Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease

Abstract

Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.

Keywords: Gastro-esophageal reflux disease; Proton pump inhibitor; Ambulatory pH-impedance monitoring; Esophageal hypersensitivity; Gastro-esophageal reflux disease treatment

Core tip: The present review focuses on the subgroup of patients in whom proton pump inhibitor refractoriness more frequently occurs, on the mechanisms possibly involved in the lack of response, the diagnostic work-up and the therapeutic strategies in these patients. Various mechanisms and factors have been demonstrated and some mechanisms have also been proposed, although not yet supported by strong evidence. In the management of these patients, a careful clinical interview might conduct the diagnostic evaluation and the therapeutic approaches.