Clinical and Endoscopic Characteristics Do Not Reliably Differentiate PPI-Responsive Esophageal Eosinophilia and Eosinophilic Esophagitis in Patients Undergoing Upper Endoscopy

A Prospective Cohort Study

Evan S Dellon MD, MPH; Olga Speck MD, PhD; Kimberly Woodward MD; Jessica H Gebhart MSHS; Ryan D Madanick MD; Sidney Levinson MD; Karen J Fritchie MD; John T Woosley MD, PhD; Nicholas J Shaheen MD, MPH


Am J Gastroenterol. 2013;108(12):1854-1860. 

In This Article

Abstract and Introduction


Objectives Proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy and determine features that distinguish the two groups.

Methods This prospective study conducted at the University of North Carolina from 2009 to 2011 enrolled consecutive adult patients undergoing outpatient upper endoscopy. Subjects had esophageal biopsies to quantify the maximum eosinophil count per high-power field (eos/hpf; hpf=0.24 mm2). If biopsies revealed ≥15 eos/hpf, subjects were treated with twice daily PPI for 8 weeks and endoscopy was repeated. If ≥15 eos/hpf persisted despite PPI therapy, EoE was diagnosed. If there were <15 eos/hpf, PPI-REE was diagnosed. The proportion of patients in each group was calculated, and patients with EoE and PPI-REE were compared.

Resulst Of the 223 subjects enrolled, 173 had dysphagia and 50 did not. Of those with dysphagia, 66 (38%) had ≥15 eos/hpf. After the PPI trial, 40 (23%) were confirmed to have EoE, and 24 (14%) had PPI-REE. Of those without dysphagia, 2 (4%) had ≥15 eos/hpf, and after the PPI trial, 1 (2%) had EoE. Compared with EoE, PPI-REE patients were more likely to be older and male and less likely to have typical endoscopic findings of EoE. However, none of the individual factors was independently predictive of PPI-REE status on multivariable analysis. Similarly, although some endoscopic findings were differentially distributed between PPI-REE and EoE, none were significantly associated with disease status on multivariable analysis.

Conclusions Esophageal eosinophilia is common among patients undergoing esophagogastroduodenoscopy for dysphagia. Although EoE was seen in nearly a quarter of patients with dysphagia, PPI-REE was almost as common, and accounted for over one-third of those with ≥15 eos/hpf. No clinical or endoscopic features independently distinguished PPI-REE from EoE before the PPI trial.


Eosinophilic esophagitis (EoE) is an immune-mediated clinicopathological condition characterized by symptoms of esophageal dysfunction in the setting of eosinophilic inflammation on esophageal biopsy.[1,2] Over the past decade, this condition has become increasingly recognized, and it is now frequently encountered in patients undergoing upper endoscopy.[3,4,5] However, the finding of esophageal eosinophilia is not specific for EoE. The differential diagnosis is relatively broad and can include infections, drug hypersensitivity, autoimmune and connective tissue disorders, and hypereosinophilic syndrome.[1,2,6,7] From a practical standpoint, however, gastroesophageal reflux disease (GERD) and proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) are the most commonly encountered conditions that must be distinguished from EoE.[1,2,8]

In particular, the recent recognition of PPI-REE has complicated the diagnostic algorithm for EoE. PPI-REE is the term used to describe patients with esophageal eosinophilia on biopsy who respond to a course of PPI therapy. It was first observed in a series of pediatric patients,[9] and now accounts for at least one-third of children and adults with esophageal eosinophilia.[10,11,12,13,14,15] Although recent guidelines require the exclusion of PPI-REE with a PPI trial before a formal diagnosis of EoE can be made,[1,2] it is currently unclear if PPI-REE is a subtype of GERD, an EoE phenotype, or an independent condition. In addition, the prevalence of PPI-REE has not been prospectively determined in a cohort in the United States. PPI-REE is poorly understood, and predictors that might distinguish EoE from PPI-REE are unknown.

The aim of this study was to determine the prevalence of PPI-REE and EoE in patients with and without dysphagia undergoing upper endoscopy and to determine whether clinical, endoscopic, or histological features could distinguish the two groups. Based on our experience, we hypothesized that no such factors would distinguish PPI-REE from those with EoE.