BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given offlabel. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n ¼ 59) or placebo (n ¼ 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity 2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label Gastroenterology 2019;157:74-86 CLINICAL AT treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

During the natural course of EoE, progression from an inflammatory to a fibrostenotic phenotype occurs. With each additional year of undiagnosed EoE the risk of stricture presence increases with 9%.

Using the EREFS, endoscopic signs of eosinophilic esophagitis were scored consistently by expert and trainee endoscopists.

SummaryBackgroundEosinophilic oesophagitis (EoE) is a chronic disease, driven by food allergens. Elemental diets are effective for the management of children with EoE, but studies on the effect of elemental diets in adults are scarce and poor palatability challenges dietary adherence.AimTo assess the effects of an elemental diet (Neocate, Nutricia, Utrecht, the Netherlands) on the inflammation, symptoms and endoscopic signs in adult EoE patients.MethodsIn this prospective study, 21 patients with active EoE, confirmed by biopsies showing ≥15 eosinophils per microscopic high power field (HPF) and symptoms of oesophageal dysfunction were included. Patients underwent endoscopy before and 4 weeks after diet. Histological disease activity (peak eosinophil count/HPF), and endoscopic signs were scored by physicians. Symptoms and adherence to the diet were evaluated by questionnaires. Serum total IgE levels and total eosinophil counts were determined and the expression of inflammatory cytokines was analysed by qPCR.ResultsIn total, 17 (81%) of the patients completed the diet, of whom 12 (71%) showed complete histological response (≤15 eosinophils/HPF) and 4 (24%) showed partial histological response (≥50% reduction of baseline eosinophil count). Peak eosinophil counts decreased significantly after the diet from 40 to 9 per HPF (P ≤ 0.001). A marked improvement in endoscopic signs was observed. Symptoms decreased significantly in all subjects, and 15 patients (88%) became completely asymptomatic (P ≤ 0.001). In 14 patients (82%), blood eosinophil count and serum IgE decreased (P ≤ 0.05).ConclusionElemental diet reduces eosinophilic inflammation and induces clinical remission in adult patients with eosinophilic oesophagitis.

Current evidence supports the use of the EoEHSS and EREFS as measures of histologic and endoscopic EoE disease activity, respectively, and the EEsAI, DSQ, or Pediatric Quality of Life Inventory EoE as measures of adult and pediatric symptoms. Additional research is needed to optimize endpoint configuration to facilitate development of new therapies.

Objectives:The esophageal mucosal integrity is impaired in eosinophilic esophagitis (EoE) and it has been suggested that the duodenal permeability is increased. The absence of food allergens may restore the integrity. The aims of this study were to assess duodenal permeability in EoE and to evaluate the effect of an elemental diet on the esophageal and duodenal integrity.Methods:In this prospective study 17 adult EoE patients and 8 healthy controls (HC) were included. Esophageal biopsy specimens were sampled before and after 4 weeks of elemental diet to measure eosinophil counts and gene expression of tight junction and barrier integrity proteins. Esophageal and duodenal impedance were measured by electrical tissue impedance spectroscopy and Ussing chambers were used to measure transepithelial resistance (TER) and transepithelial molecule flux. Small intestinal permeability was measured using a test, measuring lactulose/mannitol (L/M) ratios.Results:In EoE patients, the esophageal but not the duodenal integrity was impaired, compared with HC. We observed no significant difference between L/M ratios of HC and EoE patients. After diet, eosinophil counts decreased significantly, which was paralleled by normalization of esophageal impedance and transepithelial molecule flux. The esophageal TER improved significantly, but did not reach values seen in HC. Esophageal expression of genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was impaired at baseline and restored after diet.Conclusions:An elemental diet restores esophageal integrity, suggesting that it is at least partly secondary to allergen exposure. Duodenal integrity seems not to be affected in EoE, and possibly plays a minor role in its pathophysiology.

Background The incidence of eosinophilic esophagitis (EoE) has increased rapidly. Most epidemiologic data were gathered in single‐center studies over a short timeframe, possibly explaining the heterogeneous incidences. Aim The aim of this study was to retrospectively estimate the Dutch nationwide incidence of EoE over the last 20 years. Methods The Dutch pathology registry (PALGA) was queried to identify pathology reports describing esophageal eosinophilia from 1996 to 2016. Cases were eligible if EoE was confirmed by the pathologist. Using the annual Dutch population data, the incidence of EoE was calculated. Key Results The search yielded 11 288 reports of which 5080 described esophageal eosinophilia. Eosinophilic esophagitis was diagnosed in 2161 patients, 1574 (73%) males and 365 (17%) children. The incidence increased from 0.01 (95% CI 0‐0.02) in 1996 to 2.07 (95% CI 2.05‐2.23) per 100 000 inhabitants in 2015. The incidence was higher in males than in females, 3.02 (95% CI 2.66‐3.41) vs 1.14 (95% CI 0.93‐1.38), odds ratio (OR) 2.66 (95% CI 2.10‐3.36) and higher in adults than in children, 2.23 (95% CI 1.99‐2.49) vs 1.46 (95% CI 1.09‐1.91), OR 1.78 (95% CI 1.32‐2.40). Incidence of EoE increased more than 200‐fold, whereas endoscopy rates only tripled, from 30 in 1996 to 105 per 100 000 inhabitants in 2015. We observed no seasonal variation. Conclusions and Inferences In the last decades, the Dutch EoE incidence has increased tremendously and still continues to rise. This expansion is only partially driven by increased endoscopy rates.

SummaryBackground: The validity of the eosinophilic oesophagitis (EoE) histologic scoring