Nonerosive reflux disease: a pathophysiologic perspective

Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal reflux disease. By definition, patients with NERD have typical reflux symptoms caused by the intraesophageal reflux of gastric contents but have no visible esophageal mucosal injury. This is in contrast to patients with reflux esophagitis, also known as erosive reflux disease, and Barrett's esophagus, who have obvious esophageal mucosal injury on endoscopy. Only 50% of patients with NERD have pathologic esophageal acid contact time (ACT) as detected on 24-hour pH monitoring (ie, NERD-positive). NERD patients with physiologic esophageal ACT and good temporal correlation of symptoms with reflux events (symptom index > 50% or symptom-association probability > 95%) are considered to have esophageal hypersensitivity (ie, NERD-negative). Finally, patients with physiologic esophageal ACT but poor symptom-reflux correlation are now considered to have functional heartburn and not NERD. NERD-positive patients have motor dysfunction and acidic reflux abnormalities that are similar to patients with reflux esophagitis and Barrett's esophagus, whereas NERD-negative patients have minimal abnormalities that are not much different than healthy controls. The histopathologic feature most indicative of NERD is the presence of dilated intercellular spaces within squamous epithelium, an ultrastructural abnormality readily identified on transmission electron microscopy and on light microscopy.