Elimination Diet Effectively Treats Eosinophilic Esophagitis in Adults; Food Reintroduction Identifies Causative Factors
Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I
Eosinophilic Esophagitis and Food Allergy
Eosinophilic esophagitis (EoE) is an increasingly recognized syndrome that presents with upper gastrointestinal symptoms in association with hypereosinophilia (> 15 eosinophils/high-power field on esophageal mucosal biopsy). The pathogenesis of EoE is still unknown and is most likely multifactorial. The first of 2 leading hypotheses involves an allergic amelioration of gene expression (eotaxin-3) and cytokine production (interleukin-4, -5, and -13) caused by food and aeroallergen hypersensitivity.
The second potential etiology is acid reflux-related damage to the esophageal epithelial tight junctions. Such damage could increase permeability and lead to recruitment of and exposure to inflammatory cells, especially eosinophils. This can result in structural changes (fibrosis), which may affect the lower esophageal sphincter and peristalsis.
Strong evidence in children suggests that food allergens contribute to the pathogenesis of EoE. In a study of 146 children, Spergel and colleagues found that in nearly 50% of children, a causative food was identified by skin testing. The 6 most common food allergies were dairy, eggs, wheat, soy, peanuts, and fish/shellfish. Diets in pediatric patients have addressed these 6 foods, in a strategy known as the "six-food elimination diet" (SFED). Although dietary management (eg, elemental or restrictive/elimination diets) has been effective in pediatric patients and avoids the risks or effects of steroids or esophageal dilation, it has been hard to extrapolate Spergel and colleagues' findings to adults because they have a much broader dietary selection.
Gonsalves and colleagues conducted a prospective clinical trial from 2006-2010 at a single university medical center in the United States. Fifty adults (25 of whom were men), mean age 40 years (range, 19-76 years), with well-defined EoE underwent baseline endoscopy with biopsy and skin-prick testing for food and aeroallergens. Patients who were receiving proton pump inhibitors at baseline continued to take these agents during the study.
Patients then completed a 6-week course of SFED; if additional food allergies were identified on baseline testing, these foods were avoided as well. Endoscopy was repeated at 6 weeks, followed by a gradual reintroduction of 1 food group every 2 weeks. The order of food reintroduction was individualized by patient preference and allergy testing. Endoscopy with biopsy was repeated after 4 weeks (2 food-group reintroductions) or sooner if the patient became symptomatic. The process was continued until all 6 food groups were reintroduced.
The primary endpoint was histologic improvement in EoE. Secondary endpoints were symptoms and quality-of-life assessments.
After the 6-week SFED, 74% of patients had 15 or fewer eosinophils per high-power field, and 78% had a 50% or greater reduction in peak eosinophil density. Moreover, ki-67, a marker of cell proliferation and epithelial hyperplasia shown to be increased in patients with EoE, was reduced from 53% to 7% (P = .003). Dysphagia scores decreased in 94% of patients (P < .001). Subjectively, endoscopy scores improved in 78%. All procedures were performed by the same endoscopists.
Twenty patients completed the reintroduction portion of the trial, and a causative food agent was found in all. Median time to recurrence of symptoms was 3 days. All recurrences were associated with endoscopic and histologic indicators of relapse. The most common food triggers were wheat (60%), milk (50%), soy (10%), nuts (10%), and egg (5%). In no patient was seafood defined as a trigger.
Three patients had more than 1 food trigger. In only 13% of patients was the trigger identified by skin-prick testing, and 67% of those in whom a trigger was identified during the reintroduction process had negative skin-prick testing to all foods.
This is an important study because it provides new evidence that dietary modification therapy, which is effective in pediatric EoE, is also effective in adults. The remarkable improvements achieved by dietary restriction also provide new insight into the pathogenesis of EoE, supporting a food-driven component. Clearly, from this study, wheat and milk were the leading associations. The rapid recurrence of symptoms and endoscopic and histologic findings add further support to the causal association.
The study also shows that short-term dietary restriction does not cure EoE and that long-term treatment is probably necessary, although no data are available yet on this for adult patients. Such studies are anxiously awaited to show the durability of effect. Finally, skin-prick testing for identification of food allergens seems to have little value, at least in the adult population.
Although many patients with EoE respond to simply adding a proton pump inhibitor, in this study, most were already taking these agents. The SFED seems to be the next logical step in the management of patients with EoE who are not responding to proton pump inhibitors, before considering steroid options.
Medscape Gastroenterology © 2012 WebMD, LLC
Cite this: David A. Johnson. The Food-Elimination Diet in Adult Eosinophilic Esophagitis - Medscape - Aug 08, 2012.