Interaction with gastroesophageal reflux disease (GERD) has been a fundamental consideration in eosinophilic esophagitis (EoE) since the initial reports of this emerging entity. While studies from the '80s identified the presence of esophageal eosinophilia as being a histologic marker for the diagnosis of GERD, studies in the '90s demonstrated that high levels of esophageal eosinophilia were characteristic for a novel immune/antigen-mediated esophageal disease, EoE, that was seemingly quite distinct from GERD. However, several recent studies have demonstrated the effectiveness of proton pump inhibition (PPI) in reducing symptoms and histopathology in a subset of patients with esophageal eosinophilia and suspected EoE, leading to the terminology "PPI responsive esophageal eosinophilia." It remains uncertain as to whether these patients have EoE, GERD, or a PPI responsive esophageal inflammatory condition that is distinct from either GERD or EoE. Emerging translational research has evidenced mechanisms by which PPI response in patients with esophageal eosinophilia may be a consequence of PPI effects on the immune pathogenesis of EoE. Therefore, a symptom and histologic response to PPI in patients with esophageal eosinophilia does not necessarily "rule in" GERD. Until further studies better define the pathogenesis of PPI responsive esophageal eosinophilia, a trial of PPI therapy remains an important prerequisite to the diagnosis EoE. Following this diagnostic approach allows for the clinical application of available evidence that is derived from research trials in EoE that exclude PPI responsive eosinophilia.
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