Food Allergy Testing in Eosinophilic Esophagitis
Food Allergy Testing in Eosinophilic Esophagitis
Eosinophilic esophagitis (EoE) is a clinicopathologic disease of increasing prevalence in children and adults. The triggering antigen in EoE is often a food that initiates a cascade of Th2-associated interleukins such as interleukin-5 and interleukin-13 and chemokines such as eotaxin-3 as well as esophageal eosinophilia and mastocytosis. Amino acid– based formulas have high efficacy rates in EoE and constitute the first evidence for food-triggered esophageal eosinophilia. Animal models have demonstrated the sufficiency of food antigens in triggering both the inflammatory and remodeling complications of EoE. Food elimination diets that are followed by single food introduction with repeat biopsy have proven the efficacy of empiric and allergy testing based elimination diets in children and adults. Although the ideal allergy test for identifying food antigens in EoE remains to be elucidated, the utility of food skin prick combined with atopy patch testing has been shown in large pediatric cohorts. By comparison, smaller, non-U.S. adult cohorts have not had similar results. Currently, a positive test on food allergy evaluation suggests a food trigger for EoE but does not substitute for biopsy-based tissue evaluation after food removal and reintroduction. The higher rates of food anaphylaxis in children with EoE, potential loss of tolerance to immunoglobulin E–positive foods that can occur with food avoidance, and the high rates of other atopic diatheses in EoE subjects all support the evaluation of EoE subject by an allergist, consideration for allergy testing, and an integrated approach by allergists, gastroenterologists, and pathologists in EoE management.
Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence that affects both children and adults. EoE is a chronic, immune, antigen-mediated disorder with a pathogenesis akin to other allergic diseases such as asthma and eczema in which an antigen induces a cascade of Th2 interleukins (ILs) and chemokines in addition to inflammatory cell infiltration. The diagnosis of EoE relies on the presence of robust esophageal eosinophilia of ≥15 eosinophils per high-power field that persists after a proton pump inhibitor trial. The process is frequently pan-esophageal and accompanied by histologic remodeling inclusive of submucosal fibrosis and angiogenesis, which translates clinically into esophageal rigidity and dysmotility and symptoms of dysphagia. Important molecular factors for eosinophilia and remodeling include IL-5, IL-13, eotaxin-3, and transforming growth factorβ-1.
Food antigens clearly function as antigenic triggers for EoE induction and exacerbation in pediatric and adult populations. In 1995, Kelley et al postulated that acid-resistant esophageal eosinophilia could be due to food antigen exposure in children. On the basis of this hypothesis, these investigators treated children with gastrointestinal symptoms and esophageal eosinophilia with amino acid formula. After a minimum of 6 weeks of treatment, all of the children experienced resolution or improvement of symptoms, with significant reductions in esophageal eosinophilia. Since then, these data have been validated at multiple centers. Indeed, amino acid formulas are one of the most effective EoE therapies, with resolution rates often higher than 96% in children. The removal of all food antigens from the adult diet is also effective in resolving EoE, with improvements in endoscopic and histologic features in 72% of subjects after 4 weeks of treatment.
A second line of evidence in support of food antigens in the pathogenesis of EoE is the clinicopathologic response to specific food elimination in the form of empiric elimination diets. Empiric elimination of specific food groups (milk, egg, soy, wheat, peanuts/tree nuts, fish/shellfish) is highly effective in controlling EoE-associated symptoms, endoscopic abnormalities, and eosinophilia. In children and adults, the empiric elimination diet resolves EoE in more than 60% of subjects. Food antigen elimination can also resolve fibrosis, at least in children. As such, this food elimination diet not only provides a therapeutic remedy in EoE but also provides proof of concept that food antigens are EoE instigators. Further evidence for the sufficiency of food antigens in initiating EoE comes from experimental models in which both peanut and egg exposure can cause the accumulation of eosinophils in the murine esophagus. In these animal model systems, food antigen exposure induces many features of EoE inclusive of basal cell proliferation, esophageal eosinophilia and mastocytosis, and lamina propria remodeling with fibrosis.
Abstract and Introduction
Abstract
Eosinophilic esophagitis (EoE) is a clinicopathologic disease of increasing prevalence in children and adults. The triggering antigen in EoE is often a food that initiates a cascade of Th2-associated interleukins such as interleukin-5 and interleukin-13 and chemokines such as eotaxin-3 as well as esophageal eosinophilia and mastocytosis. Amino acid– based formulas have high efficacy rates in EoE and constitute the first evidence for food-triggered esophageal eosinophilia. Animal models have demonstrated the sufficiency of food antigens in triggering both the inflammatory and remodeling complications of EoE. Food elimination diets that are followed by single food introduction with repeat biopsy have proven the efficacy of empiric and allergy testing based elimination diets in children and adults. Although the ideal allergy test for identifying food antigens in EoE remains to be elucidated, the utility of food skin prick combined with atopy patch testing has been shown in large pediatric cohorts. By comparison, smaller, non-U.S. adult cohorts have not had similar results. Currently, a positive test on food allergy evaluation suggests a food trigger for EoE but does not substitute for biopsy-based tissue evaluation after food removal and reintroduction. The higher rates of food anaphylaxis in children with EoE, potential loss of tolerance to immunoglobulin E–positive foods that can occur with food avoidance, and the high rates of other atopic diatheses in EoE subjects all support the evaluation of EoE subject by an allergist, consideration for allergy testing, and an integrated approach by allergists, gastroenterologists, and pathologists in EoE management.
Introduction
Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence that affects both children and adults. EoE is a chronic, immune, antigen-mediated disorder with a pathogenesis akin to other allergic diseases such as asthma and eczema in which an antigen induces a cascade of Th2 interleukins (ILs) and chemokines in addition to inflammatory cell infiltration. The diagnosis of EoE relies on the presence of robust esophageal eosinophilia of ≥15 eosinophils per high-power field that persists after a proton pump inhibitor trial. The process is frequently pan-esophageal and accompanied by histologic remodeling inclusive of submucosal fibrosis and angiogenesis, which translates clinically into esophageal rigidity and dysmotility and symptoms of dysphagia. Important molecular factors for eosinophilia and remodeling include IL-5, IL-13, eotaxin-3, and transforming growth factorβ-1.
Food antigens clearly function as antigenic triggers for EoE induction and exacerbation in pediatric and adult populations. In 1995, Kelley et al postulated that acid-resistant esophageal eosinophilia could be due to food antigen exposure in children. On the basis of this hypothesis, these investigators treated children with gastrointestinal symptoms and esophageal eosinophilia with amino acid formula. After a minimum of 6 weeks of treatment, all of the children experienced resolution or improvement of symptoms, with significant reductions in esophageal eosinophilia. Since then, these data have been validated at multiple centers. Indeed, amino acid formulas are one of the most effective EoE therapies, with resolution rates often higher than 96% in children. The removal of all food antigens from the adult diet is also effective in resolving EoE, with improvements in endoscopic and histologic features in 72% of subjects after 4 weeks of treatment.
A second line of evidence in support of food antigens in the pathogenesis of EoE is the clinicopathologic response to specific food elimination in the form of empiric elimination diets. Empiric elimination of specific food groups (milk, egg, soy, wheat, peanuts/tree nuts, fish/shellfish) is highly effective in controlling EoE-associated symptoms, endoscopic abnormalities, and eosinophilia. In children and adults, the empiric elimination diet resolves EoE in more than 60% of subjects. Food antigen elimination can also resolve fibrosis, at least in children. As such, this food elimination diet not only provides a therapeutic remedy in EoE but also provides proof of concept that food antigens are EoE instigators. Further evidence for the sufficiency of food antigens in initiating EoE comes from experimental models in which both peanut and egg exposure can cause the accumulation of eosinophils in the murine esophagus. In these animal model systems, food antigen exposure induces many features of EoE inclusive of basal cell proliferation, esophageal eosinophilia and mastocytosis, and lamina propria remodeling with fibrosis.
Source...