Esophageal remodeling in pediatric eosinophilic esophagitis

Background: Eosinophils are associated with airway remodeling in asthma, but studies have not yet determined whether eosinophilic esophagitis (EE) is associated with esophageal remodeling. Objective: We performed quantitative immunohistochemical analysis of remodeling changes in esophageal biopsy specimens from children with and without EE to evaluate if there were changes in the esophagus of pediatric patients with EE akin to airway remodeling. In addition, we determined whether the esophagus of patients with EE had increased levels of expression of TGF-beta(1) and its signaling molecule, phosphorylated SMAD2/3 (phospho-SMAD2/3). Methods: To determine esophageal levels of eosinophilic inflammation, fibrosis, and vascular activation, endoscopically obtained esophageal biopsy specimens from 7 patients with EE (5 strictured, 2 nonstrictured), 7 with gastroesophageal reflux disease, and 7 normal patients were processed for immunohistology, trichrome staining, and assessment of levels of expression of TGF-beta(1), phospho-SMAD2/3, and vascular cell adhesion molecule 1. Results: Esophageal biopsies in patients with EE demonstrated increased levels of subepithelial fibrosis and increased expression of TGF-beta(1) and its signaling molecule phospho-SMAD2/3 compared with gastroesophageal reflux disease and normal control patients. In addition, esophageal biopsies in patients with EE demonstrated an increased vascular density and an increased expression of the vascular endothelial adhesion molecule, vascular cell adhesion molecule 1. Conclusion: Previously unrecognized esophageal remodeling changes analogous to aspects of airway remodeling are detectable in the subepithelial region of the esophagus in pediatric patients with EE. Clinical implications: Pediatric patients with EE demonstrate increased fibrosis, vascularity, and vascular activation in the esophagus that may contribute to stricture formation and potentially provide a basis for stratifying patients with EE on the basis of disease severity and/or prognosis.