Proton-pump inhibitor-responsive esophageal eosinophilia

Purpose of review Proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) refers to patients showing symptoms and histological findings suggestive of eosinophilic esophagitis (EoE) who achieve complete remission on PPI therapy. This article aims to review evolving evidence on this novel phenotype over the last year. Recent findings Several prospective series have reported consistent rates of PPI-REE (30-40%) in adults with suspected EoE. At baseline, PPI-REE and EoE have been shown to be indistinguishable upon clinical, endoscopic, and molecular characteristics [eotaxin-3, interleukin (IL-5), and IL-13 expression]. PPI therapy partially restores esophageal mucosal integrity in PPI-REE, but not in EoE. Anti-inflammatory effects of PPI therapy, independent of acid suppression, have been confirmed in EoE and gastroesophageal reflux disease cell cultures. PPI therapy in vivo downregulates Th2 cytokines in PPI-REE patients, in a similar fashion to that seen in steroid-responsive EoE. Summary PPI-REE has emerged as a common clinical phenotype. PPI-REE and EoE remain largely indistinguishable, suggesting that they might be the same disease at baseline. While PPI therapy has been demonstrated to partially restore epithelial integrity in PPI-REE, in-vitro and in-vivo studies suggest that the anti-inflammatory effects of PPI therapy may be responsible for this restoration through inhibition of the Th2-allergic pathway rather than only acid suppression.