Long-Term Budesonide Maintenance Treatment Is Partially Effective for Patients With Eosinophilic Esophagitis  Alex Straumann, Sebastien Conus, Lukas Degen, Cornelia Frei, Christian Bussmann, Christoph Beglinger, Alain Schoepfer, Hans–Uwe Simon  Clinical Gastroenterology and Hepatology  Volume 9, Issue 5, Pages 400-409.e1 (May 2011) DOI: 10.1016/j.cgh.2011.01.017 Copyright © 2011 AGA Institute Terms and Conditions

Figure 1 Kaplan–Meier plots displaying time to clinical relapse during the study. The median time to relapse was more than 125 days in the budesonide group and 95 days in the placebo group (P = .14). Clinical Gastroenterology and Hepatology 2011 9, 400-409.e1DOI: (10.1016/j.cgh.2011.01.017) Copyright © 2011 AGA Institute Terms and Conditions

Figure 2 Mast cell, and T-cell infiltration: expression of tumor necrosis factor (TNF)-α, epithelial cell death, apoptosis, and molecular remodeling of the epithelial layer of the esophagus in EoE patients before and after therapy, as assessed by immunofluorescence. (A) Mast cell and T-cell infiltration: specimens were stained with anti-antitryptase and anti-CD3 antibodies, respectively. (B) Expression of TNF-α by epithelial cells. (C) Epithelial cell death and apoptosis as assessed by TUNEL assay and immunostaining using an antibody to caspase-cleaved cytokeratin 18, respectively. (D) Molecular remodeling analyses: specimens were stained with anti–tenascin C and anti–TGF-β antibodies, respectively. All panels show representative immunofluorescence data. Appropriate control antibodies were used under each condition and showed no detectable staining (data not shown). Bars, 10 μm. Quantitative analyses for all markers are shown in Table 2. Clinical Gastroenterology and Hepatology 2011 9, 400-409.e1DOI: (10.1016/j.cgh.2011.01.017) Copyright © 2011 AGA Institute Terms and Conditions

Figure 3 Structure of the esophagus wall in EoE patients and in healthy controls assessed by EUS and histomorphometry. (A) EUS: before budesonide induction-treatment patients with active EoE revealed a significant thickening of the esophageal wall compared with controls involving all mural layers. Under the long-term influence of budesonide, the thickness of all layers decreased, with the most impressive reduction of the mucosa, whereas the changes in the deeper wall were less pronounced. (B) Histomorphometry: the thickness of esophageal squamous epithelium in 14 EoE patients before and after treatment with budesonide and in 19 esophagus-healthy controls showed that long-term administration of topical corticosteroids did not result in a decrease of the epithelial diameter. Clinical Gastroenterology and Hepatology 2011 9, 400-409.e1DOI: (10.1016/j.cgh.2011.01.017) Copyright © 2011 AGA Institute Terms and Conditions

Figure 4 Representative pictures of esophageal wall structure in EoE patients before and after treatment with budesonide and in esophagus-healthy controls, assessed by (A–C) histology and (D–F) EUS. Untreated EoE patients had a highly increased amount of fibrotic tissue in the (B) lamina propria compartment compared with (A) esophagus-healthy controls. (C) At the end of the treatment period the fibrosis was reduced, but still not normalized. Corresponding with histology, EUS shows an impressive thickening of all wall layers in untreated patients with (E) active EoE (white arrow) compared with (D) esophagus-healthy individuals, and, at the end of the treatment period, the (F) wall thickening was still detectable. To illustrate the layering of the healthy esophagus wall, we used a higher magnification in panel D. Clinical Gastroenterology and Hepatology 2011 9, 400-409.e1DOI: (10.1016/j.cgh.2011.01.017) Copyright © 2011 AGA Institute Terms and Conditions

Supplementary Figure 1 Flow chart of the patients included in the study. Clinical Gastroenterology and Hepatology 2011 9, 400-409.e1DOI: (10.1016/j.cgh.2011.01.017) Copyright © 2011 AGA Institute Terms and Conditions