Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Over the past three decades, the detection of oesophageal mucosal eosinophils has transitioned from a biomarker of GERD to a diagnostic criterion for eosinophilic oesophagitis (EoE). In GERD, oesophageal eosinophils are considered part of the chronic inflammatory response to acid reflux, whereas the marked eosinophilia in EoE is viewed as a central feature of the immune response to ingested food and/or environmental antigen stimulation. Descriptions of a considerable subset of patients with symptomatic, endoscopic and histological findings of EoE that resolve with PPI therapy has led to confusion and controversy regarding the distinction of EoE from GERD. Study findings indicate that PPI-responsive oesophageal eosinophilia (PPI-REE) more closely resembles EoE than GERD, both from a clinical and immunological aspect. Although responsiveness to PPI therapy should not be utilized to exclude EoE, PPI therapy is effective at reducing oesophageal eosinophilia in ∼40% of patients, and PPI therapy is both a safe and practical initial step in the management of patients with oesophageal eosinophilia. Ongoing studies elucidating the mechanism behind PPI-REE will improve our understanding and management of EoE. In this Review, the mechanisms and evidence that underlie the controversy in the distinction between GERD and EoE are evaluated.