REVIEWERS COMMENTS. For breastfed infants with food al- REVIEWERS COMMENTS. Previous attempts have been made to lergy, strict avoidance of the offending food proteins for establish wheat IgE levels that would predict clinical both mother and child is frequently recommended. Total reactivity and prognosis. This study, in attempting to do dietary avoidance of egg is difficult for patients to that, included the largest population of wheat-allergic achieve. Additional study is needed to substantiate or to patients that has yet been described. Patients were in- refute the preliminary observation that regular maternal cluded on the basis of a retrospective chart review and, ingestion of a small quantity of well-cooked egg did not because the inclusion criteria did not require an oral markedly exacerbate eczema symptoms in egg-sensitive food challenge, it is possible that at the time of initial breastfed infants. enrollment some of the patients were no longer allergic to wheat. Tolerance was appropriately determined by URL: www.pediatrics.org/cgi/doi/10.1542/peds.2009-1870X food challenge; however, not all patients were chal- Karla L. Davis, MD lenged. This might have been because a patient had a Stephen E. Scranton, MD convincing reaction after an unintentional exposure to Landstuhl, Germany wheat, but the authors did not make that clear. In ad- dition, some patients had ingestion reactions while try- ing wheat at home, which, as the authors acknowl- edged, raises the possibility that wheat allergy was The Natural History of Wheat Allergy overdiagnosed. Another limitation is that the population Keet CA, Matsui EC, Dhillon G, Lenehan P, (in which 90% of the children included had other food Paterakis M, Wood RA. Ann Allergy Asthma Immunol. allergies) might not be representative of the general population. The authors found that peak wheat-specific 2009;102(5):410–415 IgE levels were helpful in determining prognosis. How- PURPOSE OF THE STUDY. Wheat allergy is among the most ever, in clinical practice, it is difficult to determine common of food allergies, affecting ϳ0.4% of children, whether the peak wheat-specific IgE level for an indi- but little is known about its natural history. The purpose vidual patient has been reached. Because some patients of this study was to determine at what age wheat allergy with higher specific IgE levels do tolerate wheat, the is outgrown and to identify clinical and laboratory pre- authors acknowledge that wheat IgE is less helpful in dictors of tolerance development. predicting clinical reactivity and prognosis, compared with other foods. STUDY POPULATION. Participants were children from the Johns Hopkins pediatric allergy clinic who had a history of symp- URL: www.pediatrics.org/cgi/doi/10.1542/peds.2009-1870Y tomatic reaction (presumed immunoglobulin E [IgE] Mariah M. Pieretti, MD mediated) to wheat and a positive wheat-specific IgE test Kirsi M. Ja¨rvinen, MD, PhD result. Inclusion criteria were met by 103 children. New York, NY

METHODS. The study was a retrospective, medical record review. Resolution of allergy was determined by the results of food-challenge testing. Kaplan-Meier survival High Levels of IgG4 Antibodies to Foods curves were generated to depict resolution of wheat During Infancy Are Associated With Tolerance allergy. to Corresponding Foods Later in Life Tomicic´S, Norrman G, Fa¨lth-Magnusson K, Jenmalm RESULTS. The median initial wheat-specific IgE level was MC, Devenney I, Bo¨ttcher MF. Pediatr Allergy Immunol. 24 kU/L, and the median peak wheat-specific IgE level 2009;20(1):35–41 was 73 kU/L. Rates of resolution of wheat allergy were 29% by the age of 4 years, 56% by the age of 8 years, PURPOSE OF THE STUDY. To examine the serum and salivary 65% by the age of 12 years, and 70% by the age of 14 antibody responses to food-elimination diets and to iden- years. Higher wheat-specific IgE levels were associated tify immunologic parameters related to oral tolerance. with worse outcomes. A total of 63 of 103 participants STUDY POPULATION. Prospective study of 89 children Ͻ2 years underwent a food challenge during the study period. of age with eczema. The peak wheat-specific IgE level recorded was a useful predictor of persistent allergy, although many children METHODS. Children with eczema were examined at 3 time with even the highest levels of wheat IgE outgrew wheat points, that is, at enrollment, after a 6-week treatment allergy. period, and at 4.5 years of age. Treatment included top- ical emollients and/or steroids for all children and a CONCLUSIONS. The median age of resolution of wheat al- 6-week egg- and/or milk-elimination diet for 60 of the lergy was 6.5 years in this population. However, 35% of 89 children in the cohort of children who were diag- the patients remained allergic into their teenage years. nosed with an allergy to 1 or both foods. Laboratory data

PEDIATRICS Volume 124, Supplement 2, November 2009 S121 Downloaded from www.aappublications.org/news by guest on September 27, 2021 included skin-prick testing (SPT) to food allergens; total The Use of Serum-Specific IgE Measurements and specific serum immunoglobulin E (IgE) levels; se- for the Diagnosis of Peanut, Tree Nut, and rum IgA, IgG1, and IgG4 antibodies to ovalbumin and Seed Allergy ␤-lactoglobulin; total IgA levels; and saliva IgA levels. At Maloney JM, Rudengren M, Ahlstedt S, Bock SA, study completion, children were categorized as being Sampson HA. J Allergy Clin Immunol. 2008;122(1): egg or milk tolerant if the food was reintroduced into 145–151 the diet after passage of a challenge in the clinic or at PURPOSE OF THE STUDY. The authors of this study sought to home. determine the usefulness of peanut-, tree nut–, and RESULTS. Of the 89 participating children, 60 were pre- seed-specific immunoglobulin E (IgE) measurements for scribed elimination diets that were based on SPT results, the diagnosis of symptomatic allergies and to learn more as follows: 24 egg, 11 milk, and 25 both. At study com- about the relationships among these foods. pletion (4.5 years of age), 37 of 49 previously egg- STUDY POPULATION. Children and adults (N ϭ 324) referred allergic and 11 of 36 previously milk-allergic children to a private allergy practice and to an academic center were considered to be tolerant. Children who were egg allergy clinic for evaluation of suspected IgE-mediated or milk tolerant at 4.5 years of age had significantly peanut, tree nut, or seed (sesame seed, mustard seed, higher levels of ovalbumin- or ␤-lactoglobulin–specific poppy seed, rapeseed, and cottonseed) hypersensitivity IgG at enrollment, respectively. Tolerant children also 4 were enrolled in the study. Patients ranged in age from had higher food-specific IgG /IgE ratios at 4.5 years. 4 2.4 months to 40.2 years (median: 6.1 years). The male/ The highest IgG /IgE ratios were found in children who 4 female ratio was 198:126. Atopic dermatitis occurred at had circulating milk- and/or egg-specific IgE antibodies some point in life in 57% and asthma in 58%. Many had but negative SPT results at enrollment. There was no or “outgrew” other food allergies. significant difference between total or food-specific IgE levels at enrollment between the tolerant and non- METHODS. Patients answered a questionnaire about their tolerant groups; however, children in the tolerant group perceived food allergies. Allergen-specific diagnoses had significantly lower food-specific IgE antibodies at were based on questionnaire, medical history, and, 4.5 years, compared with those in the nontolerant when relevant, skin-prick test results and serum-specific group. There were no significant differences in total IgA, IgE levels. Sera were analyzed for specific IgE to peanuts, saliva IgA, or food-specific IgA levels between groups at tree nuts, and seeds by ImmunoCAP (Phadia AB, Upp- enrollment or at 4.5 years. sala, Sweden).

Ͻ RESULTS. CONCLUSIONS. High food-specific IgG4 antibodies at 2 Seventy-two percent of the patients had convinc- years of age and high IgG4/IgE ratios were related to oral ing histories of peanut allergy. Of these, 86% had sen- tolerance to milk and egg at 4.5 years of age. sitization to Ն1 tree nut, with 34% having clinical al- lergy. The majority of study patients had never ingested REVIEWER COMMENTS. This study demonstrates that early im- tree nuts, which made it difficult to determine the true munologic markers may be indicators of oral tolerance prevalence of these nut allergies. Tree nut clinical allergy acquisition among a subset of children with eczema and occurred with a frequency ranging from 16.4% for wal- milk and/or egg allergy. These data may be useful in nut to 1.5% for Brazil nut. Seventeen percent of the conjunction with other measures such as serum-specific patients reported reactions to sesame seed. The ranges of IgE levels, history of past reactions, and SPT to predict increased serum-specific IgE levels for each food varied future oral tolerance acquisition. One weakness of the widely among patients with positive histories. The rela- study was the fact that participants did not undergo a tionship between diagnoses and allergen-specific IgE diagnostic food challenge to confirm clinical reactivity at levels was estimated through logistic regression, with enrollment, and recommendations for food elimination curves illustrating the likelihood of receiving a positive were made on the basis of SPT results. It is likely that clinical diagnosis in relation to the specific IgE concen- elimination diets were prescribed for some participants tration. Positive predictive values (95%) were estab- who were actually clinically tolerant at enrollment de- lished for peanut and walnut (13 and 18.5 kUA/L, re- spite having a positive SPT result. Future studies to de- spectively) but with sensitivities of just 60% and 17%, termine the utility of immunologic markers should con- respectively. High correlations were found between IgE firm clinical reactivity by performing a diagnostic food results for walnut and pecan and between those for challenge or confirming a convincing history of past cashew and pistachio. reactions. CONCLUSIONS. Quantification of food-specific IgE is a valu- URL: www.pediatrics.org/cgi/doi/10.1542/peds.2009-1870Z able tool that can aid in the diagnosis of symptomatic Tamara T. Perry, MD food allergy and might decrease the need for double- Little Rock, AR blind, placebo-controlled, food challenges.

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Downloaded from www.aappublications.org/news by guest on September 27, 2021 High Levels of IgG4 Antibodies to Foods During Infancy Are Associated With Tolerance to Corresponding Foods Later in Life Tamara T. Perry Pediatrics 2009;124;S121 DOI: 10.1542/peds.2009-1870Z

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