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Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies

Key Points

  • Eosinophilic oesophagitis (EoE) is a chronic, immune and/or antigen-mediated, clinicopathological disease defined by symptoms of oesophageal dysfunction, oesophageal eosinophilic inflammation, and exclusion of other causes of oesophageal eosinophilia including GERD

  • Potential interactions between GERD and EoE include eosinophilia as a component of chronic inflammation in GERD, coexistence of GERD and EoE, EoE causing GERD and GERD causing EoE

  • A notable proportion (40%) of patients with clinical, endoscopic and histological features of EoE demonstrate a clinical and histological response to PPI therapy, those with so-called PPI-responsive oesophageal eosinophilia

  • Predictors of PPI response among patients with oesophageal eosinophilia and suspected EoE are presently lacking

  • On the basis of current clinical and translational research, PPI-responsive oesophageal eosinophilia more closely resembles EoE than GERD

  • Benefits of PPI therapy in EoE could be due to their ability to restore integrity of the oesophageal epithelium or direct anti-inflammatory effects

Abstract

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.

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Figure 1: Historical aspects regarding the associations between oesophageal eosinophilia, GERD and EoE.
Figure 2: Histopathology of EoE.
Figure 3: Endoscopic features of EoE.
Figure 4: Proposed mechanism identifying the role of GERD in the pathogenesis of EoE.

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Acknowledgements

The authors acknowledge research funding support from the NIH for the Consortium of Eosinophilic Gastrointestinal disease Researchers (NIH U54 AI117804, which is part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Diseases Research, NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS) and an American Society of Gastrointestinal Endoscopy Research Award.

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Correspondence to Ikuo Hirano.

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I.H. has acted as a consultant for Meritage pharma, Receptos pharma and Regeneron, these consultant roles are not relevant to the subject matter of the article under consideration. L.K. declares no competing interests.

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Kia, L., Hirano, I. Distinguishing GERD from eosinophilic oesophagitis: concepts and controversies. Nat Rev Gastroenterol Hepatol 12, 379–386 (2015). https://doi.org/10.1038/nrgastro.2015.75

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