In symptomatic patients despite empiric trials of proton pump inhibitors (PPIs) with no prior GERD evidence, endoscopy and ambulatory reflux monitoring are recommended off therapy. The novel Lyon scoring system based on the Lyon consensus 2.0 can stratify symptoms into phenotypes associated with the likelihood of GERD diagnosis and response to anti-reflux treatment. We applied the Lyon scoring system in patients with typical and/or atypical symptoms poorly responsive to a standard dose of PPIs and compared the Lyon score and phenotypes between typical and atypical symptom groups.  

In 141 patients (52.9 ± 14.9 years, M/F = 60/80) with typical (heartburn, regurgitation or esophageal chest pain) or atypical (globus, sore throat or throat clearing) symptoms poorly responsive to an empiric trial of standard dose of proton pump inhibitors, ambulatory pH-impedance monitoring was performed off antisecretory therapy using manometric localization of the LES to position the pH sensor 5 cm proximal to the LES. All patients underwent endoscopy off medication before esophageal reflux testing. The Lyon scoring system reported by Gyawali CP, et al., published in 2024, was applied and stratified the symptom groups into phenotypes. Symptom groups are subclassified as the typical symptom group (n=79), the overlap symptom group with both typical and atypical symptoms (n=26), and the atypical symptom group (n=36). The phenotypes of no GERD, isolated permeability defect and reflux hypersensitivity were classified as the group likely to respond poorly to the anti-reflux therapy, whereas the phenotypes of inconclusive or borderline GERD, conclusive GERD and severe GERD were classified as the group likely to respond well to the anti-reflux therapy. 

The prevalence (% (n)) of phenotypes including no GERD, isolated permeability defect, reflux hypersensitivity, inconclusive or borderline GERD, conclusive GERD and severe GERD is as follows; 65.8% (52), 3.8% (3), 13.9% (11), 3.8% (3), 11.4% (9), and 1.3% (1) in the typical symptom group, respectively; 61.5% (16), 3.8% (1), 11.5% (3), 3.8% (1), 15.4% (4), and 3.8% (1) in the overlap symptom group, respectively; and 69.4% (25), 5.6% (2), 22.2% (8), 2.8% (1), 0% and 0% in the atypical symptom group, respectively. The sex ratio did not significantly differ in the symptom groups (P = 0.540). The mean age of the the atypical symptom group tended to be lower than that of the overlap symptom group (49.9 ± 14.9 vs 57.0 ± 13.1 years, P=0.053). The mean age of the Lyon score was 2.1 (range 0-11). The proportion of the group likely to respond poorly to the anti-reflux therapy was greater in the atypical symptom group, compared with the overlap symptom group (P=0.023) and the typical symptom group (P=0.067)

No GERD and reflux hypersensitivity are the main phenotypes in patients with typical and/or atypical symptoms poorly responsive to PPIs. The likelihood to respond to the anti-reflux therapy is the lowest in the atypical symptom alone group.