Skip to main content

Advertisement

Log in

Inclusion Body Myositis

  • Nerve and Muscle (M Hirano and LH Weimer, Section Editors)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Sporadic inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy (IIM) after age 50 years. It presents with chronic insidious proximal leg and distal arm asymmetric muscle weakness. Despite similarities with polymyositis (PM), it is likely that IBM is primarily a degenerative disorder rather than inflammatory muscle disease. IBM is associated with a modest degree of creatine kinase (CK) elevation and an electromyogram (EMG) demonstrates a chronic irritative myopathy. Muscle histopathology demonstrates endomysial inflammatory exudates surrounding and invading non-necrotic muscle fibers often times accompanied by rimmed vacuoles. We review IBM with emphasis on recent developments in the field and discuss ongoing clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Phillips BA, Zilko PJ, Mastaglia FL. Prevalence of sporadic inclusion body myositis in Western Australia. Muscle Nerve. 2000;23(6):970–2.

    Article  PubMed  CAS  Google Scholar 

  2. Lotz BP, Engel AG, Nishino H, Stevens JC, Litch WJ. Inclusion body myositis. Observations in 40 patients. Brain. 1989;112(Pt 3):727–47.

    Article  PubMed  Google Scholar 

  3. Badrising UA, Maat-Schieman ML, van Houwelingen JC, et al. Inclusion body myositis. Clinical features and clinical course of the disease in 64 patients. Neurology. 2005;252(12):1448–54.

    Article  Google Scholar 

  4. Wilson FC, Ytterberg SR, St Sauver JL, et al. Epidemiology of sporadic inclusion body myositis and polymyositis in Olmsted County, Minnesota. J Rheumatol. 2008;35(3):445–7.

    PubMed  Google Scholar 

  5. Amato AA, Gronseth GS, Jackson, et al. Inclusion body myositis: clinical and pathological boundaries. Ann Neurol. 1995;40:581–6.

    Article  Google Scholar 

  6. Barohn RJ, Amato AA. Inclusion body myositis. Curr Treat Options Neurol. 2000;2:7–12.

    Article  PubMed  Google Scholar 

  7. Badrising UA, Maat-Schieman M, van Duinen SG, et al. Epidemiology of inclusion body myositis in The Netherlands: a nationwide study. Neurology. 2000;55:1385–7.

    Article  PubMed  CAS  Google Scholar 

  8. Lindberg C, Persson LI, Bjorkander J, Oldfors A. Inclusion body myositis: clinical, morphological, physiological, and laboratory findings in 18 cases. Acta Neurol Scand. 1994;89:123–31.

    Article  PubMed  CAS  Google Scholar 

  9. Sayers ME, Chou SM, Calabrese LH. Inclusion body myositis: analysis of 32 cases. J Rheumatol. 1992;19:1385–9.

    PubMed  CAS  Google Scholar 

  10. Needham M, James I, Corbett A, et al. Sporadic inclusion body myositis: phenotypic variability, and influence of HLA-DR3 in a cohort of 57 Australian cases. J Neurol Neurosurg Psychiatry. 2008;79(9):1056–60.

    Article  PubMed  CAS  Google Scholar 

  11. Barohn RJ, Amato AA, Sahenk Z, Kissel JT, Mendell JR. Inclusion body myositis: explanation for poor response to immunosuppressive therapy. Neurology. 1995;45(7):1302–4.

    Article  PubMed  CAS  Google Scholar 

  12. Estephan B, Barohn RJ, Dimachkie MM, et al. Sporadic IBM: a case cohort. J Clin Neuromuscul Dis. 2011;12(3):18–9.

    Google Scholar 

  13. •• Griggs RC, Askanas V, DiMauro S, et al. Inclusion body myositis and myopathies. Ann Neurol. 1995;38(5):705–13. Authors of this article propose diagnostic criteria for definite and possible sporadic inclusion body myositis based on a combination of clinical features and laboratory findings including serum creatine kinase, electromyography, and muscle histopathology. This is the first major effort to define diagnostic criteria for IBM. These criteria have withstood the test of time with some additions as in reference 14.

    Article  PubMed  CAS  Google Scholar 

  14. •• Hilton-Jones D, Miller A, Parton M, et al. Inclusion body myositis: MRC Centre for Neuromuscular Diseases, IBM workshop, London, 13 June, 2008. Neuromuscul Disord. 2010;20(2):142–7. In addition to the Griggs categories of pathologically defined IBM and possible IBM, participants of the 2008 European Neuromuscular Center workshop introduced clinically defined IBM to include IBM cases with weakness involving finger flexion more than shoulder abduction as well as knee extension more than hip flexion. The pathologic criteria for possible IBM and clinically defined IBM are invasion of non-necrotic fibers by mononuclear cells, or rimmed vacuoles, or increased MHC-1 expression on the surface of muscle fibers. This facilitates the diagnosis of patients who fulfill clinical criteria for IBM but do not have the pathologic features set forth by Griggs et al.

    Article  PubMed  CAS  Google Scholar 

  15. Amato AA, Barohn RJ. Inclusion body myositis: old and new concepts. J Neurol Neurosurg Psychiatry. 2009;80(11):1186–93.

    Article  PubMed  CAS  Google Scholar 

  16. Garlepp MJ, Laing B, Zilko PJ, et al. HLA associations with inclusion body myositis. Clin Exp Immunol. 1994;98:40–5.

    Article  PubMed  CAS  Google Scholar 

  17. Degardin A, Morillon D, Lacour A, Cotten A, Vermersch P, Stojkovic T. Morphologic imaging in muscular dystrophies and inflammatory myopathies. Skeletal Radiol. 2010;39(12):1219–27.

    Article  PubMed  Google Scholar 

  18. Cox FM, Reijnierse M, van Rijswijk CS, Wintzen AR, Verschuuren JJ, Badrising UA. Magnetic resonance imaging of skeletal muscles in sporadic inclusion body myositis. Rheumatology. 2011;50(6):1153–61.

    Article  PubMed  Google Scholar 

  19. Maetzler W, Reimold M, Schittenhelm J, et al. Increased [11C]PIB-PET levels in inclusion body myositis are indicative of amyloid beta deposition. J Neurol Neurosurg Psychiatry. 2011;82(9):1060–2.

    Article  PubMed  Google Scholar 

  20. Chahin N, Engel AG. Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM. Neurology. 2008;70(6):418–24.

    Article  PubMed  Google Scholar 

  21. Van der Meulen MF, Hoogendijk JE, Moons KG, Veldman H, Badrising UA, Wokke JH. Rimmed vacuoles and the added value of SMI-31 staining in diagnosing sporadic inclusion body myositis. Neuromuscul Disord. 2001;11:447–51.

    Article  PubMed  Google Scholar 

  22. Greenberg SA, Pinkus GS, Amato AA, Pinkus JL. Myeloid dendritic cells in inclusion-body myositis and polymyositis. Muscle Nerve. 2007;35(1):17–23.

    Article  PubMed  CAS  Google Scholar 

  23. Greenberg SA. Inclusion body myositis. Curr Opin Rheumatol. 2011;23(6):574–8.

    Article  PubMed  Google Scholar 

  24. Greenberg SA, Sanoudou D, Haslett JN, et al. Molecular profiles of inflammatory myopathies. Neurology. 2002;59(8):1170–82.

    Article  PubMed  CAS  Google Scholar 

  25. Greenberg SA, Bradshaw EM, Pinkus JL, et al. Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology. 2005;65(11):1782–7.

    Article  PubMed  CAS  Google Scholar 

  26. • Salajegheh M, Lam T, Greenberg SA. Autoantibodies against a 43 kDa muscle protein in inclusion body myositis. PLoS One. 2011;6:e20266. Since microarray studies reported abundant immunoglobulin gene transcripts in IBM muscle derived from local abundant plasma cells, this provided a rationale for searching for circulating autoantibodies. Imunoblots against normal human muscle demonstrate that 52 % of IBM patient samples recognized a 43 kDa muscle protein. None of those with other diseases or healthy volunteers had this protein.

    Article  PubMed  CAS  Google Scholar 

  27. Askanas V, Engel WK. Inclusion-body myositis: a myodegenerative conformational disorder associated with Abeta, protein misfolding, and proteasome inhibition. Neurology. 2006;66(2 Suppl 1):S39–48.

    Article  PubMed  CAS  Google Scholar 

  28. Wojcik S, Engel WK, McFerrin J, Paciello O, Askanas V. AbetaPP-overexpression and proteasome inhibition increase alpha B-crystallin in cultured human muscle: relevance to inclusion-body myositis. Neuromuscul Disord. 2006;16(12):839–44.

    Article  PubMed  Google Scholar 

  29. Askanas V, Engel WK. Sporadic inclusion-body myositis: conformational multifactorial ageing-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tau. Presse Med. 2011;40(4 Pt 2):e219–35.

    Article  PubMed  Google Scholar 

  30. Salajegheh M, Pinkus JL, Nazareno R, et al. Nature of “Tau” immunoreactivity in normal myonuclei and inclusion body myositis. Muscle Nerve. 2009;40(4):520–8.

    Article  PubMed  CAS  Google Scholar 

  31. • Nogalska A, D’Agostino C, Engel WK, Klein WL, Askanas V. Novel demonstration of amyloid-β oligomers in sporadic inclusion-body myositis muscle fibers. Acta Neuropathol. 2010;120(5):661–6. Askanas’ group reported for the first time in 2010 that IBM muscle samples had accumulation of toxic low-molecular weight amyloid β oligomers on dot-immunoblots with a variety of molecular weights and intensity but none of the control muscle biopsies had amyloid β oligomers. Nonfibrillar cytotoxic “Aβ-Derived Diffusible Ligands” originally derived from Aβ42 are prominently increased on dot-immunoblots, being consistent with the concept that intracellular toxicity of Ab42 oligomers is likely an important aspect of IBM pathogenesis. Finally, they demonstrated in cultured human muscle fibers that inhibition of autophagy is a novel cause of Aβ oligomerization.

    Article  PubMed  CAS  Google Scholar 

  32. Salajegheh M, Pinkus JL, Taylor JP, et al. Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis. Muscle Nerve. 2009;40:19–31.

    Article  PubMed  CAS  Google Scholar 

  33. Verma A, Bradley WG, Ringel SP. Treatment-responsive polymyositis transforming into inclusion body myositis. Neurology. 2008;P060.19.

  34. Benveniste O, Guiguet M, Freebody J, et al. Long-term observational study of sporadic inclusion body myositis. Brain. 2011;134(Pt 11):3176–84.

    Article  PubMed  Google Scholar 

  35. Amato AA, Barohn RJ, Jackson CE, Pappert EJ, Sahenk Z, Kissel JT. Inclusion body myositis: treatment with intravenous immunoglobulin. Neurology. 1994;44(8):1516–8.

    Article  PubMed  CAS  Google Scholar 

  36. Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology. 1997;48:712–6.

    Article  PubMed  CAS  Google Scholar 

  37. Dalakas MC, Koffman B, Fujii M, Spector S, Sivakumar K, Cupler E. A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology. 2001;56:323–7.

    Article  PubMed  CAS  Google Scholar 

  38. Muscle Study Group. Randomized pilot trial of betaINF1a (Avonex) in patients with inclusion body myositis. Neurology. 2001;57:1566–70.

    Article  Google Scholar 

  39. Muscle Study Group. Randomized pilot trial of high-dose betaINF-1a in patients with inclusion body myositis. Neurology. 2004;63:718–20.

    Article  Google Scholar 

  40. Badrising UA, Maat-Schieman ML, Ferrari, et al. Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo. Ann Neurol. 2002;51:369–72.

    Article  PubMed  CAS  Google Scholar 

  41. Lindberg C, Trysberg E, Tarkowski A, Oldfors A. Anti-T-lymphocyte globulin treatment in inclusion body myositis: a randomized pilot study. Neurology. 2003;61:260–2.

    Article  PubMed  CAS  Google Scholar 

  42. Rutkove SB, Parker RA, Nardin RA, Connolly CE, Felic KJ, Raynor EM. A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology. 2002;58(7):1081–7.

    Article  PubMed  CAS  Google Scholar 

  43. Barohn RJ, Herbelin L, Kissel JT, et al. Pilot trial of etanercept in the treatment of inclusion-body myositis. Neurology. 2006;66(2 Suppl 1):S123–4.

    Article  PubMed  CAS  Google Scholar 

  44. Dalakas MC, Rakocevic G, Schmidt J, et al. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain. 2009;132(Pt 6):1536–44.

    Article  PubMed  Google Scholar 

  45. Sancricca C, Mora M, Ricci E, Tonali PA, Mantegazza R, Mirabella M. Pilot trial of simvastatin in the treatment of sporadic inclusion-body myositis. Neurol Sci. 2011;32(5):841–7.

    Article  PubMed  Google Scholar 

  46. Saperstein DS, Levine T, Hank N, Kitazawa M, Bowser R, LaFerla F. Pilot Trial of lithium treatment in inclusion body myositis. Neurology. 2011;76 Suppl 4:A106.

    Google Scholar 

  47. Pasquali L, Longone P, Isidoro C, Ruggieri S, Paparelli A, Fornai F. Autophagy, lithium, and amyotrophic lateral sclerosis. Muscle Nerve. 2009;40(2):173–94.

    Article  PubMed  CAS  Google Scholar 

  48. Wang Y, He J, McVey AL, et al. Twelve-month change of IBMFRS in the arimocolomol inclusion body myositis pilot study. Poster 7.255 presented at the American Academy of Neurology. Annual Meeting. New Orleans, LA, USA; April 26 2012. Actual page etc from Dr. Baroh’s CV).

  49. Sekul EA, Dalakas MC. Inclusion body myositis: new concepts. Semin Neurol. 1993;13(3):256–63.

    Article  PubMed  CAS  Google Scholar 

  50. Cox FM, Titulaer MJ, Sont JK, Wintzen AR, Verschuuren JJ, Badrising UA. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain. 2011;134(Pt 11):3167–75.

    Article  PubMed  Google Scholar 

  51. Arnardottir S, Alexanderson H, Lundberg IE, Borg K. Sporadic inclusion body myositis: pilot study on the effects of a home exercise program on muscle function, histopathology, and inflammatory reaction. J Rehabil Med. 2003;35(1):31–5.

    Article  PubMed  Google Scholar 

  52. Johnson GL, et al. The effectiveness of an individualized, home-based functional exercise program for patients with sporadic inclusion body myositis. J Clin Neuromuscul Dis. 2007;8:187–94.

    Article  Google Scholar 

  53. Johnson LG, Collier KE, Edwards DJ, et al. Improvement in aerobic capacity after an exercise program in sporadic inclusion body myositis. J Clin Neuromuscul Dis. 2009;10(4):178–84.

    Article  PubMed  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mazen M. Dimachkie.

Additional information

This article is part of the Topical Collection on Nerve and Muscle

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dimachkie, M.M., Barohn, R.J. Inclusion Body Myositis. Curr Neurol Neurosci Rep 13, 321 (2013). https://doi.org/10.1007/s11910-012-0321-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-012-0321-4

Keywords

Navigation