Revenge of the NERDs: Cadherin Fragments Differentiate Functional Heartburn from Non-erosive Reflux Disease

Due to the ever-increasing use of proton pump inhibitors (PPI), the therapeutic front line in gastroesophageal reflux disease (GERD) has changed. The successful healing of esophagitis, an elusive therapeutic target a mere 25 years ago, has been eclipsed by new considerations, with emphasis now being focused on symptom resolution, in particular, heartburn. Moreover, patients with heartburn are a heterogeneous group, including subpopulations with different mechanisms responsible for their symptoms. Patients with GERD symptoms such as heartburn either have increased esophageal acid exposure with (erosive esophagitis; EE) or without (non-erosive reflux disease; NERD) erosions, or with normal acid exposure with acid hypersensitivity (functional heartburn; FH) [1]. Although EE is readily diagnosed, the distinction between patients diagnosed with NERD and those with FH can be difficult despite being highly clinically relevant: the first group mostly benefits from pharmacological suppression of acid secretion or from surgical anti-reflux therapy, whereas in the second group, prolonged therapy with proton pump inhibitors (PPI) and anti-reflux surgery are unnecessary and possibly harmful and should thus be assiduously avoided. Until now, the missing piece in this puzzle has been the existence of a biomarker useful to differentiate patients with NERD from FH and to predict the response to PPI therapy.