Do We Know What Causes Eosinophilic Esophagitis? A Mechanistic Update

The mechanisms underlying eosinophilic esophagitis (EoE) have been intensely investigated, and significant advances have been made in understanding the pathogenesis of EoE. EoE is defined as a chronic immune/antigen-mediated disease, characterized clinically by symptoms of esophageal dysfunction and histologically by an esophageal eosinophilic infiltrate. In this paper, we will review the current knowledge of EoE pathophysiology based on both animal and human data and discuss possible etiologic mechanisms from the genetic and environmental perspectives. EoE is a Th2-predominant inflammatory process triggered by allergens. Proinflammatory cytokines and chemokines recruit eosinophils and other effector cells, such as mast cells, into the esophageal epithelium, where they cause direct damage and promote esophageal remodeling. The genetic expression profile of EoE has been described, and several single nucleotide polymorphisms have been identified and associated with EoE. While this genetic contribution is important, it is difficult to postulate that EoE is primarily a genetic disease. Given the rapid epidemiologic changes in the incidence and prevalence of EoE over the past two decades, environmental factors may be the driving force. While it is not known what causes EoE in an individual patient at a specific time, the current hypothesis is that there is a complex interaction between genetic factors and environmental exposures that remains to be elucidated.