Gastroesophageal reflux disease (GERD) encompasses a heterogeneous group of patients with differences in sensitivity to esophageal acid exposure, perception of pain, and physiological tissue involvement. The most difficult patients to understand are those who have a great symptom burden but no endoscopic evidence of esophageal mucosal involvement. These patients with symptomatic GERD (also called nonerosive reflux disease and endoscopy-negative reflux disease) present a diagnostic challenge. Diagnostic tests, like ambulatory pH monitoring, the acid perfusion test, and intraesophageal balloon distension, have limited reliability in patients with this form of GERD whose symptoms may exhibit poor correlation with acid exposure or mechanostimulation. The recent interest in a proton pump inhibitor therapeutic trial to identify the group of symptomatic GERD patients (having ruled out risk factors for more morbid conditions) who will respond to these agents has considerable appeal. It has been shown effective in about 75% of patients, and offers a simple approach to managing the difficult-to-diagnose patient even while further diagnostic procedures are carried out.
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