外周型脊柱关节炎的临床特征及治疗选择分析

曾露露, 冀肖健, 胡立冬, 胡嘉文, 张奕楠, 张家鑫, 刘兴康, 杨世伟, 黄烽

曾露露, 冀肖健, 胡立冬, 胡嘉文, 张奕楠, 张家鑫, 刘兴康, 杨世伟, 黄烽. 外周型脊柱关节炎的临床特征及治疗选择分析[J]. 协和医学杂志, 2025, 16(1): 50-58. DOI: 10.12290/xhyxzz.2024-0394
引用本文: 曾露露, 冀肖健, 胡立冬, 胡嘉文, 张奕楠, 张家鑫, 刘兴康, 杨世伟, 黄烽. 外周型脊柱关节炎的临床特征及治疗选择分析[J]. 协和医学杂志, 2025, 16(1): 50-58. DOI: 10.12290/xhyxzz.2024-0394
ZENG Lulu, JI Xiaojian, HU Lidong, HU Jiawen, ZHANG Yinan, ZHANG Jiaxin, LIU Xingkang, YANG Shiwei, HUANG Feng. Clinical Characteristics and Treatment Options of Peripheral Spondyloarthritis[J]. Medical Journal of Peking Union Medical College Hospital, 2025, 16(1): 50-58. DOI: 10.12290/xhyxzz.2024-0394
Citation: ZENG Lulu, JI Xiaojian, HU Lidong, HU Jiawen, ZHANG Yinan, ZHANG Jiaxin, LIU Xingkang, YANG Shiwei, HUANG Feng. Clinical Characteristics and Treatment Options of Peripheral Spondyloarthritis[J]. Medical Journal of Peking Union Medical College Hospital, 2025, 16(1): 50-58. DOI: 10.12290/xhyxzz.2024-0394

外周型脊柱关节炎的临床特征及治疗选择分析

基金项目: 

新疆维吾尔自治区重点研发计划 2022B03002-3

青年自主创新科学基金-扶持项目 22QNFC139

北京市自然科学基金-海淀原始创新联合基金 L242143

详细信息
    通讯作者:

    黄烽, E-mail:fhuang@301hospital.com.cn

  • 中图分类号: R681.5+1;R684.3;R758.63

Clinical Characteristics and Treatment Options of Peripheral Spondyloarthritis

Funds: 

Key Research and Development Project of Xinjiang Uygur Autonomous Region 2022B03002-3

Youth Independent Innovation Science Fund Project of Chinese PLA General Hospital 22QNFC139

Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund L242143

More Information
  • 摘要:
    目的 

    比较外周型脊柱关节炎(peripheral spondyloarthritis, pSpA)与中轴型脊柱关节炎(axial spondyloarthritis, axSpA)的临床特征和治疗选择差异, 分析pSpA的临床特点及用药需求。

    方法 

    本研究为回顾性队列研究。选取2016年1月—2022年12月首次就诊于中国人民解放军总医院第一医学中心且诊断符合国际脊柱关节炎协会制定的axSpA或pSpA分类标准的患者为研究对象。通过电子病历管理系统和脊柱关节炎智能管理系统获取患者的人口学数据、临床特征、实验室检查及治疗情况。比较pSpA与axSpA患者, 以及pSpA1(除外银屑病关节炎)与axSpA患者的关节肿胀和压痛分布情况, 并比较其临床特征和治疗选择差异。

    结果 

    共纳入脊柱关节炎患者1639例, 其中pSpA患者184例(含银屑病关节炎97例), axSpA患者1455例。相较于axSpA患者, pSpA男性患者更少(62.5%比79.7%, P<0.001)、发病年龄更晚(33.8岁比22.0岁, P<0.001), 诊断延误时间更短(6.0个月比14.2个月, P=0.004), 伴随外周关节炎(71.7%比9.3%, P<0.001)和指/趾炎(6.5%比0.3%, P<0.001)更多, 合并银屑病更多(52.7%比1.1%, P<0.001), 且银屑病家族史更普遍(11.4%比3.4%, P<0.001);炎症指标更高但人类白细胞抗原(human leukocyte antigen, HLA)-B27阳性率更低(43.5%比87.4%, P<0.001), 且HLA-B27阳性与发病年龄较早、较少合并银屑病、具有强直性脊柱炎家族史相关。pSpA患者使用传统合成改善病情抗风湿药物(conventional synthetic disease-modifying antirheumatic drugs, csDMARDs)、生物类改善病情抗风湿药物(biologic disease-modifying antirheumatic drugs, bDMARDs)和口服糖皮质激素的占比更高, 同时更多采用bDMARDs与csDMARDs联合用药(19.0%比12.2%, P=0.009)或多种csDMARDs合用(65.8%比12.5%, P<0.001)。相较于axSpA患者, pSpA1患者除合并银屑病、合并葡萄膜炎、银屑病家族史及bDMARDs用药无统计学差异外, 其余变量的亚组分析与pSpA患者结果一致。

    结论 

    pSpA患者通常发病较晚, 男性和HLA-B27阳性患者占比较低, 多伴随外周关节炎、指/趾炎, 合并银屑病及家族史更普遍。pSpA在治疗方面的疾病负担并不低于axSpA, 由于伴随更多的外周症状、银屑病以及更高的炎症指标等, 对治疗药物的需求也更多。

    Abstract:
    Objective 

    To compare the differences in clinical features and treatment choices between peripheral spondyloarthritis(pSpA) and axial spondyloarthritis(axSpA), and better understand the clinical characteristics and medication needs of pSpA.

    Methods 

    Our study is a retrospective cohort study. The patients who first visited the First Medical Center of Chinese PLA General Hospital between January 2016 and December 2022 and were diagnosed with axSpA or pSpA according to the classification criteria established by the Assessment of SpondyloArthritis International Society were selected as the study subjects. Demographic data, clinical characteristics, laboratory tests, and treatment information of these patients were obtained through the electronic medical records management system and the intelligent management system for spondyloarthritis. The research compared the distribution of swollen and tender joints between pSpA and axSpA patients, as well as that between pSpA1(excluding patients with psoriatic arthritis) and axSpA patients. Additionally, we analyzed differences in clinical features and treatment options among these groups.

    Results 

    A total of 1639 patients were included in the study, of which 184 had pSpA(including 97 with psoriatic arthritis), and 1455 had axSpA. Compared to axSpA patients, pSpA patients had fewer male patients(62.5% vs. 79.7%, P < 0.001), later onset age(33.8 years vs. 22.0 years, P < 0.001), shorter diagnostic delays(6.0 months vs. 14.2 months, P=0.004), more associated peripheral arthritis(71.7% vs. 9.3%, P < 0.001) and dactylitis(6.5% vs. 0.3%, P < 0.001), more cases of psoriasis(52.7% vs. 1.1%, P < 0.001) and a more common family history of psoriasis(11.4% vs. 3.4%, P < 0.001). pSpA patients had higher levels of inflammatory markers but a lower positive rate of human leukocyte antigen(HLA)-B27(43.5% vs. 87.4%, P < 0.001). A positive HLA-B27 was associated with an earlier onset age, fewer cases of psoriasis, and a family history of ankylosing spondylitis. pSpA patients had a higher proportion of using conventional synthetic disease-modifying antirheumatic drugs(csDMARDs), biologic disease-modifying antirheumatic drugs(bDMARDs), and oral glucocorticoids, and they also more frequently used a combination of bDMARDs and csDMARDs(19.0% vs. 12.2%, P=0.009) or multiple csDMARDs(65.8% vs. 12.5%, P < 0.001). Compared to axSpA patients, pSpA1 patients(excluding psoriatic arthritis) did not show significant differences in the prevalence of psoriasis, uveitis, family history of psoriasis, or the use of bDMARDs, but the subgroup analysis of other variables was consistent with the results of pSpA patients.

    Conclusions 

    pSpA patients tend to have a later onset of disease, a lower proportion of male and HLA-B27 positivity, more associated peripheral arthritis, dactylitis, psoriasis, and a more common family history of psoriasis. The disease burden in terms of treatment for pSpA is not lower than that for axSpA. Due to the presence of more peripheral symptoms, psoriasis, and higher levels of inflammation, they also require more medication.

  • 脊柱关节炎(spondyloarthritis,SpA)是一组侵犯脊柱、外周关节和关节周围软组织的免疫介导的慢性炎症性疾病,既往被分为强直性脊柱炎(ankylosing spondylitis,AS)、银屑病关节炎(psoriatic arthritis,PsA)、反应性关节炎、炎症性肠病性关节炎及未分化的脊柱关节炎等,不同亚型间存在重叠。随着对SpA认识的逐渐深入,根据其主要受累部位,国际脊柱关节炎协会(Assessment of Spondyloarthritis International Society,ASAS)将SpA分为中轴型脊柱关节炎(axial spondyloarthritis,axSpA)和外周型脊柱关节炎(peripheral spondyloarthritis,pSpA),并分别于2009年[1]和2011年[2]发布了新分类标准。pSpA主要表现为外周症状,包括外周关节炎、指/趾炎、外周附着点炎等,涵盖既往SpA的多种亚型[3],研究间异质性较大。但到目前为止,仅少数流行病学和临床研究将pSpA视为单独疾病[4],多数研究对pSpA各亚型进行分析,且主要集中于PsA[4],较少探究pSpA全貌,尤其对治疗选择的研究较为有限[5-6]。而外周症状对axSpA亦有重要意义,伴随外周关节炎的axSpA患者比单纯axSpA患者的疾病负担更重[7-9],而外周附着点炎则是脊柱损伤的独立危险因素[10]。本研究采用回顾性分析,探究pSpA与axSpA患者在临床特征及治疗选择上的差异,旨在深入了解pSpA患者的临床特点和疾病负担,从而指导临床实践。

    本研究为回顾性队列研究,数据来源于中国强直性脊柱炎前瞻性影像队列(Chinese Ankylosing Spondy-litis Imaging Cohort,CASPIC)和中国人民解放军总医院第一医学中心电子病历数据。选取2016年1月—2022年12月首次就诊于中国人民解放军总医院第一医学中心且诊断符合ASAS制定的axSpA或pSpA分类标准的患者为研究对象。纳入标准:(1)年龄≥18岁;(2)首次就诊或住院并在1个月内确诊;(3)基线主诉、现病史及治疗资料齐全;(4) 符合ASAS制定的axSpA、pSpA分类诊断标准。排除标准:(1)缺少外周关节体格检查;(2)同时缺少红细胞沉降率(erythrocyte sedimentation rate,ESR)和C反应蛋白(C-reactive protein,CRP)两项炎症指标。

    本研究符合《赫尔辛基宣言》的伦理要求,已通过中国人民解放军总医院伦理委员会审批(审批号:S2023-169-01),并豁免患者知情同意。

    采用中国人民解放军总医院第一医学中心电子病历管理系统和脊柱关节炎智能管理系统(Smart-phone SpondyloArthritis Management System,SpAMS)收集数据。SpA患者的人口学数据、临床特征和治疗选择均为首次就诊基线数据。此外,为减少选择偏倚,对患者进行了连续招募,并对数据进行严格筛选。

    本研究收集的数据资料包括以下方面:(1)人口学数据:年龄、性别、体质量指数(body mass index,BMI)、吸烟史;(2)临床特征:发病年龄、诊断延迟时间、病程、既往是否有颈部/胸背/腰背/臀部疼痛史、炎症性肠病(inflammatory bowel disease,IBD)、葡萄膜炎、银屑病、AS家族史、葡萄膜炎家族史、IBD家族史、银屑病家族史、外周关节炎、指/趾炎;(3)实验室检查:人类白细胞抗原(human leukocyte antigen,HLA)-B27、ESR及CRP(就诊前后1周内检验结果);(4)治疗用药:非甾体抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)、传统合成改善病情抗风湿药物(conventional synthetic disease-modifying antirheumatic drugs,csDMARDs)、生物类改善病情抗风湿药物(biologic disease-modifying antirheumatic drugs,bDMARDs)、口服糖皮质激素。

    采用R统计软件(版本4.1.2)和SPSS(版本26.0)进行数据资料的统计分析。非正态分布的计量资料以中位数(四分位数)表示,组间比较采用秩和检验;计数资料以频数(百分数)表示,组间比较采用χ2检验或Fisher精确概率法。采用最小绝对值收敛与选择算子(least absolute shrinkage and selection operator,LASSO)回归筛选变量,纳入多因素Logistic回归模型,分析pSpA患者HLA-B27阳性与临床特征因素的相关性,并计算相对危险度和95% CI。采用双侧检验,以P<0.05为差异具有统计学意义。

    本研究连续纳入SpA患者1639例,包括pSpA患者184例(pSpA组)和axSpA患者1455例(axSpA组)。相较于axSpA组,pSpA组患者的男性占比相对较少(62.5%比79.7%,P<0.001)、就诊年龄更大(44.2岁比30.0岁,P<0.001),同时吸烟人数占比较低(15.2%比26.0%,P=0.001),两组患者的BMI比较差异无统计学意义(23.1 kg/m2比23.5 kg/m2P=0.537)。将除PsA外的87例pSpA患者归为pSpA1组,相较于axSpA组,pSpA1组患者的BMI更低,其余变量的亚组分析结果相似,详见表 1

    表  1  pSpA组、pSpA1组与axSpA组患者的临床特征比较
    Table  1.  Differences in clinical features between pSpA, pSpA1 and axSpA
    指标 pSpA组(n=184) pSpA1组(n=87) axSpA组(n=1455) P* P#
    男性[n(%)] 115(62.5) 51(58.6) 1159(79.7) <0.001 <0.001
    年龄[M(P25P75),岁] 44.2(32.0,55.3) 42.2(28.1,50.0) 30.0(25.0,36.0) <0.001 <0.001
    BMI[M(P25P75),kg/m2] 23.1(20.6,26.0) 22.3(20.1,24.8) 23.5(20.8,26.1) 0.537 0.008
    吸烟[n(%)] 28(15.2) 8(9.2) 378(26.0) 0.001 <0.001
    发病年龄[M(P25P75),岁] 33.8(25.7,46.9) 39.6(27.2,49.0) 22.0(18.0,28.0) <0.001 <0.001
    诊断延迟[M(P25P75),月] 6.0(1.7,25.9) 4.0(1.8,22.0) 14.2(2.3,47.5) 0.004 0.006
    病程[M(P25P75),年] 0.9(0.2,3.7) 0.3(0.1,1.8) 7.1(3.4,10.9) <0.001 <0.001
    既往颈部疼痛[n(%)] 20(10.9) 13(14.9) 163(11.2) 0.892 0.372
    既往胸背疼痛[n(%)] 1(0.5) 1(1.1) 168(11.5) <0.001 0.005
    既往腰背疼痛[n(%)] 28(15.2) 6(6.9) 744(51.1) <0.001 <0.001
    既往臀部疼痛[n(%)] 1(0.5) 1(1.1) 622(42.7) <0.001 <0.001
    合并葡萄膜炎[n(%)] 3(1.6) 2(2.3) 128(8.8) 0.001 0.055
    合并银屑病[n(%)] 97(52.7) 0(0) 16(1.1) <0.001 1.000
    合并IBD[n(%)] 8(4.3) 8(9.2) 92(6.3) 0.292 0.405
    SpA家族史[n(%)] 26(14.1) 3(3.4) 325(22.3) 0.011 <0.001
    AS家族史[n(%)] 6(3.3) 3(3.4) 261(17.9) <0.001 <0.001
    葡萄膜炎家族史[n(%)] 0(0) 0(0) 33(2.3) 0.074 0.255
    IBD家族史[n(%)] 0(0) 0(0) 17(1.2) 0.277 0.619
    银屑病家族史[n(%)] 21(11.4) 0(0) 50(3.4) <0.001 0.110
    伴随外周关节炎[n(%)] 132(71.7) 68(78.2) 136(9.3) <0.001 <0.001
    伴随指/趾炎[n(%)] 12(6.5) 3(3.4) 5(0.3) <0.001 0.008
    ESR[M(P25P75),mm/h] 37.0(13.0,81.0) 44.0(22.2,85.0) 10.0(5.0,25.0) <0.001 <0.001
    CRP[M(P25P75),mg/L] 20.3(3.2,61.4) 33.2(6.4,66.0) 5.5(2.7,16.3) <0.001 <0.001
    HLA-B27阳性[n(%)] 67(43.5) 49(57.6) 1253(87.4) <0.001 <0.001
    axSpA(axial spondyloarthritis):中轴型脊柱关节炎;pSpA(peripheral spondyloarthritis):外周型脊柱关节炎;pSpA1;除银屑病关节炎外的pSpA;BMI(body mass index):体质量指数;IBD(inflammatory bowel disease):炎症性肠病;SpA(spondyloarthritis):脊柱关节炎;AS(ankylosing spondylitis):强直性脊柱炎;ESR(erythrocyte sedimentation rate):红细胞沉降率;CRP(C-reactive protein):C-反应蛋白;HLA(human leukocyte antigen)-B27:人类白细胞抗原-B27;*pSpA组与axSpA组比较;#pSpA1组与axSpA组比较
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    相较于axSpA组,pSpA组患者发病年龄较晚(33.8岁比22.0岁,P<0.001),诊断延迟时间更短(6.0个月比14.2个月,P=0.004),病程也更短(0.9年比7.1年,P<0.001)。pSpA组患者既往胸背、腰背、臀部的疼痛发生率明显低于axSpA组(P<0.01),但既往颈部疼痛未见明显统计学差异(10.9%比11.2%,P=0.892)。pSpA组患者葡萄膜炎的患病率较低(1.6%比8.8%,P=0.001),而银屑病的患病率较高(52.7%比1.1%,P<0.001)。在家族史方面,pSpA组患者的银屑病家族史较高(11.4%比3.4%,P<0.001),而AS家族史较低(3.3%比17.9%,P<0.001)。相较于axSpA组,pSpA1组患者除合并银屑病、合并葡萄膜炎、银屑病家族史未表现出统计学差异外,其余变量的亚组分析结果相似,详见表 1

    与axSpA组相比,pSpA组患者伴外周关节炎(71.7%比9.3%,P<0.001)和指/趾炎(6.5%比0.3%,P<0.001)的占比较高。在关节肿胀分布方面,pSpA组患者最常见的肿胀部位是膝关节(60.6%)和踝关节(36.4%);除下肢大关节肿胀外,还可见肘关节(12.9 %)、腕关节(18.2%)、掌指关节(20.5%)、近端指间关节(26.5%)和远端指间关节(14.4%)肿胀;axSpA组患者常见的外周关节肿胀主要为膝关节(70.9%)和踝关节(24.6%)。在关节疼痛分布方面,pSpA组患者的关节压痛分布与肿胀分布相似,除膝关节(63.2%)和踝关节(32.8%)压痛外,还可见上肢大关节和小关节压痛。此外,2.4% 的pSpA组患者伴髋部压痛,而在关节受累的axSpA组患者中观察到32.7%的患者伴髋部压痛,详见图 1图 2

    图  1  axSpA组、pSpA组和pSpA1组患者外周关节肿胀部位分布情况
    axSpA、pSpA、pSpA1:同表 1
    Figure  1.  Distrbution rate of peripheral joints swelling in axSpA, pSpA, and pSpA1
    图  2  axSpA组、pSpA组和pSpA1组患者外周关节压痛部位分布情况
    axSpA、pSpA、pSpA1:同表 1
    Figure  2.  Distrbution rate of peripheral joint tenderness in axSpA, pSpA, and pSpA 1

    pSpA组与axSpA组患者的HLA-B27阳性率比较,存在显著统计学差异(43.5% 比87.4%,P<0.001)。此外,两组患者的炎症标志物CRP和ESR升高也存在显著差异,相较于axSpA组患者,pSpA组患者的ESR(37.0 mm/h比10.0 mm/h,P<0.001)、CRP(20.3 mg/L比5.5 mg/L,P<0.001)均更高,亚组分析结果相似,详见表 1。以HLA-B27阳性作为应变量建立Logistic回归模型,采用LASSO回归筛选变量,纳入因素包括:发病年龄、葡萄膜炎、银屑病、IBD、SpA家族史、AS家族史、葡萄炎家族史、IBD家族史、银屑病家族史、外周关节炎、指/趾炎。将初筛后的变量纳入多因素Logistic回归模型进行分析,结果显示发病年龄(OR=0.976,95% CI: 0.952~1.000)、合并银屑病(OR=0.201,95% CI: 0.095~0.425)以及AS家族史(OR=13.060,95% CI: 1.202~141.842)与pSpA患者的HLA-B27存在相关性,详见表 2

    表  2  pSpA患者HLA-B27阳性与临床特征的多因素Logistic回归分析
    Table  2.  Multivariate Logistic regression analysis of the association between HLA-B27 positivity and clinical features in patients with pSpA
    变量 OR 95% CI P
    发病年龄 0.976 0.952~1.000 0.047
    合并银屑病 0.201 0.095~0.425 <0.001
    AS家族史 13.060 1.202~141.842 0.035
    pSpA、HLA-B27、AS:同表 1
    下载: 导出CSV 
    | 显示表格

    相较于axSpA组,pSpA组患者使用NSAIDs(64.7%比96.2%,P<0.001)的比例更低,但使用csDMARDs(84.2%比60.3%,P<0.001)、bDMARDs(31.0%比23.6%,P=0.029)和口服糖皮质激素(18.5%比1.4%,P<0.001)的比例更高;同时,pSpA组患者更多采用bDMARDs和csDMARDs联合用药(19.0%比12.2%,P=0.009)或多种csDMARDs合用(65.8%比12.5%,P<0.001)。pSpA1组与axSpA组患者使用bDMARDs比较差异无显著统计学意义,详见表 3

    表  3  pSpA、pSpA1与axSpA治疗差异[n(%)]
    Table  3.  Differences in treatment between pSpA, pSpA1 and axSpA [n(%)]
    变量 pSpA组(n=184) pSpA1组(n=87) axSpA组(n=1455) P* P#
    NSAIDs 119(64.7) 67(77.0) 1399(96.2) <0.001 <0.001
    csDMARDs 155(84.2) 73(83.9) 877(60.3) <0.001 <0.001
    bDMARDs 57(31.0) 20(23.0) 344(23.6) 0.029 0.992
    糖皮质激素 34(18.5) 22(25.3) 21(1.4) <0.001 <0.001
    中成药 40(21.7) 13(14.9) 837(57.5) <0.001 <0.001
    联合用药
      NSAIDs+bDMARDs 36(19.6) 16(18.4) 308(21.2) 0.615 0.630
      NSAIDs+cDMARDs+bDMARDs 35(19.0) 15(17.2) 177(12.2) 0.009 0.220
      csDMARDs≥2种 121(65.8) 59(67.8) 182(12.5) <0.001 <0.001
    NSAIDs(non-steroidal anti-inflammatory drugs):非甾体抗炎药;csDMARDs(conventional synthetic disease-modifying antirheumatic drugs):传统合成改善病情抗风湿药物;bDMARDs(biologic disease-modifying antirheumatic drugs):生物类改变病情抗风湿药物;pSpA、pSpA1、axSpA:同表 1*pSpA组与axSpA组患者比较;#pSpA1组与axSpA组患者比较
    下载: 导出CSV 
    | 显示表格

    本研究回顾性收集了pSpA组和axSpA组患者的临床资料,通过分析两组的临床特征和治疗选择差异以进一步深入了解pSpA患者。研究结果显示,pSpA患者男性相对较少,发病更晚,但诊断更及时,炎症指标更高,而HLA-B27阳性率更低;pSpA患者更易出现外周关节炎、指/趾炎,且关节受累范围更广,既往脊柱疼痛主要集中于腰部和颈部,更多伴随银屑病, 较少伴随葡萄膜炎;同时,pSpA患者银屑病家族史更常见,而AS家族史相对较少;在治疗选择方面,pSpA患者则更多选用csDMARDs、bDMARDs和口服糖皮质激素等治疗方式。

    本研究中pSpA的发病年龄较晚、女性患者相对较多,HLA-B27阳性率较低,这一结果与既往研究结果相似,即以中轴症状发病的SpA比以外周症状为主的SpA患者发病更早[11];而axSpA组患者中男性及HLA-B27阳性占比高于pSpA组患者[3]。此外,本研究观察到pSpA组患者发生外周关节炎、指/趾炎和银屑病的比例明显更高,HLA-B27与患者的发病年龄、合并银屑病存在相关性。既往研究显示,在HLA-B27阳性患者中,pSpA发病较早[12]、更少合并银屑病[13]。此外,本研究发现pSpA组患者的银屑病家族史更多,而AS家族史更少。多因素分析结果提示,pSpA患者中HLA-B27阳性与AS家族史相关。一项全球研究显示,部分地区的axSpA患者中,AS家族史与HLA-B27阳性呈正相关,而IBD或银屑病家族史与其呈负相关[14]。总之,在pSpA和axSpA患者中,发病年龄、外周关节炎、银屑病、葡萄膜炎以及家族史等特征分布不同,其对疾病进展的影响需研究进一步深入探讨。

    本研究发现,相较于axSpA组,pSpA组患者的诊断延误时间更短,可能因axSpA涉及深部解剖结构,因此更易被忽视[15]。与此同时,pSpA往往更易引起患者重视并及时就诊,尤其是外周关节疼痛等明显症状。虽然关于pSpA患者诊断延迟的研究较少,但从银屑病发展为PsA的相关研究[16]可以看出,若银屑病患者出现关节肿痛或指/趾炎则诊断时间较短;相反,若症状表现为僵硬、疲劳、附着点炎或背部疼痛等,则需较长的诊断时间。在以附着点炎等为主要表现的pSpA患者中,诊断往往比较延迟,同时也易与纤维肌痛等其他疾病混淆。此外,PsA从皮肤病变到诊断出关节病变的中位时间为7~8年[17],皮肤病变为主伴轻微关节症状表现的患者习惯在皮肤科就诊,往往不能及时到风湿科就诊。因此,临床医生应加强对早期pSpA的识别和诊断技能的学习,同时促进不同科室之间的沟通交流和积极转诊,以有效降低pSpA患者的诊断延迟。

    在本研究中,pSpA组患者既往胸背、腰背及臀部的疼痛发生率明显低于axSpA组,但两组患者既往颈部疼痛未见明显统计学差异。在PsA患者中,脊柱受累研究以颈椎更为常见[18]。其他探究axSpA合并关节外症状的研究发现,合并银屑病的axSpA患者,全脊柱中颈椎受损情况更为严重,其脊柱影像学进展较快而骶髂关节炎病变更轻[19]。另一项研究发现,女性axSpA患者骶髂关节和脊柱进展程度出现相似表现,此类患者颈椎和胸椎MRI体征的患病率较高但骶髂关节病变程度较轻[20]。此外,本研究发现pSpA患者既往腰背疼痛患病率为15.2%,与其他pSpA队列研究结果一致[21]。既往研究发现,在axSpA和非SpA慢性腰背疼痛者中,腰椎存在相似比例的退行性病变[22]。近期,一项针对早期pSpA患者的研究发现,虽然MRI检查提示36%的患者骶髂关节水肿,但临床症状表现为炎症性腰背痛的患者占比很少[23]。目前研究表明,SpA患者脊柱易受累部位可能受疾病亚型、性别、合并银屑病等影响,pSpA患者既往发生腰背疼痛的比例与发生骶髂关节炎的比例不一致,需进一步研究探索。

    本研究发现,两组患者外周关节肿胀和压痛部位存在显著差异。axSpA组患者主要表现为下肢大关节受累,而pSpA患者除膝关节和踝关节受累外,上肢的大小关节也受影响。一项全球多中心研究发现[3],在axSpA和pSpA患者中,约50%的患者外周关节以下肢大关节受累为主,两组患病率相似;而PsA患者多为上肢和小关节受累。导致这种差异的可能原因为:不同研究对纳入的患者定义存在区别,pSpA和PsA的诊断存在一定程度的重合,风湿科医生在诊断过程中,往往将伴有银屑病和外周关节受累的患者纳入PsA组而非pSpA组。本研究中pSpA纳入了各种亚组,提高了研究的全面性,同时观察到pSpA组部分患者存在上肢大小关节受累情况,在排除了PsA的pSpA1组患者中也观察到类似情况。此外,种族差异可能是导致外周受累部位分布不一致的原因之一。需注意的是,部分pSpA患者表现为上肢小关节受累,可能误诊为类风湿关节炎,因此针对此类患者需加强鉴别诊断。

    本研究中pSpA组患者使用csDMARDs和口服糖皮质激素的比例明显高于axSpA组患者,其原因为pSpA组患者通常伴有较高比例的外周关节炎,这也与SpA的管理建议相符[24]。同时,pSpA患者使用bDMARDs的比例不低于axSpA患者,可能与伴有银屑病、外周关节炎等症状相关。目前研究表明,外周表现和关节外症状均影响患者的疾病负担和治疗方案[25]。axSpA患者出现外周关节炎时可能倾向于选择bDMARDs、csDMARDs、口服激素[7];合并银屑病的SpA患者伴有更大的疾病负担并使用更多的药物[13]。目前,药物随机对照试验研究主要针对axSpA及PsA患者,较少有研究关注pSpA,现有数据表明csDMARDs可改善外周关节炎,但对附着点炎及指/趾炎的疗效不佳[26]。少数随机对照试验研究发现,bDMARDs对于早期pSpA的治疗效果不错[5-6]。此外,本研究观察到pSpA患者更倾向于同时使用csDMARDs和bDMARDs,或2种以上csDMARDs联合用药。既往针对axSpA的临床研究发现,csDMARDs和bDMARDs联用的有效性和安全性有限,csDMARDs的应用可能提高bDMARDs的生存期[27]。总之,pSpA患者通常伴有更多的银屑病、外周关节炎等症状,其承担的疾病负担不亚于axSpA患者,需使用更多药物进行疾病治疗,本研究为pSpA的治疗提供了新的认识。

    本研究采用回顾性研究设计,故存在一定的局限性和不足,但本研究样本量较大,两组患者间具有一定的可靠性和代表性。本研究主要结果是基于差异性分析得出,因此可能受到混杂因素影响,解读时需谨慎。pSpA患者的病程较短,可能对研究结果产生一定影响,因此计划后期加强对患者进行随访,以进一步开展深入研究。axSpA和pSpA患者的脊柱和外周关节受累模式不同,二者的SpA家族史聚集也不同,而pSpA患者承担更高的炎症负担和更多的药物使用,这些结果对于改善pSpA治疗选择和疾病管理具有重要价值。同时,本研究也为未来研究提供了线索,可深入探讨HLA-B27阳性与axSpA和pSpA患者之间的关系,以及在选择药物治疗时考虑不同临床特征的影响。

    作者贡献:曾露露负责数据分析、起草和修订论文;冀肖健、胡嘉文参与修订论文;胡立冬参与数据统计分析和解释过程;张奕楠、张家鑫、刘兴康、杨世伟参与数据获取;黄烽负责研究选题设计。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1   axSpA组、pSpA组和pSpA1组患者外周关节肿胀部位分布情况

    axSpA、pSpA、pSpA1:同表 1

    Figure  1.   Distrbution rate of peripheral joints swelling in axSpA, pSpA, and pSpA1

    图  2   axSpA组、pSpA组和pSpA1组患者外周关节压痛部位分布情况

    axSpA、pSpA、pSpA1:同表 1

    Figure  2.   Distrbution rate of peripheral joint tenderness in axSpA, pSpA, and pSpA 1

    表  1   pSpA组、pSpA1组与axSpA组患者的临床特征比较

    Table  1   Differences in clinical features between pSpA, pSpA1 and axSpA

    指标 pSpA组(n=184) pSpA1组(n=87) axSpA组(n=1455) P* P#
    男性[n(%)] 115(62.5) 51(58.6) 1159(79.7) <0.001 <0.001
    年龄[M(P25P75),岁] 44.2(32.0,55.3) 42.2(28.1,50.0) 30.0(25.0,36.0) <0.001 <0.001
    BMI[M(P25P75),kg/m2] 23.1(20.6,26.0) 22.3(20.1,24.8) 23.5(20.8,26.1) 0.537 0.008
    吸烟[n(%)] 28(15.2) 8(9.2) 378(26.0) 0.001 <0.001
    发病年龄[M(P25P75),岁] 33.8(25.7,46.9) 39.6(27.2,49.0) 22.0(18.0,28.0) <0.001 <0.001
    诊断延迟[M(P25P75),月] 6.0(1.7,25.9) 4.0(1.8,22.0) 14.2(2.3,47.5) 0.004 0.006
    病程[M(P25P75),年] 0.9(0.2,3.7) 0.3(0.1,1.8) 7.1(3.4,10.9) <0.001 <0.001
    既往颈部疼痛[n(%)] 20(10.9) 13(14.9) 163(11.2) 0.892 0.372
    既往胸背疼痛[n(%)] 1(0.5) 1(1.1) 168(11.5) <0.001 0.005
    既往腰背疼痛[n(%)] 28(15.2) 6(6.9) 744(51.1) <0.001 <0.001
    既往臀部疼痛[n(%)] 1(0.5) 1(1.1) 622(42.7) <0.001 <0.001
    合并葡萄膜炎[n(%)] 3(1.6) 2(2.3) 128(8.8) 0.001 0.055
    合并银屑病[n(%)] 97(52.7) 0(0) 16(1.1) <0.001 1.000
    合并IBD[n(%)] 8(4.3) 8(9.2) 92(6.3) 0.292 0.405
    SpA家族史[n(%)] 26(14.1) 3(3.4) 325(22.3) 0.011 <0.001
    AS家族史[n(%)] 6(3.3) 3(3.4) 261(17.9) <0.001 <0.001
    葡萄膜炎家族史[n(%)] 0(0) 0(0) 33(2.3) 0.074 0.255
    IBD家族史[n(%)] 0(0) 0(0) 17(1.2) 0.277 0.619
    银屑病家族史[n(%)] 21(11.4) 0(0) 50(3.4) <0.001 0.110
    伴随外周关节炎[n(%)] 132(71.7) 68(78.2) 136(9.3) <0.001 <0.001
    伴随指/趾炎[n(%)] 12(6.5) 3(3.4) 5(0.3) <0.001 0.008
    ESR[M(P25P75),mm/h] 37.0(13.0,81.0) 44.0(22.2,85.0) 10.0(5.0,25.0) <0.001 <0.001
    CRP[M(P25P75),mg/L] 20.3(3.2,61.4) 33.2(6.4,66.0) 5.5(2.7,16.3) <0.001 <0.001
    HLA-B27阳性[n(%)] 67(43.5) 49(57.6) 1253(87.4) <0.001 <0.001
    axSpA(axial spondyloarthritis):中轴型脊柱关节炎;pSpA(peripheral spondyloarthritis):外周型脊柱关节炎;pSpA1;除银屑病关节炎外的pSpA;BMI(body mass index):体质量指数;IBD(inflammatory bowel disease):炎症性肠病;SpA(spondyloarthritis):脊柱关节炎;AS(ankylosing spondylitis):强直性脊柱炎;ESR(erythrocyte sedimentation rate):红细胞沉降率;CRP(C-reactive protein):C-反应蛋白;HLA(human leukocyte antigen)-B27:人类白细胞抗原-B27;*pSpA组与axSpA组比较;#pSpA1组与axSpA组比较
    下载: 导出CSV

    表  2   pSpA患者HLA-B27阳性与临床特征的多因素Logistic回归分析

    Table  2   Multivariate Logistic regression analysis of the association between HLA-B27 positivity and clinical features in patients with pSpA

    变量 OR 95% CI P
    发病年龄 0.976 0.952~1.000 0.047
    合并银屑病 0.201 0.095~0.425 <0.001
    AS家族史 13.060 1.202~141.842 0.035
    pSpA、HLA-B27、AS:同表 1
    下载: 导出CSV

    表  3   pSpA、pSpA1与axSpA治疗差异[n(%)]

    Table  3   Differences in treatment between pSpA, pSpA1 and axSpA [n(%)]

    变量 pSpA组(n=184) pSpA1组(n=87) axSpA组(n=1455) P* P#
    NSAIDs 119(64.7) 67(77.0) 1399(96.2) <0.001 <0.001
    csDMARDs 155(84.2) 73(83.9) 877(60.3) <0.001 <0.001
    bDMARDs 57(31.0) 20(23.0) 344(23.6) 0.029 0.992
    糖皮质激素 34(18.5) 22(25.3) 21(1.4) <0.001 <0.001
    中成药 40(21.7) 13(14.9) 837(57.5) <0.001 <0.001
    联合用药
      NSAIDs+bDMARDs 36(19.6) 16(18.4) 308(21.2) 0.615 0.630
      NSAIDs+cDMARDs+bDMARDs 35(19.0) 15(17.2) 177(12.2) 0.009 0.220
      csDMARDs≥2种 121(65.8) 59(67.8) 182(12.5) <0.001 <0.001
    NSAIDs(non-steroidal anti-inflammatory drugs):非甾体抗炎药;csDMARDs(conventional synthetic disease-modifying antirheumatic drugs):传统合成改善病情抗风湿药物;bDMARDs(biologic disease-modifying antirheumatic drugs):生物类改变病情抗风湿药物;pSpA、pSpA1、axSpA:同表 1*pSpA组与axSpA组患者比较;#pSpA1组与axSpA组患者比较
    下载: 导出CSV
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出版历程
  • 收稿日期:  2024-06-04
  • 录用日期:  2024-10-30
  • 网络出版日期:  2024-12-25
  • 发布日期:  2024-12-24
  • 刊出日期:  2025-01-29

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