Statin--induced necrotizing autoimmune myopathy as an unusual cause of extreme elevation of cardiac markers in a patient with muscle weakness and swelling

Česká verzia

Authors: J. Švarko ¹; E. Lokočová ²; E. Kourková ³; P. Zajíček ¹
Authors place of work: Interní oddělení Nemocnice Valašské Meziříčí ¹; Fakultní nemocnice Olomouc, III. interní klinika – nefrologická, revmatologická a endokrinologická ²; Hematologicko-transfuzní oddělení Vsetínské nemocnice ³
Published in the journal: Čes. Revmatol., 28, 2020, No. 1, p. 52-60.
Category: Case Report

Summary

This review article with a case report shows a patient admitted to our department for a newly developed proximal weakness of the limbs and swelling. Laboratory examination showed an enormous elevation of cardiac markers – creatine kinase (CK-MB), troponins (hs-cTnT) and myoglobin. Statin medication had been chronically used. The cardiac cause of the laboratory findings was considered very unlikely due to the examinations performed. The polymyositis was considered another potential cause, but we initially refused it on the basis of negative findings of autoantibodies. Examinations that were gradually completed resulted in a final diagnosis of Statin-Induced Necrotizing Autoimmune Myopathy (SINAM) with a positive antibody to 3-hydroxy-3-methyl- glutaryl coenzyme A reductase (anti-HMGCR). Three months after the initiation of the immunosuppressive therapy, the range of motion of the extremities was significantly improved and swelling was reduced.

Keywords:

statins – limb-girdle weakness – swelling – immune-mediated necrotizing myopathy – anti-HMGCR

Zdroje

1. Bergua C, Chiavelli H, Simon JP, et al. Immune-mediated necrotizing myopathy. Z Rheumatol 2016; 75(2): 151–156.

2. Hoogendijk, JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, et al. 119^th ENMC international workshop: Trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis. Neuromuscul Disord 2004; 14(5): 337–345.

3. Mammen AL. Statin-associated autoimmune myopathy. N Engl J Med 2016; 374(7): 664–669.

4. Kalous T, et al. Imunitně zprostředkovaná nekrotizující myopatie. Neurol Praxi 2017; 18(4): 261–264.

5. Bednařík J, Vlčková E, Horák T. Statinová myopatie. Neurol Praxi 2017; 18(1): 15–19.

6. Christopher-Stine L, Casciola-Rosen LA, Hong G, et al. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum 2010; 62(9): 2757–2766.

7. Mohassel P, Mammen AL. Anti-HMGCR Myopathy. J Neuromuscul Dis 2018; 5(1): 11–20.

8. Padala S, Thompson PD. Statins as a possible cause of inflammatory and necrotizing myopathies. Atherosclerosis 2012; 222(1): 15–21.

9. Mammen AL, Pak K, Williams EK, et al. Rarity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in statin users, including those with self-limited musculoskeletal side effects. Arthritis Care Res (Hoboken) 2012; 64(2): 269–272.

10. Allenbach Y, Drouot L, Rigolet A, Charuel JL, Jouen F, Romero NB, et al. Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Medicine (Baltimore) 2014; 93(3): 150–157.

11. Musset L, Allenbach Y, Benveniste O, Boyer O, Bossuyt X, Bentow C, et al. Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: a history of statins and experience from a large international multi-center study. Autoimmun Rev 2016; 15: 983–993.

12. Werner JL, Christopher-Stine L, Ghazarian SR, Pak KS, Kus JE, Daya NR, et al. Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Rheum 2012; 64: 4087–4093.

13. Kishi T, Rider LG, Pak K, Barillas-Arias L, Henrickson M, McCarthy PL, et al. Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A reductase autoantibodies with DRB1*07:01 and severe myositis in Juvenile myositis patients. Arthritis Care Res 2017; 69: 1088–1094.

14. Allenbach Y, Mammen AL, Stenzel W, Benveniste O. 224^th ENMC International Workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies. Neuromuscul Disord 2018; 28(1): 87–99.

15. Kadoya M, Hida A, Hashimoto Maeda M, Taira K, Ikenaga C, Uchio N, et al. Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy. Neurol Neuroimmunol Neuroinflamm 2016; 3(6): e290.

16. Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Immune-mediated necrotizing myopathy. Curr Rheumatol Rep 2018; 20(4): 21.

17. Mohassel P, Mammen AL. Anti-HMGCR Myopathy. J Neuromuscular Dis 2018; 5(1): 11-20.

18. Arouche-Delaperche L, Allenbach Y, Amelin D, et al. Pathogenic role of anti-signal recognition protein and anti-3-hydroxy-3-methylglutaryl-CoA reductase antibodies in necrotizing myopathies: Myofiber atrophy and impairment of muscle regeneration in necrotizing autoimmune myopathies. Ann Neurol 2017; 81(4): 538–548.

19. Klein M, Mann H, Pleštilová L, et al. Increasing incidence of immune-mediatednecrotizing myopathy: single-centre experience. Rheumatol (Oxford) 2015; 54: 2010–2014.

20. Mammen AL, Pak K, Williams EK, et al. Rarity of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies in statin users, including those with self-limited musculoskeletal side eﬀects. Arthritis Care Res 2012; 64: 269–272.

21. Droney L, Gillis D, Wong R. New immunoassays for anti-HMG-CoA reductase antibodies may lead to incorrect diagnosis in inflammatory myositis. Pathology 2017; 49: 638–639.

22. Stuhlmüller B, Schneider U, González-González JB, Feist E. Disease specific autoantibodies in idiopathic inflammatory myopathies. Front Neurol 2019; 10: 438.

23. Alvarado-Cardenas M, Marin-Sánchez A, Martínez MA, Martínez-Martínez L, Pinal-Fernandez I, Labrador-Horrillo M, et al. Statin-associated autoimmune myopathy: a distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories. Autoimmun Rev 2016; 15: 1161–1166.

24. Janota T. Biochemické markery nekrózy myokardu v současné klinické praxi. Interv Akut Kardiol 2013; 12(1): 28–33.

25. Sribhen K, Phankingthongkum R, Wannasilp N. Skeletal muscle disease as noncardiac cause of cardiac troponin T elevation. J Am Coll Cardiol 2012; 59(14): 1334–1335.

26. Aggarwal R, Lebiedz-Odrobina D, Sinha A, Manadan A, et al. Serum cardiac troponin T, but not troponin I, is elevated in idiopathic inflammatory myopathies. J Rheumatol 2009; 36; 2711–2714.

27. Schmid J, Liesinger L, Birner-Gruenberger R, et al. Elevated cardiac troponin T in patients with skeletal myopathies. J Am Coll Cardiol 2018; 71(14): 1540–1549.

28. Milone M. Diagnosis and Management of Immune-Mediated Myopathies. Mayo Clinic Proceedings 2017; 92(5): 826–837.

29. Cong L, Pu CQ, Shi Q, Wang Q, Lu XH. Complement membrane attack complex is related with immune-mediated necrotizing myopathy. Int J Clin Exp Pathol 2014; 7(7): 4143–4149.

30. McGrath NM, Turner CP. Isolated gluteal and paravertebral muscle weakness due to anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase antibody-associated necrotizing autoimmune myopathy. Muscle Nerve 2016; 54: 150–152. 31. Schmidt J. Current classification and management of inflammatory myopathies. J Neuromuscul Dis 2018; 5(2): 109–129.

32. Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med 2015; 373: 1680–1682.