Diagnosis and Management of Refractory Gastroesophageal Reflux Disease

In up to half of patients with symptoms suspected to stem from gastroesophageal reflux disease (GERD), these symptoms persist despite treatment with daily proton pump inhibitor (PPI) therapy. The symptoms may be characterized as typical (eg, heartburn or regurgitation) or atypical (eg, chest pain or cough). These refractory symptoms, which are frequently encountered in clinical practice, may stem from GERD as well as non-GERD etiologies. Among those patients with objective GERD proven on esophagogastroduodenoscopy (EGD) and/ or ambulatory reflux testing, approximately one-fifth may manifest suboptimal symptom response to PPI therapy. After introducing the initial evaluation of patients with suspected GERD symptoms, this article discusses approaches to the esophageal diagnostic workup of patients with refractory symptoms in the setting of proven GERD, focusing on EGD, high-resolution manometry (HRM), and pH-impedance monitoring during treatment with PPI therapy. EGD evaluates for esophagitis, peptic stricture, and hiatal hernia, as well as eosinophilic esophagitis. HRM rules out confounding esophageal motor disorders, identifies behavioral disorders, characterizes the antireflux barrier, and assesses esophageal contractile reserve to help tailor potential antireflux interventions. pH-impedance monitoring during treatment with PPI therapy can help distinguish between PPI-refractory GERD-as evidenced by pathologic acid exposure despite PPI therapy and/or excess burden of reflux events regardless of acidity-and PPI-controlled GERD. This article also discusses potential approaches for patients with symptoms stemming from refractory GERD, encompassing lifestyle, pharmacologic, endoscopic, and surgical management options.