Between GERD and NERD: the relevance of weakly acidic reflux.

Nonerosive reflux disease (NERD) is a common condition and the most frequent phenotype of gastroesophageal reflux disease (GERD). NERD is extremely heterogeneous and includes patients with negative endoscopy but abnormal esophageal acid exposure and/or positive reflux-symptom association analysis (hypersensitive esophagus). This segregation is only possible owing to the use of impedance-pH monitoring. Indeed, weakly acidic reflux represents one of the most common causes of refractory symptoms in patients evaluated off antisecretory therapy and, more importantly, during antisecretory drug treatment. Patients with heartburn who do not have any type of reflux underlying their symptoms (functional heartburn) must be excluded from the category of GERD. The drawbacks of impedance-pH are mainly due to the day-to-day variability of the test and the fact that the accuracy of the symptom-reflux correlation scores is often far from perfect. Some histopathological characteristics, such as dilated intercellular spaces, can be helpful in distinguishing patients with NERD through esophageal biopsies. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to proton pump inhibitor therapy, while those with hypersensitive esophagus to weakly acidic reflux could be treated with reflux inhibitors or surgery, although further controlled studies are required.