Mechanisms of Allergy
Idiopathic eosinophilic esophagitis is associated with a TH2-type allergic inflammatory response,☆☆

https://doi.org/10.1067/mai.2001.119917Get rights and content

Abstract

Background: Idiopathic eosinophilic esophagitis (IEE) is a chronic-inflammatory disorder of the esophagus of unknown origin. The established cornerstone of diagnosis is a dense infiltration of the esophagus with eosinophils, but neither the precise pattern of inflammatory cell infiltration nor the mechanisms that likely contribute to induction and maintenance of the inflammatory response have been described. Objective: The intention of this study was to characterize the esophageal inflammatory infiltrate and the expression of cytokines in the esophagus in this disease. In addition, we searched for immunologic abnormalities of blood leukocytes to exclude major primary hyporeactive and hyperreactive conditions of the immune system. Methods: Infiltration of inflammatory cells in the esophagus, stomach, and duodenum was analyzed by immunohistochemistry through use of mAbs against lineage-associated molecules. Cytokine expression was measured by ELISA and immunohistochemical analysis. Lymphocyte subpopulations in blood were determined by means of flow cytometry. Results: High eosinophil infiltration into the esophageal squamous epithelium was observed in patients with IEE but not in control subjects. Interestingly, increased T-cell and mast cell numbers were also found within the epithelium in these patients. In contrast, the numbers of inflammatory cells were not increased in the stomach and duodenum in patients with IEE, suggesting a specific inflammatory process within the esophagus. Moreover, increased expression of IL-5 and TNF-α was observed in esophageal epithelial biopsy specimens. The distribution of lymphocyte subsets in the peripheral blood and their capacity to generate cytokines did not reflect the changes observed at the inflammatory site. Conclusions: IEE is a selective inflammatory response of the esophagus. T cells, IL-5, eosinophils, and IgE-mediated mechanisms appear to be involved, giving rise to the possibility that allergic reactions might play a role in the pathogenesis of the disease. (J Allergy Clin Immunol 2001;108:954-61.)

Section snippets

Study population

Eight patients (7 men and 1 woman; mean age, 46.5 years; age range, 22-63 years) with clinically, endoscopically, and histologically diagnosed IEE were investigated (Table I). The average duration of the disease was 10.4 years. The only presenting symptom was acute recurrent dysphagia with food impaction. Gastroesophageal reflux disease was excluded by (1) a lack of clinical and histologic response to acid blockade, (2) normal pH probe monitoring of the distal esophagus, and (3) esophageal

Patients

The clinical features of the 8 patients with IEE and the 3 control patients are shown in Table I. Patients reported that the dysphagia events had lasted between 1 minute and 2 hours. The duration of the events varied considerably in most of the patients. Only patients 2, 5, and 7 had brief events (not exceeding 5 minutes). Most of the patients had had IEE for many years, suggesting that it is a chronic disease. Physical examination of all patients revealed no abnormalities. In 6 patients with

Discussion

Esophageal eosinophilia has been observed in several diseases, including reflux esophagitis,5 eosinophilic gastroenteritis,4 parasitic infection,13 and drug-induced reactions.14 These diseases must be ruled out before the diagnosis of IEE can be established. In agreement with previous reports,1, 2, 3 we note that IEE was mostly found in male individuals. The primary symptom of IEE is dysphagia. All of the patients in this study had exclusively esophageal symptoms with uniform attacks of

Acknowledgements

We thank Martina Weber for technical assistance, Dr Hanspeter Spichtin for biopsy specimens, and Dr Niklaus Schaub for suggestions and discussions.

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    Supported by the Swiss National Science Foundation (grant no. 31-58916.99), AstraZeneca, Zug, and Essex Chemie AG, Lucerne, Switzerland.

    ☆☆

    Reprint requests: Hans-Uwe Simon, MD, PhD, Department of Pharmacology, University Bern, Friedbühlstrasse 49, CH-3010 Bern, Switzerland.

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