Abstract
Objective: 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. Design: 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. Results: 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 with 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). Conclusion: 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2520-2533 |
| Number of pages | 14 |
| Journal | Allergy: European Journal of Allergy and Clinical Immunology |
| Volume | 77 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2022 |
Funding
We thank Dr David A. Katzka for performing critical review of an earlier version of the manuscript. Open Access Funding provided by Universitat Zurich. Funding information This work was supported by grants from the Swiss National Science Foundation to HUS (grant no. 310030_184816), AMS (grant no. 32003B_135665/1), AS (grant no. 32003B_160115), and TG (grant no. P2ZHP3_168561), a young investigator award from the Swiss Society of Gastroenterology to TG, research grants from the Novartis Foundation for Medical-Biological Research to TG and HUS, a research award from the Swiss IBDnet to TG, and a training grant from the National Institutes of Health (NIH): Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) to TG. CEGIR (U54AI117804) is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and NCATS. CEGIR is also supported by patient advocacy groups including the American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC).
Keywords
- dysphagia
- eosinophilic esophagitis
- esophageal eosinophilia
- lymphocytic esophagitis
- next generation rna sequencing
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology