Phenotyping and symptom diagnostic accuracy in unproven gastroesophageal reflux disease (GERD): An experience from Saudi GI Motility Labs.

Abstract

Background: The recent Saudi Gastroenterology Association (SGA) clinical care pathway for gastroesophageal reflux disease (GERD) recommends objective physiologic testing in patients with persistent reflux symptoms and normal endoscopy. This study aimed to phenotype patients with unproven GERD using 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring and high-resolution manometry (HRM), and to evaluate the diagnostic utility of reflux symptoms.

Methods: In this retrospective cohort study, adult patients with reflux-like symptoms and either normal endoscopy or Los Angeles grade A esophagitis underwent off-proton pump inhibitor MII-pH monitoring and HRM, between July 2020 and September 2025. GERD phenotypes were classified as non-erosive reflux disease (NERD), reflux hypersensitivity (RH), or functional heartburn (FH) according to the Lyon Consensus v2.0 and SGA clinical care pathway guidelines. Manometric findings were interpreted using the Chicago Classification criteria. The sensitivity and specificity of typical and extra-esophageal symptoms for identifying NERD were assessed.

Results: A total of 117 patients were included (median age 39 years; 53.85% male). Phenotyping identified 27.35% as NERD, 47.86% as RH, and 24.79% as FH. Symptom profiles overlapped across groups. Median acid exposure time and mean nocturnal baseline impedance showed expected physiologic gradients, with the highest acid burden and lowest impedance in NERD. Abnormal esophageal motility was present in 34.2%, most commonly ineffective esophageal motility. Heartburn and regurgitation were highly sensitive (93.75% and 90.62%, respectively), but poorly specific (8.24% and 15.29%, respectively) for NERD, whereas cough and laryngitis were highly specific (88.24% and 84.71%, respectively), but minimally sensitive (6.25% and 9.38%, respectively).

Conclusion: RH and FH predominate in patients with unproven GERD. Symptom assessment alone is insufficient for accurate diagnosis, although typical symptoms retain screening value due to their high sensitivity. These findings highlight the need for integrated physiologic testing to guide precise phenotyping and individualized management.