Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids

Abstract

Background: Esophageal remodeling occurs in eosinophilic esophagitis (EE) patients but whether the components of remodeling in the subepithelium are reversible by administration of topical oral corticosteroids is unknown. Methods: We quantitated the degree of lamina propria remodeling in esophageal biopsies obtained before and after at least 3 months of therapy with budesonide in 16 pediatric EE subjects. In addition, we investigated whether corticosteroid therapy modulated vascular activation (expression of VCAM-1; level of interstitial edema), TGFβ₁ activation (levels of TGFβ₁, phosphorylated Smad2/3), and performed a pilot analysis of a polymorphism in the TGFβ₁ promoter in relation to EE subjects who had reduced remodeling with budesonide therapy. Results: EE subjects were stratified based on the presence (n = 9) or absence (n = 7) of decreased epithelial eosinophilia following budesonide. Patients with residual eosinophil counts of ≤7 eosinophils per high power field in the epithelial space (responders) demonstrated significantly reduced esophageal remodeling with decreased fibrosis, TGFβ₁ and pSmad2/3 positive cells, and decreased vascular activation in association with budesonide therapy. Responders were more likely to have a CC genotype at the −509 position in the TGFβ₁ promoter. Conclusions: Reductions in epithelial eosinophils following budesonide therapy were associated with significantly reduced esophageal remodeling.