Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Current Role and Future Perspectives

Abstract

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized by symptoms related to esophageal dysfunction, eosinophil-predominant inflammation, and lack of response to high-dose proton pump inhibitor (PPI) therapy. Responsiveness to PPI therapy in patients with suspected EoE has been historically assumed as evidence of gastroesophageal reflux disease (GERD), but this concept has rapidly changed over the past few years. A novel phenotype, termed PPI-responsive esophageal eosinophilia (PPI-REE), was described in 2011. PPI-REE refers to patients who appear to have EoE, but who achieve complete remission after PPI therapy. Currently, a PPI trial is mandatory before diagnosing EoE since 30–40 % of EoE patients will be eventually diagnosed with PPI-REE. Evolving evidence on PPI-REE suggests it is not simply GERD but actually a subphenotype of EoE, given the fact PPI-REE and EoE remain genetically and phenotypically indistinguishable. Instead of PPI-REE, the term PPI-responsive EoE might be more accurate to name this entity. PPI-REE might occur with either normal or pathological esophageal pH monitoring. PPI therapy can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Whether esophageal barrier impairment is the cause of the effect of esophageal eosinophilia and whether PPI therapy primarily targets barrier or inflammation healing in PPI-REE have not been yet elucidated. The natural history of the disease, long-term doses, and duration of PPI therapy, as well as factors influencing symptom and/or inflammation relapse remain yet unknown. The mechanism as to why among identical patients, some respond to PPI therapy (PPI-REE) while others do not (EoE), warrants further research.