Therapies Targeting Mucosal Eosinophils in Eosinophilic Gut Diseases From Esophagus to Colon

Eosinophilic gastrointestinal disorders (EGIDs) comprise eosinophilic oesophagitis (EoE) and non-EoE EGIDs; these diseases may be increasing in prevalence and are likely underdiagnosed. Mortality is not increased in EoE but is in gastric and small intestinal EGIDs. A subtle increase in eosinophils has also been observed in other GI diseases including functional dyspepsia in the duodenum. Targeted drug therapy can markedly reduce eosinophil infiltration, although symptom response is more variable, suggesting that non-eosinophil pathways play a role in pathogenesis. Current standard therapies for EoE supported by randomized trials include proton pump inhibitors, corticosteroids (topical), diet restriction, and dupilumab, inhibiting IL-4/IL-13 signaling. In non-EoE EGIDs where little randomized trial data exist, management is based on a combination of dietary elimination and corticosteroids or immunomodulators; mast cell stabilizers and antihistamine therapy may have a role. The role of combination therapies is unclear. Pharmacologic approaches in testing include new steroid preparations and delivery systems; dupilumab in eosinophilic gastritis; and anti-IL-13, anti-IL-5, anti-IL-2, and anti-IL-15 receptor targeting monoclonal antibodies.