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Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (6): 989-995. doi: 10.19723/j.issn.1671-167X.2019.06.002

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Clinical and pathological characteristics of immune mediated necrotizing myopathy

Hong-xia YANG1,2,Xiao-lan TIAN2,Wei JIANG2,Wen-li LI2,Qing-yan LIU2,Qing-lin PENG2,Guo-chun WANG2,Xin LU1,△()   

  1. 1. Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
    2. Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China
  • Received:2019-08-17 Online:2019-12-18 Published:2019-12-19
  • Contact: Xin LU E-mail:luxin_n@163.com
  • Supported by:
    Supported by Beijing Municipal Science and Technology Commission(Z171100001017208)

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Abstract:

Objective: To investigate the clinical and pathological features of immune-mediated necro-tic myopathies (IMNM) with different myositis-specific antibodies (MSAs).Methods: In the study, 104 IMNM patients who met any of the following three criteria were selected from idiopathic inflammatory myopathy patients who had MSAs results and underwent muscle biopsy from 2008 to 2018 in China-Japan Friendship Hospital: (1) Anti-signal recognition particle (SRP) antibody positive; (2) Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibody positive; (3) MSAs negative and consistent with the pathological diagnostic criteria of IMNM defined by the European Neuromuscular Centre in 2004. The clinical, laboratory and muscle pathological information of the IMNM patients were retrospectively collected and compared in anti-SRP, anti-HMGCR and MSAs negative groups.Results: Of 104 IMNM patients, 47 patients (45.2%) were positive for anti-SRP antibody, 23 (22.1%) were positive for anti-HMGCR antibody, and 34 (32.7%) were negative for MSAs. The common symptoms of IMNM patients were muscle weakness (92.3%), elevated serum creatine kinase level (92.3%), dysphagia (33.7%) and interstitial lung diseases (ILD) (49.5%). The anti-HMGCR-positive patients were more frequent to have “V” sign (30.4% vs. 4.3% and 5.9%, P<0.01) as compared with the anti-SRP-positive and MSAs-negative patients. The incidence of ILD in the anti-SRP-positive patients was higher than that in the anti-HMGCR-positive and MSAs negative patients (64.4% vs. 34.8% and 29.0%, P<0.01). The prevalence of the patients combined with other connective tissue diseases in MSAs-negative IMNM was higher than that in the other two groups (32.4% vs. 8.5% and 4.3%, P<0.01). 93.3% of the anti-SRP-positive patients were found with antinuclear antibody positivity, higher than those of the anti-HMGCR-positive and MSAs-negative patients (93.3% vs. 36.4% and 58.8%, P<0.001). The common pathological features of IMNM were muscle fibre necrosis (94.2%), regeneration (67.3%) and phagocytosis (65.4%), overexpression of major histocompatibility complex-1 on sarcolemma (78.8%), infiltration of CD4 + T cells (81.7%) and CD68 + macrophage (79.8%) and expression of membrane attack complex (MAC) (77.8%). The endomysial infiltration of CD4 + T cells and CD68 + macrophage and MAC expression on sarcolemma in the MSAs-negative group were more common than that in the anti-SRP and anti-HMGCR groups (88.2% vs. 57.4% and 60.9%, 91.2% vs. 59.1% and 38.1%, 76.5% vs. 45.5% and 42.9%, respectively, P<0.01).Conclusion: There is heterogeneity in anti-SRP-positive, anti-HMGCR-positive or MSAs-negative patients. The detection of MSAs and performing of muscle biopsy are useful for distinguishing different types of IMNM.

Key words: Myositis, Autoimmune diseases, Signal recognition particle, Hydroxymethylglutaryl CoA reductases, Pathology

CLC Number: 

  • R593.26

Table 1

Comparisons of clinical features of different serological subgroups of IMNM"

Features IMNM(n=104) Anti-SRP(n=47) Anti-HMGCR(n=23) MSAs negative(n=34) P
Female 73 (70.2) 38 (80.9) 13 (56.5) 22 (64.7) 0.078
Age/years 46.24±15.38 47.49±15.76 46.09±18.08 44.62±12.02 0.712
Age of onset/years 44.63±16.03 46.11±16.21 44.13±20.83 42.91±11.82 0.671
Duration/months 20.85±27.79 19.01±25.08 25.5±35.03 10.23±26.36 0.652
Chronic progression (>12 months) 59 (56.7) 28 (59.6) 12 (52.2) 19 (55.9) 0.836
Fever 5 (4.8) 3 (6.4) 1 (4.3) 1 (2.9) 0.763
Loss of weight 31 (29.8) 14 (29.8) 4 (17.1) 13 (32.8) 0.241
Muscle weakness 96 (92.3) 44 (93.6) 21 (91.3) 31 (91.1) 0.902
Severe muscle weakness 48 (46.2) 22 (46.8) 9 (39.1) 17 (50.0) 0.716
Muscle atrophy 15/73(20.5) 5/33 (15.6) 4/17 (23.5) 6/24 (25.0) 0.651
Myalgia 29 (27.9) 13 (27.7) 8 (34.8) 8 (23.5) 0.649
Arthritis 10 (9.6) 4 (8.5) 1 (4.3) 5 (14.7) 0.404
Skin involvement 27 (26.0) 12 (25.5) 8 (34.8) 7 (20.6) 0.485
Heliotrope rash 7 (7.7) 3 (6.4) 2 (8.7) 3 (8.8) 0.902
Gottron’s sign 2 (1.9) 1 (2.1) 0 1 (2.9) 0.723
“V” sign 11 (10.6) 2 (4.3) 7 (30.4) 2 (5.9) 0.002*
Shawl sign 6 (5.8) 2 (4.3) 4 (17.4) 0 0.018
Raynaud phenomenon 4 (3.8) 3 (6.4) 0 1 (2.9) 0.404
ILD 46/99 (46.5) 29/45 (64.4) 7/23 (30.4) 10/31 (29.0) 0.004#
Cough 2/46 (4.3) 2/29 (6.9) 0/7 0/10 0.542
Dyspnea 4/46 (8.7) 3/29 (10.3) 0/7 1/10 (10.0) 0.675
Asymptomatic 41/46 (89.1) 25/29 (86.2) 7/7 (100.0) 9/10 (90.0) 0.572
Dysphagia 35 (33.7) 17 (36.2) 8 (34.8) 10 (29.4) 0.576
Cancer 4 (3.8) 3 (6.4) 1 (4.3) 0 0.334
With other CTD 16 (15.4) 4 (8.5) 1 (4.3) 11 (32.4) 0.003△
Death 5 (4.8) 3 (6.4) 1 (4.3) 1 (2.9) 0.769

Table 2

Comparisons of laboratory characteristics of different serological subgroups of IMNM"

Features a IMNM (n=104) Anti-SRP (n=47) Anti-HMGCR (n=23) MSAs negative (n=34) P
Anti-Ro-52 25 (24.0) 16 (34.0) 1 (4.3) 8 (23.5) 0.024
ANA 74/101 (73.3) 42/45 (93.3) 8/22 (36.4) 20/34 (58.8) <0.001*
Peak CK/(IU/L) 5 100 (2 749, 9 916) 5 070 (2 975, 9 994) 5 728 (3 320, 11 435) 4 827 (1 324, 9 831) 0.546
ALT (0-40 U/L) 96 (51, 208) 120 (55, 221) 93 (51, 209) 92 (38, 154) 0.500
AST (0-40 U/L) 62 (36, 127) 83 (37, 151) 64 (36, 124) 54 (29, 114) 0.306
LDH (100-250 IU/L) 522 (317, 770) 587 (339, 783) 569 (330, 836) 387 (258, 615) 0.113
CK (26-200 IU/L) 2 157 (810, 4 645) 1 753 (771, 4 241) 2 157 (861, 5 481) 2 326 (612, 4 709) 0.956
CRP (<8 mg/L) 2.9 (1.9, 5.5) 2.9 (1.9, 5.2) 4.3 (2.2, 8.6) 2.6 (1.6, 5.2) 0.198
ESR (<20 mm/h) 8 (4, 16) 9 (4, 20) 8 (4, 20) 6 (3, 13) 0.466
Fet (11.0-306.8 μg/L) 123.0 (48.9, 231.1) 120.0 (58.9, 218.2) 172.0 (109.9, 716.7) 86.0 (22.0, 205.0) 0.126
IgG (6.94-16.20 g/L) 10.50 (8.28, 14.13) 11.60 (8.73, 15.65) 8.59 (6.03, 11.28) 10.50 (8.87, 13.40) 0.033#
IgA (0.68-3.78 g/L) 1.67 (1.17, 2.35) 1.86 (1.35, 2.58) 1.32 (1.03, 1.92) 1.56 (0.09, 2.54) 0.105
IgM (0.60-2.63 g/L) 1.12 (0.79, 1.45) 1.19 (0.82, 1.76) 0.88 (0.66, 1.21) 1.18 (0.84, 1.42) 0.109
C3 (0.70-1.28 g/L) 0.86 (0.75, 1.01) 0.87 (0.77, 0.99) 0.88 (0.78, 1.05) 0.82 (0.71, 1.03) 0.336
C4 (0.16-0.47 g/L) 0.18 (0.15, 0.22) 0.19 (0.15, 0.23) 0.20 (0.17, 0.24) 0.17 (0.12, 0.20) 0.067
T cell (1 000-3 000 cell/mL) 2 060 (1 555, 2 650) 1 870 (1 480, 2 240) 1 990 (1 370, 2 350) 2 620 (1 570, 3 350) 0.027△
CD3+ T cell (808-2 072 cell/mL) 1 500 (1 038, 1 877) 1 400 (999, 1 686) 1 458 (903, 1 978) 1 767 (1 125, 2 378) 0.760
CD4+ T cell (380-1 280 cell/mL) 853 (608, 1 283) 817 (604, 1 114) 758 (456, 1 123) 1 767 (1 125, 2 378) 0.042
CD8+ T cell (229-982 cell/μL) 493 (375, 761) 477 (378, 678) 653 (345, 797) 554 (348, 812) 0.586

Table 3

Comparisons of pathological features of different serological subgroups of IMNM"

Features IMNM (n=104) Anti-SRP (n=47) Anti-HMGCR (n=23) MSAs negative (n=34) P
Muscle fibre
Necrosis 98 (94.2) 43 (91.5) 21 (91.3) 34 (100.0) 0.213
Regeneration 70 (67.3) 33 (70.2) 11 (47.8) 26 (76.5) 0.066
Phagocytosis 68 (65.4) 27 (57.4) 14 (60.9) 27 (79.4) 0.107
Connective tissue proliferation 36 (34.6) 17 (36.2) 8 (34.8) 11 (32.4) 0.938
MHC-Ⅰ expression on sarcolemma 82 (78.8) 35 (74.5) 17(73.9) 30 (88.2) 0.263
Partial expression 56 (53.8) 24 (51.1) 11 (47.8) 21 (61.8) 0.512
Diffuse expression 26 (25.0) 11 (23.4) 6 (26.1) 9 (26.5) 0.953
Inflammation infiltration
CD4+T cell 85 (81.7) 35 (74.5) 18 (78.3) 32 (94.1) 0.045
Endomysial 71 (68.3) 27 (57.4) 14 (60.9) 30 (88.2) 0.009*
Perivascular 30 (28.8) 17 (36.2) 6 (26.1) 7 (20.6) 0.295
CD8+T cell 57 (54.8) 21 (44.7) 11 (47.8) 25 (73.5) 0.027#
Endomysial 48 (46.2) 17 (36.2) 8 (34.8) 23 (67.6) 0.009*
Perivascular 17 (16.3) 8 (17.0) 4 (17.4) 5 (14.7) 0.951
CD20+B cell 7 (6.7) 2 (4.3) 1 (4.3) 4 (11.8) 0.361
Endomysial 4 (3.8) 1 (2.1) 0 3 (8.8) 0.168
Perivascular 3 (2.9) 1(2.1) 1 (4.3) 1 (2.9) 0.124
CD68+ macrophage 79/99 (79.8) 35/44 (79.5) 11/21 (52.4) 32 (94.1) 0.002△
Endomysial 65/99 (65.7) 26/44 (59.1) 8/21 (38.1) 31 (91.2) <0.001*
Perivascular 24/99 (24.2) 18/44 (40.9) 3/21 (15.0) 3 (8.8) 0.003#
MAC 77/99 (77.8) 34/44 (77.3) 11/21 (52.4) 32 (94.1) 0.001△
Sarcolemma 55/99 (55.6) 20/44 (45.5) 9/21 (42.9) 26 (76.5) 0.015*
Sarcoplasm 18/99 (18.2) 8/44 (18.2) 3/21 (14.3) 7 (20.6) 0.841
Capillaries 31/99 (31.3) 19/44 (43.2) 4/21 (19.0) 8 (23.5) 0.070

Figure 1

The pathological features of IMNM The expression of MHC-Ⅰ on sarcolemma (B, F, J); the endomysial infiltration of CD68 (C, G); the perivascular infiltration of CD4 (K); the deposition of membrane attack complex (MAC) in muscle fiber (D) or sarcolemma (H); CD8 surrounding non-necrotic muscle fiber (L). A, E, I, scattered necrotic muscle fibres in HE staining; B-D, F-H, J-L, immunohistochemistry staining. "

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