This review examines the underlying mechanisms of disease pathogenesis in eosinophilic esophagitis with the aim of identifying how current and emerging therapies target specific pathologic pathways. Over the past three decades, the incidence and prevalence of EoE have risen significantly and it is now a leading cause of dysphagia and food impaction in both children and adults. Recent studies highlight how genetic predisposition, environmental exposures, epithelial barrier dysfunction, and abnormal type 2 immune responses interact to contribute to EoE pathogenesis. Key mechanisms include the release of epithelial alarmins, elevated type 2 cytokine signaling, and the recruitment of immune effector cells, all of which lead to chronic inflammation, tissue remodeling, and fibrostenosis. Current treatments include dietary management, proton pump inhibitors, swallowed corticosteroids, and dupilumab, the first approved biologic. New biologics and agents targeting the epithelial barrier, IL-13, TSLP, and related pathways offer hope for more personalized, mechanism-based therapies. Current therapies for EoE aim to reduce inflammation and prevent fibrostenotic complications, but challenges such as treatment nonresponse and long-term disease progression still exist. Mechanism-based therapies, particularly biologics targeting type 2 inflammatory pathways and barrier dysfunction, represent a promising frontier for more personalized treatment strategies. Understanding the interplay of immune signaling and epithelial dysfunction can inform the development of next-generation therapies with the potential to transform outcomes in EoE.
Gautam et al. (Thu,) studied this question.