Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Abstract

Over the past three decades, the detection of oesophageal mucosal eosinophils has transitioned from a biomarker of GERD to a diagnostic criterion for eosinophilic oesophagitis (EoE). In GERD, oesophageal eosinophils are considered part of the chronic inflammatory response to acid reflux, whereas the marked eosinophilia in EoE is viewed as a central feature of the immune response to ingested food and/or environmental antigen stimulation. Descriptions of a considerable subset of patients with symptomatic, endoscopic and histological findings of EoE that resolve with PPI therapy has led to confusion and controversy regarding the distinction of EoE from GERD. Study findings indicate that PPI-responsive oesophageal eosinophilia (PPI-REE) more closely resembles EoE than GERD, both from a clinical and immunological aspect. Although responsiveness to PPI therapy should not be utilized to exclude EoE, PPI therapy is effective at reducing oesophageal eosinophilia in ~40% of patients, and PPI therapy is both a safe and practical initial step in the management of patients with oesophageal eosinophilia. Ongoing studies elucidating the mechanism behind PPI-REE will improve our understanding and management of EoE. In this Review, the mechanisms and evidence that underlie the controversy in the distinction between GERD and EoE are evaluated.

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis

“…[2] However, a rigid distinction between EoE and GORD is difficult due to overlapping clinical and histological features, not to mention their frequent coexistence and potential partially shared pathogenic pathways. [3] The presence of heartburn and marked oesophageal eosinophilia, for instance, might be fairly common in both entities. [3,4] In pediatric patients, this differentiation is even more complex due to a wider spectrum of clinical manifestations, difficulties in expressing symptoms and subtle or absent endoscopic abnormalities.…”

“…[3] The presence of heartburn and marked oesophageal eosinophilia, for instance, might be fairly common in both entities. [3,4] In pediatric patients, this differentiation is even more complex due to a wider spectrum of clinical manifestations, difficulties in expressing symptoms and subtle or absent endoscopic abnormalities. [5]…”

“…[3] Endoscopically, nearly all adult EoE patients demonstrate one or more characteristic features of loss of vascular markings, rings, white exudates, longitudinal furrows, narrow caliber oesophagus and strictures, whereas some children may have a visually normal mucosa. [11,12] Reflecting the natural history of oesophageal remodelling, rings and strictures are common in adults but rare findings in children with EoE.…”

“…3 Patients with GORD present with heartburn, regurgitation and bitter/sour taste of gastric content. Dysphagia as a dominant symptom is rare in GORD, unless a peptic stricture is present.…”

The Immunologic Mechanisms of Eosinophilic Esophagitis

“…However, recent findings that a subset of patients with esophageal eosinophilia have improvement or resolution of disease with PPI therapy alone has led some investigators and clinicians to examine the relationship between EoE, esophageal eosinophilia, and GERD. Specifically, proton pump inhibitor-responsive esophageal eosinophilia is an active area of research [162]. Nevertheless, it is likely that the underlying inflammatory mechanisms of GERD and EoE are distinct and that the presence of eosinophils in the esophagus represents a common inflammatory endpoint [163, 164].…”