Background Gastroesophageal reflux disease (GERD) is highly prevalent in systemic sclerosis (SSc) and frequently persists despite proton pump inhibitor (PPI) therapy. However, the mechanisms underlying PPI-refractory GERD in SSc remain incompletely understood.

Methods We conducted a singlel7lcentre, retrospective study of adults with SSc who underwent ambulatory pH-multichannel intraluminal impedance (pH/MII) monitoring while receiving twicel7ldaily PPI therapy (2021–2025). Esophageal motility (highl7lresolution 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 PPIl7lrefractory 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.

The authors have declared no competing interest.

This work was supported by the Instituto de Salud Carlos III and co-financed by the European Union (FEDER/FSE) [PI22/01804, PI25/00647]. LA was supported by a Gonzalo Mino Grant Asociacion Espanola de Gastroenterologia (AEG) (Recipient March 2026). ZM is funded by NIH (1 R01 AR081382-01A1).

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