Heterogeneity of endoscopy negative heartburn: epidemiology and natural history

It has now become clear that only about 40% or less of patients with heartburn and/or regurgitation have esophagitis, and that the majority of them lack visible distal esophageal mucosa breaks. These subjects are referred to as non-erosive gastroesophageal reflux disease (NERD) patients. It has been estimated that in the Western world at least one tenth of the general population has at least weekly heartburn. This proportion seems to be lower in Asia, while prevalence is rapidly increasing. Although it would be extremely useful to have prospective information regarding the fate of such patients, the natural history of NERD is largely unknown, and very few studies in the literature have addressed this issue. These studies are for the greater part old, not well conducted, and suffer from methodological drawbacks including ill-defined entry criteria. However, a review of these studies indicates that a consistent minority of NERD patients may develop erosive disease at an approximate rate of about 10% per year.