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)

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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
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