Food allergy: Update on prevention and tolerance

Abstract

Of the many possible hypotheses that explain the recent increase in childhood food allergy (FA), the dual-allergen exposure hypothesis has been the most extensively investigated. This chapter serves as a review and update on the prevention of FA and focuses on recently published randomized controlled trials exploring the efficacy of oral tolerance induction in infancy for the prevention of FA. As a result of these RCTs, National Institutes of Health recommendations now actively encourage the early introduction of peanut for the prevention of peanut allergy, and other countries/settings recommend the inclusion of potential common food allergens, including peanut and egg, in complementary feeding regimens commencing at approximately 6 months but not before 4 months of age. Further studies that explore the efficacy of oral tolerance induction to other common food allergens and that focus on optimal timing, duration, and adherence are required.

Keywords: Food allergy; allergy prevention; egg allergy; peanut allergy.

FIG 1.

Integration of the vitamin D deficiency, hygiene, and dual-allergen exposure hypotheses. Sufficient levels of vitamin D, a diverse microbiota, and oral allergen exposure support the development of tolerance. Conversely, allergic sensitization is promoted through cutaneous exposure, reduced diversity of the microbiota, and vitamin D deficiency. Diminished microbial diversity and vitamin D deficiency are thought to interrupt the regulatory mechanisms of oral tolerance, with the latter also contributing to decreased epidermal barrier function. GI, Gastrointestinal; T-reg, regulatory T cells. Graphic modified from Lack. Copyright © 2008 Elsevier. Reprinted with permission.

FIG 2.

LEAP study primary outcome findings. A and B, The prevalence of peanut allergy at 60 months of age is shown among participants with a negative SPT response at baseline, among participants with a positive response at baseline, and in both groups combined in the ITT (Fig 2, A) and per-protocol (Fig 2, B) analyses. Among the 640 participants who underwent randomization, peanut allergy status was determined by means of an oral food challenge in 617 (96.4%) and by means of a diagnostic algorithm in 11 (1.7%). Peanut allergy could not be evaluated by using the diagnostic algorithm in 2 participants (0.3%). A total of 10 participants (1.6%) withdrew voluntarily or were lost to follow-up. C, The worst-case imputation analysis assumes that participants with missing data in the peanut consumption group would have been allergic to peanuts and that participants with missing data in the peanut avoidance group would have been nonallergic. P values are based on χ² analyses. From Du Toit et al. Copyright © 2015 Massachusetts Medical Society. Reprinted with permission from the Massachusetts Medical Society.

FIG 3.

EAT study outcome findings. The prevalence of IgE-mediated FA is shown with respect to 1 or more of the 6 early intervention foods (peanut, cooked egg, cow’s milk, sesame, whitefish, and wheat; A), to peanut (B), and to egg (C). The first column shows the ITT analysis, the second column shows the per-protocol analysis, and the third column shows an adjusted per-protocol analysis. The ITT analysis included all the participants with data that could be evaluated; the per-protocol population included all participants who adhered adequately to the assigned regimen. The adjusted per-protocol analysis was a conservative per-protocol analysis that adjusted the prevalence of FA in the standard introduction group by subtracting the number of participants in the early introduction group with a positive result on the challenge at enrollment and who completed the trial with a confirmed FA from both the numerator (number of participants with allergy in the standard introduction group) and the denominator (number of participants in the standard introduction group who adhered to the protocol). P values are based on χ² analyses or the Fisher exact test, as appropriate. From Perkin et al. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

FIG 4.

EAT dose-response analysis of the relationship between mean weekly dose of peanut or egg protein consumed and allergy or positive result on SPTs to peanut, egg, and raw egg white. Shown are predictive probability plots generated from statistical models of the prevalence of peanut and egg allergy (A) and of positive SPT responses to peanut and egg at 12 months (B) and to peanut, egg, and rawegg white at 36 months (C), according to the mean weekly consumption of peanut and egg protein between enrollment and 6 months of age. The prevalence of both FA and a positive SPT response diminishes with increasing levels of mean weekly consumption. Insets show the same data on an enlarged y-axis. From Perkinetal. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

FIG 5.

Changes that occur with IgE and IgG levels and IgE/IgG₄ ratios over time in children who consumed or avoided peanuts in the frame of the LEAP and LEAP-On studies. From Du Toit et al. Copyright © 2016 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.