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Eosinophilic esophagitis (EoE): Genetics and immunopathogenesis

Marc E Rothenberg, MD, PhD
Section Editor
Scott H Sicherer, MD, FAAAAI
Deputy Editor
Elizabeth TePas, MD, MS


Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation [1]. The pathogenesis of EoE is the result of an interplay between genetic, environmental, and host immune system factors.

This topic reviews the genetics and immunopathogenesis underlying EoE. The clinical features, diagnosis, and management of EoE are discussed in greater detail separately. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis" and "Allergy testing in eosinophilic esophagitis" and "Treatment of eosinophilic esophagitis" and "Dietary management of eosinophilic esophagitis".)


The pathogenesis of EoE is incompletely understood but involves genetic, environmental, and host immune system factors. Differentiating gastroesophageal reflux disease (GERD), proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), and EoE is reviewed in greater detail separately. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis", section on 'Distinction from GERD'.)

The esophagus is normally devoid of eosinophils, although they are permanent residents in the rest of the gastrointestinal tract beginning during early embryonic development. Thus, the finding of esophageal eosinophils denotes pathology, typically EoE or GERD [2,3]. The diagnosis of EoE requires the presence of esophageal eosinophilia that is resistant to PPI therapy, but it is now appreciated that a substantial number of patients with esophageal eosinophilia can respond to PPI therapy. This entity is now referred to as PPI-responsive esophageal eosinophilia (PPI-REE) [4].

Antigenic proteins, typically derived from food and less commonly from inhaled proteins, trigger an adaptive T helper type 2 (Th2) cell-mediated response that produces cytokines, such as interleukin (IL)-5 and IL-13 [5]. IL-13 subsequently triggers resident cells, such as esophageal epithelial cells, to produce a large set of proteins. The most strongly induced gene in this process is eotaxin-3, which in turn recruits eosinophils from the peripheral blood into the tissue [6]. Antigen-driven Th2 cells also produce IL-5, which is a chief eosinophil growth and activation factor that primes eosinophils to have enhanced responsiveness to eotaxin-3 and prolongs their cellular survival.

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Literature review current through: Nov 2017. | This topic last updated: Nov 18, 2016.
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