Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory esophagitis. We performed a cross-sectional study in a single-center cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an esophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive esophagitis were compared with those with endoscopically normal esophageal mucosa. A total of 69 patients were included, from these, 23 patients (33%) had PPI-refractory esophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal esophageal mucosa. On univariate analysis, patients with PPI-refractory esophagitis were more frequently diffuse SSc subset (43% vs 17%; p= 0.041). Evaluating gastrointestinal motility tests, neither absent esophageal contractility (39% vs 25%, p= 0.292) nor hypotensive lower esophageal sphincter (47% vs 44%, p= 0.980) were significantly associated with PPI-refractory esophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory esophagitis (66 vs 8%, p = <0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (β = 0.751, p= 0.010) was independently associated with PPI-refractory esophagitis, while absent esophageal contractility (β = 0.044, p= 0.886) or a hypotensive LES were not (β=-0.131, p= 0.663). Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory esophagitis in patients with systemic sclerosis.

Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by microvascular damage and fibrosis. Mortality in patients with SSc has significantly decreased. Consequently, patients with SSc have longer life expectancy, and health-related quality of life (HrQoL) has become more relevant in the comprehensive management of the disease. Objective To evaluate the impact between gastrointestinal (GI) symptom burden and psychological well-being on HrQoL in patients with SSc. Design Nested cross-sectional study conducted between January and July 2022. Participants A single-centre cohort of 166 patients with SSc, including 103 (55%) with limited cutaneous SSc, 43 (24%) with diffuse SSc and 37 (21%) with sine-sclerosis SSc. Main measures GI symptom burden was assessed using the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract 2.0 (UCLA SCTC GIT 2.0) questionnaire, psychological well-being was measured with the Hospital Anxiety and Depression Scale (HADS), and HrQoL was evaluated using the Short Form 36 (SF-36) questionnaire. Demographic, clinical and immunological data were collected from a prospectively maintained database. Key results Patients with moderate to severe GI symptoms (UCLA SCTC GIT 2.0 score >0.5, n=95, 57%) reported decreased HrQoL in all subdomains except vitality by SF-36, and higher anxiety and depression scores by HADS (all p<0.05). The severity of GI symptom burden and depression were independently associated with a decline in the physical component of QoL (β=−0.273 and β=−0.411, respectively, p<0.01 for both). Only the severity of depression and anxiety (β=−0.482 and β=−0.213, respectively, p<0.05), but not GI symptom burden, were independently associated with a decline in the mental component of QoL. Conclusions Our data suggest that in patients with SSc, GI and psychological burden negatively influence quality of life independently, highlighting the need for a holistic approach to patient’s care.

Objectives: Oesophageal dysmotility is a common manifestation of SSc, contributing to substantial morbidity. We sought to determine whether oesophageal dysmotility patterns by high-resolution oesophageal manometry were associated with distinct SSc clinical phenotypes and different outcomes. Methods: We analysed a cohort of SSc patients with detailed clinical and immunological data. Oesophageal motility was classified using Chicago 4.0 criteria, and baseline characteristics were compared across motility patterns [absent contractility (AC), ineffective oesophageal motility (IEM) and normal motility]. Associations with adverse outcomes (death or lung transplantation) were evaluated using Kaplan–Meier and Cox regression analyses. Results: Our cohort included 201 patients with SSc (84% female, mean age 45 ± 17 years, follow-up 442 person-years). Oesophageal dysmotility patterns were classified as AC in 86 (43%), IEM in 57 (28%) and normal motility in 58 (29%). AC was associated with dcSSc, more severe digital ulcers, gastric vascular ectasia, anti-Ro60 antibodies and a late pattern on nailfold capillaroscopy (P < 0.05), while IEM was linked to limited SSc, anti-centromere antibodies and an early/active nailfold pattern. Multivariate time-to-event analysis identified AC as an independent risk factor for lung transplantation (HR = 7.004, 95%CI: 1.481–33.135, P = 0.014) after adjusting for both interstitial lung disease and male sex, and for SSc-related death (HR = 3.472, 95%CI: 1.071–10.969, P = 0.038) after adjusting for DcSSc and interstitial lung disease. Conclusions: We found that patients with AC and IEM have distinct clinical phenotypes, suggesting they are distinct entities. In patients with SSc, AC is independently associated with worse outcomes. These data suggest that HREM may be useful in risk stratification and outcome predictions in patients with SSc.

Objectives: To determine the prevalence of objectively defined gastric dysmotility in SSc and to evaluate its associations with SSc clinical and immunological features and adverse outcomes (SSc-related death and/or lung transplantation). Methods: We conducted a retrospective cohort study. All participants underwent a standardized 4-h solid gastric emptying scintigraphy. Gastric dysmotility was defined as ≥20% gastric retention at 4-h. We examined associations between gastric dysmotility and demographic, clinical and immunologic characteristics of SSc, as well as relevant clinical outcomes. Results: Ninety-four patients were included (mean age 48 ± 12 years; 81% female). Gastric dysmotility was identified in 33 patients (35%). Patients with gastric dysmotility had a higher prevalence of interstitial lung disease (63.6% vs 30.3%, P = 0.033) and absent oesophageal contractility (75.8% vs 45.9%, P < 0.001) compared with those without. Gastric dysmotility was less frequent in patients with ACAs (27.3% vs 55.0%, P = 0.009) but more common in those with anti-U1RNP antibodies (15.6% vs 1.7%, P = 0.011). During follow-up (mean duration 2.8 ± 1.7 years; 260 person-years), 16 patients (17.0%) experienced the composite end point of SSc-related death and/or lung transplantation. In unadjusted Cox regression, gastric dysmotility was strongly associated with adverse outcomes (HR = 6.47, 95% CI: 2.09–20.10, P = 0.001), which remained significant after adjustment for confounders (HR = 4.23, 95% CI: 1.25–14.33, P = 0.020). Conclusions: In SSc, we have confirmed that gastric dysmotility is associated with a distinct clinical and serological phenotype and that it independently predicts serious adverse outcomes. These findings underscore the importance of objective assessment of gastric function and its potential role in risk stratification.

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 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 to 2025). Esophageal motility (high resolution manometry, HREM) and gastric emptying scintigraphy were integrated to examine associations between gastroesophageal dysmotility and reflux phenotypes. Results. Thirty patients were included, of whom 67% had PPI refractory reflux symptoms and 33% were undergoing prelung 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.