Mechanistic insight into eosinophilic enteritis and related disorders

Eosinophilic gastrointestinal diseases (EGIDs) affecting the gastrointestinal tract outside of the esophagus are categorized as non-EoE EGIDs, and knowledge regarding their natural history and pathophysiology is rapidly advancing. This review synthesizes evolving mechanistic insights in non-EoE EGID immunopathogenesis, emerging paradigms of disease development, and how these insights influence potential therapeutic options for these conditions.

The prevalence of non-EoE EGIDs is rising, though overall prevalence remains much lower than that of eosinophilic esophagitis (EoE). Recent standardization of the nomenclature and histologic diagnostic thresholds for non-EoE EGIDs has facilitated progress in understanding the epidemiology, pathogenesis, and therapeutic targets of these conditions. Transcriptomic signatures of disease in the proximal tract, including the esophagus, stomach, and small intestine, are distinct from those in the colon, suggesting that segment-specific therapeutics may be appropriate. Mechanisms beyond eosinophilic inflammation, including mast cell activation, Th2 cytokine signaling, and structural remodeling, may also contribute to disease pathogenesis.

Mechanistic insights elucidated from extensive transcriptomic studies and clinical trials have revealed the broader type 2 pathophysiology of non-EoE EGIDs, thereby offering a valuable opportunity to identify novel therapeutic targets and inform the design of future clinical trials.