Savage JH, Matsui EC, Skripak JM, Wood RA. J Allergy Clin Immunol. 2007;120(6):1413–1417 PURPOSE OF THE STUDY. To estimate the proportion of children with egg allergy who develop egg tolerance and to identify predictors of tolerance development. STUDY POPULATION. Subjects were 881 egg-allergic children identified by chart review from an academic allergy practice. Egg allergy was defined as a clear history of immunoglobulin E (IgE)–mediated allergic reaction to egg ingestion or an egg-specific IgE level of >2 kU/L without known tolerance. METHODS. Information was collected and included demographics, symptoms at egg-allergy diagnosis, presence of other atopic diseases and food allergies, dietary history, age/symptoms with egg exposure, egg skin-prick tests, egg-specific IgE, oral food challenge results, and outcome of egg and other food allergies. Three definitions were used to define oral tolerance to egg in all 881 subjects: definition 1 included those children who passed a formal oral food challenge or had successful home introduction of egg; definition 2 included children who met definition 1 and had an egg-specific IgE level of <2 kU/L and no reaction within the previous year; and definition 3 included children who met definition 2 but had an egg-specific IgE level of <6 kU/L. RESULTS. Of the 881 subjects, the median age at the initial visit was 14 months, and median follow-up was 4.9 years with 68% male subjects. Most (93%) had at least 1 other food allergy, 54% had asthma, 55% had allergic rhinitis, and 81% had eczema. Of 881 subjects, 375 (43%) had a documented history of allergic reaction to egg and evidence of egg sensitization. The other 506 subjects were included on the basis of an egg-specific IgE level of >2 kU/L. When defined by the most conservative definition (definition 1), 4% outgrew their egg allergy by 4 years of age, 26% by 8 years of age, 48% by 12 years of age, and 68% by 16 years of age. Using definition 2, 11% were tolerant at 4 years of age, 41% by 8 years of age, 65% by 12 years of age, and 82% by 16 years of age. Using definition 3, 19% developed tolerance by 4 years of age, 55% by 8 years of age, 76% by 12 years of age, and 91% by 16 years of age. When the relationship of peak egg IgE levels and the development of tolerance was examined, children with a peak IgE level of <2 kU/L had the fastest rate of tolerance development, those with a peak IgE level between 2 and 49.9 kU/L developed tolerance at a much slower rate, and those with a peak IgE level of >50 kU/L were the slowest and generally did not develop tolerance. The median time to tolerance was higher in children with other atopic disease (eg, 13.5 years for asthmatic children versus 8.5 years for nonasthmatic children [P < .001]; 12.6 years with rhinitis versus 11.8 years without rhinitis [P < .001]; 12.3 years with eczema versus 11.1 years without eczema [P = .055]). CONCLUSIONS. This study supports the general idea that most children with egg allergy will eventually outgrow their allergy, but at an older age than previously implicated. Egg-specific IgE levels are predictive of tolerance development, and the presence of other atopic disease delays the process. REVIEWER COMMENTS. This study provides the largest comprehensive natural-history evaluation of children with egg allergy. The work done by this group serves to highlight the importance of specific IgE measurements in children with egg allergy and is very useful for our overall understanding of the delayed development of tolerance. This information is very helpful for anticipatory guidance and disease management of children with egg allergy.