Jessica Rajan1, Robert O Newbury2, Arjun Anilkumar3, Ranjan Dohil4, David H Broide5, Seema S Aceves6. 1. Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Center for Immunity, Infection, and Inflammation, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. 2. Division of Pathology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. 3. Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Center for Immunity, Infection, and Inflammation, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. 4. Division of Gastroenterology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. 5. Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. 6. Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Center for Immunity, Infection, and Inflammation, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. Electronic address: saceves@ucsd.edu.
Abstract
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic TH2 inflammatory disease characterized by tissue remodeling that leads to esophageal strictures and food impactions. Effects of therapy on long-term remodeling in patients with pediatric eosinophil-associated diseases have not been previously described. OBJECTIVE: We sought to understand the long-term control of esophageal remodeling in patients with EoE. METHODS: We assessed endoscopic and histologic remodeling and TGF-β1 expression in esophageal biopsy specimens from children (n = 32) with EoE treated with topical corticosteroids (TCSs) over 10 years (mean, 4.5 years). We used standardized EoE scoring tools to gauge endoscopic and symptom features. RESULTS: Seven hundred thirty-eight biopsy specimens from 246 endoscopic procedures were evaluated over 10 years. Four hundred eighty-six biopsy specimens had adequate lamina propria for evaluation of subepithelial remodeling. The severity of epithelial esophageal eosinophilia correlated with epithelial remodeling (basal zone hyperplasia, desquamation, and dilated intercellular spaces; P < .0001), lamina propria eosinophilia (P < .0001), and fibrosis (P < .0001). Sixteen subjects were initial responders (<15 eosinophils/high-power field) to TCSs. Responders and nonresponders spent 54% and 97% of their total disease duration with active EoE (P < .001) and 23% and 53% (P < .02) with maximal fibrosis scores, respectively. Responders had lower endoscopy scores during their disease duration (P = .013). Having less than 15 eosinophils/high-power field at any time correlated with lower fibrosis and endoscopic severity. TGF-β1(+) cell counts decreased in responders at the first biopsy, but this was not sustained. Symptoms did not correlate with other disease features. CONCLUSIONS: Children with EoE have substantial esophageal remodeling, which associates with inflammation and can improve in a sustainable manner with TCSs. Although endoscopic features correspond to histologic features, symptoms did not correlate with inflammation or fibrosis.
BACKGROUND:Eosinophilic esophagitis (EoE) is a chronic TH2 inflammatory disease characterized by tissue remodeling that leads to esophageal strictures and food impactions. Effects of therapy on long-term remodeling in patients with pediatric eosinophil-associated diseases have not been previously described. OBJECTIVE: We sought to understand the long-term control of esophageal remodeling in patients with EoE. METHODS: We assessed endoscopic and histologic remodeling and TGF-β1 expression in esophageal biopsy specimens from children (n = 32) with EoE treated with topical corticosteroids (TCSs) over 10 years (mean, 4.5 years). We used standardized EoE scoring tools to gauge endoscopic and symptom features. RESULTS: Seven hundred thirty-eight biopsy specimens from 246 endoscopic procedures were evaluated over 10 years. Four hundred eighty-six biopsy specimens had adequate lamina propria for evaluation of subepithelial remodeling. The severity of epithelial esophageal eosinophilia correlated with epithelial remodeling (basal zone hyperplasia, desquamation, and dilated intercellular spaces; P < .0001), lamina propria eosinophilia (P < .0001), and fibrosis (P < .0001). Sixteen subjects were initial responders (<15 eosinophils/high-power field) to TCSs. Responders and nonresponders spent 54% and 97% of their total disease duration with active EoE (P < .001) and 23% and 53% (P < .02) with maximal fibrosis scores, respectively. Responders had lower endoscopy scores during their disease duration (P = .013). Having less than 15 eosinophils/high-power field at any time correlated with lower fibrosis and endoscopic severity. TGF-β1(+) cell counts decreased in responders at the first biopsy, but this was not sustained. Symptoms did not correlate with other disease features. CONCLUSIONS:Children with EoE have substantial esophageal remodeling, which associates with inflammation and can improve in a sustainable manner with TCSs. Although endoscopic features correspond to histologic features, symptoms did not correlate with inflammation or fibrosis.
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