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Immune-mediated necrotizing myopathy

Immunvermittelte nekrotisierende Myopathie

Zeitschrift für Rheumatologie volume 75, pages 151–156 (2016)Cite this article

Abstract

Background

Immune-mediated necrotizing myopathy (IMNM) is a newly identified subgroup of idiopathic inflammatory myopathies. It is defined as a rare and severe disease, with symmetrical and proximal muscle weakness and a characteristic histology. An autoimmune aspect of IMNM is suggested by its association with autoantibodies directed against signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the majority of patients. Statin use is strongly associated with anti-HMGCR-positive IMNM. The pathophysiological mechanisms of this disease are still poorly understood, and as a result, no therapeutic strategy has been validated to date.

Objective

The aim of this article is to provide an overview of the current knowledge about epidemiology, clinical features, and pathophysiology of IMNM, as well as treatment strategies.

Results and conclusion

IMNM is a subject of widespread interest, with quick and meaningful advances being made. In recent years, huge progress has been made in terms of diagnosis and patient management. However, the understanding of pathophysiological mechanisms and treatment strategies still requires further investigation.

Zusammenfassung

Hintergrund

Immunvermittelte nekrotisierende Myopathie (IMNM) ist eine neu identifizierte Untergruppe der idiopathischen entzündlichen Myopathien. Sie ist als seltene und schwere Erkrankung mit symmetrischer und proximaler Muskelschwäche und einer charakteristischen Histologie definiert. Auf einen Autoimmunaspekt von IMNM weist ihre Verbindung mit Autoantikörpern hin, die sich bei der Mehrheit der Patienten gegen die Signalerkennungspartikel (SRP) und 3-Hydroxy-3-Methylglutaryl-Coenzym-A-Reduktase (HMGCR) richten. Statingebrauch steht in enger Verbindung mit Anti-HMGCR-positiver IMNM. Das Verständnis der pathophysiologischen Mechanismen dieser Erkrankung ist bislang nur dürftig , weshalb bis jetzt keine therapeutische Strategie anerkannt ist.

Ziel

Das Ziel dieses Artikels ist es, einen Überblick über das derzeitige Wissen hinsichtlich Epidemiologie, klinischer Merkmale und der Pathophysiologie von IMNM sowie zu Behandlungsstrategien zu liefern.

Ergebnisse und Schlussfolgerung

IMNM ist Gegenstand breiten Interesses, wobei schnelle und bedeutsame Fortschritte gemacht werden. In den vergangenen Jahren gab es enorme Entwicklungen bei der Diagnose und im Patientenmanagement. Das Verständnis der pathophysiologischen Mechanismen und Behandlungsstrategien erfordert allerdings weitere Forschung.

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References

  1. Dalakas MC (2015) Inflammatory muscle diseases. N Engl J Med 372:1734–1747

    Article  PubMed  Google Scholar 

  2. Hoogendijk JE et al (2004) 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands. Neuromuscul Disord 14:337–345

    Article  PubMed  Google Scholar 

  3. Christopher-Stine L et al (2010) A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum 62:2757–2766

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Hengstman GJD et al (2006) Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann Rheum Dis 65:1635–1638

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Liang C, Needham M (2011) Necrotizing autoimmune myopathy. Curr Opin Rheumatol 23:612–619

    Article  PubMed  Google Scholar 

  6. Reeves WH, Nigam SK, Blobel G (1986) Human autoantibodies reactive with the signal-recognition particle. Proc Natl Acad Sci U S A 83:9507–9511

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Mastaglia FL, Phillips BA (2002) Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic criteria. Rheum Dis Clin North Am 28:723–741

    Article  PubMed  Google Scholar 

  8. Rouster-Stevens KA, Pachman LM (2008) Autoantibody to signal recognition particle in African American girls with juvenile polymyositis. J Rheumatol 35:927–929

    CAS  PubMed  Google Scholar 

  9. Alshehri A, Choksi R, Bucelli R, Pestronk A (2015) Myopathy with anti-HMGCR antibodies: Perimysium and myofiber pathology. Neurol Neuroimmunol Neuroinflamm 2:e124

    Article  PubMed  PubMed Central  Google Scholar 

  10. Drouot L et al (2014) Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies. Arthritis Res Ther 16:R39

    Article  PubMed  PubMed Central  Google Scholar 

  11. Miller T, Al-Lozi MT, Lopate G, Pestronk A (2002) Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry 73:420–428

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Allenbach Y et al (2014) Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Medicine (Baltimore) 93:150–157

    CAS  Article  Google Scholar 

  13. Mammen AL et al (2012) Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Care Res 64:1233–1237

    CAS  Article  Google Scholar 

  14. Mammen AL et al (2011) Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum 63:713–721

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Werner JL et al (2012) Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Rheum 64:4087–4093

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Limaye V et al (2014) Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve 52(2):196–203. doi:10.1002/mus.24541

    Article  Google Scholar 

  17. Watanabe Y et al (2015) Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan. Medicine (Baltimore) 94:e416

    CAS  Article  Google Scholar 

  18. Mammen AL et al (2012) 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 64:269–272

    CAS  Article  Google Scholar 

  19. Chung T, Christopher-Stine L, Paik JJ, Corse A, Mammen AL (2015) The composition of cellular infiltrates in anti-HMG-CoA reductase-associated myopathy. Muscle Nerve 52(2):189–195. doi:10.1002/mus.24642

    CAS  Article  PubMed  Google Scholar 

  20. Kao AH, Lacomis D, Lucas M, Fertig N, Oddis CV (2004) Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum 50:209–215

    CAS  Article  PubMed  Google Scholar 

  21. Römisch K, Miller FW, Dobberstein B, High S (2006) Human autoantibodies against the 54 kDa protein of the signal recognition particle block function at multiple stages. Arthritis Res Ther 8:R39

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bronner IM et al (2003) Necrotising myopathy, an unusual presentation of a steroid-responsive myopathy. J Neurol 250:480–485

    CAS  Article  PubMed  Google Scholar 

  23. Iaccarino L et al (2014) Assessment of patients with idiopathic inflammatory myopathies and isolated creatin-kinase elevation. Auto Immun Highlights 5:87–94

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Benveniste O et al (2011) Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy. Arthritis Rheum 63:1961–1971

    CAS  Article  PubMed  Google Scholar 

  25. Targoff IN, Johnson AE, Miller FW (1990) Antibody to signal recognition particle in polymyositis. Arthritis Rheum 33:1361–1370

    CAS  Article  PubMed  Google Scholar 

  26. Claeys KG et al (2013) Diagnostic challenge and therapeutic dilemma in necrotizing myopathy. Neurology 81:932–935

    Article  PubMed  Google Scholar 

  27. Aouizerate J et al (2014) Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy. Acta Neuropathol Commun 2:154

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mahler M, Miller FW, Fritzler MJ (2014) Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 13:367–371

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. Mescam-Mancini L et al (2015) Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis. Brain J Neurol 138:2485–2492

    Article  Google Scholar 

  30. Stenzel W et al (2015) Nuclear actin aggregation is a hallmark of anti-synthetase syndrome-induced dysimmune myopathy. Neurology 84:1346–1354

    CAS  Article  PubMed  Google Scholar 

  31. Chatterjee S (2013) Antisynthetase syndrome: Not just an inflammatory myopathy. Cleve Clin J Med 80(10):655–666

    Article  PubMed  Google Scholar 

  32. Smith B (1969) Skeletal muscle necrosis associated with carcinoma. J Pathol 97:207–210

    CAS  Article  PubMed  Google Scholar 

  33. Wegener S, Bremer J, Komminoth P, Jung HH, Weller M (2010) Paraneoplastic Necrotizing Myopathy with a mild inflammatory component: a case report and review of the literature. Case Rep Oncol 3(1):88–92

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M (2015) Clinical features and treatment outcomes of Necrotizing Autoimmune Myopathy. JAMA Neurol 72(9):996–1003. doi:10.1001/jamaneurol.2015.1207

    Article  PubMed  Google Scholar 

  35. Dalakas MC (2010) Immunotherapy of myositis: issues, concerns and future prospects. Nat Rev Rheumatol 6:129–137

    Article  PubMed  Google Scholar 

  36. Valiyil R, Casciola-Rosen L, Hong G, Mammen A, Christopher-Stine L (2010) Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: a case series. Arthritis Care Res 62:1328–1334

    CAS  Article  Google Scholar 

  37. Curtin D et al (2014) Novel antibody associations in immune-mediated necrotising myopathy without inflammation. Ir J Med Sci. doi:10.1007/s11845-014-1207-z

    Google Scholar 

  38. Grable-Esposito P et al (2010) Immune-mediated necrotizing myopathy associated with statins. Muscle Nerve 41:185–190

    CAS  PubMed  Google Scholar 

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Author information

Affiliations

  1. Normandie University, IRIB, Rouen, France

    C. Bergua, H. Chiavelli, O. Boyer, F. Jouen & J. Martinet

  2. INSERM, U905, Rouen, France

    C. Bergua, H. Chiavelli, O. Boyer & J. Martinet

  3. Department of Neuropathology, Caen University Hospital, Caen, France

    J. P. Simon

  4. Department of Immunology, Rouen University Hospital, 22 bd Gambetta, 76000, Rouen, France

    O. Boyer, F. Jouen & J. Martinet

  5. Department of Neuropathology, Charité – Universitätsmedizin, Berlin, Germany

    W. Stenzel

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  1. C. Bergua
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  2. H. Chiavelli
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  7. J. Martinet
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Correspondence to J. Martinet.

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C. Bergua, H. Chiavelli, J.P. Simon, O. Boyer, F. Jouen, W. Stenzel, and J. Martinet state that there are no conflicts of interest.

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Bergua, C., Chiavelli, H., Simon, J.P. et al. Immune-mediated necrotizing myopathy. Z Rheumatol 75, 151–156 (2016). https://doi.org/10.1007/s00393-015-0029-3

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Keywords

  • Pathophysiology
  • Autoantibodies
  • Autoimmune disease
  • Statins
  • Myositis

Schlüsselwörter

  • Pathophysiologie
  • Autoantikörper
  • Autoimmunerkrankung
  • Statine
  • Myositis