search
for
 About Bioline  All Journals  Testimonials  Membership  News


Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 58, Num. 1, 2010, pp. 3-5

Neurology India, Vol. 58, No. 1, January-February, 2010, pp. 3-5

Editorial

Drug treatment of polymyositis and dermatomyositis

J. M. K. Murthy

Department of Neurology, the Institute of Neurological Sciences, CARE Hospital, Exhibition Road, Nampally, Hyderabad - 500 001, India

Correspondence Address: J. M. K. Murthy, Department of Neurology, The Institute of Neurological Sciences, CARE Hospital, Exhibition Road, Nampally, Hyderabad - 500 001, India, jmkmurthy@satyam.net.in

Date of Acceptance: 25-Jan-2010

Code Number: ni10002

DOI: 10.4103/0028-3886.60386

Idiopathic immune-mediated myopathies, notably polymyositis (PM) and dermatomyositis (DM) are relatively uncommon diseases and are associated with considerable morbidity and mortality if not recognized early and treated, in some cases as high as 50%, primarily related to life-threatening muscle weakness, cardiac and lung complications. [1],[2],[3],[4] The morbidity and mortality associated with PM and DM can be reduced to some extent by early diagnosis and institution of appropriate treatment. [2],[5],[6],[7],[8],[9] The importance of early drug therapy in PM and DM has once again been emphasized by Peyman et al., [10] in the article published in this issue of the journal. In their study early institution of drug therapy was associated with early and higher remission rates.

The evolving evidence suggests that the underlying immunopathogenesis of inflammatory myopathies may determine the response to drug treatment and also long-term prognosis. In DM a complement-dependent humoral process thought to be initiated by antibodies to endothelial cells results in microangiopathy with secondary ischemic changes in muscles, while in PM there is a T-cell response with invasion of muscle fibers by CD8 + lymphocytes and perforin-mediated cytotoxic necrosis. [11] The PM/DM complex is associated with several autoantibodies: Antisynthetase antibodies (Jo1, Pl7, PL12), anti-Mi2 antibody, anti-SRP antibody, anti-Ku antibody, anti-Ro, anti-U1-RNP antibodies and, notably, anti-PM-Scl antibody. [12] Presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung (interstitial lung disease, ILD) and esophageal involvement as well as with malignancy. [13] The most common of the antisynthetases is the Jo-1 antibody which is associated with ILD and Raynaud phenomena (antisynthetase syndrome). [14],[15] ILD associated with PM/ DM is recognized as an important condition because it frequently causes death. [2],[4],[16],[17],[18],[19],[20]

PM and DM are highly treatable diseases and may achieve a complete or worthwhile functional remission. Treatment in PM and DM is very similar, with drugs that suppress the immune system the mainstay of therapy. However, there are no defined guidelines or best treatment protocols agreed internationally and the treatment thus remains largely empirical. There are only a few prospective, double-blinded, placebo-controlled trials in the treatment of PM [21] and DM. [22]

Corticosteroids, prednisolone, is the initial drug of choice. High dose of prednisolone is maintained until muscle strength normalizes, improvement in strength reaches a plateau or serum creatine kinase (CK) normalizes, which usually takes three to six months. Subsequently the prednisolone dose is tapered over a few weeks. Most of the patients need to remain on at least a small dose of prednisolone to remain in sustained remission. [23] Significant improvement is noted in 60-80% of the patients. [16],[17] In patients with severe disease, weakness of the bulbar and respiratory muscles or delay in the diagnosis, a more rapid response may be obtained by commencing treatment with intravenous methylprednisolone followed by oral prednisolone. [11] Initial combination therapy with prednisolone and azathioprine has been used to achieve better disease control and allowing quicker steroid withdrawal. In addition combination therapy appears to reduce the risk of relapse [24],[25] and also improve long-term outcome. [26] It appears that patients of PM and DM with associated ILD may require initial combination therapy. [13],[20] Similarly, patients with anti-synthetase syndrome who often have refractory myositis and ILD, or those with anti-SRP antibodies who typically have a severe necrotizing myopathy with little inflammation may require an aggressive immunosuppressive therapy, usually a combination therapy. [11] It may be prudent to avoid methotrexate in patients with ILD as it is one of the adverse events of methotrexate.

In a proportion of patients with PD or DM (20-30%) it is not possible to achieve complete remission with corticosteroids and relapses are not uncommon. Patients who are resistant to steroids or who relapse with reduction of steroid dosage require other immunosuppressive or immunomodulatory treatment. In a controlled trial intravenous immunoglobulin (IVIg) has been shown to be effective in patients with DM as an add-on treatment [22] and in uncontrolled trials in patients with PM and overlap syndromes. [27],[28] In patients with refractoriness to steroids initial IVIg dosage is 2 g/kg over a five-day period (0.4 g/kg/ day), followed by monthly three-day courses for three to six months during which period prednisolone and other immunosuppressive agents are also controlled. Treatment needs to be individualized. [11] In an open study IVIg as an add-on treatment with mycophenolate mofetil in patients with severe PM/DM (steroid-dependency, refractoriness to steroids and/or immunosuppressants, and life-threatening disease) has been shown to be effective, moreover as a safe and steroid-sparing agent. [29] IVIg treatment has been shown to be safe and an effective salvage therapy for refractory ILD associated with PM/ DM in certain cases. [20]

Methotrexate and azathioprine are the two immuno suppressive agents used in patients refractory to steroids or who relapse during prednisolone taper. Another advantage of these drugs is their potential steroid-sparing effect. Methotrexate has been shown to be effective in DM and PM, mostly in the retrospective studies [30],[31],[32],[33],[34],[35] and is administered only one day a week. Careful attention should be paid to the serious adverse events associated with methotrexate treatment: Bone marrow, renal and liver toxicity and ILD. Retrospective studies [31],[36] and an open-label follow-up study of the prospective double-blind study [26] indicate that azathioprine is an effective drug in DM and PM. Complete blood counts and liver function tests need to be followed closely. If there is no improvement with either of the drugs after six to eight weeks other options have to be considered which include mycophnolate, cyclosporine, tacrolimus, cyclophosphamide, and tumor necrosis Factor-a blockers (infliximab, etanercept). [23] Cyclophosphamide is usually reserved for patients refractory to most other modalities. [37],[38],[39],[40] B-cell depletion therapy with rituximab used alone or in combination with other immunosuppressive therapies is another viable option in the treatment of refractory DM [41],[42],[43],[44] and PM, [45],[46] in both myositis-specific autoantibody-positive and-negative patients.

PM and DM are potentially treatable diseases and an early institution of appropriate therapies is likely to be associated with early and higher remission rates and probably reduced morbidity and mortality. Better understanding of the underlying immunopathogenesis of PM and DM, as well as carefully performed clinical trials is going to be necessary to make better recommendations in the future.

References

1.Danko K, Pnyi A, Constantin T, Borgulya G, Szegedi G. Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features: A longitudinal study of 162 cases. Medicine (Baltimore) 2004;83:35-42.  Back to cited text no. 1    
2.Marie I, Hachulla E, Hatron PY, Hellot MF, Levesque H, Devulder B, et al. Polymyositis and dermatomyositis: Short term and long term outcome, and predictive factors. J Rheumatol 2001;28:2230-7.  Back to cited text no. 2    
3.Marie I, Hachulla E, Cherin P, Hellot MF, Herson S, Levesque H, et al. Opportunistic infections in polymyositis and dermatomyositis. Arthritis Rheum 2005;53:155-65.  Back to cited text no. 3    
4.Marie I, Hartron PY, Levesque H, Hachulla E, Hellot MF, Michon-Pasturel U, et al. Influence of age on characteristics of polymyositis and dermatomyositis in adults. Medicine (Baltimore) 1999;78:139-47.  Back to cited text no. 4    
5.Fafalak R, Peterson M, Kagen L. Strength in polymyositis and dermatomyositis: Best outcome in patients treated early. J Rheumatol 1994;2:643-8.  Back to cited text no. 5    
6.Sultan S, Ioannou Y, Moss K, Isenberg D. Outcome in patients with idiopathic inflammatory Myositis: Morbidity and mortality. Rheumatology 2002;41:22-6.  Back to cited text no. 6    
7.Chowdhary V, Wakhlu A, Agarwal A, Misra R. Outcome in juvenile dermatomyositis. Indian Pediatr 2002;39:931-5.  Back to cited text no. 7  [PUBMED]  
8.Tymms K, Webb J. Dermato-polymyositis and other tissue diseases: A review of 105 cases. J Rheumatol 1985;12:1140-8.  Back to cited text no. 8    
9.Airio A, Kautiainen H, Hakala M. Prognosis and mortality of polymyositis and dermatomyositis patients. Clin Rheumatol 2006;25:234-9.  Back to cited text no. 9  [PUBMED]  
10.Peyman N, Farhad S, Adbolhadi N, Fereydoun D. Effect of early treatment in polymyositis and dermatomyositis. Neurol India 2010;58:58-61.  Back to cited text no. 10    
11.Mastaglia FL. Inflammatory muscle diseases. Neurol India 2008;56:263-70.  Back to cited text no. 11  [PUBMED]  Medknow Journal
12.Troyanov Y, Targoff IN, Tremblay JL, Goulet JR, Raymond Y, Senécal JL. Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: Analysis of 100 French Canadian patients. Medicine (Baltimore) 2005;84:231-49.   Back to cited text no. 12    
13.Marie I, Lahaxe L, Benveniste O, Delavigne K, Adoue D, Mouthon L, et al. Long-term outcome of patients with polymyositis/dermatomyositis and anti-PM-Scl antibody. Br J Dermatol 2010;162;337-44.   Back to cited text no. 13    
14.Hochberg MD, Feldman D, Stevens MB, Arnett FC, Reichlin M. Antibody to Jo-1 in polymyositis/dermatomyositis: Association with interstitial pulmonary disease. J Rheumatol 1984;11:663-5.  Back to cited text no. 14    
15.Hengstman GJ, Brouwer R, Egberts WT, Seelig HP, Jongen PJ, van Venrooij WJ, 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;249:69-75.   Back to cited text no. 15    
16.Bohan A, Peter JB, Bowman RL, Pearson CM. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;86:255-86.  Back to cited text no. 16    
17.Henriksson KG, Lindvall B. Polymyositis and dermatomyositis 1990-diagnosis, treatment and prognosis. Prog Neurobiol 1990;35:181-93.   Back to cited text no. 17  [PUBMED]  
18.Henriksson KG, Sandstedt P. Polymyositis-treatment and prognosis. Acta Neurol Scand 1982;65:280-300.  Back to cited text no. 18  [PUBMED]  
19.de Vere R, Bradley WG. Polymyositis: Its presentation, morbidity and mortality. Brain 1975;98:637-66.   Back to cited text no. 19    
20.Suzuki Y, Hayakawa H, Miwa S, Shirai M, Fujii M, Gemma H, et al. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis. Lung 2009;187:201-6.   Back to cited text no. 20    
21.Bunch TW, Worthington JW, Combs JJ, Ilstrup DM, Engel AG. Azathiprine with prednisone for polymyositis. Ann Intern Med 1980;92:365-9.  Back to cited text no. 21  [PUBMED]  
22.Dalakas MC, IIIa I, Dambrosia JM. A controlled trial of high dose intravenous immunoglobulin infusions as treatment for dermatomyositis. N Engl J Med 1993;329:1992-2000.   Back to cited text no. 22    
23.Amato AA, Barohn RJ. Evaluation and treatment of inflammatory myopathies. J Neurol Neurosurg Psychiatry 2009;80:1060-8.   Back to cited text no. 23  [PUBMED]  
24.Mastaglia FL, Phillips BA, Zilko PJ, Garlepp MJ. Relapses in idiopathic inflammatory myopathies. Muscle Nerve 1999;22:1160-1.   Back to cited text no. 24    
25.Miro' O, Laguno M, Grau JM. Relapses in idiopathic inflammatory myopathies. Muscle Nerve 1999;22:1159-60.   Back to cited text no. 25    
26.Bunch TW. Prednisone and azathiprine for polymyositis. Arthritis Rheum 1981;24:45-8.  Back to cited text no. 26  [PUBMED]  
27.Cherin P, Herson S, Wechsler B, Piette JC, Bletry O, Coutellier A, et al. Efficacy of intravenous immunoglobulin therapy in chronic refractory polymyositis and dermatomyositis: An open study with 20 adult patients. Am J Med 1991;91:162-8.   Back to cited text no. 27    
28.Mastaglia FL, Philips BA, Zilko PJ. Immunoglobulin therapy in inflammatory myopathies. J Neurol Neurosurg Psychiatry 1998;65:107-10.   Back to cited text no. 28    
29.Danieli MG, Calcabrini L, Calabrese V, Marchetti A, Logullo F, Gabrielli A. Intravenous immunoglobulin as add on treatment with mycophenolate mofetil in severe myositis. Autoimmun Rev 2009;9:124-7.  Back to cited text no. 29  [PUBMED]  
30.Cagnoli M, Marchesoni A, Tosi S. Combined steroids, methotrexate and chlorambucil therapy for steroid resistant dermatomyositis. Clin Exp Rheumatol 1991;9:658-9.  Back to cited text no. 30  [PUBMED]  
31.Giannini M, Callen JP. Treatment of dermatomyositis with methotexate and prednisone. Arch Dermatol 1979;115:1251-2.   Back to cited text no. 31  [PUBMED]  
32.Metzger AL, Bohan A, Goldberg LS, Bluestone R, Pearson CM. Polymyositis and dermatomyositis: Combined methotrexate and corticosteroid therapy. Ann Inter Med 1974;81:182-9.   Back to cited text no. 32    
33.Sokoloff MC, Goldberg LS, Pearson CM. Treatment of corticosteroid-resistant polymyositis with methotrexate. Lancet 1971;1:14-6.   Back to cited text no. 33  [PUBMED]  
34.Miller LC, Sisson BA, Tucker LB, DeNardo BA, Schaller JG. Methotrexate treatment of recalcitrant childhood dermatymyositis. Arthritis Rheum 1992;35:1143-9.  Back to cited text no. 34  [PUBMED]  
35.Joffe MM, Love LA, Leff RL, Fraser DD, Targoff IN, Hicks JE, et al. Drug therapy of idiopathic inflammatory myopathies: Predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Am J Med 1993;94:379-87.  Back to cited text no. 35    
36.Amato AA, Gronseth GS, Jackson CE, Wolfe GI, Katz JS, Bryan WW, et al. Inclusion body myositis: Clinical and pathological boundaries. Ann Neurol 1996;40:581-6.  Back to cited text no. 36    
37.Kono DW, Klashman DJ, Gilbert RC. Successful IV pulsed cyclophophamide in refractory PM in 3 patients with SLE. J Rheumatol 1990;17:982-3.  Back to cited text no. 37    
38.Leroy JP, Drosos AA, Yiannopoulos DI, Youinou P, Moutsopoulos HM. Intravenous pulse cyclophophamide therapy in myositis and Sjogren's syndrome. Arthritis Rheum 1990;33:1579-81.  Back to cited text no. 38  [PUBMED]  
39.Niakan E, Pitner SE, Whitaker JN, Bertorini TE. Immunosuppressive agent in corticosteroid-refractory childhood dermatomyositis. Neurology 1980;30:286-91.  Back to cited text no. 39  [PUBMED]  
40.Fries JF, Sharp GC, McDevitt HO, Holman HR. Cyclophophamide therapy in systemic ertyhematosis and polymyositis. Arthritis Rheum 1973;16:154-62.  Back to cited text no. 40    
41.Sultan SM, Ng KP, Edwards JC, Isenberg DA, Cambridge G. Clinical outcome following B cell depletion therapy in eight patients with refractory idiopathic inflammatory myopathy. Clin Exp Rheumatol 2008;26:887-93.  Back to cited text no. 41  [PUBMED]  
42.Cooper MA, Willingham DL, Brown DE, French AR, Shih FF, White AJ. Rituximab for the treatment of juvenile dermatomyositis: A report of four paediatric patients. Arthritis Rheum. 2007;56:3107-11.  Back to cited text no. 42    
43.Chiappetta N, Steier J, Gruber B. Rituximab in the treatment of refractory dermatomyositis. J Clin Rheumatol. 2005;11:264-6.  Back to cited text no. 43    
44.Levine TD. Rituximab in the treatment of dermatomyositis: An open-label pilot study. Arthritis Rheum. 2005;52:601-7.  Back to cited text no. 44    
45.Lambotte O, Kotb R, Maigne G, Blanc FX, Goujard C, Delfraissy JF. Efficacy of rituximab in refractory polymyositis. J Rheumatol 2005;32:1369-70.  Back to cited text no. 45  [PUBMED]  
46.Mok CC, Ho LY, To CH. Rituximab for refractory polymyositis: An open-label prospective study. J Rheumatol 2007;34:1864-8.  Back to cited text no. 46  [PUBMED]  

Copyright 2010 - Neurology India

Home Faq Resources Email Bioline
© Bioline International, 1989 - 2024, Site last up-dated on 01-Sep-2022.
Site created and maintained by the Reference Center on Environmental Information, CRIA, Brazil
System hosted by the Google Cloud Platform, GCP, Brazil