Inclusion Body Myositis Treatment & Management
- Author: Michael P Collins, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE more...
No definitive treatment has been proven effective for s-IBM.
Early anecdotal reports documented the failure of patients to respond to steroids, methotrexate, azathioprine, and cyclophosphamide. Subsequent clinical studies of various immunosuppressive or immunomodulatory therapies have largely been disappointing. Individual responses, functional improvement, or mild regional improvement in strength have been reported, but sustained remission and improvement in whole-body strength have not been demonstrated.
- A long-term observational study of a large cohort of patients in Paris and Oxford found that immunosuppressive treatments do not ameliorate sporadic inclusion body myositis and could modestly exacerbate the progression of disability. However, the results from this study are limited due to the semi-retrospective nature of data collection and possible bias in patients selected for immunosuppressive treatment.
- An open-label study of high-dose prednisone in 8 patients showed no improvement in strength or functional disability scores despite a decrease in creatine phosphokinase (CPK) and inflammatory cell infiltration. Posttreatment muscle biopsy samples showed increased vacuole formation and amyloid deposition, suggesting that mechanisms other than the inflammatory response play a role in disease propagation.
- A randomized, controlled study of oxandrolone in 19 patients reported a regional improvement in upper extremity strength, but only borderline improvement in whole-body strength.
- A randomized, controlled study of methotrexate in 44 patients likewise showed no improvement in strength despite a significant decrease in CPK levels.
- An early small, uncontrolled study reported improvement in strength in 4 patients following intravenous immunoglobulin (IVIg) treatment. However, subsequent larger and placebo-controlled studies have failed to duplicate these results.[100, 22, 101] Two studies suggest some benefit in patients with severe dysphagia.[102, 103] A subsequent controlled study of IVIg in combination with prednisone likewise showed no treatment response despite a reduction in endomysial inflammation.
- An open-label, randomized study of anti-T-lymphocyte globulin treatment followed by 12 months of oral methotrexate (vs methotrexate alone) reported regional improvement in distal upper extremity strength, but continued deterioration of the proximal muscle groups.
- Beta interferon-1a at standard (30 µg IM/wk) and high-dosage (60 µg IM/wk) regimens were found to be well tolerated but produced no significant improvement in muscle strength or muscle mass.[106, 107]
- A pilot trial of etanercept, a tumor necrosis factor (TNF) alpha blocker, did not show significant benefit in composite muscle strength scores at 6 months. However, with 12 months of treatment, slight improvement in grip strength was noted. . A double-blinded, randomized, placebo-controlled study is currently underway to assess the efficacy of etanercept treatment in patients with IBM.
- A study of alemtuzumab, a T-cell–depleting monoclonal antibody, involved 13 patients who underwent infusion of 0.3 mg/kg/d for 4 days. It reported slowed disease progression, improvement of strength in some patients, and reduction in endomysial inflammation. This preliminary study holds promise for future studies.
- Follistatin, an antagonist of the myostatin pathway, has been shown to produce a dramatic increase in muscle mass in animals. These results are promising for future gene therapy trials to improve muscle mass in patients with neuromuscular disease.
- Arimoclomol, a heat shock protein (HSP) coinducer may slow down the process of protein misfolding and aggregation. A study of its safety and efficacy in IBM is underway.
- Lithium is an inhibitor of the glycogen synthase kinase (GSK) enzyme, the latter of which is involved in the development of phosphorylated tau (p-tau). A recent study has shown that in biopsied s-IBM muscle fibers, GSK3b activity is increased, with increased ABPP phosphorylation. Treatment with lithium showed decreased GSK3b activity, decreased amounts of total and phosphorylated ABPP and AB oligomers, and increased proteosomal function. These findings suggest that treatment of patients with s-IBM with lithium may be beneficial.
- Empiric therapies include coenzyme Q10, carnitine, and antioxidants. They may provide benefit to some patients, but, to date, none of these has been studied in a controlled clinical trial.
- Routine follow-up visits at intervals contingent upon the progression and severity of involvement are indicated to assess the patient's strength, tolerance of exertion, and compromise in occupation or activities of daily living. Hicks has outlined a strategy for care of patients with inflammatory myopathies, including s-IBM.
Muscle biopsy is performed for diagnosis.
Severe dysphagia may require cricopharyngeal myotomy or placement of a gastrostomy tube. Chemodenervation with botulinum toxin A injection into the upper esophageal sphincter has also been shown to be of benefit.
Depending on degree of weakness, physical therapy or physiatry consultation may be useful in optimizing the patient's abilities.
If dysphagia occurs, referral to a speech therapist would be of benefit for instruction regarding swallowing techniques and aspiration precautions. In patients with severe dysphagia, referral to ear, nose, and throat (ENT) specialist is indicated for consideration of botulinum toxin injections or cricopharyngeal myotomy.
No dietary modification is required in most cases unless symptomatic dysphagia occurs.
Appropriate activity level depends on the condition of the patient.
Strength training and exercise regimens have been subjects of debate, given concerns that physical activity might instigate increased muscle breakdown and inflammation. However, 3 recent studies have shown that an exercise program can be instituted safely.[114, 87, 115] In the study by Arnardottir, 6 of 7 patients reported a subjective positive effect on muscle function after a 12-week exercise regimen. No improvement or deterioration in strength was observed, and no increase in inflammation was noted in pretreatment and posttreatment muscle biopsy specimens. In the study by Johnson, 7 patients underwent a combined aerobic and functional exercise regimen. The patients exhibited improved aerobic and functional exercise capacity and strength without significant increase in creatine kinase.
Argov Z. Hereditary inclusion body myopathies. In: Engel AG, Franzini-Armstrong C, eds. Myology. 3rd ed. New York: McGraw Hill. 2004:1311-1320.
Malicdan MC, Noguchi S, Nishino I. Recent advances in distal myopathy with rimmed vacuoles (DMRV) or hIBM: treatment perspectives. Curr Opin Neurol. 2008 Oct. 21(5):596-600. [Medline].
Karpati G, O'Ferrall EK. Sporadic inclusion body myositis: pathogenic considerations. Ann Neurol. 2009 Jan. 65(1):7-11. [Medline].
Pruitt JN, Showalter CJ, Engel AG. Sporadic inclusion body myositis: counts of different types of abnormal fibers. Ann Neurol. 1996 Jan. 39(1):139-43. [Medline].
Greenberg SA. Pathogenesis and therapy of inclusion body myositis. Curr Opin Neurol. 2012 Oct. 25(5):630-9. [Medline].
Engel AG, Arahata K. Monoclonal antibody analysis of mononuclear cells in myopathies. II: Phenotypes of autoinvasive cells in polymyositis and inclusion body myositis. Ann Neurol. 1984 Aug. 16(2):209-15. [Medline].
Greenberg SA, Bradshaw EM, Pinkus JL, Pinkus GS, Burleson T, Due B. Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology. 2005 Dec 13. 65(11):1782-7. [Medline].
Greenberg SA, Pinkus GS, Amato AA, Pinkus JL. Myeloid dendritic cells in inclusion-body myositis and polymyositis. Muscle Nerve. 2007 Jan. 35(1):17-23. [Medline].
Tateyama M, Fujihara K, Misu T, Itoyama Y. CCR7+ myeloid dendritic cells together with CCR7+ T cells and CCR7+ macrophages invade CCL19+ nonnecrotic muscle fibers in inclusion body myositis. J Neurol Sci. 2009 Apr 15. 279(1-2):47-52. [Medline].
Arahata K, Engel AG. Monoclonal antibody analysis of mononuclear cells in myopathies. V: Identification and quantitation of T8+ cytotoxic and T8+ suppressor cells. Ann Neurol. 1988 May. 23(5):493-9. [Medline].
Orimo S, Koga R, Goto K, et al. Immunohistochemical analysis of perforin and granzyme A in inflammatory myopathies. Neuromuscul Disord. 1994 May. 4(3):219-26. [Medline].
Schmidt J, Barthel K, Wrede A, Salajegheh M, Bähr M, Dalakas MC. Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle. Brain. 2008 May. 131(Pt 5):1228-40. [Medline]. [Full Text].
Amemiya K, Granger RP, Dalakas MC. Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time. Studies in repeated muscle biopsies. Brain. 2000 Oct. 123 (Pt 10):2030-9. [Medline].
Muntzing K, Lindberg C, Moslemi AR, Oldfors A. Inclusion body myositis: clonal expansions of muscle-infiltrating T cells persist over time. Scand J Immunol. 2003 Aug. 58(2):195-200. [Medline].
Salajegheh M, Rakocevic G, Raju R, Shatunov A, Goldfarb LG, Dalakas MC. T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis. Neurology. 2007 Oct 23. 69(17):1672-9. [Medline].
De Paepe B, Creus KK, De Bleecker JL. Chemokine profile of different inflammatory myopathies reflects humoral versus cytotoxic immune responses. Ann N Y Acad Sci. 2007 Aug. 1109:441-53. [Medline].
Greenberg SA, Sanoudou D, Haslett JN, et al. Molecular profiles of inflammatory myopathies. Neurology. 2002 Oct 22. 59(8):1170-82. [Medline].
Raju R, Dalakas MC. Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes. Brain. 2005 Aug. 128(Pt 8):1887-96. [Medline].
Bradshaw EM, Orihuela A, McArdel SL, Salajegheh M, Amato AA, Hafler DA, et al. A local antigen-driven humoral response is present in the inflammatory myopathies. J Immunol. 2007 Jan 1. 178(1):547-56. [Medline].
Koffman BM, Rugiero M, Dalakas MC. Immune-mediated conditions and antibodies associated with sporadic inclusion body myositis. Muscle Nerve. 1998 Jan. 21(1):115-7. [Medline].
Badrising UA, Schreuder GM, Giphart MJ, et al. Associations with autoimmune disorders and HLA class I and II antigens in inclusion body myositis. Neurology. 2004 Dec 28. 63(12):2396-8. [Medline].
Dalakas MC, Illa I, Gallardo E, Juarez C. Inclusion body myositis and paraproteinemia: incidence and immunopathologic correlations. Ann Neurol. 1997 Jan. 41(1):100-4. [Medline].
Cupler EJ, Leon-Monzon M, Miller J, et al. Inclusion body myositis in HIV-1 and HTLV-1 infected patients. Brain. 1996 Dec. 119 (Pt 6):1887-93. [Medline].
Tsuruta Y, Furuta A, Furuta K, Yamada T, Kira J, Iwaki T. Expression of the lysosome-associated membrane proteins in myopathies with rimmed vacuoles. Acta Neuropathol. 2001 Jun. 101(6):579-84. [Medline].
Dalakas MC. Inflammatory, immune, and viral aspects of inclusion-body myositis. Neurology. 2006 Jan 24. 66(2 Suppl 1):S33-8. [Medline].
Matsuura E, Umehara F, Nose H, Higuchi I, Matsuoka E, Izumi K. Inclusion body myositis associated with human T-lymphotropic virus-type I infection: eleven patients from an endemic area in Japan. J Neuropathol Exp Neurol. 2008 Jan. 67(1):41-9. [Medline].
Carpenter S. Inclusion body myositis, a review. J Neuropathol Exp Neurol. 1996 Nov. 55(11):1105-14. [Medline].
Karpati G, Pouliot Y, Carpenter S. Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. Ann Neurol. 1988 Jan. 23(1):64-72. [Medline].
Mikol J, Engel AG. Inclusion body myositis. In: Engel AG, Franzini-Armstrong C, eds. Myology. 3rd ed. NY: McGraw Hill. 2004: 1367-1388.
Askanas V, Engel WK, Nogalska A. Inclusion body myositis: a degenerative muscle disease associated with intra-muscle fiber multi-protein aggregates, proteasome inhibition, endoplasmic reticulum stress and decreased lysosomal degradation. Brain Pathol. 2009 Jul. 19(3):493-506. [Medline].
Lee C, Yu MH. Protein folding and diseases. J Biochem Mol Biol. 2005 May 31. 38(3):275-80. [Medline].
Ciechanover A. The ubiquitin proteolytic system: from a vague idea, through basic mechanisms, and onto human diseases and drug targeting. Neurology. 2006 Jan 24. 66(2 Suppl 1):S7-19. [Medline].
Jayaraman M, Kannayiram G, Rajadas J. Amyloid toxicity in skeletal myoblasts: Implications for inclusion-body myositis. Arch Biochem Biophys. 2008 Jun 1. 474(1):15-21. [Medline].
Glabe CG, Kayed R. Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis. Neurology. 2006 Jan 24. 66(2 Suppl 1):S74-8. [Medline].
Vattemi G, Engel WK, McFerrin J, et al. BACE1 and BACE2 in pathologic and normal human muscle. Exp Neurol. 2003 Feb. 179(2):150-8. [Medline].
Askanas V, Engel WK. Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer''s and Parkinson''s disease brains. Acta Neuropathol. 2008 Dec. 116(6):583-95. [Medline]. [Full Text].
Vattemi G, Nogalska A, King Engel W, D'Agostino C, Checler F, Askanas V. Amyloid-beta42 is preferentially accumulated in muscle fibers of patients with sporadic inclusion-body myositis. Acta Neuropathol. 2009 May. 117(5):569-74. [Medline].
Greenberg SA. Comment on 'Interrelation of inflammation and APP in sIBM: IL-1beta induces accumulation of beta-amyloid in skeletal muscle'. Brain. 2009 Apr. 132(Pt 4):e106; author reply e107. [Medline].
Mori K. Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell. 2000 May 26. 101(5):451-4. [Medline].
Zhang K, Kaufman RJ. Protein folding in the endoplasmic reticulum and the unfolded protein response. Handb Exp Pharmacol. 2006. 69-91. [Medline].
Vattemi G, Engel WK, McFerrin J, Askanas V. Endoplasmic reticulum stress and unfolded protein response in inclusion body myositis muscle. Am J Pathol. 2004 Jan. 164(1):1-7. [Medline].
Nakano S, Akiguchi I, Nakamura S, et al. Aberrant expression of cyclin-dependent kinase 5 in inclusion body myositis. Neurology. 1999 Nov 10. 53(8):1671-6. [Medline].
Kitazawa M, Trinh DN, LaFerla FM. Inflammation induces tau pathology in inclusion body myositis model via glycogen synthase kinase-3beta. Ann Neurol. 2008 Jul. 64(1):15-24. [Medline].
Kumamoto T, Ueyama H, Tsumura H, et al. Expression of lysosome-related proteins and genes in the skeletal muscles of inclusion body myositis. Acta Neuropathol (Berl). 2004 Jan. 107(1):59-65. [Medline].
Lunemann JD, Schmidt J, Schmid D, Barthel K, Wrede A, Dalakas MC. Beta-amyloid is a substrate of autophagy in sporadic inclusion body myositis. Ann Neurol. 2007 May. 61(5):476-83. [Medline].
Greenberg SA, Pinkus JL, Amato AA. Nuclear membrane proteins are present within rimmed vacuoles in inclusion-body myositis. Muscle Nerve. 2006 Oct. 34(4):406-16. [Medline].
Nalbantoglu J, Karpati G, Carpenter S. Conspicuous accumulation of a single-stranded DNA binding protein in skeletal muscle fibers in inclusion body myositis. Am J Pathol. 1994 May. 144(5):874-82. [Medline].
Nakano S, Shinde A, Fujita K, Ito H, Kusaka H. Histone H1 is released from myonuclei and present in rimmed vacuoles with DNA in inclusion body myositis. Neuromuscul Disord. 2008 Jan. 18(1):27-33. [Medline].
Santorelli FM, Sciacco M, Tanji K, et al. Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a study of 56 patients. Ann Neurol. 1996 Jun. 39(6):789-95. [Medline].
Horvath R, Fu K, Johns T, Genge A, Karpati G, Shoubridge EA. Characterization of the mitochondrial DNA abnormalities in the skeletal muscle of patients with inclusion body myositis. J Neuropathol Exp Neurol. 1998 May. 57(5):396-403. [Medline].
Oldfors A, Moslemi AR, Jonasson L, Ohlsson M, Kollberg G, Lindberg C. Mitochondrial abnormalities in inclusion-body myositis. Neurology. 2006 Jan 24. 66(2 Suppl 1):S49-55. [Medline].
Askanas V, McFerrin J, Baqué S, Alvarez RB, Sarkozi E, Engel WK. Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle. Proc Natl Acad Sci U S A. 1996 Feb 6. 93(3):1314-9. [Medline]. [Full Text].
Dalakas MC. Molecular immunology and genetics of inflammatory muscle diseases. Arch Neurol. 1998 Dec. 55(12):1509-12. [Medline].
Parker KC, Kong SW, Walsh RJ, Salajegheh M, Moghadaszadeh B, Amato AA, et al. Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositis. Muscle Nerve. 2009 Jun. 39(6):739-53. [Medline]. [Full Text].
Ferrer I, Martin B, Castano JG. Proteasomal expression, induction of immunoproteasome subunits, and local MHC class I presentation in myofibrillar myopathy and inclusion body myositis. J Neuropathol Exp Neurol. 2004 May. 63(5):484-98. [Medline].
Dahlmann B. Proteasomes. Essays Biochem. 2005. 41:31-48. [Medline].
Lunemann JD, Munz C. Autophagy in CD4+ T-cell immunity and tolerance. Cell Death Differ. 2009 Jan. 16(1):79-86. [Medline].
Dalakas MC. Interplay between inflammation and degeneration: using inclusion body myositis to study "neuroinflammation". Ann Neurol. 2008 Jul. 64(1):1-3. [Medline].
Banwell BL, Engel AG. AlphaB-crystallin immunolocalization yields new insights into inclusion body myositis. Neurology. 2000 Mar 14. 54(5):1033-41. [Medline].
Muth IE, Barthel K, Bähr M, Dalakas MC, Schmidt J. Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of alphaB-crystallin is associated with amyloid precursor protein and accumulation of beta-amyloid. J Neurol Neurosurg Psychiatry. 2009 Dec. 80(12):1344-9. [Medline].
Badrising UA, Maat-Schieman M, van Duinen SG, et al. Epidemiology of inclusion body myositis in the Netherlands: a nationwide study. Neurology. 2000 Nov 14. 55(9):1385-7. [Medline].
Phillips BA, Zilko PJ, Mastaglia FL. Prevalence of sporadic inclusion body myositis in Western Australia. Muscle Nerve. 2000 Jun. 23(6):970-2. [Medline].
Davenport TE, Benson K, Baker S, Gracey C, Rakocevic G, McElroy B, et al. Lower extremity peak force and gait kinematics in individuals with inclusion body myositis. Arthritis Care Res (Hoboken). 2014 Sep 8. [Medline].
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 Nov. 134:3167-75. [Medline].
Shamim EA, Rider LG, Pandey JP, O'Hanlon TP, Jara LJ, Samayoa EA. Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: ethnogeographic influences in the genetics and clinical expression of myositis. Arthritis Rheum. 2002 Jul. 46(7):1885-93. [Medline].
Lotz BP, Engel AG, Nishino H, et al. Inclusion body myositis. Observations in 40 patients. Brain. 1989 Jun. 112 (Pt 3):727-47. [Medline].
Lindberg C, Persson LI, Bjorkander J, Oldfors A. Inclusion body myositis: clinical, morphological, physiological and laboratory findings in 18 cases. Acta Neurol Scand. 1994 Feb. 89(2):123-31. [Medline].
Beyenburg S, Zierz S, Jerusalem F. Inclusion body myositis: clinical and histopathological features of 36 patients. Clin Investig. 1993 May. 71(5):351-61. [Medline].
Sayers ME, Chou SM, Calabrese LH. Inclusion body myositis: analysis of 32 cases. J Rheumatol. 1992 Sep. 19(9):1385-9. [Medline].
Badrising UA, Maat-Schieman ML, van Houwelingen JC, et al. Inclusion body myositis. Clinical features and clinical course of the disease in 64 patients. J Neurol. 2005 Dec. 252(12):1448-54. [Medline].
Lotz BP, Engel AG, Nishino H, Stevens JC, Litchy WJ. Inclusion body myositis. Observations in 40 patients. Brain. 1989 Jun. 112 ( Pt 3):727-47. [Medline].
Hund E, Heckl R, Goebel HH, Meinck HM. Inclusion body myositis presenting with isolated erector spinae paresis. Neurology. 1995 May. 45(5):993-4. [Medline].
Kraemer P, Sagui E, Brosset C, et al. [Inclusion myositis associated with primary biliary cirrhosis of the liver]. Presse Med. 2003 Mar 15. 32(10):460. [Medline].
Kanellopoulos P, Baltoyiannis C, Tzioufas AG. Primary Sjogren's syndrome associated with inclusion body myositis. Rheumatology (Oxford). 2002 Apr. 41(4):440-4. [Medline].
Williams SF, Mincey BA, Calamia KT. Inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura. South Med J. 2003 Jul. 96(7):721-3. [Medline].
Cherin P, Menard D, Mouton P, et al. Macrophagic myofasciitis associated with inclusion body myositis: a report of three cases. Neuromuscul Disord. 2001 Jul. 11(5):452-7. [Medline].
Wenzel J, Uerlich M, Gerdsen R, et al. Association of inclusion body myositis with subacute cutaneous lupus erythematosus. Rheumatol Int. 2001 Oct. 21(2):75-7. [Medline].
Derk CT, Vivino FB, Kenyon L, Mandel S. Inclusion body myositis in connective tissue disorders: case report and review of the literature. Clin Rheumatol. 2003 Oct. 22(4-5):324-8. [Medline].
Massawi G, Hickling P, Hilton D, Patterson C. Inclusion body myositis evolving in systemic lupus erythematosus? A case report. Rheumatology (Oxford). 2003 Aug. 42(8):1012-4. [Medline].
Kovacs GG, Lindeck-Pozza E, Chimelli L, et al. Creutzfeldt-Jakob disease and inclusion body myositis: abundant disease-associated prion protein in muscle. Ann Neurol. 2004 Jan. 55(1):121-5. [Medline].
Arnardottir S, Ansved T, Nennesmo I, Borg K. Report of a patient with inclusion body myositis and CD8+ chronic lymphocytic leukaemia--post-mortem analysis of muscle and brain. Acta Neurol Scand. 2001 Feb. 103(2):131-5. [Medline].
Hengstman GJ, Brouwer R, Egberts WT, et al. Clinical and serological characteristics of 125 Dutch myositis patients. Myositis specific autoantibodies aid in the differential diagnosis of the idiopathic inflammatory myopathies. J Neurol. 2002 Jan. 249(1):69-75. [Medline].
Sekul EA, Chow C, Dalakas MC. Magnetic resonance imaging of the forearm as a diagnostic aid in patients with sporadic inclusion body myositis. Neurology. 1997 Apr. 48(4):863-6. [Medline].
Phillips BA, Cala LA, Thickbroom GW. Patterns of muscle involvement in inclusion body myositis: clinical and magnetic resonance imaging study. Muscle Nerve. 2001 Nov. 24(11):1526-34. [Medline].
Arnardottir S, Svanborg E, Borg K. Inclusion body myositis--sensory dysfunction revealed with quantitative determination of somatosensory thresholds. Acta Neurol Scand. 2003 Jul. 108(1):22-7. [Medline].
Rodríguez Cruz PM, Needham M, Hollingsworth P, Mastaglia FL, Hillman DR. Sleep disordered breathing and subclinical impairment of respiratory function are common in sporadic inclusion body myositis. Neuromuscul Disord. 2014 Aug 20. [Medline].
Brady S, Squier W, Sewry C, Hanna M, Hilton-Jones D, Holton JL. A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis. BMJ Open. 2014 Apr 28. 4(4):e004552. [Medline]. [Full Text].
Mendell JR, Sahenk Z, Gales T, Paul L. Amyloid filaments in inclusion body myositis. Novel findings provide insight into nature of filaments. Arch Neurol. 1991 Dec. 48(12):1229-34. [Medline].
Griggs RC, Askanas V, DiMauro S, et al. Inclusion body myositis and myopathies. Ann Neurol. 1995 Nov. 38(5):705-13. [Medline].
Salajegheh M, Pinkus JL, Taylor JP, Amato AA, Nazareno R, Baloh RH, et al. Sarcoplasmic redistribution of nuclear TDP-43 in inclusion body myositis. Muscle Nerve. 2009 Jul. 40(1):19-31. [Medline]. [Full Text].
Breithaupt M, Schmidt J. Update on treatment of inclusion body myositis. Curr Rheumatol Rep. 2013 May. 15(5):329. [Medline].
Needham M, Mastaglia FL. Sporadic inclusion body myositis: A review of recent clinical advances and current approaches to diagnosis and treatment. Clin Neurophysiol. 2016 Mar. 127 (3):1764-73. [Medline].
Benveniste O, Guiguet M, Freebody J, Dubourg O, Squier W, Maisonobe T, et al. Long-term observational study of sporadic inclusion body myositis. Brain. 2011 Nov. 134:3176-84. [Medline].
Barohn RJ, Amato AA, Sahenk Z, et al. Inclusion body myositis: explanation for poor response to immunosuppressive therapy. Neurology. 1995 Jul. 45(7):1302-4. [Medline].
Rutkove SB, Parker RA, Nardin RA, et al. A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology. 2002 Apr 9. 58(7):1081-7. [Medline].
Badrising UA, Maat-Schieman ML, Ferrari MD, et al. Comparison of weakness progression in inclusion body myositis during treatment with methotrexate or placebo. Ann Neurol. 2002 Mar. 51(3):369-72. [Medline].
Soueidan SA, Dalakas MC. Treatment of inclusion-body myositis with high-dose intravenous immunoglobulin. Neurology. 1993 May. 43(5):876-9. [Medline].
Amato AA, Barohn RJ, Jackson CE, et al. Inclusion body myositis: treatment with intravenous immunoglobulin. Neurology. 1994 Aug. 44(8):1516-8. [Medline].
Walter MC, Lochmuller H, Toepfer M, et al. High-dose immunoglobulin therapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study. J Neurol. 2000 Jan. 247(1):22-8. [Medline].
Cherin P, Pelletier S, Teixeira A, et al. Intravenous immunoglobulin for dysphagia of inclusion body myositis. Neurology. 2002 Jan 22. 58(2):326. [Medline].
Dalakas MC, Somies B, Dambrosia J, et al. Treatment of inclusion-body myositis with IVIg: A double blind, placebo-controlled study. Neurology. 1997. 48:712-716. [Medline].
Dalakas MC, Koffman B, Fujii M, et al. A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM. Neurology. 2001 Feb 13. 56(3):323-7. [Medline].
Lindberg C, Trysberg E, Tarkowski A, Oldfors A. Anti-T-lymphocyte globulin treatment in inclusion body myositis: a randomized pilot study. Neurology. 2003 Jul 22. 61(2):260-2. [Medline].
Muscle Study Group. Randomized pilot trial of betaINF1a (Avonex) in patients with inclusion body myositis. Neurology. 2001 Nov 13. 57(9):1566-70. [Medline].
Muscle Study Group. Randomized pilot trial of high-dose betaINF-1a in patients with inclusion body myositis. Neurology. 2004 Aug 24. 63(4):718-20. [Medline].
Barohn RJ, Herbelin L, Kissel JT, King W, McVey AL, Saperstein DS. Pilot trial of etanercept in the treatment of inclusion-body myositis. Neurology. 2006 Jan 24. 66(2 Suppl 1):S123-4. [Medline].
Dalakas MC, Rakocevic G, Schmidt J, Salajegheh M, McElroy B, Harris-Love MO. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain. 2009 Jun. 132(Pt 6):1536-44. [Medline].
Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009 Mar. 39(3):283-96. [Medline].
Terracciano C, Nogalska A, Engel WK, Askanas V. In AbetaPP-overexpressing cultured human muscle fibers proteasome inhibition enhances phosphorylation of AbetaPP751 and GSK3beta activation: effects mitigated by lithium and apparently relevant to sporadic inclusion-body myositis. J Neurochem. 2010 Jan. 112(2):389-96. [Medline]. [Full Text].
Hicks J. Comprehensive rehabilitative management of patients with polymyositis and dermatomyositis. In: Dalakas M, ed. Polymyositis and Dermatomyositis. Boston, Mass: Butterworth-Heinemann; 1988. 293-318.
Liu LW, Tarnopolsky M, Armstrong D. Injection of botulinum toxin A to the upper esophageal sphincter for oropharyngeal dysphagia in two patients with inclusion body myositis. Can J Gastroenterol. 2004 Jun. 18(6):397-9. [Medline].
Spector SA, Lemmer JT, Koffman BM, et al. Safety and efficacy of strength training in patients with sporadic inclusion body myositis. Muscle Nerve. 1997 Oct. 20(10):1242-8. [Medline].
Johnson LG, Collier KE, Edwards DJ, Philippe DL, Eastwood PR, Walters SE, et al. Improvement in aerobic capacity after an exercise program in sporadic inclusion body myositis. J Clin Neuromuscul Dis. 2009 Jun. 10(4):178-84. [Medline].
Rose MR, McDermott MP, Thornton CA, et al. A prospective natural history study of inclusion body myositis: implications for clinical trials. Neurology. 2001 Aug 14. 57(3):548-50. [Medline].
Peng A, Koffman BM, Malley JD, Dalakas MC. Disease progression in sporadic inclusion body myositis: observations in 78 patients. Neurology. 2000 Jul 25. 55(2):296-8. [Medline].
Amato AA, Gronseth GS, Jackson CE, et al. Inclusion body myositis: clinical and pathological boundaries. Ann Neurol. 1996 Oct. 40(4):581-6. [Medline].
Askanas V, Engel WK. Inclusion-body myositis: a myodegenerative conformational disorder associated with Abeta, protein misfolding, and proteasome inhibition. Neurology. 2006 Jan 24. 66(2 Suppl 1):S39-48. [Medline].
Askanas V, Engel WK. New advances in the understanding of sporadic inclusion-body myositis and hereditary inclusion-body myopathies. Curr Opin Rheumatol. 1995 Nov. 7(6):486-96. [Medline].
Askanas V, Engel WK, McFerrin J, et al. Transthyretin Val122Ile, accumulated Abeta, and inclusion-body myositis aspects in cultured muscle. Neurology. 2003 Jul 22. 61(2):257-60. [Medline].
Barkhaus PE. The electrodiagnostic evaluation of the patient with suspected myopathy. In Kincaid JC, ed. The Young, the Old, and the Weak: A Basic Course in Electrodiagnostic Medicine. Rochester, MN: American Association of Electrodiagnostic Medicine. 1998.
Barkhaus PE, Periquet MI, Nandedkar SD. Quantitative electrophysiologic studies in sporadic inclusion body myositis. Muscle Nerve. 1999 Apr. 22(4):480-7. [Medline].
Barohn RJ. The therapeutic dilemma of inclusion body myositis. Neurology. 1997 Mar. 48(3):567-8. [Medline].
Behrens L, Kerschensteiner M, Misgeld T, et al. Human muscle cells express a functional costimulatory molecule distinct from B7.1 (CD80) and B7.2 (CD86) in vitro and in inflammatory lesions. J Immunol. 1998 Dec 1. 161(11):5943-51. [Medline].
Brannagan TH, Hays AP, Lange DJ, Trojaborg W. The role of quantitative electromyography in inclusion body myositis. J Neurol Neurosurg Psychiatry. 1997 Dec. 63(6):776-9. [Medline].
Chou SM. Myxovirus-like structures in a case of human chronic polymyositis. Science. 1967 Dec 15. 158(807):1453-5. [Medline].
Civatte M, Bartoli C, Schleinitz N, et al. Expression of the beta chemokines CCL3, CCL4, CCL5 and their receptors in idiopathic inflammatory myopathies. Neuropathol Appl Neurobiol. 2005 Feb. 31(1):70-9. [Medline].
Dabby R, Lange DJ, Trojaborg W, et al. Inclusion body myositis mimicking motor neuron disease. Arch Neurol. 2001 Aug. 58(8):1253-6. [Medline].
Dahlbom K, Lindberg C, Oldfors A. Inclusion body myositis: morphological clues to correct diagnosis. Neuromuscul Disord. 2002 Nov. 12(9):853-7. [Medline].
Danon MJ, Friedman M. Inclusion body myositis associated with progressive dysphagia: treatment with cricopharyngeal myotomy. Can J Neurol Sci. 1989 Nov. 16(4):436-8. [Medline].
De Paepe B, De Bleecker JL. Beta-chemokine receptor expression in idiopathic inflammatory myopathies. Muscle Nerve. 2005 May. 31(5):621-7. [Medline].
De Paepe B, De Keyzer K, Martin JJ, De Bleecker JL. Alpha-chemokine receptors CXCR1-3 and their ligands in idiopathic inflammatory myopathies. Acta Neuropathol (Berl). 2005 Jun. 109(6):576-82. [Medline].
Dion E, Cherin P, Payan C, et al. Magnetic resonance imaging criteria for distinguishing between inclusion body myositis and polymyositis. J Rheumatol. 2002 Sep. 29(9):1897-906. [Medline].
Ferrer I, Carmona M, Blanco R, et al. Involvement of clusterin and the aggresome in abnormal protein deposits in myofibrillar myopathies and inclusion body myositis. Brain Pathol. 2005 Apr. 15(2):101-8. [Medline].
Ferrer I, Martin B, Castano JG, et al. Proteasomal expression, induction of immunoproteasome subunits, and local MHC class I presentation in myofibrillar myopathy and inclusion body myositis. J Neuropathol Exp Neurol. 2004 May. 63(5):484-98. [Medline].
Figarella-Branger D, Civatte M, Bartoli C, Pellissier JF. Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies. Muscle Nerve. 2003 Dec. 28(6):659-82. [Medline].
Fratta P, Engel WK, McFerrin J, et al. Proteasome inhibition and aggresome formation in sporadic inclusion-body myositis and in amyloid-beta precursor protein-overexpressing cultured human muscle fibers. Am J Pathol. 2005 Aug. 167(2):517-26. [Medline].
Fratta P, Engel WK, Van Leeuwen FW, et al. Mutant ubiquitin UBB+1 is accumulated in sporadic inclusion-body myositis muscle fibers. Neurology. 2004 Sep 28. 63(6):1114-7. [Medline].
Hermanns B, Molnar M, Schroder JM. Peripheral neuropathy associated with hereditary and sporadic inclusion body myositis: confirmation by electron microscopy and morphometry. J Neurol Sci. 2000 Oct 1. 179(S 1-2):92-102. [Medline].
Jaworska-Wilczynska M, Wilczynski GM, Engel WK, et al. Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle. Neurology. 2002 Feb 12. 58(3):438-45. [Medline].
Krivickas LS, Amato AA, Krishnan G, et al. Preservation of in vitro muscle fiber function in dermatomyositis and inclusion body myositis: a single fiber study. Neuromuscul Disord. 2005 May. 15(5):349-54. [Medline].
Li M, Dalakas MC. The muscle mitogen-activated protein kinase is altered in sporadic inclusion body myositis. Neurology. 2000 Apr 25. 54(8):1665-70. [Medline].
Luciano CA, Dalakas MC. Inclusion body myositis: no evidence for a neurogenic component. Neurology. 1997 Jan. 48(1):29-33. [Medline].
Monsonego A, Zota V, Karni A, et al. Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J Clin Invest. 2003 Aug. 112(3):415-22. [Medline].
Nakano S, Shinde A, Kawashima S, et al. Inclusion body myositis: expression of extracellular signal-regulated kinase and its substrate. Neurology. 2001 Jan 9. 56(1):87-93. [Medline].
Nishino H, Engel AG, Rima BK. Inclusion body myositis: the mumps virus hypothesis. Ann Neurol. 1989 Mar. 25(3):260-4. [Medline].
Oldfors A, Larsson NG, Lindberg C, Holme E. Mitochondrial DNA deletions in inclusion body myositis. Brain. 1993 Apr. 116 (Pt 2):325-36. [Medline].
Oldfors A, Lindberg C. Diagnosis, pathogenesis and treatment of inclusion body myositis. Curr Opin Neurol. 2005 Oct. 18(5):497-503. [Medline].
Parissis D, Karkavelas G, Taskos N, Milonas I. Inclusion body myositis in a patient with a presumed diagnosis of post-polio syndrome. J Neurol. 2003 May. 250(5):619-21. [Medline].
Price P, Santoso L, Mastaglia F, et al. Two major histocompatibility complex haplotypes influence susceptibility to sporadic inclusion body myositis: critical evaluation of an association with HLA-DR3. Tissue Antigens. 2004 Nov. 64(5):575-80. [Medline].
Raju R, Vasconcelos O, Granger R, Dalakas MC. Expression of IFN-gamma-inducible chemokines in inclusion body myositis. J Neuroimmunol. 2003 Aug. 141(1-2):125-31. [Medline].
Sekul EA, Dalakas MC. Inclusion body myositis: new concepts. Semin Neurol. 1993 Sep. 13(3):256-63. [Medline].
Van der Muelen MF, Hoogendijk JE, Moons KG, et al. Rimmed vacuoles and the added predictive value of SM-31 staining in diagnosing sporadic inclusion body myositis. Neuromuscular Disorders. 2001. 11:447-451.
Verma A, Bradley WG, Adesina AM, et al. Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia. Muscle Nerve. 1991 May. 14(5):470-3. [Medline].
Verma A, Tandan R. TDP-43: a reliable immunohistochemistry marker for inclusion body myositis?. Muscle Nerve. 2009 Jul. 40(1):8-9. [Medline].
Wiendl H, Mitsdoerffer M, Schneider D, et al. Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies. FASEB J. 2003 Oct. 17(13):1892-4. [Medline].
|Disease||Points of Differentiation|
|h-IBM||Clinically and genetically heterogeneous group of diseases; positive family history; muscle biopsy features similar to s-IBM, but no inflammation|
|Polymyositis (PM)*||Weakness usually symmetric and proximally predominant; occasional cardiac and pulmonary involvement; similar to s-IBM, biopsy shows endomysial inflammation with invasion of non-necrotic fibers by CD8+ cells, but unlike s-IBM, rimmed vacuoles and ragged red fibers are infrequent and amyloid deposits and tubulofilaments not seen (see Histologic Findings)|
|Dermatomyositis (DM)||Weakness usually symmetric and proximally predominant; occasional cardiac and pulmonary involvement; characteristic skin lesions; characteristic biopsy findings (eg, perifascular atrophy, muscle infarcts, microvascular MAC deposits in the endomysium, focal capillary depletion, and conspicuous alterations in endothelial cells of endomysial microvasculature)|
|Oculopharyngeal muscular dystrophy (OPMD)||Predominant involvement of oculopharyngeal musculature (no extraocular muscle involvement in s-IBM); biopsy shows vacuoles, myopathic changes, and infrequent tubulofilaments (similar to s-IBM) but no inflammation; biopsy also shows pathognomonic intranuclear filamentous inclusions having smaller diameters than s-IBM tubulofilaments in 2-9% of nuclei; genetic testing is available for OPMD (PABPN1 gene); rare, genetically distinct oculopharyngodistal variant in Japan|
|Late-onset distal myopathies||Clinically and genetically heterogeneous group of diseases; positive family history unless sporadic case; biopsy may show rimmed vacuoles and tubulofilamentous inclusions in Welander, distal myopathy, Nonaka distal myopathy, and tibial muscular dystrophy, all of which can be classified as h-IBM. Gene testing is available for Nonaka distal myopathy (GNE) and tibial muscular dystrophy (titin).|
|Overlap myositis||PM- or DM-like clinical and myopathological presentation but with additional systemic and serologic features diagnostic of an underlying connective tissue disease (eg, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, or mixed connective tissue disease)|
|Myasthenia gravis||Unlike s-IBM, extraocular muscles are routinely involved; weakness is usually symmetric and tends to fluctuate, increasing with repeated or sustained exertion; spontaneous remissions can occur; motor unit action potentials (MUAPs) are unstable (increased jitter), whereas jitter is typically normal in s-IBM; repetitive nerve stimulation often shows abnormal decrement (rare in s-IBM); antibodies to acetylcholine receptors or muscle-specific kinase (MuSK) absent in s-IBM|
|Motor neuron disease||Upper motor neuron signs such as hyperreflexia and extensor plantar responses are not present in s-IBM; EMG in s-IBM may show neurogenic changes (ie, enlarged MUAPs), but these changes are relatively minor compared with predominance of smaller MUAPs, suggesting myopathy; fasciculation potentials are characteristic of motor neuron disease but rarely reported in s-IBM; recruitment is decreased in motor neuron disease and "early" in s-IBM; muscle biopsy in motor neuron disease shows denervation atrophy.|
|Acid maltase deficiency||Weakness is typically proximal-predominant (torso included); respiratory failure seen in about one third of adults; EMG is myopathic, similar to that of s-IBM, but in acid maltase deficiency, insertional activity is prominently increased, with profuse complex repetitive and myotonic discharges, whereas myotonic discharges are not seen in s-IBM and complex repetitive discharges are uncommon; muscle biopsy shows lysosomal (acid phosphatase-positive), glycogen-laden (PAS-positive) vacuoles, foci of acid phosphatase reactivity in nonvacuolated fibers, and glycogen accumulation by electron microscopy.|
|Chronic inflammatory demyelinating polyradiculoneuropathy||Weakness is usually both proximal and distal and mildly asymmetric, similar to s-IBM, but more often distally accentuated and lacking in the characteristic quadriceps/deep finger flexor emphasis of s-IBM; almost all patients have sensory signs and symptoms; examination shows diffuse hypo/areflexia; nerve conductions are abnormal, consistent with demyelination; EMG shows chronic reinnervational and no myopathic changes; serum creatine kinase (CK) is typically normal.|
|*Patients whose polymyositis does not respond to treatment and who have a clinical picture suggestive of s-IBM should be reevaluated. A repeat biopsy should be considered, as they may have s-IBM. Failure to confirm the diagnosis on initial biopsy may have been due to sampling error or insufficient processing.|
|Condition||Changes in MUAP Features|
|Nonspecific abnormality||Increased complexity (ie, phases, turns, late components)|
Only amplitude reduced
|Specific for myopathy||Shortened duration (simple or nonpolyphasic MUAPs)|