Proton pump inhibitor-responsive oesophageal eosinophilia and eosinophilic oesophagitis: more similarities than differences

Abstract

Purpose of review: The purpose of this study is to discuss the clinical, endoscopic and histologic features, pathogenesis and disease mechanisms of proton pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-REE), and to highlight similarities and differences with eosinophilic oesophagitis (EoE).

Recent findings: PPI-REE is a condition in which patients have clinical and histologic findings similar to EoE, but achieve complete remission with PPI treatment. More than one-third of patients who have oesophageal symptoms associated with oesophageal eosinophilia respond to PPI treatment. Emerging data elucidating the pathogenesis of PPI-REE have shown that Th2-related inflammatory factors such as interleukin (IL)-13, IL-5, eotaxin-3 and major basic protein (MBP) are elevated in PPI-REE, similar to EoE. PPI-REE also shares a genetic expression signature with EoE that reverses with PPI treatment. Mechanisms proposed to explain the PPI response include an acid-independent, anti-inflammatory action of PPIs and PPI-induced restoration of oesophageal barrier function.

Summary: Multiple features of PPI-REE overlap extensively with EoE. This raises the question of whether PPI-REE is merely a subtype of EoE rather than an independent condition. This similarity may have future implications for algorithms informing evaluation and treatment of oesophageal eosinophilia.

Figure 1

Rethinking the complex relation between GERD, EoE, PPI-REE, and esophageal eosinophilia for the future. The pink circle represents all cases of esophageal eosinophilia. Some may be due to other, non-esophageal causes. However, the majority are likely due to EoE (red circle). Given the similarities between EoE and PPI-REE, it is possible that the majority of PPI-REE cases are due to EoE, and these EoE patients respond to PPIs as a first-line agent (orange circle). The impact of GERD can be seen as well. Many GERD cases do not have significant esophageal eosinophilia (blue circle). There are some cases where esophageal eosinophilia is caused by GERD and responds to a PPI (yellow semi-circle), some cases where GERD and EoE overlap and where the eosinophilia is due to EoE (light blue area), and some cases where there is GERD and esophageal eosinophilia, but not PPI-response (purple area).