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

• Published in: Allergy (Copenhagen) 2010-01, Vol.65 (1), p.109-116
• Main Authors: Aceves, S.S, Newbury, R.O, Chen, D, Mueller, J, Dohil, R, Hoffman, H, Bastian, J.F, Broide, D.H
• Format: Article
• Language: English
• Subjects: Administration, Oral; Administration, Topical; Adolescent; Biological and medical sciences; Biopsy; budesonide; Budesonide - administration & dosage; Child; Child, Preschool; Children & youth; Dermatology; Eosinophilia - drug therapy; Eosinophilia - etiology; Eosinophilia - pathology; eosinophilic esophagitis; Esophagitis - drug therapy; Esophagitis - genetics; Esophagitis - immunology; Esophagus; Female; Fibrosis - drug therapy; Fibrosis - etiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Glucocorticoids - administration & dosage; Humans; Male; Medical sciences; Mucous Membrane - drug effects; Mucous Membrane - immunology; Mucous Membrane - pathology; Other diseases. Semiology; pediatric; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; remodeling; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Steroids; Transforming Growth Factor beta1 - biosynthesis; Transforming Growth Factor beta1 - drug effects; Transforming Growth Factor beta1 - genetics; transforming growth factor-beta (TGFβ); Vascular Cell Adhesion Molecule-1 - biosynthesis; Vascular Cell Adhesion Molecule-1 - drug effects
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2009.02142.x

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. 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. 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 [less-than or equal to]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. Reductions in epithelial eosinophils following budesonide therapy were associated with significantly reduced esophageal remodeling.