Food, drug, insect sting allergy, and anaphylaxis
The natural history of milk allergy in an observational cohort

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Objective

There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.

Methods

Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion.

Results

The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting.

Conclusions

In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.

Section snippets

Subjects, study definitions, and procedures

The subjects of this study are a subset of a larger cohort of 512 infants originally enrolled at 3 to 15 months of age at 5 sites: Mount Sinai School of Medicine, New York, New York; Duke University Medical Center, Durham, NC; Johns Hopkins University School of Medicine, Baltimore, Maryland; National Jewish Health, Denver, Colorado; and Arkansas Children's Hospital, Little Rock, Arkansas, as described previously17; the North Carolina subjects moved with the investigative team from Duke to the

Results

Of the 512 enrolled infants, the cohort with milk allergy consisted of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Among the remaining 49 children, the diagnosis was categorized as uncertain at their entry visit, but milk allergy was subsequently confirmed. Key baseline characteristics are summarized in Table I. A majority (178/293) of subjects were enrolled between 6 and 12 months of age; 192 were male, and 101 were female. AD was present in 261 subjects and

Discussion

In this report we have described the natural history of milk allergy in a cohort of children enrolled in an observational study with a diagnosis of milk allergy. The study demonstrates a resolution rate of just more than 50% through age 5 years, which falls somewhere in the middle of previously published studies.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16

Review of those prior studies reveals 2 salient points as to why interstudy results can differ so widely. First, results of studies from

References (30)

  • S.H. Sicherer

    Immunologic features of infants with milk or egg allergy enrolled in an observational study (Consortium of Food Allergy Research) of food allergy

    J Allergy Clin Immunol

    (2010)
  • C. Garcia-Ara

    Specific IgE levels in the diagnosis of immediate hypersensitivity to cows' milk protein in the infant

    J Allergy Clin Immunol

    (2001)
  • D.Y. Leung

    Disease management of atopic dermatitis: an updated practice parameter. Joint Task Force on Practice Parameters

    Ann Allergy Asthma Immunol

    (2004)
  • J.S. Kim

    Dietary baked milk accelerates the resolution of cow's milk allergy in children

    J Allergy Clin Immunol

    (2011)
  • J.A. Boyce et al.

    Guidelines for the Diagnosis and Management of Food Allergy in the United States: report of the NIAID-sponsored expert panel

    J Allergy Clin Immunol

    (2010)
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    Supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases grants U19AI066738 and U01AI066560. The project was also supported by grant nos. UL1 RR025780 (National Jewish), UL1 1TR000067 (Mount Sinai), UL 1 TR000039 (Arkansas), UL 1 RR024128 (North Carolina) and UL1 RR 025005 (Johns Hopkins) from the National Center for Research Resources (NCRR), a component of the NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or the NIH.

    Disclosure of potential conflict of interest: R. A. Wood has consultant arrangements with the Asthma and Allergy Foundation of America, is employed by Johns Hopkins University, has received research support from the National Institutes of Health (NIH), and receives royalties from UpToDate. S. H. Sicherer has received grants from the NIH/National Institute of Allergy and Infectious Diseases (NIAID) and has consultant arrangements with the Food Allergy Initiative. B. P. Vickery has received grants and travel support from the NIH/NIAID; has consultant arrangements with Mead Johnson; has received grants from the NIH/NIAID, the Thrasher Research Fund, the American Lung Association, and Cephalon. S. M. Jones is a member of the medical advisory board for the Food Allergy & Anaphylaxis Network (FAAN); has received grants from the NIH, the FAAN, and the National Peanut Board; has received payment for lectures, including service on speakers' bureaus, from Abbott Nutrition International, the Kentucky Society for Allergy, Asthma & Immunology, the New England Allergy Society, the American College of Allergy, Asthma & Immunology, Indiana University Medical School and Riley Children's Hospital, the Spanish Society of Allergy & Clinic Immunology, and the Oregon Allergy Asthma & Immunology Society; has served on the NIAID Safety Monitoring Committee, the Arkansas Medicaid Drug Review Committee, and the NIAID Study Section. D. M. Fleischer has received grants from the NIH/NIAID, has consultant arrangements with Sanofi-Aventis, and receives royalties from UpToDate. A. K. Henning has received grants from the NIH. A. W. Burks has received grants or has grants pending from the NIH, the Department of Defense, and the Wallace Research Foundation; is a board member for the American Academy of Allergy, Asthma & Immunology, the NIH Hypersensitivity, Autoimmune, and Immune-mediated Disease Study Section, the Journal of Allergy and Clinical Immunology, and the US Food and Drug Administration; is on advisory boards for ExploraMed Development, LLC, the FAAN, and ActoGeniX; has consultant arrangements with Merck & Co, Novartis Pharma AG, the Dannon Company, McNeill Nutritionals, and Schering-Plough; is employed by UNC Children's Hospital and Duke University; has received payment for lectures from Mylan Specialty; has received royalties from UpToDate; has received payment for development of educational presentations from Current Views; has stock/stock options in Allertein, Mastcell Pharmaceuticals, and Dow AgroSciences; and has received travel expenses from the European Academy of Allergy & Clinical Immunology. A. Grishin has received grants from the NIH/NIAID and has consultant arrangements with Allertein Therapeutics. D. Stablein has received grants from the NIH. H. A. Sampson has received grants from the NIH and the NIAID, has received travel support from the NIAID, is on the Danone Scientific Advisory Board, has consultant arrangements with Allertein Therapeutics and the Food Allergy Initiative, is employed by Mount Sinai Medical School, and has received royalties from Elsevier-Wiley and UpToDate. The rest of the authors declare that they have no relevant conflicts of interest.

    These authors contributed equally to this manuscript.

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