ALLERGY AND IMMUNOLOGY
BOARD REVIEW
NOVEMBER 8, 2012
TEST QUESTION
True or False. I love daylight savings.
A. True
B. False
INTRODUCTION
GENERAL FACTS
 Atopy
represents the genetic predisposition to
develop allergic diseases
Atopic dermatitis
 Allergic rhinitis
 Asthma
 Food allergy

A
child with one component of atopy syndrome
has a 3x greater risk of developing a second
component
INFLUENTIAL FACTORS
 History
of atopy in a first-degree relative or
parent is the greatest risk factor for atopy
Neither parent: 10-15% risk
 One parent: 20-40% risk
 Both parents: 30-60% risk

 Early
childcare exposure reduces the risk for
development of asthma…“hygiene hypothesis”
 Non-genetic
risk factors
Aeroallergen sensitivity
 Environmental exposures
 Diet (mom’s and baby’s)

ENVIRONMENTAL EXPOSURE
 Early
exposure to tobacco smoke, especially
the mother’s, increases the frequency of
asthma in children!!!

This is even true for babies whose mom smokes
during pregnancy
 Passive
exposure to cigarette smoke may
exacerbate asthma and allergic rhinitis!
 1-800-QUIT-NOW

QUESTION #1
You are seeing an 8yo female with atopy syndrome back in
clinic after referring her to Allergy/Immunology for some
help. Skin prick testing was positive for various indoor
allergens, including dog and cat. The family has a dog that
has been around since your patient was 3yo. How should
you counsel this family regarding their pet?
A.
B.
C.
D.
E.
Nothing. The dog is not affecting her symptoms.
Tell the parents that they must sell the dog or find
someone take her.
Tell the parents that they must sell the child or find
someone to take her.
Keep the dog from the bedroom and decrease her exposure
to pillows, carpeted areas, and stuffed animals.
Bathe the dog once a week and things should be fine.
ENVIRONMENTAL EXPOSURE
 Identification
of indoor allergens is important
Dust mites among most common
 Animal dander from indoor pets…cat, dog, rodents
 Cockroach, especially in inner-city areas
 Mold

 Avoidance

Pet removal
May not always be correct answer because of attachment
 Removal/isolation from patient’s bedroom more likely!!

Impermeable covers, HEPA filters, vacuuming frequently
 Removal of carpet and stuffed animals
 No single intervention alone is likely to have a
significant overall effect

DIET
 Maternal
diet during pregnancy and/or
breastfeeding has NOT been shown to significantly
alter the incidence of atopy

Restricting the mother’s diet will not be the correct
answer!!!
 Breastfeeding
for the first 3-6 months after birth
reduces the risk of atopic dermatitis in “at risk”
babies

The AAP recommends exclusive breastfeeding for at least
4 months with supplementation of hypoallergenic formula
if needed in “high risk” newborns (both parents or one
parent and one sibling have atopy)
ALLERGIC RHINITIS
RHINITIS
 Rhinitis:
Inflammation of the membrane lining
the nose and/or postnasal drainage
 Chronic
rhinitis can be either allergic or non-
allergic




Stimuli (allergens, medications, hormones) cause mast
cells and basophils to degranulate
Chemical mediators are released causing rhinorrhea and
nasal congestion
Histamine release causes sneezing and itching
Allergic rhinitis: IgE-mediated hypersensitivity
reaction to specific allergens
ALLERGIC RHINITIS
 History





Nasal congestion: mouth breathing, snoring, nasal voice
Nasal irritation: sneezing, nasal pruritis, nose blowing,
sniffing, snorting, coughing
Itchy eyes and postnasal drip
Impact on quality of life, seasonality, triggers, alleviating
factors, and medication use are also important
Comorbidities…sinusitis and otitis media
 Physical





exam
Pale, edematous turbinates
Cobblestoning of posterior OP from lymphoid hyperplasia
“Allergic shiners” from venous engorgement
Dennie lines from edema
Allergic salute: transverse nasal crease
QUESTION #2
What is the MOST common cause of perennial
(persistent) allergic rhinitis?
A.
B.
C.
D.
E.
Using Afrin (a nasal decongestant) for longer than a
week.
Cold weather or change in temperatures.
Eggs, wheat, milk, peanuts, and soy.
Outdoor allergens…different pollens and grasses.
Indoor allergens like animal dander, molds, and dust
mites.
ALLERGIC RHINITIS
 Triggers


Seasonal rhinitis: outdoor plant allergens or specific molds that
vary depending on the time of year
Perennial rhinitis: indoor allergens such as dust mites and animal
dander
 Testing


to identify allergen hypersensitivity
Percutaneous (prick or puncture) skin testing remains the most
specific and cost-effective diagnostic modality
RAST testing (for IgE) in blood can also be used
 Nasal
eosinophilia (nasal smear >4% eosinophils)
QUESTION #3
A 12yo girl presents with recurrent rhinorrhea,
sneezing, ocular pruritis, and nasal congestion each
spring and fall. On PE, she has bilateral conjunctival
erythema, enlarged and pale nasal turbinates, and a
transverse nasal crease.
Which medication will be your BEST first choice
medication for symptom improvement?
A.
B.
C.
D.
E.
Intranasal decongestant
Intranasal corticosteroid
Ocular antihistamine
Oral decongestant
Oral leukotriene antagonist
TREATMENT

Allergen avoidance = initial management



Intranasal corticosteroids: first-line pharmacotherapy



Intermittent symptoms: indoors during high pollen times, AC
during spring and fall pollen seasons
Indoor allergens: decrease humidity (<50%), bed/pillow covers;
remove pets from home OR decrease exposure by eliminating
from bedroom and areas with rugs/pillows/heavy upholstery
Regular use can reduce nasal blockage, rhinorrhea, sneezing, and
nasal itching
Most common adverse effect = epistaxis
Antihistamines (H1 or H2)


Decreased sneezing, itching, and rhinorrhea
NOT effective at treating congestion
ASTHMA…GET EXCITED!!
ONLY 29 CONTENT SPECS 
PATHOPHYSIOLOGY
 Disease
of airway inflammation mediated by a
variety of cell types, resulting in hyper-responsive
airways
Airway bronchoconstriction
Airway edema
Exaggerated mucus production
Airway hyperresponsiveness
Airway remodeling
QUESTION #4
What is the primary mediator during the early phase of
an asthma exacerbation?
A.
B.
C.
D.
E.
Cytokines and chemokines
Eosinophils
IgE
IgA
T-lymphocytes
PATHOPHYSIOLOGY
 Early
phase
IgE mediated
 Mast cells and basophils
degranulate causing
bronchospasm
 Short-acting beta
agonists!!

 Late
phase
Inflammatory
 Increased bronchial
hyperresponsiveness
 4-12 hours after exposure to
environmental insult
 STEROIDS!!!

PREDISPOSING CONDITIONS



Family history of asthma
Atopy syndrome: allergic rhinitis and eczema
Most children with asthma (60-80%) are sensitized
to at least 1 aeroallergen
Common indoor allergens: house dust mite, mold,
cockroach, and animal dander
 Skin testing should be considered for any child with
persistent asthma


Exposure to tobacco smoke
Potent airway irritant
 More likely to have mod-severe asthma with decreased
lung function

QUESTION #5
16-year-old boy who runs on his high school cross-country
team has been having trouble with coughing and
wheezing during exercise. He has a history of
intermittent asthma that is well controlled when he is
not running. His coach is worried that he may have
exercise-induced asthma (EIA). Which of the following is
NOT characteristic of this diagnosis??
A.
B.
C.
D.
E.
EIA is sometimes the only presentation of asthma.
The symptoms often resolve with or without medication
once the exercise is stopped.
Long acting beta agonists are the preferred treatment
and the effect will continue even with long-term use.
The onset of wheezing 5 minutes after exercise starts
with resolution within 20-30 minutes after stopping.
Is often a sign of poorly controlled/more severe asthma.
TRIGGERS
Medications
Aspirin
NSAIDS
Beta Blockers


Exercise induced asthma: Coughing and
wheezing after 5-6 minutes of exercise, gradual
improvement after 20-30 minutes of rest (with or
without med); smog increases severity!!
Can be the only presentation OR a sign of
underlying, poorly controlled/more severe asthma
EARLY WHEEZING

Transient wheezers cease to wheeze after age 3

Often associated with a LRTI, especially RSV

RSV and future development of asthma…




Exact data varies
Risk increases with severe infection (ie. hospitalization)
More than 80% of infants with a history of wheezing in
the first postnatal year (especially with URIs) do not
wheeze after age 3
Atopic wheezers are most likely to develop persistent
asthma

Kids with early onset asthma (<3y) with a parental history
of asthma, confirmed atopic dermatitis, or sensitization to
aeroallergens are least likely to outgrow asthma.
CLINICAL MANIFESTATIONS

Cough (may be the only symptom)





Wheezing
Difficulty breathing
“Chest tightness”
Symptoms often worsen in presence of triggers


Nighttime symptoms are common!
Be sure discharge planning includes a full assessment of
potential triggers in the home, school, or neighborhood!
Other signs of atopy
ASTHMA CLASSIFICATION

Severity is initially best determined at time of
diagnosis, before starting therapy





Determined by the most severe level of symptoms
Exercise-induced symptoms do not count towards severity
Four categories: intermittent, mild/moderate/severe
persistent
The most important distinction is between intermittent
and persistent asthma because all individuals with
persistent asthma should be started on long-term
controller medication (inhaled corticosteroids)
2007 Guidelines breaks down into 3 age categories
QUESTION #6
You are rounding on Purple team with Dr. Hescock. You
are presenting a 7yo male patient to the team who is
here with status asthmaticus. Dr. Hescock asks you to
classify his asthma at baseline. Per mom, he usually
coughs one night per week and uses his albuterol at
home 4-5 days/week. He saw a pulmonologist last month
for PFTs, and his FEV1 was 75%. How would you BEST
classify his asthma?
A.
B.
C.
D.
Intermittent
Mild Persistent
Moderate Persistent
Severe Persistent


Major risk factors (one required): parental history of
asthma, eczema, aeroallergen sensitivity
Minor risk factors (2 required): sensitization to foods,
more the 4% eosinophilia, wheezing apart from colds


PFTs should be performed at the initial time of
asthma diagnosis (if old enough…5-6 years)
PFTs should also be assessed every 6-12 month in
ALL patients with persistent asthma!
QUESTION #7
You have determined that a 4yo patient you are seeing in
clinic today has mild persistent asthma. You have given
mom a prescription for her albuterol MDI. What is the
other MOST important prescription you need to write?
A.
B.
C.
D.
E.
Inhaled corticosteroid
Long acting beta agonist
Nasonex
Leukotriene receptor antagonist (Montelukast)
Theophylline
OUTPATIENT TREATMENT



Short-acting beta agonists (rescue med)…work on the
early (bronchospasm) phase
Treatment of ANY persistent asthma should include a
long-term controller medication for prevention.
First-line = inhaled corticosteroids
Decreases bronchial inflammation and hyperresponsiveness
 Block the late response to allergen (inflammatory phase)
 Most effective anti-inflammatory medication for asthma





Reduce asthma symptoms
Improve lung function
Reduce acute exacerbations
Reduce the risk of death from asthma
OUTPATIENT TREATMENT

Inhaled Corticosteroids

Side effects: oral candidiasis, dysphonia (hoarseness), reflex
cough, bronchospasm

Can be reduced by using a “spacer” with MDI, slowing the rate of
inhalation, as well as rinsing the mouth with water after use
High dose ICS may have an initial early affect on growth
velocity, but no data suggests effect on final adult height; no
known decrease in bone mineral density
ALTERNATIVE MEDICATIONS

Leukotriene receptor antagonists (montelukast and
zafirlukast)






Interfere with the action of leukotrienes…potent inflammatory
mediators that are released from mast cells, eosinophils, and
basophils
Alternative (not preferred) therapy for patients with mild
persistent asthma
“Add-on” therapy for patients who do not achieve good control
with medium-dose ICS
Theophylline
Omalizumab
Cromolyn sodium and nedocromil
ALTERNATIVE MEDICATIONS

Long acting beta agonists (LABA)
12 hours of bronchodilation by stimulation beta-2 receptors
in the airway  Increased cAMP  Relaxation of smooth
muscle
 Available as dry powder inhaler (formoterol) or in
combination with ICS (salmeterol/formoterol)
 NOT





To be used to treat acute exacerbations
Anti-inflammatory…so do NOT use as monotherapy
Prevent exercise-induced bronchospasm, but effect deteriorates
with long-term administration
Preferred “add-on” medication in kids > 12 years
QUESTION #8
You are in the ER seeing a patient with asthma for
increased WOB that started with the weather change
yesterday. His last admission was during the winter last
year. He is afebrile and other than his wheezing and
increased WOB with a dry cough, ROS is negative. On
PE, you hear diffusely decreased breath sounds,
wheezes, and no crackles. His CXR is shown. What
other medication would you start besides Albuterol and
Steroids?
A.
B.
C.
D.
E.
Rocephin
Azithromycin
Both Rocephin and Azithromycin
Augmentin
None of the above
EXACERBATIONS

Patients who have any degree of asthma severity can
have a severe exacerbation.

Symptoms of severe obstruction
Dyspnea at rest, inability to speak whole phrases
Cyanosis, accessory muscle use (retractions)
Quiet breath sounds (NO wheeze = bad)
Peak flow less than 40% predicted or personal best
 Failure to respond to initial treatments





Patients with exacerbations uncontrolled by home
medications should present to the ER!

Atelectasis on CXR is common
Antibiotics are NOT indicated unless there is true
evidence of bacterial infection
 CPT is not helpful

EXACERBATION TREATMENT

An inhaled short-acting beta agonist is first-line
(albuterol, levalbuterol)





Oxygen if increased WOB or with low O2 Saturations
Consider MIVFs



Relax smooth muscle within minutes, peak effect at15-30
minutes, wears off at 4-6 hours
Often patients will need a continuous treatment
Side effects: tachycardia, tremulousness, irritability, hypokalemia
Patients are prone to increased HR because of chest hyperexpansion that impedes venous return
Albuterol increases HR even further
Ipratropium bromide (anticholinergic) in ER can
decrease admission rates
EXACERBATION TREATMENT

For severe exacerbations that are unresponsive to SABAs
alone…systemic corticosteroids to treat late phase
Improve airway responsiveness to SABAs, improve lung
function (FEV1) and oxygenation, and decrease the risk of
relapse from acute exacerbation
 2mg/kg/day (3-10 days depending on severity)

NO difference between IV/PO steroids in terms of efficacy
 IF a patient is having a moderate to severe exacerbation
with increased WOB, IV steroids should be ordered



Can give higher doses…varies but 1mg/kg q6h and possibly up
to 2mg/kg q6h!
Magnesium sulfate IV and MORE…but no content
specs on this 
RISKS OF SEVERITY
 Risk
factors for ICU admission OR higher rate of
death






One or more life-threatening exacerbations of asthma
Severe asthma requiring chronic oral steroids
Abnormal FEV1
Poor adherence
Poor control of daily asthma symptoms
Frequent daily short-acting beta agonist use

Excessive use (>2 days/week) has been associated with poorly
controlled asthma and an increased risk of hospitalization and
death!
Low socioeconomic status, family dysfunction
 Patient psychological problems…depression/stress

SELF ASSESSMENT
 Teaching
the patient and/or family ways to
recognize exacerbations is extremely important to
patient outcome!
 Counseling
the family at EVERY visit regarding
proper use of daily controller medications and
rescue medications is essential to good control!
 Be
sure your patients know when an ER visit is
necessary!
URTICARIA, ANGIOEDEMA, &
ANAPHYLAXIS
ANAPHYLAXIS
Immediate and potentially life-threatening
reaction to an allergen
 Symptoms typically develop within minutes up to
2 hours



Rare cases of delayed reactions >2hrs after exposure
Most common symptoms = cutaneous
Pruritus, flushing, urticaria, angioedema
 Occur in up to 90% of patients

ANAPHYLAXIS
ANAPHYLAXIS - TRIGGERS

Foods


Most common: milk, egg, soy, wheat, peanut/tree nut,
seafood
Drugs

Most common: Penicillin



Low-risk of cephalosporin cross-reactivity
Other antibiotics (sulfa, etc), aspirin,
NSAIDs, chemo
Insects
Hymenoptera (vespids, bees, stinging ants)
 Large local reactions increase risk for anaphylaxis


Latex

Rubber tree antigens
ANAPHYLAXIS - TRIGGERS

Vaccines
Egg: influenza, yellow fever
 Gelatin, Neomycin: MMR


Perioperative


Muscle relaxants, latex, antibiotics, opioids, blood
products
Exercise

Can be food-dependent
Immunotherapy
 Idiopathic

QUESTION #9
The parents of a 10-year-old boy who has a peanut allergy ask
your advice on treatment of food allergy reactions at school.
Last year, their son started itching diffusely and had
difficulty breathing during lunchtime after accidentally
eating some of his friend's chocolate candy bar that
contained peanuts. The child is allowed to carry his own
self-injectable epinephrine at school. His current weight is
90 lb (41 kg).
A.
B.
C.
D.
E.
Of the following, the BEST advice for the child, if a similar
situation occurs, is to
Have the school call emergency services (911), who should
evaluate and administer epinephrine if needed
Have the school nurse observe the child for 10 to 15
minutes while calling his parents
Immediately administer 0.15 mg of self-injectable
epinephrine
Immediately administer 0.30 mg of self-injectable
epinephrine
Take an oral antihistamine immediately
ANAPHYLAXIS - TREATMENT
Most important = recognize symptoms!!
 Early administration of epinephrine

Best route = IM (lateral thigh)
 Dose = 0.01mg/kg (max. 0.5mg)
 EpiPen

0.15mg for <30kg
 0.30mg for >30kg


Corticosteroids to help prevent the late-phase or
biphasic reaction


20% will have symptoms 4-24hrs after initial reaction
+/- H1-antihistamines
URTICARIA
Can be associated with anaphylaxis;
but often occurs without systemic symptoms
 Typical lesion: raised, erythematous, pruritic or
burning, resolves within 24 hours


Acute vs chronic

Acute: symptoms last <6 weeks


60% are due to proven or probable infection (usually viral)**
Chronic: symptoms lasting > 6 weeks

Do NOT order skin or serum IgE food testing without
substantial clinical history**
QUESTION #10
A 10yo M presents for evaluation of hives that have
occurred daily over the past 4 months. They are
raised, erythematous, pruritic, 1-2cm lesions on
his trunk and extremeties. They resolve
spontaneously in a few hours and can occur at
any time of day or night. His parents are
frustrated by the lack of response to changes in
soap and laundry detergents. What is the MOST
likely cause of this child’s hives?
A. Allergy to food additive or preservative
B. Allergy to dust mite
C. Autoantibody to the immunoglobulin E receptor
D. Autoimmune thyroid disease
E. Systemic mastocytosis
CHRONIC URTICARIA - TRIGGERS

Autoimmune: 30-50%
Circulating autoantibody directed against IgE receptor
on mast cells and basophils
 Autologus serum skin test (ASST) positive

Artificial flavors, colors, additives: 1-2%
 Physical urticaria:

Dermatographism
 Heat-induced
 Cold-induced
 Pressure-induced
 Contact




Localized IgE reaction to food, enviornmental, animal, etc
Solar
Unknown
CHRONIC URTICARIA - TREATMENT
Goal = block histamine and tryptase
 Most common medication: antihistamines


Second-generation H1-antihistamines: first line therapy
Cetirizine, loratidine, fexofenadine, etc
 Low adverse effects
 Can increase dose up to 4x’s usual dose


First-generation H1-antihistamine for rescue


Diphenhydramine, hydroxyzine
Other medications (no approved indication, but
clinical use suggests they are helpful)

H2-antihistamines, leukotriene receptor antagonists,
thyroxine, plasmaphoresis, IVIG, cyclosporine,
colchicine, dapsone, sulfasalazine, omalizumab,
corticosteroids
ANGIOEDEMA
Transient swelling of the dermis
or subcutaneous tissue
 Can be a symptom of anaphylaxis; can occur
during episodes of urticaria
 Causes:


Hereditary: 3 types


Type 1 = most common; low C1 esterase inhibitor (C1INH)
concentration
 Inability to stop the complement cascade  low C4
Acquired

Associated with lymphoproliferative disorders,
autoantibodies to C1INH
Idiopathic (most common)
 Secondary to ACE inhibitors

FOOD ALLERGY
FOOD ALLERGY
Immune-mediated adverse reaction to foods
 Symptoms involve skin, GI tract, respiratory
 Can be IgE and non-IgE mediated


Common foods causing allergy:

Milk, eggs, soy, peanut/tree nut, wheat, seafood
Milk, egg, and soy allergies typically outgrown by age 5
 Peanut, tree nut, and seafood allergies are rarely outgrown


90% of food-allergic individuals demonstrate
clinical response to only 1 or 2 foods
FOOD ALLERGY: CLINICAL MANIFESTATIONS

IgE: starts within minutes  up to 2 hours


Non IgE-mediated:


Ranges from cuteanous reaction to anaphylaxis
Food-induced proctocolitis, pulmonary hemosiderosis,
celiac disease
Mixed IgE and non-IgE

Atopic dermatitis, esosinophilic esophagitis
ORAL ALLERGY SYNDROME

IgE-mediated allergic manifestation affecting the
oropharynx
Tingling/itching of lips, palate, tongue
 Occasionally abdominal discomfort, nausea/vomiting
 No symptoms when the food is cooked or processed


Affects 50% of adults with allergic rhinitis to
inhalent pollens
Most common adult food allergy
 Due to cross-reactivity between proteins of pollens
and those in fruits/vegetables

Birch: apple, plum, peach, nectarine, cherry, almond
 Ragweed: melon, banana, tomatoe
 Grass: melon, kiwi
 Mugwort: celery, spices, carrot

ORAL ALLERGY VS ANAPHYLAXIS**
FOOD ALLERGY: DIAGNOSIS
History: Most important!
 Skin Prick Testing
 Radioallergosorbent Test (RAST)

Identify food-specific IgE antibodies
 Typically correlates closely with skin test**
 Indicated when oral antihistamines cannot be
stopped, when pt has dermatographism, or if h/o
anaphylaxis to the agent being tested

Oral Food Challenge
 Double-blind, placebo-controlled Food challenge


Gold standard
QUESTION #11
A 12-month-old boy presents with a 7-month history of
a worsening skin rash. The rash is pruritic and
involves his neck, anterior and posterior trunk,
antecubital and popliteal fossae, and hands and feet.
Use of a moisturizer and topical corticosteroid has
resulted in some improvement. The remainder of his
past medical history is unremarkable. Physical
examination is consistent with severe atopic
dermatitis. Of the following, the MOST helpful next
step is to:
A.
B.
C.
D.
E.
Eliminate milk, eggs, soy, and wheat from the diet
Eliminate fruit and acidic juices from the diet
Perform aeroallergen allergy testing
Perform food allergy testing
Refer for a skin biopsy
FOOD ALLERGY AND ECZEMA
30-40% of children with moderate-severe eczema
have IgE-mediated food allergy
 In some infants, food ingestion may result in
immediate worsening of eczema severity


However, most infants do not demonstrate this
immediate reaction
Food avoidance should be guided by the dietary
history, eczema severity, and results of allergy
testing
 Aeroallergens (mold, trees, weeds) are not
associated with eczema in infants

IMMUNODEFICIENCIES
(GET READY FOR SOME WORDY SLIDES)
IMMUNODEFICIENCIES
Group of disorders that increase susceptibility to
infection, malignancy, and autoimmunity
 Can be congenital or acquired


Common clinical findings in many types:
Recurrent or chronic respiratory infections
 2+ episodes of bacterial PNA
 5+ episodes of otitis media in 1 year or 7 in 2 years
 Recurrent or persistent sinusitis

IMMUNE SYSTEM

Antibody-mediated (B-cells)


Immunodeficiency due to subnormal immunoglobulin
levels OR defective specific antibody responses
Cell-mediated (T-cells)

Typically cause a combined immunodeficiency
because T-cells provide signals for B-cell
differentiation
Phagocytosis
 Complement system


Defects of any component can cause an
immunodeficiency!
QUESTION #12
A 17-year old boy presents with a 3-4 year history
of receiving antibiotics every other month for
sinusitis and pneumonia. He has also had one
episode of diarrhea due to Giardia. CT of the
lungs shows bronchiectasis. He has low IgG, IgA
and IgM concentrations but normal numbers of T
and B cells. What is the most likely diagnosis?
A. Common variable immunodeficiency
B. Severe combined immunodeficiency
C. X-linked agammaglobulinemia
D. Wiskott-Aldrich syndrome
E. Hyper IgE syndrome
ANTIBODY DEFICIENCY SYNDROMES
Presentation
 Presents after 4-6mos of age






Types to know:
 Selective IgA deficiency
Often into adulthood
Recurrent bacterial
sinopulmonary infections
Unexplained bronchiectasis
Diarrhea secondary to
Giardia or enterovirus
Pathogens: gram-positive
pyogenic bacteria;
extracellular
encapsulated organisms
(S. pneumoniae, H influenza
type B, GAS); enterovirus
Typically do not have
growth problems

X-linked
agammaglobulinemia

Common Variable
Immunodeficiency


Transient
hypogammaglobulinemia of
infancy
Hyper-IgM (combined B and
T cell problem)
SELECTIVE IGA DEFICIENCY
Low or absent IgA
 Other Ig levels are normal
 Cell-mediated immunity is intact
 Can be asymptomatic
 Sinusitis, otitis, diarrhea (giardia)

Treatment? symptomatic
 Anaphylaxis with IVIG!

X-LINKED AGAMMAGLOBULINEMIA
(BRUTON’S)
Infections begin at 6-9 months
 Pneumonia, otitis, sinusitis are prevalent
 Infections with pneumococcus, streptococcus, and
Haemophilus
 Recurrent enteroviral infections
 Low/absent immunoglobulins, NO mature B-cells


Normal or increased T-cell number

Absent/decreased tonsils and lymph nodes

Treatment? IVIG, avoid live vaccines
COMMON VARIABLE IMMUNODEFICIENCY


Onset 15-35 years of age
Varying degrees of immunoglobulin deficiency and impaired
antibody responses
Low IgG, IgA, IgM (Typically 2 subtypes will be low; may be all)
 Poor response to protein (DTaP) and polysaccharide (PCV)
vaccines



Pneumonia, bronchiectasis, sinusitis, GI infxns
Normal number of mature B cells




But fail to differentiate
Intact cell-mediated immunity, but depressed T-cell function
over time
Increased incidence of malignancy (NHL, gastric carcinoma),
autoimmunity (RA, thyroid abnormalities)
Treatment? IVIG
TRANSIENT HYPOGAMMAGLOBULINEMIA
OF INFANCY

Self-limited antibody deficiency


Normal infants have time of low Ig levels at 3-6
months


No intrinsic B cell deficiency; decreased T-helper
functions
In some infants this persists
Detected at 1-2 years of age

Typically resolved by 3-6 years of age
Low IgG, low/normal IgA, normal IgM
 B cells present, normal number


Treatment? supportive
HYPER IGM (COMBINED B AND T CELL
PROBLEM)
X-linked
 Severe respiratory infections, sinusitis
 IgM is high, IgG, IgA, IgE are very low



Absence of CD40 ligand found on T cells  No Ig
class switching
Normal T-cell number/cellular function, but Tcell immunity weakens with time

Can be classified as combined deficiency

Associated with autoimmunity, malignancy

Treatment? IVIG
QUESTION #13
You are seeing a 3-month old baby with suspected
severe combined immunodeficiency (SCID). Of
the following options, which would be the MOST
suggestive for SCID?
A.
B.
C.
D.
E.
Acute otitis media
Preterm delivery
Neisseria meningitis
Failure to thrive
Delayed umbilical cord separation
CELLULAR/COMBINED IMMUNODEFICIENCIES
Presentation:
 Present in first few
months after birth
 FTT, chronic diarrhea,
overwhelming infections
 Pathogens: gram-negative
bacteria, fungi, protozoa,
viruses, mycobacteria,
PCP pneumonia
 Respond poorly to
antibiotics
 GVHD
 High incidence of
malignancy
 Poor survival beyond
infancy
Types to know:
 DiGeorge

Severe Combined
immunodeficiency

Wiscott-Aldrich

Ataxia Telangiectasia

Hyper-IgE*
DIGEORGE (22Q11 DELETION)
Defect in embryogenesis: heart, thymus,
parathyroid
 Hypoparathyroidism  Hypocalcemia
 Abnormal facies, cleft palate
 Absent thymus
 Decreased number of T cells
 Normal number of B cells



May have low Ig levels or poor specific antibody
responses
Treatment? Thymus transplant, BMT
SCID
Life threatening infections shortly after birth
 FTT, oral thrush, chronic diarrhea, pneumonia
(especially PCP), sepsis, dermatitis
 Susceptible to overwhelming viral infection


Varicella, CMV, herpes
Blood transfusions cause GVHD
 Failure of lymphoid precursors to differentiate
into B cells and T cells



Both T-cell and B cell immunity markedly decreased
Treatment? BMT
WISCOTT-ALDRICH






X-linked, WASP gene
Triad: eczema,
thrombocytopenia,
recurrent sinopulmonary
infections
Small platelets
Poor antibody response to
polysaccharide antigens
and defective T-cell
function
Normal B and T cell
number
Associated with
autoimmune disorders,
malignancy (hematologic)
ATAXIA-TELANGIECTASIA



AR
Occulocutaneous telangiectasia
Cerebellar ataxia






Presents first (around 2yo)
Recurrent sinopulmonary infections; bronchiectasis
Lymphopenia, normal or depressed T-cell numbers
No response to delayed hypersensitivity tests
Variable low Ig levels (IgA, IgG2, IgG4)
Increased susceptibility to malignancy

Increased sensitivity to radiation, defective DNA repair,
frequent chromosomal breakages
HYPER-IGE
Autosomal Dominant
 Eczema and recurrent bacterial infections
of skin, lungs, middle ear, sinuses
 Boils, abscesses, pneumatoceles
 Most common: S. aureus, Candida infections
 Very high IgE
 Eosinophilia
 +/- problems with chemotaxis
 Associated with scoliosis, retained primary
teeth, coarse facies


Treatment? Antibiotics, steroids
QUESTION #14
An 11 month old boy is being hospitalized for a
prolonged febrile illness. His WBC is 32x103, with
82% neutrophils, 6% bands, and 12% lymphocytes.
He has a large left upper lobe infiltrate and
bronchoscopy was positive for Aspergillus. He has
multiple enlarged mediastinal lymph nodes and
surgical biopsy reveals necrotizing granulomas.
What is the most likely diagnosis?
A. HIV
B. DiGeorge Syndrome
C. Transient hypogammaglobulinema of infancy
D. Hyper IgM
E. Chronic granulomatous disease
PHAGOCYTIC DISORDERS
Presentation:
 Recurrent dermatologic
bacterial infections
 Pathogen: catalasepositive bacteria (S.
aureus, E. Coli, Serratia)
 Subcutaneous, lymph
node, lung, liver abscesses
 Pulmonary infections
including abscess and
pneumoatocele formation
 Bone and joint infections
 Peridontal disease
 Delayed separation of cord
Types to know:
 Chronic granulomatous
disease


Leukocyte adhesion
deficiency
Chediak-Higashi syndrome
CGD










XL or AR
Disorder of bactericidal function of neutrophils
Granulomatous lesions of skin, lymph node, lung
Liver, spleen, lung abscesses
Infections with catalase-positive bacteria (staph, El
coli, Klebsiella, Proteus) and fungal (Aspergillus,
candida)
Also see Serratia, nocardia, Burkholderia infxns
Defective H202 production/NADPH oxidase system
B and T cell immunity is normal
Diagnosis: NBT, DHR assays
Treatment? Antibiotics, interferon-gamma, BMT
LEUKOCYTE ADHESION DEFICIENCY
(LAD)
AR
 Defect in chemotaxis
 VERY high WBC
 Delayed umbilical stump separation; omphalitis
 Gingivostomatitis/peridontal disease, skin
infections
 Delayed wound healing
 Infected areas have no pus/minimal
inflammation


Treatment? BMT
CHEDIAK-HIGASHI SYNDROME
Abnormal chemotaxis
 Oculocutaneous
albinism
 Peripheral
neuropathy
 Easy bruisability
 Diagnosis: bone
marrow smear



Lysosomal granules
in WBCs
Treatment? BMT,
frequent antibiotics
COMPLEMENT DISORDERS
Presentation:
 Recurrent bacterial
infections with
extracellular encapsulated
organisms (S. pneumo, H.
influenza)
 Recurrent meningococcal
or disseminated
gonorrheal infection
 Increased incidence of
autoimmune disease
 Severe or recurrent skin
and respiratory tract
infections
 Angioedema of face, hands,
feet, GI tract
Types to know:
 C5-9 terminal complement
deficiency

C1 esterase inhibitor
deficiency

C2, C3, C4 deficiency
COMPLEMENT DEFICIENCY
C2 most frequently deficient protein
 Terminal components (C5-C9) Deficiency

Recurrent Neisseria infections
 Total complement (CH50) is very low/absent
 Treatment? Antibiotics, immunizations, symptomatic
care

SCREENING TESTS FOR PRIMARY
IMMUNODEFICIENCIES
CBC with differential
 CXR, sinus xrays, bone films (if warranted by
history)
 Cultures, if appropriate


Testing for antibody and cellular immune
responses

Investigate phagocytic and complement disorders
when there are normal antibody and celluar immune
responses
QUESTION #15
You are seeing a baby in the NICU for hypocalcemia.
You note low-set ears, hypertelorism and a murmur
on exam. Lab work shows a low total T cell count,
with normal B cell number. Which of the following
tests is most likely to be diagnostic?
A.
B.
C.
D.
E.
Nitro Blue Tetrazolium (NBT) test
HIV serology
Immunoglobulin G concentration
FISH for 22q11 deletion
T-cell subset assessment
SECONDARY IMMUNODEFICIENCIES
Malignancy
 HIV
 Asplenia
 Nephrotic Syndrome

EXTRA CONTENT SPECS
RADIOCONTRAST MEDIA (RCM) REACTION
NonIgE-mediated
 Initially, reactions were believed to be due to the
iodine



But studies have demonstrated that the osmolarity
of the solution is the primary cause
Pre-treating individuals who have a history of
RCM reactions with corticosteroids and a
combination of histamine-1 and histamine-2
antihistamines significantly reduce the risk of
reaction
SKIN TESTING

Indications for skin testing







Severe atopic dermatitis
Allergic rhinitis unresponsive to routine treatment
Food allergy
Asthma triggered by airborne allergens
Vaccine or drug allergy
Latex allergy
Antihistamines alter the results of skin testing
1st and 2nd generation
 Antidepressants with antihistaminic effect


Amitryptiline
IMMUNOTHERAPY

Used to treat allergic rhinitis, allergic asthma,
allergic conjunctivitis, stinging insect
hyepersensitivity


Most effective in treating allergic rhinitis**
There is a risk for anaphylaxis!!
Mandatory 30 minute waiting period after injection
of immunotherapy
 Epinephrine is the treatment


Antihistamines, corticosteroids too
THE END! YAY 