EoE ToT Module 2 References-OShea et al Gastroenterology 2018 Pathophysiology of eosinophilic esophagitis

OShea et al Gastroenterology 2018 Pathophysiology of eosinophilic esophagitis

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Eosinophilic esophagitis (EoE) is a chronic inflammatory condition distinguished by marked eosinophilic infiltration of the esophagus, often resulting in various gastrointestinal symptoms and fibrostenotic complications. Unlike gastroesophageal reflux disease (GERD), EoE features a unique esophageal transcriptome and is influenced by genetic susceptibilities, particularly linked to loci like TSLP on 5q22 and CAPN14 on 2p23. Understanding the interplay between genetic predisposition and environmental factors, such as food allergens, is crucial, as these allergens typically trigger the disease. <br /><br />Key immune players in EoE pathogenesis are eosinophils, mast cells, and cytokines like IL-5 and IL-13, driven by Th2-type immune responses. Genetic studies have identified significant genes associated with EoE (e.g., TSLP, CAPN14, STAT6, and others) which regulate immune responses and epithelial barrier function. Interestingly, a specific EoE transcriptome differs from that of GERD, highlighting the unique pathophysiological pathways in EoE.<br /><br />Allergic sensitization to foods is a pivotal contributor, evidenced by the high incidence of concurrent atopic conditions and the effectiveness of dietary elimination therapies. Th2 cytokines, particularly IL-13, play critical roles in disease development, promoting epithelial dysfunction and eosinophil recruitment. Emerging therapies targeting these pathways, such as IL-13 and IL-5 antibodies, show promise in reducing eosinophil levels and improving clinical outcomes.<br /><br />Environmental factors, including Cesarean section deliveries and early antibiotic use, and their resultant effects on the microbiome may also contribute to disease etiology. The potential role of dysbiosis in EoE pathogenesis is being explored, with findings suggesting differences in the esophageal microbiome between patients with active EoE and healthy controls.<br /><br />Esophageal fibrostenosis is a long-term complication of untreated EoE, driven by persistent inflammation and tissue remodeling. Studies show that topical steroids and dietary therapies can lead to partial reversibility of these histological changes.<br /><br />The recent establishment of research consortia like the CEGIR underscores a growing focus on understanding EoE’s pathophysiology and developing targeted treatments to disrupt the allergic and Th2-mediated inflammatory responses. This integration of gastroenterology and allergy expertise aims to enhance clinical care through advanced diagnostic and therapeutic strategies.

Keywords

Eosinophilic esophagitis

EoE

chronic inflammatory condition

genetic susceptibilities

food allergens

Th2-type immune responses

IL-13

dietary elimination therapies

esophageal fibrostenosis

CEGIR