880 Acid Suppression Restores Impaired Esophageal Mucosal Integrity in Patients With Esophageal Eosinophilia

Abstract

Introduction: Gastroesophageal reflux and allergies are both thought to play a role in the pathophysiology of eosinophilic esophagitis (EoE). It has been suggested that acid-induced esophageal mucosal damage promotes transepithelial allergen flux. Anecdotal evidence suggests that patients with typical signs and symptoms of EoE benefit from acid-suppressive therapy. The aim of our study was to evaluate esophageal mucosal integrity in patients with significant esophageal eosinophilia (SEE) and to study the effects of acid-suppressive therapy with PPI on symptoms, endoscopic signs, mucosal integrity, dilation of epithelial intercellular spaces (DIS), and peak eosinophilia and mastocytosis. Methods: We included 11 untreated adults with SEE (.15 eosinophils/hpf) and predominant symptoms of dysphagia and/or food impaction and typical endoscopic signs of EoE, and 11 controls. All study subjects underwent endoscopy at baseline; in SEE patients endoscopy was repeated after 8 weeks of esomeprazole 40 mg BID. Esophageal mucosal integrity was measured in vivo during endoscopy with a through-the-scope electrical tissue impedance spectroscopy probe (ETIS) at 5 cm proximal of the LES. At the same location, we obtained 2 biopsies for electron microscopic analysis of DIS and 4 biopsies for mucosal integrity experiments in Ussing chambers. In the Ussing chambers, we measured transepithelial electrical resistance (TER) and transmucosal flux of fluorescently-labelled molecules sized 0.3 and 40 kDa (size of food allergens) during 1 hour. In SEE patients, we additionally scored symptoms and endoscopic signs of EoE. Furthermore, eosinophilia and mastocytosis were scored in biopsies taken at the proximal, midand distal esophagus of SEE patients at each endoscopy. Results: Both structural (DIS) and in vivo and in vitro functional measurements (ETIS, TER, and molecule flux) of mucosal integrity showed significant impairment in SEE patients compared to HC (table 1). After acid-suppressive therapy, mucosal integrity was significantly improved in patients with SEE, but still did not reach the levels seen in controls. Esophageal peak eosinophilia andmastocytosis as well as dysphagia and endoscopic signs of EoE also decreased after acid-suppressive therapy. Conclusion: Patients with SEE have an impaired esophageal mucosal integrity, which is partially restored after acid-suppressive therapy. The observed reduction of transmucosal flux of molecules with a similar size as food allergens after acidsuppressive therapy supports the hypothesis that acid-induced mucosal damage facilitates transepithelial food allergen flux, which results in esophageal eosinophilia. Study parameters in HC and SEE patients