系统性硬化症–重叠综合征患者的临床特点及影响因素分析

Analysis of Clinical Characteristics and Influencing Factors of Systemic Sclerosis Overlap Syndrome

摘要: 目的：探讨系统性硬化症(SSc)合并重叠综合征(SSc-OS)的临床特征及相关影响因素，为临床诊治提供参考依据。方法：收集2019年1月1日至2023年12月31日广西医科大学第一附属医院风湿免疫科住院SSc患者的临床资料，按是否合并OS分为OS组与非OS组。比较两组在人口学特征、临床表现及实验室检查方面的差异，采用二元Logistic回归分析SSc-OS的独立影响因素，进一步将OS组分为SSc-IIM组、SSc-SS组及其它组进行亚组分析，最后通过Kaplan-Meier曲线比较两组患者的生存差异。结果：共纳入298例SSc患者，平均发病年龄为(51.8 ± 11.9)岁，男女比例为1:1.9；其中弥漫型202例(67.8%)、局限型92例(30.9%)、无皮肤型4例(1.3%)。SSc-OS患者66例(22.1%)，其中重叠特发性炎性肌病(IIM)28例(42.4%)、干燥综合征(SS) 20例(30.3%)、系统性红斑狼疮(SLE) 7例(10.6%)、类风湿关节炎(RA)5例(7.6%)，另有6例(9.1%)同时重叠了3种结缔组织病。与非OS组相比，OS组中口眼干燥、消化道症状、肌肉受累、肾功能不全及抗Ro-52抗体阳性比例更高，而血红蛋白、白蛋白及补体C3水平较低，抗Scl-70抗体阳性率较低(均P < 0.05)。OS组糖皮质激素(GC)使用剂量及羟氯喹、沙利度胺应用率显著增加(均P < 0.05)。Logistic回归分析显示，口眼干燥及肌肉受累为SSc-OS的危险因素，抗Scl-70抗体阳性为保护因素。亚组分析显示，SSc-SS组中男性患者比例、MRSS评分及喝酒人数比例均低于SSc-IIM组，而抗Ro-52抗体阳性的比例高于SSc-IIM组，口眼干燥的比例明显高于另两组，此外，SSc-IIM组肌肉受累的比例高于另两组(均P < 0.05)。平均随访2.5 (1.4, 4.0)年，两组在生存时间与死亡率方面无统计学差异(均P > 0.05)。OS组死亡的主要原因为间质性肺病合并感染，占50%。结论：SSc-OS的发生率为22.1%，以重叠IIM及SS最为常见。此类患者更易出现口眼干燥、消化道症状、肌肉受累、肾功能不全及抗Ro-52抗体阳性，糖皮质激素使用剂量相对较高。口眼干燥与肌肉受累是SSc-OS发生的危险因素，抗Scl-70抗体阳性具有潜在保护作用。

Abstract: Objective: To investigate the clinical characteristics and influencing factors of systemic sclerosis-overlap syndrome (SSc-OS) and provide a reference for clinical diagnosis and management. Methods: Clinical data of SSc patients hospitalized in the Department of Rheumatology and Immunology at the First Affiliated Hospital of Guangxi Medical University from January 1, 2019, to December 31, 2023, were retrospectively analyzed. Patients were classified into an OS group and a non-OS group according to the presence of overlap syndrome. Demographic data, clinical manifestations, and laboratory findings were compared between the two groups. Binary logistic regression analysis was used to identify independent influencing factors. The OS group was further stratified into SSc-IIM, SSc-SS, and other subgroups for subgroup analysis. Finally, Kaplan-Meier survival analysis was performed to compare survival outcomes. Results: A total of 298 SSc patients were included, with a mean age of onset of 51.8 ± 11.9 years and a male-to-female ratio of 1:1.9. Diffuse cutaneous SSc accounted for 202 cases (67.8%), limited cutaneous SSc for 92 cases (30.9%), and sine scleroderma for 4 cases (1.3%). Among the 66 patients (22.1% ) with SSc-OS, the most common overlap was with idiopathic inflammatory myopathy (IIM) in 28 cases (42.4%), followed by Sjögren’s syndrome (SS) in 20 cases (30.3%), systemic lupus erythematosus (SLE) in 7 cases (10.6%), and rheumatoid arthritis (RA) in 5 cases (7.6%). Additionally, 6 patients (9.1%) had overlap with three types of connective tissue diseases simultaneously. Compared with the non-OS group, the OS group had significantly higher frequencies of sicca symptoms, gastrointestinal involvement, muscle involvement, renal insufficiency, and anti-Ro-52 antibody positivity, and lower levels of hemoglobin, albumin, and complement C3, as well as a lower prevalence of anti-Scl-70 antibody positivity (all P < 0.05). The OS group received higher doses of glucocorticoids and had higher rates of hydroxychloroquine and thalidomide use (all P < 0.05). Logistic regression analysis identified sicca symptoms and muscle involvement as risk factors for OS, while anti-Scl-70 antibody positivity was a protective factor. The subgroup analysis showed that in the SSc-SS group, the proportion of male patients, the MRSS score, and the proportion of alcohol drinkers were all lower than those in the SSc-IIM group. The proportion of positive anti-Ro-52 antibodies was higher than that in the SSc-IIM group, the proportion of sicca symptoms was significantly higher than that in the other two groups, and the proportion of muscle involvement in the SSc-IIM group was higher than that in the other two groups (all P < 0.05). During a median follow-up of 2.5 (1.4, 4.0) years, no significant differences in survival rate or survival time were observed between the two groups (both P > 0.05). Interstitial lung disease with infection was the leading cause of death in the OS group, accounting for 50% of cases. Conclusion: The incidence of SSc-OS was 22.1%, with IIM and SS as the most common overlaps. SSc-OS patients were more likely to present with sicca symptoms, gastrointestinal manifestations, muscle involvement, renal insufficiency, and anti-Ro-52 antibody positivity, and required higher glucocorticoid doses. Sicca symptoms and muscle involvement were independent risk factors for OS, whereas anti-Scl-70 antibody positivity was a protective factor.