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Juvenile Dermatomyositis – was gibt es Neues?

Juvenile dermatomyositis—what’s new?

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Zusammenfassung

Die juvenile Dermatomyositis (JDM) ist die häufigste chronisch-entzündliche Myopathie des Kindesalters, die immer noch oft zu einem komplizierten Verlauf führt. In dieser Übersicht werden basierend auf einer Literatursuche neue Erkenntnisse zur JDM dargestellt. Myositisspezifische Antikörper liegen häufig vor und korrelieren mit klinischen Phänotypen und dem Verlauf der Erkrankung. Die Aktivierung von Typ-I-Interferonen spielt eine wichtige Rolle in der Pathogenese und ist verknüpft mit den Hauptmanifestationen der Erkrankung; möglicherweise kann dies in der Zukunft zu gezielten Therapien führen. Derzeit gibt es keine speziell für die JDM zugelassenen Medikamente. Die Standardtherapie umfasst basierend auf einer randomisierten kontrollierten Studie und gemäß Expertenkonsens immer Glukokortikoide und Methotrexat. Verbreitete Medikamente bei refraktärer JDM sind u. a. Azathioprin, Ciclosporin A, intravenöses Immunglobulin, Mycophenolatmofetil und Rituximab. Eine optimale Therapie der JDM ist nicht etabliert, jedoch existieren mittlerweile nationale und internationale Konsensusempfehlungen und Therapiepläne, die bei der Entscheidungsfindung helfen können. Zahlreiche validierte Messinstrumente stehen zur Verfügung, um die Krankheitsaktivität der JDM, eine resultierende Schädigung und die Therapieantwort zu erfassen. Diese Instrumente sollten regelhaft bei Patienten mit JDM angewendet und idealerweise in Registern dokumentiert werden, um so verschiedene Behandlungsweisen vergleichen zu können. Die PRO-KIND-Initiative der Gesellschaft für Kinder- und Jugendrheumatologie hat praxis- und konsensbasiert in Deutschland sowohl eine diagnostische als auch eine Treat-to-Target-Behandlungsstrategie entwickelt.

Abstract

Juvenile dermatomyositis (JDM) is the most common chronic inflammatory myopathy of childhood, which is still frequently characterized by a complicated disease course. In this review, novel findings relating to JDM are presented based on a review of the literature. Myositis-specific antibodies are often detected and may correlate with clinical phenotypes and disease course. Activation of type I interferon pathways plays an important pathogenic role and relates to the main clinical manifestations of the disease. This may lead to targeted therapies in the future. Currently, there are no treatments specifically approved for the treatment of JDM. Standard therapy is currently considered to include glucocorticoids and methotrexate based on a randomized controlled study and expert consensus. Several medications are commonly used in cases of refractory JDM, including azathioprine, ciclosporin, intravenous immune globulins, mycophenolate mofetil, and rituximab. An optimal treatment of JDM has not yet been established; however, there are national and international consensus recommendations and treatment plans that may aid in the decision-making process. Several validated tools are available to assess disease activity, disease damage, and treatment responses. Such tools should be routinely used in patients with JDM, and ideally be documented in registries in order to allow comparative effectiveness studies. The PRO-KIND initiative of the German Society for Pediatric Rheumatology has developed a diagnostic and a treat-to-target strategy based on a practice- and consensus-based process.

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Literatur

  1. Aeschlimann FA, Fremond ML, Duffy D et al (2018) A child with severe juvenile dermatomyositis treated with ruxolitinib. Brain 141:e80

    PubMed  Google Scholar 

  2. Aggarwal R, Bandos A, Reed AM et al (2014) Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis. Arthritis Rheumatol 66:740–749

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Aggarwal R, Oddis CV, Goudeau D et al (2016) Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. Rheumatology (Oxf) 55:1710

    Google Scholar 

  4. Bader-Meunier B, Gitiaux C, Belot A et al (2019) French expert opinion for the management of juvenile dermatomyositis. Arch Pediatr 26(2):120. https://doi.org/10.1016/j.arcped.2018.12.002

    Article  PubMed  CAS  Google Scholar 

  5. Baechler EC, Bilgic H, Reed AM (2011) Type I interferon pathway in adult and juvenile dermatomyositis. Arthritis Res Ther 13:249

    PubMed  PubMed Central  CAS  Google Scholar 

  6. Bohan A, Peter JB (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347

    PubMed  CAS  Google Scholar 

  7. Gemeinsamer Bundesausschuss (2013) Beschluss des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie (AM-RL)/Anlage VI: Off-Label-Use Intravenöse Immunglobuline (IVIG) bei Polymyositis und bei Dermatomyositis (BAnz AT 09.07.2013 B1)

    Google Scholar 

  8. Dressler F, Huppertz HI (2006) Juvenile dermatomyositis. Z Rheumatol 65:587–590 (592–584)

    PubMed  CAS  Google Scholar 

  9. Enders FB, Bader-Meunier B, Baildam E et al (2017) Consensus-based recommendations for the management of juvenile dermatomyositis. Ann Rheum Dis 76:329–340

    Google Scholar 

  10. Fujimoto M, Hamaguchi Y, Kaji K et al (2012) Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins. Arthritis Rheum 64:513–522

    PubMed  CAS  Google Scholar 

  11. Higgs BW, Zhu W, Morehouse C et al (2014) A phase 1b clinical trial evaluating sifalimumab, an anti-IFN-alpha monoclonal antibody, shows target neutralisation of a type I IFN signature in blood of dermatomyositis and polymyositis patients. Ann Rheum Dis 73:256–262

    PubMed  CAS  Google Scholar 

  12. Hinze CH, Oommen PT, Dressler F et al (2018) Development of practice and consensus-based strategies including a treat-to-target approach for the management of moderate and severe juvenile dermatomyositis in Germany and Austria. Pediatr Rheumatol Online J 16:40

    PubMed  PubMed Central  Google Scholar 

  13. Hinze CH, Speth F, Oommen PT et al (2018) Current management of juvenile dermatomyositis in Germany and Austria: An online survey of pediatric rheumatologists and pediatric neurologists. Pediatr Rheumatol Online J 16:38

    PubMed  PubMed Central  Google Scholar 

  14. Hornig J, Weinhage T, Schmidt LH et al (2018) Response of dermatomyositis with lung involvement to Janus kinase inhibitor treatment. Z Rheumatol 77:952–957

    PubMed  CAS  Google Scholar 

  15. Huber AM, Kim S, Reed AM et al (2017) Childhood arthritis and rheumatology research alliance consensus clinical treatment plans for juvenile dermatomyositis with persistent skin rash. J Rheumatol 44:110–116

    PubMed  CAS  Google Scholar 

  16. Huber AM, Robinson AB, Reed AM et al (2012) Consensus treatments for moderate juvenile dermatomyositis: Beyond the first two months. Results of the second Childhood Arthritis and Rheumatology Research Alliance Consensus Conference. Arthritis Care Res 64:546–553

    Google Scholar 

  17. Kim S, Kahn P, Robinson AB et al (2017) Childhood Arthritis and Rheumatology Research Alliance consensus clinical treatment plans for juvenile dermatomyositis with skin predominant disease. Pediatr Rheumatol Online J 15:1

    PubMed  PubMed Central  Google Scholar 

  18. Kishi T, Rider LG, Pak K et al (2017) Association of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies with DRB1*07:01 and severe myositis in juvenile myositis patients. Arthritis Care Res 69:1088–1094

    CAS  Google Scholar 

  19. Kobayashi N, Takezaki S, Kobayashi I et al (2015) Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis. Rheumatology (Oxf) 54:784–791

    CAS  Google Scholar 

  20. Ladislau L, Suarez-Calvet X, Toquet S et al (2018) JAK inhibitor improves type I interferon induced damage: Proof of concept in dermatomyositis. Brain 141:1609–1621

    PubMed  Google Scholar 

  21. Lazarevic D, Pistorio A, Palmisani E et al (2013) The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis. Ann Rheum Dis 72:686–693

    PubMed  CAS  Google Scholar 

  22. Liang WC, Uruha A, Suzuki S et al (2017) Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies. Rheumatology (Oxf) 56:287–293

    Google Scholar 

  23. Lilleker JB, Vencovsky J, Wang G et al (2018) The EuroMyositis Registry: An international collaborative tool to facilitate myositis research. Ann Rheum Dis 77:30–39

    PubMed  Google Scholar 

  24. Lundberg IE, Tjarnlund A, Bottai M et al (2017) 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 76:1955–1964

    PubMed  PubMed Central  Google Scholar 

  25. Mamyrova G, Katz JD, Jones RV et al (2013) Clinical and laboratory features distinguishing juvenile polymyositis and muscular dystrophy. Arthritis Care Res 65:1969–1975

    CAS  Google Scholar 

  26. Mamyrova G, Rider LG, Ehrlich A et al (2017) Environmental factors associated with disease flare in juvenile and adult dermatomyositis. Rheumatology (Oxf) 56:1342–1347

    Google Scholar 

  27. Miller FW, Cooper RG, Vencovsky J et al (2013) Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum 65:3239–3247

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Oddis CV, Reed AM, Aggarwal R et al (2013) Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo-phase trial. Arthritis Rheum 65:314–324

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Papadopoulou C, Hong Y, Omoyinmi E et al (2019) Janus kinase 1/2 inhibition with baricitinib in the treatment of juvenile dermatomyositis. Brain 142(3):e8. https://doi.org/10.1093/brain/awz005

    Article  PubMed  PubMed Central  Google Scholar 

  30. Piper CJM, Wilkinson MGL, Deakin CT et al (2018) CD19+CD24hiCD38hi B cells are expanded in juvenile dermatomyositis and exhibit a pro-inflammatory phenotype after activation through toll-like receptor 7 and interferon-alpha. Front Immunol 9:1372. https://doi.org/10.3389/fimmu.2018.01372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Reed AM, Peterson E, Bilgic H et al (2012) Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course. Arthritis Rheum 64:4078–4086

    PubMed  PubMed Central  CAS  Google Scholar 

  32. Rice GI, Melki I, Fremond ML et al (2017) Assessment of type I interferon signaling in pediatric inflammatory disease. J Clin Immunol 37:123–132

    PubMed  CAS  Google Scholar 

  33. Rider LG, Aggarwal R, Pistorio A et al (2017) 2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol 69:911–923

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Rider LG, Werth VP, Huber AM et al (2011) Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis. Arthritis Care Res 63(Suppl 11):S118–S157 (Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF-36), Child Health Questionnaire (CHQ), physician global damage, Myositis Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-2 (FI-2), Myositis Activities Profile (MAP), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI))

    Google Scholar 

  35. Ringold S, Nigrovic PA, Feldman BM et al (2018) The childhood arthritis and rheumatology research alliance consensus treatment plans: Toward comparative effectiveness in the pediatric rheumatic diseases. Arthritis Rheumatol 70:669–678

    PubMed  Google Scholar 

  36. Rodero MP, Decalf J, Bondet V et al (2017) Detection of interferon alpha protein reveals differential levels and cellular sources in disease. J Exp Med 214:1547–1555

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Ruperto N, Pistorio A, Oliveira S et al (2016) Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: A randomised trial. Lancet 387:671–678

    PubMed  Google Scholar 

  38. Montealegre Sanchez GA, Reinhardt A, Ramsey S et al (2018) JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest 128:3041–3052

    Google Scholar 

  39. Shah M, Targoff IN, Rice MM et al (2013) Brief report: Ultraviolet radiation exposure is associated with clinical and autoantibody phenotypes in juvenile myositis. Arthritis Rheum 65:1934–1941

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Solomon DH, Bitton A, Katz JN et al (2014) Review: Treat to target in rheumatoid arthritis: Fact, fiction, or hypothesis? Arthritis Rheumatol 66:775–782

    PubMed  PubMed Central  Google Scholar 

  41. Tansley SL, Betteridge ZE, Simou S et al (2017) Anti-HMGCR autoantibodies in juvenile idiopathic inflammatory myopathies identify a rare but clinically important subset of patients. J Rheumatol 44:488–492

    PubMed  Google Scholar 

  42. Tansley SL, Simou S, Shaddick G et al (2017) Autoantibodies in juvenile-onset myositis: Their diagnostic value and associated clinical phenotype in a large UK cohort. J Autoimmun 84:55–64

    PubMed  PubMed Central  CAS  Google Scholar 

  43. Tenbrock K, Foell D, Minden K et al (2018) Handlungs- und Therapie-Protokolle in der Kinder-Rheumatologie. Arthritis Rheuma 38:368

    Google Scholar 

  44. Tiniakou E, Pinal-Fernandez I, Lloyd TE et al (2017) More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxf) 56:787–794

    CAS  Google Scholar 

  45. Yeker RM, Pinal-Fernandez I, Kishi T et al (2018) Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis. Ann Rheum Dis 77:714–719

    PubMed  PubMed Central  CAS  Google Scholar 

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  1. Klinik für Pädiatrische Rheumatologie und Immunologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude W30, 48149, Münster, Deutschland

    C. Hinze

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C. Hinze hat für die Teilnahme an Advisory Boards Honorare von Novartis und von Shire erhalten.

Für diesen Beitrag wurden von dem Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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H.-I. Huppertz, Bremen

K. Minden, Berlin

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Hinze, C. Juvenile Dermatomyositis – was gibt es Neues?. Z Rheumatol 78, 627–635 (2019). https://doi.org/10.1007/s00393-019-0643-6

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