Endoscopy-negative reflux disease: concepts and clinical practice.

Endoscopy-negative reflux disease is used to describe a heterogeneous group of disorders with symptoms that mimic those of gastroesophageal reflux disease in the absence of visible esophageal injury at endoscopy. Compared with patients who have gastroesophageal reflux-related erosive esophagitis, those with endoscopy-negative disease are more likely to be younger, female, of lower body weight, and without a hiatal hernia. Approximately 50% of those with endoscopy-negative reflux have abnormal intraesophageal acid exposure and are considered to have nonerosive acid reflux disease. Those with symptoms of >12 consecutive or intermittent weeks' duration during the prior year, with normal acid exposure and without achalasia or other motility disorder with a recognized pathologic basis, are considered to have functional heartburn. In the absence of pathologic reflux, a number of etiologies may contribute to the symptoms of heartburn, including motor events, reflux of nonacidic gastric contents, minute changes in intraesophageal pH (pH <4), visceral hypersensitivity, and emotional or psychological abnormalities. Although persons with endoscopy-negative reflux disease experience decrements in their quality of life that are similar to those for individuals with erosive esophagitis, the response to traditional therapies for acid reflux may differ between the 2 groups. Studies have found that approximately 50% of patients with endoscopy-negative reflux disease experience complete symptom relief after 4 weeks of proton pump inhibitor treatment. In those with persistent heartburn symptoms, other structural or nonacid reflux etiologies for their symptoms should be explored.