Endoscopy-negative reflux disease.

Endoscopy-negative reflux disease (ENRD) is more prevalent than reflux esophagitis, especially in a primary care setting. Acid-sensitive esophagus (ie, reflux-related symptoms with normal acid exposure at 24-hour pH monitoring) is part of the gastroesophageal reflux disease spectrum. ENRD is not a mild disease (symptoms return frequently and have an impact on quality of life), but it rarely progresses to the erosive stage. In patients with atypical or extra-esophageal manifestations, pH monitoring remains useful, and symptom analysis (symptom index or symptom-associated probability) is of pivotal importance. A proton pump inhibitor (PPI) test may represent a cost-effective alternative to 24-hour pH monitoring. However, well-designed validation studies are necessary to assess the diagnostic value of PPI tests and improve specificity without reducing sensitivity. Management of ENRD is based on the same principles as that of reflux esophagitis. Restoration of quality of life is the major goal. Proton pump inhibitors are not more (and are sometimes even less) effective in non-erosive reflux disease than in reflux esophagitis. Different long-term strategies (continuous maintenance, intermittent or on-demand therapy) are available, depending on the needs of the patient. Antireflux surgery may be indicated in carefully selected patients. In the future, pharmacologic approaches targeted to transient lower esophageal sphincter relaxation or visceral perception should be developed.