Pathophysiology of Eosinophilic Esophagitis

Abstract

Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming growth factor beta production and signaling, to eosinophilic esophagitis pathophysiology. Experimental modeling has defined a cooperative role of activated eosinophils, mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization to multiple foods. Understanding these processes is opening the way to better treatment based on disrupting allergic inflammatory and type 2 cytokine-mediated responses, including anti-cytokine therapeutics and dietary therapy.

Keywords: Allergy; Desmosome; Genetics; Inflammation.

Figure 1. Clinical, pathologic, and therapeutics of EoE

Allergens drive eosinophilic esophagitis (EoE); however, current (glucocorticoid and dietary therapy) and future interventions can treat the disease. The presenting symptoms are shown, leading to esophageal inflammation, remodeling, rigidity, and dysfunction.

Figure 2. Pathophysiologic overview of EoE

Environmental factors, including foods and the microbiome, interact with the esophageal epithelium to elicit production of the pro-atopy cytokines IL-33 and TSLP. Activated T regulatory and Th2 cells secrete bioactive cytokines including TGF-β, IL-4, IL-13, and IL-5, which elicit barrier disruption, tissue remodeling, and eosinophilic inflammation.

Figure 3. Factors that contribute to the development of EoE