Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties

Abstract

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial–mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient’s age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.

Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics

“…Eotaxin-3 is the most upregulated gene in the esophageal mucosa of EoE patients [17], with its transcription depending on the STAT6 nuclear factor [18]. This results in a long-lasting inflammatory response, which affects the different layers of the esophageal wall [19], causing esophageal dysmotility [20] and promoting a fibrous remodeling that may progress into esophageal strictures [21,22].…”