Consensus diagnostic recommendations to distinguish gastro-oesophageal reflux disease (GORD) from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPI) unexpectedly uncovered an entity called “PPI-responsive oesophageal eosinophilia” (PPI-REE). PPI-REE refers to patients with clinical and histologic features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that PPI-REE and EoE patients at baseline are clinically, endoscopically and histologically indistinguishable, and have significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in PPI-REE patients, similar to the effects of topical steroids in EoE patients. Additionally, recent series have reported that EoE patients responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunologic mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic, and therapeutic features cannot be reliably distinguished. For patients with symptoms and histologic features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment, before diet and topical steroids. The reasons why some EoE patients respond to PPI, while others do not, remain to be elucidated.

BACKGROUND & AIMS Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings. METHODS We collected information from 186 patients with EoE in Switzerland and the US (69.4% male; median age, 43 years) via surveys (n = 135), focus groups (n = 27), and semi-structured interviews (n = 24). Items were generated for the instruments to assess biologic activity based on physician input. Linear regression was used to quantify the extent to which variations in patient-reported disease characteristics could account for variations in patients’ assessment of EoE severity. The PRO instrument was prospectively used in 153 adult patients with EoE (72.5% male; median age, 38 years), and validated in an independent group of 120 patients with EoE (60.8% male; median age, 40.5 years). RESULTS Seven PRO factors that are used to assess characteristics of dysphagia, behavioral adaptations to living with dysphagia, and pain while swallowing accounted for 67% of the variation in patients’ assessment of disease severity. Based on statistical consideration and patient input, a 7-day recall period was selected. Highly active EoE, based on endoscopic and histologic findings, was associated with an increase in patient-assessed disease severity. In the validation study, the mean difference between patient assessment of EoE severity and PRO score was 0.13 (on a scale from 0 to 10). CONCLUSIONS We developed and validated an EoE scoring system based on 7 PRO items that assesses symptoms over a 7-day recall period. Clinicaltrials.gov number: NCT00939263.

Background Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing two entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen–driven, Th2-associated allergic disorder, whereas the etiology of PPI-REE remains a mystery. Objective In this study, our aim was to investigate the pathogenesis of PPI-REE using a recently described esophageal based EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts, and to determine if PPI therapy reverses any esophageal transcriptional abnormalities. Methods We evaluated the EDP signature in biopsy samples obtained from adult and pediatric PPI-REE subjects from four institutions and compared the pre and post PPI therapy expression profiles of these subjects with those of active EoE subjects. Results The EDP identified EoE from control subjects with 100% accuracy amongst the four clinical sites. Bioinformatic analysis revealed largely overlapping transcriptomes between PPI-REE and EoE, including the genes for eosinophil chemotaxis (CCL26), barrier molecules (DSG1), tissue remodeling (POSTN), and mast cells (CPA3). After PPI-mono therapy, PPI treatment alone almost completely reversed the allergic inflammatory transcriptome of PPI-REE. Furthermore, we identified a set of candidate genes to differentiate EoE from PPI-REE before treatment. Conclusion These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many subjects with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus may constitute a sub-phenotype of EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE particularly that associated with classic features of allergic inflammation provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.

Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

SUMMARY BackgroundAeroallergens have been implicated in the pathogenesis of eosinophilic oesophagitis.