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北京大学学报（医学版） ›› 2020, Vol. 52 ›› Issue (6): 1001-1008. doi: 10.19723/j.issn.1671-167X.2020.06.003

• 论著 • 上一篇    下一篇

临床无肌病性皮肌炎与皮肌炎临床及免疫学特征比较

甘雨舟1,李玉慧1,张丽华2,马琳3,何文雯4,金月波1,安媛1,栗占国1,叶华1,△()   

  1. 1. 北京大学人民医院风湿免疫科,北京 100044
    2. 呼伦贝尔市人民医院风湿免疫科,内蒙古呼伦贝尔市 021008
    3. 河北省中医院风湿免疫科,石家庄 050011
    4. 重庆医科大学附属第一医院内分泌内科,重庆 400016
  • 收稿日期:2020-07-27 出版日期:2020-12-18 发布日期:2020-12-13
  • 通讯作者: 叶华 E-mail:yehbmu@126.com
  • 基金资助:
    国家自然科学基金(81801615);国家自然科学基金(81871289);国家自然科学基金(81801617)

Comparison of clinical and immunological features between clinically amyopathic dermatomyositis and typical dermatomyositis

Yu-zhou GAN1,Yu-hui LI1,Li-hua ZHANG2,Lin MA3,Wen-wen HE4,Yue-bo JIN1,Yuan AN1,Zhan-guo LI1,Hua YE1,△()   

  1. 1. Department of Rheumatology & Immunology, Peking University People’s Hospital, Beijing 100044, China
    2. Department of Rheumatology, Hulunbeier People’s Hospital, Hulunbeier 021008, Inner Mongolia, China
    3. Department of Rheumatology, Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050200, China
    4. Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • Received:2020-07-27 Online:2020-12-18 Published:2020-12-13
  • Contact: Hua YE E-mail:yehbmu@126.com
  • Supported by:
    National Natural Science Foundation of China(81801615);National Natural Science Foundation of China(81871289);National Natural Science Foundation of China(81801617)

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摘要：

目的:比较临床无肌病性皮肌炎(clinically amyopathic dermatomyositis, CADM)和皮肌炎(dermatomyositis, DM)的临床及免疫学特征。方法:选择2010年1月—2019年12月在北京大学人民医院风湿免疫科住院的106例CADM和158例DM患者的病例资料进行回顾性分析,对两组患者的临床及免疫学指标进行比较,探讨肌炎抗体在CADM和DM中的的分布特点及临床意义,其中,肌炎抗体的检测采用免疫印迹法。结果:在临床表现方面,与DM相比,CADM更多地以肺间质病变(interstial lung diseases, ILD)起病(20.7% vs. 7.6%, P=0.002),且以急性ILD为主(58.3% vs. 26%, P<0.001),而在皮疹、合并其他结缔组织病和恶性肿瘤等方面,CADM与DM差异无统计学意义,CADM类风湿因子和抗核抗体的阳性率均低于DM。CADM最常见的肌炎特异性抗体(myositis specific autoantibodies, MSAs)为抗黑色素瘤分化相关基因5(melanoma differentiation related genes, MDA5, 36%)、抗PL-7(11.2%)及抗TIF-1γ(10.1%);DM最常见的MSAs为抗Jo-1(19.2%)、抗TIF-1γ(11.5%)及抗MDA5(11.5%)。抗MDA5与急性ILD及皮肤破溃相关,但在CADM中皮肤破溃与抗MDA5的滴度无关,而在DM中皮肤破溃与高滴度的抗MDA5相关。在DM中,抗TIF-1γ与向阳疹、V领/披肩征、甲周炎,以及合并恶性肿瘤相关,且合并恶性肿瘤的比例与抗TIF-1γ的滴度无关;在CADM中,抗TIF-1γ与临床表现及合并症无明显相关性。CADM及DM中最常见肌炎相关抗体均为抗Ro-52,抗Ro-52在CADM中与雷诺现象和慢性ILD相关,在DM中与技工手、发热,以及合并其他结缔组织病相关。结论:与DM相比,CADM-ILD以急性为主,肌炎抗体在CADM与DM中具有不同的分布特点;同一种肌炎抗体在CADM及DM中的临床意义也存在区别,且部分肌炎抗体的临床意义还与滴度相关。

关键词: 皮肌炎, 临床无肌病性皮肌炎, 肌炎抗体

Abstract:

Objective: To study the differences between clinically amyopathic dermatomyositis (CADM) and typical dermatomyositis (DM) on clinical and immunological features. Methods: By collecting clinical data of 106 CADM patients and 158 DM patients from January 2010 to June 2019 in the department of Rheumatology and Immunology, Peking University People’s Hospital, the clinical characteristics and immunological features in the two groups were compared, and the distribution characters and the clinical meanings of myositis autoantibodies were discussed in the two groups respectively. Myositis autoantibodies were measured by immunoblotting according to the manufacturers’ instructions. Results: In the aspects of clinical manifestations, CADM presented more with onset of interstial lung diseases (ILD) compared with DM (20.7% vs. 7.6%, P=0.002), and CADM-ILD was more likely to be acute ILD (58.3% vs. 26%, P<0.001), and there were no differences between CADM and DM in cutaneous manifestations, accompanied with connective tissue disease (CTD) and malignancy. In CADM, the positive rate of rheumatoid factors and antinuclear antibodies was lower in DM. The most common myositis specific autoantibodies (MSAs) in CADM were anti-MDA5 (36%), anti-PL-7 (11.2%) and anti-TIF-1γ (10.1%). The most common MSAs in DM were anti-Jo-1 (19.2%), anti-TIF-1γ (11.5%) and anti-MDA5 (11.5%). Anti-MDA5 was correlated with acute ILD and skin ulceration both in CADM and DM; in CADM, skin ulceration was not associated with the titer of anti-MDA5; while in DM, skin ulceration was associated with high titer of anti-MDA5. In DM, anti-TIF-1γ was correlated with heliotrope eruption, V/shawl neck sign, perionychia erythma and malignancy, and higher rate of malignancy was seen in all titers of the anti-TIF-1γ positive patients. In CADM, anti-TIF1-γ showed no correlation with clinical manifestations. The most common myositis associated autoantibody was anti-Ro-52 both in CADM and DM. In CADM, anti-Ro-52 was associated with Raynaud’s phenomenon and chronic ILD, while in DM, anti-Ro-52 was associated with mechanic’s hands, noninfectious fever and accompanied CTD. Conclusion: Compared with DM, ILD is more likely to be acute in CADM. It is different between CADM and DM about the distribution of myositis autoantibodies and the clinical significance of the same myositis antibody, and the clinical significance of some myositis antibodies is related to titers.

Key words: Clinically amyopathic dermatomyositis, Dermatomyositis, Myositis autoantibody

中图分类号: 

  • R593.26

表1

CADM与DM的临床表现及实验室指标比较"

Items CADM (n=106) DM (n=158) F/χ2 P
Age/years, x-±s 50.47±12.44 51.63±13.85 0.484 0.487
Gender, female:male (%female) 82:24 (77.4) 109:49 (69.0) 2.222 0.136
Age of onset/years, x-±s 48.84±13.07 48.92±14.79 0.001 0.969
Cutaneous manifestation
Gottron’s sign/papule, n(%) 85 (80.2) 115 (72.8) 1.894 0.169
Mechanic’s hands, n(%) 41 (38.7) 56 (35.4) 0.286 0.593
Heliotrope eruption, n(%) 59 (55.7) 82 (51.9) 0.361 0.548
V shawl neck sign, n(%) 59 (55.7) 92 (58.2) 0.171 0.679
Skin ulceration, n(%) 13 (12.3) 17 (10.8) 0.143 0.706
Perionychia erythma, n(%) 21 (19.8) 35 (22.2) 0.208 0.648
Skin calcinosis, n(%) 7 (6.6) 8 (5.1) 0.281 0.596
Pulmonary involvement
ILD, n(%) 84 (79.2) 131 (82.9) 0.564 0.453
Acute, n(%) 49 (58.3) 34 (26.0) 22.640 <0.001
Asymptomatic, n(%) 17 (20.2) 43 (32.8) 4.030 0.045
ILD onset before CADM diagnosed, n(%) 22 (20.7) 12 (7.6) 9.792 0.002
Systemic symptoms
Noninfectious fever, n(%) 41 (38.7) 56 (35.4) 0.286 0.593
Arthralgia, n(%) 56 (52.8) 65 (41.1) 3.493 0.062
Raynaud phenomenon, n(%) 12 (11.3) 22 (13.9) 0.383 0.536
Splenomegaly, n(%) 11 (10.4) 10 (6.3) 1.383 0.240
Weight loss, n(%) 38 (35.8) 44 (27.8) 1.897 0.168
Accompanied CTD, n(%) 20 (18.9) 31 (19.6) 0.023 0.879
Accompanied malignancy, n(%) 5 (4.7) 14 (8.9) 1.631 0.202
Serum TAAs
CEA/(μg/L), M(P25, P75) 2.89 (1.76, 5.27) 2.00 (1.10, 4.03) 2.750 0.006
AFP/(μg/L), M(P25, P75) 2.45 (1.89, 3.17) 2.45 (1.78, 3.46) 0.297 0.767
CA19-9/(U/mL), M(P25, P75) 11.81 (4.97, 16.53) 9.92 (5.78, 18.87) 0.471 0.638
CYFRA21-1/(μg/L), M(P25, P75) 3.38 (2.05, 5.49) 3.06 (2.36, 4.81) 0.260 0.795
NSE/(μg/L), M(P25, P75) 14.08 (11.15, 17.20) 16.20 (12.39, 23.47) 2.848 0.004
Immunological parameters
RF positive, n(%)* 11 (10.8) 32 (20.5) 4.203 0.040
ANA (≥1:80), n(%)* 36 (35.3) 78 (50.0) 6.538 0.011

表2

肌炎抗体在CADM与DM中分布的比较"

Items CADM (n=89) DM (n=130) Comparison by
overall positive
rate		 Comparison
by titers
Overall + ++ +++ Overall + ++ +++ χ2 P χ2 P
Myositis specific autoantibodies (MSAs)
Mi-2α 1 (1.1) 1 (1.1) 0 0 7 (5.4) 3 (2.3) 3 (2.3) 1 (0.8) - 0.146 3.124 0.077
Mi-2β 4 (4.5) 3 (3.4) 0 1 (1.1) 6 (4.6) 3 (2.3) 3 (2.3) 0 - 1 0.001 0.970
TIF-1γ 9 (10.1) 8 (9.0) 1 (1.1) 0 15 (11.5) 3 (2.3) 5 (3.8) 9 (6.9) 0.444 0.505 4.202 0.040
MDA5 32 (36.0) 6 (6.7) 6 (6.7) 20 (22.5) 15 (11.5) 5 (3.8) 2 (1.5) 8 (6.2) 20.65 <0.001 18.697 <0.001
NXP2 5 (5.6) 2 (2.2) 1 (1.1) 2 (2.2) 7 (5.4) 1 (0.8) 3 (2.3) 3 (2.3) 0.006 0.941 0.022 0.883
SAE1 3 (3.4) 0 0 3 (3.4) 1 (0.8) 0 0 1 (0.8) - 0.306 - 0.306
SRP 4 (4.5) 4 (4.5) 0 0 8 (6.2) 2 (1.5) 2 (1.5) 4 (3.1) - 0.765 2.108 0.147
Jo-1 7 (7.9) 2 (2.2) 2 (2.2) 3 (3.4) 25 (19.2) 2 (1.5) 3 (2.3) 20 (15.4) 5.47 0.019 7.255 0.007
PL-7 10 (11.2) 5 (5.6) 3 (3.4) 2 (2.25) 10 (7.7) 2 (1.5) 4 (3.1) 4 (3.1) 0.799 0.371 0.067 0.796
PL-12 7 (7.9) 1 (1.1) 1 (1.1) 5 (5.6) 7 (5.4) 3 (2.3) 0 4 (3.1) 0.543 0.461 1.034 0.309
EJ 0 (0.0) 0 0 0 10 (7.7) 1 (0.8) 1 (0.8) 8 (6.2) - 0.006 6.744 0.009
OJ 2 (2.2) 2 (2.25) 0 0 4 (3.1) 3 (2.3) 1 (0.8) 0 - 1 0.336 0.562
Myositis associated autoantibodies (MAAs)
PM-Scl100 6 (6.7) 5 (5.6) 1 (1.12) 0 5 (3.8) 1 (0.8) 1 (0.8) 3 (2.3) 0.928 0.335 0.055 0.815
PM-Scl75 6 (6.7) 3 (3.4) 1 (1.12) 2 (2.2) 9 (6.9) 2 (1.5) 4 (3.1) 3 (2.3) 0.003 0.958 0.089 0.766
Ku 9 (10.1) 4 (4.5) 2 (2.2) 3 (3.4) 4 (3.1) 2 (1.5) 1 (0.8) 1 (0.8) - 0.041 4.218 0.040
Ro-52 44 (49.4) 8 (9.0) 5 (5.6) 31 (34.8) 70 (53.8) 4 (3.1) 4 (3.1) 62 (47.7) 0 1 1.952 0.162
Both MSAs and
MAAs positive		 79 (88.8) - - - 112 (86.1) - - - 1.143 0.285 - -
Only MSAs positive 62 (69.7) - - - 99 (76.1) - - - 0 0.989 - -
Only MAAs positive 54 (60.1) - - - 79 (60.8) - - - 0.323 0.570 - -

表3

在CADM与DM中肌炎抗体的临床表现及合并疾病的相关性的比较"

Items CADM DM
TIF-1γ MDA5 Ro-52 TIF-1γ MDA5 Ro-52
r P r P r P r P r P r P
Mechanic’s hands -0.058 0.524 0.117 0.275 0.101 0.344 0.004 0.961 0.058 0.509 0.196 0.026
Heliotrope eruption 0.025 0.818 0.165 0.123 -0.335 0.001 0.310 <0.001 0.146 0.098 -0.121 0.171
V/shawl neck sign 0.111 0.302 0.014 0.893 -0.157 0.141 0.280 0.001 0.127 0.151 -0.256 0.003
Skin ulceration -0.013 0.907 0.289 0.006 -0.167 0.117 -0.022 0.805 0.310 <0.001 0.013 0.882
Perionychia erythma 0.017 0.875 0.115 0.281 -0.148 0.167 0.287 <0.001 0.300 0.001 0.024 0.783
Skin calcinosis -0.078 0.465 -0.169 0.112 0.063 0.560 -0.087 0.323 -0.079 0.372 -0.179 0.042
Noninfectious fever 0.012 0.912 -0.015 0.892 0.094 0.381 -0.238 0.006 -0.082 0.354 0.257 0.003
Arthralgia -0.156 0.144 0.107 0.317 0.102 0.343 -0.165 0.060 0.204 0.020 0.141 0.109
Raynaud’s phenomenon -0.013 0.907 -0.106 0.322 0.246 0.020 -0.046 0.601 -0.025 0.775 0.052 0.556
Malignancy -0.070 0.516 -0.022 0.840 -0.078 0.465 0.476 <0.001 -0.124 -0.160 -0.102 0.247
Accompanied CTD -0.089 0.407 0.073 0.498 0.066 0.540 -0.135 0.124 -0.110 0.214 0.329 <0.001

表4

在CADM与DM中肌炎抗体与不同类型肺间质病变相关性的比较"

Items CADM DM
Non-ILD
(n=16)		 Acute ILD
(n=44)		 Chronic ILD
(n=29)		 P Non-ILD
(n=22)		 Acute ILD
(n=27)		 Chronic ILD
(n=81)		 P
TIF-1γ 3 (18.7) 5 (11.4) 1 (3.4) 0.234 8 (36.4) 0* 9 (11.1)* 0
MDA5 3 (18.7) 22 (50.0)* 7 (24.1)§ 0.027 0 8 (29.6)* 7 (8.6)§ 0.002
Jo-1※ - - - - 1 (4.5) 7 (25.9)* 17 (21.0)* 0.039
Ro-52 4 (25.0) 21 (47.7) 19 (65.5)*§ 0.018 9 (40.9) 17 (63.0) 44 (54.3) 0.415

图1

不同滴度的肌炎抗体阳性的CADM患者临床表现的比较"

图2

不同滴度肌炎抗体阳性的DM患者临床表现的比较"

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