Alcala-Gonzalez Luis G, Guillen-Del-Castillo Alfredo, Aguilar Cayuelas Ariadna, Barber Caselles Claudia, Codina-Clavaguera Claudia, Marin García Antonio, Serra Jordi, Malagelada Carolina, Simeón-Aznar Carmen P
Digestive System Research Unit, Department of Digestive Diseases, Vall d'Hebron University Hospital, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd).
Rheumatology (Oxford). 2025 May 1;64(5):3074-3079. doi: 10.1093/rheumatology/keae481.
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 oesophagitis.
We performed a cross-sectional study in a single-centre cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an oesophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive oesophagitis were compared with those with endoscopically normal oesophageal mucosa.
A total of 69 patients were included. From these, 23 patients (33%) had PPI-refractory oesophagitis (Grade A, n = 11; Grade B, n = 7; Grade C, n = 2; Grade D, n = 3) and 46 (67%) had an endoscopically normal oesophageal mucosa. On univariate analysis, patients with PPI-refractory oesophagitis were more frequently diffuse SSc subset (43% vs 17%; P = 0.041). Evaluating gastrointestinal motility tests, neither absent oesophageal contractility (39% vs 25%, P = 0.292) nor hypotensive lower oesophageal sphincter (47% vs 44%, P = 0.980) were significantly associated with PPI-refractory oesophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory oesophagitis (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 oesophagitis, while absent oesophageal 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 oesophagitis in patients with systemic sclerosis.
系统性硬化症患者常伴有严重的胃食管反流病，且对质子泵抑制剂（PPI）治疗往往无效。本研究旨在确定与PPI难治性食管炎相关的因素。
我们在一个单中心队列中对诊断为系统性硬化症的患者进行了一项横断面研究。我们纳入了正在接受PPI治疗且接受过食管胃十二指肠镜检查的患者。将PPI难治性糜烂性食管炎患者与食管黏膜内镜检查正常的患者进行比较。
共纳入69例患者。其中，23例患者（33%）患有PPI难治性食管炎（A级，n = 11；B级，n = 7；C级，n = 2；D级，n = 3），46例（67%）食管黏膜内镜检查正常。单因素分析显示，PPI难治性食管炎患者更常属于弥漫性系统性硬化症亚型（43%对17%；P = 0.041）。评估胃肠动力测试时，食管无收缩力（39%对25%，P = 0.292）和食管下括约肌低压（47%对44%，P = 0.980）均与PPI难治性食管炎无显著相关性。定义为胃排空异常和/或小肠扩张肠袢的胃肠动力障碍与PPI难治性食管炎显著相关（66%对8%，P =<0.001）。在一个多变量回归模型中，为评估经弥漫性亚型调整后的动力测试结果之间的关联，胃肠动力障碍（β = 0.751，P = 0.010）与PPI难治性食管炎独立相关，而食管无收缩力（β = 0.044，P = 0.886）或食管下括约肌低压则不然（β = -0.131，P = 0.663）。
我们的研究结果表明，胃和小肠运动功能障碍可能是系统性硬化症患者发生PPI难治性食管炎的重要因素。
