Diagnostik und Therapie der Myositis

Zusammenfassung

In den letzten Jahren gelingt es durch den Nachweis differenzierender Antikörper, subtilere bildgebende und histopathologische Diagnostik immer besser, die idiopathischen inflammatorischen Myopathien (IIM) einzuordnen. Neben der Polymyositis (PM) und Dermatomyositis (DM) sowie Einschlusskörperchenmyositis (IBM) grenzt sich das Anti-Synthetase-Syndrom ab. Nach auslösenden Ursachen wie myotoxischen Substanzen sollte besonders bei der nekrotisierenden Myositis gesucht werden. Ein Malignom-Ausschluss muss bei deutlich erhöhtem Risiko immer, insbesondere bei Nachweis von anti-TIF-1 gamma- und anti-NXP-2-Antikörpern erfolgen, dabei kann die Myositis dem Tumorleiden vorausgehen, sodass auch ein follow-up diesbezüglich erforderlich ist. Therapiestandard bleiben weiter die Glukokortikoide und Immunglobuline. Rituximab (RTX) stellt einen Meilenstein in der Therapie der schweren IIM dar. Auch wenn die RIM-Studie ihren primären Endpunkt verfehlt hat, zeigt sie wie, die inzwischen vorliegenden zahlreichen Fallberichte und Fallserien mit großen Patientenzahlen, das klare Ansprechen der meisten Patienten. Dabei benötigen viele Patienten nur einen Kurs (RTX), eine Reihe von Patienten erhält Kurse in großen Abständen bei sehr guter Verträglichkeit. In der Zukunft wird es noch besser gelingen, Subgruppen zu definieren und Responder und Nonresponder im Voraus zu erkennen. Auch für die IBM zeichnen sich nach Nachweis des ersten Antikörpers und den ersten Daten zu Bimagrumab erfolgversprechende neue Therapieoptionen ab. Eine Herausforderung bleibt das Management von Infektionen, der Dysphagie, der schweren Organbeteiligung sowie der Multimorbidität bei immer älter werdenden Patienten.

Abstract

The identification of differentiating antibodies and the use of more subtle imaging procedures and diagnostic histopathological procedures have allowed for idiopathic inflammatory myopathies (IIM) to be classified more accurately in the past few years. In addition to polymyositis, dermatomyositis and inclusion body myositis (IBM), the antisynthetase syndrome has been identified. Causative factors like myotoxic substances should be looked for especially in cases of necrotising myositis. Malignant diseases should always be ruled out in myositis patients, especially when anti-TIF1 gamma or anti-NXP-2 antibodies have been identified. As myositis may be a forerunner of a tumour, follow-up investigations are essentiell in this setting. Glucocorticoids and immunoglobulins still constitute the standard treatment for this condition. Rituximab (RTX) is a milestone in the treatment of severe IIM. Although the RIM study missed its primary endpoint, it has shown obvious responses in the majority of patients, as has also been demonstrated in several case reports and case series with large numbers of patients. Many patients need just one course of treatment (RTX). A number of patients receive several courses at large intervals and tolerate the treatment well. Subgroups will be defined even more specifically in the future, and it will be possible to differentiate responders from non-responders in advance. The detection of the first antibody and preliminary data on bimagrumab lead to the emergence of promising new treatment options for IBM. The management of infections, dysphagia, severe organ involvement and multimorbidity in an aging patient population continues to be a challenge in this context.

Schlüsselwörter

idiopathische inflammatorische Myopathie - Dermatomyositis - Polymyositis - Einschlusskörperchenmyositis - Therapiestandards

Key words

dermatomyositis - polymyositis - inclusion body myositis - standard treatment - idiopathic inflammatory myopathy

• Literatur

• 1 Sato S, Kuwana M, Fujita T et al. Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol 2013; 23: 496-502
• 2 Mahler M, Miller FW, Fritzler MJ. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 2014; 13: 367-371
• 3 Hozumi H, Enomoto N, Kono M et al. Prognostic significance of anti-aminoacyl-tRNA synthetase antibodies in polymyositis/dermatomyositis-associated interstitial lung disease: a retrospective case control study. PLoS One 2015; 10: e0120313
• 4 Ghirardello A, Bassi N, Palma L et al. Autoantibodies in polymyositis and dermatomyositis. Curr Rheumatol Rep 2013; 15: 335
• 5 Cox FM, Titulaer MJ, Sont JK et al. A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities. Brain 2011; 134: 3167-3175
• 6 Rose MR. Group EIW. 88^th ENMC International workshop: Inclusion Body Myositis. Neuromusc Disord 2013; 23: 1044-1055
• 7 Lloyd TE, Mammen AL, Amato AA et al. Evaluation and construction of diagnostic criteria for inclusion body myositis. Neurology 2014; 83: 426-433
• 8 Larman HB, Salajegheh M, Nazareno R et al. Cystosolic 5′-nucleotidase 1 A autoimmunity in sporadic inclusion body myositis. Ann Neur 2013; 73: 408-418
• 9 Malattia C, Damasio MB, Madeo A et al. Whole-body MRI in the assessment of disease activity in juvenile dermatomyositis. Ann Rheum Dis 2014; 73: 1083-1090
• 10 Pipitone N, Notarnicola A, Scardapane A et al. Does MRI Provide an Added Value Over Serum Creatine Kinase Measurement in Myositis? . Ann Rheum Dis 2015; 74: 177
• 11 Tateyama M, Fujihara K, Misu T et al. Clinical values of FDG PET in polymyositis and dermatomyositis syndromes: imaging of skeletal muscle inflammation. BMJ Open 2015; Jan 12; 5: e006763
• 12 Buchbinder R, Forbes A, Hall S et al. Incidence of malignant disease in biopsy-proven inflammatory myopathy: a population-based cohort study. Ann Intern Med 2001; 134: 1087-1095
• 13 Zantos D, Zhang Y, Felson D. The overall and temporal association of cancer with polymyositis and dermatomyositis. J Rheumatol 1994; 21: 1855-1859
• 14 Reichmann H, Schmiedel J, Schäfer J. Toxische Myopathien Management of neuromuscular diseases Letter Nr.25, ARCIS Verlag GmbH München 7. Jahrgang 2002;
• 15 Glueck CJ, Aregawi D, Agloria M et al. Rosuvastatin 5 and 10 mg/d: a pilot study of the effects in hypercholesterolemic adults unable to tolerate other statins and reach LDL cholesterol goals with nonstatin lipid-lowering therapies. Clin Ther 2006; 28: 933-942
• 16 Backes JM, Venero CV, Gibson CA et al. Effectivenes and tolerability of every-other-day rosuvastatin dosing in patiens with prior statin intolerance. Ann Pharmacother 2008; 42: 341-346
• 17 Steinmetzt A, Degen H. Grenzen und Alternativen einer Statintherapie: Wenn Statine krank machen. Der Allgemeinarzt 2014; 3617: 48-52
• 18 Banach M, Serben C, Sahebkar A et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015; 90: 24-34
• 19 Skarlovnik A, Janić M, Lunder M et al. Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. Med Sci Monit 2014; 20: 2183-2188
• 20 Kuhm C, Klopstock T. Toxische Myopathien. Arzneimitteltherapie 2014; 32: 87-92
• 21 Cardin SP, Martin JG, Saad-Magalhães C. Clinical and laboratory description of a series of cases of acute viral myositis. J Pediatr (Rio J) 2015; Jun 25. pii: S0021-7557(15)00072-8 [Epub ahead of print]
• 22 Rider LG, Giannini EH, Brunner HI. International Myositis Assessment and Clinical Studies Group. International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis Rheum 2004; 50: 2281-2290
• 23 Ruperto N, Pistorio A, Ravelli A et al. The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis. Arthritis Care Res (Hoboken) 2010; 62: 1533-1541
• 24 Vencovsky J. on behalf of ACR-EULAR Myositis Response Criteria Project. NEW ACR/EULAR RESPONSE CRITERIA FOR MYOSITIS.
• 25 Alemo Munters L, Dastmalchi M, Katz A et al. Improved exercise performance and increased aerobic capacitiy after endurance training of patients with stable polymyositis and dermatomyositis. Arthritis Res Ther 2013; 15: R83
• 26 Lundberg IE, Venovsky J, Alexanderson H. Therapy of myositis: biological and physical. Curr Opin Rheumatol 2014; 26: 704-711
• 27 Kitamura T, nakase H, Iizuka H. Risk factors for aspiration pneumonia after percutaneous endoscopic gastrostomy. Gerontology 2007; 53: 224-227
• 28 Murata KY, Kouda K. TajimaF et al. Balloon dilatation in sporadic inclusion body myosits with dysphagia. Clin med Insights Case Rep 2013; 6: 1-7
• 29 Oh TH, Brumfield KA, Hoskin TL et al. Dysphagia in inflammatory myopathy: clinical characteristics, treatment strategies, and outcome in 62 patients. Mayo Clin Proc 2007; 82: 441-447
• 30 Liu LW, Tarnopolsky M, Armstrong D. Injection of botulinum toxin A tot he upper esophageal sphincter for oropharyngeal dysphagia in two patients with inclusion body myositis. Can J Gastroenterol 2004; 18: 397-399
• 31 Langdon PC, Mulcahy K, Shepherd KL et al. Pharyngeal dysphagia in inflammatory muscle diseases resulting from impaired suprahyoid musculature. Dysphagia 2012; 27: 408-417
• 32 Villalba L, Hicks JE, Adams EM et al. Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimes. Arthritis Rheum 1998; 41: 392-399
• 33 Rouster-Stevens KA, Morgan GA, Wang D et al. Mycophenolate mofetil: a possible therapeutic agent for children with juvenile dermatomyositis. Arthritis Care Res (Hoboken) 2010; 62: 1446-1451
• 34 Shimojima Y, Ishii W, Matsuda M et al. Coadministration of tacrolimus with corticosteroid accelerates recovery in refractory patients with polymyositis/dermatomyositis: a retrospective study. BMC Musculoskeletal Disord 2012; 13: 228
• 35 Nagappa M, Taly AB, Sinha S et al. Efficacy and limitation of pulse cyclophosphamide therapy in polymyositis and dermatomyositis. J Clin Neuromuscul Dis 2013; 14: 161-168
• 36 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
• 37 Cherin P, Pelletier S, Teixeira A et al. Results and longterm followup of intravenous immunoglobulin infusions in chronic, refractory polymyositis: an open study with thirty.five adult patients. Arthritis Rheum 2002; 46: 467-474
• 38 Lundberg IE, Vencovsky J, Alexanderson H. Therapy of myositis: biological and physical. Curr Opin Rheumatol 2014; 26: 704-711
• 39 Mok CC, Ho LY, To CH. Rituximab for refractory polymoysitis: an open-label prospective study. J Rheumatol 2007; 34: 1864-1868
• 40 Oddis CV, Reed AM, Aggarwal R et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo-phase trial. Arthitis Rheum 2013; 65: 314-324
• 41 Miller FW, Rider LG, Chung YL et al. Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies. Rheumatol 2001; 40: 1262-1273
• 42 Aggarwal R, Bandos A, Reed AM et al. Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis: Clinical and Serological Predictor of Improvement in Myositis. Arthritis Rheumatol 2014; 66: 740-749
• 43 Unger L, Kampf S, Lüthke K et al. Rituximab therapy in patients with refractory dermatomyositis or polymyositis: differential effects in a real-life population. Rheumatology (Oxford) 2014; 53: 1630-1638
• 44 Mahler EAM, Blom M, Voermans NC et al. Rituximab treatment in patients with refractory inflammatory myopathies. Rheumatology 2011; 50: 2206-2213
• 45 Basnayake C, Cash K, Blumbergs P et al. Use of rituximab in histologically confirmed idiopathic inflammatory myositis: a case series. Clin Rheumatol 2015; 34: 371-377
• 46 Nalotto L, Laccarino L, Zen M et al. Rituximab in refractory idiopathic inflammatory myopathies and antisynthetase syndrome: personal experience and review of the literature. Immunol Res 2013; 56: 362-370
• 47 Chen D, Wang XB, Zhou Y et al. Efficacy of infliximab treatment for dermatomyositis with acute interstitial pneumonia: a study of fourteen cases and literature review. Rheumatol Int 2013; 33: 2455-2458
• 48 Dastmalchi M, Grundtman C, Alexanderson H et al. A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann Rheum Dis 2008; 67: 1670-1677
• 49 Coyle K, Pokrovnichka A, French K et al. A randomized double blind placebo controlled trial of infliximab in patients with polymyositis and dermatomyositis. Arthritis Res 2008; 58: S293
• 50 Hengstman GJ, De Bleecker JL, Feist E et al. Open-label trial of anti-TNF-alpha in dermato- and polymoysitis treated concimitantly with methotrexate. Eur Neurol 2008; 59: 159-163
• 51 Brunasso AM, Aberer W, Massone C. New onset of dermatomyositis/polymyositis during anti-TNF-a therapies: a systematic literature review. ScientificWorldJournal 2014; 2014: 179-180
• 52 Zong M, Dorph C, Dastmalchi M et al. Anakinra treatment in patients with refractory inflammatory myopathies and possible predictive response biomarkers: a mechanistic study with 12 months follow-up. Ann Rheum Dis 2014; 73: 913-920
• 53 Kerola AM, Kauppi MJ. Abatacept as a succesfull therapy for myositis – a case based review. Clin Rheumatol 2015; 34: 609-612
• 54 Narazaki M, Hagihara K, Shima Y et al. Therapeutic effect of tocilizumab on two patients with polymyositis. Rheumatology (Oxford) 2011; 50: 1344-1346
• 55 Kondo M, Murakawa Y, Matsumara T et al. A case of overlap syndrome succesfull treated with tocilzumab: a hopefull treatment strategy for refractory dermatomyositis?. Rheumatology (Oxford) 2014; 53: 1907-1908
• 56 Muscle Study Group. Randomized pilot trial of betaI FN-1a (Avonex) in patients with inclusion body myositis. Neurology 2001; 57: 1566-1570
• 57 Muscle Study Group. Randomizes pilot trial of high-dose betaIFN-1a in patients with inclusion body myositis. Neurology 2004; 63: 718-720
• 58 Dalakas MC, Rakocevic G, Schmidt J et al Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis. Brain 2009; 132: 1536-1544
• 59 Cherin P, Pelletier S, Teixeira A et al. Intravenous immunglobulin for dysphagia of inclusion body myositis. Neurology 2002; 58: 326
• 60 Dalakas MC, Sonies B, Dambrosia J et al. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology 1997; 48: 712-716
• 61 Walter MC, Lochmuller H, Toepfer M et al. High-dose immunglobulin threapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study. J Neurol 2002; 247: 22-28
• 62 Amato AA, Sivakumar K, Goyal N et al. treatment of sporadic inclusion body myositis with bimagrumab. Neurology 2014; 83: 2239-2246
• 63 Machado P, Miller A, herbelin L et al. LB002 safety and tolerability of arimoclomol in patients with sporadic inclusion body myositis: a randomised, double-blind, placebo-contolled, phase IIa proof-of-concept trial. Ann Rheum Dis 2013; 72: 164
• 64 Mendell JR, Rodino-Klapac L, Sahenk Z et al. Gene therapy for muscular dystrophy: lessons learned and path forward. Neurosci let 2012; 527: 90-99
• 65 Danieli MG, Gambini S, Pettinari L et al. Impact of treatment on survival in polymyositis and dermatomyositis. A single-centre long-term follow-up study. Autoimmun Rev 2014; 13: 1048-1054
• 66 Taborda AL, Azevedo P, Isenberg DA. Retrospective analysis of the outcome of patients with idiopathic inflammatory myopathy: a long-term follow-up study. Clin ExpRheuamtol 2014; 32: 188-193
• 67 Breithaupt M, Schmidt J. zertifizierte Fortbildung Inflammatorische Muskelerkrankungen. Neuro Transmitter 2014; 25: 46-54
• 68 Oldroyd AGS, Newton LR, New RP et al. The standardised mortality rate in UK adult-onset myositis patients is seven times higher than in the UK general population. Ann Rheum Dis 2015; 74 (Suppl. 02) 177-178