类风湿关节炎临床分层及其特征的横断面研究

A cross-sectional study on the clinical phenotypes of rheumatoid arthritis

目的:探索类风湿关节炎(rheumatoid arthritis,RA)临床分层及其特征,为RA的发病机制、临床诊治和转归评估提供依据。方法:选择2018—2021年于北京大学人民医院就诊的RA患者,收集患者一般情况、关节受累部位及数量、关节外表现、合并症及实验室检查结果等信息,采用统计及生物信息分析的方法,以受累关节部位、有无系统受累或合并其他自身免疫性疾病等进行临床分层,并对各亚型患者的特征进行分析。结果:共纳入411例RA患者,平均年龄(48.84±15.17)岁,其中女性346例(84.2%)。患者被分为小关节型(74,18.0%)、全关节型(154,37.5%)、系统型(100,24.3%)、重叠型(83,20.2%)4个亚型。小关节型者无中大关节受累,其中35.1%有系统表现,红细胞沉降率(erythrocyte sedimentation rate,ESR)及C反应蛋白(C-reaction protein,CRP)水平和血小板计数较其他亚型低,而IgA及IgG类风湿因子阳性率较高;全关节型者中大关节和小关节均可受累,关节外表现少见,晨僵发生率和抗核抗体(antinuclear antibodies,ANA)阳性率显著低于其他亚型,而ESR及CRP水平相对较高;系统型者以合并肺间质纤维化和口、眼干燥症状常见,病情活动指数高;重叠型至少合并另一种风湿病或自身免疫性疾病,以桥本甲状腺炎和原发性干燥综合征最为常见,与其他亚型相比,女性多见,高免疫球蛋白血症、低补体血症和斑点型ANA为其特征。结论:根据类风湿关节炎的临床特征,可初步将其分为小关节型、全关节型、系统型、重叠型4个亚型,各有其临床和实验室特征,有助于进一步认识RA和为患者进行个体化治疗提供依据。

Objective: To explore the characteristics and clinical phenotypes of rheumatoid arthritis(RA) and provide the basis for further understanding, interventions and outcomes of this disease. Methods: RA patients attended at Peking University People’s Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations(EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. Results: A total of 411 patients with RA were enrolled. The mean age was(48.84±15.17) years, and 346(84.2%) were females. The patients were classified into 4 subtypes: small joint subtype(74,18.0%), total joint subtype(154,37.5%), systemic subtype(100,24.3%), and overlapping subtype(83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) levels and platelet count(PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors(RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies(ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjogren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count(DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto’s thyroiditis or primary Sjogren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. Conclusion: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.