Refractory Gastroesophageal Reflux Disease: Diagnosis and Management

Abstract

Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.

Keywords: Endoscopy; Esophageal pH monitoring; Gastroesophageal reflux; Refractory GERD.

Figure 1

Algorithm for evaluation and management of esophageal symptoms suspicious for reflux disease. The concepts of proven gastroesophageal reflux disease (GERD) (prior objective evidence for GERD is present) and unproven GERD (no prior objective evidence for GERD) determine the optimal methodology of investigation of symptoms that persist despite proton pump inhibitor (PPI) therapy. The intent of evaluation of unproven GERD is to determine if GERD exists, while the intent in proven GERD is to determine if GERD persists despite therapy, which may need to be escalated if testing suggests persisting GERD evidence. LA, Los Angeles classification; RH, reflux hypersensitivity; RSA, reflux-symptom association; FH, functional heartburn.

Figure 2

Management of refractory gastroesophageal reflux disease (GERD). Lifestyle adjustments are useful in any patient with reflux symptoms. Antisecretory therapy should be optimized and escalated if indicated. Adjunctive and topical agents, as well as adjunctive measures can be employed to improve symptoms. In patients with objective evidence of refractory GERD, escalation of management to anti-reflux surgery or other invasive interventions may be appropriate. H2RA, histamine H2 receptor antagonist; PPI, proton pump inhibitor; PCAB, potassium competitive acid blocker; G-POEM, gastric peroral endoscopic myotomy.