,
TMP-SMX was considered. Due to the concern of poor GI absorption in this
CF patient, IV TMP-SMX was recommended. TMP-SMX caused acute urticaria
about 3 yrs prior to this hospitalization and she was successfully desensitized
to oral TMP-SMX about 1.5 yrs prior for an exacerbation of her CF. The IV
desensitization protocol was designed with a starting dose of 12.5 ng of TMP
in 50cc normal saline over 20 minutes, at about 1/100 of the starting dose for
oral desensitization. We waited for 10 minutes between each dose. The highest dose, dose No.13, was 32 mg of TMP in 50cc normal saline (NS) over 20
minutes. This was similar to the concentration of the therapeutic dose, 400mg
of TMP in 500cc NS over 200 minutes. The patient did not have any reaction
during this desensitization and the therapeutic dose was started 8 hrs later at
400mg in 500 cc of NS IV every 8hrs. Her symptoms and lung function were
improved at the time of discharge. CONCLUSION: Rapid IV desensitization
to TMP-SMX was successful in a patient with CF and a history of a previous
allergic reaction to TMP-SMX.
J. Wheeler*, P. Brown, M.F. Sands, Buffalo, NY.
Introduction: We describe a 44 y/o white female with a previously unidentified FAS gene mutation and clinical criteria for both ALPS and CVID. This
is the second case wherein a CVID phenotype evolved into ALPS, the first with
identification of an associated gene defect. Background: ALPS (type I or II )
is due to gene defects in the apoptosis pathway (FAS or caspase 8 or 10) or type
III (defect unknown) resulting in lymphoproliferation, autoimmune disease,
hypergammaglobulemia and high double negative (CD3+,CD4-,CD8-) T cells
(DNTs). CVID has multiple causes and some features similar to ALPS (lymphadenopathy and autoimmunity), but hypogammaglobulemia and functional
antibody defects. Results: The mother has both CVID and ALPS and her two
sons have ALPS. Gene analysis of all three showed FAS mutation (517 A>G;
p. D92G). She developed splenomegaly and ITP as a child. Infections (pneumococcal meningitis, recurrent sinusitis) prompted immune evaluation as an
adult. In 1990 she had reduced IgA and IgG2 and was started on IVIG for low
IgG2 and recurrent infection. In 2003 her blood flow cytometry showed: high
CD3 2603 (690-2540 cells/Вµl), CD4 1650 (755-1357 cells/Вµl), CD19 949 (162410 cells/Вµl), CD56 420 (58-328 cells/Вµl) and DNTs 7% (<1% normal). We
first consulted in 2010, and Ig levels were: IgG 378 (700-1600 Вµg/dL), IgA 21
(70-390 Вµg/dL), IgM 32 (50-300 Вµg/dL), with undetectable antibody titers to
rubella, S. pneumoniae and influenza A. Lymphocyte flow showed: high CD3
2744 (1174-2102 cells/Вµl), CD4 1861 (688-1341 cells/Вµl), CD19 1948 (162410 cells/Вµl), normal CD8 847 (380-848 cells/Вµl), DNT count was 3.7% (Nl.<1
%). In 2003, sons ages 5 and 8, had lymphadenopathy, hypergammaglobulinemia, and refractory cytopenias. The younger had high CD19 435 (162-410
cells/Вµl) and low CD4 599 (755-1357 cells/Вµl), CD8 877 (1084-1428 cells/Вµl),
CD56 29 (58-328 cells/Вµl) with normal CD3 1633 (1174-2101 cells/Вµl) and
DNTs 11% by estimate. The older son had recurrent otitis and sinusitis and low
serum CD4 330(755-1357 cells/Вµl), CD8 430(1084-1428 cells/Вµl), with normal CD3 889 (1174-2102 cells/Вµl), and CD56 108 (58-328 cells/Вµl) and DNTs
15% by estimate. Conclusion: We report the 2nd case of ALPS and CVID occurring in the same patient. The mother manifested a transition from CVID to
ALPS phenotypes while her children exhibit only ALPS.
Introduction: Several factors can be responsible for uncontrollable asthma.
We present a case of intractable asthma in spite of adequate standard management (environmental control and pharmacotherapy for asthma, allergic rhinitis, sinusitis and gastroesophageal reflux). Case: A 40-y-o African American
female had asthma since childhood. She was referred to our clinic because of
frequent exacerbations. Within the past year, she had 5 hospitalizations for
asthma that was preceded by respiratory infections, including sinusitis and
pneumonia. She seemed to be compliant with her medications of fluticasone
500 mcg in combination with salmeterol 50 mcg b.i.d, montelukast 10 mg daily,
cetirizine 10 mg daily, and albuterol-HFA 2 puffs q 6 hr p.r.n. She claimed no
stress or exposure to pets, tobacco smoke or significant environmental irritants.
PFT showed FVC 60%, FEV1 57% and FEF25-75% 43% predicted, and
FEV1/FVC ratio 80%. CXR revealed bilateral mild interstitial markings and a
calcified left hilar lymphnode. Sinus CT showed occluded osteomeatal complexes on both sides, moderate to severe mucosal edema in most sinuses and
retention cyst in the anterior left sphenoid and right maxillary sinuses. IgE level
was 18 IU/ml and skin prick test was positive to house dust mites and grass
pollens. IgG, IgA and IgM levels were 1082, 215 and 190 mg/dl respectively.
Her asthma remained uncontrolled despite environmental control, appropriate
pharmacotherapy for asthma, sinusitis and a trial of anti-reflux medication. Her
antibody levels were normal to tetanus but low to diphtheria and pneumococcus in spite of revaccination. Because her asthma continued to be poorly controlled and immunotherapy could not be initiated, a trial of IVIG (400 mg/kg
q 4 wk) was instituted based on specific antibody deficiency. Within a month,
she reported definite improvement in symptoms and within 4 months, PFT
showed increase in FEV1 by 12%, FEV1/FVC by 14% and FEF25-75% by
36%. She continues to receive monthly IVIG with adequate asthma control and
no recurrence of infections. Conclusion: In addition to common causes of poorly
controlled asthma, evaluation for immunodeficiency should be considered, and
IVIG should be instituted for specific antibody deficiency or common variable
C.K. Woo*, A. Casillas, Shreveport, LA.
Introduction: ACE inhibitors are recommended as the anti-hypertensive
medication of choice for diabetics. They have a favorable effect on cardiovascular outcomes and retard the development and progression of nephropathy in
diabetics. We present a case report of a diabetic patient who developed psoriatic erythroderma after being started on lisinopril. Case: A 60 year old white
male with diabetes, hypertension and psoriasis was initially admitted for leg
cellulitis. He was diagnosed with uncontrolled diabetes and hypertension. After
treatment with IV ceftriaxone, his cellulitis improved and he was discharged
on a 10 day course of doxycycline. At discharge, he was started on insulin for
diabetes and lisinopril for hypertension. 12 days later, he is readmitted to the
hospital with generalized erythroderma. Consultation was requested to evaluate for immunological cause of the dermatitis. Patient was afebrile, physical
exam revealed generalized erythroderma with serous drainage involving 90%
of body surface area; the mucus membranes and conjunctiva were uninvolved.
Laboratory studies revealed eosinophilia of 14%, normal LFT, negative ANA,
negative anti-histone antibody and negative hepatitis A, B, C serology. Skin
biopsies were done which revealed psoriasiform acanthosis, spongiotic dermatitis with mild eosinophilia and no immune complex deposition. A diagnosis of adverse drug reaction with underlying psoriasis was made. He was started
on prednisone 40 mg q day and lisinopril was discontinued. The erythroderma
improved within 2 days and a slow prednisone taper was instituted at discharge.
Discussion: Psoriasis is one of the most common dermatologic diseases, affecting 1-2% of the world’s population. It is a chronic inflammatory skin disorder
typically characterized by sharply demarcated plaques covered by silvery scale.
Drugs that have been known to cause psoriasis flares include ACE inhibitors,
anti-malarials, beta-blockers, indomethacin, lithium and progesterone. In a case
controlled-study, psoriasis was associated with ACE inhibitor with OR of 4.0
and in the case-crossover group, the OR was 9.9. The pathogenesis for ACE
inhibitor induced psoriasis flare is currently not known. Conclusion: It is important to be aware of severe exacerbation of psoriasis with ACE inhibitors.
S. Yee*1, S. Jariwala2, G. Hudes2, D. Rosenstreich2, 1. Englewood Cliffs,
NJ; 2. Bronx, NY.
R. Zeballos-Chavez*1, J. Hein2, 1. Detroit, MI; 2. Newburyport, MA.
INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease of
unknown etiology that most commonly involves the lungs. This condition is
suggested by bilateral hilar adenopathy on chest radiography and noncaseating granulomas on histology. We report two cases of nasal sarcoidosis in the
setting of nasal polyps. METHODS: Case series; literature review RESULTS:
Patient One - A 65-year-old female with chronic rhinosinusitis presented with
severe nasal congestion and postnasal drip. Physical exam revealed enlarged
nasal turbinates and bilateral nasal polyps; skin prick testing (SPT) was positive for tree pollen, dust, and cat. Non-contrast CT sinuses showed extensive
opacification of the sinuses with polyps. Chest x-ray reported bilateral hilar
adenopathy. Laboratory testing was significant for an elevated ACE of 58 (normal range: 8-52) and increased ESR of 56 (normal range < 31). The patient
underwent a nasal polypectomy with pathology revealing noncaseating granulomas and negative AFB and fungal stains, thereby suggesting the diagnosis
of sarcoidosis. Patient Two - A 30-year-old female with asthma and seasonal
allergic rhinitis presented with severe nasal congestion. Physical exam demonstrated bilaterally enlarged turbinates with nasal polyps; SPT was positive for
tree pollen, mite, feathers, cat, cockroach and mold. Chest x-ray was clear,
although CT chest showed mildly enlarged hilar lymph nodes. Laboratory
testing was unremarkable and demonstrated a normal ACE level of 22. Nasal
polypectomy pathology revealed non-necrotizing granulomatous disease, which
was consistent with nasal sarcoid. CONCLUSION: The two cases reported
demonstrate that although almost 90% of sarcoidosis patients present with pulmonary symptoms, this disease may present solely with nasal congestion. It is
important to keep nasal sarcoidosis on the differential in patients who present
with severe allergic rhinitis and chronic sinusitis with nasal polyposis.
S.Yee*1, S. Jariwala2, G. Hudes2, D. Rosenstreich2, E. Jerschow2, 1. Englewood Cliffs, NJ; 2. Bronx, NY.
INTRODUCTION: Drug rash with eosinophilia and systemic symptoms(DRESS) is a rare life-threatening adverse reaction classically triggered
by antiepileptic drugs. DRESS is characterized by rash, eosinophilia, lympadenopathy, internal organ involvement, and HHV-6 reactivation. Therapy with
steroids and removal of the offending agent may be successful, although DRESS
leads to death in about 10-40% of cases. We describe a case of phenytoininduced DRESS in a patient with acute liver failure and positive anti-mitochondrial antibody(AMA). METHODS: Case description RESULTS: A 43year-old female with a history of seizure disorder presented with three weeks
of subjective fevers, headache, and generalized pruritus. Home medications
included phenytoin(started 2 months prior), escitalopram(started 1 year prior),
levitiracetam(started 1 month prior), and as-needed ibuprofen(since 3 years
prior). In the Emergency Department, the patient had a fever of 104 degrees F
and found to have anterior cervical lymphadenopathy and an erythematous
macular rash on the upper chest. Signficant labs were high AST of 225, ALT
of 148, alkaline phosphatase of 185, and peripheral eosinophilia of 11%(absolute
count of 0.8). The following were unremarkable: chest x-ray, CT head,
blood/urine cultures, lumbar puncture cell count and culture, HIV testing, EBV,
ANA, hepatitis serologies, anti-smooth muscle antibody, phenytoin and acetaminophen levels. The patient was continued on all home medications and
developed worsening liver failure – AST/ALT increased the day after admission to 4188 and 2697, respectively, while total/direct bilirubin increased to 5.3
and 3.6, respectively; eosinophils also increased to 22 % (absolute count of
2.1). DRESS was suspected and phenytoin was discontinued along with the
initiation of 60 mg prednisone twice daily. Liver enzymes and eosinophilia subsequently normalized. Interestingly, the patient was found to have a positive
AMA, and was scheduled for outpatient biopsy to evaluate for primary biliary
cirrhosis. CONCLUSION: In this case of DRESS, it is interesting to note that
the patient was positive for AMA. Along with transaminitis, the patient developed an elevated alkaline phosphatase and hyperbilirubinemia. Further studies would be necessary to investigate the link between DRESS and positive
AMA and/or primary biliary cirrhosis.
Introduction: Poultry meat is rarely reported as being a significant allergen contributing to urticaria or anaphylaxis. Chicken allergy usually manifests in the form of egg allergy in children or feather hypersensitivity in adults.
Prior studies have demonstrated cross reactivity among chicken, turkey and
other poultry meat. We report a case of urticaria following ingestion of bologna
containing turkey/chicken/pork. Case: A 4 year old Caucasian male with no
prior medical history presented with multiple episodes of urticaria after consumption of bologna. The symptoms occurred fifteen minutes following bologna
and ground turkey intake. The skin lesions were described as pruritic, raised,
erythematous wheals,and were predominantly localized on the face and extremities. Outbreaks occurred on six different occasions. Symptoms resolved with
diphenhydramine. Concomitantly there was a history of intermittent episodes
of nasal congestion and rhinorrhea unrelated to bologna intake. His environmental history is remarkable for cat exposure and feather pillows at home. Family history was significant for shellfish allergy in his maternal grandfather. On
Physical exam he was a well appearing child, with pale and swollen nasal
turbinates. There were no active skin lesions. Methods: Skin prick testing was
performed with Quintip devices. Prick test was considered positive if wheal
response was ≥ 4 mm. ImmunoCAP specific-IgE testing was performed by
Quest labs. Data: Skin prick testing was positive for turkey, chicken, pork and
feather mix (chicken- duck-goose). Subsequent RAST testing demonstrated
elevated levels of specific IgE to turkey (7.99 kU/L), pork (1.05 kU/L), chicken
(15.6 kU/L), egg white (4.14 kU/L) and yolk (8.10 kU/L). Conclusions: We
report a patient with poultry meat allergy who also is sensitized to eggs and
bird feathers. This case demonstrates that poultry meat allergy can induce
clinical symptoms. Physicians should be aware of the presence of chicken allergy
with or without concomitant feather or egg allergy.
S.A. Leonard*, C. Cunningham-Rundles, New York, NY.
Introduction: Common variable immunodeficiency (CVID) represents a
rare genetic disorder characterized by low serum IgG level, low IgA and/or
IgM levels, and diminished antibody production. We present three patients with
low IgG levels who were incorrectly diagnosed with CVID. Case series: Patient
1 is a 35-year-old woman with a complex medical history including steroiddependent asthma and multiple hospitalizations for infections. She has taken
daily oral steroids for the past three years with intermittent high doses of Solumedrol. Her lowest IgG level was 415 mg/dL; she had low B cell numbers,
normal mitogen and antigen responses, and normal titers to tetanus, diphtheria, meningococcal and pneumococcal. A diagnosis of CVID was given, and a
port placed for IVIG led to Enterococcus fecalis endocarditis and a possible
TIA. Patient 2 is a 27-year-old woman with a history of steroid-dependent
asthma and multiple ICU admissions for infections. Her lowest IgG level was
373 mg/dL; she had normal IgA and IgM levels and low CD4 T cell numbers.
A diagnosis of CVID was given, and a port placed for IVIG led to septicemia.
She developed two episodes of aseptic meningitis and receives weekly high
doses of steroids as premedication. Patient 3 is a 39-year-old woman with a
history of severe persistent asthma, multiple ICU admissions for infections,
allergic rhinitis, and recurrent urticaria. Sputum cultures grew Haemophilus
influenza, Pseudomonas, and Moraxella. She was treated with up to 40-60 mg
oral steroids daily for one year. Her lowest IgG level was 524 mg/dL; she had
normal T and B cells numbers, and protective pneumococcal titers. A diagnosis of CVID was given and she was started on subcutaneous Ig, often experiencing hives at her injection sites lasting up to one week. Discussion: All three
patients have a history of lung disease and were on systemic steroids when
IgG levels were measured. They were diagnosed with CVID but do not fit the
criteria and did not improve with Ig, instead experiencing side effects from
indwelling ports and infusions. More likely, systemic steroids reduced IgG levels. Conclusion: It is tempting to diagnose CVID in the setting of recurrent
infections and low IgG levels. A complete immune work-up after discontinuation of Ig replacement will be needed in these patients to exclude any underlying immunodeficiency or other condition.
D.J. Accetta*, H. Olteanu, J. Routes, Milwaukee, WI.
P.M. Bailey*1, G.C. Tsokos2, J.C. Crispin2, A. Kovalszki2, 1. Winchester,
MA; 2. Boston, MA.
Background: Common variable immunodeficiency (CVID) is a primary
immunodeficiency that is characterized by low levels of serum immunoglobulin G (IgG) and decreased ability make specific antibodies in response to
exogenous antigens. Based on our experience, we hypothesize that granulomatous and lymphocytic interstitial lung disease (GLILD) is a premalignant,
lymphoproliferative disorder that frequently progresses to frank lymphoma. In
support of this hypothesis, we report on the natural history of a patient with
CVID and biopsy-proven GLILD who subsequently developed an extranodal
marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the lung. Methods: Ten years ago at an outside facility, a 35 year old
female with CVID underwent an open lung biopsy, which demonstrated follicular bronchiolitis, one histological variant of GLILD. No specific therapy
was prescribed and she presented at our immunodeficiency clinic 3 years ago
with a restrictive pulmonary defect secondary to diffuse ILD, splenomegaly,
and diffuse adenopathy. Repeat open lung biopsy was again consistent with
GLILD, but the patient moved out of state and declined treatment. Three years
later, she returned to our clinic with progressive restrictive pulmonary disease
and new nodular infiltrates on CT scan of the chest. Results: Open lung biopsy
showed MALT lymphoma and treatment with rituximab was begun. Conclusions: This case supports the hypothesis that GLILD is a “premalignant” lymphoproliferative disorder that may progress to lymphoma over time. Such
patients should be carefully monitored for the development of lymphoma and
biopsies should be performed when the nature and character of the pulmonary
infiltrates, adenopathy or splenomegaly change.
J.T. Anderson*, H.W. Schroeder, Birmingham, AL.
BACKGROUND: Wells Syndrome (Eosinophilic Cellulitis) is a rare, recurrent dermatitis with histopathologic findings of eosinophilic infiltration of dermal and epidermal layers, development of “flame figures” and infiltration of
phagocytic histiocytes, associated with multiple triggers including insect bites.
The rash is variable, including bullous formation, papulovesicular, papulonodular, and plaque appearance. Certain patients have peripheral eosinophilia
and elevated IgE. Here, we report a patient who developed Wells Syndrome,
who was found to have hypogammaglobulinemia in addition to an elevated IgE.
CASE: 69 year old female presented with 3 months of recurrent rash after insect
bites (thought to be mosquito) characterized by swelling, erythema, pustules
and bullae over her arms and legs, lasting weeks. Her rash failed to improve
with antibiotics and antihistamines, but resolved with prednisone. She had no
prior history of chronic sino-pulmonary disease, chronic skin infections or
atopy. RESULTS: Evaluation revealed total IgG (589-665mg/dl) and IgG2 (156195mg/dl) subclass deficiency as well as elevated IgE (7,479-10,940KU/I) on
repeat occasions. She had poor response to pneumococcal vaccine provocation, but did show protective titers to tetanus and diphtheria. T and B cell lymphocyte markers had a normal distribution, but low absolute values. Biopsy of
her rash showed interstitial lymphohistiocytic infiltrate with neutrophils and
eosinophils of the dermis with a flame figure, characteristic of Wells Syndrome.
Evaluation for celiac disease, HIV and parasites was negative, as was ESR,
RF, ANA. Blood counts off steroids showed no peripheral eosinophilia. At 1
year follow up, the rash had resolved, but her low IgG persisted. DISCUSSION:
Like many patients with Wells Syndrome, our patient received further evaluation after antibiotic failure. Flame figures on skin biopsy are the most common finding, but are not pathognomonic and can be seen on insect bite separately. While elevated IgE occurs in Wells syndrome, our patient’s values are
higher than previous reports. Hypogammaglobulinemia can be a consequence
of steroid use; however repeat values off steroids demonstrated persistent low
total IgG. CONCLUSIONS: To our knowledge this is the first description of
Wells Syndrome with associated elevated IgE and persistent hypogammaglobulinemia.
Idiopathic CD4+ T–cell lymphocytopenia (ICL) is a rare acquired immune
disorder defined by a profound reduction in CD4+ T cell number in the absence
of any clear infectious, neoplastic, or other underlying process accounting for
CD4+ depletion. Our understanding of the clinical course, immunological features, and pathogenesis of T-cell depletion in ICL is limited. The majority of
the data comes from patients with significant underlying infections. It is not
clear if patients with ICL without evidence of opportunistic infections have similar features. We present the case of a 37 year-old priest who was found to have
a low CD4+ cell count and subsequently diagnosed with ICL but without evidence of opportunistic infection. At the time of initial evaluation, he reported
a one-year history of episodic fevers and night sweats. His CD4 count was found
to be 324 with normal CD8 and B cell counts and normal immunoglobulin
subclasses. Immunophenotypic analysis demonstrated CD4 lymphocytopia and
increased CD4- CD8- T cells (16.9%) with ОіОґ cell predominance (95%) (fig
1). Increased double negative T cells have been associated with autoimmune
and infectious diseases but all testing for these was negative, including HIV
PCR, ANA, and anti-lymphocyte antibodies. Cytokine studies revealed that
secretion of INF-Оі, IL-2, IL-17, and IL-6 was similar to normal controls. His
CD4 count has continued to trend down to < 300, with most recent being 260.
He had one episode of community acquired pneumonia one year ago. NIH evaluation has been negative for opportunistic infections. He has remained free of
symptoms such as febrile episodes for the past six months. This case contributes
to a growing body of data suggesting that while ICL is a disease of varied clinical manifestations, many immunological features among patients are similar.
Interestingly, in contrast to ICL patients having opportunistic infections we find
intact T cell responses in this patient. Data from HIV patients has shown that
T cell responses are inversely correlated with control of viral load. Whether
the presence of a cellular response despite lymphocytopenia is protective against
significant infection is currently being investigated. Studying patients such as
ours will further understanding of this rare entity and possibly contribute to
treatment modalities in those more severely affected.
N. Baman*, N. Rider, G. Ghaffari, Hershey, PA.
Introduction Chronic Granulomatous Disease (CGD) is a genetically heterogenous disease due to a primary defect of the phagocytic NADPH oxidase.
Characterized by recurrent life-threatening bacterial and fungal infections as
well as dysregulated granuloma formation, CGD is one of the most common
primary immunodeficiency syndromes, with an incidence of 1 case per 250,000
in the United States. There is thought to be a risk of autoimmune disease in
patients with CGD. We present a case of CGD with Type 1 diabetes mellitus
(DM) and a literature review of case reports suggesting CGD association with
autoimmune diseases. Methods OVID and PubMed were searched with the
following key terms: CGD, chronic granulomatous disease, diabetes mellitus, autoimmune diseases. Case Report A 3 year-old male with a history of
failure to thrive and Type 1 DM presented with fevers, weight loss, recurrent
suppurative lymphadenitis and respiratory distress. On admission, he was
found to be in diabetic ketoacidosis and developed respiratory failure requir-
ing mechanical ventilation. He was diagnosed with Nocardia farcinia pneumonia following bronchoalveolar lavage. Dihydrorhodamine-123 (DHR) test
revealed that only 12% of neutrophils exhibited normal oxidative activity at
24 hours (normal ≥ 90%); remainder of the immune workup was within normal limits. Confirmation of the diagnosis of x-linked CGD after genomic
sequencing mutation analysis revealed a gene mutation for CYBB 1222A>G
of gp91phox. Following resolution of his pneumonia, the patient underwent
hematopoietic cell transplantation from a fully-matched sibling. Since transplantation, the patient has done well from an infection standpoint. Results Literature review revealed seven pediatric case reports of autoimmune disease
association with CGD including sarcoidosis, IgA nephropathy, juvenile idiopathic arthritis, antiphospholipid syndrome, cutaneous lupus erythematosus,
inflammatory bowel disease and steroid-responsive recurrent pericardial effusions. Conclusion Infections and granulomas continue to be the most common manifestations of CGD; however, there is a subset of patients with CGD
who experience autoimmunity. As autoimmune disease leads to abnormal healing and autoinflammation, maintaining a high index of suspicion for autoimmune disorders in patients with CGD could minimize unnecessary tests and
allow early initiation of appropriate care.
W. Aberer*1, T.K. Hoffmann2, M. Wiednig1, B.J. Bloom3, N. Nair3, B. Hoch4,
A. Lachman4, J. Greve2, 1. Graz, Austria; 2. Essen, Germany; 3. Cambridge, MA; 4. Berlin, Germany.
Introduction: A self-administered subcutaneous treatment for HAE may
decrease the burden of this therapy on the patient and healthcare system. We
describe preliminary results of an open label study of the safety, tolerability
and efficacy of self-administered subcutaneous injections of icatibant during
acute attacks of HAE. Methods: Patients with HAE Type I or II could participate. Subjects naГЇve to icatibant received treatment their first attack in the hospital setting, by a healthcare professional. First attacks in non-naГЇve subjects,
and second attacks in naГЇve subjects were self-treated. The study is ongoing;
the data as summarized below is from the first 10 self-treated attacks (7 nonnaГЇve and 3 naГЇve patients). Safety was assessed by adverse event (AE) reporting and separate assessment of local tolerability of injections. Efficacy was
assessed based on severity of symptoms using the Visual Analog Scale (VAS)
for skin swelling, skin pain, and abdominal pain. Results: Adverse events were
symptoms of HAE and rhinitis. There were no severe AE’s. About 90% experienced injection site reactions (erythema,swelling, burning/itching or pain),
which were generally rated as mild; a majority resolved within 6 hrs. 9/10 subjects achieved symptom relief during with icatibant treatment with their selftreated attack, achieving onset of 50% relief in the composite VAS endpoint
by a median of 4 hrs after injection (95% CI: 2-6 hrs). When using time of onset
to relief of the primary VAS symptom alone, the median time was 2 hrs after
injection (95% CI: 2-6 hrs). Of the 3 icatibant-naГЇve subjects treated, the time
of onset to relief was at least as good for the second, self-treated attack as for
the first, healthcare provider-treated attack, as measured by both the primary
symptom and 3-component VAS score. 1/10 subject received rescue medication 29 hrs after treatment of a naГЇve attack by health care provider, while 2/10
subjects received rescue medication, 17 and 27.5 hrs respectively, after selftreated attacks, one of whom also did not respond to the rescue medication.
The time to symptom relief analysis was unaffected even after adjusting for
the use of rescue medication. Conclusion: Preliminary data show that selfinjected icatibant treatment was generally well-tolerated and most patients
achieved a clinical response.
K. Bork*1, S. Fremann2, W. Kreuz3, 1. Mainz, Germany; 2. Marburg, Germany; 3. Frankfurt, Germany.
RATIONALE: Hereditary angioedema (HAE) is a rare disorder due to functional deficiency in C1 inhibitor (C1-INH), resulting in periodic attacks of acute
edema that can be highly distressing. Replacement of the deficient C1-INH is
recommended as first-line therapy for these attacks, demonstrating rapid onset
of symptom relief within 30 minutes or less, depending on the location of the
attack. CSL Behring’s pasteurized C1 INH concentrate has been marketed since
1985 in Europe and other countries worldwide for the treatment of acute HAE
attacks. METHODS: We reviewed spontaneous reports for adverse drug reactions (ADRs) received by CSL Behring’s Global Pharmacovigilance for the
company’s pasteurized C1-INH concentrate, covering the 25-year period from
the product’s launch in 1985 until 30 June 2010. RESULTS: C1-INH concentrate for more than 500,000 treatments was distributed during the reporting
period. A total of 70 cases of suspected ADR have been reported worldwide,
of which 47 cases were covered by the product’s known safety profile: allergic- or anaphylactic-type reactions (7) (in very rare cases involving shock),
chills and fever (3), lack of effect (17), suspected virus transmission (5), and
thrombosis (15). None of the suspected virus transmissions could be attributed to C1-INH concentrate. Only one case of thrombosis occurred when C1INH concentrate was used in the labeled indication; causality was excluded
after autopsy revealed pre-existing cerebromalacia in this patient. The other
14 cases of thrombosis occurred during off-label use in cardiac surgery, involving substantially higher doses of C1-INH than indicated in the label. 23 of the
70 cases involved isolated reports of varying symptoms not covered by the
known safety profile of C1-INH concentrate, including one case of pulmonary
microemboli. A causal relationship to the product could not be established for
any of these unlisted ADRs. According to CIOMS criteria, the overall ADR
reporting rate for C1-INH concentrate is “rare”. CONCLUSIONS: C1-INH
concentrate has a well-established safety profile based on more than 25 years
of post-marketing experience with more than 500,000 treatments. The product
is safe and well tolerated when used at the recommended dosage in the treatment of HAE attacks.
T.F. Carr*, P. Avila, Chicago, IL.
Introduction: Atopic dermatitis is a chronic skin disease in which the disruption of the epithelium and increased fibronectin causes frequent staphylococcal skin infection and may predispose patients to the development of staphylococcus aureus bacteremia or other deep-seated infections. This is the first
case report to document development of staphylococcus aureus bacteriuria,
osteomyelitis, and native valve endocarditis in the same patient. Case presentation: A 19 year old male with a lifelong history of severe refractory eczema,
allergic rhinitis, and asthma presented to an outside hospital with fever, fatigue,
and back pain. Initial evaluation revealed staphylococcus aureus bacteremia
and renal infarct. Five years ago, he developed MRSA osteomyelitis and discitis that was treated with intravenous antibiotics. He developed staphylococcus
aureus bacteriuria 18 months ago. He has also developed severe viral respiratory infections yearly and occasional skin abcesses. His family history is significant for severe eczema, atopy, and autoimmune disease. Physical exam
revealed a young, ill-appearing teenager frequently scratching his skin. Skin
examination was remarkable for erythema and scaling of the face, arms, and
torso, with diffuse excoriation and crusted scabs, hyperkeratosis and hyperpigmentation of the neck, as well as splinter hemorrhages, Janeway lesions,
and Osler’s nodes. Laboratory evaluation revealed absolute eosinophil count
of 800/uL (14%), with IgE 3807 IU/mL, 3/14 protective anti-pneumococcal
antibody titers and IgG2 177(nl 242-700). Extensive additional immunodeficiency testing was performed, including negative stat-3 mutation; neutrophil
function, lymphocyte subsets, complements, mannose-binding lectin, HIV antibody and vitamin levels were normal. Transthoracic echocardiography was consistent with mitral valve endocarditis. The patient underwent open heart surgery with mitral valve replacement; examination of the native valve revealed
large vegetation without underlying defect. He will receive ongoing antibiotic
prophylaxis as well as aggressive treatment of eczema. Discussion: This case
illustrates how disruption of the skin barrier with staphylococcus aureus colonization in atopic eczema without immunodeficiency can give rise to severe
deep-seated infections.
W. Chan*, R.L. Roberts, E.R. Stiehm, Los Angeles, CA.
Background: Hematopoietic stem cell transplantation is the treatment of
choice for severe combined immunodeficiency (SCID). Despite successful Tcell engraftment in transplanted patients, B-cell engraftment is not achieved
in most patients, with up to 62% of patients still requiring IV immunoglobu-
lin therapy post transplant. Methods: We report two half sibling males with Xlinked common Оіchain SCID. Sibling 1 was treated with T-cell depleted haploidentical bone marrow from the mother at 2.5 months of age and sibling 2 was
treated with 7/8 HLA-matched unrelated cord blood at 3.5 months of age. Both
patients received pre-transplant conditioning with busulfan and cytoxan as well
as GvHD prophylaxis with cyclosporine. Results: Both siblings had evidence
of T cell engraftment. Sibling 1 exhibited neutrophil engraftment > 500/mm3
by 18days, platelets > 50x x109 /L by 20days, and T cells > 200cells/ВµL by 110
days. Sibling 2 exhibited neutrophil, platelet, and T cell engraftment by 12,
32, and 90 days, respectively. Grade I GvHD limited to the skin developed in
sibling 2. Lymphocytes from sibling 2 expressed 99% donor chimerism compared to 29% in sibling 1. Natural killer cell function was normal in sibling 2
and decreased in sibling 1. Sibling 1 continues to have hypogammaglobulinemia, abnormal antibody responses, and requires monthly IVIG. Sibling 2 was
able to reconstitute B cell function by 3 months, maintain normal IgG levels
with protective antibody responses, and is not dependent on IVIG. A literature
review of 19 cases of cord blood transplant in SCID revealed 8 of 13(61%)
achieved B cell engraftment, 15 of 18(83%) do not need IVIG post transplant,
and 9 of 9 have normal antibody responses to vaccines at their last follow up.
Two patients developed grade III, one with grade IV and five with grade I GvHD
of the skin. Fourteen of 19(74%) are alive and well with 2 deaths in ADA deficient patients who died of pre-existing inflammatory complications prior to
transplant and parainfluenza pneumonitis and 3 deaths in X-linked SCID from
graft failure, multisystem organ failure and grade III GvHD. Conclusion: Unrelated umbilical cord blood is an alternative source of stem cells for transplantation in children with SCID and may provide a higher likelihood of B cell
reconstitution compared to HLA-haploidentical bone marrow transplants.
E. Chang*, S.P. Jariwala, E. Jerschow, G. Hudes, D. Rosenstreich,
Bronx, NY.
Introduction: Angioedema is classified as hereditary, acquired, or idiopathic,
but can result from allergies, medications, or systemic diseases. When recurrent without clear triggers, screening for complement abnormalities is routine.
We describe three patients with angioedema associated with C2 deficiency.
Methods: Case series Results: Patient One - A 46-year-old female with 9 months
of episodic abdominal pain, nausea, and vomiting had a CT of the abdomen
revealing intestinal angioedema. Laboratory testing revealed C2 deficiency
with undetectable levels, low C1-esterase INH and C4, normal C3, and positive ANA (titer 1:40) (Table). Interestingly, this patient had been on oral contraceptives on initial presentation, and symptoms improved following discontinuation. Patient Two - A 69-year-old female with a history of low C4 (diagnosed
at another hospital), positive lupus anticoagulant without previous thromboses,
and a generalized rash diagnosed on biopsy as urticarial vasculitis, was evaluated for recurrent facial swelling. Laboratory analysis revealed undetectable
C2, low C3 and C4, and normal C1-esterase INH (Table). She was diagnosed
with angioedema associated with C2 deficiency, and treated with prednisone
and hydroxychloroquine for urticarial vasculitis. Patient Three - A 60-year-old
female developed multiple episodes of facial, extremity, and oropharyngeal
swelling after rhytidectomy in Puerto Rico. She was then found to have C1esterase INH deficiency and low total complement. Further testing with our
evaluation revealed undetectable C2, low C4 and C1-esterase INH, decreased
functional C1-esterase INH, undetectable C1q, normal C3, and negative C1q
autoantibody (Table). C1-INH autoantibody results are pending. The patient
continues to have recurrent angioedema despite therapy with prednisone, danazol, and Cinryze. Conclusion: The etiologies for angioedema are vast, and identifying underlying causes can be a clinical challenge. We report three patients
with recurrent angioedema and C2 deficiency. Of note, C2 deficiency has been
associated with autoimmune diseases, such as systemic lupus erythematosus
and anti-cardiolipin antibody formation. Identifying the precise mechanisms
surrounding angioedema is imperative as treatment options markedly differ.
Laboratory testing on three patients with angioedema and C2 deficiency.
*Laboratory values are listed in chronologic order with numbers in parentheses representing the order of each test.
S.I. Dever*, J. Baldwin, Ann Arbor, MI.
Introduction: We report a 51-year-old man with a history of hypogonadism, depression/anxiety, ADHD, bipolar disorder and hyperlipidemia
who was referred for evaluation of hypogammaglobulinemia and assessment of the appropriateness of IVIG treatment in the setting of relentless
viral infectious symptoms. His primary physician had obtained immunoglobulin levels: IgG 567 mg/dL (694-1618), IgM 31 mg/dL (48-271), and IgA
273 mg/dL (81-463). Methods: An infection history was conducted which
revealed meningitis at age 23, two cellulitis infections, Helicobacter pylori
with ulcers, and pruritic sores located in the nares and ears. The patient
stated “antibiotic failure” had occurred in treatment of the H. pylori infection. He also complained of unremitting viral symptoms with a negative
work-up by his primary physician. He denied history of pneumonias, sinusitis, urinary tract infections, pyelonephritis and osteomyelitis. A comprehensive social history was also conducted. Results: The social history
revealed that the patient was under significant economic hardship. Detailed
inquiry about his financial burden enabled us to discover that the patient
was donating plasma four to six times per month to supplement his income.
Upon reflection, the patient agreed that the onset of his symptoms was
contemporary to the start of his aggressive plasma donation. Improvement
of immunoglobulin levels were noted two weeks after cessation of plasma
donation: IgG 678 mg/dL, IgA 261 mg/dL, and IgM 36 mg/dL. Conclusion:
We believe this case illustrates the importance of conducting a thorough
history to correctly diagnose patients and thereby prevent serious infection
and increased strain on limited medical resources.
L.P. Titov*1, O.O.Yanovich1, E.S. Nosova1, M.V. Doroshko1, L.M. DuBuske2,
1. Minsk, Belarus; 2. Gardner, MA.
Background: Helicobacter pylori (H. pylori.) chronically colonizes the gastric epithelium, infecting nearly half of the world’s population while causing
chronic gastritis which is related to bacterial, environmental and host genetic
factors which together define the degree of gastric damage. Genetic polymorphisms in the regions promoting genes that encode inflammatory cytokines and
are associated with an increase in synthesis of cytokines may be related to
clinical disease induced by H. pylori. Methods: Genomic DNA was extracted
from the biopsies of 59 patients with various gastrointestinal diseases. Polymorphisms in IL-1RN and TNF-alpha genes were analyzed using the PCR and
allele-specific PCR. The study population included H. pylori positive gastritis
(n=36) and duodenal ulcer patients (n=23). Results: A comparison of the frequencies of various polymorphisms studied demonstrated that the genotype IL1RN*2/L was more frequent among patients with gastric ulcers in comparison
with chronic gastritis patients (70.6% vs. 39.1%, OR=3.8, CI – 0.9-15.8,
p<0.05). The -308 G/G genotype was found more often in patients with chronic
gastritis and duodenal ulcer (72.2% and 43.5%). Carriage of the alleles for
TNF-alpha-308 A was associated with increased risk for gastric ulcer development (OR=3, CI – 11.0 – 8.2, p<0.05). Conclusions: There is an association
between TNF-alpha and IL-1RN gene polymorphisms and the development of
gastric ulcers in patients in Belarus. These polymorphisms in cytokine related
genes may provide a basis for serious disease progression for patients with H.
pylori infections.
L.P. Titov*1, A.Y. Hancharou1, A.M. Skrahina1, N.S. Shpakovskaya1,
N.P. Antonova1, T.S. Novokhatsko1, A.M. Zalutskaya1, L.M. DuBuske2, 1.
Minsk, Belarus; 2. Gardner, MA.
Background: Dendritic cell (DC) based therapy, which has been well studied as a treatment of cancer, may be effective as therapy for chronic infections
including multiple drug resistant pulmonary tuberculosis (TB). Methods: To
obtain DC peripheral blood samples were drawn from 10 patients with multiple drug resistant TB. Monocytes were cultured in AIM-V medium with GMCSF and IL4 to produce immature DC (iDC) which were primed with M. tuberculosis lysates obtained from each patient and next cultured with TNF-alpha
and dibutyryl cAMP for 15–18 hours to obtain mature DC. DC were then
assayed for immunophenotype and sterility and injected subcutaneously three
times at 2–3-week intervals. Clinical monitoring, sputum assessments, chest
X-rays, and immune status were monitored. Results: DC from all patients
were sterile and morphologically intact with expression of CD83 by DC from
all patients being > 90%. The number of DC injected into each patient averaged 16.1 (range: 8.5–25.2) × 106. Injections of autologous DC were well tolerated by all patients. No local or systemic adverse effects were observed.
6/10 patients exhibited a good clinical response to therapy, which resulted in
mycobacterium clearance from sputum and X-ray improvement. 5/10 patients
had an increase in CD T-cell count, and 6/10 had an increase in INF-Оі positive
cells after treatment. Conclusion: Safety and tolerability of DC-based treatment of multiple drug resistant TB patients was seen with 60% of patients
having at least short term efficacy, suggesting that this may be a valuable new
cell based immunotherapy for this disease.
and common urogenital infections (p=0.085). The relationship between the
presence of polymorphic allele T (genotype carriers Thr/Ile and Ile/Ile) of the
TLR4 gene and risk of urogenital infections was not significant (p=0.683).
Conclusions: Immunodeficiency in patients with urogenital infections may be
hereditary and associated with TLR2 Arg753Gln and TLR4 Asp299Gly single
nucleotide polymorphisms, confirming the role of genetic variant Toll like
receptors in the pathogenesis and susceptibility for these infectious diseases.
M. Eisenfeld*, A. Rubinstein, Bronx, NY.
Introduction:There have been no prior reports of a patient with the novelV408M
FOXP3 mutation exhibiting signs of common variable immunodeficiency (CVID)
and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Methods: We evaluated a 20-year-old male with autoimmune disorders,
recurrent infections, and severe enteropathy. Results: The patient required 5 years
of parenteral hyperalimentation for malabsorption with small bowel villous atrophy, and was later diagnosed with hemorrhagic inflammatory bowel disease with
nodular hyperplasia. He has also suffered from Coombs positive autoimmune
hemolytic anemia, recurrent sepsis, a post-encephalitis seizure disorder, alopecia
areata, and autoimmune thyroiditis. His symptoms were refractory to treatment with
prednisone, cyclophosphamide, cyclosporine, tacrolimus, and azathioprine. CVID
was diagnosed with IgM, IgA, and IgG deficiency, decreased specific antibody
responses, and poor in vitro lymphocyte mitogenic and antigenic responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, Candida, and tetanus. Stool
О±-1 antitrypsin and serum IgE were both normal. CD19+ and CD20+ B cells were
initially elevated at 38% (Table 1). CD4+CD25+FOXP3+ T cells were present at
normal percentages, but genetic testing revealed an unusual point mutation atV408M
(c.1222G>A) in the forkhead box domain of the FOXP3 gene, leading to an amino
acid substitution. The patient’s mother is an unaffected carrier of the same mutation. His immunodeficiency improved on high-dose intravenous gammaglobulin,
and his autoimmune disorder was later treated with 3 doses of the anti-CD20 monoclonal antibody, rituximab, 375 mg/m2. His unremitting enteropathy markedly
improved and then remained normal over the next 4 years, when he required another
dose of rituximab and again saw immediate recovery. Conclusion: This is the first
case report of this novel V408M FOXP3 mutation causing a mixed clinical and
immunological picture of IPEX and CVID, in a patient whose enteropathy responded
only to rituximab. IPEX syndrome could not have been diagnosed solely by the phenotypic absence of regulatory T cells, but required genetic studies to define this
unusual mutation.
I.P. Kaidashev*1, O.V. Izmaylova1, O.A. Shlykova1, N.A. Bobrova1,
L.M. DuBuske2, 1. Poltava, Ukraine; 2. Gardner, MA.
Background: The prevalence of single-nucleotide polymorphisms of genes
Toll-like receptor genes such as TLR2 Arg753Gln (rs5743708) and TLR4
Asp299Gly (rs4986790) and Thr399Ile (rs4986791) may differ among healthy
individuals and patients with common urogenital diseases, and may lead to susceptibility to these infections. Methods: 299 healthy inhabitants of the Poltava
region of Ukraine balanced by gender, age from 19 to 62 years, were assessed.
The genomic DNA from blood lymphocytes was isolated by phenol-chloroform extraction. There were 156 patients in the group with urogenital infections. Scrapings of urethral and cervical epithelial cells were used to determine
the presence of DNA from urogenital pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma genitalium, Gardnerella vaginalis, Neisseria gonorrhoeae, and Trichomonas vaginalis which were assessed
by PCR. Determinations of polymorphisms of the genes TLR2 Arg753Gln,
TLR4 Asp299Gly and Thr399Ile were performed by PCR using specific
oligonucleotide primers, followed by restriction analysis. Restriction products
were revealed by electrophoresis in 3% agarose gels. Results: There was a strong
link between the presence of polymorphic allele A (genotype carriers of Arg/Gln
and Gln/Gln) of the TLR2 gene (p=0.0018), as well as the presence of polymorphic allele G (genotype carriers Asp/Gly and Gly/Gly) of the TLR4 gene
Table 1: Immune Parameters at Presentation
Table 1: Immune Parameters
S.B. Sindher*, M. Eisenfeld, N. Madhok, A. Djukic, J. Shliozberg, Bronx,
Introduction: Rett syndrome (RTT) is a neurodevelopmental disorder that
occurs almost exclusively in females. Affected patients initially develop normally, but then gradually lose speech and purposeful hand use. Stereotypic hand
movements, autistic features, ataxia, and breathing abnormalities subsequently
develop. Seizures occur in the majority of RTT patients. According to Steffenburg et al, Sweden, 2001, seizures are controlled with antiepileptic medication
in 46% of patients, while the remaining patients have intractable epilepsy. Methods: We evaluated a 4-year-old girl with RTT and intractable seizures, who presented with hypogammaglobulinemia (Table 1). Results: The patient was diagnosed with RTT at 20 months of age due to loss of milestones, and subsequent
genetic testing revealed a R255X nonsense mutation of the MECP2 gene. She
suffered from 10-15 short absence seizures per day, which were refractory to
treatment with carbamazepine and divalproex sodium. She also experienced multiple yearly episodes of prolonged sinusitis, bacterial conjunctivitis, and almost
monthly upper respiratory infections, some requiring long courses of antibiotics.
She was referred to immunology clinic for abnormal immunological data obtained
by her neurologist. On initial immune evaluation, the patient had a deficiency of
IgG and IgA, and poor specific antibody responses to tetanus, pertussis, diphtheria, hepatitis B, and the conjugated pneumococcal polyvalent-7 vaccines,
despite up to date immunizations. To treat the hypogammaglobulinemia and concurrent intractable seizures, she was started on high-dose intravenous gammaglobulin (IVIG) at 800 mg/kg every 3 weeks. Within 6 weeks of initiation of IVIG
therapy, her seizure frequency decreased to 0-5 episodes per day. She became
more alert and interactive, and has experienced no major infections to date.
Conclusion: A possible role of immune dysregulation in the pathogenesis of
pervasive developmental disorders has been postulated, and the connection may
extend to RTT as well, involving a skewed profile of pro-inflammatory cytokines
and overall activation of the immune system. Our patient is unique to RTT due
to her documented immunodeficiency, and here we present the first case report
of a patient with RTT and hypogammaglobulinemia whose seizures and infections improved dramatically with IVIG therapy.
M. Eisenfeld*, A. Rubinstein, Bronx, NY.
Introduction: Transient hypogammaglobulinemia of infancy (THI) is a selflimited disease, marked by recovery of delayed maturation of the humoral
immune system. Once adequate immune function is obtained, children are often
discharged from follow up. A percentage of patients with common variable
immunodeficiency (CVID) display mutations of the TNFRSF13B gene, also
known as TACI (transmembrane activator and calcium-modulator and
cyclophilin ligand interactor). THI has been noted in the history of adult patients
with CVID and in their family members. Patients with a diagnosis of THI have
not been routinely evaluated for the presence of the TACI mutation, and therefore, early diagnosis of potential CVID may have been missed. Methods: We
evaluated a 2-year-old child with recurrent otitis and sinusitis over a period of
2 years. Results: The patient has experienced chronic, antibiotic-resistant sinusitis, and later underwent a tonsillectomy and adenoidectomy for recurrent otitis and tonsillitis. On initial immune evaluation, the patient had a deficiency
of IgM and IgG, and poor specific antibody responses to measles, mumps, varicella, and the conjugated pneumococcal polyvalent-7 vaccines. Further testing revealed normal lymphocyte mitogenic responses to phytohemagglutinin,
concanavalin A, and pokeweed mitogen. Upon revaccination with a half-dose
of the MMR vaccine and the 23-valent pneumococcal vaccine, he initially developed adequate antibody responses suggesting THI. However, on further follow up he has lost his specific pneumococcal antibodies, and quantitative
immunoglobulins gradually decreased over a 2 year period with persistence of
chronic infections. Genetic testing revealed an autosomal heterozygous missense mutation of the TNFRSF13B (TACI) gene, with a c.512T>G nucleotide
change. Family evaluation revealed a maternal grandfather and aunt with both
the same TACI mutation and clinical CVID requiring intravenous gammaglobulin treatment. His mother is an unaffected carrier. Conclusion: Patients
with THI may need genetic testing and/or regular immune surveillance into
adulthood. Presence of a TACI mutation may signify a predisposition to develop
lifelong immunodeficiency.
Table 1: Immune Parameters during the Study Period
A. Gaye*, M. Girdhar, K. Lindgren, M. Sarvida, R.J. Mittel, A.D. Korenblit,
Chicago, IL.
Rationale: Raising awareness of the presentation of Primary ImmunoDeficiency (PID) Methods: Report of 2 cases and review of the literature
Results: Male 2 month old fraternal twins of non-consanguinous parents presented with fever (1) and rapid deterioration from an upper respiratory infection. Hepatosplenomegaly (2), bi-cytopenia (3) (neutropenia, thrombocytopenia), liver failure, hypertriglyceridemia, and disseminated intravascular
coagulation (4) were present. Hemophagocytosis (5) was seen in the bone
marrow. The serum ferritin level was elevated (6). NK cell activity studies
(7) and serum or CSF IL2-r level (8) were not obtained before starting therapy. Both children were placed on chemo-immunotherapy protocol HLH2004, including dexamethasone, cyclosporine, and etoposide. One child succumbed after 2 months of intensive therapy; the other, now 8 months old,
received an allogeneic stem cell transplant. The Familial Hemophagocytic
Lympho-Histiocytosis (HLH) syndromes are autosomal recessive diseases
of immune regulation – Table 1. Prevalence is 1:50,000 live births or less.
Circulating T and B cell and immunoglobulin levels are normal. NK cell and
CTL activity is decreased. Patients have fever and marked elevation of all
markers of inflammation. Conclusions: A rare PID was diagnosed in 2 children who presented together with an illness first mistaken for an acquired
infection, as supported by its sudden onset and their exposure to siblings.
While the dizygotic pregnancy made possible all recessive and X-linked PID,
the compilation of 6 of the 8 criteria (5 suffice) suggested by the American
Histiocyte Society for diagnosis of HLH lead to rapid institution of therapy.
Genetic studies confirmed the diagnosis. The odds of a fraternal twin presentation of perforin deficiency are 1/5 million.
Table 1 - 8 forms of HLH with protein-encoding gene mutations are
described to date
S.Z. Faghih*, E. Secord, Detroit, MI.
Introduction: Autoimmune disease (AID) is a common complication in
Common Variable Immune Deficiency (CVID), occurring in up to 25% of
patients in some studies. There are case reports of patients presenting with
autoimmune disease. A case series of patients from our pediatric primary
immune deficiency (PID) clinic reveals that autoimmune disease often predates the onset of infectious complications in our Pediatric CVID patients.
Objective: To determine the temporal relation between autoimmune disease
and common variable immunodeficiency (CVID) in a case series from a pediatric and adolescent clinic. Method: A chart review of pediatric CVID patients
seen in the primary immunodeficiency clinic at a children’s hospital over the
past ten years was conducted. The presenting symptom and date of diagnosis of both autoimmune disease and CVID was recorded and the temporal
relation was examined. Results: A survey of our pediatric and adolescent
CVID patients revealed that 6/10 had autoimmune disease prior to the diagnosis of CVID. Four out of the six patients had a diagnosis of Evan’s syndrome, while one of patients had a diagnosis of autoimmune hepatitis and the
other vitiligo. One of the patients with the Evans syndrome also presented
with autoimmune hepatitis, as well as diabetes mellitus type I. Discussion/Conclusion: CVID is the most symptomatic PID in the adult. Autoimmune manifestations occur in twenty-two percent of patients with CVID. In
a study by Heeney et al., it was established that four children whom presented
with autoimmune cytopenia were screened to reveal low serum immunoglobulin levels with the subsequent diagnosis of CVID. 6/10 CVID patients in our
pediatric PID clinic had autoimmune disease prior to diagnosis with CVID.
Therefore, it may be advantageous to screen for immunodeficiency when a
child is first diagnosed with autoimmune disease.
S.G. Gendi*1, L. Geng1, H. Corey2, H. Jyonouchi1, 1. Newark, NJ; 2. Summit, NJ.
Introduction: Clinical features of APECED, caused by mutations in the
autoimmune regulator gene (AIRE), are characterized by multiple autoimmune
conditions as well as chronic mucocutaneous candidiasis (CMC). Given the
crucial role of AIRE in central tolerance, development of autoimmunity is
expected, however, the pathogenesis of CMC in APECED is poorly understood.
Recent studies indicate a crucial role of Th17 cells in anti-fungal immune
defense. Moreover, others reported the development of autoantibodies against
Th17 cytokines in APECED patients. These findings prompted us to examine
Th17 function and differentiation in one APECED patient. Case: A 13 yr-old
Asian Indian male presented with a history of hypoparathryoidism, Addison’s
disease, alopecia totalis, CMC, recurrent sinopulmonary infections, and chronic
renal failure. Mutation analysis revealed a homozygous deletion of
c.967_997del13 in the AIRE gene, a known mutation in APECED. Methods:
Enumeration of T cell subsets was conducted by intracellular staining of lineage-specific cytokines (IFN-Оі, IL-4, IL-17A, and IL-10/TGF-ОІ) following stimulation by a polyclonal stimulant (Staphylococcal enterotoxin B) or Candida
antigen (Ag). T cell cytokine production was measured by stimulating peripheral blood mononuclear cells (PBMCs) with T cell mitogens, candida Ag, and
IFN-Оі inducing cytokines. Function of innate immunity was assessed by stimulating PBMCs with agonists of toll like receptors (TLR) and a dectin-1 agonist. Results: In response to TLR agonists, PBMCs from the APECED patient
produced elevated levels cytokines important for Th17 differentiation (IL-6,
IL-1ОІ, and TGF-ОІ). Proinflammatory cytokine production in response to TLR2/6
agonists and dectin 1 agonists were normal. When stimulating T cells, his
PBMCs produced equivalent levels of Th1 cytokines (IFN-Оі and IL-12) as a
control but little IL-17A. This is in contrast to the presence of a normal frequency of IL-17A+Th cells. However, most of his IL-17A+Th cells also coexpressed IFN-Оі. Conclusions: Our results reveal impaired Th17 function and
Th17 differentiation in this APECED patient, suggesting that the lack of Th17
mediated defense predisposes APECED patients to CMC. Increased production of cytokines important for Th17 differentiation may reflect compensatory
mechanisms for impaired Th17 differentiation.
T. Harvey*1, K. Paris2, 1. Metairie, LA; 2. New Orleans, LA.
Rationale: We identified two female patients with diagnosed with thymoma
and recurrent infections, one evaluated by an immunologist prior to thymectomy and the second diagnosed with Good syndrome one year post-thymectomy. Good syndrome is an acquired immunodefiency characterized by the
association of thymoma with hypogammaglobulinemia and variable defects in
cell-mediated immunity. The immunological abnormalities do not correct after
thymectomy. Methods: A review of the clinical and laboratory findings and
therapeutic interventions prior to medical care by an immunologist. Results:
The first patient presented at age 60 years to a gastroenterologist with a three
year history of diarrhea, dysphagia, and severe, recurrent esophageal candidiasis. She had no history of immunosuppression or antibiotic use. She was
referred to an immunologist, and immunologic evaluation showed lymphopenia with normal total immunoglobulins. Despite normal lymphocyte subpopulations, she demonstrated anergy to Candida by DTH testing. A chest CT was
ordered due to recognition of the known association of thymoma with the clinical phenotype of chronic mucocutaneous candidiasis. The CT revealed a thymoma which was resected. Post-thymectomy, she developed a positive ANA
and anti-Ach receptor antibodies, consistent with myasthenia gravis. The second patient presented at age 47 years to a pulmonologist with a two year history of chronic bronchitis and sinusitis. Chest CT ordered by the pulmonologist showed a thymoma which was resected. Her chronic infections persisted,
and she had sinus surgery three months later. She then developed chronic otitis media and worsening sinusitis requiring antibiotics for nearly one year prior
to referral to an immunologist. Immunological evaluation showed agammaglobulinemia with absent B cells, consistent with classic Good syndrome. She
was treated with replacement IgG therapy with resolution of her infections. A
repeat chest CT showed bronchiectasis. Conclusions: Good syndrome is associated with heterogeneous clinic presentations and immunologic phenotypes.
The association of thymoma with defects in antibody-mediated or cell-mediated immunity is not widely recognized. Early diagnosis and treatment by an
immunologist may improve the clinical outcome and quality of life of these
patients, and may be life-saving.
H.S. Hernandez-Trujillo*, K.E. Sullivan, S. Jyonouchi, Philadelphia, PA.
Introduction: Dyskeratosis Congenita (DKC) is a rare bone marrow failure
syndrome caused by a defect in telomere maintenance. It is a clinically and genetically heterogeneous syndrome characterized by mucocutaneous features, immunodeficiency, pancytopenia, and increased risk of malignancy.We describe an infantile severe case of DKC, also known as Hoyeraal-Hreidarsson Syndrome, with a
novel mutation of the DKC1 gene. Case: A male infant presented at 14 mo to an
outside facility with respiratory failure from Pneumocystis jiroveci pneumonia along
with FTT and bloody diarrhea. Colonoscopy showed apoptosis of epithelial cells
suggestive of gut GVHD. Immune evaluation revealed a low normal CD3 count
(1461 cells/mm3) but profoundly decreased CD19 count (52 cells/mm3) and CD16/56
count (7 cells/mm3).T cell proliferation to mitogen stimulation was normal. He also
had low IgG and was started on IVIG therapy. A small thymic shadow on CXR,
prompted consideration of DiGeorge, but FISH for 22q11.2 deletion was negative.
XLA was also considered initially based on the very low B cell count but genetic
testing for BTK mutations was negative. At 17 mos old, the patient was transferred
to our institution for further evaluation of severe enteropathy with malabsorption,
FTT, developmental delay, andT+B-NK- immunodeficiency.A brain MRI revealed
marked cerebellar hypoplasia.Telomere flow-FISH of lymphocytes revealed telomere lengths well below the 1st percentile for age and genetic testing confirmed a
diagnosis of DKC with a novel missense mutation in the DKC1 gene. Discussion:
DKC is a primary immunodeficiency caused by mutations (X-linked, AD, or AR)
that result in defective telomere maintenance. Highly proliferative cells such as lymphocytes, hematopoietic stem cells, and skin/gut epithelium are particularly sensitive to telomerase dysfunction. Premature telomere attrition triggers cell senescence
and apoptosis, resulting in many of the immunologic and clinical findings of DKC.
This disease can present in infancy or adulthood, with more severe somatic and
immunologic abnormalities present in the infant-onset form. DKC can pose a diagnostic dilemma due to significant phenotypic overlap with other conditions such as
HIV infection, SCID, or agammaglobulinemia.Thus, DKC should be very high on
the differential for infants presenting with IUGR, FTT, enteropathy, cerebellar
hypoplasia and agammaglobulinemia.
S. Bantz*, T. Biason, R. Herzog, J.E. Yu, New York, NY.
Background: Intestinal lymphangiectasia (IL) is characterized by hypoalbuminemia and edema resulting from dilation of intestinal lymphatic vessels.
It is also associated with hypogammaglobulinemia and lymphocytopenia which
can prompt an evaluation for a primary immunodeficiency. Methods: We
describe a patient with IL who was referred for evaluation and management of
his hypogammaglobulinemia and profound T cell lymphocytopenia. Results:
Our patient was a 3 year old male with a history of progressive generalized
edema, emesis, and diarrhea. Abdominal CT and ultrasound, sweat chloride
test, and renal and cardiac evaluations were normal. He had an elevated stool
О±1-antitrypsin level, an upper gastrointestinal series with small bowel followthrough demonstrating jejunal nodularity, and a biopsy showing dilated lymphatics, all of which were suggestive of IL. He had no history of severe or recurrent bacterial infections. Physical exam was remarkable for a well-appearing,
well-developed boy with unilateral non-pitting edema of the lower leg. Initial
laboratory testing was remarkable for albumin 2.1 g/dL, total protein 4.0 g/dL,
IgG 133 mg/dL (441-1135), IgA < 5 mg/dL (2.5-6.8), and IgM 19 mg/dL (29160). Lymphocyte subsets revealed normal total lymphocyte count, profoundly
low CD4 T cells 292 cells/mm3 (562-2696), CD8 T cells 310 cells/mm3 (3311445), normal B cells 638 cells/mm3, and normal NK cells 492 cells/mm3.
Despite treatment with biweekly subcutaneous immunoglobulin replacement
therapy, trough immunoglobulin levels were significant for IgG 156 mg/dL,
IgM 72 mg/dL, and IgA 28 mg/dL. Subsequent functional testing, however,
demonstrated protective specific antibody titers for 5 of 14 pneumococcal
serotypes, and normal lymphocyte mitogen responses to phytohemagglutinin,
pokeweed, and concanavalin A. Conclusions: Patients with IL can present with
an apparent immunodeficiency of both humoral and cellular compartments
which can be suggestive of severe combined immunodeficiency (SCID). Functional immunologic assessment is helpful in determining whether this is due
to the underlying disease or a primary immune deficiency.
H. Jin*, J.E. Yu, R. Herzog, New York, NY.
INTRODUCTION: Increased risk for serious infection, malignancy and
autoimmunity have described after anti-tumor necrosis factor (TNF) therapy, including reactivation of latent tuberculosis, lupus like syndromes, antibodies to infliximab and adalimumab, lymphomas and other malignancies. METHODS:We present a patient who developed disseminated (MAC) lympadenopathy after receiving
anti-TNFО± therapy for gastrointestinal inflammation. RESULTS: An 11 year old
girl with history of renal hypertension presented with diarrhea, fatigue, weight
loss and anemia. Endoscopy and colonoscopy revealed focal active duodenitis, gas-
tritis with no granulomas, and mild crypt epithelial regenerative changes in colonic
and rectal mucosa. She was treated with three months of oral steroids and another
three months of 6 mercapto-purine (6MP), but developed elevated liver enzyme
levels. She was then started on anti-TNFО± therapy consisting of two months of
Infliximab followed by 5 months of Adalimumab. During the course of the antiTNFО± therapy, she developed enlarged cervical and supraclaricular lymph nodes.
Biopsies of her lymph nodes and serum Quantiferon Gold test revealed disseminated MAC infection. She was treated with ethambutol, clarithromycin and rifampin
with subsequent negative blood culture and decreased Quantiferon level. HIV1/2
antibodies and bone marrow biopsy were negative. Immunologic workup revealed
normal distribution of hematopoietic cells and lymphocyte subsets, low IgM 14
mg/dL (52-367), elevated IgG 693-2380 mg/dL (70-432), and normal to elevated
IgA ranging 70-312 mg/dL (70-321). DHR testing for CGD was normal. Rheumatoid factor (RF) was weakly positive.Antinuclear antibodies (ANA) and anti-dsDNA
were negative and C3 and C4 were normal. Specific antibodies for tetanus and diphtheria were normal but antibodies to pneumococcal were absent following 23-valent
pneumococcal vaccination. Lymphocyte mitogen response assay revealed mildly
decreased cellular response. CONCLUSIONS:This case demonstrates an increasing risk of anti-TNFО± therapy. Mycobacterium other than tuberculosis (MOTT) is
rare, but is an emerging complication of anti-TNFО± therapy, and tends to rapidly
progress. Patients receiving anti-TNFО± therapy should be screened for immunodeficiency prior to therapy and clinically monitored thereafter for potentially progressive infectious complications.
Primary Immunodeficiency (PID) was diagnosed in patients with DS. Results:
Of the 170 total (prevalent) cases available for study, 59 (34.7%) were incident
cases. Two subjects had identified primary immunodeficiency in the cohort, one
with CD4 lymphopenia and one with selective polysaccharide unresponsiveness.
The incidence of PID was 42 per 100,000 person years. Lymphopenia: 127 subjects had a CBC with differential count performed (74.7%). Persistent lymphopenia
(defined as absolute lymphocyte count [ALC] < 1. 5X109/L in children 2-11 years,
<1.2X109/L in children 12-16 years and <0.9X109/L in older adolescents and
adults; was present in 27 subjects (21%).Subjects with lymphopenia were more
likely to have pneumonia (OR: 6.69, CI: 2.65-16.9; p<0.0001) and episodes of
recurrent pneumonia (OR: 4.0, CI: 1.38-11.5, p=0.007). Hospitalization: Data
regarding hospitalization was available for 156 subjects (92%). One or more
episodes of hospitalization were reported in 97 (62%) of these 156 subjects. Lymphopenia was significantly associated with hospitalization (OR: 6.13, CI: 1.7221.7, p=0.002).The median duration of hospitalization was longer in subjects with
lymphopenia (4 days, IQR: 2-5 days) as compared with subjects without lymphopenia (2 days, IQR: 1-4 days, P<0.001). Conclusion: 1)The presence of PID
in this cohort was higher than in the general population( similar study from Olmsted County showed that the incidence of PID was 10.3 per 100,000 p-y) 2)There
was a significant correlation between the presence of lymphopenia and episodes
of pneumonia, hospitalization rates, and duration of hospitalization. Whether lymphopenia is a cause of infections leading to hospitalization or is a surrogate of some
other factor leading to hospitalization is not clear. However, detecting lymphopenia in a patient with DS may warrant further immunologic testing to assess the
possibility of additional immune dysfunction.
S.P. Jariwala*, N. Jinjolava, J. Fodeman, G. de Vos, D. Rosenstreich, Bronx,
Introduction: Legionellosis is characterized by varied clinical presentations
ranging from mild respiratory symptoms to severe pneumonia. Risk factors for
infection include advanced age, chronic alcohol or tobacco use, COPD, corticosteroid use, and other immunosuppressive therapies. Previous reports have
suggested that cell-mediated immunity plays a role in host defense against
Legionella. We present a case of legionellosis in the setting of persistently
decreased serum IgM. Methods: Case description Results: A 61-year-old female
with a history of mild asthma and tobacco dependence initially presented with
subjective fevers and non-productive cough for three days. The patient was previously well, and was only taking as-needed albuterol. Of note, the patient had
two previous episodes of pneumonia (six and twelve months prior to this presentation), which resolved with outpatient antibiotic therapy. The patient denied
alcohol/drug abuse, recent steroid therapy, or previous infections requiring hospitalization. Exam was notable for rales in the right middle lobe region. Labs
were significant for increased liver enzymes (AST/ALT of 273/101), elevated
CPK of 4260, and positive legionella urine antigen. Chest x-ray demonstrated
a right-sided infiltrate, and the patient was started on moxifloxacin. The patient
was also found to have decreased serum immunoglobulins with IgG 596 (normal: 700-1600), IgG1 310(382-929), IgG2 113(241-700), and IgM less than
40 (normal: 40-230). Pneumococcal titers were decreased and post-vaccination titers are pending. The following tests were unremarkable: hepatitis serologies, HIV testing, MMR vaccination titers, absolute neutrophil and lymphocyte counts. In light of the severe infection, history of repeated infections, and
decreased immunoglobulins, one dose of IVIG (260 mg/kg) was administered.
The patient subsequently improved on antibiotics and was discharged. Interestingly, the patient had persistently low IgM (less than 5) three months postdischarge; the other immunoglobulins had normalized. Conclusion: Legionella
pneumonia has been associated with distinct predisposing factors including
defective cell-mediated immunity. Here were report the first association between
this infection and IgM deficiency. In the setting of legionellosis, physicians
may consider evaluation for humoral defects in order to guide appropriate
replacement therapy, if indicated.
A.Y. Joshi*, T.G. Boyce, Rochester, MN.
Introduction: Down syndrome (DS) is a prototype of the undefined primary
immunodeficiency syndrome where some immunologic aberrations have been
found but no unifying abnormality has been described so far. Methods: We undertook a historical cohort study of all patients with DS in Olmsted County from January 1990 to December 2006 to determine the extent to which lymphopenia and
Incidence of Primary immunodeficiency in subjects with Down syndrome
and in general population (P<0.001)
M.D. Keller*, J.S. Orange, Philadelphia, PA.
Introduction: Ectodermal dysplasia (ED) represents an uncommon group
of disorders resulting in variable abnormalities of ectoderm-derived structures.
Hypomorphic mutations in the NF-kB essential modulator (NEMO) gene can
cause ED with severe immunodeficiency, including defects in humoral, cellular and innate immunity with high susceptibility to mycobacteria and pyogenic bacteria. Treatment for patients with a NEMO mutation includes prophylactic antibiotics, immunoglobulin replacement and in some cases
hematopoeitic stem cell transplantation (HSCT). The ED in patients with NEMO
mutations, however, is very similar to that found in other genetic defects not
associated with immunodeficiency, including X-linked hypohidrotic ED, due
to mutations in EDA. Here, we describe a kindred with defects in both EDA
and NEMO which appeared together in the male proband due to an X-chromosome crossover event. Methods: Family members were enrolled in an IRBapproved investigational protocol and chart review performed. Biochemical
and immunological analyses were undertaken to confirm immunological and
NEMO defects. Gene sequencing for EDA1 and NEMO was performed using
standard protocols with genomic DNA from the patient and family. Results:
Sequencing of the EDA1 gene revealed a G to A missense mutation in exon 3
resulting in a predicted change from arginine to histidine at amino acid position 153 (R153H) in the mutated EDA protein. Sequence analysis of NEMO
revealed a change of G to A at the +5 position of the splice donor site in intron
6 (IVS6+5G-A) that has been identified in another large cohort. Western blot
analysis revealed an abnormal NEMO protein. The probands grandmother carried the mutant NEMO and his grandfather carried the mutant EDA alleles.
The mother inherited both mutant alleles, and the proband’s x-chromosome
contained both mutations, thus demonstrating an unprecedented crossover event.
Interestingly, male patients in the cohort with the mutated EDA allele alone
showed minimal clnical impact, while two uncles of the proband died in early
childhood from infection, suggesting the impact of the NEMO allele. Conclusion: Patients with ectodermal dysplasia warrant an early immunologic evaluation if there is history of infection, and diagnosis of an defect in EDA does
not necessarily rule-out a more serious NEMO mutation.
A.H. Latiff*1, F. Mohamed Jamli2, N. Wahab2, 1. Bandar Sunway, Malaysia;
2. Serdang, Malaysia.
Primary immunodeficiency disorders (PID) require specialized immunological services for diagnosis and management. In a developing nation, where
resources for these are limited, efforts are mainly focused on creating awareness amongst general practitioners and general specialists for PID, upgrading
laboratory facilities for diagnostic purposes and the need for immunology
subspecialty training. The aim of this study was to evaluate demographic characteristics, clinical features and outcome of patients with PID in our clinic. This
was a retrospective study and data were collected of patients referred to an
allergy clinic of a district hospital from June 2006 (when the clinic started its
clinical services) to December 2009. Twenty-eight patients were identified, and
16 out of 28 patients referred were confirmed to have PID. The rest of the
patients were still waiting for confirmation of diagnosis, given the limited
resources for more specialized laboratory test to confirm a diagnosis of possible PID. Nevertheless we were able to make molecular diagnoses in 3 of the
patients using laboratory facilities in an established immunology centre abroad.
The age of presentation ranged from one month to 25 years. Male preponderance over female with ratio of 1.6:1 was noted, and 81.2% were from Malay
ethnic group. Recurrent respiratory tract infections were the most common clinical manifestations. Others included recurrent skin infection/abscess, sepsis,
recurrent diarrhea, bronchiectasis and chronic lymphadenopathy. The most
common form of PID was chronic granulomatous disease (37.5%). Antibiotic
prophylaxis and early treatment of infections are the main modalities of management. Two patients required immunoglobulin replacement therapy. One
patient is currently on the waiting list for bone marrow transplant, whilst another
died of septicemia. In a 4-year period, a significant number of patients with
possible PID were referred to the allergy clinic expanding the services of this
clinic, in diagnosing and managing these patients. Given this situation, the services of the allergy clinic is now re-structured as an allergy/immunology clinic
and steps are taken to streamline the outsourcing of diagnostic tests, and establishing a network with other clinics serviced by a pediatric immunologist for
consultation of management.
number of given doses ranged from 1-13 per patient, with dosing at 0.2-1.1g/kg.
Pre- and post-IVIG mean IgG levels were 201 mg/dL and 441 mg/dL, respectively. B and T cell subsets were obtained in 8 patients, of which 7 had low
total T cells for post-gestational age. A subset of these patients (6) had preIVIG level <100 mg/dL. Two patients from this group died. One received a total
of 13 doses and expired from aortic thrombosis. The other patient had renal
failure, tracheitis, and anasarca that prevented chest closure. Overall, postsurgical complications included chylothorax, sepsis, lower respiratory tract
infection, and renal failure. Average length of hospitalization was 69 days (range
17-313). Eight of the 27 patients died, ranging from 1 month to 6.5 months
post-gestational age. Extremely low IgG level (<100) correlated with higher
mortality rate at 33% compared to 29% of patients with IgG level 101-400
mg/dL. Conclusion: IVIG use for hypogammaglobulinemia is common in the
NICU, particularly in post-cardiac surgical patients. The causes are multifactorial, including blood loss, extravasation into tissues, and accelerated IgG
catabolism associated with stress. We label this as immunodeficiency of the
stressed infant.
M. Longley*, A. Petrovic, M. Dorsey, E. Perez, J. Sleasman, St Petersburg, FL.
Introduction: Chronic Granulomatous Disease (CGD) is a genetically heterogeneous primary immune deficiency, resulting in defective microbicial
killing by phagocytes due to diminished production of superoxide anions. We
report a novel mutation in a child with autosomal recessive CGD, whose granulocyte function was monitored following hematopoietic stem cell transplantation (HSCT) through oxidative burst function via dihydrorhodamine (DHR)
testing. Methods: Complete genetic sequencing of the CYBA gene was performed. DHR testing was used diagnostically pre-HSCT, as well as post-HSCT
to monitor percentage of functioning granulocytes. Lineage specific short tandem repeat (STR) analysis was measured to monitor ratio of donor cell engraftment. Results: A ten month old Pakistani female presented to our clinic with
history of recurrent pneumonia, cutaneous infection with Serratia and MRSA,
and pulmonary necrotizing granuloma. DHR testing revealed absence of granulocyte oxidative burst. Mutational analysis of the CYBA gene revealed a novel
homozygous single base change from AÇG, called IVS3-2 a>g, in the canonical splice acceptor site for exon 4. The patient underwent match related donor
HSCT using a reduced intensity conditioning regimen. Neutrophils engrafted
on day +12. At four weeks post transplant, 100% of granulocytes had normal
oxidative burst function with 99% of myeloid fraction of donor origin. By 24
weeks, 33% of granulocytes had normal function with corresponding donor
myeloid fraction of 17%. Three years post transplant, the patient had 1% remaining functional granulocytes while myeloid cells revealed 3% donor chimera.
The patient is currently undergoing preparation for second transplant. Conclusions: DHR testing is an invaluable method of assessing granulocyte function in CGD patients in the post transplant period, and correlates well with
current conventional methods of monitoring immune reconstitution.
K.J. Lim*, I.B. Purdy, V. Milisavljevic, E.R. Stiehm, Los Angeles, CA.
Introduction: The UCLA NICU cares for many critically ill newborns, a
number of whom receive intravenous immunoglobulin (IVIG) as part of their
management. The most common diagnosis among those who received IVIG
was surgical intervention for major cardiac anomalies. Objective: To characterize clinical and laboratory features of infants with hypogammaglobulinemia
associated with cardiac surgery. Methods: After appropriate consent, we evaluated the records of 1973 infants admitted to the UCLA NICU between January 2004 and June 2008. IVIG use was identified in 100 patients by crosslinking pharmacy records, the NICU clinical database, and electronic medical
records. Laboratory tests were obtained before and after IVIG administration.
Data analyses included descriptive statistics and cross tabulations. Results: The
most common indications for IVIG are: hypogammaglobulinemia (47%), sepsis (23%), hemolytic disease of the newborn (16%), and neutropenia (12%).
Among the 32 infants given IVIG for post-cardiac surgical complications,
hypogammaglobulinemia (IgG <400 mg/dL) was identified in 27 patients. Lymphopenia (<1700) was common, as was hypoalbuminemia (<3.5 g/dL). The
Figure 1: Line graph depicting loss off functional granulocytes due to graft
M.R. Gonzalez Galarza*, M.L. Garcia Cruz, G.F. Pavon Romero, F. Ramirez
Jimenez, L.L. Juarez Martinez, A. Fuentes, L.M. Teran Juarez, Mexico
City, Mexico.
INTRODUCTION: The immunoglobulin A (IgA) is the most abundant antibody in mucous membranes and the second highest concentration in the blood.
Its concentration is less than 7 IU / ml is defined as selective IgA deficiency,
which can be asymptomatic or have respiratory infections and digestive recurrent or associated with allergic symptoms. There are few reports describing
the clinical characteristics of patients with partial deficiency of Ig A. OBJECTIVE: To report the frequency of history, symptoms and severity of atopic and
non atopic diseases in patients with subnormal levels of Ig A in a tertiary hospital in Mexico City. METHODS A cross sectional study in children with allergy
consultation IgA levels <80UI/ml, the population was stratified by age group,
analyzing the frequency of atopic diseases and nonatopic with П‡ 2 p <0.05%
with SPSS 16.0. RESULTS We analyzed 61 patients of which 88.5% have partial IgA deficiency and 11.5% is selective. Reported 52.3% men and 47.5%
women. 90% have symptoms suggestive of allergy, elevated IgE 44.3% and
16.4% had positive skin tests. The most common allergen Dermatophagoides
pt was 13.1% (p <0.05). The frequency of allergic diseases is: 88.5% allergic
rhinitis (59% moderate persistent) asthma 13.1% (62% uncontrolled), 32.1%
early wheezing, persistent wheezing 9.8%, 3.3% late wheezing, 19.7% protein
allergy milk, atopic dermatitis 4.9%, in relation to non-atopic disease: Gastroesophageal reflux 41% syndrome, obstructive sleep apnea 6.6%. As background, tonsillectomy was 14.8%, 32.8% had a history of pneumonia, the womb
was 49.2% and 24.6% whole milk was weaned. CONCLUSION:This study
shows that partial deficiency of IgA is associated with increased frequency and
severity of allergic rhinitis and asthma, as well as greater number of respiratory infections which coincides with history of pneumonia by nearly 50% of
them. Knowing this condition will help the doctor evaluate other factors exacerbating allergic disease and optimize treatment of the same
B. Zuraw*1, J. Baker2, D. Hurewitz3, M. White4, A. Vegh5, L. Bielory6,
W. Lumry7, M. Riedl8, M. Davis-Lorton9, R. Levy10, J.A. Grant11, P. Busse12,
A. Banerji13, H. Li4, I. Kalfus12, 1. La Jolla, CA; 2. Lake Oswego, OR; 3.
Tulsa, OK; 4. Wheaton, MD; 5. Tacoma, WA; 6. Newark, NJ; 7. Dallas,
TX; 8. Los Angeles, CA; 9. Long Island, NY; 10. Atlanta, GA; 11. Galveston, TX; 12. New York, NY; 13. Boston, MA.
Background: HAE is a genetic disease characterized by recurrent, painful
and potentially life-threatening swelling episodes. This study evaluated the
safety and efficacy of Cinryze for routine prophylaxis of HAE attacks. Methods: This open-label, multicenter study (47 sites) enrolled 146 subjects aged
≥1 year with HAE and ≥1 attack per month or history of laryngeal edema.
Approval was obtained from WIRB and informed consent obtained from all
subjects. Cinryze was administered prophylactically at 1000 U IV every 3 to
7 days. Subjects were also eligible to receive treatment with Cinryze for acute
attacks. Subjects were instructed to document all attacks on a daily basis. Safety
was monitored through the recording of AEs, vital signs, virology and anti-C1
INH antibody assessments. Results: Mean age was 37 years (range 3-82).
Pre-enrollment, subjects had a median HAE attack rate of 3.0 per month (range:
0.08-28.0). On Cinryze prophylaxis, the median number of HAE attacks per
month was 0.2 (range: 0 4.6) and 86% experienced an average of ≤1 attack per
month; 35% reported no attacks during the study. Exposure to Cinryze varied
(range: 8 to 959 days), 73% received Cinryze over a period of at least 6 months.
For subjects receiving therapy for at least one year, the median attack rate was
consistently low at 0.3 per month (range 0-4.0). Irrespective of age, laboratory
analysis demonstrated persistent rise in C1 INH antigenic and functional levels following Cinryze therapy. Of 74 subjects tested, there were no detectable
anti-C1 INH antibodies following C1 INH administration. Adverse events most
frequently reported related to Cinryze were: headache 5.5%, nausea 4.1%, rash
2.7%, erythema 2.1% and diarrhea 2.1%. The most commonly reported SAE
was HAE attack (11.6%). Five subjects experienced thrombotic SAEs: MI,
DVT, PE, and 2 CVA; none of these was considered to be related to Cinryze.
There were no severe hypersensitivity reactions related to Cinryze. There was
no evidence of transmission of HBV, HCV, or HIV during this study. Conclu-
sions: Administration of Cinryze reduced the median monthly HAE attack rate.
The distribution of monthly attack rates per subject over a 1-year period showed
persistent effects of prophylactic Cinryze. These data support the safety and
efficacy of Cinryze for routine prophylaxis of HAE attacks.
D. Hurewitz*1, J.A. Grant2, P. Busse3, M. Davis-Lorton4, J. Baker5,
M. Riedl6, A. Banerji7, R. Levy8, T. Craig9, I. Kalfus3, 1. Tulsa, OK; 2.
Galveston, TX; 3. New York, NY; 4. Long Island, NY; 5. Lake Oswego,
OR; 6. Los Angeles, CA; 7. Boston, MA; 8. Atlanta, GA; 9. Hershey, PA.
Introduction: HAE is an autosomal dominant disease of deficient functional C1 inhibitor (C1 INH) manifested by attacks of angioedema commonly
involving the gastrointestinal lining, extremities, face, larynx, and genitalia.
Symptoms of HAE typically begin in childhood and worsen around puberty.
Stanozolol is FDA approved for pediatric prophylaxis but has undesirable AEs,
such as masculinization, premature puberty, and premature epiphyseal plate
closure. This subset analysis evaluates the use of Cinryze for routine prophylaxis in pediatric subjects with HAE<18 years of age. Methods: This openlabel, multicenter study evaluated subjects aged ≥1 year with a diagnosis of
HAE who experienced ≥1 HAE attack per month or had any history of laryngeal edema. Cinryze was administered as prophylactic therapy at a dose of 1000
U IV every 3 to 7 days. Efficacy was based on the frequency of all HAE attacks
experienced. Subjects were instructed to record all attacks on a daily basis.
Safety was monitored through the recording of AEs and vital signs pre- and
post-infusion. Virology and immunogenicity testing were also performed.
Approval was obtained from WIRB and informed consent obtained from all
subjects. Results: Prior to enrollment, the 23 children in this study reported a
mean HAE attack rate of 4.4 В± 5.7 per month. During Cinryze therapy, the mean
monthly attack rate was 0.7 В± 0.98 in those aged 2-5 years old (n=2), 0.4 В±
0.45 in those aged 6-11 years old (n=9), and 0.7 В± 0.90 in those aged 12-17
years old (n=12). Overall, 87% of the 23 children experienced ≤1 HAE attack
per month with Cinryze prophylaxis. The only treatment emergent AEs considered to be related were headache, nausea, and infusion-site erythema; none
of which were severe. There were no severe hypersensitivity reactions, including anaphylaxis. There were no subjects who discontinued study drug due to
AEs, had detectable anti-C1 INH antibodies, or had evidence of transmission
of HBV, HCV, or HIV. Conclusion: Cinryze therapy reduced HAE attacks to
≤1 per month in most of the pediatric subjects in this study. Cinryze was shown
to be efficacious and well tolerated when administered for prophylaxis of HAE
attacks in pediatric subjects.
W. Lumry*1, J. Baker2, M. Davis-Lorton3, M. Manning4, T. Craig5,
I. Kalfus6, 1. Dallas, TX; 2. Lake Oswego, OR; 3. Long Island, NY; 4.
Scottsdale, AZ; 5. Hershey, PA; 6. New York, NY.
Introduction: HAE is an autosomal dominant disease of deficient functional C1 inhibitor (C1 INH) manifested by attacks of angioedema commonly
involving the gastrointestinal lining, extremities, face, larynx, and genitalia.
HAE typically begins in childhood and worsens around puberty. Children have
smaller airways complicating intubation during laryngeal attacks and are likely
to suffer from upper respiratory infections which can trigger attacks, emphasizing the importance of appropriate treatment options for this age group. Methods: Overall, this open-label, multicenter study evaluated subjects aged ≥1 year
with a diagnosis of HAE; this subset analysis presents data on subjects aged
<18 years. Cinryze treatment was administered as 1000 U IV with a second
1000 U dose 60 minutes later, if needed. The presence of three consecutive
assessments of improvement at 15-minute intervals within the 4-hr post-treatment period constituted relief. Safety was monitored through the recording of
AEs and vital signs pre- and post-infusion. Viral safety labs and immunogenicity
testing were also performed. Approval was obtained from WIRB and informed
consent obtained from all subjects. Results: Twenty-two pediatric subjects experienced a total of 121 HAE attacks, with 89% (108/121) achieving relief within
4 hours of Cinryze administration. 91% (69/76) and 89% (39/44) of attacks in
subjects aged 6-11 and aged 12-17 achieved relief within 4 hours of Cinryze
administration, respectively. A two-year-old subject was given two 500 unit
doses for a facial attack and reported symptom relief within 3 hours. Gastrointestinal attacks were the most common HAE manifestation. Of the 64 gastrointestinal attacks in 6-11 and 12-17 year olds, 97% (35/36) and 89% (25/28),
respectively, experienced relief within 4 hours. No subjects with a laryngeal
attack required intubation. There were no treatment emergent AEs reported as
related to Cinryze in these subjects. No subjects discontinued study drug due
to AEs, had clinically relevant anti-C1 INH antibodies, or had evidence of transmission of HBV, HCV, or HIV. Conclusion: Administration of 1000U of Cinryze was well-tolerated and effective for the treatment of acute HAE attacks in
children. In addition, intubation due to HAE was avoided in all subjects with
a laryngeal attack.
level of 1001 approximately eight months after the last dose of IVIG was administered and almost one year after hospitalization. Conclusion: Glucocorticoids
are known to have immunosuppressive effects, however, literature states that
glucocorticoids have less effect on humoral immunity. (Baschant U, Tuckermann J. The Role of the Glucocorticoid Receptor in Inflammation and Immunity. J Steroid Biochem Mol Biol. 2010;120(2-3):69-75.) In this patient, chronic
prednisone use appears to have caused a CVID-like clinical picture including
Table 1. Immunoglobulin Levels.
K. Marks*, P. Takach, Philadelphia, PA.
Rationale: There is a paucity of literature regarding the management of
acute arthritis in adults with X-linked agammaglobulinemia (XLA). Methods:
Case review. Results: A 33 year old African American male with a history of
XLA, diagnosed at age 2, was admitted to the adult general medicine inpatient
service for complaints of three days of left ankle pain and swelling. He received
monthly IVIG up until five months prior to admission when he lost his insurance. His IgG level on admission was <33 mg/dL. His MRI showed findings
suggestive of infectious versus inflammatory arthritis of the left ankle. He was
diagnosed with probable septic arthritis, started on broad spectrum IV antibiotics, which included Vancomycin, Azithromycin and Ceftriaxone, and was
sent to the operating room for multiple washouts. He was given 400mg/kg of
IVIG on hospital day two, which increased his IgG level to 366 mg/dL. He
remained febrile with leukocytosis for one week with no identified organism
as the cause of his monoarthritis. He was administered a second 400 mg/kg
dose of IVIG one week later as well as continued broad spectrum antibiotic
coverage. The anaerobic culture of his synovial fluid revealed moderate
Mycoplasma on hospital day twelve, and he was started on Levofloxacin. His
symptoms, fever curve and leukocytosis slowly improved. His IgG level a week
later was only 435 mg/dL, so he was given a 700 mg/kg dose of IVIG. Five
days later, on the day of discharge, he was given another dose of 500 mg/kg of
IVIG. The Mycoplasma was speciated as Mycoplasma hominis by 16S rRNA
analysis on hospital day sixteen and Doxycycline was added to his antibiotic
regimen a few days prior to discharge. He was discharged home with negative
pressure wound therapy and an indefinite course of Levofloxacin and Doxycycline. Conclusion: This case report illustrates the need to consider atypical
organisms, such as Mycoplasma, when evaluating acute arthritis in adults with
humoral immune deficiencies for expedited initiation of appropriate antibiotic therapy. Moreover, adults who are found to have septic arthritis caused by
Mycoplasma should be screened for immune deficiency. Immunoglobulins
from immunocompent donors may not contain high levels of immunoglobulin
to Mycoplasma. Thus, increased doses and/or frequency of administration of
IVIG may be required during an acute mycoplasmal infection.
A. Mathew*, B. Feigenbaum, K. Miro, J. Weinfeld, New York, NY.
Introduction: Chronic use of systemic glucocorticoids can result in immunosuppression of varying degree. Case Report: A 23-year-old female was prescribed prednisone ranging from 20 mg to 40 mg daily for approximately one
year, apparently for a history of asthma and bronchiectasis. The patient developed recurrent respiratory infections and was eventually admitted to our institution with pneumonia. She did not improve as expected and additional labs
were ordered. Laboratory evaluation was remarkable for a decreased IgG level
of 347 (repeat level 335), a decreased IgA level of 56, and a normal IgM level
of 109. The patient was thought to have common variable immunodeficiency
(CVID) and treatment with intravenous immune globulin (IVIG) was initiated.
She received two more monthly treatments of IVIG and improved. After obtaining the patient’s records from an outside facility, it was noted that her IgG
level three years prior had been normal at 803. Prednisone was tapered and discontinued over a course of several months. IgG levels returned to normal upon
cessation of prednisone and have remained normal. The patient had an IgG
J.I. Mendez de Inocencio*1, R. Ovilla-Martinez1, M.A. Ramirez-Crescencio1, Y. Luna-Garcia1, J.A. Bellanti2, 1. Mexico City, Mexico; 2. Washington, DC.
CD19 regulates the signaling for B lymphocyte development, activation
and proliferation. Some studies have demonstrated that lowered CD19 expression resulting from mutations in the CD19 gene is associated with hypogammaglobulinemia and antibody-deficiency in patients with CVID and more
recently in patients with SLE. The following is a case study of a patient with
inactive SLE and CD19 deficiency who presented with Ab deficiency and
susceptibility to infection that was correctable with IVIG. A 41 y/o woman with
an 8 year history of inactive SLE presented with persistent fever (101-103oF)
for 30 days that was initiated by a UTI, cough and chest pain refractory to treatment with oseltamivir and ciprofloxacin. Chest CT scan revealed an enlarged
conglomerate of mediastinal lymph nodes and hepatosplenomegaly. Biopsy of
the lymph nodes showed nonspecific inflammatory changes, few atypical cells
and no evidence of lymphoma. Following initiation of IVIG 600 mg/ kg every
21 to 28 days and a tapered dose of prednisone 2 mg/kg during a 6 month period,
complete control of all her symptoms was achieved Lab results. CBC: Hb 12.3
(12-16 g/dL), total WBC= 10.2 (4.5-10.8 x 103 /uL), PMNs= 7.9 (1.8-8.0 x
103 /uL L), lymphocytes 1.3 (1.0-4.8 x 103 /uL), platelets 296 (130-450 x 103
/uL), PCR 16.940 (0.010-0.744 mg/dL). Nasal, pharyngeal, blood, urine and
lymph-node cultures for HIV, EBV. HSV I and II, and HBV were all negative;
mycobacterial cultures and TST were also negative. Serum IgG, IgA, IgM,
IgE and IgG subclass levels normal. Post immunization specific antibody
responses to S. pneumonia (14 serotypes) showed 12 with < 2.0 and 2 with 2.0
> mcg/mL. H. influenzae type b IgG, anti-diphtheria, Anti ANA and anti DNA
ds normal; C3= 127 (52.8-170.9 mg/dL), C4 15.8 (12.1-39.5 mg/dL). Levels
of CD19 absolute 84 (110-660 cells/uL). This case study suggests that there
may be a shared mechanism of SLE control and clinical expression of immunodeficiency. It also suggests that in patients with SLE and fever, the inclusion
of a CD19 study might not only provide a predictive marker to elucidate the
mechanism for maintenance of SLE in an inactive state but also may play a role
in the initiation of an immunodeficiency, both of which can be treated effectively by the use of IVIG and steroids.
K.S. Nelson*1, S. Miller2, B. Pinsky1, M.J. Butte1, D.B. Lewis1, 1. Stanford, CA; 2. San Francisco, CA.
An 11-month old previously healthy boy presented with a one-month history of fever, respiratory distress, and progressive weakness. On exam, he was
febrile, tachypneic and hypoxic with muscle weakness and disconjugate gaze.
A CBC was significant for profound neutropenia that proved unresponsive to
G-CSF therapy. The patient developed flaccid paralysis and respiratory failure
requiring intubation and mechanical ventilation. A CPK at the time of intubation was elevated at 1171 units/L. Direct immunofluorescence of respiratory
secretions was positive for enterovirus. Lumbar puncture was within normal
limits with a negative enteroviral PCR. Serum IgM was 23mg/dL, IgG and IgA
were undetectable. T-and B-cell subsets of peripheral blood were significant
for absent B cells, a predominance of CD8+ T cells, and normal numbers of
CD4+ T cells. Bone marrow examination showed absence of B-lineage cells,
including a lack of CD19+ pro-B cells, as well as myeloid maturational arrest.
Muscle biopsy was significant for normal muscle fibers with a prominent CD8+
lymphocytic infiltrate. The patient was started on high doses of IVIG with gradual improvement in respiratory status and resolution of paralysis. Preliminary
BTK-mutation analysis by sequencing was negative. Hypogammaglobulinemia (absent IgM and IgA) and undetectable peripheral blood B cells persist. A
viral culture isolate from the respiratory sample was sent to a research laboratory, where it was identified as human parechovirus (HPeV). HPeV, previously
classified as ECHO viruses 22 and 23, are members of the family Picornaviridae.
Ten human parechoviruses have been described to date, of which types 1, 2,
and 3 are the most widely recognized and are typically associated with mild
respiratory or gastrointestinal disease. HPeV1 and 3 infections have rarely been
described as causing severe disease including sepsis, encephalitis, meningitis,
and flaccid paralysis. To the best of our knowledge, this abstract is the first to
report severe HpeV infection associated with primary immunodeficiency. This
case highlights the importance of a timely immune workup in a patient with
acute flaccid paralysis/myopathy and of humoral immunity in controlling HpeV
infection. Severe HpeV infections should be considered in patients with humoral
immune defects.
a high incidence (30-40%) of Vitamin D deficiency in HIV infected patients.
This vitamin D deficient may be secondary to defects in renal hydroxylation
and the used of antiretroviral medication, especially NNRTIs. We performed a
pilot study to identify approximate prevalence of vitamin D deficiency in HIV
infected youth in Detroit prior to initiating a Vitamin D treatment study. Method:
Serum vitamin D level (25 hydroxyvitamin D; 25 OHD) were obtained from
10 HIV infected patients during a clinic visit. The levels of < 20 ng/mL were
considered as vitamin D deficiency, the levels between 20-30 ng/mL were considered as vitamin D insufficiency. We compared serum vitamin D level with
other parameters included current antiretroviral medications, HIV RNA viral
load, CD 4 + T cell counts and length of infection. Results: The subjects were
aged 16-23 yr. 8/10 were African American. 7/10 were vitamin D deficient,
2/10 were vitamin D insufficient and 1/10 had low level of vitamin D (49 ng/mL)
but not insufficient. 2/10 were infected perinatally and both were vitamin D
deficient (0 and 7 ng/mL). 7/10 were on antiretroviral medications. In this pilot
HIV RNA viral load and CD 4 + T cell counts did not correlate with level of
vitamin D. Conclusion: 90% (9/10) of the HIV infected youth in our pilot were
vitamin D deficient or insufficient. The combination of HIV infection, poor
sun exposure due to inner city Detroit residency, and possible dietary insufficiencies appear to render our population of patients even more vulnerable than
other HIV infected persons, to vitamin D deficiency. Future studies are needed
to elucidate the extent of this deficiency in HIV infected youth, and to determine the effect of treatment.
The RCDP belongs from a large group of dysplasias characterized by punctuate calcifications in the cartilage We described a child with RCDP diagnosis who had recurrent infections associated with hypogammaglobulinemia. A
2 years old boy was diagnosed with rhizomelic chondrodysplasia punctata
(RCDP) based on the clinical and radiological phenotype.Has clinical history
of neonatal lung disease secondary to pneumonia, a exploratory laparotomy
was performed secondary to spontaneous intestinal perforation, founding
abscess with necrosis areas spreading to the peritoneum. Other diseases gastrointestinal infection, pustular miliaria, intertrigo due to candida infection,septic
shock,bacterial acute otitis media, candidemia. The laboratory show: CBC
Hb14.1,Hto41%,WBC20,300, neutrophils 15,428,lymph 4060,4% bands. NBT
in 38%, IgG 317. In de evidence of numerous persistent infections in different
levels, even the great spectrum of antibiotics and hypogammaglobulinemia suspecting a immunodeficiency substitutive therapy with intravenous gammaglobulin was given as part of the treatment; nevertheless he dies because of
severe septic condition.
A.M. Gaye1, S. Patel*2, 1. Brussels, Belgium; 2. Rochester, MN.
A 14 year old Caucasian male was seen for severe atopic syndrome (asthma,
environmental and dietary allergies, chronic sinusitis, eczema), short stature,
and anemia. Routine work-up showed eosinophilia (2.8K/mm3), IgE>4000
IU/mL, IgG>500 mg/dL, IgA 64 mg/dL and IgM 48 mg/dL, normal T & B
cell count and distribution, and normal humoral response to childhood vaccines. Anemia, malabsorption, celiac disease, cystic fibrosis and allergic bronchopulmonary aspergillosis investigations were non-contributory. While on
long-term oral steroids for atypical inflammatory enteropathy, all atopic manifestations, pulmonary function, and linear and ponderal growths improved.
After discontinuation of steroids, IgE increased to >8000 IU/mL, and
eosinophilia, asthma, sinusitis, and eczema returned. Omalizumab was given
with dramatic improvement of all atopic manifestations, followed by successful wean of asthma and allergy medications, but eosinophilia remained
unchanged. Intravenous gammaglobulin infusions (IVIG) were started 2 years
later, when 2 measurable immunoglobulin types fell below the 2 standard deviation level of their respective expected values.The progression of the CVID
picture of this patient is ongoing with various auto-immune manifestations hypothyroidism, thrombocytopenia, and hypercoagulability, while his atopic
disease has remained quiescent. Eosinophilia persists (3.4K/mm3).The genetic
search for polyendocrinopathy with enteropathy was negative (FoxP3). Testing for CD25 deficiency, for STAT5b deficiency, and for ACEPED, was not
available. Measurement of free IgE level was not feasible. Results: The control of the atopic manifestations of a syndromic-appearing immune dysregulation was attributed to omalizumab. This effect may have been enhanced by a
decrease in IgE formation, a possible aspect of CVID. The latter was unmasked
by routine laboratory follow-up and responds to IVIG. Conclusion: Each case
of CVID is unique in its etiology. It is likely that CVID was affecting this patient
with severe atopy before initiating the treatment with omalizumab. We recommend a routine immune follow-up of patients on omalizumab, as the improvement of their atopic syndrome could be one of the manifestations of CVID.
P. Poowuttikul*, W. Alame, D. Richmond, E. Secord, Detroit, MI.
Introduction: Emerging evidence suggests that vitamin D plays a critical
role in regulating both innate and cell-mediated immune system. Studies report
N. RamГ­rez*, S. Arablin-Oropeza, B. Llamas-Guillen, C. Villarroel-CortГ©s,
J. GonzГЎlez-Zamora, A. Gutierrez-HernГЎndez, Mexico City, Mexico.
M. Rasheed*, A. Rubinstein, Bronx, NY.
Introduction: The spectrum of DiGeorge syndrome (DGS) spans from profound combined immune deficiency to a near normal immunity. There are few
studies of older children and adults with DGS. Most have mild to moderate T
cell defects with little or no progression of their immune aberrations. We report
here of a 22-year-old patient with DGS who has demonstrated a progressive
immunodeficiency with Ebstein-Barr viremia. Methods: We evaluated a 22year-old female with DGS and noted a progressive decline in immunologic
function with coexistent Ebstein-Barr Virus (EBV) reactivation and viremia.
Results: Immunologically, the patient was unaffected until late adolescence
when she developed pan-hypogammaglobulinemia. Immune evaluation demonstrated CD4+ T cell lymphopenia and markedly decreased lymphocyte mitogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen. Additionally, there was a lack of specific antibodies in the protective range
to prior vaccinations, including rubella, rubeola, and the 23-valent pneumococcal vaccine. EBV serology was suggestive of reactivation with elevated EBV
Early Antigen D antibody >150 U/ml (Reference Range <11). Her clinical
immune deterioration was manifested by the presence of EBV DNA detected
by PCR and a recent hospital admission for severe pneumonia despite maintenance on subcutaneous immunoglobulin therapy. Antiviral therapy with maribavir is planned to prevent the development of EBV-associated lymphoproliferative disorders. There is consideration for a thymic transplant. Conclusion:
This is the first case report describing a patient with DiGeorge syndrome with
a late progression of an immune defect manifested by chronic Ebstein-Barr
virus reactivation and viremia. We submit it is vital to monitor the immune
status of patients with DGS well into adulthood as there is a subset of patients
who experience a late progressive decline in immunity.
J.K. Shorten*1, P. Nandi2, 1. London, United Kingdom; 2. Birmingham,
United Kingdom.
A 45 year old man presented with melaena thought due to use of nonsteroidal anti-inflammatory medication.Interestingly, initial work-up revealed
a significant thrombocytopaenia and eosinophilia.The former was treated with
intravenous immune globulin and an upper gastroenterological endoscopy
carried out.An impressive painful vasculitic-type rash developed symmetrically on both feet (see photograph); in addition, a short-lived episode of psychosis intervened.Rheumatological and haematological opinions were sought
and bone marrow biopsy with trephine carried out; the latter was a dry tap, but
the trephine revealed megakaryocytosis, a left shift and an excess of mast cells
(showing up to 30 kpf c-kit proto-oncogene)- see photomicrograph. 30% of the
mast cells were spindle-shaped providing 1 minor criterion for systemic mastocytosis.A link with clonal mast cell proliferation with hyperplastic
change(eosinophils and megakaryocytes) awaits verification at this point in
time.Serum mast cell tryptase and cytogenetic studies (c-kit mutational screen
and PDGFR alpha-FIPlLl fusion) are also pending.
P. Shroff*, L. Potocki, J. Chinen, I.C. Hanson, Houston, TX.
Introduction: We report abnormal immune findings in a patient with a zinc
finger protein deficiency and MWS Case Description: A 2.5 year old male with
Hirschprung’s disease and MWS presented for evaluation of asplenia. MWS
was diagnosed at birth with genetic testing demonstrating chromosome 2q22.3
mutation and ZEB2 deficiency. At 2 days of life, a small spleen was noted and
PCN prophylaxis started. No history of serious infections were reported except
enterocolitis at age 1. Killed childhood vaccinations were up to date; the patient
never received live viral vaccines. Immune evaluation revealed CBC with mildly
elevated eosinophil count. Peripheral smear confirmed asplenia. Serum
immunoglobulins revealed low IgA and IgM but normal IgG and IgE. Oxidative burst assay was normal. Serologic vaccine responses showed 2 of 7 protective antibody levels to Prevnar vaccine and indeterminate response to tetanus.
Lymphocyte phenotyping revealed low CD3+ T cells, low levels of CD3+CD8+
T cells (3.9%; normal lower limit of 16.0%) but normal levels of CD3+CD4+
T cells. B cell, Natural Killer cell, and HLA-DR measurements were appropriate. T cells demonstrated adequate response to mitogen and antigen stimulation. Four weeks after revaccination (Prevnar 13, DTaP), protective antibody
levels of all 13 pneumococcal serotypes, tetanus, diphtheria and haemophilus
were demonstrated. Repeat lymphocyte phenotyping again showed low CD3+
T cells and low CD3+CD8+ T cells. Evaluation for latent viral infection was
negative. Discussion: ZEB2 is the zinc finger E-box binding homeobox 2 gene
responsible for embryonic development of neural crest cells. CD8 homeostasis is not defined but abnormalities in CD8 cell expression have been reported
in MHC Class I deficiency, ZAP 70 deficiency and IL-7 deficiency. Our patient
does not appear to have IL-7 perturbations as CD3+CD4+ cells are present in
normal number; there is no evidence of MHC Class I deficiency. ZAP 70 defi-
ciency, another zinc finger deficiency, presents with T cell dysfunction not seen
in this patient. Neurologic disorders have been linked with immune deficiency,
e.g. ataxia telangiectasia, ADA deficiency, Chediak-Higashi syndrome. Patients
with MWS (impaired neural crest development) should be evaluated for evidence of immunologic abnormalities including asplenia.
L.M. Tourangeau*, T. Doherty, La Jolla, CA.
Abstract Immune dysregulation, polyendocrinopathy, enteropathy, X-linked
syndrome (IPEX) is a rare entity that causes life-threatening systemic autoimmunity from underlying immune dysregulation. The case presented is of particular importance as the patient experienced cardiac arrest with resulting anoxic
encephalopathy prior to diagnosis confirmation. Methods We report the case
of a 21-year-old male with a history of autoimmune nephritis status-post renal
transplant x 2, peripheral eosinophilia, eosinophilic esophagitis, and enteropathy who developed subacute worsening cardiomyopathy with systolic dysfunction. Results Results from cardiac MRI and laboratory studies were not
consistent with an inflammatory etiology of his cardiomyopathy. However,
given his history of long standing immune dysregulation along with marked
eosinophilia and elevated IgE, FoxP3 mutational analysis and FoxP3 protein
expression were performed. FoxP3 studies revealed a one-codon deletion in the
leucine zipper domain of FoxP3 previously found to be critical to oligomerization. The deletion was located at 748_750 del AAG (K250 del). FoxP3 protein expression was only modestly decreased at 80% (reference range: 84-95).
Conclusions To our knowledge this is the first case of cardiomyopathy and
resulting cardiac arrest in an adult patient with IPEX syndrome. Individuals
with a history of systemic autoimmunity and cardiac dysfunction should undergo
a complete evaluation including FoxP3 protein expression and FoxP3 mutational analysis.
V. Yelisetty*, J. McGowan, Manhasset, NY.
Introduction: Pneumatosis Intestinalis (PI) refers to air in the wall of small
or large intestine. The pathogenesis of PI is not fully understood but can be
idiopathic or seen with various conditions that weaken and disrupt the intestinal mucosa enabling air to enter the wall. Gastrointestinal causes include bowel
inflammation, ischemia, and various infections including clostridium, MAI,
CMV and HIV. PI is also associated with collagen vascular diseases, immunosuppressive states, lymphoproliferative and pulmonary diseases. Clinical presentation can vary from an asymptomatic course to a life threatening emergency.
We report a case of PI in an AIDS patient who was admitted with chronic diarrhea. Case Report: A 22 year old female with past medical history of perinatally acquired HIV, AIDS, PCP, MAI, cryptococcosis and invasive chest wall
aspergillosis was admitted with chronic watery diarrhea for 3 months and failure to thrive. She denied fever, nausea, vomiting, headaches, any recent travel
or sick contacts. Her diarrhea was not felt to be related to her long-term outpatient medications. CD4 count was 6 and viral load 48,474. Abdominal exam
was benign without tenderness, guarding or rigidity. She was stabilized with
IV fluid and electrolyte support. HAART, PCP prophylaxis, MAI and aspergillosis treatment were continued. She was observed off antibiotics. Stool studies
including C-difficle toxin assays, ova/ parasites (including cryptospora, isopora and microsporidium), enteric bacteria, and blood CMV PCR were negative. Blood and stool cultures for AFB were negative. However, patient’s diarrhea persisted. A CT scan of the abdomen/ pelvis obtained a few weeks later
showed extensive pneumatosis involving the ascending, transverse and proximal descending colon without evidence of bowel ischemia, obstruction or perforation. Surgery was not indicated as patient was clinically stable without signs
of acute abdomen. HIV enterocolitis was presumed to be the cause of diarrhea
in the absence of other identifiable causes. Conclusion: PI is an unusual entity
increasingly seen in AIDS patients. In this case, HIV enterocolitis is presumably the cause of PI. Although our patient had a benign course, PI can result in
life threatening bowel perforation if not properly managed. Further research is
indicated to understand the pathogenesis and significance of PI in AIDS patients.
H.R. James, S.P. Commins*, Charlottesville, VA.
H.S. Earl, S.J. Apaliski*, N.A. Singhania, Arlington, TX.
Introduction: Recent reports describe the occurrence of a novel mammalian
meat allergy attributed to an IgE antibody (ab) against the carbohydrate galactose-О±-1,3-galactose (alpha-gal). Patients who develop these reactions report
that symptoms occur 3-6 hours after eating red meat. As with many other food
allergies, there is no known cure for this mammalian meat allergy. Methods:
IRB approval was obtained for basophil activation studies and patients electively sought Traditional Chinese Medical (TCM) treatment that included acupressure, acupuncture and alignment of meridians. Basophils from these subjects were isolated pre- and post- TCM therapy. CD63 and CD203c were used
as markers of basophil activation in response to allergens to assess for the development of tolerance post-TCM treatments. Results: Sera analysis and clinical
history identified patients with IgE ab to alpha-gal. These patients described a
similar history of anaphylaxis or urticaria 3-6 hours after the ingestion of meat
and reported fewer or no episodes when following an avoidance diet. Following 30 minute stimulation with cetuximab (1ug/mL), beef thyroglobulin, antiIgE or fMLP, basophil cell surface expression of CD63 and CD203c were
increased in pre-TCM samples (40%, 38%, 24% and 42% for CD203c and
21%, 16%, 11% and 22% for CD63, respectively). Following TCM, basophil
activation was repeated and again showed increased cell surface expression of
CD63 and CD203c but to a lesser extent than in pre-TCM (24%, 14%, 10%
and 23% for CD203c and 11%, 7%, 9% and 13% for CD63, respectively; p>0.05
for each). Conclusion: Reduction in basophil activation to alpha-gal related
epitopes following TCM may indicate the initial development of tolerance to
specific mammalian food allergens in patients with IgE to alpha-gal. This may
represent a widely applicable method to monitor for tolerance following TCM
This is a report of our experience with food patch testing in patients with
eosinophilic esophagitis from 2008 to 2010 in a private practice setting in Arlington, Texas. During this time period we performed food patch testing and either
skin prick food testing or RAST food testing on 15 eosinophilic esophagitis
patients. These patients had documented elevated eosinophil counts on
eophageal biopsies compatible with eosinophilic esophagitis. The patients were
on reflux medication and either swallowed fluticasone or budesonide. The age
range of the individuals ranged from 18 months to 19 years of age. There were
10 males and 5 females. The patch test was read by the doctor ordering the test
based on standard patch testing procotols. The number of food patch tests ranged
form 11 to 24 tests. The food antigens were either commercial baby food, fresh
food or dry grains made into a paste. Patch Testing: There were 11 patients with
at least 1+ positive food patch test. 4 patients had negative food testing. 2 patients
had more than one positive food test. The most prevalent food antigen that was
positive was rice. 6 out of 15 patients tested positive to rice (40%). Skin Prick
Testing: 12 of the patients had skin prick testing to foods: 2 of these patients
had positive reactions to peanuts. There was no correlation between food prick
testing and food patch testing. RAST testing: 2 of the patients had RAST testing to foods: although both patients had positive RASTs, only one RAST correlated with patch test results and that was for wheat. We have reports of 3 of
the patients improving on follow-up endoscopy. Eosinophilic esophagitis is an
illness of rising importance that allergists can play a key role in managing. Patch
testing is easy to perform in a private practice setting and can provide useful
information in the management of these patients. The high rate of positive rice
patch tests was surprising - although our rice testing material were prepared
according to standard protocols, we did not try repeat tests with other rice preparations to further suggest causality. Nonetheless, this high rate of reactivity to
rice might represent a regional phemenoma due to regional diets or other factors. Further research is needed to standardize and document the utility of
food patch testing in managing eosinophilic esophagitis.
S.I. Dever*, M. McMorris, N. Polmear-Swendris, A. Baptist, Ann Arbor,
Introduction: Food allergies affect 12 million Americans. While quality of
life (QoL) has been shown to be decreased in these patients, the specific factors associated with this decrease have not been well studied. In addition, self
efficacy (SE) in food allergy and the factors associated with it have previously
been unexamined. Our goal was to determine (1) factors that influence QoL
and SE in food allergic families and (2) how those factors affect QoL. Methods: The parents of 59 children ages 0-17 years with IgE-mediated food allergies participated in this IRB-approved study. They gave written consent and
completed the following questionnaires: a validated Food Allergy QoL Parental
Burden questionnaire and a questionnaire we developed on food allergy SE.
Factors investigated were: age, race, years of diagnosis, anaphylaxis, physician interaction, income, food allergy education, other atopic diseases, medications for other atopic diseases, and number of allergic foods. Results were
analyzed using a chi square test. Results: Eight factors influenced QoL and five
factors influenced SE. The factors that affected both QoL and SE were age,
years of diagnosis, number of allergic foods, food allergy education, and physician interaction. The additional factors that affected QoL were anaphylaxis,
other atopic diseases, and need for medications for other atopic diseases. Age
and years of diagnosis were the most important factors in determining QoL,
with age and years of diagnosis being inversely correlated to five and four
aspects of QoL, respectively. Factors that negatively affected QoL were increased
number of allergic foods, increased food allergy education, increased physician interaction, anaphylaxis, other atopic diseases, and taking medication for
other atopic diseases. SE was positively affected by increased age of the child,
years of diagnosis, increased number of allergic foods, increased food allergy
education, and increased physician interaction. Conclusion: Multiple factors
affect QoL and SE in food allergic families. Some of these factors, such as food
allergy education and number of physician visits, are potential areas where
interventions may be made to improve patient care.
M.K. Elias*, C.R. Weiler, Rochester, MN.
Introduction: Food allergy is suspected by patients more often than it is
actually diagnostically present. This may be due to the heterogeneity of the clinical presentation of food allergies. We hypothesize that clinical reactions of
children and adults with food intolerance are more likely to involve gastrointestinal signs and symptoms than those with IgE-mediated food allergy. Methods: A retrospective chart review of adults and children who had a food challenge at our institution between 1991 and 2009 was performed. We examined
the clinical presentation and diagnostic test results in patients with IgE-mediated food allergy compared to those with food intolerance. The institutional
review board approved this study. Results: Thirty-seven patients had oral food
challenges at our institution. The mean age of the patients was 45 years and
81% were female. Five patients were diagnosed with an IgE- mediated food
allergy based on a score of greater than one on an oral food challenge symptom scoring system. The positive oral food challenges were to egg, milk, tree
nut, strawberry and wheat. All five patients presented with classic allergic symptoms of angioedema, urticaria or pruritus. None of these patients had gastrointestinal symptoms at the time of their reaction. Forty percent of the patients
who reacted during the oral food challenge had negative skin prick test or foodspecific IgE to the food item used during the oral challenge. Sixty percent of
the five patients who presented with gastrointestinal symptoms also had
angioedema of the tongue or lips at the time of their reactions. These reactions
were not reproducible during the oral food challenge. All of the patients with
gastrointestinal symptoms had negative skin prick tests or food- specific IgE
to the food items used during the oral challenges. Seventy –two percent of the
patients with negative oral food challenges presented with urticaria, rash, pruritus or angioedema during their food reaction. Conclusion: Patients with food
intolerance are more likely to present with gastrointestinal symptoms. In patients
being evaluated for possible food allergies and who present with gastrointestinal symptoms, an oral food challenge testing should be performed to differentiate between food allergy and food intolerance.
M. Frieri*, S. Rao, East Meadow, NY.
J.P. Garrett*, J.M. Spergel, Philadelphia, PA.
INTRODUCTION: Seafood allergens may cause non-IgE immunological
reactions in adults which can form antigen protein complexes stimulating a
non-IgE mediated reaction such as enterocolitis involving B and T cells, and
inflammatory cytokines. Objective: We report a case of a 60 y/o white female
with a past medical history of hypertension, cervical cancer s/p total abdominal hysterectomy, Barrett’s esophagus, valvular heart disease admitted to the
medical ICU with hypotension nausea, vomiting, and diarrhea. METHODS:
In the ED her vital signs were: 72/49-80-16-98.6. She had watery stools without blood for 5 days and complained of sharp, non-radiating lower abdominal
pain, with a sudden onset 15 minutes after she ate clams. Physical examination was unremarkable. RESULTS: CT abdomen/pelvis showed nonspecific
duodenitis and mild diffuse thickening of the colon distal to the mid transverse
colon. Stool cultures, C. Difficile toxin, and blood cultures were all negative.
Urinalysis and TSH were normal. EGD showed a gastric ulcer and esophagitis and the colonoscopy report was positive for colonic ulcers with the following biopsy results: gastric antrum-normal, gastroesophageal junction no squamous mucosa, colonic and rectal ulcer-mild mucosal edema, small bowel
mucosa-no villous blunting. Ciprofloxacin and flagyl were started empirically
on admission and ciprofloxacin was later changed to zosyn 3 days later. She
had no temperature spikes during her entire hospital course and stool and laboratory cultures were negative. CONCLUSION: Diarrhea, abdominal cramping and nausea may begin 1 to 6 hours after ingestion of seafood and duration
of symptoms may vary based on the severity. Controversy remains on whether
such a reaction is toxin mediated or an immunological phenomenon. Non-IgE
mediated enterocolitis is mainly a clinical diagnosis that may be suspected in
patients who had several previous episodes of GI symptoms after seafood ingestion and IgE levels are undetectable. Infection should be ruled out. Awareness
of non-mediated IgE reactions to seafood is an important differential to consider along with infectious/food poisoning etiology. Future research can give
a better understanding of this immunological reaction to seafood and increase
public awareness.
Background and Aims: Eosinophilic Esophagitis(EoE) and Celiac Disease
(CD) are both T cell mediated gastrointestinal diseases with multiple overlapping clinical symptoms. Recent studies have attempted to ascertain if a direct
association exists between the two diseases. We examined the relationship in
our thousand patient cohort. Methods: A retrospective review of a database of
patients diagnosed with Eosinophilic Esophagitis was conducted. Patients with
personal or family history of Celiac Disease were identified. Their age at time
of diagnosis, symptom presentation, endoscopic and histologic findings, treatment plan, family history and response to treatment were analyzed. Results:
Of the 971 patients with eosinophilic esophagitis, 30 patients (3.1%) had a positive family history for Celiac Disease. 22 patients (2.3%) in total carried formal diagnoses of Celiac Disease. 80% of those affected by both were male. The
median age of presentation was 7.79. The most common symptom at the time
of presentation was abdominal pain (7 patients). 13 patients had endoscopic
changes consistent with Celiac Disease. Interestingly, 2 patients were diagnosed
with CD after follow-up endoscopy from positive serology prior to their EoE
diagnosis. Treatments followed were mainly food elimination with 2 patients
being offered swallowed fluticasone given their non-adherence to the exclusionary diet. Of note, only 1 patient responded to just a gluten free diet. Conclusion: For patients who are diagnosed with celiac disease, it is prudent to consider and evaluate for eosinopilic esophagitis as a possible comorbidity.
I. Fung*, J.M. Spergel, Philadelphia, PA.
Introduction: Environmental factors in early life are important in the development of atopic disease. Recent studies suggest that birth in the winter season and implicated lack of vitamin D is associated with food allergy. To date,
this concept has not been studied in eosinophilic esophagitis (EoE). Methods:
We retrospectively identified season of birth in a single-center cohort of pediatric EoE patients. Season of birth was obtained by classifying month of birth
into spring (Mar, April, May), summer (June, July, August), fall (September,
October, November), and winter (December, January, February). Average age
at time of EoE diagnosis was determined for subjects born in each season of
birth. Month of birth for control patients from the United States (US), Pennsylvania (PA) and New Jersey (NJ) was obtained from public sources. Chisquared analysis was used to analyse for significant difference between: 1)
numbers of EoE patients in each season of birth; and 2) percent of EoE patients
and percent of general US population cohorts by season of birth. Results: 988
patient charts were evaluated. Age range at time of diagnosis was 28 days to
20 years, with an average of 6.8 years. Average age of diagnosis distributed by
season of birth was: spring 6.9 years, summer 6.9 years, fall 6.0 years, and winter 6.4 years. There was no significant difference in seasonal distribution of
births: spring 23.1%, summer 28.2%, fall 24.1%, and winter 24.5% (p=0.96).
The distribution for US was 24.8%, 26.0%, 25.2%, 24.1%; NJ 25.3%, 26.1%,
24.7%, 23.9%; and PA 25.4%, 26.0%, 24.4%, 24.2% for spring, summer, fall
and winter, respectively. No significant difference was seen between season of
birth data from the EoE cohort compared to birth data in the evaluated entire
US population (p=0.9) as well as individual states of NJ and PA. Conclusions:
EoE patients in our cohort did not have an increased propensity to be born in
the winter. Further studies are needed to identify early environmental factors
that influence development of EoE.
R. Karanicolas*, S. Kumar, I. Katayeva, R. Joks, Brooklyn, NY.
Rationale: Previous prevalence of self-reported allergy for American adults
is 5.3% (Vierk, 2007). Inner city populations are at greater risk for morbidity
and mortality from allergic asthma. We sought to determine the local selfreported prevalence of food allergy, as this is can be associated with life threatening anaphylaxis and increased asthma morbidity. Methods: A cross sectional
questionnaire was completed by adults receiving treatment for non-allergy
related illness at SUNY clinics. Results: Of 345 adults (76% female, 95% Black,
58% foreign born) 12.9% reported having a food allergy, with most prevalent being seafood (5.8%) and peanut (2.9%). Of all patients surveyed, 16.2%
have a history of asthma and 5.5% have a history of eczema. There was a
significant association between food allergies with asthma (p<0.01), but not
with eczema (p=0.074). Conclusions: Self- reported food allergy among our
inner city immigrant minority population is more than double the national
average. Our population has asthma as a significant co-morbidity for those
with food allergy. While self- reported symptoms may overestimate the true
prevalence, these findings nonetheless are consistent with previous reports
that inner city populations are especially at risk for allergic disease and its
morbidity and mortality.
K. Lindgren*, E. Dawson, A.M. Gaye, Chicago, IL.
Rationale:Raising awareness of an unusual presentation of food allergy
Methods:Report of 3 cases and review of the literature Results: -A 5 month
old girl was given rice cereal (RC) for reflux (GERD). Profuse vomiting was
attributed in the ER to viral illness. After recovery, severe vomiting returned
within 2 hours of re-introduction of RC. Rice avoidance was implemented. At
8 months, a commercial jar of vegetables, later found to contain rice, caused,
within 2-3 hours, first severe emesis, then diarrhea. -A boy had received very
small amounts of RC at 4 and 6 weeks of age for emesis. At 3 months, within
2 hours of his first meal of RC given for GERD, profuse emesis necessitated
IV re-hydration. Rice was suspected and avoided. At 11 months, an inadvertent exposure to rice flour was followed within 2 hours by emesis, lethargy, and
cyanosis, and required IV re-hydration. Minimal amounts of rice led to similar profound reactions on a few more occasions. -A girl placed on RC at 6
months had chronic diarrhea, attributed to lactose intolerance. Soy formula,
without RC, for 4 weeks, provided relief. At 7 months, within 3 hours of an
RC meal, profuse emesis and lethargy required re-hydration. Avoidance of
rice was advised. The children had no demonstrable rice-specific IgE (SIgE)
in the skin or serum and no clinical atopy. All had at least one positive, inadvertent, double-blind oral food challenge. Atopy patch tests were not done. The
prevalence of food allergy is the highest in infants and toddlers. IgE-mediated
dietary allergy is the leading cause of anaphylaxis in children. FPIES is an
immune, non-IgE-mediated, reaction of infants, where increased staining for
TNF-α is found on duodenal biopsies. Most reported offending agents are cow’s
milk, soy, and grains. Chronic exposure leads to emesis, diarrhea, and failure
to thrive. Upon re-exposure after restriction, there is a typical 1-3 hour minimum delay to onset of profuse emesis, lethargy, cyanosis, and later, occasionally, diarrhea, without cutaneous or respiratory manifestations. The reaction is
unresponsive to anti-histamines and epinephrine. Conclusions: In depth history and clinical exam remain keys to diagnosis. While the absence of SIgE to
the suspected dietary protein supports the diagnosis, there are no validated laboratory tests readily available for confirmation. FPIES is a rare, severe, immunemediated condition to basic infants’ foods.
M. Lunn*, T. Fausnight, Hershey, PA.
IgE-mediated food allergies affect 6 to 8% of children in the United States.
Symptoms of food allergy range from localized hives to life-threatening anaphylaxis. Intravenous lipid emulsions are a vital component of total parenteral
nutrition (TPN) as they provide essential fatty acids. Intralipid is a sterile fat
emulsion that contains soybean oil and egg yolk phospholipids. Although allergy
to egg is listed as a contraindication, adverse reactions are uncommon. We
report a case of hypersensitivity to intralipid in a patient with previously undocumented egg allergy. We present a 2 year old female with Stage IV neuroblastoma who was placed on TPN and 20% intralipid emulsion. Fourteen days after
initiation, she had diffuse pruritus without urticaria or additonal symptoms of
anaphylaxis. She had transient improvement with intravenous antihistamine
but her symptoms did not resolve until intralipid was stopped. Within a few
hours, she had complete resolution of her symptoms and remained asymptomatic off intralipid. Initial history did not document food allergy. On further
discussion, the patient was averse to eating plain egg and had emesis with ingestion but tolerated baked egg. Her symptoms occurred without urticaria or pruritus. Based on history, we completed skin prick testing to peanut, soy, and egg
with positive results to egg white. Serum testing confirmed allergy to both egg
yolk and egg white. This is the first case described in a pediatric patient with
a history suggestive of egg allergy, positive skin prick and serum testing to egg,
and reaction to intralipid infusion. One case in the pediatric literature describes
allergy to soy protein and reaction to intralipid. Additionally, isolated cases suggestive of allergy to intralipid in the adult population with identification of
egg and soy allergy are reported. Although ingestion of egg lecithin in cooked
food is generally tolerated by egg allergic individuals, administration of intravenous egg containing lipid emulsions may cause significant adverse reactions.
As the intralipid formulation contains egg yolk, its use is contraindicated in
patients with egg hypersensitivities. Currently, there are no available egg free
intralipid products. This case is presented to educate physicians that intralipid
contains egg protein and the potential for allergic reactions.
lation were dysphagia, abdominal pain, and diarrhea. Finn chamber testing with
fresh foods revealed rice, peanut, and chicken as the most offending agents.
Patients were advised to avoid offending foods and were also prescribed corticosteroids for treatment. Of the thirty-one positive biopsied eosinophil patients,
thirteen patients reported marked improvements in symptoms. Thirteen patients
reported full resolution, one patient showed no improvement, and four patients
were lost to follow-up. Conclusions: A significant number of patients with
GERD and abdominal pain have EE. Finn chamber testing paired with dietary
elimination leads to a good prognosis for patients.
J. Spergel*1, M. Boguniewicz2, L. Schneider3, J.M. Hanifin4, A.S. Paller5,
M. Figliomeni6, F. Kianifard6, J. Preston6, J. Nyirady6, L.F. Eichenfield7,
1. Philadelphia, PA; 2. Denver, CO; 3. Boston, MA; 4. Portland, OR; 5.
Chicago, IL; 6. East Hanover, NJ; 7. San Diego, CA.
Background: Atopic Dermatitis (AD) is a common pediatric skin disorder.
The association of food allergies with AD is controversial, however in some
studies one third of AD patients were reported to have a food allergy. The predictive value of food-specific IgE (sIgE) in an AD population is unknown, as
most values were calculated from patients with known food allergy. Methods:
1065 Infants (aged 3-18 months) with at least mild AD, at least one parent or
sibling with a history of atopy, and no known food allergies were enrolled in a
trial to examine the long-term safety and efficacy of 1% pimecrolimus cream.
Development of food allergy was followed throughout the study, which had a
36-month, randomized, double-blind (DB) phase followed by an open-label (OL)
extension of up to 33 months. In addition, sIgE for cow’s milk, egg white, peanut,
wheat, fish mix, and soybean was measured by ImmunoCAP assay at baseline,
end of DB phase, and end of OL phase. Approval was obtained from the Independent Ethics Committee or IRB of each center and written informed consent
was obtained from caretakers. Results: 15.9% Of subjects had at least one
reported food allergy by the end of the OL phase. Allergy to peanut was most
common (6.6%), followed by cow’s milk (4.3%) and egg white (3.9%). Fish,
soy, and wheat allergies were rare, comprising 0.4%, 0.4% and 0.3% of the study
population, respectively. Mean sIgE concentrations for milk, egg, and peanut
increased with increasing Investigator’s Global Assessment score at all measured time points. Using logistic regression, we tested novel and published sIgE
cutoffs for their ability to predict food allergy. The odds ratios for developing
allergy to milk, egg, or peanut for subjects with baseline sIgE concentrations
above the cutoffs versus those with sIgE below cutoff were between 2 and 12.
Sensitivities and positive predictive values were low, however (Table 1). Conclusion: Baseline and end-of-DB food-specific IgE levels were poor predictors
for development of common food allergies during the study and were entirely
nonpredictive of allergies to fish, soy, and wheat. Thus, in a large cohort of infants
with AD at risk for development of food allergy, sIgE concentrations were not
a good indicator of allergy development within the first 6 years of life.
Table 1: Predictive value of sIgE for subjects who developed allergy1 to cow’s
milk, egg white, and peanut
L. Nayak*1, D. Dalback2, A.S. Nayak2, 1. Bloomington, IL; 2. Normal, IL.
Rationale: To study the prevalence of eosinophilic esophagitis (EE) in
patients with gastroesophageal reflux disease (GERD) and food intolerance in
a large Midwest allergy practice. Methods: A review was performed of new
patient referrals from gastroenterologists and primary care physicians to the
clinic over a three-year period. Patients identified presented symptoms of GERD,
food impaction, abdominal pain, and food allergy. EGD biopsy consisted of a
minimum of 20 eosinophils per high-powered field. Offending foods were identified through Finn chamber testing of fresh and raw food applied directly to
the skin of the patient for 72 hours via chamber. Upon food removal, tissue
swelling and skin color changes were analyzed. Tissue swelling ranged from
extreme positive reactions to doubtful reactions. Results: Out of 302 patients
diagnosed for food intolerance, 46 patients were diagnosed with EE. Of the 46
patients, 31 had positive biopsy based on eosinophil count. Most subjects diagnosed had underlying atopy. The leading symptoms among the patient popu-
Food allergy reported between study visits 3 and 20. 2Positive predictive
value. 3Negative predictive value.
C.J. Siegel*1, M.J. Siegel2, 1. Kansas City, MO; 2. Madison, WI.
A.A. Babakhin*1, O.O. Maksimenko1, S.M. Andreev1, S.E. Gelperina1,
M.R. Khaitov1, L.M. DuBuske2, 1. Moscow, Russian Federation; 2. Gardner, MA.
Introduction: Immunotherapy(IT)practices vary among allergists (AL),
which may be based on training, published guidelines, relevant literature and
clinical experience. Parameters reviewed changes in office waiting times after
IT. It is unclear as to when the majority of severe IT reactions (SR) occur. Articles question the administration of IT to pts taking beta blockers (BB) and
angiotension converting enzyme inhibitors (ACE). AL may prescribe epinephrine (E) for their IT patients to carry. This survey attempts to identify practice patterns on IT issues. Methods: An online survey (MONKEY) on IT practices was sent to 400 AL(future mailing planned later 2010). Included were
onset time of SR to aeroallergen(A)IT determined as grade IV or V (WHO Subcutaneous Immunotherapy Systemic Reaction Grading System),severe asthma,
severe laryngeal edema or airway obstruction, in the last 2 years, how many
SR received treatment E,and practice regional location. It queried the recommendation to carrying E on IT days, and if IT is given to pts on ACE or BB
Results were obtained from 112 AL(28%). There were 25 practices (21.7%)
reporting SRs to A IT with a total of 56 individual SRs. SR onset was variable:
14 occurring between 0-10 min, 14 at 11-20min, 10 at 21-30, 9 at 31-59min,
and 8 at ≥60 min. 55 of the 56 SR to A IT received E corresponding to the
reaction onset. The Great Lakes region had the largest occurrences of SRs to
A IT (7 of 22) followed by the Southwest (4 of 22). AL routinely rx E to their
A IT patients 27.8% of the time, 39.8% only for patients at high risk for systemic reactions, 32.4% do not rx E.32.4% of AL exclude patients on BB from
A IT, 27.6% do not and 40% will exclude pts on BB, with exceptions. Most
AL, 85.8% and 89.4%, will allow pts on ACE to receive IT to A and hymenoptera
(H) respectively. Whereas 12.3% and 9.6% will exclude pts on ACE from receiving A and H IT respectively with exceptions. 1% of AL excludes pts on ACE
from receiving A or H IT. Conclusion: This small but relevant survey evaluates practice trends on IT. Results point out that current guidelines suggesting
a 30 minutes waiting after A IT may need to be reviewed. Certain geographical areas may be at higher risk of SR. AL vary as to whether pts on BB should
receive A and will allow pts on ACE to receive A and H IT although there are
exceptions. Studies are needed to confirm and establish evidence based guidelines on these IT issues.
F.M. Al-sharif*, O. Al-jiffri, Z. El-sayed, Jeddah, Saudi Arabia.
Prevention Of Congenital Rubella Syndrome(CRS) is the ultimate goal of
any nation by wide vaccination programs for pregnant women and young
females. In the present study blood samples were collected from 220 female
aged from <5-25 years old and 102 pregnant women during labour, in addition,
102 cord blood samples were collected from their new born infants. These samples were screened for rubella antibodies (IgG) using the Haemagglutination
Inhibition Test (HIT) and Enzyme Linked Immunosorbent Assay (ELIZA) methods. We aimed to assess the immunity of young female in an attempt to evaluate the need of mass immunization. Also, we want to evaluate the seronegative pregnant women to know the percentage of susceptibility and to detect the
transfer of the passive immunity to their infants which may prevent teratogenic effect. We detected that 94.1% and 93.2% of young females were seropositive for rubella by both ELIZA and HIT methods; respectively. Also, we detected
the prevalence of seropositivity among examined young females from urban
areas who were more prevalent than others from rural areas. According to age
group, the age group 15-<20 was the most susceptible group for rubella infection. We also detected the susceptibility to rubella infection with 12.5% and
15.7% among pregnant women by both ELIZA and HIT methods. The mean
titer of pregnant women was nearly the same as their newborn infants. The
percentage of immunity of women and their infants were nearly 87.3% and
83.3%; respectively. No-significant differences were recorded between titers
of women and titers of their new infants. HIT proved 98 %, 96.2% sensitivity
and specificity. An overall agreement between the two methods were 97.8 %,
while discrepancies were recorded as 2.2%. We recommended vaccination of
young female before adolescent also immunization of seronegative pregnant
women because one attack of rubella doesn’t give long life immunity and many
cases of infection were detected among multiparous women.
Background: Subcutaneous (s/c) allergen-specific immunotherapy (ASIT)
may be enhanced in efficacy and safety by using modified allergens adsorbed
on polymeric nanoparticles (NP). Methods: Polylactide-co–glycolide (PLGA)
nanoparticles with end COOH groups (PLGA-COOH) were synthesized. The
particle size was 175В±46 nm. Ovalbumin (OVA) was succinylated (sOVA) with
modification of 80% of epsilon-amino groups. (CBAxC57Bl/6)F1 mice were
immunized intraperitoneally 3 times with 10 Вµg OVA/mouse. Between the second and third immunizations, the mice were treated as follows: Group 1: 12
s/c injections of saline (control); Group 2: 12 s/c injections of OVA (increasing doses from 1 to 1000 Вµg/mouse); Group 3: 6 s/c injections of sOVA (increasing doses from 100 to 1000 Вµg/mouse); Group 4: 4 s/c injections of sOVA preincubated with PLGA-COOH NPs (two doses of 100 Вµg/mouse and two doses
of 1000 Вµg/mouse); Group 5: 4 s/c injections of PLGA-COOH NPs only (2
mg/mouse); Group 6: non-immunized and non-treated mice (control). The
serum levels of anti-OVA IgE, IgG, IgG1, IgG2a antibodies (Abs) before, during, and after treatment were detected by ELISA. Results: Mice treated with
sOVA PLGA-COOH NPs (sOVA-NPs) (Group 4) induced anti-OVA IgE similar to mice treated with sOVA (Group 3) but greater than mice in Groups 1
and 2. Anti-OVA IgG in Groups 2, 3, and 4 were similar but significantly greater
than Group 1 (non-treated group). Anti-OVA IgG1 in Groups 2, 3, and 4 were
also significantly elevated as compared to Group 1 while in all groups antiOVA IgG2a were similar. In Group 5 (mice treated with NPs only) there was
no elevation of anti-OVA IgE and IgG. Conclusion: Treatment of sensitized
mice with modified allergen adsorbed on the biodegradable polymeric NPs
induced substantial anti-allergen IgG antibody responses suggesting the use
of NPs as an adjuvant with modified allergens for the development of novel
vaccines for ASIT.
R. Erskine*1, L. Powell1, D. Rohulich1, M. Tringale2, A. Waldron2, 1. Round
Rock, TX; 2. Washington, DC.
Rationale: Patient perceptions about allergy immunotherapy (IT) are not
well documented. We sought to learn more about patients’ understanding of IT
in order to identify areas for improving patient education. Methods: In June
of 2009, the Asthma and Allergy Foundation of America (AAFA) conducted
the first annual ITreatTM Survey (Immunotherapy Recognition, Education, Attitudes, and Thoughts). The online survey included 32 multiple choice and openended questions. Invitations were sent to 9,706 contacts on AAFA’s constituent
database. Results: From the invitations sent, 918 completed responses were
received (9% response rate) and over 770 open-ended verbatim comments were
obtained. The majority of respondents were Caucasian females between the
ages of 35-44. Ninety-one percent of respondents had “heard of IT” and 81%
were “aware of how IT works”. Most respondents from this survey (78%) were
“very committed” to finding a long-term solution for their allergies and 78%
would consider a treatment regimen that included weekly and monthly visits.
Interestingly, 98% of respondents reported that they had visited an allergy
specialist after being referred. However, 50% stated that they do not believe
there is a “long-term solution for allergies”. Of those respondents not choosing IT after physician recommendation, 46% reported that they were unsure of
its effectiveness. Other barriers to patients not seeking IT included time commitment (40%), cost (27%), and inconvenience (26%). Conclusion: Allergy
patients have a general awareness about IT, are committed to finding a longterm solution, and will see a specialist when referred. However, barriers to treatment include a lack of understanding about IT effectiveness, cost and inconvenience. Opportunities exist to improve patient education about the long term
effectiveness of IT. Also, further data comparing the potential cost accumulation of symptomatic treatments with the costs of allergy immunotherapy may
help patients make more informed decisions about their allergy treatment
J.Yin*1, L. Wang1, Z. Cao1, G. Wang1, K. Huang1, G. Liu2, C. Liu3, C. Shen4,
C. Bai4, J. Zhou5, H.Yang6, C. Wang6, X. Sun7, H. Shen5, P. Sun8, R. Fadel9,
1. Beijing, China; 2. Wuhan, China; 3. Chengdu, China; 4. ShanghaГЇ,
China; 5. Hangzhou, China; 6. Chongqing, China; 7. X’ian, China; 8.
Nanjing, China; 9. Antony, France.
Introduction: House Dust Mites (HDM) are the most prevalent inhalant
allergen in China. Few studies have demonstrated the efficacy of SLIT in HDMinduced asthma. Objectives: To assess the efficacy and safety of SLIT in Chinese asthmatic patients allergic to HDM. Methods: A double-blind placebocontrolled exploratory study was performed in adult patients with mild and
moderate persistent asthma treated with inhaled corticosteroid (ICS) at a dose
comprised between 200Вµg to 1000Вµg/budesonide/day. After a 3-month baseline, patients were randomized to receive either SLIT with a HDM extract
( solution (Staloral 300IR,Stallergenes,France) or placebo during 12
months. Well-controlled asthma (WCA) was the primary outcome. Totally-controlled asthma (TCA), asthma exacerbations, quality of life, Asthma Control
Questionnaire (ACQВ®), lung function test (FEV1), HDM-specific IgE,IgG4
antibodies and safety were assessed as secondary outcomes. Results: 484
patients (mean age:31.2В±8.7 yrs) were randomized (active N=308;placebo
N=157). For the WCA, the proportion of success was 85.4 % in the active group
compared to 81.5% in the placebo group (OR=1.37;95%CI:0.812.33;p=0.2).The proportion of success for TCA was 61% in the active group
vs 52.9% in the placebo group (OR=1.41;95%CI:0.95-2.09;p=0.08). In moderate persistent asthmatics (treated with >400 µg–800 µg/budesonide/day) WCA
and TCA were significantly achieved in the active group compared to the
placebo (OR=2.1;95%CI:1.01-4.36;p=0.04 and OR=2.4;95%CI:1.284.61;p=0.007 respectively) In mild persistent asthmatics (treated with 200
µg–400 µg/budesonide/day) no significant differences were seen between the
active and placebo groups for both the WCA and TCA.FEV1 values were above
80% predictive values in both groups indicating no asthma worsening during
the study.ACQ and AQLQ scores improved in both groups. In the active group
HDM-specific IgE and IgG4 levels increased significantly, and not changes
were seen in the placebo group.No serious adverse events related to SLIT
were reported and the overall safety was good.Conclusion:This was the first
large SLIT controlled study performed in China.In patients with moderate
persistent asthma due to HDM,SLIT with Staloral 300 was safe and effective
for asthma control,measured by WCA and TCA.
prescriptions containing pollen. When comparing one and >1 injection prescriptions, mixing of molds with pollens was found in 73.7% and 16.1% of prescriptions respectively. Conclusions: Since the recommendation in 1/2003 of
separation of molds from pollen extracts (except ragweed), changes in prescribing patterns have led to a 46% increase in the separation pollens and molds.
However, 30% of AIT prescriptions continue to contain mold and pollen, particularly single injection prescriptions.
S.P. Jariwala*, N. Vernon, C. Witty, G. de Vos, Bronx, NY.
Introduction: Fungal infections are common in HIV-infected patients, and
range from skin infections to oral or esophageal candidiasis to cryptococcal
meningitis. Fluconazole is one of the mainstay therapies for such infections.
Fluconazole hypersensitivity has been described, and if acceptable alternate
therapy is not available, desensitization may be required. Published desensitization protocols to fluconazole in HIV-infected patients have ranged in duration from 7 to 15 days. We describe a case of successful desensitization to fluconazole in 3 days in an AIDS patient with cryptococcal meningitis. Methods:
Case description Results: A 29-year-old female with HIV/AIDS (recent CD4
count of 14, HAART with intermittent compliance) presented with a headache
for 1.5 weeks and was found to have a positive serum cryptococcal antigen.
This patient was initially started on flucytosine and amphotericin. Nine days
after flucytosine and amphotericin were started, the patient experienced a neck
rash and low-grade fever; flucytosine and amphotericin were discontinued and
her rash improved. The patient was subsequently started on fluconazole
(400mg/day) and within 10 minutes of the first dose, the patient became febrile
and developed a pruritic, maculopapular rash on her face, neck, and back with
no mucosal involvement. The patient had a similar rash one year prior to admission when treated with fluconazole for oral candidiasis; the rash had then
improved when the medication was discontinued. Given the necessity for maintenance therapy for cryptococcal meningitis, the patient underwent fluconazole desensitization starting with approximately 1mg of fluconazole. The starting dose was gradually increased every 8 hours. Within 3 days, the patient was
able to tolerate full, therapeutic dose of 200 mg twice per day of oral fluconazole. This protocol was completed without any adverse reactions, and premedication with diphenhydramine 25mg and famotidine 20mg was performed
before and during the protocol. Conclusion: Fluconazole is the preferred maintenance suppressive therapy for cryptococcal meningitis in AIDS patients. This
case demonstrates the possibility of rapid fluconazole desensitization in AIDS
patients with hypersensitivity to this medication. To date, this case represents
the most rapid fluconazole desensitization regimen that has been performed in
an AIDS-infected patient.
S.M. Gada*, B.R. Haymore, Washington, DC.
Background: The effectiveness of allergen immunotherapy (AIT) is dependent on maintenance of allergen potency. A number of factors can influence allergen potency, including the proteolytic activity of allergens. The protease activity of molds when mixed with pollen has been the most consistent concern in
the literature and Practice Parameters. We describe the frequency with which
mold and pollen are placed in the same AIT prescription in a large health care
setting and the impact of Practice Parameters on these patterns. Methods: Data
from the U.S. Army Centralized Allergen Extract Laboratory (USACAEL) was
extracted and analyzed to determine the number of prescriptions containing
mold between 1/1990 and 5/2010. Mold prescriptions were divided into those
mixed with and without pollen. Ragweed was excluded from the analysis. Data
was subdivided into total, single prescription (1 injection) and multiple prescriptions (>1 injection) over a 20-year period. Results: From 1/1990-5/2010,
a total of 26,351 prescriptions were written containing molds. Prior to publication of the first AIT Practice Parameter (1/1990-12/1996), 65.2% of mold
prescriptions contained pollen. After its publication, from the period spanning
1/1997-1/2003, 51.7% (6568/12697) of overall mold prescriptions contained
pollen. Mixing of mold with pollen occurred in 75% of single injection prescriptions and 30.7% of multiple injection prescriptions. After specific recommendations on separation of molds and pollen (except ragweed) were published in the 1/2003 update to the AIT Practice Parameters, 33.8% (2306/6818)
of total mold prescriptions contained pollen, distributed among 68.4% of single injection and 20.3% of multiple injection prescriptions. The trend towards
separation of pollens and molds continued from 10/2007-5/2010 following
the second AIT Parameter update, with only 30.2% (1089/3611) of all mold
P.B. Keiser*, Washington, DC.
J. Seyerle*1, R. Scherzer2, E.A. Erwin2, 1. Bexley, OH; 2. Columbus, OH.
Introduction: It is known that plasma fibrinogen increases following some
vaccinations and we previously found an increase with a NOMV vaccine for
Neisseria meningitidis containing detoxified (penta-acylated or ∆lpxL1)
lipooligosaccharide (LOS). Methods: We looked at fibrinogen levels from a
previous clinical trial of a NOMV vaccine which contained a significantly lower
concentration (3% versus 18%) of a less endotoxic (tetra-acylated, ∆lpxL2)
LOS and compared them with the ∆lpxL1 NOMV results and with clinical
parameters of endotoxin activity. Three doses of ∆lpxL1 NOMV had been given
at six week intervals to four dose groups: 10, 25, 50 or 75mcg with aluminum
hydroxide (AH). Three doses of NOMV with ∆lpxL2 NOMV were given at 0,
6 and 24 weeks at 25mcg with AH, and 25 or 50mcg without AH. Fibrinogen
was measured the day of, just prior to, vaccination, and again 2 days later.
Approval was obtained from the WRAIR IRB and written informed consent
obtained from all research subjects. Results: Plasma fibrinogen at 2 days
increased 23mg/dL (P=0.036, 95% C.I. 1.62 to 46.79) with 25 or 50mcg of
∆lpxL1 NOMV and by 14.9 mg/dL (P=0.010, 95% C.I. 3.69 to 26.12) with 25
or 50mcg of ∆lpxL2 NOMV vaccination. One-way ANOVA showed no difference in the increase with any of the 25 or 50mcg dose groups of either vaccine. Comparing all changes in fibrinogen from ∆lpxL2 NOMV (n=71) with
those from ∆lpxL1 NOMV given at 25 or 50mcg (n=54), no difference was
seen (power = 0.866). Increased fibrinogen did not correlate with increased
WBC or temperature with either vaccine. Correlation with injection site pain
fell short of significance with the ∆lpxL1 vaccine (P=0.059, Spearman’s ranking), and was not significant for the ∆lpxL2. Conclusion/Significance: Plasma
fibrinogen increases slightly following vaccination with ∆lpxL1 or ∆lpxL2
NOMV vaccines. Although containing only one sixth the concentration of LOS
as the ∆lpxL1 NOMV, the increase in fibrinogen was not significantly less with
the ∆lpxL2 NOMV. The lack of correlation with increased WBC and temperature further suggests that these increases in plasma fibrinogen are not related
to endotoxin activity in NOMV vaccines.
M.A. Rank*, P. Markus, K. Kloos-Olson, C. Oslie, J.T. Li, Rochester, MN.
Introduction: Data from recent studies suggest that the utility of skin tests to
predict allergy to influenza vaccine in patients with egg allergy may be limited.
Methods: We performed a retrospective review of our Influenza Vaccine Allergy
Clinic database from 2009-2010. Skin testing results (neat skin prick and 1:100
intradermal) were compared between patients with egg allergy (identified by clinical history and/or allergy testing) and those without egg allergy using Fischer’s
exact test. This study was approved by our IRB. Results: There were 120 patient
visits to our Influenza Vaccine Allergy Clinic in 2009-2010 made by 79 unique
patients (55 with a history of egg allergy). Vaccinations were administered either
in full dose, split dose, or graded dose in 111 of the 120 patient visits (93%). Two
patients reported mild reactions after vaccine administration (both felt lightheaded);
no other reactions were reported. Intradermal (1:100) tests to seasonal influenza
vaccine were positive in 26/51 tested (51%); of the positive tests, 25/26 had egg
allergy and of the negative tests, 14/25 had egg allergy (p<0.001). Neat prick tests
to seasonal influenza vaccine were positive in 4/52 tested (8%); of the positive tests,
4/4 had egg allergy while 35/48 with negative prick tests to influenza vaccine had
egg allergy (p=0.56). Intradermal (1:100) tests to 2009 H1N1 influenza vaccine
were positive in 11/32 tests (34%); of the positive tests 10/11 had egg allergy and
of the negative tests, 17/21 had egg allergy (p=0.64). Neat prick tests to 2009
H1N1 influenza vaccine were positive in only 1/32 tests (3%). Assays measuring
average ovalbumin content revealed higher concentrations in the seasonal influenza
vaccine than the 2009 H1N1 vaccine (350 ng/ml and 21 ng/ml, respectively) from
lots sampled in 2009-2010. Conclusions: False positive intradermal testing (1:100)
is associated with egg allergy for seasonal influenza vaccine but not for 2009 H1N1
vaccine, likely because ovalbumin content was higher in seasonal influenza vaccine than 2009 H1N1 influenza vaccine. Intradermal and prick testing for influenza
vaccine appears to have limited value in patients with egg allergy due to a high rate
of false positive tests but may still have utility in evaluations of influenza vaccine
allergy in those without egg allergy.
Rationale: Influenza vaccine is known to contain small amounts of egg protein. Egg allergy has traditionally been a relative contraindication to administration of both nasal and IM forms of influenza vaccinations. With the outbreak
of pandemic influenza in 2009, two different flu vaccines were recommended.
While guidelines have been proposed for the safe administration of a single
influenza vaccine to egg-allergic patients, there are no formal protocols for
simultaneous testing of both H1N1(pandemic) and seasonal influenza vaccines.
Methods: We administered pandemic influenza vaccine to 41 egg-allergic individuals following a protocol adopted from 2009 Joint Task Force and CDC
guidelines. Each patient was tested to pandemic influenza vaccine using SPT
and intradermal testing. Patients were also offered testing for the seasonal
influenza vaccine. Immunization with one or both of the influenza vaccines
was then administered as a single dose or if testing was positive, in divided
doses over 60-90 minutes. Results: Of the 41 individuals tested to the pandemic
influenza vaccine, 4 tested positive. 40 of the 41 were given the vaccine as a
single injection or via a graded dose, while one parent refused the vaccine
after positive SPT. Thirty-three of the patients were also tested to seasonal
influenza vaccine, with 14 positive tests. 28 of those patients received the seasonal influenza vaccine during the same visit. If testing was positive, they
were given the vaccine via graded challenge. One patient tolerated the pandemic vaccine but could not complete graded dose seasonal influenza vaccination due to wheezing. In our study, 14 of the 41 patients had a positive test
to one of the vaccines while 2 patients tested positive to both vaccines. Conclusions: Based on our test results involving 41 egg allergic patients, pandemic and seasonal influenza vaccines can be safely administered to egg allergic patients in a single visit using our protocol. Given the variable allergic
response to each of the vaccines, our findings suggest that testing to one vaccine may not be a reliable predictor of sensitivity to another influenza vaccine.
A. Nayak*1, G. Atiee2, J. Maloney3, H. Nolte3, D. Bernstein4, 1. Normal,
IL; 2. San Antonio, TX; 3. Kenilworth, NJ; 4. Cincinnati, OH.
Background: Allergen immunotherapy is effective in reducing symptoms of
seasonal allergic rhinoconjunctivitis (SAR). A sublingual allergy immunotherapy
tablet (AIT) may be safer than subcutaneous immunotherapy formulations. Two
clinical trials were conducted in adults to assess the safety of a new short (s.) ragweed AIT. Methods: Adverse events (AE) were assessed in 2 randomized, doubleblind, placebo (PBO)-controlled, 28-day safety trials of Ambrosia artemisiifolia
(Amb a) AIT conducted outside the ragweed season in subjects with SAR (aged
18–50 y [RT-01]; ≥50 y [P06081]). In RT-01, s. ragweed AIT doses of 3, 6, 12, 24,
50, or 100 Amb a 1-Units (U) once-daily (QD) were planned for administration
successively at 7-day intervals with no buildup schedule. AEs were reviewed after
each dose before escalating to the next dose. In P06081, s. ragweed AIT doses of
6 and 12Amb a 1-U were evaluated for safety compared with placebo. IRB approval
was obtained; all subjects provided signed informed consent. Results: In RT-01
(N=53), AEs generally increased with dose, and the 50 Amb a 1-U group discontinued after 4 subjects reported AEs needing medical treatment. The 100 Amb a 1U arm was not initiated. Doses ≤24 Amb a 1-U were acceptable to the majority of
subjects and mainly associated with mild to moderate AEs (Table). The most frequent AEs after active treatment were pruritus (mouth, ear, eye, skin), and nasal
passage irritation (Table), which resolved within minutes. No differences in AEs
were observed in subjects with ragweed-induced asthma. In P06081 (N=203), the
most frequently reportedAEs after active treatment were pruritus (mouth, ear, eye),
and throat irritation that were mild to moderate (Table). There were no treatmentrelated seriousAEs, events of anaphylaxis, or anaphylactic shock reported in either
trial. Conclusions: Ragweed AIT at QD doses ≤24Amb a 1-U in adults 18–50
years without a buildup schedule was well tolerated. Doses <24Amb a 1-U were
considered suitable for further investigation. Similar tolerability was confirmed in
adults over 50 years of age.
Table. Treatment-Related Adverse Event Frequency, Severity, and
Relationship to Treatment
M. Aktaruzzaman*1, P. Zaman2, 1. Hannibal, MO; 2. Ellisville, MO.
Introduction: A number of chiropractors are known to treat allergies and
asthma. We decided to find out what percentage of practicing chiropractors
are treating allergies and asthma. Method: We goggled and selected one hundred chiropractor offices located in East Coast, Midwest, South West and West
Coast. We randomly called the office of 50 offices and asked the specific question: “Do you treat patients for allergies and asthma?”. Result: 35 offices (70%)
answered in the affirmative. 15 offices (30%) answered in the negative. Conclusion: 70% of a randomly selected chiropractic offices offer treatment for
allergies and asthma is an unexpectedly large number. We suspect that allergic
patients being treated by them are substantial in number and they are being subject to inappropriate and unproven therapy. This poses a substantial risk and
requires more attention by policy makers in the ACAAI and other similar organizations.
AIT=allergy immunotherapy tablet; Amb a=Ambrosia artemisiifolia;
PBO=placebo; TRAE=treatment-related adverse events.
* n (%) in the trial involving adults ≥50 y.
A.A. Williams*, S.M. Fung, J.R. Cohn, Philadelphia, PA.
RATIONALE: Specific allergen immunotherapy (IT) targeted towards cat
dander has been proposed to decrease allergic symptoms. This study examines
whether cat exposed asthmatic patients treated with CIT show a beneficial effect
on the incidence of acute exacerbations. METHODS: With approval from the
institutional review board, chart review identified patients on CIT В± other
immunotherapy for at least three years since 2005. An equal number of patients
on IT for at least three years during this period were identified. The follow-up
period included the 2nd and 3rd years of immunotherapy. Markers of asthma
control were evaluated in both groups. The groups were also stratified by concomitant inhaled corticosteroid (ICS) use and the same outcome variables were
investigated. Values of p<0.05 were regarded as significant. RESULTS: Thirtyfive patients were identified in each group. Sixty-nine of the 70 patients had
allergic rhinitis. Patients on CIT were significantly less likely than IT patients
to be on pollen IT (46% vs 71%, p =.015), mold IT (9% vs 43%, p =.001) and
dust/mite IT (57% vs 94%, p =.001). There were no significant differences in
the CIT group compared to the IT group in regards to total number of prednisone tapers (p =.583), number requiring prednisone tapers (p=1.00), number
of acute visits ( p=.376), and number requiring acute visits ( p=.151). When
stratified by concomitant ICS use, there were a total of 26 patients in the CIT
group and 23 patients in the IT group. CIT patients using ICS were significantly less likely than IT patients using ICS to be on pollen IT (42% vs 83%,
p =.004), mold IT (12% vs 57%, p =.001) and dust/mite IT (50% vs 96%, p
=.001). CIT patients on ICS were significantly less likely than IT patients on
ICS to require an acute visit (46% vs 78%, p =.023). CONCLUSIONS: CIT is
beneficial in cat allergic asthmatics. Asthmatic patients on CIT compared to
those on IT demonstrate no significant difference in regards to number of prednisone tapers, number of patients requiring prednisone tapers, number of acute
visits, and number of patients requiring acute clinic visits. Asthmatic patients
on CIT using concomitant ICS were significantly less likely to require an acute
visit compared to IT patients on ICS. Asthmatic patients on CIT are less likely
to be on concomitant pollen, mold, and dust/mite immunotherapy.
N. Baghaie*, M. Masjedi, S. Khalilzadeh, N. Parsanejad, Tehran, Iran,
Islamic Republic of.
Introduction: Regarding inverse correlation between TB infection and state
of atopy (Asthma), we aimed to study pattern of high IgE and PPD reaction
both in asthmatic and TB patients. Method: In a cross-sectional study we selected
50 asthmatic and 30 TB patients aged 4-15 years old. All had history of BCG
vaccination. PPD test was performed for all the patients in each group. Induration equal or more than 15mm were regarded positive. From all patients 5ml
venus blood was taken and IgE titer were measured. According to the Mono
Bind kit, IGE titer more than 280 Iu/ml was regarded high. Distribution of
positive PPD and High IGE among all the patents in each group were calculated and compared using x squared test. Results: Among asthmatic patients
33(66%) had high IgE titer and 11(22%) were PPD positive. The picture in Tb
patients were 3(10%) for high level of IGE and 24(80%) for positive PPD respectively. The comparison of two groups according to high IgE titer and positive
PPD were statistically significant.(p=0.000) Conclusion: We found an inverse
association between PPD and IgE in asthmatic patients but not in TB group.
E. Banta*1, C. Zalonis2, G. Ghaffari2, T. Craig2, 1. Hummelstown, PA; 2.
Hershey, PA.
Splenic abscesses can offer a diagnostic dilemma. Most often, an infectious
etiology is found. However, in cases where the abscess is sterile, diagnosis and
treatment are less clear. We present a case of aseptic splenic abscess and review
the literature on this subject. An OVID, Google and PubMed search was performed using the terms splenic abscess, sterile abscess and aseptic abscess from
1996 to present. 20yo female with 6 month history of recurrent lower extremity (LE) pustular lesions and splenic abscesses, refractory to multiple courses
of broad spectrum antibiotics, presented for evaluation for possible underlying immunodeficiency. The patient had been well until developing cellulitis of
the ankle with pustules after a minor injury 6 months prior. She had recurrent
episodes of pustular lesions on both feet and ankles which failed to resolve with
antibiotics. Cultures of these lesions were negative. She began to have intermittent fevers. ESR and CRP were markedly elevated. As part of her evaluation, abdominal CT scan was obtained, showing multiple splenic abscesses.
Fluid aspirated from a splenic lesion was negative for bacterial or fungal growth.
Empiric IV antibiotics were given without improvement. She continued to have
pustular lesions and skin biopsy revealed acute and chronic inflammation, but
no evidence of Sweet’s syndrome. Full immune workup was normal. Upper and
lower GI endoscopy revealed inflammation consistent with early inflammatory
bowel disease (IBD). IBD serologies were consistent with Crohn’s disease with
S. cerevisiae IgA 49.9U (>25 considered +) and S. cerevisiae IgG 29.3U (20.129.9 equivocal). Antibiotics were stopped and oral prednisone begun with rapid
improvement in size and number of splenic lesions. LE pustular lesions resolved.
Gastroenterology weaned steroids and started azathioprine with further resolution of splenic lesions. She remains on azathioprine without new LE lesions
and no gastrointestinal symptoms. In a series of 30 patients with aseptic
abscesses, 21 patients had IBD, which is often asymptomatic as in the case of
our patient. These patients tended to present with elevated WBC, ESR and negative infectious work-up. Aseptic splenic abscess can be an early manifestation of IBD. In patients with abscess, leukocytosis, elevated ESR and poor
response to IV antibiotics, IBD should be considered in the differential diagnosis.
R.P. Bhui*, R. Bhui, P. Bhui, Surrey, BC, Canada.
The measurement of Peak Expiratory Flow Rate (PEFR) plays a key role
in the monitoring and management of reactive airway diseases in children.
While studies have provided clinicians with data to develop reliable nomograms
relating patient height to expected PEFRs for North American children, a paucity
of parallel data exists for Indian children – even though the rate of asthma is
as high as 29.5% in some parts of the country. Hence, the goal of this study
was to investigate and analyze the PEFRs of healthy Indian children. Using a
Mini Wright Peak Flow Monitor, in 1995 the PEFRs of 129 children without
a history of respiratory disease were collected. The children ranged in age from
9 to 16 years and were between 49 and 65 inches in height. Our data revealed
that Indian children had consistently lower PEFRs than their North American
counterparts of the same height. Interestingly, while the commonly used North
American nomogram developed by Polger et. al. has an increase of 13
Litres/minute in PEFR per inch of increased height, our study also showed an
incremental increase of 13.125 Litres/minute in PEFR per inch of increased
height for Indian children. The incremental changes in the PEFRs for Indian
children were noted to be least between the height groups of 58 and 59 inches
(only a difference of 3 L/min). The largest incremental difference (45 L/min)
in PEFR was found between children of the 50 and 51 inch height groups. The
results of our investigation suggest that North American PEFR standardizations may not be fully applicable to Indian children and as such it is imperative that further research be conducted in this field.
A.K. Cormier*, A.M. Casillas, Shreveport, LA.
Introduction: Immunology is poorly represented in medical school curricula resulting in students’ lack of exposure to the this field. We were interested
in creating a computer-based learning module that incorporates clinical
immunology within a medical school curriculum. The emphasis is to bring out
immunological differential diagnoses commonly encountered in clinical medicine. We hypothesized that medical students do not receive enough exposure
to immunology during their medical education and that clinical case modules
would augment their immunological diagnostic skills. Methods: We created
computer-based scenarios deployed through the internet which requires the student to collect clinical lab and procedural data in order to make a diagnosis. In
some cases, the student is required to enact a specific treatment plan. A transaction database is created of student performances for each case. Our interactive case modules included the following scenarios:anaphylaxis due to food
allergy, anaphylaxis due to insect sting and hereditary angioedema. Results:
Information from student performances were collected. The students completed
the three cases in an average of 30.1 minutes with a range from 26 to 36 +/3.4 minutes. The cases have an average of 59 laboratory and procedural options
used to collect data. A positive response to the exercise was expressed by 38.5%
of the students tested. The remaining students expressed neutral responses. Of
the students, 23.0% were able to deduce the diagnosis from the case history
alone from at least one of the cases presented. Conclusion: Clinical case scenarios are an effective tool for integrating clinical immunology for medical
school curricula for 3rd and 4th year students. These exercises expose the students to clinical immunology frequently encountered in practice. The majority of medical students tested do not have adequate knowledge of clinical
G. Cortes Morales*, A.A. Velasco-Medina, A. Barreto, G. VelГЎzquezSГЎmano, Mexico City, Mexico.
Allergic conjunctivitis is a common clinical problem in allergy and ophthalmology. The conjunctiva is an immunologically active structure of the external eye, which can have lymphoid hyperplasia in response to a stimulus. Allergic conjunctivitis is an inflammatory disease of the eye. It is a type I
hypersensitivity reaction, involving the production of IgE in response to diverse
stimulus related to allergens. Objective: to determine the most frequent allergens related to the development of allergic conjunctivitis in patients attending
our clinic. Materials and methods: We performed a clinical, transversal, observational and descriptive study, which included 85 patients with allergic conjunctivitis who attended our hospital from March to June 2010. They all had
skin prick tests, ocular and nasal cytology, total serum IgE and serum
eosinophilia. We investigated their symptoms frequency and other allergic
diseases. Results: we included 85 patients, 58 (68%) female and 27 (32%)
males. The most frequent allergens identified were Quercus in 47 patients (55%),
alnus 41 patients (48%), fraxinus 28 patients (33%), Cynodon 21 patients (25%),
Dermatophagoides pteronissinus and farinae 21patients (25%). Other allergic
diagnoses were allergic rhinitis 71 patients (84%, asthma 18 patients (21%),
oral allergy syndrome 5 patients (6%), atopic dermatitis 5 (6%) and urticaria
2 (2%). The most common symptoms found in our patients were pruritus (98%),
conjunctival hyperemia (87%), epiphora (86%), foreign body sensation (52%)
and photophobia (38%). Conclusions: Patients with allergic conjunctivitis must
be diagnosed and treated by the allergist in conjunction with an ophthalmologist. The frequency of allergic comorbidities and symptoms was similar to what
is reported previously. The identified allergens in our clinic are frequent in Mexico City and correlates with their pollination season.
V. Dimov*1, T. Hamieh2, R. Wolf3, T. Casale1, 1. Omaha, NE; 2. Minneapolis, MN; 3. Chicago, IL.
RATIONALE Our aim was to evaluate the utility of aggregates of regional
search engine data for health education initiatives in allergy and immunology.
( has recorded billions of online search queries
since 2004. Search volumes for the different allergy and immunology related
terms such as “asthma”, “hay fever”, “food allergy”, etc. were recorded for the
last 6 years (January 2004-January 2010), across different geographic regions.
Data was displayed on a scale of 0-100, after normalization. Query volume in
a given geographic region was divided by number of queries in that region at
a point in time to cancel out the effect of population size on data. RESULTS
Google Search Insights showed a detailed list of “top searches” and “rising
searches” tailored to a specific geographic region. The data preserved consistency at the level of state, county and city. The model quantified the data on a
0-100 scale showing the relative interest of the general public in a particular
health topic and revealed “breakout” searches when a new trend emerges. This
algorithmic approach showed both geography- and time-dependent variations
in the search queries. For example, searches for “ragweed” peaked during
August-October in the Midwest and searches for “cedar pollen” peaked in
December-January in Texas. CONCLUSIONS The data model of Google Search
Insights has a potential utility for health educators who can target their initiatives to the specific interests of the patient population in a particular geographic
region such as state, county or city as well as specific time of the year.
V. Dimov*1, T. Hoai Nguyen1, T. Hamieh2, T. Casale1, 1. Omaha, NE; 2.
Minneapolis, MN.
Purpose The Internet has gradually become one of the first sources for reference information for many fellows in training in allergy and immunology.
Our aim was to explore the utility of the free communication service Google
Wave as educational resource and reference database for allergy and immunology. Methods We used the communication service Google Wave
( owned by Google, Inc. and provided free of charge
to registered users. Two fellows in training initiated a new messaging board
(“wave”) on Google Wave by sharing useful references, links and embedded
clinical images and videos. Results The allergy and immunology fellows in
training were able to successfully build a Google wave by adding useful references and embedding interactive resources such as audio and video files. Further links of interest, questions, answers and replies were appended to the wave
during the learning sessions. A faculty member was invited to guide, comment,
and collaborate on the didactic process through the wave. The whole recorded
wave could be played in one consecutive sequence and thus provided a consistent record of the learning process. However, all participating parties noted
difficulties navigating the Google Wave web interface. Conclusion Google Wave
has a potential as an educational resource for allergy and immunology fellows
in training but its usefulness is limited by the non intuitive web interface.
temperature, humidity, and initial weight of the pMDI were recorded. Final
weight of each pMDI was recorded to determine the spray weight of individual actuations. pMDIs were primed and operated according to instructions provided in the package insert. One minute was allowed between actuations to
allow for temperature equilibration. P values were calculated using a Student
2-tailed t test at 95% confidence interval.
Results: Three lots containing 10 units/lot (totaling 30 units) of ProAir HFA
and Ventolin HFA were tested. Minimum plume temperatures recorded were
7.2± 0.7°C and –35.9± 12.7°C for ProAir HFA and Ventolin HFA, respectively.
Compared with Ventolin HFA, ProAir HFA produced more than twice the plume
duration (385В± 46 ms vs 156 В± 58 ms; P < 0.001). ProAir HFA produced a
mean maximum spray force of 33.6В± 11.4 mN, which was significantly lower
than that of Ventolin HFA (75.9В± 12.0 mN; P < 0.0001). Conclusion: ProAir
HFA delivers a warmer, lower spray force, and longer-lasting plume compared
with Ventolin HFA, which may provide a more consistent, comfortable experience for patients using a pMDI.
H.M. Druce*, D.L. Bortniker, K. Wenk, Somerville, NJ.
D. Kennedy*, F. Koppenhagen, J. Blair, X. Zeng, Waterford, Ireland.
75% of adults age 15-24 search the internet for health information and 60%
of doctors in the U.S. are actively using social media or plan to do so this year.
An integrated structured workflow approach was taken to use SN techniques
for 3 purposes: to inform prospective patients about a new allergy practice, to
inform physicians about hospital-based educational activities and to encourage clients for a consulting practice. Twitter, LinkedIn, Facebook, Sermo and
dedicated websites were linked. Twitter was used as a primary portal to direct
viewers to blogs, which secondarily directed viewers to specific websites. The
medical center website was linked to a patient website and vice versa, and a
separate website connected to LinkedIn. Sermo was used by one of the physicians. Effectiveness of the techniques was measured at the website level by
measuring separate page views on and by increases in Twitter followers. A mail address was offered for contact on the websites. Results:
Unique visitors to the practice website were routed mainly by Google searches
and the hospital link. Visitors to the consulting website were routed mainly
from LinkedIn. Increases in website visitors paralleled increase in postings on
Twitter (tweets). The increase was not matched by new patient visits which were
still driven by physician referral and patient research on insurance company
websites, followed by Google searches. No new patient admitted that they were
directed to the practice from Twitter or the blog. Cases posted on Sermo received
a rapid response from allergy and immunology peers. However, the anonymous
nature of Sermo does not lead to patient referrals. The mailbox on both websites was used very infrequently. Conclusion: Regular maintenance of a chain
of communications requires novel information to be posted on a daily or twicedaily basis. Redundancy in posting may be necessary as patients and physicians do not follow the workflow scheme proposed. SN participants typically
use only 1 or 2 tools and do not necessarily follow a logical direction even if
directed. At this point the tools available to measure response to this integrated
approach are limited. The effort placed on web-based notification has not yet
been reflected in practice referrals. Further work is needed to make this a valueadded activity.
Introduction: Drug build-up within the actuator of a pressurized metereddose inhaler (pMDI) may ultimately cause clogging of the actuator, and improper
storage and cleaning of the pMDI may lead to suboptimal drug delivery. For
these reasons, manufacturers recommend cleaning the actuator a minimum of
once weekly to prevent drug build-up. The new ProAirВ® hydrofluoroalkane
(HFA) actuator was studied under different cleaning regimens to determine
the tendency to clog.
Methods: Canisters from 3 batches of ProAir HFA coupled with new actuators were fired to waste, in air, in sets of 2 actuations, with ≥1 hour between
sets. Washing was performed weekly after every 56 actuations (mimicking 2
actuations 4 times a day for 7 days). 200 actuations were fired from each actuator. Four studies were performed based on 4 different cleaning regimens –
study 1: actuators washed, tapped to remove excess water, then dried overnight
under ambient conditions; study 2: actuators not washed at all; study 3: actuators washed but not dried; study 4: actuators washed, shaken to remove excess
water, then dried overnight under ambient conditions. An actuator was deemed
clogged if its spray was quieter and plume was thinner and took longer to exit
the actuator than that of a non-clogged actuator.
Results: Thirty new ProAir HFA actuators were included in each of the 4
studies. In study 1, none of the ProAir HFA with new actuators clogged when
washed according to updated patient instructions. Study 2 and study 3 were
undertaken as potential misuse scenarios with results also showing no clogging
of the new actuators. No clogging occurred with the new actuators in study 4
when washed according to current patient instructions. In summary, even when
subjected to different cleaning conditions, none of the new ProAir HFA actuators used in the study were found to clog during the 200 actuations.
Conclusion: Within this small, controlled, laboratory study, the new ProAir
HFA actuator did not clog under several cleaning regimens. However, as with
all albuterol pMDI’s, regular cleaning of the inhalers remains essential to ensure
proper functioning.
J. McCabe*1, F. Koppenhagen1, J. Blair2, X. Zeng1, 1. Miami, FL; 2. Waterford, Ireland.
Introduction: Inhaler technique and spray characteristics are critical for adequate management of asthma symptoms by pressurized metered-dose inhalers
(pMDIs). A lower spray force has been directly associated with a decrease in
throat deposition of asthma medication, and a higher spray temperature may
alleviate the “cold Freon effect” associated with pMDIs. A pMDI that delivers
a warmer, longer-lasting plume with a lower spray force may improve the patient
experience in using pMDIs. The objective of the study was to characterize and
compare the temperature, maximum spray force, and duration of the emitted
plume from 2 pMDIs: the new ProAirВ® hydrofluoroalkane (HFA) and VentolinВ®
Methods: Spray force tester model SFT1000 and temperature probe were
used to test 10 units of each inhaler type. Three consecutive actuations were
tested at a spray distance of 40 mm from the edge of the mouthpiece. Room
G.J. Janss*, Rapid City, SD.
A 13-year-old girl was taken to Mayo Clinic with a 2 year history of urinary frequency, suprapubic pressure, pain during most episodes of urination.
She voided 7–8 per day, but did not feel like she completely emptied her bladder. She had a cystoscopy and biopsy was done. Received a call a few days later
that the biopsy was consistent with eosinophilic infiltrate of the bladder. Her
parents were told to take her to an allergist close by for work-up. She came to
our office on December 13, 2005 with a history of severe colic as an infant,
allergic rhinoconjunctivitis with reactive airway disease. She had seasonal exacerbation, which started at age 2 years old when her father took her with him in
the tractor during harvest time. Skin tests revealed sensitivity to molds, weeds,
dust, grass, trees, animal danders, dust mite and several of the foods tested. She
was treated with medications, environmental control, diet and started on
immunotherapy. After immunotherapy was started her bladder symptoms
receded. She was receiving build up injections at weekly intervals; however
when she missed her weekly injection, during the second week her bladder
symptoms recurred, cleared again when she restarted her immunotherapy. After
reaching full dose, needed injections every 2 weeks. Discussion: Eosinophilic
cystitis is rare disease which was first described in 1960, manifested by difficulty and pain when urinating, frequent urinations, blood in the urine and lower
abdominal pain. When a drug reaction or allergen can be identified, removing
the drug or the allergen might improve symptoms. Occasionally it has been
shown to resolve on its own in some children. (1) Other times, lesions occur
in the bladder that do not heal on their own and partial cystectomy has been
done. (2) Cyclosporin has been described as being useful in treating the condition. (3) This young girl improved with immunotherapy and her symptoms
recurred when the interval between immunotherapy injections were prolonged.
Receiving her scheduled injections she has been symptoms free for the last 4
1 2
⁄ years. References: Eosinophilic Cystitis–Document ID 432, Eosinophilic
Cystitis Resource Center Eosinophilic Cystitis–Verhagen et Allegra. 84 (4);
344–Archives of Disease in Childhood Eosinophilic Cystitis in 4-Year-Old Boy:
Successful Long-Term Treatment w/ Cyclosporin A Avishalom Pomeranz, (el)
Pediatrics 2001; 108;e113
L.M. Landmesser*, G. Tillotson, D. Mariano, Exton, PA.
Background: Management of HAE has previously involved therapy with
fresh frozen plasma or attenuated androgens. Approval of Cinryze in the USA
for routine prophylaxis of HAE has progressed its clinical management, allowing self-administration for this unpredictable disease. Methods: In a dynamic
internal Cinryze database of HAE patients, demographic data, as reported by
patients, was examined to determine the site of care (SOC) of Cinryze in the
US. Results: Five hundred and sixteen HAE patients received Cinryze. Of
those, 243 (47%) administered Cinryze at home, 142 (28%) in the physician’s
office, and 120 (23%) received treatment at an infusion center (6 & 11 patients,
age & SOC unknown). Further data are presented in the table regarding the
age and gender by SOC. Of those treated at home, 42% reported self-administration, while 16% and 23% reported drug administration by a family member or home healthcare, respectively. Age ranged from 5 to 84 years. None in
the 0-12yr or >65yr age groups reported self-administration. Patients between
the ages of 30-64 were the largest age group in which 50% self-administered.
Overall, self-administration occurred in 20% of patients. Patients who selfadministered ranged geographically, 38%, 45%, 48%, and 55% in Midwest,
West, South, and Northeast, respectively. Conclusion: Patients’ age and geographic location but not gender may influence the reported site of care for
Cinryze administration. Self-administration is a feasible and viable option for
HAE patients using Cinryze.
Age/Gender Breakdown of Patients with Respect to Site of Care
L.H. Potter*, N. Pollock, D. Guo, I. Stallman-Jorgensen, H. Zhu, D. Ownby,
Y. Dong, Augusta, GA.
the effects of 400 and 2000 IU/d of vitamin D3 supplementation on circulating total IgE and allergen-specific IgE levels in black adolescents. Subjects and
Methods: 46 black adolescents participated in a randomized clinical trial of
vitamin D supplementation. 24 participants (400 IU group, n=9; 2000 IU group,
n=15) who tested positive on Immunocap assay for allergen specific-IgE production(≥0.10 kUA/l) were included in this analysis. Serum concentrations of
25-hydroxyvitamin D [25-(OH) D], total IgE, fire ant venom (FAV) IgE
(Solenopsis invicta) were analyzed at baseline and 16 weeks. Repeated measures ANCOVA, controlling for sex and BMI, was used to compare outcome
variables between groups. Total IgE and FAV-specific IgE were log-transformed
to follow a normal distribution. The magnitude of difference between groups
was calculated using Cohen’s d (d) effect size. Values of 0.2, 0.5, and 0.8 for
Cohen’s d indicate small, medium, and large effects, respectively. Results: Mean
(В±SD) plasma 25(OH)D values at baseline and 16 weeks were 28.7В±8.6 and
55.2В±21.5 nmol/L, for the 400 IU group, and 32.6В±8.7 and 85.5В±33.5 nmol/L,
for the 2000 IU group. The change in total IgE in the 400 IU group was (+)
44% compared to (+) 0.2% in the 2000 IU group (p=0.06, d=0.91). There were
no significant changes between groups in FAV-specific IgE; the 400 IU group
increased +1.8%, while the 2000 IU group decreased -3.8% (p=0.36, d=0.31).
Conclusion: In this small sample, it appears that 2000 IU/d of vitamin D supplementation may provide benefit to allergic-sensitized African American adolescents. Additional study of vitamin D supplementation and allergic sensitization is warranted.
J.A. Bernstein*1, P.T. Horn2, W.E. Pullman2, 1. Cincinnati, OH; 2. Cambridge, MA.
Introduction: Hereditary angioedema (HAE) is a genetic disorder resulting in unpredictable, acute swelling attacks. Ecallantide is a plasma kallikrein
inhibitor approved for treatment of acute HAE attacks. A second dose of ecallantide (Dose B) may be required in some patients. We analyzed characteristics
of Dose B patients to try to identify predictive factors. Methods: The EDEMA
development program evaluated the safety and efficacy of ecallantide for the
treatment of moderate to severe acute HAE attacks. An open-label dose of 30
mg subcutaneous (SC) ecallantide (Dose B) was allowed in the EDEMA2,
EDEMA3 Repeat-Dosing, EDEMA4, and DX-88/19 studies for no response,
incomplete response or relapse following initial treatment with 30 mg SC
ecallantide. Patients requiring Dose B were compared to patients with no Dose
B. The appropriate IRB approved each study; all patients provided written
informed consent. Results: The analysis included 200 patients treated for 810
HAE attacks; 49 patients required Dose B for 86 attacks and 151 patients were
treated for 724 attacks without Dose B. The most common reason for Dose B
was incomplete response (81%). Mean age was similar for Dose B and nonDose B patients (36 vs 35 years). More Dose B patients were naГЇve to ecallantide (84%) than non-Dose B patients (69%). Approximately 35% of Dose B
patients and 30% of non-Dose B patients had a body mass index (BMI) >30
kg/m2. The majority of patients were treated for peripheral attacks (55% Dose
B vs 56% of non-Dose B patients). A greater proportion of non-Dose B patients
than Dose B patients were treated for an abdominal attack (55% vs 37% of
Dose B patients, P=0.03). Laryngeal attacks were the least common for both
groups (24% of Dose B vs 30% of non-Dose B patients). The time between
onset of attack symptoms and initial treatment did not appear to affect the
need for Dose B. Symptom improvement was demonstrated following Dose
B. Treatment-emergent adverse events (TEAEs) were reported in 82% of Dose
B patients vs 65% of non-Dose B patients. The most common TEAEs in Dose
B patients were nausea, headache, and diarrhea. Conclusion: A second dose
of ecallantide is indicated in some patients experiencing acute HAE attacks.
This second dose appears to be well tolerated. Further study may identify possible predictors for the need to have Dose B.
Background: The prevalence of allergic sensitization and vitamin D deficiency has been reported as higher in black adolescents compared to other races.
In the southeastern United States, sensitization to fire ant venom (FAV) is common. It remains unclear whether low vitamin D levels are a causal contributing factor to allergic sensitization. Study of vitamin D supplementation may
help clarify the role of vitamin D in allergic disease. Objective: To determine
P.M. Ratner*1, A. Melchior2, S.A. Dunbar2, S.K. Tantry2, P.M. Dorinsky2,
1. San Antonio, TX; 2. Horsham, PA.
Introduction: The primary objective of this study was to compare systemic
levels of beclomethasone-17-monoproprionate (17-BMP—the pharmacologically active metabolite of beclomethasone dipropionate [BDP]) after intranasal
administration of BDP HFA (hydrofluoroalkane) with those of orally inhaled
BDP HFA (QVARВ®) in healthy volunteers. Methods: A single-center, randomized, open-label, 3-period crossover study was conducted to assess the pharmacokinetics, safety, and tolerability of BDP HFA nasal aerosol. Healthy subjects (18-45 years, N=30) were randomized to receive a single dose of
intranasally administered BDP HFA (80 Вµg/d or 320 Вµg/d) or orally administered BDP HFA (320 Вµg/d). A total of 17 blood samples were obtained (predose through 24 hours) for pharmacokinetic analysis of 17-BMP. The primary
pharmacokinetic parameters analyzed were area under the concentration-time
curve until the last measurable value (AUClast) for 17-BMP and maximum
plasma concentration (Cmax) for 17-BMP. Plasma concentration of 17-BMP was
analyzed using a validated LC/MS/MS method. The lower limit of quantitation of the 17-BMP assay was 20 pg/mL. The safety and tolerability of BDP
HFA also was evaluated. Results: Mean plasma concentrations of 17-BMP after
intranasal administration of BDP HFA (80 Вµg/d and 320 Вµg/d) was substantially less than mean plasma concentrations of 17-BMP after oral inhalation of
BDP HFA (320 Вµg) across all timepoints. AUClast following administration of
BDP HFA nasal aerosol (320 Вµg/d) was approximately 27.5% of that of orally
inhaled BDP (320 Вµg/d) and Cmax was approximately 19.5% of that of orally
inhaled BDP (320 Вµg/d). Similarly, AUClast and Cmax following BDP HFA nasal
aerosol (80 mcg/day) of that of orally inhaled BDP (320 Вµg/d) were 7.1% and
7.0%, respectively. All doses of intranasal BDP HFA and orally inhaled BDP
HFA were well tolerated and no treatment-related adverse events were reported.
No differences in adverse events profiles were observed between intranasal
doses. Conclusions: The results of this study demonstrated that 80 Вµg/d and
320 Вµg/d BDP HFA nasal aerosol have substantially lower systemic bioavailability compared with orally inhaled BDP 320 Вµg/d. These data suggest that
the safety profile of intranasal BDP HFA is likely to be substantially better relative to that of orally inhaled BDP HFA.
M. Hedlund, J.L. Larson, D. Wurtman, R.B. Moss*, F. Fang, San Diego,
Introduction: DAS181, an inhaled sialidase fusion protein as a potential
broad-spectrum anti-viral for influenza-like illness now in a Phase 2 trial, was
previously shown to reduce airway resistance and mucus production in animal
models of allergic asthma, suggesting potential usefulness in asthma and chronic
inflammatory lung diseases. Here we studied muscarinic receptor desialylation
as a potential mechanism for these observations, using in vivo and in vitro models. Methods: BALB/c mice (N=4) were treated intranasally with PBS, DAS181
or DAS185 (>400-fold lower sialidase activity than DAS181) at 0.06, 0.1 and
0.6 mg/kg daily for three days. Eight hours after final treatment animals were
challenged with the muscarinic receptor agonist methacholine (Mch) at 3, 6,
12, 24, 48 mg/ml. Airway resistance was assessed using whole body plethysmography. Human chem-1 cells stably transfected with M2 or M3 muscarinic
receptor were treated with 0.4, 2 or 10 mM of DAS181 for 30 min at 37В°C prior
to addition of acetylcholine. Results: We have previously demonstrated
DAS181’s beneficial effect in animal models of airway disease. Here, DAS181
treatment of naive mice significantly reduced airway resistance to Mch compared to PBS treatment at all three dose levels tested (p<0.05). In contrast, the
enzymatically impaired variant DAS185 offered no protection in response to
Mch suggesting that the inhibitory effect was sialidase dependent. In vitro treatment of human chem-1 cells transfected with M2 or M3 muscarinic receptor
increased signaling through M2 while decreasing M3 receptor signaling
(p<0.0001), which was determined using a fluorescence reporter for intracellular calcium. These findings were indicative of positive allosteric modulation
of the M2, and either antagonist or negative allosteric modulation of the M3
receptor. Conclusion: This report addresses a possible mechanism of action
for DAS181 mediated reduction of airway resistance in mice. Contrary to prior
reports in the literature, we found that muscarinic receptor desialylation reduced
airway resistance. The effect was maintained in vivo at very low once-daily
doses of DAS181. In vitro data further elucidated a dual mechanism of action,
reduction of the stimulatory M3 pathway while enhancing signaling through
the inhibitory M2 receptor.
M. Magerl*, K. Krause, K. Weller, M. Maurer, Berlin, Germany.
Introduction: Icatibant, a selective bradykinin B2 receptor antagonist, is
a novel treatment for acute attacks of hereditary angioedema (HAE) in adults
with C1-esterase-inhibitor (C1-INH) deficiency. Icatibant is an investigational
treatment in the US. We present 6 cases of patients with HAE and acquired
angioedema (AAE) due to C1-INH deficiency who were treated with icatibant.
Methods: Three patients suffered from HAE and 3 patients from AAE. Patients
were treated with a single dose of icatibant subcutaneously during an acute
attack. Results: The patients were aged between 30–64 years (average, 50 years).
The average age at onset of symptoms was 12.3 years for patients with HAE,
and 60 years for patients with AAE. In the last year, the patients suffered from
acute angioedema attacks at least once every 3 months (maximum 5 attacks
per month). Three patients were treated with icatibant for abdominal attacks,
and 3 for cutaneous attacks. Following treatment with icatibant, the first signs
of improvement were observed at a median time of 35 min (range, 10–120 min).
Significant improvement was observed at a median time of 2.5 h (range, 0.5–18
h). Side effects (local erythema and burning) were reported by all patients; these
were described as �negligible’ or �slight’. Other side effects reported in 1 patient
were painful injection, hypotonic dysregulation and local swelling. The local
side effects in this patient were initially described as �severe’, but were considered �negligible’ 1 h after injection. Five of the 6 patients reported that
treatment with icatibant �met their expectations’. Conclusion: Icatibant was
effective and generally well tolerated in 3 patients with HAE and 3 with AAE.
A. MalbrГЎn*1, M. Bas2, 1. Buenos Aires, Argentina; 2. Munich, Germany.
Introduction: Data describing icatibant treatment in repeated potentially
life-threatening laryngeal attacks in patients with hereditary angioedema (HAE)
are currently limited. We evaluated the efficacy of subcutaneously (sc) administered open-label icatibant (30 mg) for the treatment of laryngeal attacks in
the controlled and open-label extension (OLE) phases of 2 phase III trials (FAST
[For Angioedema Subcutaneous Treatment]-1 and -2). Methods: During the
controlled phases of both studies, patients presenting with a laryngeal HAE
attack (first attack) were treated open-label with a single dose of icatibant (30
mg sc). Any patient experiencing a subsequent laryngeal HAE attack of sufficient severity to require treatment was included in the OLE phase and treated
with 1 sc injection of 30 mg icatibant. If an attack worsened within 48 h of initial treatment, additional injections of icatibant (up to 3 injections per attack,
≥6 h apart) could be administered. Symptoms occurring >48 h post-initial treatment was considered a new attack. Study assessments included time to symptom regression (patient-reported) and overall patient improvement (investigator-reported). Each study was approved by the independent ethics committee
for each center. All patients gave written informed consent. Results: Overall,
78 laryngeal attacks in 38 patients were treated with icatibant (45 attacks/26
patients, FAST-1; 33 attacks/12 patients, FAST-2). Median times to symptom
regression in the controlled phases of FAST-1 and FAST-2 were 0.6 h and 1.0
h, respectively. In the OLE phase, these times ranged from 0.3–1.2 h in FAST1 and 0.3–4.0 h in FAST-2. Overall patient improvement was seen in 88% of
patients in FAST-1 and in 100% of patients in FAST-2 (median times of 0.7 h
and 0.8 h, respectively). Overall, only 7 (≈10%) laryngeal attacks required more
than 1 injection of icatibant (2 injections, n=6 attacks; 3 injections, n=1 attack)
during the OLE phase. There were no deaths, drug-related serious adverse events
(AEs), or discontinuations due to AEs. Almost all patients experienced injection-site reactions (erythema, swelling, itching, burning and pain) which were
generally mild-to-moderate in intensity and resolved spontaneously without
medical intervention. Conclusion: Icatibant was effective and generally welltolerated in the treatment for acute laryngeal HAE attacks.
S. Nsouli*, Danville, CA.
Although increased retropharyngeal mucus secretion (postnasal-drip syndrome) is commonly seen in allergic rhinitis, its clinical management has not
been fully established. Three parallel investigations were conducted for a period
of 4 weeks. 20 patients were treated with topical intranasal corticosteroid Mometasone Furoate (MF) 100 mcg/nostril once daily (groupA), 20 patients were treated
with topical intranasal antihistamine Olopatadine (OLO) 1330 mcg/nostril twice
daily (group B), and 20 patients were treated with the combination of the two
pharmacologic agents intranasal Mometasone Furoate (MF) and intranasal
Olopatadine (OLO)(group C). The efficacy of the treatment in the three different groups was monitored by rhinomanometry, flexible rhinoscopy and subjective symptom scoring system. The severity and duration of the postnasal-drip
decreased in 10/20 (50%) of group A patients (MF), in 7/20 (35%) of group B
patients (OLO) and in 16/20 (80%) of group C patients (MF and OLO). Thus
although, intranasal Mometasone Furoate or intranasal Olopatadine used individually showed therapeutic benefit, the combined use of intranasal Mometasone and intranasal Olopatadine led to more significant resolution of the postnasal-drip syndrome due to the possible synergistic effect of the combination
drug regimen.
domized 1:1 to once-daily grassAIT (oral lyophilisate, Phleum pratense, 2800 BAU)
or placebo (PBO), starting approximately 16 weeks before and continuing throughout the grass pollen season.AEs were monitored and assessed for severity. Results:
All randomized subjects but 1 in each study (344/345, study 1; 438/439, study 2)
received ≥1 study treatment dose.The most common treatment-emergent (TE)AEs
were oral pruritus, throat irritation, and nasopharyngitis in study 1; oral pruritus,
throat irritation, and upper respiratory tract infection in study 2. TE asthma and
urticaria were rare (≤4%). Treatment-related (TR) AEs (Table) were reported by
122/175 (70%) of AIT subjects and 43/169 (25%) of PBO subjects in study 1, and
155/213 (73%) of AIT subjects and 62/225 (28%) of PBO subjects in study 2.
Most TRAEs were mild or moderate; <2% of subjects had severe TRAEs. The
majority of grassAITTRAEs were local, application site reactions that began shortly
after treatment initiation and resolved within a few days; the rate of new local
application site AEs diminished with treatment over time. Few subjects discontinued because of AEs (study 1: AIT=13/175; PBO=5/169; study 2: AIT=11/213,
PBO=8/225). One subject from each study received epinephrine in response to an
AIT-related reaction (study 1: moderate [lip angioedema/dysphagia/cough]; study
2: mild [flush/rash/chest discomfort]) at first dose. One subject (study 1) reported
a possible AIT-related systemic reaction (dyspnea, chest discomfort, neck pruritus, racing heart, mouth pain). No serious or life-threatening AIT TRAEs or new
safety concerns were reported for either study. Conclusions: Timothy grass AIT
was found to be safe and well tolerated in NorthAmerican adults and children. The
incidence and severity of AEs were similar across age groups, supporting the use
of the same dose of grass AIT independent of age.
Table. Treatment-Related Adverse Events in ≥5% of Subjects
M. Riedl*, Los Angeles, CA.
Introduction: Hereditary angioedema (HAE) is a rare, genetic disorder
characterized by unpredictable, recurrent attacks of edema affecting the skin
and mucous membranes. The efficacy and safety of icatibant, a selective and
specific bradykinin B2 receptor antagonist, was assessed in patients with acute
HAE attacks type I or II during the FAST (For Angioedema Subcutaneous Treatment)-1 Phase III trial. Methods: Placebo-controlled phase: patients with moderate-to-very severe cutaneous or abdominal HAE attacks were randomized
(1:1) to 1 subcutaneous injection of icatibant (30 mg) or placebo. Open-label
extension (OLE) phase: subsequent HAE attacks were treated with icatibant
only. Primary symptoms (cutaneous swelling, cutaneous pain, or abdominal
pain) were assessed using visual analog scale (VAS) scores. The most severe
symptom pre-treatment was evaluated for the primary endpoint, time to onset
of symptom relief ≥30% (TOR30+). Approval was obtained from the independent ethics committee for each center. All participants gave written informed
consent. Results: Placebo-controlled phase: In 56 randomized subjects, time
to TOR30+ was shorter for icatibant (2.5 h) versus placebo (4.6 h; P=0.142).
Post-hoc evaluation showed TOR30+ for icatibant was significantly faster for
cutaneous swelling (P=0.039) and cutaneous pain (P=0.007), but not abdominal pain (P=0.056). Mean VAS reduction was significantly greater for icatibant at 4 h (P=0.002) and 12 h (P=0.028). Time to patient-assessed first symptom improvement was 0.8 h for icatibant versus 16.9 h for placebo (P<0.001).
Time to almost complete symptom relief (TOR90+) was shorter with icatibant
(8.5 h) versus placebo (19.4 h). OLE phase: TOR30+ for subsequent attacks
(≥10 patients) was 1–2h, response rate was 72.7–90.9%, and TOR90+ (attack
number 2 involving most patients, n=55) was 10.0 h. No drug-related serious
adverse events were reported. Changes in safety parameters were unremarkable. Transient local injection-site reactions (erythema, swelling, itching, burning, and pain) occurred in most patients administered icatibant, none led to
patient withdrawal. Conclusions: FAST-1 supports the efficacy and safety of
icatibant in treating acute HAE attacks of type I or II.
P. Creticos*1, M. Blaiss2, H. Nolte3, J. Maloney3, H. Nelson4, 1. Baltimore,
MD; 2. Memphis, TN; 3. Kenilworth, NJ; 4. Denver, CO.
Introduction: Immunotherapy for allergic rhinoconjunctivitis (AR) via sublingual tablets may be safer, and more convenient than immunotherapy via subcutaneous injection. We report adverse events (AEs) from 2 clinical trials (1 adult; 1
pediatric) that investigated the efficacy and safety of Timothy grass allergy
immunotherapy tablet (AIT) in NorthAmerica. Methods: Subjects (study 1: 5–17y;
study 2: 18–65y) with grass pollen–induced AR with or without asthma were ran-
AIT=allergy immunotherapy tablet.
*Mild erythema, not ulcerative lesions or infection.
J. Herzog*, New York, NY.
Background: Prior studies evaluating competitive swimming in indoor chlorinated pools indicate that increased asthmatic symptoms are among the deleterious effects. Recent publications have concluded that increased nasal congestion is one of the side-effects of swimming in indoor chlorinated pools. This
study compares the prevalence of nasal congestion in competitive swimmers
who swim in indoor chlorinated pools versus those who swim in indoor ozone
treated pools. Method: Seventy pediatric swim team members, between the
ages of six and fifteen, were surveyed regarding their congestion and allergic
symptoms before and after swimming in an ozone treated or chlorinated indoor
pool. Results: Five of the thirty-five swimmers who swam in the ozone treated
pool (14 percent) and eleven of the thirty-five swimmers who swam in the chlorinated pool (31 percent) reported having stuffier nose after swim practice.
Conclusion: In comparison to competitive swimming in ozone treated pools,
competitive swimming in chlorinated indoor pools results in a statistically significant increase in nasal congestion. Further studies are needed to evaluate the
significance of this difference.
P. Bajaj*1, A. Donato2, N. Patel2, S. Lakshminarayanan2, C. Leer2, 1.
Lebanon, PA; 2. Reading, PA.
Introduction - The primary objective of this study was to investigate if
self-reported nasal obstructive symptoms or allergic rhinitis is related independently to OSA severity or degree of sleepiness. Also we evaluated whether
self-reported nasal stuffiness increased predisposition towards using facemask
for CPAP. Methods- Data was collected from retrospective chart analysis on
patients who underwent sleep study during six month period (January 2010 –
June 2010). Self reported nasal congestion, sinus headaches and allergic rhinitis was obtained from pre-sleep study questionnaire. Patient age, sex, body mass
index(BMI) and epworth sleep score were recorded along with information on
apnea hypopnea index(AHI), snoring, sleep architecture data, and final mask
used in CPAP trial. The project received IRB exemption. Result Out of 465
sleep studies, 362 matched the inclusion criteria. 258(71.2%) subjects reported
presence of nasal obstruction as compared to 104(28.8%) without it. There were
203 males and 159 females. Mean age was 46.5 years. Mean BMI in both groups
was comparable (35.41 vs 35.62). We found slight worsening of AHI with presence of nasal stuffiness (20.71 vs 25.46) but this trend was not significant.
There was no difference in snoring in both the groups. There was significant
worsening of epworth sleep score in patients with nasal stuffiness (8.12 vs 9.75,
p <0.05). AHI showed a significant correlation with age, male sex and BMI.
There was no correlation between nasal stuffiness and sleep architecture(efficiency, latency and arousal index). No significant predisposition was
seen towards facemask use in patients with nasal stuffiness. Multiple logistic
regression for AHI showed a significant variance with sex and BMI. Although
nasal stuffiness did not contribute significantly towards AHI, it was associated
significantly with higher epworth score when BMI, sex, age, smoking were
controlled for(variance 1.9%). Conclusion We conclude that presence of self
reported nasal stuffiness shows a positive trend toward AHI and is associated
with significantly higher epworth sleep score but it does not predict the type
of CPAP mask. Such trends were not found with allergic rhinitis.
M.H. Bashir*, P. Buddiga, J. Ko, M.N. Baz, Fresno, CA.
Purpose: Nasal polyps are associated with various conditions including
Asthma, Chronic Rhinosinusitis and Cystic Fibrosis. It was felt empirically that
association of aspirin intolerance with nasal polyps was not as high as was
reported in previous studies. It has previously been reported to be associated
with 14% to 23% of patients who have nasal polyps depending on the method
of data collection. This retrospective analysis was done to confirm the association of aspirin intolerance with nasal polyps in our office. Methods: We retrospectively reviewed one year data (2009) in a stable outpatient population
with nasal polyps in a busy allergy practice. Patients who were suspected to
have nasal polyps on clinical exam and had a CT scan showing nasal polyps
were included in the study. Their charts were further reviewed for history of
aspirin intolerance. Results: 676 patients were found to have nasal polyps on
CT scan out of which history of 517 patients was reviewed for aspirin intolerance (159 charts were not reviewed because of patients being from other clinics). The mean age was 43 years with gender distribution being 36% males
and 64% females. 7 (1%) patients were found to have aspirin intolerance out
of which 5 (71%) were female and 2(29%) were male. Conclusion: Aspirin
intolerance was only found to be associated with 1% of patients with nasal
polyps. The prevalence of nasal polyps and associated aspirin intolerance is
greater in females compared to males. Further assessment will be done by
contacting all the patients whose charts were reviewed to document patients
who might have missed reporting the aspirin allergy on their clinic visit.
from sinuses. Nasal endoscopy is done by some allergists but mostly by otolaryngologists. Swollen turbinates can easily be confused for polyps on otoscopic examination. Polyps not protruding into the nasal cavities (Maxillary,
Frontal, Ethmoid and Sphenoid Polyps) cannot be visualized even by endoscopic exam. Methods: We retrospectively reviewed Sinus CT Scans done in
2009 for presumptive diagnosis of sinusitis and polyps in a busy allergy practice in Central California. Xoran MiniCAT was used for imaging. Patient data
base was also searched for patients who were thought to have sinusitis and nasal
polyps on clinical history and nasal examination but CT scan was not done
because of insurance denial or financial reasons. Results: 3276 patients were
diagnosed clinically with either sinusitis or polyps in 2009. Out of these 765
patients had a CT scan done and 676 (88%) were found to have polyps. The
mean age was 45 years with gender distribution being 36% male and 64%
female. Conclusion: 88% of patients who had the CT scan done were positive
for polyps. Considering this high percentage of polyp prevalence on imaging,
it’s concluded that a large number of all the patients who are seen for sinusitis
and polyps are missed due to lack of access to CT Scans either because of not
being readily available to allergists or because of insurance restrictions. Upright
CT scan use exposed patients to minimum radiation with great yield in diagnosing sinus polyps. Definitive diagnosis of polyps after having the scan done
also significantly increased the treatment and follow up compliance in patients
for nasal polyps.
A. Didier1, F. Horak2, M. Worm3, M. Melac4, O. de Beaumont*4, M. Le
Gall4, A. Montagut4, S. Galvain4, H. Malling5, 1. Toulouse, France; 2.
Vienna, Austria; 3. Berlin, Germany; 4. Antony, France; 5. Copenhagen,
Background: In single-season clinical trials, once-daily pre-coseasonal treatment with a 300IR 5-grass pollen SLIT tablet was shown to be safe and effective in adults and children. The aim of this study was to evaluate the sustained
efficacy and safety of pre-coseasonal treatment with 5-grass pollen SLIT tablet
in adults with grass pollen allergic rhinoconjunctivitis. Methods: 633 patients
aged between 18 and 51 years were included in a DBPC, international, multicentre Phase III trial to evaluate the sustained efficacy and safety of the 300IR
5-grass pollen SLIT tablet over 3 consecutive seasons. Patients were randomized to a placebo and 2 active groups, receiving either 4 or 2 months of preseasonal treatment and co-seasonal treatment. Use of rescue medication was
permitted. The primary efficacy endpoint was the Average Adjusted Symptom
Score (AAdSS, a score that integrates the symptoms and rescue medication
use) over the 3rd pollen season. Results: 457 patients completed 3 consecutive
seasons (2007, 2008 and 2009). Preliminary results of the 3rd pollen period
showed a mean AAdSSВ±SD of 3.51В±3.68 and 3.39В±3.23 for the 4 and 2 months
pre-seasonal treatment groups respectively, compared with 5.28В±3.95 in placebo
group. The efficacy of 300IR 5-grass pollen SLIT tablet seems to increase at
every season, reaching a mean AAdSS improvement vs. placebo of 34% (median
= 48%) in season 3 (4-month pre-seasonal treatment group). In this group, the
mean AAdSSВ±SD was 3.79В±3.95 in monosensitized patients and 3.31В±3.49 in
polysensitized patients. The treatment effect seemed to appear at lower pollen
levels in the 2nd and 3rd seasons (booster effect). Treatment-related adverse
events were mostly transient and mild to moderate in intensity, and their number decreased in the 2nd and 3rd treatment seasons. Conclusion: Three years
of pre-coseasonal treatment with a 300IR 5-grass pollen SLIT tablet showed a
sustained effect with statistical and clinically significant improvement of
rhinoconjunctivitis symptoms in adults and a booster effect was observed. Efficacy was good in mono and in polysensitized patients. A potentially diseasemodifying effect is now being investigated by discontinuing the SLIT and scoring the patients’ symptoms for 2 additional seasons.
M.H. Bashir*, P. Buddiga, J. Ko, M.N. Baz, Fresno, CA.
Purpose: Polyps may be visible on otoscopic or endoscopic nasal examination when they are in the nasal cavity or protruding into the nasal cavities
S. Daly*, K. Sundar, Provo, UT.
Sarah E. Daly, DO ; Krishna M. Sundar, MD, FCCP Departments of Family Practice and Medicine, Utah Valley Pulmonary Clinic and Merrill Gappmayer Family Medicine Center, Provo, UT 84604. Background: Chronic cough
is a common complaint in primary care, ENT and pulmonary practices. Current guidelines suggest the occurrence of upper airway cough syndrome (UACS),
gastroesophageal reflux (GERD) and cough variant asthma (CVA) as major
etiologies for chronic cough although a number of patients remain refractory
to therapy. A significant seasonal variation of chronic cough occurs that is commonly noted but has not been reported before. Whether there is any relation
between seasonal variation and etiology of cough is unclear. Methods: A retrospective review of chronic cough patients (duration between 8 weeks and 1
year) from a community-based pulmonary practice was done. Abnormal chest
radiographs and pulmonary function tests, history of known parenchymal lung
disease, and inadequate followup prompted exclusion. Charts were reviewed
for duration of cough, seasonal onset, and cough characteristics and etiology.
Results: 85 patients with chronic cough were reviewed over a 6 year period,
with 60 patients having cough durations ≤ 1 year and 25 with duration ≥ 1
year. 31/60 of the patients with cough ≤ 1 year had an onset of chronic cough
in the winter months with 39% of these patients starting with an inciting respiratory illness at the onset (Table 1a). The most common etiologies associated with winter onset of chronic cough were GERD (35%) and GERD/UACS
(39%), which was similar to etiologies of chronic cough in the remainder of
the seasons (Table 1b). Conclusions: Chronic cough often has a seasonal onset
in the winter months and follows a respiratory infection as an inciting event in
39% of patients. The lack of correlation with seasonal allergic diatheses rules
against UACS being a prominent cause of chronic cough.
to CIC-HFA 80 Вµg (N=237), CIC-HFA 160 Вµg (N=237), or placebo (N=235)
once-daily in the morning for 2 weeks. Subject-reported diaries were used to
record change from baseline in morning and afternoon reflective total nasal
symptom score (rTNSS) and instantaneous total nasal symptom score (iTNSS)
averaged over the 2 week treatment period and were calculated as a sum of
the 4 individual nasal symptoms of congestion, runny nose, sneezing, and
nasal itching each on a scale of 0 (no signs/symptoms evident) to 3
(signs/symptoms hard to tolerate and interfered with daily activities). Change
from baseline in the individual reflective and instantaneous nasal symptom
scores of congestion, itching, sneezing, and runny nose averaged over the 2
week treatment period were also evaluated. Treatment-emergent adverse events
(TEAEs) were monitored throughout the study. Results: CIC-HFA 80 Вµg
and CIC-HFA 160 Вµg demonstrated a statistically significant improvement
in rTNSS, iTNSS (P<0.0001 for both) and improvements in the individual
reflective and individual instantaneous nasal symptoms of congestion, nasal
itching, sneezing, and runny nose (P<0.0001 for all, unadjusted for multiplicity) from baseline (Table). The overall incidence of TEAEs was low and
comparable between the CIC treatment groups and placebo. The most frequently reported TEAEs (≥2% of subjects in any treatment group) were epistaxis, nasal discomfort, and nasal septum disorder. Conclusions: In this study,
once-daily treatment with CIC-HFA 80 Вµg or CIC-HFA 160 Вµg demonstrated
statistically significant improvements in the nasal symptoms of SAR. Both
active treatments were well tolerated.
Table. Change in reflective and instantaneous nasal symptom scores averaged
over the 2 week treatment period (ITT population)
Table 1a.
Table 1.b.
Data are least squares means (standard error). ITT=Intent to treat; CICHFA=Ciclesonide hydrofluoroalkane nasal aerosol; rTNSS=Reflective total
nasal symptom score; iTNSS=Instantaneous total nasal symptom score.
D. Mohar*1, R. Jacobs2, P. Ratner2, H. Huang3, S.Y. Desai3, J. Hinkle3,
F. Bode3, 1. Kerrville, TX; 2. San Antonio, TX; 3. Marlborough, MA.
P.H. Ratner*1, R. Jacobs1, D. Mohar2, H. Huang3, S.Y. Desai3, J. Hinkle3,
F. Bode3, 1. San Antonio, TX; 2. Kerrville, TX; 3. Marlborough, MA.
Background: Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is
currently in development as a potential treatment for allergic rhinitis. The
objective of this study was to determine the efficacy and safety of CIC-HFA
compared to placebo in subjects ≥12 years of age with seasonal allergic rhinitis (SAR). Methods: Subjects with a ≥2 year history of SAR were randomized in a placebo-controlled, double-blind, parallel group, multicenter study
Background: Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is
currently in development as a potential treatment for allergic rhinitis. The
ability of CIC-HFA to improve the rhinoconjunctivitis related quality of life
associated with seasonal allergic rhinitis (SAR) as measured by the rhinoconjunctivitis quality of life questionnaire with standardized activities (RQLQ[S])
was evaluated in subjects ≥12 years of age who were administered either
CIC-HFA or placebo. Methods: Data for this analysis was collected as part
of a placebo-controlled, double-blind, parallel group, multicenter study in
subjects randomized to CIC-HFA 80 Вµg (N=237), CIC-HFA 160 Вµg (N=235),
or placebo (N=235) once-daily in the morning for 2 weeks. The RQLQ[S]
was self-administered by subjects prior to randomization and at the end of
the double-blind study medication period. Change in overall RQLQ[S] scores
was recorded for the intent-to-treat population and was calculated in subjects with baseline RQLQ[S] ≥3.0. Subjects were asked to recall their experiences during the previous week for the individual domains of activities,
sleep, non-nose/eye symptoms, practical problems, nasal symptoms, and eye
symptoms recorded on a scale of 0 (not troubled) to 6 (extremely troubled)
and on a scale of 0 (none of the time) to 6 (all of the time) for the emotional
domain of the RQLQ[S]. Change from baseline in the overall RQLQ[S]
scores was calculated as the average of the individual domains of RQLQ[S]
over the 2 week treatment period. Results: CIC-HFA 80 Вµg and CIC-HFA
160 Вµg demonstrated improvement in overall RQLQ[S] (P<0.0001) and individual domains of RQLQ[S] (P<0.05 for all) compared to placebo over the
2 week treatment period (Table). P-values were unadjusted for multiplicity.
Conclusions: In this study, once-daily treatment with CIC-HFA 80 Вµg or
CIC-HFA 160 Вµg demonstrated improvements in the rhinoconjunctivitis
related quality of life in subjects with SAR.
Change in reflective and instantaneous ocular symptom scores averaged
≥5 and
over the 2 week treatment period in subjects with baseline rTOSS≥
baseline iTOSS≥
≥3 and indiChange in overall RQLQ[S] in subjects with baseline RQLQ≥
vidual RQLQ[S] domains averaged over the 2 week treatment period
Data are least squares means change from baseline (standard error).
rTOSS=Reflective total ocular symptom score; iTOSS=Instantaneous total
ocular symptom score; CIC-HFA=Ciclesonide hydrofluoroalkane nasal
Data are least squares means (standard error). RQLQ=Rhinoconjunctivitis
quality of life questionnaire with standardized activities; CICHFA=Ciclesonide hydrofluoroalkane nasal aerosol.
R. Jacobs*1, D. Mohar2, P. Ratner1, H. Huang3, S.Y. Desai3, J. Hinkle3,
F. Bode3, 1. San Antonio, TX; 2. Kerrville, TX; 3. Marlborough, MA.
Background: Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is
currently in development as a potential treatment for allergic rhinitis. The
ability of CIC-HFA to relieve the ocular symptoms associated with seasonal
allergic rhinitis (SAR) was evaluated in subjects ≥12 years of age who were
administered either CIC-HFA or placebo. Methods: Data for this analysis was
collected as part of a placebo-controlled, double-blind, parallel group, multicenter study in subjects with a ≥2 year history of SAR randomized to CICHFA 80 µg (N=237), CIC-HFA 160 µg (N=235), or placebo (N=235) oncedaily in the morning for 2 weeks. Subject reported diaries were used to record
change from baseline in morning and afternoon reflective total ocular symptom score (rTOSS) and instantaneous total ocular symptom score (iTOSS) calculated as a sum of the 3 ocular symptoms of itchy eyes, tearing eyes, and redness of eyes each rated on a scale of 0 (no signs/symptoms evident) to 3
(signs/symptoms that were hard to tolerate and interfered with daily activities)
averaged over the 2 week treatment period. The rTOSS and iTOSS were recorded
in the intent-to-treat subject population and were evaluated in subjects with
baseline rTOSS≥5 and iTOSS≥5 respectively. Change from baseline in individual reflective and individual instantaneous ocular symptom scores of tearing eyes, itchy eyes, and redness of eyes averaged over the 2 week treatment
period were also evaluated. Results: CIC-HFA 80 Вµg and CIC-HFA 160 Вµg
demonstrated a statistically significant improvement in rTOSS (P<0.001 for
both) and improvement in iTOSS (P<0.001 for both, unadjusted for multiplicity). CIC-HFA 80 µg and CIC-HFA 160 µg also demonstrated improvements in individual reflective (P≤0.0044 for all, unadjusted for multiplicity)
and individual instantaneous (P<0.003 for all, unadjusted for multiplicity) ocular symptom scores of tearing eyes, itchy eyes, and redness of eyes compared
to placebo over the 2 week treatment period (Table). Conclusions: In this study,
once-daily treatment with CIC-HFA 80 Вµg or CIC-HFA 160 Вµg demonstrated
statistically significant improvements in rTOSS, improvements in iTOSS and
individual reflective and instantaneous ocular symptoms of SAR.
E.O. Meltzer*1, B. Wang2, J. Karafilidis2, 1. San Diego, CA; 2. Marlborough,
Background: Ciclesonide aqueous nasal spray (CIC-AQ) is indicated for the
treatment of seasonal allergic rhinitis (SAR, ≥6 years old) and perennial allergic
rhinitis (≥12 years old). This post-hoc analysis evaluated the correlation between
improvement in reflective total nasal symptoms score (rTNSS) and instantaneous
TNSS (iTNSS) and rhinoconjunctivitis related quality of life as measured by
rhinoconjunctivitis related quality of life questionnaire (RQLQ) following treatment with CIC-AQ in subjects with SAR. Methods: This was a post-hoc analysis
of data from a double-blind, placebo controlled, multicenter, efficacy and safety
study of 327 subjects aged ≥12 years with SAR (Ratner et al, 2006) who received
200Вµg CIC-AQ (n=164) or placebo (PBO, n=163) once-daily (QD) for 28 days.
Subject-assessed rTNSS (severity scale 0=no symptoms, 3=severe symptoms),
iTNSS (severity scale 0=no symptoms, 3=severe symptoms), and RQLQ (severity scale 0=not troubled, 6=extremely troubled) were reported as primary and key
secondary endpoints respectively. Two post-hoc correlation analyses were performed. First in subjects with baseline rTNSS≥6 (moderate severity) and iTNSS≥6
(moderate severity, n=137 for CIC-AQ, n=132 for PBO), and the second in subjects with baseline rTNSS≥6 and RQLQ≥3 (moderate severity, n=119 for CICAQ, n=110 for PBO) respectively. Within treatment correlations for the change
from baseline in rTNSS and iTNSS and in rTNSS and RQLQ following first 14
days of treatment with CIC-AQ 200Вµg QD or PBO were evaluated. Results: In
this post-hoc analysis, improvement in rTNSS was highly correlated with improvement in iTNSS regardless of treatment group (r=0.95 for CIC-AQ, r=0.91 for PBO).
Improvement in rTNSS was more correlated with improvement in RQLQ for the
CIC-AQ group than for the placebo group (r=0.61 for CIC-AQ, r=0.45 for PBO).
Conclusion: In this post-hoc analysis of a 28 day study of subjects with SAR, following 14 days of treatment with CIC-AQ 200Вµg QD or PBO, correlation of change
in rTNSS with change in iTNSS was high and similar for the two treatment groups
in subjects with baseline rTNSS≥6 and iTNSS≥6. The correlation of change in
rTNSS with change in RQLQ was higher in the CIC-AQ treatment group than in
PBO in subjects with baseline rTNSS≥6 and RQLQ≥3.
E.O. Meltzer*1, B. Wang2, J. Karafilidis2, 1. San Diego, CA; 2. Marlborough,
M. Dykewicz*1, S. Spector2, A. Teper3, T. Shekar3, 1. Winston-Salem, NC;
2. Los Angeles, CA; 3. Kenilworth, NJ.
Background:Ciclesonide aqueous nasal spray (CIC-AQ) is indicated for the
treatment of seasonal allergic rhinitis (SAR, ≥6 years old) and perennial allergic rhinitis (≥12 years old). This post-hoc analysis evaluated relief of symptoms of nasal congestion following treatment with CIC-AQ in subjects with
SAR. Methods:This was a post-hoc analysis of data from a double-blind, placebo
controlled, multicenter, efficacy and safety study of 327 subjects aged ≥12 years
with SAR (Ratner et al, J Allergy Clin Immunol, 2006) who received 200Вµg
CIC-AQ (n=164) or placebo (PBO, n=163) once-daily (QD) in the morning for
28 days. Subject-assessed reflective total nasal symptoms scores (rTNSS) and
individual reflective nasal symptoms of itching, sneezing, runny nose and
congestion (severity scale 0=no symptoms 3=severe symptoms) for days 1-14
were primary and key secondary endpoints respectively. Statistically significant improvements in rTNSS were observed in the intent-to-treat population
(LS mean change from baseline CIC-AQ=–2.40, PBO=–1.50, treatment difference 0.9 [95%CI 0.45, 1.36]; p<0.001). A post-hoc analysis of improvement
in symptoms of nasal congestion following first 14 days of CIC-AQ treatment
was performed in subjects with baseline nasal congestion scores of <2 and ≥2
with mean baseline congestion scores of 1.7 and 2.6 respectively. Results:There
were 44 subjects (CIC-AQ=21; PBO=23) in the <2 and 280 subjects (CICAQ=141; PBO=139) in the ≥2 baseline nasal congestion group. Improvements
in nasal congestion in the <2 congestion group (LS mean change from baseline CIC-AQ=–0.48 [95%CI –0.70, –0.27], PBO=–0.19 [95%CI –0.39, 0.02],
treatment difference, 0.30 [95%CI -0.00, 0.60], p=0.052) and greater improvements in the ≥2 congestion group were observed (LS mean change from baseline CIC-AQ=–0.59 [95%CI –0.68, –0.50], PBO=–0.35 [95%CI –0.44, –0.26],
treatment difference, 0.24 [95%CI 0.11, 0.37], p<0.001) following 14 days of
treatment with CIC-AQ 200Вµg QD or PBO. Conclusion:In this post-hoc analysis of a 28 day efficacy and safety study of subjects with SAR, improvements
in nasal congestion were observed in subjects with baseline nasal congestion
scores of <2 and greater improvements in nasal congestion were observed in
subjects with baseline nasal congestion scores of ≥2 following 14 days of treatment with CIC-AQ 200µg QD or PBO.
Introduction: Patients with allergic rhinitis (AR) value the ability of treatment to provide sustained relief between doses and convenience of once-daily
dosing. This analysis was performed to determine the level of nasal symptom
relief achieved by once-daily mometasone furoate nasal spray (MFNS) 24h
after dosing. Methods: Data were pooled from 5 15-day, multicenter, placebo
(PL)-controlled studies of MFNS 200 mcg once daily (QD) in the AM in subjects aged ≥12y with seasonal AR (SAR; 5 studies; 4 double-blind phase 3 and
1 single-blind phase 2). Subjects rated instantaneous (NOW) and PRIOR (reflective over the previous 12h) nasal symptom severity twice daily (AM predosing and PM). Individual symptom severity (nasal congestion/stuffiness, discharge, and itching; and sneezing) was scored on a 4-point scale (0=none:
3=severe); scores were summed for total nasal symptom score (TNSS). Eligible patients had baseline nasal congestion/stuffiness score ≥2 and TNSS ≥6.
Mean changes from baseline in AM NOW congestion/stuffiness score and
AM NOW TNSS were evaluated as indicators of effect 24h after dosing.
Approvals were obtained from appropriate IRBs and written informed consent
obtained from all research subjects. Results: 1812 subjects received MFNS 200
mg QD (n=912) or PL (n=900). Baseline nasal congestion/stuffiness (2.65 vs
2.64) and TNSS (9.51 vs 9.56) scores were similar between MFNS and PL
groups, respectively. Over days 2-15, mean decrease from baseline in AM NOW
nasal congestion/stuffiness was significantly greater with MFNS vs PL (в€’0.59
vs в€’0.39; P<0.001). The difference in nasal congestion/stuffiness between treatments was significant on day 2 (в€’0.28 vs в€’0.19; P=0.001), and MFNS remained
significantly superior on all subsequent study days (all P<0.001). Similarly,
mean changes from baseline in AM NOW TNSS were significantly greater with
MFNS vs PL on day 2 (в€’1.26 vs в€’0.78; P<0.001) and each day thereafter
(P<0.001), as well as when averaged over days 2-15 (в€’2.57 vs в€’1.68; P<0.001).
Conclusions: MFNS 200 mcg QD demonstrated superiority over PL spray in
improving the severity of nasal congestion/stuffiness and TNSS measured just
before each AM dosing, reflecting effect 24h after dosing that became evident
on day 2 and was maintained until study end in this large population of subjects with moderate to severe SAR.
R. Gawlik*1, B. Jawor1, B. Rogala1, L.M. DuBuske2, 1. Zabrze, Poland; 2.
Gardner, MA.
M. Blaiss*1, E.O. Meltzer2, M. Spann3, C. Fairchild3, 1. Germantown, TN;
2. San Diego, CA; 3. Fort Worth, TX.
Background: More than 70% of allergic rhinitis patients are sensitive to dust
mites. Sensory nerve activation and release of Substance P may augment development of sneezing, rhinorrhea, and congestion in allergic rhinitis patients. Azelastine an H1 antagonist may also reduce Substance P release in perennial allergic rhinitis (PAR) patients. Methods: 34 patients (18 males and 16 females) mean
age 29.4В±5.6 years with dust mite induced PAR were investigated. 20/34 patients
used intranasal azelastine for 14 days as 2 sprays each nostril twice daily while
14/34 served as a control group receiving no treatment except placebo nasal spray
twice daily for 14 days. Nasal allergen provocation with dust mite D.pteronyssinus
followed after 15 minutes by lavage were performed before and after 14 days treatment with azelastine or placebo. The concentrations of Substance P (SP) in nasal
lavage fluid were determined by EIA methods (Cayman Chemical, USA). All
patients recorded daily nasal symptoms including rhinorrhea, sneezing, pruritus,
and congestion using a VRS (Visual Rating Scale). Results: The baseline concentrations of SP did not differ in either group of PAR patients, being 129.2В±45.5
pg/mL in the azelastine group and 122.4В±39.8 pg/mL in the placebo group and
after baseline dust mite provocation were also similar in both groups, being
212.2В±52.5 pg/mL and 218.2В±48.3 pg/mL, respectively. Significantly lower concentrations of substance P were seen in nasal lavage fluid after 14 days in the azelastine group being 96.2В±31.3 pg/mL versus the plaacebo group, 118.9В±37.34
pg/mL and remained lower even after dust mite nasal provocation 154.8В±56.9
pg/mL versus 209.8В±52.8 pg/mL. Symptom scores byVRS in the azelastine treated
group over 14 days were reduced from 8.7В±2.4 to 5.2В±2.4 while in the placebo
group there was no change in VRS score ranging from 8.9В±3.0 to 8.6В±3.3. Conclusions: Intranasal azelastine reduces substance P release into nasal lavage from
dust mite sensitive PAR rhinitis patients in parallel with symptom reduction.
Background: Olopatadine, 0.6% nasal spray (PATANASEВ®), 1 spray per
nostril BID, is a SAR treatment approved for use in children 6 years of age and
older. Objective: The goal of this study was to provide a comprehensive report
of Olopatadine 0.6% RCT studies conducted in children by means of pooled
analysis. Methods: Two double-blind randomized placebo-controlled IRBapproved studies compared Olopatadine 0.6% and 0.4% vs. placebo for 2 weeks
in children ages 6 to11. Only data from the Olopatadine 0.6%, 1 spray/nostril
and placebo treatment groups from both studies are presented here. Each study
utilized daily symptom diary information to assess a total nasal symptom score
(TNSS) and total ocular symptom score (TOSS). The Pediatric Rhinoconjuctivitis Quality of Life Questionnaire (PRQLQ) was administered to the children by structured interview at baseline and end of treatment. Caregivers completed the Caregiver Treatment Satisfaction Questionnaire for Allergic Rhinitis
(CGTSQ-AR) at the end of treatment. The TNSS, TOSS, PRQLQ, and CGTSQAR were analyzed using analysis of covariance model adjusted for age and
where appropriate, baseline scores. Safety information reported here is the integrated safety information on all children who have been exposed to Olopatadine 0.6% in these studies and pharmacokinetic studies. Results: In total, 944
children completed the 2 studies (42% were female; 39% were < 9 years of
age). Olopatadine mean changes from baseline in TNSS and TOSS scores were
significantly greater that placebo (p=0.0012, and p=0.0094, respectively). Similarly significant improvements were seen in the mean overall RQLQ and all
RQLQ domain scores (P<.05). The mean summary CGTSQ-AR and all
CGTSQ-AR domain scores for Olopatadine were statistically better than placebo
(p<0.01). The most common adverse events reported as related to study drug
among 522 children exposed to Olopatadine 0.6% 1 spray BID were: epistaxis
(3.6%) and dysgeusia (1.5%). Conclusion: Olopatadine is a safe and effective
treatment for SAR in children ages 6-11. It improves nasal and ocular allergy
symptoms and QoL in children. Furthermore, caregivers report greater satisfaction with Olopatadine treatment of their children.
C. Fairchild*1, E.O. Meltzer2, P. Meuse1, 1. Fort Worth, TX; 2. San Diego,
Background: There are many effective AR treatments for children. Some
of the medications have adverse effects which negatively impact the patient’s
ability to function and quality of life. Dissatisfaction impacts the patient’s
adherence to the medication, which in turn leads to inadequate disease control. Caregiver treatment satisfaction is an outcome in clinical trials useful to
provide insight into attitudes toward treatment, particularly when comparative
treatments are equally efficacious. The Caregiver Treatment Satisfaction Questionnaire for Allergic Rhinitis (CGTSQ-AR) was designed to address the aspects
of treatment satisfaction that are important to caregivers of children with AR.
It is a 12-item questionnaire with 4 domains: efficacy, function, family disruption, and overall satisfaction. Objectives: Evaluate the validity of the
CGTSQ-AR. Methods: The validation study utilized QoL (Pediatric Rhinoconjuctivitis Quality of Life Questionnaire), symptom severity (Total Nasal Symptoms Score) and caregiver treatment satisfaction visual analog scale (TS-VAS)
data from 2 clinical trials of a nasal treatment for SAR in children 6-11 years
of age. A priori, construct validity of the CGTSQ was considered to be affirmed
if the summary score strongly correlated (r >.70) with the TS-VAS, and positive moderate correlations (r> 0.30) with the PRQLQ and TNSS. Reliability
would be affirmed if internal consistency reliability estimates were strong (Intraclass correlation [ICC] >0.70). Results: Reliability results for each CGTSQAR scale exceeded ICC of 0.70 for the overall and domain scores. The correlation with another treatment satisfaction scale, the TS-VAS was r =0.75. The
TNSS and PRQLQ correlations were positive (r =0.32 and r =0.22, respectively). Conclusions: The study results suggest that the CGTSQ-AR is a reliable and valid tool for measuring caregiver treatment satisfaction with AR treatments. In future research, the CGTSQ-AR may be used to better understand
of the impact of allergic rhinitis and its treatment of the lives on the children
who suffer from it and the families affected by it.
J.P. Forester*, J.M. Swartz, E.K. Weitzel, K.S. Johnson, C.W. Calabria,
Lackland AFB, TX.
Case:62 year old male was referred to Allergy for evaluation of progressive nasal congestion and left sided nasal obstruction. Prior exam by Otolaryngology (ENT) revealed left sided polyposis and concern for allergic fungal sinusitis. ENT started a 3 week course of oral steroids and intranasal steroids.
The steroids had no effect on polyp size and the left sided nasal obstruction
persisted. At Allergy, skin prick testing revealed sensitization to 2 trees which
did not correspond with patient’s symptoms. Sinus CT revealed complete opacification of the left frontal and maxillary sinuses without hyperattenuation. He
was again seen by ENT where biopsy confirmed diagnosis of inverted papilloma. Surgical excision of the mass resolved his symptoms. Discussion:Asymmetric or unilateral nasal symptoms should lead the clinician to
expand their differential diagnosis beyond allergic or vasomotor rhinitis. Common diagnoses which can cause asymmetric nasal symptoms include normal
physiologic nasal cycling, turbinate hypertrophy, nasal polyps, nasal septal deviation, chronic rhinosinusitis, nasal spurs, mucous retention cysts, or concha
bullosa. Nasal polyps are more common in patients with asthma, aspirin sensitivity, or cystic fibrosis. Grossly, nasal polyps generally appear as pale-gray,
semi-translucent, round mucosal protrusions in the nasal cavity. Clinical findings that should raise the suspicion of neoplasm include chronic sinusitis or
polyps that are unresponsive to therapy, recurrent nasal symptoms, and/or unilateral nasal symptoms. Neoplasms can be malignant or benign and represent
a diverse group which have similar presentations. Benign tumors of the sinonasal
tract can be divided into several groups: fibro-osseous, neural-related, hamartomatous, odontogenic, vascular, and inverted papilloma (IP). IP is a benign
primary tumor of the sinonasal tract with an incidence of up to 4% of primary
nasal tumors. It is associated with up to a 10% lifetime incidence of malignant
transformation. IP appears polypoid and more vascular than an inflammatory
polyp and may be gray to pink with irregular surface. IP can appear identical
to inflammatory polyps and is a good imitator of nasal polyposis. Diagnosis of
IP is based on tissue biopsy. The etiology of IP is unknown. Conclusion:This
case emphasizes that Allergists need to keep a broad differential when evaluating patients with asymmetric or unilateral congestion.
C.R. Pollack1, M. Wu2, K.B. Franklin1, E. Urdaneta1, 1. Fort Washington,
PA; 2. Morris Plains, NJ.
RATIONALE: Many adults require regular use of 2nd generation antihistamines for an extended period to obtain relief from perennial allergic rhinitis
(PAR) symptoms. To evaluate whether cetirizine provides consistent symptomatic relief with continued use, a longitudinal analysis of 4 multicenter clinical trials lasting 4 to 8 weeks was performed. METHODS: The 4 clinical trials were conducted at 36 sites, spanning the years from 1985 to 1998, to evaluate
the efficacy of cetirizine for the symptomatic relief of PAR. Prior to initiation
of these 4 studies, approval was obtained from institutional review boards
(IRBs), including a central IRB (Essex IRB) as well as local IRBs of several
universities. Written consent was obtained from all research subjects. Otherwise healthy adults with a history of PAR and experiencing symptoms received
cetirizine 5 mg or 10 mg once daily in 4 randomized, double-blind, placebocontrolled clinical studies. The severity of the subject’s individual PAR symptoms was rated on a 4-point scale. The Total Symptom Severity Complex (TSSC)
score was defined as the sum of the subject’s 6 - 7 individual PAR symptom
severity scores. The mean change from baseline TSSC was calculated weekly
for 4 weeks in 2 studies, at week 1 and week 4 in one study, and weekly for 8
weeks in one study. RESULTS: In 4 double-blind studies, 463 subjects were
randomized to daily doses of cetirizine (5 mg or 10 mg) and 391 subjects were
randomized to placebo for the relief of at least moderate PAR symptoms. An
analysis of daily symptom scores demonstrates that, in all 4 PAR studies, the
mean percent reduction in the TSSC compared to baseline on the first day was
maintained throughout the first treatment week. Analyses of the weekly symptom scores demonstrate that, in all 4 PAR studies, the mean percent reduction
in the TSSC compared to the baseline was maintained for each week throughout 4 to 8 weeks of treatment. Significant symptomatic relief compared to
placebo (P<0.05) was demonstrated over the entire study period in all 4 trials.
CONCLUSIONS: In adults with a history of PAR, 5 or 10 mg daily doses of
cetirizine improved PAR symptoms and provided long-term, consistent symptom relief that lasted up to 8 weeks.
E. Urdaneta*, C.R. Pollack, K.B. Franklin, C.L. Lin, Fort Washington, PA.
RATIONALE: The January 2008 switch of cetirizine from prescription to
over-the-counter (OTC) availability provides allergy sufferers an accessible
alternative to prescription antihistamines with similar efficacy. To better understand how the switch of cetirizine to OTC status affects allergy sufferers, patients
were queried about their treatment decisions and symptom responses. METH-
ODS: Data regarding prescription and OTC antihistamine use, patients’ reasons for use, and symptom relief were collected from interviews, questionnaires, and ailment diaries. Patients’ personal decisions regarding allergy management in the year following the switch of cetirizine to OTC status were
summarized. Surveys of patient perception and behavior were recorded in such
a manner that subjects remained anonymous; no treatment was administered.
Formulary data were analyzed to evaluate prescription trends following the cetirizine switch. RESULTS: Patient-reported reasons for using OTC cetirizine
included: strong efficacy profile, prior availability as prescription, brand loyalty, and specialists’ recommendations. During the first year of OTC cetirizine
availability, among approximately 5100 allergy sufferers queried, a higher
percentage took OTC cetirizine more than 90 days annually (44%) compared
with loratadine (30%) and with a frequency that was comparable to fluticasone (43%). Among households completing ailment diaries, similar percentages
of branded OTC cetirizine doses were taken for extremely severe and severe
symptoms in 2008 (37%) compared with prescription cetirizine doses in 2007
(33%). In 2008, households rated 74% of branded OTC cetirizine doses effective (47%) or extremely effective (27%) for allergic rhinitis symptoms. Similarly, in 2007, households rated 79% of prescription doses effective (56%) or
extremely effective (23%) for symptom relief. Formulary data demonstrate a
27% reduction in the number of antihistamine prescriptions filled from 2007
to 2008, predominantly related to a 91% reduction in cetirizine prescriptions.
CONCLUSIONS: Since switching from prescription to OTC status, cetirizine
is widely used by allergy sufferers, including severe allergy sufferers. Likely
the combination of patient-proven effectiveness, ease of accessibility, and allergists’ recommendations influence patients to use OTC cetirizine for effective
management of their allergy symptoms.
E. Urdaneta*1, C.R. Pollack1, M. Wu2, K.B. Franklin1, C.L. Lin1, 1. Fort
Washington, PA; 2. Morris Plains, NJ.
RATIONALE: Many adults require regular use of 2nd generation antihistamines to manage the symptoms of seasonal allergic rhinitis (SAR). To evaluate
whether cetirizine provides continued symptomatic relief over time in patients with
documented SAR symptoms, the data from 6 multicenter, randomized, placebocontrolled studies that assessed the efficacy of cetirizine 5 mg and 10 mg over a 2to 4-week period were evaluated. METHODS:The 6 clinical trials were conducted
at 84 sites, spanning the years from 1985 to 1999, to evaluate the efficacy of cetirizine for symptomatic relief of SAR. Prior to initiation of these 6 studies, approval
was obtained from institutional review boards (IRBs), including a central IRB (Essex
IRB) as well as local IRBs of several universities. Written consent was obtained
from all research subjects. Otherwise healthy adults with a history of SAR and experiencing symptoms were randomly allocated to treatment with cetirizine 5 mg
once daily, 10 mg once daily, or 5 mg twice daily for 2 to 4 weeks. The severity of
individual SAR symptoms was rated on a 4-point scale.TheTotal Symptom Severity Complex (TSSC) score was defined as the sum of the subject’s 5 – 6 individual
SAR symptom severity scores. The mean change from baseline TSSC was calculated weekly for 2 weeks in 4 studies and weekly for 4 weeks in 2 studies. RESULTS:
Efficacy was compared weekly for 156 subjects taking 5 mg cetirizine daily and
for 911 subjects taking 10 mg cetirizine daily in these 6 trials. An analysis of daily
symptom scores demonstrates that, in all 6 SAR studies, the mean percent reduction in theTSSC compared to the baseline on the first day was maintained throughout the first week of treatment. Significant symptomatic relief compared to placebo
(P<0.05) was demonstrated over the entire study period in 5 of 6 studies; statisti-
cal significance was not reached in 1 study (SAR 3, P=0.053 for 5 mg; P=0.066
for 10 mg). Analyses of weekly symptom scores demonstrate that, in all 6 SAR
studies, the mean percent reduction in theTSSC compared to the baseline was maintained for each week throughout 2 to 4 weeks of treatment. CONCLUSIONS: In
adults with a history of SAR, 5- or 10-mg daily doses of cetirizine improved SAR
symptoms and maintained a consistent level of relief throughout 2 to 4 weeks of
use regardless of dose or dosage regimen.
J. van Bavel*1, N.J. Amar2, A. Melchior3, S.A. Dunbar3, S.K. Tantry3,
P.M. Dorinsky3, 1. Austin, TX; 2. Waco, TX; 3. Horsham, PA.
Introduction: Although aqueous corticosteroid nasal sprays are effective in
the treatment of allergic rhinitis (AR), an aerosol corticosteroid formulation
may be preferred to avoid the “wet feeling” and postnasal drip associated with
aqueous nasal sprays. However, aerosol corticosteroid nasal products are no
longer available due to the phase out of chlorofluorocarbon containing products. To satisfy this unmet need, beclomethasone dipropionate hydrofluoroalkane
(BDP HFA) nasal aerosol is in development for the treatment of AR. The primary objective of this study was to demonstrate efficacy of BDP HFA nasal
aerosol in subjects with seasonal AR (SAR). Methods: A 2-week, phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study
was conducted in subjects with SAR during the 2009-2010 mountain cedar
pollen season. Following a 7-10 day run-in period, eligible subjects (N=340;
≥12 years) were randomized to receive placebo or BDP HFA 320 µg/day. The
primary end point was average AM and PM subject-reported reflective Total
Nasal Symptom Score (rTNSS) over the 2-week treatment period. The safety
and tolerability of BDP HFA also was evaluated. Results: The change from
baseline in the average AM and PM subject-reported rTNSS for BDP HFA
320 Вµg treatment group was significantly greater compared with placebo (LS
mean difference = –0.91 [95% CI: –1.3, –0.5]; P<0.001). Significant improvements in rTNSS with BDP HFA 320 µg were evident by Day 2 and were maintained throughout the treatment period. Similarly, the change from baseline in
the average AM and PM subject-reported instantaneous TNSS also was significantly greater for BDP HFA 320 µg compared with placebo (LS mean difference = –0.92 [95% CI: –1.3, –0.5]; P<0.001). Additionally for both of these
measures, all 4 individual nasal symptom scores (sneezing, runny nose, nasal
itching, and nasal congestion) showed statistically significant improvement
with BDP HFA 320 Вµg compared with placebo. Finally, BDP HFA 320 Вµg was
well tolerated and the safety profile was similar to that of placebo. Conclusions: This study demonstrated that BDP HFA nasal aerosol provides significant improvement in nasal symptoms in subjects with SAR and is well tolerated. Thus, BDP HFA nasal aerosol should provide a new, effective alternative
treatment for patients with SAR.
J.I. Williams*, J.A. Gow, T.R. McNamara, Irvine, CA.
W. Howland*1, W. Wheeler2, H. Sacks2, 1. Austin, TX; 2. Somerset, NJ.
Purpose: To establish the safety and efficacy of bepotastine besilate ophthalmic solution 1.5%, a dual acting histamine H1 receptor antagonist approved
by the United States FDA for treatment of ocular itching associated with allergic conjunctivitis, compared to placebo in reducing summed nonocular composite symptom (NOCS) scores at 15 minutes and 8 hours after ophthalmic
dosing using the Conjunctival Allergen Challenge (CAC) model of allergic conjunctivitis. Methods: Two CAC clinical trials (1 single site, 1 multi-site) were
each 7 week, double-masked, randomized, placebo-controlled studies. Approval
was obtained from an IRB and written informed consent was obtained from
all research subjects. Eligible subjects were assigned randomly to either bepotastine besilate 1.5% (n=78) or placebo (n=79). Nonocular symptoms were considered secondary efficacy variables and were not a basis for determining study
participation by subjects. The NOCS is composed of summed subject-graded
scores for ear or palate pruritus, nasal pruritus, nasal congestion, and rhinorrhea, each using a 0-4 unit grading scale. The principal statistical test for data
analysis was a 2-sample t-test. Results: In both the Intent-to-Treat (ITT) population and the Per-Protocol (PP) population, clinical effectiveness was demonstrated for bepotastine besilate ophthalmic solution 1.5% compared to placebo
for summed NOCS scores. There was strong statistical significance for both
analysis populations at all observation time points at 15 minutes (P≤0.0003)
and 8 hours (P<0.0001) post-dosing. Discontinued subjects included placebo
group subjects (n=8) for non-compliance, and bepotastine besilate ophthalmic
solution 1.5% subjects for non-compliance (n=5) or other reasons (n=3). Additional study visits were not needed for any enrolled subjects. Conclusions:
Bepotastine besilate ophthalmic solution 1.5% was clinically and statistically
superior to placebo in reducing summed NOCS scores in 2 CAC clinical trials
after ophthalmic dosing. These data support clinical effectiveness for reduction of nonocular symptoms associated with allergic conjunctivitis in patients
dosing with bepotastine besilate ophthalmic solution 1.5% similar to findings
with a systemic version of bepotastine.
J.A. Gow*, J.I. Williams, T.R. McNamara, Irvine, CA.
Title: Bepotastine Besilate Ophthalmic Solution 1.5% Reduces Tearing Following Dosing in the Conjunctival Allergen Challenge (CAC) Model of Allergic Conjunctivitis Purpose: To establish the safety and efficacy of bepotastine
besilate ophthalmic solution 1.5%, a dual acting histamine H1 receptor antagonist approved by the United States FDA for treatment of ocular itching associated with allergic conjunctivitis, compared to placebo in reducing tearing at
15 minutes and 8 hours after ophthalmic dosing using the Conjunctival Allergen Challenge (CAC) model of allergic conjunctivitis. Methods: Two CAC clinical trials (1 single site, 1 multi-site) were each 7 week, double-masked, randomized, placebo-controlled studies. Approval was obtained from an IRB and
written informed consent was obtained from all research subjects. Eligible subjects were assigned randomly to either bepotastine besilate 1.5% (n=78) or
placebo (n=79). Tearing was graded as either absent or present. The principal
statistical test for data analysis was a Fisher’s exact test. Results: In both the
Intent-to-Treat (ITT) population and the Per-Protocol (PP) population, clinical effectiveness was demonstrated for bepotastine besilate ophthalmic solutions 1.5% compared to placebo for tearing and demonstrated statistical and
clinical significance for all observation time points at 15 minutes (P≤0.0002)
and 8 hours (P≤0.0003) post-dosing. Discontinued subjects included placebo
group subjects (n=8) for non-compliance, and bepotastine besilate ophthalmic
solution 1.5% subjects for non-compliance (n=5) or other reasons (n=3). Additional study visits were not needed for any enrolled subjects. Conclusions:
Bepotastine besilate ophthalmic solution 1.5% was clinically and statistically
superior to placebo in reducing tearing in 2 CAC clinical trials after ophthalmic
dosing. These data support clinical effectiveness for reduction of tearing associated with allergic conjunctivitis in patients dosing with bepotastine besilate
ophthalmic solution 1.5%.
Introduction: The objective of this study was to determine the ability of azelastine nasal spray 0.15% at a dosage of 2 sprays per nostril once daily to treat
the primary nasal symptoms and a complex of secondary symptoms associated
with seasonal allergic rhinitis (SAR). Azelastine nasal spray 0.15% is formulated with a 50% increase in the concentration of active ingredient compared
to the original azelastine 0.10% nasal spray formulation. Methods: This was a
2-week, double-blind, placebo-controlled trial conducted during the 2007/2008
Texas Mountain Cedar season. A total of 536 patients were randomized to treatment with azelastine 0.15% or placebo spray. The primary efficacy variable
was the 12-hour reflective total nasal symptom score (TNSS), made up of nasal
congestion, sneezing, itchy nose, and runny nose. A secondary symptom complex score (SSCS), consisting of postnasal drip, itchy eyes, cough, and headache
was used to evaluate additional symptoms commonly associated with SAR.
Results: The improvement in TNSS was statistically significant (P<.001) with
azelastine 0.15% nasal spray (18.7%) compared to placebo (10.5%). The
improvement in the SSCS also was statistically significant (P≤.002) with azelastine 0.15% (16.8%) compared to placebo (8.4%). The most frequent adverse
events with azelastine 0.15% were bitter taste (4.5%) and nasal discomfort
(4.5%). Conclusions: Azelastine 0.15% nasal spray administered once daily
was effective in treating the primary nasal symptoms associated with SAR as
well as a complex of secondary symptoms.
H.G. Mariano*1, G. Solomon2, E.C. Steward3, H.H. Albrecht4, 1. Fresno,
CA; 2. Morristown, NJ; 3. Long Valley, NJ; 4. Miami, FL.
Introduction: Although URIs are typically caused by viruses that are not
treatable with antibiotics (ABs), many health care providers are asked for and
often prescribe an AB to treat these conditions. Addressing pt concerns and
recommending symptom-relieving products may be as important to pt satisfaction as an AB prescription for URI. This study investigated whether an oral
extended-release (ER) combination expectorant and decongestant product
(guaifenesin [G] and pseudoephedrine HCl [PSE]; MucinexВ® D) can reduce
use of ABs, and pt desire for ABs, by offering a symptomatic treatment for
signs and symptoms associated with URIs. Methods: Pts aged 18-75 years presenting with symptoms diagnostic for an acute URI (eg common cold, acute
bronchitis, acute sinusitis) within 5 days of onset were randomized to G 1200
mg + PSE 120 mg ER bi-layer tablets (MucinexВ® D), or matching placebo, b.i.d.
for 7 days. Eligible pts had a total respiratory symptom score ≥12 and met the
physician’s criteria for AB therapy but were considered suitable for a �wait and
see’ approach (withholding ABs ≥48 hrs). Approval was obtained from the IRB
(Chesapeake Research Review, Inc, Columbia, MD) and written informed consent was obtained from all pts. Results: 1189 pts were enrolled; data are presented for the modified intent-to-treat population (n=1179). Approximately
80% of pts, regardless of treatment group, did not receive ABs. At Day 8, significantly fewer pts receiving ER G+PSE vs. placebo desired ABs (4.2% vs.
8.0%). A statistically significant reduction in URI symptoms was observed for
ER G+PSE vs. placebo, from Day 1, and on each study day thereafter. However, the proportion of pts experiencing overall relief at Day 4 pm (primary
endpoint) did not reach statistical significance. Treatment-related adverse events
were reported in 9.8% and 4.7% of pts receiving ER G+PSE and placebo, respectively. Conclusions: ER G+PSE offers a well-tolerated first-line symptomatic
treatment that physicians can offer to pts instead of an AB prescription for URIs.
A �wait and see’ approach using symptom-relieving products (such as Mucinex®
D) may reduce pt desire for ABs and offer an alternative treatment, without
compromising pt satisfaction.
E.O. Meltzer*1, S.R. Shah2, A. Teper3, T. Shekar3, 1. San Diego, CA; 2. Collegeville, PA; 3. Kenilworth, NJ.
H. Nelson*1, D. Graft2, G. Gopalan3, D. Gates3, 1. Denver, CO; 2. Burnsville,
MN; 3. Kenilworth, NJ.
Introduction: Seasonal allergic rhinitis (SAR) substantially impairs sleep
and quality of life. Nasal congestion is one of its most prevalent and bothersome symptoms; it is often responsible for AR-related sleep problems. Nasal
congestion severity is worse at night and in early morning, exacerbating its negative effects on sleep. This post hoc analysis evaluated effectiveness of mometasone furoate nasal spray (MFNS) for relief of nighttime and morning congestion in subjects with SAR. Methods: In 5 randomized, placebo-controlled clinical
studies (4 double-blind, phase 3; 1 single-blind, phase 2), subjects aged ≥12 y
with ≥2-y history of SAR and symptomatic at baseline received MFNS 200
mcg or placebo (PL) once daily for 15 days; pooled results were retrospectively
analyzed. Approval was obtained from appropriate IRBs and written informed
consent obtained from all research subjects. Subjects rated individual nasal
symptoms (rhinorrhea, congestion, sneezing, itching) comprising total nasal
symptom score (TNSS) twice daily on a 4-point scale (0=none; 3=severe), based
on status at time of evaluation (NOW) and over the previous 12 hours (PRIOR).
Comparison between MFNS and PL for change from baseline in AM PRIOR
(reflective of nighttime status) congestion scores and TNSS (daily and average
for Days 2-15) were evaluated with an analysis of covariance (ANCOVA) model
extracting sources of variation due to treatment, site, and baseline score as a
covariate. Results: 1812 subjects were treated with MFNS (n=912) or PL
(n=900). Mean baseline congestion score and TNSS were the same or similar
for both groups (Table). MFNS showed superior reductions vs PL in mean
change from baseline in AM PRIOR congestion scores averaged over Days 215 (Table) and in daily mean change from baseline for Days 2 through 15
(P<0.001; mean % change from baseline ranged from -11.7% on Day 2 to 30.5% on Day 15 for MFNS and -6.9% on Day 2 to -20.7% on Day 15 for PL).
Mean AM PRIOR TNSS was also reduced to a greater extent by MFNS vs PL,
both averaged over Days 2-15 (Table) and daily (P<0.001; mean % change from
baseline ranged from -13.2% on Day 2 to -35.6% on Day 15 for MFNS and 8.2% on Day 2 to -24.5% on Day 15 for PL). Conclusion: MFNS has a clinically meaningful effect on nighttime nasal congestion and other nasal symptoms in subjects with SAR.
Introduction: Perennial allergic rhinitis (PAR) has a substantial negative
impact on health-related quality of life (HRQOL). Several surveys demonstrate
a negative correlation between HRQOL score and number of symptom-free
days, an increased QOL burden with increasing symptom severity, a significant correlation between daily total nasal symptom scores (TNSS) and all 6
domains of the rhinitis QOL questionnaire (RQLQ), and a greater negative
impact on QOL in those with more persistent vs intermittent AR. This post
hoc analysis evaluated the effectiveness of MFNS in increasing the number of
minimal-symptom days and reducing symptom severity. Methods: Four double-blind, placebo (PL)-controlled, phase 3 trials randomly assigned symptomatic subjects aged ≥12 y with a ≥2-year history of PAR to MFNS 200 mcg
or PL once daily for 12 weeks. Results were pooled for retrospective analysis.
Subjects scored individual nasal symptoms (rhinorrhea, congestion, sneezing,
itching) comprising TNSS twice daily on a 4-point scale (0=none; 3=severe).
Approval was obtained from the appropriate IRBs and written informed consent obtained from all research subjects. This analysis defined a minimal-symptom day (MSD) as a day during which none of the 4 individual nasal symptoms’ AM/PM (morning and afternoon average) score was >1.0. The proportion
of MSDs (across Days 1–85) was computed for each patient, the median proportion of MSDs reported by treatment, and the median test applied to determine treatment difference. Comparison of AM/PM TNSS 4-week averages for
MFNS and PL were evaluated with an analysis of covariance (ANCOVA) model,
with treatment and study effects and baseline score as a covariate. Results:
The analysis included 1306 subjects treated with MFNS (n=651) or PL (n=655)
over 12 weeks. Subjects treated with MFNS experienced significantly more
MSDs than those receiving PL (49.4% vs 22.7%; P<0.001). Mean baseline
TNSS was similar between groups (Table). Mean reductions in TNSS from
baseline were significantly greater in MFNS-treated subjects vs PL-treated subjects for each 4-week interval analyzed (Table). Conclusions: During 12 weeks
of treatment for PAR, MFNS 200 mcg daily was associated with significantly
more symptom-free days than PL, and effectively reduced total nasal symptoms.
Analysis of Covariance—Change from Baseline AM PRIOR: Nasal
Congestion and TNSS (%)
Analysis of Covariance–Total Nasal Symptom Score (TNSS) 4-week averages (AM/PM mean)
LS means, Pstd (pooled std), and 95% confidence intervals (CI) are obtained
from ANCOVA model with treatment and site effect with baseline as a covariate.
Mean percent changes are raw means.
Post-Baseline Least Squares means and Pstd (pooled standard deviations) are
obtained from an ANCOVA model with treatment and study effects with
baseline score as a covariate. Baseline estimates exclude the Baseline covariate.
Mean percent changes are raw means.
Diff=Treatment Difference (>0 favors MFNS).
Day 1 includes PM scores only.
S. Nsouli*, Danville, CA.
For Seasonal Allergic Rhinitis (SAR) patients that remain symptomatic on
an intranasal antihistamine, Olopatadine or intranasal corticosteroid, Mometasone furoate, the combination of intranasal antihistamine, Olopatadine with
an intranasal corticosteroid Mometasone may provide additional efficacy in
sub-optimally controlled Seasonal Allergic Rhinitis Patients. In this open labeled
8-week trial 40 patients with symptomatic SAR currently using Olopatadine1330 mcg/nostril BID or Mometasone furoate, 100 mcg/nostril QD were
randomized to receive the combination Olopatadine 1330 mcg/nostril BID +
Mometasone, 100 mcg/nostril QD. The end points of the trial include: rhinomanometry, nasal symptom score (composite score of nasal congestion, rhinorrhea, sneezing, post nasal drip and itching) and flexible rhinopharyngolaryngoscopy examination. Mean efficacy measurements at the end of the
8-week trial revealed significant improvements in all parameters examined in
the combination treatment group as compared to baseline measurements. In
conclusion, the combination nasal Olopatadine plus nasal Mometasone is more
effective than monotherapy nasal Olopatadine or nasal Mometasone. It appears
that in the combination treatment Olopatadine and Mometasone, the primary
end points (rhinomanometry and symptom scores) are significantly improved.
IgE, peripheral blood eosinophil count, nasal smear were conducted. The nasal
symptom score was calculated for each patient from a questionnaire and correlated with laboratory data. Bivariate correlation analysis and multiple linear
regression analysis were done to compare the correlation among clinical markers and symptom score. RESULTS: Levels of all allergic markers in children
with AR were significantly different from those in non-allergic children. All
of the markers were related to the severity of AR in Pearson correlation analysis. On logistic regression analysis, only serum allergen-specific IgE were independent predictors. CONCLUSION: These results suggest that serum allergenspecific IgE is correlated with the severity of HDM AR in children.
Background: Eosinophils trigger symptoms in allergic rhinitis. New diagnostic methods for identifying nasal eosinophils are needed as the only current method is through nasal cytology. High concentrations of flavin adenine
dinucleotide (FAD) in cytoplasmic granules of eosinophils result in an intense
auto fluorescence. Two-photon excitation is a powerful method for detecting
this intrinsic fluorescence. Objectives: To demonstrate the use of two-photon
excited fluorescence (TPEF) to detect eosinophils in nasal mucosa. We aim to
characterize the fluorescence signature of eosinophils from fresh nasal smears
of the nasal mucosa on a conventional (laboratory based) two-photon microscope. Histologic review of the nasal cytology will be used to validate imaging performance. Methods: Healthy patients (n=30) aged 18-65 years with rhinitis were recruited. Approval was obtained from the IRB and written informed
consent was obtained from all research subjects. Bilateral nasal cytology smear
was performed. Fluorescence images of eosinophils and epithelial cells were
collected with a two photon microscope, evaluated for intensity and size, and
compared to standard nasal smears (HanselВ® stain). Correlation of cell count
was made by linear regression, and diagnostic performance was evaluated by
varying the intensity threshold. Results: A comparison of eosinophils versus
epithelial cells on fluorescence intensity was 13.8В±4.3 versus 3.7В±1.8 (p<0.01),
respectively, and on size was 27.0В±10.2 versus 392.0В±214.6 Вµm2 (p<0.01),
respectively. At a fluorescence threshold of 7.5 arb units, intensity alone produced a sensitivity, specificity, PPV, NPV, and total accuracy of 100%, 94%,
94%, 100%, 97%, respectively, for identifying eosinophils with an area-underthe-curve (AUC) on receiver-operator characteristic (ROC) curve of 98%. Using
both fluorescence intensity and size, 100% for all parameters was achieved.
The correlation between eosinophil count on two-photon with that on histology was R2 =0.91. Conclusions: TPEF is a promising novel technique for identifying and quantifying nasal eosinophils on nasal cytology specimens collected
from patients with rhinitis. Future development of a rhinoscope-compatible
microscope could be used as a clinical adjunct for the diagnosis and management of rhinitis, and possibly other eosinophilic disease states such as
eosinophilic esophagitis.
B. Prenner*1, A. Pedinoff2, A. Teper3, T. Shekar3, 1. San Diego, CA; 2.
Princeton, NJ; 3. Kenilworth, NJ.
Introduction: In surveys of patients with allergic rhinitis (AR), nasal discharge is one of the most frequently reported symptoms, and an especially bothersome one. Optimal therapy for seasonal AR (SAR) should relieve this troublesome symptom. Methods: Five 15-day, multicenter, placebo (PL)-controlled
studies (4 double-blind, phase 3; 1 single-blind, phase 2) randomly assigned
SAR subjects aged ≥12 y to mometasone furoate nasal spray (MFNS) 200
mcg QD or PL. Approval was obtained from appropriate IRBs and written
informed consent obtained from all research subjects. Eligibility criteria at
screening included baseline nasal congestion/stuffiness score ≥2 and total nasal
symptom score (TNSS; combined nasal discharge, nasal congestion/stuffiness,
sneezing, nasal itching scores [0=none to 3=severe]) ≥6. Subjects recorded
instantaneous (NOW) and reflective (over previous 12 h, PRIOR) symptom
scores in AM and PM diaries. LS means were obtained from an ANCOVA model
with treatment and site effect with baseline score as a covariate. We report LS
mean and mean percentage change from baseline in AM/PM PRIOR (average
of AM and PM scores) nasal discharge over days 1-15 and daily throughout
the treatment period. Subjects with baseline and postbaseline efficacy data were
included in the analysis. Results: Subjects (aged 12-79 y) were randomized to
MFNS 200 mcg QD (n=914) or PL (n=906). Demographic characteristics were
similar between groups. Baseline LS mean AM/PM prior nasal discharge score
was 2.55 in the MFNS group and 2.54 in the PL group, indicating subjects had
moderate-to-severe nasal discharge at study entry. LS mean reduction in AM/PM
prior nasal discharge score over days 1-15 was significantly greater for MFNS
vs PL (–0.66 [mean % change, –24.3%] vs –0.45 [–16.0%]; P<0.001). A significant treatment effect on AM/PM prior nasal discharge was seen on day 1
(–0.26 [–8.7%] vs –0.20 [–6.2%]; P=0.023) and each successive day of MFNS
dosing (P≤0.023). MFNS was well tolerated, with no unusual or unexpected
adverse events; its adverse event profile was similar to that of PL. Conclusions:
Five prospective studies in subjects with moderate-to-severe SAR showed that
MFNS 200 mcg QD provided safe, effective relief of nasal discharge as early
as day 1 and maintained a significant treatment effect throughout the 15-day
study period.
Y. Rha*1, M. Kim2, S. Choi1, 1. Seoul, Korea, Republic of; 2. Daegu, Korea,
Republic of.
BACKGROUND: Allergic rhinitis (AR) is induced by immunoglobulin E
(IgE) mediated allergic reaction following allergen exposure to nasal mucosa
and is associated with eosinophilic inflammation. Elevated levels of blood total
eosinophil count, serum specific IgE are considered to be associated with AR,
but the correlation between these allergic markers and the severity of AR symptoms remain controversial. This study aimed to elucidate these relationship.
METHODS: Ninety-six children aged 3 to 17 years old were recruited, including 80 with house dustmite (HDM) AR and 16 with non-AR as controls. Medical history was taken and physical examination, serum specific IgE, total
N. Safdarian*, Z. Liu, T. Wang, E. Wang, Ann Arbor, MI.
S. Shah*1, W. Wheeler2, H. Sacks2, 1. Collegeville, PA; 2. Somerset, NJ.
Introduction: The objective of this study was to evaluate the efficacy of a
reformulated azelastine nasal spray (Astepro 0.15%) at a dosage of 2 sprays
per nostril twice daily in treating nasal and non-nasal symptoms of seasonal
allergic rhinitis (SAR). Methods: This 2-week, double-blind, placebo-controlled
trial randomized 526 patients to treatment with azelastine 0.15% at 2 sprays
per nostril twice daily, azelastine 0.10%, or placebo spray. The primary efficacy variable was the 12-hour reflective total nasal symptom score (TNSS),
consisting of nasal congestion, sneezing, itchy nose, and runny nose. A key secondary efficacy variable was the change from baseline in the 12-hour reflective secondary symptom complex score (SSCS), consisting of postnasal drip,
itchy eyes, cough, and headache. All symptoms were scored twice daily on a
4-point scale such that the maximum daily symptom score was 24. Results:
After 2 weeks of treatment, the mean TNSS improvement scores were statistically significant (P < .001) with azelastine 0.15% (5.36; 29.7%) compared to
placebo (2.36; 12.0%). The overall SSCS improvement score was also statistically significant (P < .001) with azelastine 0.15% (4.15; 28.3%) compared to
placebo (1.72; 10.2%). With the exception of bitter taste (8.4%), all other adverse
events with the 0.15% formulation were reported with an incidence similar to
placebo. Conclusions: Azelastine 0.15% nasal spray was effective in treating
nasal and non-nasal symptoms associated with SAR, and was well tolerated
when administered at a dosage of 2 sprays per nostril twice daily.
P. Beerelli*1, D. Sheth2, K. Pier3, D. Ein4, 1. Gainsville, FL; 2. Denver, CO;
3. Tacoma, WA; 4. Washington DC.
Rationale: Intranasal steroid sprays are the most consistently effective treatment for allergic rhinitis and relieve a wide range of symptoms. There have
been anecdotal suggestions that gender may determine patient preferences in
use of these agents. A survey was performed to determine if this is the case.
Methods: A total of 448 participants at approximately70 institutions were randomly asked to take part in this study over a three-year period. Those choosing to participate completed a 16 question, IRB approved survey about their
preferred use of tablets or nasal sprays for allergy treatment. Statistical analysis was completed by Excel computation. Results: When comparing men and
women who have used both oral medications and nasal sprays, there is no statistical difference between genders in their preference for either type of treatment. However, females are 1.39 times more likely to be concerned about side
effects of nasal spray than men. Chi-squared analysis reveals there is no statistical significance regarding the concern for side effects of nasal spray when
comparing three stratified age groups: 25 and younger, 26 to 49, and older than
50. Conclusions: While an odds ratio suggests no difference between the number of men and women using nasal sprays, other statistics suggest that women
are more likely to be apprehensive about side effects. Such data suggests that
a detailed history, particularly with women, is necessary to learn about concerns regarding nasal spray use. Based on this understanding, various options
should be offered. Further, unlike with other medications, compliance and concern for side effects with nasal spray use is not increased with older age groups.
Several studies have evaluated patient adherence to asthma medication regimens. Similarly, this study is prompting health-care providers to be knowledgeable about the many side effect concerns with nasal spray use that may
take a role in overall patient satisfaction and adherance.
L. Lee*, W. Wu, L.B. Sutton, Research Triangle Park, NC.
Introduction: It is estimated that 17% of the US population will be ≥65
years by 2020. Although skin test reactivity decreases with increasing age and
allergic symptoms may become milder, allergic rhinitis remains a common condition in this population with a prevalence of approximately 17% (Ventura, et
al. Immunopharmacol Immunotoxicol 2010;32:165-70). There is limited data
on the efficacy of intranasal corticosteroids for the treatment of allergic rhinitis in the elderly. Methods: This retrospective analysis focused on outcomes in
patients ≥65 years (n=44) enrolled in perennial allergic rhinitis (PAR) studies
(FFR30002/FFR106080/FFU111439). The analyses utilized all subjects across
all groups who were randomized to fluticasone furoate nasal spray (FFNS)
110mcg once daily or vehicle placebo and were based on a 4 or 6 week treatment period. Results: Greater improvements for FFNS vs. placebo were noted
for self-reported reflective total nasal symptom scores (rTNSS) in both age
groups (see Table). Adverse events were similar between treatments in subjects
≥65 years. The most common events (occurring in >3% of subjects) were
headache, diarrhea, nasal ulceration and epistaxis. Conclusion: This analysis
demonstrated that FFNS 110Вµg once daily was well tolerated and effective in
elderly subjects with PAR. Although the number of elderly subjects in this analysis was relatively small, improvements were similar to younger subjects receiving FFNS. Additional data are needed in this population.(GSK-funded)
For each age subgroup, test for treatment difference was performed using
ANCOVA, including baseline value, age, sex, and study as covariates in the
analysis model
H. Nelson*1, H. Nolte2, P. Creticos3, J. Maloney2, D. Bernstein4, 1. Denver, CO; 2. Kenilworth, NJ; 3. Baltimore, MD; 4. Cincinnati, OH.
Background: Until now, the efficacy of grass sublingual immunotherapy
has not been demonstrated in North America. This phase III trial investigated
the efficacy and safety of daily administration of grass allergy immunotherapy
tablet (AIT) (oral lyophilisate, Phleum pratense, 2800 BAU) in allergic rhinoconjunctivitis (AR) subjects with or without asthma. Methods: 439 adults with
Timothy grass pollen-induced AR were randomized 1:1 to once-daily grass AIT
or placebo for approximately 16 weeks before and during the 2009 grass pollen
season (GPS). Subjects used daily e-diaries to record AR symptoms from randomization through the end of the study. The use of symptomatic medications
was also recorded in the e-diary during the GPS. The primary efficacy endpoint comprised the average total combined daily symptom and medication
score (TCS) during the entire GPS. Key secondary endpoints were individual
daily symptom score (DSS), daily medication score (DMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ[S]) with standardized activities. Immunologic endpoints included specific IgG4 and IgE-blocking factor.
Safety was assessed by monitoring adverse events (AEs). IRB approval was
obtained for all sites, and each subject provided written informed consent.
Results: 85% of the subjects were multisensitized. The grass AIT group showed
a mean 20% improvement in TCS compared with the placebo group (P=0.005).
Similar positive outcomes in the AIT group relative to placebo were demonstrated for the DSS (18%, P=0.015), DMS (26%, P=0.084), and RQLQ(S)
(17%, P=0.022). In the grass AIT group, significant increases in IgG4 and IgE
blocking factor were observed at peak and end of GPS compared with placebo
(P<0.001). The majority of AEs were mild local application site reactions that
were transient in nature, with no treatment-related serious AEs in active subjects, one treatment-related serious AE in a placebo subject, and no reports of
anaphylactic shock. Conclusions: Grass AIT is effective in a predominantly
multisensitized North American adult population with Timothy grass polleninduced AR. Once-daily administration of grass AIT was well tolerated and
will provide a new therapeutic modality for patients with Timothy and related
grass pollen-induced allergy.
E.O. Meltzer*1, A. Darter2, M.J. Tort3, P. Lieberman4, 1. San Diego, CA;
2. Edmond, OK; 3. Fort Worth, TX; 4. Germantown, TN.
Introduction: Vasomotor rhinitis (VMR) is non-allergic, non-infectious,
perennial, and of unknown etiology, which can make it difficult to treat. This
study compared olopatadine nasal spray, 0.6%, with azelastine nasal spray,
0.1%, for the treatment of VMR. Methods: In this randomized, multi-center,
double-masked study, eligible patients were ≥12 years old, had a history of nonallergic rhinitis for ≥2 years, had negative skin tests to allergens, had a positive skin test response to histamine, and scored ≥6 (out of 12) on the reflective
Total VMR Symptom Score (rTVSS) questionnaire. The rTVSS assessed nasal
congestion, rhinorrhea, post-nasal drip, and sneezing (each scored from
0=absent to 3=severe). Patients were randomized to olopatadine HCl 0.6% nasal
spray or to azelastine 0.1% nasal spray; 2 sprays per nostril, twice daily. Patients
entered rTVSS responses in diaries twice daily. At the end of the 14-day study,
patients completed a Treatment Satisfaction Questionnaire for Medication and
a Patient Global Assessment of symptoms. Ethics board approval and signed
informed consent forms were obtained. Results: A total of 129 patients were
enrolled. Mean baseline rTVSS scores were similar between groups: 8.4В±1.6
in the azelastine group and 8.0В±1.2 in the olopatadine group. Significant
improvements (P<0.01) were demonstrated after 1 day of treatment in both
groups. After 2 weeks, mean rTVSS scores were 2.8В±2.0 in the azelastine group
and 2.9В±2.4 in the olopatadine group (p=0.80 between groups). On the Treatment Satisfaction Questionnaire, mean scores (out of 100) were similar between
groups for all parameters, including convenience (82В±14 with azelastine and
78В±21 with olopatadine), effectiveness (62В±20 with azelastine and 61В±18 with
olopatadine), and side effects (91В±18 with azelastine and 90В±16 with olopatadine). On the Patient Global Assessment, 79% of olopatadine-treated patients
and 74% of azelastine-treated patients indicated that their symptoms had
improved (a little, moderately, or very much better). Conclusions: Patients with
non-allergic vasomotor rhinitis (VMR) who were treated with olopatadine
hydrochloride nasal spray 0.6% reported good efficacy and tolerability scores;
these scores were similar to scores for VMR patients treated with azelastine
nasal spray 0.1%, a therapy currently approved for VMR treatment in the US.
N. Chen*1, L. Yao2, L. Johnson3, 1. Columbia, MO; 2. Phoenix, AZ; 3.
Shreveport, LA.
Rationale: Although exercise-induced rhinitis has been reported, there are
few effective treatments available. We present a case of exercise-induced rhinitis that was successfully treated by an intranasal antihistamine, Azelastine Nasal
Spray (0.15%). Case report: A 24 year old female presented to the Allergy and
Immunology Clinic for evaluation of nasal congestion and rhinorrhea during
aerobic exercise, jogging and yoga activities. Progressive worsening of her
symptoms especially the nasal congestion during exercise had forced her to
stop exercising. Skin prick testing for inhalant and food allergens as well as CT
of the sinuses were negative. Spirometry testing was normal. She had been on
a number of oral antihistamines including Cetirizine and Loratadine; however,
these offered no relief of her symptoms. The patient was instructed to use Azelastine (0.15%) with two sprays in each nostril five minutes before exercise.
The patient’s symptoms were significantly relieved after using the medication,
and she now tolerates exercise without difficulty. Conclusion: Exercise-induced
rhinitis not only adversely affects athletic performance, but it can also interfere with the general population in maintaining active lifestyles. Intranasal antihistamines are easy to use and have low side-effect profiles. Although further
study is needed, intranasal antihistamines including Azelastine (0.15%) may
be effective treatments in exercise-induced rhinitis.
U. Amon*, S. Mangalo, A. Roth, Hersbruck, Germany.
Background: Enhanced photosensitivity of patients with atopic dermatitis
(AD) has become an increasing problem with respect to our investigations with
a large population of patients with inflammatory skin diseases. Aim of the study:
We were interested whether these group of patients does need more intensive
treatment in comparison to AD patients without photosensitivity. Patients and
Methods: In a retrospective analysis 983 patients with AD were screened for
photosensitivity by personal history regarding disease exacerbation following
sun exposure or UV-phototherapy, clinical aspects for light sensitivity, standard
UV-testing (UVB, UVA). Intensity of treatment was compared for AD patients
with and without photosensitivity. Results: In 298 cases with AD (30.3%) a
clinical relevant photosensitivity was demonstrated. A reduced minimal erythematous dose (MED) to UVB was dominant (99.6 % vs. 3.9 % UVA alone
or UVB and UVA). AD patients with reduced photosensitivity received a systemic medication for their skin disease in 17.5% whereas the control group
(AD patients without reduced MED, n=685) did need systemic medication in
only 6.1% of all cases (p<0.01). For systemic treatment cyclosporine A,
methotrexate, azathioprine, oral corticosteroids and other drugs were used in
30.8%, 28.3%, 11.8%, 12.7%, and 16.4% of all patients, respectively. Patients
with AD and photosensitivity were much more difficult to treat: the in-patients
periods was 16.7 days in comparison with 13 days of the AD control group.
Conclusions: Increased sensitivity to UV-light in patients with AD appears to
influence both treatment intensity with respect to systemic medication as well
as duration of hospitalization. The reasons for this important clinical observa-
tion remain to be further investigated. However, these findings are of high
economic relevance.
L.C. Bautista*1, A. Mendoza2, M. Sumpaico2, M. Recto2, M. Castor2, J. de
Leon2, 1. Bacolod City, Negros Occidental, Philippines; 2. Manila, Philippines.
Rationale: Polyunsaturated fatty acids found in marine fish oils modulate
immune responses, exerting beneficial effects in a variety of inflammatory disorders like bronchial asthma. However, its use on atopic dermatitis is not elucidated. Objectives: This study aims to determine the effects of fish oil supplementation on serum levels of IL-10 and total IgE, as adjunct to treatment
of atopic dermatitis among pediatric patients. Study Design: Randomized Controlled Single Blind Clinical Trial Setting: Allergy and Dermatology Out-patient
clinics of a tertiary government hospital. Patients: Twenty eight pediatric patients
were included in the study. Approval was obtained from the UP-PGH Review
Board. Written informed consent was obtained from all subjects and their respective guardians. All underwent standard treatment for atopic dermatitis. Thirteen were randomized to receive daily oral fish oil supplementation for 2 consecutive months as adjunct treatment and the remaining fifteen subjects received
no additional treatment. Results: Baseline clinical, serum levels, and demographic characteristics of both groups were comparable. After 2 months, there
was still no significant difference in the serum levels of IL-10 (p=0.951), total
IgE (p=0.901), SCORAD index (p=0.372) and corneometer moisture readings (normal skin p=0.136 and lesional skin p=0.056) between the fish oil and
the no fish oil group. However, within each group, there was significant increase
in IL-10 serum levels and corneometer moisture reading (lesional skin) and a
significant decrease in SCORAD index after treatment. Conclusion: This study
showed that fish oil supplementation has no effect on serum levels of IL-10,
total IgE, SCORAD index and corneometer moisture readings among patients
with atopic dermatitis. However, there was a trend towards a greater rate of
decrease in the SCORAD index and a higher rate of increase in corneometer
moisture readings in the fish oil group. A longer observation period, a larger
sample size, higher fish oil dose and the use of other immunologic markers
are recommended.
A. Chomiciene1, L. Jurgauskiene1, A. Blaziene*1, L.M. DuBuske2, 1. Vilnius, Lithuania; 2. Gardner, MA.
Background: A subset of patients with chronic urticaria (CU) has been
recently classified as autoimmune on the basis of finding functional autoantibodies against FceRIО± (high-affinity IgE receptor) or against IgE. About onefifth of patients have CU associated with antithyroid antibodies. The nature of
the relationship between chronic autoimmune urticaria (CAU) and autoimmune
thyroiditis remains uncertain. This study assessed the correlation between CAU
markers and thyroid autoimmunity. Methods: Sera were obtained from 128
patients with CU. Autologous serum skin tests (ASST) were performed on all
CU patients. Patients sera were incubated with atopic donor whole blood, and
activated basophils were identified by flow cytometry based on presence of
CD63 or CD203c on high-expressing IgE positive cells. Thyroid peroxidase
antibodies (TPO) were detected in patients sera by immunoassay. Results: ASST
was positive in 33.6% of patients with CU. Sera from 36.7% patients induced
up-regulation of CD63 and sera from 45.3% of patients up-regulated CD203c
molecule expression. TPO antibodies were found in 25% of CU patients. There
was no significant correlation between elevated TPO and CAU markers such
as positive ASST or up-regulated CD63 and CD203c expression on donor
basophils. Conclusions: Chronic autoimmune urticaria and autoimmune thyroiditis are two separate, parallel autoimmune events. All patients with CU
should be screened for both conditions in order to optimize their treatment.
J. Fodeman, S.P. Jariwala*, E. Jerschow, G. Hudes, D. Rosenstreich, Bronx,
Introduction: Contact dermatitis is characterized as skin inflammation triggered by contact with an irritant or allergen. Irritant dermatitis typically involves
contact with materials such as acids, detergents, solvents, and chemicals. Some
common allergens known to cause allergic contact dermatitis include poison
ivy, metals, and fragrances. Treatment includes avoidance of the trigger, topical steroids, and oral antihistamines. We describe a case of contact dermatitis
where contrary to expectation, hydroxyzine worsened symptoms. Methods:
Case description; literature review. Results: A 33-year-old female with a history of asthma, chronic sinusitis, and anemia was referred to our Allergy clinic
for evaluation of suspected contact dermatitis. The patient first noticed symptoms soon after starting treatment with neomycin. She developed small and
painful, tender blisters on her hands, elbows, shoulders, and feet (Figure). The
patient had gone to the emergency room and was started on prednisone and
daily hydroxyzine. The rash was initially localized and improved somewhat on
the prednisone. The patient also described an intense burning and generalized
itch. After two months of worsening symptoms on hydroxyzine, the patient presented to our clinic for additional evaluation. On exam, a scaly lesion was appreciated bilaterally on the elbows and fingers. A patch test was conducted, which
was positive for neomycin sulfate 20% +3, ethylenediamine dihydrochloride
1% +3, epoxy resin 1% +2, p-tert-butylphenol formaldehyde resin 1% +3,
imidazolidinyl urea 2% +3 and nickel sulfate +3. In light of the published crossreactivity between ethylenediamine and hydroxyzine chemical structures, the
latter was promptly discontinued with rapid clinical improvement. Prednisone
was subsequently tapered and although the patient suffers from occasional hand
eczema, she has markedly improved since hydroxyzine was discontinued. Conclusion: Antihistamines are the mainstay treatment for pruritus secondary to
most etiologies. While the topical use of antihistamines has been known to
induce hypersensitivity reactions, it is rare for systemic antihistamines to do
so. Hydroxyzine is an ethylenediamine dihydrochloride and thus even though
it rarely has been reported, cross reaction is possible.
ized by a combination of distinct clinical and histopathologic findings including a diffuse eosinophilic infiltrate, dermal edema and characteristic “flame
figures.” Wells Syndrome has been separated into seven clinical variants and
can be further differentiated into three phases. This rare dermatosis has been
associated with infections, arthropod bites, pharmacologic agents, immunizations, myeloproliferative disorders, and malignancies. At this time, the etiology of Wells’ Syndrome is not known. CONCLUSIONS: As with most dermatoses, a broad differential diagnosis must be explored. The differential
diagnosis of Wells’ Syndrome includes Churg-Strauss syndrome (CSS),
eosinophilic fasciitis, bacterial cellulitis, hypereosinophilic syndrome (HES),
and episodic angioedema with eosinophilia (EAE). Yet, the rarity of this illness
has made the diagnosis much more difficult than most other eosinophilic cellulitides. As our knowledge of this unique condition expands, we will be able
to further characterize this illness, with the ultimate goal of providing our
patients with a diagnosis and treatment options.
S. Sridhara*, C. Weiler, Rochester, MN.
Introduction: Mastocytoma is the most common presentation of cutaneous
mastocytosis. It is an uncommon benign pediatric tumor that results from hyperplasia of mast cells in papillary dermis. The objective of this study is to analyze the clinical presentation and course of mastocytoma patients at our institution over a period of 18 years. Methods: A retrospective chart review of all
patients with a diagnosis of mastocytoma at our institution between the years
1992 and 2009 was performed, after obtaining IRB approval. The clinical presentation, diagnosis and course of mastocytoma were analyzed. Results: A total
of 57 patients were included in this review. The male to female ratio was found
to be 1.5:1. About 80% presented before 1 year of age of which 25 % were present at birth. Symptoms were predominantly local in that the lesion would turn
red and/or itchy on irritation. Blistering was noted in 18% of patients, all of
them being infants. History of generalized flushing on irritation of the lesion
was elicited in only 6 % of the patients. The typical appearance of the lesion
was of an orange red or yellow colored or hyper pigmented, solitary or very
few plaques or nodules. Sizes ranged from 0.5 to 5 cm in diameter. Lesions
were distributed mainly in the areas of trunk and extremities. The diagnosis
was made by positive Darier’s sign (The urtication of skin lesions upon stroking)
in 76% of patients and by biopsy in the rest, except in 6 patients where none
was documented. The biopsy results in 3 patients with a clinical diagnosis of
mastocytoma were found to be dermatofibroma and nevus of Spitz. The treatment mainly included avoidance of mechanical irritation and anti-histamines
and local care. Patients with history of blistering were provided with intramuscular epinephrine injection though none of them required to use it. Of the
40 % of the patients who were followed up over 6 months to 1 year, half showed
improvement in the size and appearance of the lesions as well as symptoms.
Conclusion: Mastocytoma is one of the causes of blistering lesions in infancy
which can be diagnosed with a positive Darier’s sign in majority of patients. It
resolves spontaneously and surgical excision is not required unless associated
with severe local and systemic effects.
Figure 1.
J.L. Mutnick*, New London, MN.
RATIONALE: Wells Syndrome was first described in 1971 in a group of
four patients by G.C. Wells. The illness falls under the class of eosinophilic cellulitides, as eosinophils are one of the pathognomonic cells found in biopsy.
As we learn more about the eosinophilic cellulitides we will further be able to
understand the uniqueness of Wells Syndrome. METHODS: An extensive literature review of MEDLINE/Pub Med was undertaken to determine the number of clinical reviews or case reports looking specifically at cases of Wells
Syndrome between 1971 and 2009. RESULTS: Only about 80 cases have been
reported worldwide in the literature. Wells’ Syndrome is rare in both pediatric
and adult patients. Nevertheless, it may appear at any age; although it has been
reported less frequently in young people. Wells’ Syndrome can occur in persons of any race and no sexual predilection has been reported. It is character-
Disclosure of Significant Relationships
with Relevant Commercial Companies/Organizations
Oral and Poster Abstract Presenters
American College of Allergy, Asthma & Immunology
Annual Meeting
Continuing Medical Education
November 14-15, 2010
As required by the Accreditation Council for Continuing Medical Education and in accordance with the American College of
Allergy, Asthma & Immunology (ACAAI) policy, all educational planners, presenters, instructors, moderators, authors,
reviewers, and other individuals in a position to control or influence the content of an activity must disclose all relevant financial relationships with any commercial interest that have occurred within the past 12 months. This disclosure in no way implies
that the information presented is biased or of lesser quality. Attendees of this meeting should be aware of these factors in interpreting the program contents and evaluation recommendations. Moreover, views of faculty do not necessarily reflect the
opinons of the ACAAI.
The following have disclosed commercial relationships; all others have reported that they have nothing to disclose:
Aberer, W – P236
Grant/Research Support: Shire
Albrecht, H – P349
Consultant: Reckitt Benckiser, Inc.
Allen-Ramey, F – P36
Employee: Merck
Altrich, M – P166
Consultant: Viracor – Ibt Laboratories
Andersen, J – 53
Employee: ALK-Abello
Anderson, S – 9
Royalties: Pharmaxis Ltd; Scientific
Advisory Committee: Pharmaxis Ltd;
Consultant: Pharmaxis Ltd;
Shareholder: Pharmaxis Ltd
Atiee, G – P301
Grant/Research Support: Merck &
Baker, J – 27, 28, P262, P263, P264
Study Investigator/Study Researcher:
ViroPharma Incorporated, Lev
Pharmaceuticals; Advisory Board:
Lev Pharmaceuticals
Beigelman A – 42
Recipient of Young Faculty Research
Award: ACAAI
Berger, W – P81
Consultant, Grant/Research Support,
Speaker: Alcon, Altana, Apieron,
AstraZeneca, Dey, Genentech,
GlaxoSmithKline, Medpointe,
Novartis, Sanofi-Aventis, Merck &
Co., Sepracor, and Teva
Bernstein, D – P36, P301
Consultant, Grant/Research Support,
Speaker's Bureau: Merck & Co.
Bernstein, J – 21, P317
Consultant/Advisory Board: Dyax
Corp., CSL Behring, Viropharm,
Dynova; Research Grant or Research
Support: Dyax Corp., Dynova
Laboratories; Speaker: Dyax Corp.,
CSL Behring, Viropharma,
AstraZeneca, Teva; Journal Editor:
Journal of Asthma
Bewtra, A – 25, 26
Research support: CSL Behring
Bielory, L – 28, P262
Grant/Research Support: ViroPharma
Inc., Lev Pharmaceu