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Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms

Schoepfer, Alain M MD1,14; Simko, Audrey BMed1,14; Bussmann, Christian MD2; Safroneeva, Ekaterina PhD3; Zwahlen, Marcel PhD3; Greuter, Thomas MD4; Biedermann, Luc MD4; Vavricka, Stephan MD4,5; Godat, Sébastien MD1; Reinhard, Antoine MD6; Saner, Catherine PhD7; Maye, Hugo MD8; Sempoux, Christine MD, PhD9; Brunel, Christophe MD9; Blanchard, Carine PhD10; Simon, Dagmar MD11; Simon, Hans-Uwe MD,PhD12; Straumann, Alex MD13,4

American Journal of Gastroenterology: March 2018 - Volume 113 - Issue 3 - p 348–357
doi: 10.1038/ajg.2017.493

OBJECTIVES: For technical reasons, the histologic characterization of eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based on those found in the esophageal epithelium, whereas little is known about subepithelial abnormalities. In this study, we aimed to systematically assess the nature of subepithelial histologic alterations, and analyze their relationship with epithelial histologic findings, endoscopic features, and symptoms.

METHODS: Adult patients with established EoE diagnosis were prospectively included during a yearly follow-up visit. Patients underwent assessment of clinical, endoscopic, and histologic disease activity using EoE-specific scores.

RESULTS: We included 200 EoE patients (mean age 43.5±15.7 years, 74% males) with a median peak count of 36 intraepithelial eosinophils/hpf (IQR 14−84). The following histologic features were identified in the subepithelial layer: eosinophilic infiltration (median peak count of 20 eosinophils/hpf (IQR 10−51)), eosinophil degranulation (43%), fibrosis (82%), and lymphoid follicles (56%). Peak intraepithelial eosinophil counts were higher, identical, and lower when compared to the subepithelial layer in 62.5%, 7%, and 30.5% of patients, respectively. Anti-eosinophilic treatment at inclusion did not influence the relation between subepithelial and epithelial peak eosinophil counts. Subepithelial histologic activity correlated with epithelial histologic activity (rho 0.331,P<0.001), endoscopic severity (rho 0.208,P=0.003), and symptom severity (rho 0.179,P=0.011). Forty percent (21/52) of patients with <15 intraepithelial eosinophils/hpf had subepithelial peak counts of ≥15/hpf.

CONCLUSIONS: There is a significant but modest correlation between subepithelial histologic activity and epithelial histologic activity, endoscopic severity, and symptom severity. The long-term clinical impact of assessing subepithelial alterations in EoE needs to be further elucidated.

1Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

2Institute of Pathology, Viollier AG, Basel, Switzerland

3Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

4Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland

5Division of Gastroenterology and Hepatology, Triemlispital, Zurich, Switzerland

6Division of Otorhinolaryngology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

7Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

8Division of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

9Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

10Nestlé Research Center, Lausanne, Switzerland

11Division of Dermatology and Allergy, Inselspital/University Hospital Bern, Bern, Switzerland

12Institute of Pharmacology, University of Bern, Bern, Switzerland

13Swiss EoE Clinic, Praxis Römerhof, Olten, Switzerland

Correspondence: Alain M. Schoepfer, MD, PD+MERClin, Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 44/07/2409, CH-1011, Lausanne, Switzerland. E-mail:

14These authors contributed equally to this work.

published online 16 January 2018

SUPPLEMENTARY MATERIAL accompanies this paper at,

Received 21 May 2017; accepted 12 November 2017

© The American College of Gastroenterology 2018. All Rights Reserved.
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