北京大学学报(医学版) ›› 2020, Vol. 52 ›› Issue (6): 995-1000. doi: 10.19723/j.issn.1671-167X.2020.06.002

• 论著 • 上一篇    下一篇

肌炎合并血栓栓塞患者的临床及免疫学特征

朱冯赟智1,邢晓燕2,汤晓菲3,李依敏1,邵苗1,张学武1,李玉慧1,(),孙晓麟1,何菁1   

  1. 1. 北京大学人民医院风湿免疫科,北京 100044
    2. 北京大学人民医院心脏电生理室,北京 100044
    3. 航天中心医院肾内风湿科,北京 100069
  • 收稿日期:2020-08-10 出版日期:2020-12-18 发布日期:2020-12-13
  • 通讯作者: 李玉慧 E-mail:liyuhui84@163.com
  • 基金资助:
    国家自然科学基金(81801617);北京大学人民医院研究与发展基金(RDY2018-01);北京大学人民医院研究与发展基金(RS2018-02);北京大学人民医院研究与发展基金(RDE2019-02);北京大学教学新思路基金(2020YX006)

Clinical and immunological characteristics of myositis complicated with thromboembolism

Feng-yun-zhi ZHU1,Xiao-yan XING2,Xiao-fei TANG3,Yi-min LI1,Miao SHAO1,Xue-Wu ZHANG1,Yu-hui LI1,(),Xiao-lin SUN1,Jing HE1   

  1. 1. Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing 100044, China
    2. Department of Cardiac Electrophysiology, Peking University People’s Hospital, Beijing 100044, China
    3. Department of Nephrology and Rheumatology, Aerospace Center Hospital, Beijing 100069, China
  • Received:2020-08-10 Online:2020-12-18 Published:2020-12-13
  • Contact: Yu-hui LI E-mail:liyuhui84@163.com
  • Supported by:
    National Natural Science Foundation of China(81801617);Peking University People’s Hospital Research and Development Funds(RDY2018-01);Peking University People’s Hospital Research and Development Funds(RS2018-02);Peking University People’s Hospital Research and Development Funds(RDE2019-02);New Teaching Approach Funds of Peking University(2020YX006)

摘要:

目的:探讨合并血栓栓塞的肌炎患者的临床及免疫学特征。方法:回顾性分析2003—2019年于北京大学人民医院住院的390例肌炎患者的病历资料,包括人口学特征、皮肤、肌肉表现、脏器受累、实验室指标(肌酶、白蛋白、凝血功能、炎性指标、肌炎特异性/相关性抗体)、治疗方案,并根据有无合并血栓栓塞将患者进行分组比较,应用Logistic回归分析明确肌炎合并血栓栓塞的危险因素。结果:肌炎患者平均起病年龄(49.6±13.4)岁,男女比例为0.31:1,血栓栓塞发生率为4.62%(18/390),其中,55.6%(10/18)为下肢深静脉血栓形成,其次为脑梗塞(22.2%,4/18)、肺栓塞(11.1%,2/18)、肾动脉栓塞(5.6%,1/18)、上肢静脉血栓形成(5.6 %,1/18)。血栓栓塞发生时间方面,38.9%(7/18)发生在肌炎诊断的前后6个月内,50%(9/18)发生在肌炎确诊后。合并血栓栓塞的肌炎患者起病年龄偏大,平均(58.3±11.7)岁,合并糖尿病(44.4% vs. 16.4%,P=0.006)、冠心病(22.2% vs. 3.0%,P=0.003)、 90 d内手术史(16.7% vs. 3.5%,P=0.032)等并发症均高于无血栓栓塞组。实验室检查方面,合并血栓栓塞的肌炎患者C-反应蛋白(12.2 mg/L vs. 4.1 mg/L,P<0.001)、血清铁蛋白(20 085.5 μg/L vs. 216.6 μg/L,P<0.001)、血清白蛋白水平(32.4 g/L vs. 36.5 g/L,P=0.002)、D-二聚体(529.0 μg/L vs. 268.0 μg/L,P=0.002)均明显升高,活化部分凝血酶原时间(26.9 s vs. 28.7 s,P=0.049)显著低于无血栓栓塞组。肌炎发生血栓栓塞的危险因素包括:白蛋白水平降低(OR=0.831,95%CI:0.736~0.939,P=0.003)、合并糖尿病(OR=4.468,95%CI:1.382~14.448,P=0.012)、合并冠心病(OR=22.079,95%CI:3.589~135.837,P=0.001)。未见肌炎特异性抗体与血栓栓塞发生的相关性。结论:肌炎患者可发生血栓栓塞事件,合并白蛋白水平降低、糖尿病、冠心病的肌炎患者发生血栓栓塞的风险高,临床应高度警惕。

关键词: 肌炎, 自身免疫疾病, 血栓栓塞, 自身抗体

Abstract:

Objective: To investigate and analyse the clinical and immunological features of patients with myositis complicated with thromboembolism. Methods: We identified a cohort of 390 myositis patients diagnosed with myositis admitted to People’s Hospital of Peking University from 2003 to 2019. The patients were retrospectively enrolled in this investigation. According to the outcome of the color Doppler ultrasound, CT pulmonary angiography, pulmonary ventilation and perfusion scan patients were divided into myositis with and without thromboembolism group. Demographic, clinical (heliotrope rash, Gottron’s sign/papules, periungual erythema, skin ulceration, subcutaneous calcinosis, Mechanic’s hands, myalgia, interstitial lung disease, pulmonary arterial hypertension), laboratory, immunological [anti-autoantibodies including melanoma differentiation associated gene 5 (anti-MDA5), anti-Mi-2, anti-transcription intermediary factor-1γ (anti-TIF-1γ, anti-nuclear matrix protein 2 (anti-NXP2), anti-small ubiquitin-like modifier activating enzyme (anti-SAE), anti-synthetase], imaging and therapeutic status data of the patients at the diagnosis of myositis with and without thromboembolism were collected and the differences in these data were analyzed. Logistic regressive analysis was used to identify the risk factors of thromboembolism. Results: In the retrospective study, 390 myositis patients were investigated. The mean age of onset was (49.6±13.4) years, male to female ratio was 0.31:1. Thromboembolism was identified in 4.62% (18/390) of the myositis patients, which was lower than the published reports. Out of 18 patients with thromboembolism, 55.6% (10/18) of them were deep venous thrombosis, followed by cerebral infarction (22.2%, 4/18), pulmonary embolism (11.1%, 2/18), renal artery embolism (5.6%, 1/18) and embolism of upper extremity (5.6%, 1/18). Fifty percent of thromboembolism events occurred 6 months after the diagnosis of myositis, 38.9% of thromboembolism events occurred 6 months within the diagnosis of myositis, 11.1% of thromboembolism events occurred 6 months before the diagnosis of myositis. As compared with the myositis patients without thromboembolism, the myositis patients complicated with thromboembolism were older [(58.3±11.7) years vs. (49.3±13.4) years, P=0.006]. C-reaction protein (CRP) (12.2 mg/L vs. 4.1 mg/L, P<0.001), ferritin (20 085.5 μg/L vs. 216.6 μg/L, P<0.001) and D-dimer (529.0 μg/L vs. 268.0 μg/L, P=0.002) were significantly higher in thromboembolism group. Diabetes (44.4% vs. 16.4%, P=0.006), coronary heart disease (22.2% vs. 3.0%, P=0.003) and surgery (16.7% vs. 3.5%, P=0.032) were observed more common in thromboembolism group than those without thromboembolism. Activated partial thromboplastin time (APTT) (26.9 s vs. 28.7 s, P=0.049) and albumin (32.4 g/L vs. 36.5 g/L, P=0.002) was lower in thromboembolism group. The risk factors of thromboembolism in the myositis patients were low level of albumin (OR=0.831, 95%CI: 0.736-0.939, P=0.003), diabetes (OR=4.468, 95%CI: 1.382-14.448, P=0.012), and coronary heart disease (OR=22.079, 95%CI: 3.589-135.837, P=0.001) were independent significant risk factors for thromboembolism in the patients with myositis. There was no significant difference in clinical manifestations, myositis-specific antibodies or myositis-associated antibodies between the two groups. Conclusion: Thromboembolism is a complication of myositis. Lower levels of albumin, diabetes, and coronary heart disease might be risk factors of thromboembolism in myositis patients.

Key words: Myositis, Autoimmune diseases, Thromboembolism, Autoantibodies

中图分类号: 

  • R593.2

表1

肌炎患者的一般特征"

Variables Myositis (n=390)
Demographics
Age at onset/years, x-±s 49.6±13.4
Female, n(%) 297 (76.2)
Duration/months, M (P25, P75) 6 (2, 20)
Types of TE, n(%)
DVT 10 (55.6)
Cerebral infarction 4 (22.2)
PE 2 (11.1)
Others 2 (11.1)

图1

18例肌炎患者发生血栓栓塞的时间"

表2

肌炎合并血栓栓塞患者的一般特征"

Variables Myositis with TE (n=18) Myositis without TE (n=372) P
Demographics
Female, n(%) 14 (77.8) 283 (76.1) 0.565
Age at onset/years, x-±s 58.3±11.7 49.3±13.4 0.006
Duration/months, M (P25, P75) 9 (3.3, 42.0) 6 (2.0, 18.5) 0.276
Survival, n(%) 17 (94.4) 357 (96.0) 0.538
PM, n(%) 3 (16.7) 45 (12.1) 0.584
DM, n(%) 8 (44.4) 211 (56.7) 0.584
CADM, n(%) 7 (38.9) 116 (31.2) 0.584
Risk factors
BMI/(kg/m2), M (P25, P75) 23.8 (23.0, 26.1) 23.5 (21.3, 25.8) 0.373
Cigarette, n(%) 6 (33.3) 57 (15.3) 0.053
Hypertension, n(%) 7 (38.9) 85 (22.9) 0.151
Diabetes, n(%) 8 (44.4) 61 (16.4) 0.006
Coronary heart disease, n(%) 4 (22.2) 11 (3.0) 0.003
Malignancy, n(%) 3 (16.7) 31 (8.3) 0.200
Varicose veins, n(%) 0 5 (1.3) 1.000
Surgery, n(%) 3 (16.7) 13 (3.5) 0.032

表3

肌炎合并血栓栓塞患者的临床和实验室特征"

Variables Myositis with TE (n=18) Myositis without TE (n=372) P
Clinical features, n(%)
Heliotrope rash 11 (61.1) 171 (46.0) 0.208
Gottron’s sign (papules) 11 (61.1) 238 (64.0) 0.805
Periungual erythema 1 (5.6) 69 (18.6) 0.217
Skin ulceration 1 (5.6) 17 (4.6) 0.581
Subcutaneous calcinosis 1 (5.6) 6 (1.6) 0.284
Mechanic’s hands 2 (11.1) 103 (27.7) 0.173
Myalgia 1 (5.6) 38 (10.2) 1.000
ILD 13 (72.2) 237 (63.7) 0.462
PAH 6 (33.3) 61 (16.4) 0.100
Laboratory features
CK/(U/L), M (P25, P75) 41.0 (22.5, 944.8) 116.0 (40.0, 674.0) 0.141
CRP/(mg/L), M (P25, P75) 12.2 (7.2, 39.0) 4.1 (1.4, 14.3) <0.001
ESR/(mm/h), M (P25, P75) 25.0 (9.3, 56.8) 23.0 (11.0, 42.0) 0.779
Ferritina /(μg/L), M (P25, P75) 20 085.5 (1 039.3, 28 069.3) 216.6 (83.0, 879.7) <0.001
Elevated cTnI, n(%) 6 (35.3) 34 (21.8) 0.729
D-dimer/(μg/L), M (P25, P75) 529.0 (258.0, 1156.5) 268.0 (122.0, 492.0) 0.002
Fibrinogen/(g/L), M (P25, P75) 3.6 (2.4, 4.6) 3.1 (2.6, 3.6) 0.492
PT/s, M (P25, P75) 10.9 (10.4, 11.8) 11.0 (10.3, 11.7) 0.965
APTT/s, M (P25, P75) 26.9 (25.9, 29.0) 28.7 (26.7, 31.3) 0.049
Alb/(g/L), M (P25, P75) 32.4 (28.5, 35.8) 36.5 (33.0, 39.0) 0.002
MSAsb, n(%)
Anti-MDA5 positivity 2/14 (14.3) 43/221 (19.5) 1.000
Anti-Mi-2 positivity 2/14 (14.3) 12/221 (5.4) 0.199
Anti-TIF-1γ positivity 1/14 (7.1) 14/221 (6.3) 1.000
Anti-NXP2 positivity 1/14 (7.1) 13/221 (5.9) 0.587
Anti-SAE positivity 1/14 (7.1) 5/221 (2.3) 0.311
Anti-synthetase positivity 3/14 (21.4) 76/221 (34.2) 0.394
MAAsb, n(%)
Anti-PM-Scl75/100 positivity 1/14 (7.1) 15/221 (6.8) 1.000
Anti-Ro-52 positivity 9/14 (64.3) 105/221 (47.5) 0.276
Anti-Ku positivity 0/14 (0) 9/221 (4.1) 1.000
Glucocorticoid pulse therapy, n(%) 5 (27.8) 83 (22.3) 0.569
Cyclophosphamide, n(%) 10 (55.6) 145 (39.0) 0.217
Other immunosuppressants, n(%) 4 (22.2) 71 (19.1) 0.760
Anticoagulant drug, n(%) 1 (5.6) 9 (2.4) 0.380

表4

肌炎患者发生血栓栓塞的危险因素"

Variables OR 95%CI P
Albumin 0.831 0.736-0.939 0.003
Diabetes 4.468 1.382-14.448 0.012
Coronary heart disease 22.079 3.589-135.837 0.001
[1] Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups[J]. Arthritis Rheumatol, 2017,69(12):2271-2282.
doi: 10.1002/art.40320 pmid: 29106061
[2] Ogdie A, Kay McGill N, Shin DB, et al. Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: A general population-based cohort study[J]. Eur Heart J, 2018,39(39):3608-3614.
doi: 10.1093/eurheartj/ehx145 pmid: 28444172
[3] Aviña-Zubieta JA, Vostretsova K, De Vera MA, et al. The risk of pulmonary embolism and deep venous thrombosis in systemic lupus erythematosus: A general population-based study[J]. Semin Arthritis Rheum, 2015,45(2):195-201.
doi: 10.1016/j.semarthrit.2015.05.008 pmid: 26364556
[4] Carruthers EC, Choi HK, Sayre EC, et al. Risk of deep venous thrombosis and pulmonary embolism in individuals with polymyositis and dermatomyositis: A general population-based study[J]. Ann Rheum Dis, 2016,75(1):110-116.
doi: 10.1136/annrheumdis-2014-205800 pmid: 25193998
[5] Antovic A, Notarnicola A, Svensson J, et al. Venous thromboembolic events in idiopathic inflammatory myopathy: Occurrence and relation to disease onset[J]. Arthritis Care Res (Hoboken), 2018,70(12):1849-1855.
[6] Bohan A, Peter J B. Polymyositis and dermatomyositis (first of two parts)[J]. N Engl J Med, 1975,292(7):403-407.
[7] Sontheimer RD. Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis siné myositis) as a distinctive subset within the idiopathic inflammatory dermatomyo-pathies spectrum of clinical illness?[J]. J Am Acad Dermatol, 2002,46(4):626-636.
pmid: 11907524
[8] Smith SC Jr, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute[J]. Circulation, 2006,113(19):2363-2372.
pmid: 16702489
[9] Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism[J]. J Thromb Thrombolysis, 2016,41(1):3-14.
pmid: 26780736
[10] Holmqvist M, Ljung L, Askling J. Acute coronary syndrome in new-onset rheumatoid arthritis: A population-based nationwide cohort study of time trends in risks and excess risks[J]. Ann Rheum Dis, 2017,76(10):1642-1647.
doi: 10.1136/annrheumdis-2016-211066 pmid: 28710095
[11] Schoenfeld SR, Choi HK, Sayre EC, et al. Risk of pulmonary embolism and deep venous thrombosis in systemic sclerosis: A general population-based study[J]. Arthritis Care Res (Hoboken), 2016,68(2):246-253.
[12] Zöller B, Li X, Sundquist J, et al. Risk of pulmonary embolism in patients with autoimmune disorders: A nationwide follow-up study from Sweden[J]. Lancet, 2012,379(9812):244-249.
[13] Xu J, Lupu F, Esmon CT. Inflammation, innate immunity and blood coagulation[J]. Hamostaseologie, 2010,30(1):5-9.
pmid: 20162248
[14] Choi HK, Rho YH, Zhu Y, et al. The risk of pulmonary embo-lism and deep vein thrombosis in rheumatoid arthritis: A UK population-based outpatient cohort study[J]. Ann Rheum Dis, 2013,72(7):1182-1187.
pmid: 22930596
[15] Saghazadeh A, Rezaei N. Inflammation as a cause of venous thromboembolism[J]. Crit Rev Oncol Hematol, 2016,99:272-285.
doi: 10.1016/j.critrevonc.2016.01.007 pmid: 26811138
[16] Mussbacher M, Salzmann M, Brostjan C, et al. Cell type-specific roles of NF-κB linking inflammation and thrombosis [J/OL]. Front Immunol, (2019-02-04)[2020-04-30]. doi: 10.3389/fimmu.2019.00085.
[17] Ramagopalan SV, Wotton CJ, Handel AE, et al. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: Record-linkage study [J/OL]. BMC Med, (2011-01-10)[2020-04-30]. doi: 10.1186/1741-7015-9-1.
[1] 肖云抒,朱冯赟智,罗澜,邢晓燕,李玉慧,张学武,沈丹华. 88例重叠肌炎的临床及免疫学特征[J]. 北京大学学报(医学版), 2021, 53(6): 1088-1093.
[2] 罗澜,邢晓燕,肖云抒,陈珂彦,朱冯赟智,张学武,李玉慧. 抗合成酶综合征合并心脏受累患者的临床及免疫学特征[J]. 北京大学学报(医学版), 2021, 53(6): 1078-1082.
[3] 张朴丽,杨红霞,张立宁,葛勇鹏,彭清林,王国春,卢昕. 血清YKL-40在诊断抗黑色素瘤分化相关基因5阳性皮肌炎合并严重肺损伤中的价值[J]. 北京大学学报(医学版), 2021, 53(6): 1055-1060.
[4] 伊文霞,魏翠洁,吴晔,包新华,熊晖,常杏芝. 长疗程利妥昔单抗治疗难治性幼年型特发性炎症性肌病3例[J]. 北京大学学报(医学版), 2021, 53(6): 1191-1195.
[5] 吴燕芳,高飞,林滇恬,陈志涵,林禾. 托法替布联合治疗抗MDA5抗体阳性的无肌病皮肌炎并发快速进展型间质性肺病5例临床分析[J]. 北京大学学报(医学版), 2021, 53(5): 1012-1016.
[6] 郑艺明,郝洪军,刘怡琳,郭晶,赵亚雯,张巍,袁云. Ro52抗体与其他肌炎抗体共阳性的相关性研究[J]. 北京大学学报(医学版), 2020, 52(6): 1088-1092.
[7] 甘雨舟,李玉慧,张丽华,马琳,何文雯,金月波,安媛,栗占国,叶华. 临床无肌病性皮肌炎与皮肌炎临床及免疫学特征比较[J]. 北京大学学报(医学版), 2020, 52(6): 1001-1008.
[8] 赵静,孙峰,李云,赵晓珍,徐丹,李英妮,李玉慧,孙晓麟. 抗α-1C微管蛋白抗体在系统性硬化症中的表达及临床意义[J]. 北京大学学报(医学版), 2020, 52(6): 1009-1013.
[9] 杨红霞,田小兰,江薇,李文丽,刘青艳,彭清林,王国春,卢昕. 免疫介导坏死性肌病的临床和病理特征分析[J]. 北京大学学报(医学版), 2019, 51(6): 989-995.
[10] 李英妮,相晓红,赵静,李云,孙峰,王红彦,贾汝琳,胡凡磊. 抗类瓜氨酸化抗体在系统性红斑狼疮中的意义[J]. 北京大学学报(医学版), 2019, 51(6): 1019-1024.
[11] 徐婧,徐静,李鹤,唐杰,舒建龙,张婧,石连杰,李胜光. 皮肌炎合并IgA血管炎1例[J]. 北京大学学报(医学版), 2019, 51(6): 1173-1177.
[12] 张志刚,刘新民. 急性肾梗死的临床特征:单中心52例临床分析[J]. 北京大学学报(医学版), 2019, 51(5): 863-869.
[13] 张玮,张培训. 老年髋部骨折患者围手术期血栓预防时限分析[J]. 北京大学学报(医学版), 2019, 51(3): 501-504.
[14] 杨伊莹,左晓霞,朱红林,刘思佳. 皮肌炎/多肌炎表观遗传学标志物的研究进展[J]. 北京大学学报(医学版), 2019, 51(2): 374-377.
[15] 王永福,刘媛. 自身抗体在肿瘤及感染性疾病发生、发展中的作用[J]. 北京大学学报(医学版), 2018, 50(6): 952-955.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 田增民, 陈涛, Nanbert ZHONG, 李志超, 尹丰, 刘爽. 神经干细胞移植治疗遗传性小脑萎缩的临床研究(英文稿)[J]. 北京大学学报(医学版), 2009, 41(4): 456 -458 .
[2] 郭岩, 谢铮. 用一代人时间弥合差距——健康社会决定因素理论及其国际经验[J]. 北京大学学报(医学版), 2009, 41(2): 125 -128 .
[3] 成刚, 钱振华, 胡军. 艾滋病项目自愿咨询检测的技术效率分析[J]. 北京大学学报(医学版), 2009, 41(2): 135 -140 .
[4] 卢恬, 朱晓辉, 柳世庆, 郑杰, 邱晓彦. 白细胞介素2促进宫颈癌细胞系HeLaS3免疫球蛋白G的表达[J]. 北京大学学报(医学版), 2009, 41(2): 158 -161 .
[5] 袁惠燕, 张苑, 范田园. 离子交换型栓塞微球及其载平阳霉素的制备与性质研究[J]. 北京大学学报(医学版), 2009, 41(2): 217 -220 .
[6] 徐莉, 孟焕新, 张立, 陈智滨, 冯向辉, 释栋. 侵袭性牙周炎患者血清中抗牙龈卟啉单胞菌的IgG抗体水平的研究[J]. 北京大学学报(医学版), 2009, 41(1): 52 -55 .
[7] 董稳, 刘瑞昌, 刘克英, 关明, 杨旭东. 氯诺昔康和舒芬太尼用于颌面外科术后自控静脉镇痛的比较[J]. 北京大学学报(医学版), 2009, 41(1): 109 -111 .
[8] 祁琨, 邓芙蓉, 郭新彪. 纳米二氧化钛颗粒对人肺成纤维细胞缝隙连接通讯的影响[J]. 北京大学学报(医学版), 2009, 41(3): 297 -301 .
[9] 李宏亮*, 安卫红*, 赵扬玉, 朱曦. 妊娠合并高脂血症性胰腺炎行血液净化治疗1例[J]. 北京大学学报(医学版), 2009, 41(5): 599 -601 .
[10] 李伟军, 邢晓芳, 曲立科, 孟麟, 寿成超. PRL-3基因C104S位点突变体和CAAX缺失体的构建及表达[J]. 北京大学学报(医学版), 2009, 41(5): 516 -520 .