PPI-Refractory GERD in systemic sclerosis is driven by distinct esophageal and gastric motility abnormalities
Luis G Alcala-Gonzalez, Alfredo Guillen-del-Castillo, Francisco A Felix-Tellez, Ariadna Aguilar, Claudia Barber, Carolina Malagelada, Laura Polo Figueras, Laura Triginer, Claudia Codina-Clavaguera, Michael Hughes, Carmen P Simeón-Aznar, Jordi Serra, Zsuzsanna H McMahanAbstract
Objectives
Gastroesophageal reflux disease (GERD) is highly prevalent in systemic sclerosis (SSc) and frequently persists despite proton pump inhibitor (PPI) therapy. We aimed to characterize the contribution of esophageal and gastric dysmotility to PPI-refractory GERD in SSc.
Methods
We conducted a single‑centre, retrospective study of adults with SSc who underwent ambulatory pH-multichannel intraluminal impedance (pH/MII) monitoring while receiving twice‑daily PPI therapy (2021–2025). Esophageal motility (high‑resolution manometry, HREM) and gastric emptying scintigraphy were integrated to examine associations between gastro-esophageal dysmotility and reflux phenotypes.
Results
Thirty patients were included, of whom 67% had PPI-refractory reflux symptoms and 33% were undergoing pre–lung transplantation evaluation. Refractory GERD was present in 29/30 patients (97%) based on Lyon 2.0 classification, with conclusive evidence in 53% and borderline evidence in 43%. Esophageal dysmotility was identified in 80%, most commonly absent contractility (67%), and was associated with impaired reflux clearance, reflected by longer acid clearance times (2.20 [1.15–3.75] vs 1.15 [0.43–1.90] min) and prolonged reflux episode duration (16.60 [4.38–40.63] vs 1.95 [0.53–20.43] min). Gastric dysmotility was identified in 60.7% and was associated with an increased reflux episode burden (51.00 [30.00–81.50] vs 25.00 [21.00–54.00] episodes/24h).
Conclusions
PPI‑refractory GERD is nearly universal in this SSc cohort and reflects heterogeneous, quantifiable abnormalities across the foregut, including impaired esophageal clearance and increased reflux burden related to gastric retention. These findings support integrated physiologic evaluation to define reflux mechanisms, inform risk stratification (including lung transplantation), and guide targeted, mechanism-based therapies beyond acid suppression.