Refractory heartburn to proton pump inhibitors: epidemiology, etiology and management

Patients with refractory heartburn to proton pump inhibitors (PPIs) represent a distinctive group which is difficult to manage. In a systematic review of the relative literature we found that approximately 20% of patients with erosive esophagitis and 15-25% of patients with normal endoscopy and abnormal 24-hour esophageal pH monitoring continue to report heartburn despite treatment with standard dose PPIs. Furthermore, approximately 30-40% of patients with normal endoscopy and 24-hour pH studies and 15-20% of patients with Barrett's esophagus have refractory heartburn to double dose PPIs. In such cases, compliance to therapy, duodeno-gastroesophageal reflux, gastro-esophageal motility disorders and eradication of Helicobacter pylori infection may contribute to symptoms. Based on the available evidence, we suggested an algorithm for the evaluation and management of these patients.