Recent insights on functional heartburn and reflux hypersensitivity

Abstract

Purpose of reviewRome IV experts have proposed that gastroesophageal reflux disease (GERD) should be diagnosed only in patients with abnormal esophageal acid exposure, and that reflux hypersensitivity (RH) and functional heartburn (FH) both should be considered functional conditions separate from GERD. Although past and recent evidence support that FH can be completely distinguished from GERD, the concept that RH is not GERD is highly questionable. This review attempts to provide current data on these issues.Recent findingsMany recent investigations have provided new data on the different pathophysiological features characterizing RH and FH. Major differences have emerged from analyses of impedance-pH monitoring studies using the novel impedance metrics of baseline impedance (an index of mucosal integrity) and the rate of postreflux swallow-induced peristaltic waves (a reflection of the integrity of esophageal chemical clearance).SummaryThe better ability to interpret impedance-pH tracings together with earlier data on the different prevalence of microscopic esophagitis in RH and FH patients, and recent studies documenting poor therapeutic efficacy of pain modulators and good results of antireflux surgery for RH support recategorization of RH within the GERD world. Further research is needed to correctly phenotype patients who have heartburn without mucosal breaks, and to guide their effective management.

A perspective on the clinical relevance of weak or nonacid reflux

“…RH is defined by the presence of esophageal symptoms in response to reflux events despite normal total AET, with positive reflux‐symptom correlation using SI and/or SAP. Mechanistically, this can be explained by esophageal hypersensitivity, with lowered threshold for chemo‐ and mechanosensitivity, abnormal central processing of sensation, and hypervigilance 40–42 . However, Savarino et al found that the prevalence of dilated intracellular spaces in RH patients was increased similar to nonerosive reflux when compared to functional heartburn or healthy controls, indicating that some RH patients have characteristics within the GERD realm rather than a pure disorder of brain–gut interaction 43 .…”

“…Mechanistically, this can be explained by esophageal hypersensitivity, with lowered threshold for chemo-and mechanosensitivity, abnormal central processing of sensation, and hypervigilance. [40][41][42] However, Savarino et al found that the prevalence of dilated intracellular spaces in RH patients was increased similar to nonerosive reflux when compared to functional heartburn or healthy controls, indicating that some RH patients have characteristics within the GERD realm rather than a pure disorder of brain-gut interaction. 43 This raises the likelihood of even WAR having epithelial access in activating chemosensitive receptors, thereby contributing to damage to esophageal mucosal integrity.…”

Improved diagnosis of reflux hypersensitivity

“…After the exclusion of eosinophilic esophagitis and major motility disorders, approximately 1/3 of such patients will be categorized as having reflux hypersensitivity (RH) or functional heartburn (FH) according to the existence or not of a correlation between symptoms and reflux episodes 2,3 . FH and RH are characterized by normal esophageal acid exposure, 4 although, patients with RH show a positive correlation of their symptoms to reflux episodes and may be benefited by proton pump inhibitor (PPI) therapy 5 . On the contrary, patents with FH have an increased rate of other Functional Gastrointestinal diseases 6,7 …”

“…reflux episodes and may be benefited by proton pump inhibitor (PPI) therapy. 5 On the contrary, patents with FH have an increased rate of other Functional Gastrointestinal diseases. 6,7 Previous studies showed that, compared to patients with FH, patients with RH show higher rates of hiatus hernia (HH) existence, acid exposure time (AET), increased total number of refluxes (acid and nonacid) and refluxes with proximal extent.…”

“…8,9 The existence of such differences led experts in the field to propose that RH should not be considered as a disorder of brain-gut interaction, but rather one belonging in the spectrum of GERD. 5 There is no clear written consensus on the criteria that should be used in order to diagnose RH. 4,10,11 Some clinicians ask for both SI and SAP positivity, while many studies rely on the positivity of one of them in order to set RH diagnosis.…”