Treatment resistant myositis

Authors: H. Mann 1;  J. Vencovský;  Lundberg Ie 1 2
Authors‘ workplace: Revmatologický ústav a Revmatologická klinika 1. LF UK, Praha, 2Rheumatology Unit, Department of Medicine Karolinska University Hospital, in Solna, Karolinska Institutet, Stockholm Sweden 1
Published in: Čes. Revmatol., 18, 2010, No. 2, p. 97-108.
Category: Overview Reports


When confronted with a dermatomyositis or polymyositis patient not responding to immunosuppressive treatment, physician must firstly ask whether the original diagnosis was correct. In this review we provide a guide to the clinical features and ancillary tests, which might be helpful in the differential diagnosis of myositis. A particular attention is paid to the role of autoantibody detection, as some of them are not only relatively specific for the disease but also associated with unique clinical features including resistance to treatment. Subsequently other possible explanations of treatment resistance are listed and a short overview of treatment options for resistant myositis patients is given.

Key words:
polymyositis, dermatomyositis, inclusion body myositis (IBM)


1. Christopher-Stine L, Plotz PH. Adult inflammatory myopathies. Best Pract Res Clin Rheumatol 2004;18:331-344.

2. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292:344-347.

3. Needham M, Mastaglia FL. Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches. Lancet Neurol 2007;6:620-631.

4. Alexanderson H, Lundberg IE. The role of exercise in the rehabilitation of idiopathic inflammatory myopathies. Curr Opin Rheumatol 2005;17:164-171.

5. Miller FW, Rider LG, Chung YL, et al. Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies. Rheumatology (Oxford) 2001;40:1262-1273.

6. Dugan EM, Huber AM, Miller FW, et al. Photoessay of the cutaneous manifestations of the idiopathic inflammatory myopathies. Dermatol Online J 2009;15:1.

7. Gerami P, Schope JM, McDonald L, et al. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis sine myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J Am Acad Dermatol 2006;54:597-613.

8. Hoffman EP, Rao D, Pachman LM. Clarifying the boundaries between the inflammatory and dystrophic myopathies: insights from molecular diagnostics and microarrays. Rheum Dis Clin North Am 2002;28:743-757.

9. Chahin N, Engel AG. Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM. Neurology 2008;70:418-424.

10. Walsh RJ, Amato AA. Toxic myopathies. Neurol Clin 2005;23:397-428.

11. Seidler A, Gottlieb A. Dermatomyositis induced by drug therapy. J Am Acad Dermatol 2008;59:872-880.

12. Yazici Y, Kagen LJ. Clinical presentation of the idiopathic inflammatory myopathies. Rheum Dis Clin North Am 2002;28:823-832.

13. Wortmann RL, DiMauro S. Differentiating idiopathic inflammatory myopathies from metabolic myopathies. Rheum Dis Clin North Am 2002;28:759-778.

14. Lundberg IE. The heart in dermatomyositis and polymyositis. Rheumatology (Oxford) 2006;45:18-21.

15. Rider LG. Outcome assessment in the adult and juvenile idiopathic inflammatory myopathies. Rheum Dis Clin North Am 2002;28:935-977.

16. Marguerie C, Bunn CC, Beynon HL,, et al. Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. Q J Med 1990;77:1019-1038.

17. Brouwer R, Hengstman GJ, Vree Egberts W, et al. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 2001;60:116-123.

18. Betteridge Z, Gunawardena H, North J, et al. Anti-synthetase syndrome: a new autoantibody to phenylalanyl transfer RNA synthetase (anti-Zo) associated with polymyositis and interstitial pneumonia. Rheumatology (Oxford) 2007;46:1005-1008.

19. Hashish L, Trieu EP, Sadanandan P, et al. Identification of autoantibodies to tyrosyl-tRNA synthetase in dermatomyositis with features consistent with antisynthetase syndrome (abstract). Arthritis Rheum 2005;52:S312.

20. Tillie-Leblond I, Wislez M, Valeyre D, et al. Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset. Thorax 2008;63:53-59.

21. Stone KB, Oddis CV, Fertig N, et al. Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum 2007;56:3125-3131.

22. Kao AH, Lacomis D, Lucas M, et al. Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum 2004;50:209-215.

23. Miller T, Al-Lozi MT, Lopate G, et al. Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry 2002;73:420-428.

24. Hengstman GJ, Vree Egberts WT, Seelig HP, et al. Clinical characteristics of patients with myositis and autoantibodies to different fragments of the Mi-2 beta antigen. Ann Rheum Dis 2006;65:242-245 .

25. Marguerie C, Bunn CC, Copier J, et al. The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl. Medicine (Baltimore) 1992;71:327-336 .

26. Cavazzana I, Ceribelli A, Quinzanini M, et al. Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune diseases. Lupus 2008;17:727-732.

27. Targoff IN, Mamyrova G, Trieu EP, et al. A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum 2006;54:3682-3689.

28. Kaji K, Fujimoto M, Hasegawa M, et al. Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy. Rheumatology (Oxford) 2007;46:25-28.

29. Gunawardena H, Wedderburn LR, North J, et al. Juvenile Dermatomyositis Research Group UK. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology (Oxford) 2008;47:324-328.

30. Chinoy H, Fertig N, Oddis CV, et al. The diagnostic utility of myositis autoantibody testing for predicting the risk of cancer-associated myositis. Ann Rheum Dis 2007;66:1345-1349.

31. Gunawardena H, Wedderburn LR, Chinoy H, et al. Juvenile Dermatomyositis Research Group, UK and Ireland. Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis. Arthritis Rheum 2009;60:1807-1814.

32. Sato S, Hirakata M, Kuwana M, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 2005;52:1571-1576.

33. Sato S, Hoshino K, Satoh T, et al. RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease. Arthritis Rheum 2009;60:2193-2200.

34. Betteridge ZE, Gunawardena H, Chinoy H, et al. Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis. Ann Rheum Dis 2009;68:1621-1625.

35. Christopher-Stine L, Hong G, Casciola-Rosen L, et al. A Novel Autoantibody against 200/100 Kd Proteins Is Associated with Necrotizing Myopathy (abstract). Arthritis Rheum 2009;60:S430.

36. Lovitt S, Moore SL, Marden FA. The use of MRI in the evaluation of myopathy. Clin Neurophysiol 2006;117:486-495.

37. Tomasova-Studynkova J, Charvat F, Jarosova K, Vencovsky J. The role of MRI in the assessment of polymyositis and dermatomyositis. Rheumatology 2007;46:1174-1179.

38. Curiel RV, Jones R, Brindle K. Magnetic resonance imaging of the idiopathic inflammatory myopathies: structural and clinical aspects. Ann NY Acad Sci 2009;1154:101–114.

39. *Dalakas MC. Muscle biopsy findings in inflammatory myopathies. Rheum Dis Clin North Am 2002;28:779-798.

40. van der Pas J, Hengstman GJ, ter Laak HJ, et al. Diagnostic value of MHC class I staining in idiopathic inflammatory myopathies. J Neurol Neurosurg Psychiatry 2004;75:136-139.

41. Jain A, Sharma MC, Sarkar C, et al. Major histocompatibility complex class I and II detection as a diagnostic tool in idiopathic inflammatory myopathies. Arch Pathol Lab Med 2007;131:1070-1076.

42. Lundberg I, Kratz AK, Alexanderson H, Patarroyo M. Decreased expression of interleukin-1alpha, interleukin-1beta, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis. Arthritis Rheum 2000;43:336-348.

43. Madan V, Chinoy H, Griffiths CE, Cooper RG. Defining cancer risk in dermatomyositis. Clin Exp Dermatol 2009;34:451-455.

44. Villalba L, Hicks JE, Adams EM, et al. Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. Arthritis Rheum 1998;41:392-399.

45. Dalakas MC, Illa I, Dambrosia JM, et al. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1993-2000.

46. Barbasso Helmers S, Dastmalchi M, Alexanderson H, et al. Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. Ann Rheum Dis 2007;66:1276-1283.

47. Pisoni CN, Cuadrado MJ, Khamashta MA, et al. Mycophenolate mofetil treatment in resistant myositis. Rheumatology (Oxford) 2007;46:516-518.

48. Yamasaki Y, Yamada H, Yamasaki M, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology (Oxford) 2007;46:124-130.

49. Wilkes MR, Sereika SM, Fertig N, et al. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum 2005;52:2439-2446.

50. Noss EH, Hausner-Sypek DL, Weinblatt ME. Rituximab as therapy for refractory polymyositis and dermatomyositis. J Rheumatol 2006;33:1021-1026.

51. Arlet JB, Dimitri D, Pagnoux C, et al. Marked efficacy of a therapeutic strategy associating prednisone and plasma exchange followed by rituximab in two patients with refractory myopathy associated with antibodies to the signal recognition particle (SRP). Neuromuscul Disord 2006;16:334-336.

52. Furlan A, Botsios C, Ruffatti A, et al. Antisynthetase syndrome with refractory polyarthritis and fever successfully treated with the IL-1 receptor antagonist, anakinra: A case report. Joint Bone Spine 2008;75:366-367.

53. Alexanderson H, Stenström CH, Jenner G, Lunberg I. The safety of a resistive home exercise program in patients with recent onset active polymyositis or dermatomyositis. Scand J Rheumatol 2000;29:295-301.

54. Dalakas, Rakocevic G, Schmidt J, et al. Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain 2009:132;1536–1544.

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