Characterization of eosinophilic esophagitis variants by clinical, histological and molecular analyses: A cross-sectional multi-center study.

Greuter, Thomas; Straumann, Alex; Fernandez-Marrero, Yuniel; Germic, Nina; Hosseini, Aref; Yousefi, Shida; Simon, Dagmar; Collins, Margaret H; Bussmann, Christian; Chehade, Mirna; Dellon, Evan S; Furuta, Glenn T; Gonsalves, Nirmala; Hirano, Ikuo; Moawad, Fouad J; Biedermann, Luc; Safroneeva, Ekaterina; Schoepfer, Alain M; Simon, Hans-Uwe (2022). Characterization of eosinophilic esophagitis variants by clinical, histological and molecular analyses: A cross-sectional multi-center study. Allergy, 77(8), pp. 2520-2533. Wiley 10.1111/all.15233

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Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants.


Patients from six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro-esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)-histological and molecular features were determined and compared with EoE, GERD and healthy controls.


We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE-like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%) and non-specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed - in contrast to EoE - no significant increase in inflammatory cell infiltrates compared to GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE-typical Th2-response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE-like (characterized by eotaxin-3 expression), non-specific and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression).


All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

Fernández Marrero, Yuniel, Germic, Nina, Hosseini, Aref, Yousefi, Shida, Simon, Dagmar, Safroneeva, Ekaterina, Simon, Hans-Uwe


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services






[4] Swiss National Science Foundation




Andrea Studer-Gauch

Date Deposited:

14 Feb 2022 14:47

Last Modified:

05 Dec 2022 16:06

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Disease activity dysphagia eosinophilic esophagitis esophageal eosinophilia esophagus immunohistochemistry lymphocytic esophagitis next generation RNA sequencing real-time polymerase chain reaction




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