Review article: gastro-oesophageal reflux disease as a functional gastrointestinal disorder

Gastro-oesophageal reflux disease encompasses a family of disorders united by a common pathogenesis: the excessive reflux of gastric contents. The best defined disorder is oesophagitis, but it is now evident that proton pump inhibitor therapy can resolve oesophagitis in virtually every case. The same cannot be said for gastro-oesophageal reflux disease symptoms, however, thus moving the frontier to symptom control. Endoscopy-negative reflux disease is a heterogeneous group, no longer bound by the common denominator of endoscopic findings. In fact, three distinct patient subgroups emerge: (i) individuals who in essence have oesophagitis, but are either in remission or simply fail to meet the endoscopic criteria; (ii) patients with hypersensitivity to oesophageal stimuli; and (iii) patients with 'functional heartburn' whose symptoms are not related to reflux. Given this heterogeneity, it is not surprising that the efficacy of antisecretory drugs is less impressive. This has led to new therapeutic approaches beyond acid control: mucosal protective agents, either central nervous system or peripherally acting compounds aimed at normalizing hyperalgesia, and reflux inhibitors and serotonergic agents, such as tegaserod.