CONCLUSIONS. Milk allergy is highly prevalent among the US
pediatric population, accounting for one-fifth of all food
allergies. Nearly one-third of these children present with
severe symptoms. Diagnostic testing is being performed
in less than half of the children. There is a significant
ethnic variation in milk allergy.
2.09). The authors use these 3 baseline characteristics to
calculate a composite score for prediction of an individual
patient’s likelihood of milk allergy resolution. Baseline
characteristics that were not significant predictors of
resolution included milk-specific IgG 4, milk-specific
IgE/IgG 4 ratios, and casein-stimulated T-cell studies.
REVIEWER COMMENTS. This study presents some interesting
CONCLUSIONS. This longitudinal, multisite prospective co-
epidemiologic data on milk allergy in the United States.
Confirmatory testing is not often performed, and many of
these children may be incorrectly diagnosed, leading to
unnecessary avoidance and dietary restrictions.
hort study provides a natural history of food allergy over
a follow-up period of ∼5 years. Approximately 50% of
children with milk allergy will experience resolution by
5 years of age. Milk-specific IgE, SPT wheal size, and AD
severity at baseline are significant predictors of likelihood
of resolution.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.2013–2294Z
Paul V. Williams, MD
Seattle, WA
The Natural History of Milk Allergy in an
Observational Cohort
Wood RA, Sicherer SH, Vickery BP, et al; for the
Consortium of Food Allergy Research. J Allergy Clin
Immunol. 2013;131(3):805–812
PURPOSE OF THE STUDY. Previous studies on the natural history
of milk allergy have been limited in duration and in geographic area. Through this multisite, longitudinal study, the
authors provide a natural history of milk allergy and identify
means for early prediction of likelihood of resolution.
REVIEWER COMMENTS. The exceptional follow-up rate supports
the validity of the findings, the large size of the cohort and
use of multiple sites strengthen its generalizability, and the
length of follow-up and identification of significant
predictors of milk allergy resolution highlight the utility
of the study. Additional investigation may more rigorously
identify age at resolution through food challenges at
regular intervals and may focus on identifying additional
modifiers in resolution of milk allergy, particularly ingestion of baked milk products at the start of and during the
study period.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.2013–2294AA
Elizabeth J. Feuille, MD
Anna H. Nowak-We˛ grzyn, MD
New York, NY
STUDY POPULATION. Children aged 3 to 15 months were re-
cruited from 5 food allergy referral centers, using the
following inclusion criteria: history of immediate allergic
reaction to cow’s milk or egg with positive skin-prick test
(SPT) to the inciting food; or moderate-to-severe atopic
dermatitis (AD) with positive SPT to either milk or egg.
METHODS. The children in this cohort with milk allergy,
diagnosed either at time of enrollment or during the
study, were followed over time. At enrollment, investigators assessed baseline characteristics (more detail in
the next section). Participants were again assessed at
6 months and yearly thereafter, with more frequent
follow-up as needed. Resolution of milk allergy was
established by ingestion of whole uncooked milk products
without reaction. Analyses were performed to assess the
effect of various baseline characteristics on likelihood of
resolution of milk allergy.
RESULTS. Of 293 children in the cohort diagnosed with milk
allergy, 154 (53%) participants experienced resolution of
milk allergy at a median age of ∼5.3 years and a median
age at last follow-up of 5.5 years. Baseline characteristics
most predictive of milk allergy resolution, all with
P values ,.001, were milk-specific immunoglobulin (Ig)E
(,2 vs $10 kUA/L with hazard ratio 5.7), SPT wheal size
(,5 vs .10 mm with hazard ratio 3.7), and severity of AD
(mild/none versus moderate/severe with hazard ratio
S18
BEST ARTICLES RELEVANT TO PEDIATRIC ALLERGY AND IMMUNOLOGY
Natural Course and Risk Factors for Persistence
of IgE-Mediated Cow’s Milk Allergy
Elizur A, Rajuan N, Goldberg MR, Leshno M, Cohen A,
Katz Y. J Pediatr. 2012;161(3):482–487, e1
PURPOSE OF THE STUDY. To describe the natural course of
immunoglobulin (Ig)E-mediated cow’s milk (IgE-CMA)
and the risk factors for its persistence in a prospective
population-based study.
STUDY POPULATION. There were 54 infants identified with
IgE-CMA from a population of 13 019 who were recruited
and completed the study from the Assaf-Harofeh Hospital
in Israel. This occurred during a 2-year period between
June 2004 and June 2006. The children were followed
from birth until 4 to 6 years.
METHODS. Diagnosis of IgE-CMA was done based on history, skin-prick test, and an oral food challenge. These
infants were followed for 48 to 60 months with families
being contacted every 6 months to ask about exposures
and reactions to milk. Children were invited to return
annually for an oral food challenge for potential recovery
unless an adverse reaction occurred within the preceding 3
months or they had already been exposed to milk without
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any adverse events. Statistical analysis was done through
SPSS software (IBM SPSS Statistics, IBM Corporation,
Chicago, IL).
RESULTS. Thirty-one infants (57.4%) recovered from IgECMA, most recovering within the first 2 years
(70.9%). Risk factors for persistence of milk allergy
included clinical reactions to ,10 mL of milk on oral
food challenge or on first exposure as determined by
guardian, larger wheal size on skin testing with 6 mm as
the cutoff determined to best differentiate between
transient and persistent allergy, and an age of ,30
days at time of first reaction.
CONCLUSIONS. Resolution occurs in most infants with IgE-
CMA, but infants who react to ,10 mL of milk, react
within the first month of life, or have a wheal size larger
than 6 mm are at increased risk for persistence of milk
allergy.
REVIEWER COMMENTS. This study helps to describe the clinical
factors that can help the clinician counsel parents on the
persistence of IgE-CMA. It does not, however, also describe whether the severity of reaction changes with
this persistence. Continued studies to further delineate
these factors will be of great benefit to parents with
children who have milk allergy.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.2013–2294BB
Sandy Jung-Wu, MD
Los Angeles, CA
Allergic Reactions to Foods in Preschool-Aged
Children in a Prospective Observational Food
Allergy Study
Fleischer D, Perry T, Atkins D, et al. Pediatrics. 2012;130
(e25):25–32
PURPOSE OF THE STUDY. To determine the frequency and
circumstances of allergic reactions to common food
allergens in a multicenter, prospective study of preschoolaged children.
STUDY POPULATION. The cohort examined was already
details about the occurrence of an immunoglobulin
E–mediated reaction, including symptoms and time of
occurrence, trigger, route of exposure (accidental versus
purposeful), and response to reaction.
RESULTS. Over the median follow-up of 36 months,
annualized reaction rate was 0.81 per year for all foods
(367/512 subjects reporting 1171 reactions) with 56%
reporting .1 reaction. Most were triggered by milk
(42.0%), egg (21.0%), and peanut (7.9%). Most (64.9%)
accidental allergic reactions were attributed to lack of
vigilance (eg, label-checking errors and unintentional
ingestion). Additional errors included cross-contact in
meal preparation and food not provided by actual
caregivers. Approximately 11% of reactions were
attributed to nonaccidental exposure. Of the 11.4% of
reactions that were severe, only 29.0% of them were
treated with epinephrine because the caregiver did not
recognize the severity, the epinephrine was unavailable,
or the caregiver was afraid to administer it.
CONCLUSIONS. Because of the high frequency of reactions in
preschool-aged subjects, there needs to be an emphasis
on improving education in the parent and other
caregivers about exposure prevention and anticipatory
guidance. The education needs to include indications
for epinephrine use and proper technique, as well as
potential complications.
REVIEWER COMMENTS. This novel prospective, observational
study used a large cohort of preschool-aged children.
The number of purposeful exposures and the lack of
vigilance, despite initial anticipatory guidance, is
remarkable. This article emphasizes the importance of
providing patients and all caregivers with anticipatory
guidance at every clinic visit and reviewing their knowledge of the potential reaction on exposure. It is very important to emphasize the need for supervision, label reading,
possible dangers of unsupervised allergen reintroduction,
and the symptoms that warrant treatment with epinephrine. The study is limited by parental bias in reporting reaction and circumstances, as well as recall bias.
URL: www.pediatrics.org/cgi/doi/10.1542/peds.2013–2294CC
participating in an observational study to monitor for
development of peanut allergy in patients with history of milk/egg allergy. There were 512 infants
enrolled between the ages of 3 and 15 months from
5 US sites.
METHODS. In a prospective, 5-site observational study,
subjects were scheduled for a clinical evaluation at 6month intervals for 2 visits, then yearly with telephone
contacts between each visit. Baseline immunoglobulin E
to specific allergen was also obtained. Written and verbal
specific food allergen avoidance instructions, along with
treatment plans with prescriptions for self-injectable epinephrine were provided. A 36-item questionnaire obtained
Poneh Davoodi, MD
William K. Dolen, MD
Augusta, GA
Oral Immunotherapy for Treatment of Egg
Allergy in Children
Burks AW, Jones SM, Wood RA, et al; Consortium of Food
Allergy Research (CoFAR). N Engl J Med. 2012;367
(3):233–243
PURPOSE OF THE STUDY. To determine that oral immunotherapy (OIT) to egg is safe and effective to desensitize
patients and induce sustained unresponsiveness.
PEDIATRICS Volume 132, Supplement 1, October 2013
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S19
Natural Course and Risk Factors for Persistence of IgE-Mediated Cow's Milk
Allergy
Sandy Jung-Wu
Pediatrics 2013;132;S18
DOI: 10.1542/peds.2013-2294BB
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Natural Course and Risk Factors for Persistence of IgE-Mediated Cow's Milk
Allergy
Sandy Jung-Wu
Pediatrics 2013;132;S18
DOI: 10.1542/peds.2013-2294BB
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/132/Supplement_1/S18.2.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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