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Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment

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Abstract

Background

Juvenile dermatomyositis (JDM) is a chronic autoimmune disease characteristic by inflammation of small vessels within the skin, muscle and vital organs. But the clinical features and treatment of JDM have not been fully clarified.

Data sources

Databases underwent through PubMed for articles about the clinical features, myositis-specific antibodies of JDM and its treatment, and we selected publications written in English which were relevant to the topic of this review.

Results

Clinical features and myositis-specific antibodies may predict the severity and prognosis of disease. Although the mortality rate has been lower with traditional treatments, such as corticosteroid, intravenous immunoglobulin, and disease-modifying anti-rheumatic drugs such as methotrexate, their usages are variable. Novel biological therapies seem to be effective for refractory JDM patients, but more clinical trials are necessary.

Conclusions

JDM is a sever disease of childhood. We need to better understand recent advances of JDM in the context of clinical features including skin manifestations, muscle weakness and organ damage, myositis-specific antibodies and their associated outcomes and the treatment of disease.

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References

  1. Meyer A, Meyer N, Schaeffer M, Gottenberg JE, Geny B, Sibilia J. Incidence and prevalence of inflammatory myopathies: a systematic review. Rheumatology (Oxford). 2015;54:50–63.

    CAS  Google Scholar 

  2. Shah M, Mamyrova G, Targoff IN, Huber AM, Malley JD, Rice MM, et al. The clinical phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine (Baltimore). 2013;92:25–41.

    CAS  Google Scholar 

  3. Ramanan AV, Feldman BM. Clinical features and outcomes of juvenile dermatomyositis and other childhood onset myositis syndromes. Rheum Dis Clin North Am. 2002;28:833–57.

    CAS  PubMed  Google Scholar 

  4. Guseinova D, Consolaro A, Trail L, Ferrari C, Pistorio A, Ruperto N, et al. Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis. Clin Exp Rheumatol. 2011;29:117–24.

    PubMed  Google Scholar 

  5. McCann LJ, Juggins AD, Maillard SM, Wedderburn LR, Davidson JE, Murray KJ, et al. The Juvenile Dermatomyositis National Registry and Repository (UK and Ireland) -clinical characteristics of children recruited within the first 5 years. Rheumatology (Oxford). 2006;45:1255–60.

    CAS  Google Scholar 

  6. Robinson AB, Hoeltzel MF, Wahezi DM, Becker ML, Kessler EA, Schmeling H, et al. Clinical characteristics of children with juvenile dermatomyositis: the Childhood Arthritis and Rheumatology Research Alliance Registry. Arthritis Care Res (Hoboken). 2014;66:404–10.

    Google Scholar 

  7. Pachman LM, Lipton R, Ramsey-Goldman R, Shamiyeh E, Abbott K, Mendez EP, et al. History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry. Arthritis Rheum. 2005;53:166–72.

    PubMed  Google Scholar 

  8. van Dijkhuizen EHP, De Iorio M, Wedderburn LR, Deakin CT. Clinical signs and symptoms in a joint model of four disease activity parameters in juvenile dermatomyositis: a prospective, longitudinal, multicenter cohort study. Arthritis Res Ther. 2018;20:180.

    PubMed  PubMed Central  Google Scholar 

  9. Huber AM, Mamyrova G, Lachenbruch PA, Lee JA, Katz JD, Targoff IN, et al. Early illness features associated with mortality in the juvenile idiopathic inflammatory myopathies. Arthritis Care Res (Hoboken). 2014;66:732–40.

    Google Scholar 

  10. Stringer E, Singh-Grewal D, Feldman BM. Predicting the course of juvenile dermatomyositis: significance of early clinical and laboratory features. Arthritis Rheum. 2008;58:3585–92.

    PubMed  Google Scholar 

  11. Rider LG, Katz JD, Jones OY. Developments in the classification and treatment of the juvenile idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2013;39:877–904.

    PubMed  Google Scholar 

  12. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344–7.

    CAS  PubMed  Google Scholar 

  13. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292:403–7.

    CAS  PubMed  Google Scholar 

  14. Lundberg IE, Tjarnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups. Arthritis Rheumatol. 2017;69:2271–82.

    PubMed  PubMed Central  Google Scholar 

  15. Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet. 2008;371:2201–12.

    PubMed  Google Scholar 

  16. Okong'o LO, Esser M, Wilmshurst J, Scott C. Characteristics and outcome of children with juvenile dermatomyositis in Cape Town: a cross-sectional study. Pediatr Rheumatol Online J. 2016;14:60.

    PubMed  PubMed Central  Google Scholar 

  17. Hoeltzel MF, Oberle EJ, Robinson AB, Agarwal A, Rider LG. The presentation, assessment, pathogenesis, and treatment of calcinosis in juvenile dermatomyositis. Curr Rheumatol Rep. 2014;16:467.

    PubMed  PubMed Central  Google Scholar 

  18. Balin SJ, Wetter DA, Andersen LK, Davis MD. Calcinosis cutis occurring in association with autoimmune connective tissue disease: the Mayo Clinic experience with 78 patients, 1996–2009. Arch Dermatol. 2012;148:455–62.

    CAS  PubMed  Google Scholar 

  19. Sato JO, Sallum AM, Ferriani VP, Marini R, Sacchetti SB, Okuda EM, et al. A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases. Clin Exp Rheumatol. 2009;27:1031–8.

    CAS  PubMed  Google Scholar 

  20. Efthimiou P, Kukar M, Kagen LJ. Images in rheumatology: Severe adult-onset calcinosis in a patient with a history of juvenile dermatomyositis. J Rheumatol. 2010;37:194.

    PubMed  Google Scholar 

  21. Sallum AM, Pivato FC, Doria-Filho U, Aikawa NE, Liphaus BL, Marie SK, et al. Risk factors associated with calcinosis of juvenile dermatomyositis. J Pediatr (Rio J). 2008;84:68–74.

    Google Scholar 

  22. Ravelli A, Trail L, Ferrari C, Ruperto N, Pistorio A, Pilkington C, et al. Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients. Arthritis Care Res (Hoboken). 2010;62:63–72.

    Google Scholar 

  23. Mamyrova G, Kleiner DE, James-Newton L, Shaham B, Miller FW, Rider LG. Late-onset gastrointestinal pain in juvenile dermatomyositis as a manifestation of ischemic ulceration from chronic endarteropathy. Arthritis Rheum. 2007;57:881–4.

    PubMed  PubMed Central  Google Scholar 

  24. Lowry CA, Pilkington CA. Juvenile dermatomyositis: extramuscular manifestations and their management. Curr Opin Rheumatol. 2009;21:575–80.

    CAS  PubMed  Google Scholar 

  25. Mitchell JP, Dennis GJ, Rider LG. Juvenile dermatomyositis presenting with anasarca: a possible indicator of severe disease activity. J Pediatr. 2001;138:942–5.

    CAS  PubMed  Google Scholar 

  26. Saygi S, Alehan F, Baskin E, Bayrakci US, Ulu EM, Ozbek N. Juvenile dermatomyositis presenting with anasarca. J Child Neurol. 2008;23:1353–6.

    PubMed  Google Scholar 

  27. Bertolazzi C, Cutolo M, Smith V, Gutierrez M. State of the art on nailfold capillaroscopy in dermatomyositis and polymyositis. Semin Arthritis Rheum. 2017;47:432–44.

    PubMed  Google Scholar 

  28. Gowdie PJ, Allen RC, Kornberg AJ, Akikusa JD. Clinical features and disease course of patients with juvenile dermatomyositis. Int J Rheum Dis. 2013;16:561–7.

    CAS  PubMed  Google Scholar 

  29. Spencer-Green G, Crowe WE, Levinson JE. Nailfold capillary abnormalities and clinical outcome in childhood dermatomyositis. Arthritis Rheum. 1982;25:954–8.

    CAS  PubMed  Google Scholar 

  30. Gitiaux C, De Antonio M, Aouizerate J, Gherardi RK, Guilbert T, Barnerias C, et al. Vasculopathy-related clinical and pathological features are associated with severe juvenile dermatomyositis. Rheumatology (Oxford). 2016;55:470–9.

    Google Scholar 

  31. Barth Z, Schwartz T, Flatø B, Aalokken TM, Koller A, Lund MB, et al. Association between nailfold capillary density and pulmonary and cardiac involvement in medium to longstanding juvenile dermatomyositis. Arthritis Care Res (Hoboken). 2019;71:492–7.

    CAS  Google Scholar 

  32. Schmeling H, Stephens S, Goia C, Manlhiot C, Schneider R, Luthra S, et al. Nailfold capillary density is importantly associated over time with muscle and skin disease activity in juvenile dermatomyositis. Rheumatology (Oxford). 2011;50:885–93.

    Google Scholar 

  33. Huemer C, Kitson H, Malleson PN, Sanderson S, Huemer M, Cabral DA, et al. Lipodystrophy in patients with juvenile dermatomyositis-evaluation of clinical and metabolic abnormalities. J Rheumatol. 2001;28:610–5.

    CAS  PubMed  Google Scholar 

  34. Bingham A, Mamyrova G, Rother KI, Oral E, Cochran E, Premkumar A, et al. Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity. Medicine (Baltimore). 2008;87:70–86.

    Google Scholar 

  35. Verma S, Singh S, Bhalla AK, Khullar M. Study of subcutaneous fat in children with juvenile dermatomyositis. Arthritis Rheum. 2006;55:564–8.

    PubMed  Google Scholar 

  36. Rider LG, Aggarwal R, Machado PM, Hogrel JY, Reed AM, Christopher-Stine L, et al. Update on outcome assessment in myositis. Nat Rev Rheumatol. 2018;14:303–18.

    PubMed  PubMed Central  Google Scholar 

  37. Huber AM, Feldman BM, Rennebohm RM, Hicks JE, Lindsley CB, Perez MD, et al. Validation and clinical significance of the Childhood Myositis Assessment Scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies. Arthritis Rheum. 2004;50:1595–603.

    PubMed  Google Scholar 

  38. Huber AM, Hicks JE, Lachenbruch PA, Perez MD, Zemel LS, Rennebohm RM, et al. Validation of the Childhood Health Assessment Questionnaire in the juvenile idiopathic myopathies: Juvenile Dermatomyositis Disease Activity Collaborative Study Group. J Rheumatol. 2001;28:1106–11.

    CAS  PubMed  Google Scholar 

  39. Rider LG, Koziol D, Giannini EH, Jain MS, Smith MR, Whitney-Mahoney K, et al. Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies. Arthritis Care Res (Hoboken). 2010;62:465–72.

    Google Scholar 

  40. Sato S, Uejima Y, Nanbu M, Suganuma E, Takano T, Tanaka R, et al. Clinical analysis and outcome of interstitial lung disease complicated with juvenile dermatomyositis and juvenile polymyositis. Mod Rheumatol. 2017;27:652–6.

    CAS  PubMed  Google Scholar 

  41. Sanner H, Aaløkken TM, Gran JT, Sjaastad I, Johansen B, Flatø B. Pulmonary outcome in juvenile dermatomyositis: a case-control study. Ann Rheum Dis. 2011;70:86–91.

    PubMed  Google Scholar 

  42. Tansley SL, Betteridge ZE, Gunawardena H, Jacques TS, Owens CM, Pilkington C, et al. Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study. Arthritis Res Ther. 2014;16:R138.

    PubMed  PubMed Central  Google Scholar 

  43. Pouessel G, Deschildre A, Le Bourgeois M, Cuisset JM, Catteau B, Karila C, et al. The lung is involved in juvenile dermatomyositis. Pediatr Pulmonol. 2013;48:1016–25.

    PubMed  Google Scholar 

  44. Bellutti Enders F, Bader-Meunier B, Baildam E, Constantin T, Dolezalova P, Feldman BM, et al. Consensus-based recommendations for the management of juvenile dermatomyositis. Ann Rheum Dis. 2017;76:329–40.

    PubMed  Google Scholar 

  45. Jayakumar D, Zhang R, Wasserman A, Ash J. Cardiac manifestations in idiopathic inflammatory myopathies: an overview. Cardiol Rev. 2019;27:131–7.

    PubMed  Google Scholar 

  46. Schwartz T, Sanner H, Gjesdal O, Flato B, Sjaastad I. In juvenile dermatomyositis, cardiac systolic dysfunction is present after long-term follow-up and is predicted by sustained early skin activity. Ann Rheum Dis. 2014;73:1805–10.

    PubMed  Google Scholar 

  47. Schwartz T, Sanner H, Husebye T, Flato B, Sjaastad I. Cardiac dysfunction in juvenile dermatomyositis: a case-control study. Ann Rheum Dis. 2011;70:766–71.

    PubMed  Google Scholar 

  48. Barth Z, Nomeland-Witczak B, Schwartz T, Gjesdal K, Flato B, Koller A, et al. In juvenile dermatomyositis, heart rate variability is reduced, and associated with both cardiac dysfunction and markers of inflammation: a cross-sectional study median 13.5 years after symptom onset. Rheumatology. 2016;55:535–43.

  49. Gadiparthi C, Hans A, Potts K, Ismail MK. Gastrointestinal and hepatic disease in the inflammatory myopathies. Rheum Dis Clin North Am. 2018;44:113–29.

    PubMed  Google Scholar 

  50. Ebert EC. Review article: the gastrointestinal complications of myositis. Aliment Pharmacol Ther. 2010;31:359–65.

    CAS  PubMed  Google Scholar 

  51. Tse S, Lubelsky S, Gordon M, Al Mayouf SM, Babyn PS, Laxer RM, et al. The arthritis of inflammatory childhood myositis syndromes. J Rheumatol. 2001;28:192–7.

    CAS  PubMed  Google Scholar 

  52. Elst EF, Kamphuis SS, Prakken BJ, Wulffraat NM, van der Net J, Peters AC, et al. Case report: severe central nervous system involvement in juvenile dermatomyositis. J Rheumatol. 2003;30:2059–63.

    PubMed  Google Scholar 

  53. Tansley S, Wedderburn LR. Comparing and contrasting clinical and serological features of juvenile and adult-onset myositis. Curr Opin Rheumatol. 2015;27:601–7.

    CAS  PubMed  Google Scholar 

  54. Tansley SL, Simou S, Shaddick G, Betteridge ZE, Almeida B, Gunawardena H, et al. Autoantibodies in juvenile-onset myositis: their diagnostic value and associated clinical phenotype in a large UK cohort. J Autoimmun. 2017;84:55–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Rider LG, Nistala K. The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes. J Intern Med. 2016;280:24–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Wedderburn LR, McHugh NJ, Chinoy H, Cooper RG, Salway F, Ollier WE, et al. HLA class II haplotype and autoantibody associations in children with juvenile dermatomyositis and juvenile dermatomyositis-scleroderma overlap. Rheumatology (Oxford). 2007;46:1786–91.

    CAS  Google Scholar 

  57. Rider LG, Shah M, Mamyrova G, Huber AM, Rice MM, Targoff IN, et al. The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine (Baltimore). 2013;92:223–43.

    CAS  Google Scholar 

  58. Mahler M, Raijmakers R. Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmun Rev. 2007;6:432–7.

    CAS  PubMed  Google Scholar 

  59. 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.

    CAS  PubMed  Google Scholar 

  60. Lega J-C, Fabien N, Reynaud Q, Durieu I, Durupt S, Dutertre M, et al. The clinical phenotype associated with myositis-specific and associated autoantibodies: a meta-analysis revisiting the so-called antisynthetase syndrome. Autoimmun Rev. 2014;13:883–91.

    CAS  PubMed  Google Scholar 

  61. Coppo P, Clauvel JP, Bengoufa D, Oksenhendler E, Lacroix C, Lassoued K. Inflammatory myositis associated with anti-U1-small nuclear ribonucleoprotein antibodies: a subset of myositis associated with a favourable outcome. Rheumatology (Oxford). 2002;41:1040–6.

    CAS  Google Scholar 

  62. Rigolet A, Musset L, Dubourg O, Maisonobe T, Grenier P, Charuel JL, et al. Inflammatory myopathies with anti-Ku antibodies. Medicine (Baltimore). 2012;91:95–102.

    CAS  Google Scholar 

  63. Marie I, Hatron PY, Dominique S, Cherin P, Mouthon L, Menard JF, et al. Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Semin Arthritis Rheum. 2012;41:890–9.

    CAS  PubMed  Google Scholar 

  64. Váncsa A, Csípő I, Németh J, Dévényi K, Gergely L, Dankó K. Characteristics of interstitial lung disease in SS-A positive/Jo-1 positive inflammatory myopathy patients. Rheumatol Int. 2009;29:989–94.

    PubMed  Google Scholar 

  65. Prestridge A, Morgan G, Ferguson L, Huang CC, Pachman LM. Pulmonary function tests in idiopathic inflammatory myopathy: association with clinical parameters in children. Arthritis Care Res (Hoboken). 2013;65:1424–31.

    CAS  Google Scholar 

  66. Li L, Wang H, Wang Q, Wu C, Liu C, Zhang Y, et al. Myositis-specific autoantibodies in dermatomyositis/polymyositis with interstitial lung disease. J Neurol Sci. 2019;397:123–8.

    CAS  PubMed  Google Scholar 

  67. Sabbagh S, Pinal-Fernandez I, Kishi T, Targoff IN, Miller FW, Rider LG, et al. Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis. Ann Rheum Dis. 2019;78:988–95.

    PubMed  Google Scholar 

  68. Iwata N, Nakaseko H, Kohagura T, Yasuoka R, Abe N, Kawabe S, et al. Clinical subsets of juvenile dermatomyositis classified by myositis-specific autoantibodies: experience at a single center in Japan. Mod Rheumatol. 2019;29:802–7.

    PubMed  Google Scholar 

  69. Gunawardena H, Wedderburn LR, North J, Betteridge Z, Dunphy J, Chinoy H, et al. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology (Oxford). 2007;47:324–8.

    Google Scholar 

  70. Fiorentino DF, Kuo K, Chung L, Zaba L, Li S, Casciola-Rosen L. Distinctive cutaneous and systemic features associated with antitranscriptional intermediary factor-1γ antibodies in adults with dermatomyositis. J Am Acad Dermatol. 2015;72:449–55.

    PubMed  PubMed Central  Google Scholar 

  71. Gunawardena H, Wedderburn LR, Chinoy H, Betteridge ZE, North J, Ollier WE, et al. Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis. Arthritis Rheum. 2009;60:1807–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Tansley SL, Betteridge ZE, Shaddick G, Gunawardena H, Arnold K, Wedderburn LR, et al. Calcinosis in juvenile dermatomyositis is influenced by both anti-NXP2 autoantibody status and age at disease onset. Rheumatology (Oxford). 2014;53:2204–8.

    Google Scholar 

  73. Kobayashi N, Takezaki S, Kobayashi I, Iwata N, Mori M, Nagai K, et al. Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis. Rheumatology (Oxford). 2015;54:784–91.

    CAS  Google Scholar 

  74. Kobayashi I, Okura Y, Yamada M, Kawamura N, Kuwana M, Ariga T. Anti-melanoma differentiation-associated gene 5 antibody is a diagnostic and predictive marker for interstitial lung diseases associated with juvenile dermatomyositis. J Pediatr. 2011;158:675–7.

    CAS  PubMed  Google Scholar 

  75. Hall JC, Casciola-Rosen L, Samedy LA, Werner J, Owoyemi K, Danoff SK, et al. Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res (Hoboken). 2013;65:1307–15.

    CAS  Google Scholar 

  76. Muro Y, Sugiura K, Akiyama M. Cutaneous manifestations in dermatomyositis: key clinical and serological features—a comprehensive review. Clin Rev Allergy Immunol. 2016;51:293–302.

    PubMed  Google Scholar 

  77. Ghirardello A, Zampieri S, Iaccarino L, Tarricone E, Bendo R, Gambari PF, et al. Anti-Mi-2 antibodies. Autoimmunity. 2005;38:79–83.

    CAS  PubMed  Google Scholar 

  78. Aggarwal R, Bandos A, Reed AM, Ascherman DP, Barohn RJ, Feldman BM, et al. Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis. Arthritis Rheumatol. 2014;66:740–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Petri MH, Satoh M, Martin-Marquez BT, Vargas-Ramirez R, Jara LJ, Saavedra MA, et al. Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara. Arthritis Res Ther. 2013;15:R48.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Betteridge ZE, Gunawardena H, McHugh NJ. Novel autoantibodies and clinical phenotypes in adult and juvenile myositis. Arthritis Res Ther. 2011;13:209.

    PubMed  PubMed Central  Google Scholar 

  81. Afzali AM, Ruck T, Wiendl H, Meuth SG. Animal models in idiopathic inflammatory myopathies: how to overcome a translational roadblock? Autoimmun Rev. 2017;16:478–94.

    PubMed  Google Scholar 

  82. Bergua C, Chiavelli H, Allenbach Y, Arouche-Delaperche L, Arnoult C, Bourdenet G, et al. In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. Ann Rheum Dis. 2019;78:131–9.

    CAS  PubMed  Google Scholar 

  83. Allenbach Y, Mammen AL, Benveniste O, Stenzel W, Immune-Mediated Necrotizing Myopathies Working Group. 224th ENMC International Workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14–16 October 2016. Neuromuscul Disord. 2018;28:87–99.

    Google Scholar 

  84. Watanabe Y, Uruha A, Suzuki S, Nakahara J, Hamanaka K, Takayama K, et al. Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry. 2016;87:1038–44.

    PubMed  Google Scholar 

  85. Wang L, Liu L, Hao H, Gao F, Liu X, Wang Z, et al. Myopathy with anti-signal recognition particle antibodies: clinical and histopathological features in Chinese patients. Neuromuscul Disord. 2014;24:335–41.

    CAS  PubMed  Google Scholar 

  86. Rouster-Stevens KA, Pachman LM. Autoantibody to signal recognition particle in African American girls with juvenile polymyositis. J Rheumatol. 2008;35:927–9.

    CAS  PubMed  Google Scholar 

  87. Hengstman GJ, ter Laak HJ, Vree Egberts WT, Lundberg IE, Moutsopoulos HM, Vencovsky J, et al. Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann Rheum Dis. 2006;65:1635–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63:713–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Tansley SL, Betteridge ZE, Simou S, Jacques TS, Pilkington C, Wood M, et al. Anti-HMGCR autoantibodies in juvenile idiopathic inflammatory myopathies identify a rare but clinically important subset of patients. J Rheumatol. 2017;44:488–92.

    PubMed  Google Scholar 

  90. Kishi T, Rider LG, Pak K, Barillas-Arias L, Henrickson M, McCarthy PL, et al. 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 (Hoboken). 2017;69:1088–94.

    CAS  Google Scholar 

  91. Tiniakou E, Pinal-Fernandez I, Lloyd TE, Albayda J, Paik J, Werner JL, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017;56:787–94.

    CAS  Google Scholar 

  92. Stringer E, Bohnsack J, Bowyer SL, Griffin TA, Huber AM, Lang B, et al. Treatment approaches to juvenile dermatomyositis (JDM) across North America: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey. J Rheumatol. 2010;37:1953–61.

    CAS  PubMed  Google Scholar 

  93. Ruperto N, Pistorio A, Oliveira S, Zulian F, Cuttica R, Ravelli A, et al. Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial. Lancet. 2016;387:671–8.

    PubMed  Google Scholar 

  94. Huber AM, Giannini EH, Bowyer SL, Kim S, Lang B, Lindsley CB, et al. Protocols for the initial treatment of moderately severe juvenile dermatomyositis: results of a children's arthritis and rheumatology research alliance consensus conference. Arthritis Care Res (Hoboken). 2010;62:219–25.

    CAS  Google Scholar 

  95. Rouster-Stevens KA, Gursahaney A, Ngai KL, Daru JA, Pachman LM. Pharmacokinetic study of oral prednisolone compared with intravenous methylprednisolone in patients with juvenile dermatomyositis. Arthritis Rheum. 2008;59:222–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Huber AM, Robinson AB, Reed AM, Abramson L, Bout-Tabaku S, Carrasco R, et al. 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 (Hoboken). 2012;64:546–53.

    PubMed  PubMed Central  Google Scholar 

  97. Giancane G, Lavarello C, Pistorio A, Oliveira SK, Zulian F, Cuttica R, et al. The PRINTO evidence-based proposal for glucocorticoids tapering/discontinuation in new onset juvenile dermatomyositis patients. Pediatr Rheumatol Online J. 2019;17:24.

    PubMed  PubMed Central  Google Scholar 

  98. Ramanan AV, Campbell-Webster N, Ota S, Parker S, Tran D, Tyrrell PN, et al. The effectiveness of treating juvenile dermatomyositis with methotrexate and aggressively tapered corticosteroids. Arthritis Rheum. 2005;52:3570–8.

    CAS  PubMed  Google Scholar 

  99. Hinze CH, Speth F, Oommen PT, Haas JP. Current management of juvenile dermatomyositis in Germany and Austria: an online survey of pediatric rheumatologists and pediatric neurologists. Pediatr Rheumatol Online J. 2018;16:38.

    PubMed  PubMed Central  Google Scholar 

  100. Huber AM, Kim S, Reed AM, Carrasco R, Feldman BM, Hong SD, et al. Childhood arthritis and rheumatology research alliance consensus clinical treatment plans for juvenile dermatomyositis with persistent skin rash. J Rheumatol. 2017;44:110–6.

    CAS  PubMed  Google Scholar 

  101. Kim S, Kahn P, Robinson AB, Lang B, Shulman A, Oberle EJ, et al. Childhood Arthritis and Rheumatology Research Alliance consensus clinical treatment plans for juvenile dermatomyositis with skin predominant disease. Pediatr Rheumatol Online J. 2017;15:1.

    PubMed  PubMed Central  Google Scholar 

  102. Jacobs JC. Methotrexate and azathioprine treatment of childhood dermatomyositis. Pediatrics. 1977;59:212–8.

    CAS  PubMed  Google Scholar 

  103. Rouster-Stevens KA, Morgan GA, Wang D, Pachman LM. Mycophenolate mofetil: a possible therapeutic agent for children with juvenile dermatomyositis. Arthritis Care Res (Hoboken). 2010;62:1446–511.

    Google Scholar 

  104. Dagher R, Desjonquères M, Duquesne A, Quartier P, Bader-Meunier B, Fischbach M, et al. Mycophenolate mofetil in juvenile dermatomyositis: a case series. Rheumatol Int. 2012;32:711–6.

    PubMed  Google Scholar 

  105. Riley P, Maillard SM, Wedderburn LR, Woo P, Murray KJ, Pilkington CA. Intravenous cyclophosphamide pulse therapy in juvenile dermatomyositis: a review of efficacy and safety. Rheumatology (Oxford). 2004;43:491–6.

    CAS  Google Scholar 

  106. Deakin CT, Campanilho-Marques R, Simou S, Moraitis E, Wedderburn LR, Pullenayegum E, et al. Efficacy and safety of cyclophosphamide treatment in severe juvenile dermatomyositis shown by marginal structural modeling. Arthritis Rheumatol. 2018;70:785–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Al-Mayouf SM, Laxer RM, Schneider R, Silverman ED, Feldman BM. Intravenous immunoglobulin therapy for juvenile dermatomyositis: efficacy and safety. J Rheumatol. 2000;27:2498–503.

    CAS  PubMed  Google Scholar 

  108. Lam CG, Manlhiot C, Pullenayegum EM, Feldman BM. Efficacy of intravenous Ig therapy in juvenile dermatomyositis. Ann Rheum Dis. 2011;70:2089–94.

    CAS  PubMed  Google Scholar 

  109. Bamrungsawad N, Chaiyakunapruk N, Upakdee N, Pratoomsoot C, Sruamsiri R, Dilokthornsakul P. Cost-utility analysis of intravenous immunoglobulin for the treatment of steroid-refractory dermatomyositis in Thailand. Pharmacoeconomics. 2015;33:521–31.

    PubMed  Google Scholar 

  110. Chiu YE, Co DO. Juvenile dermatomyositis: immunopathogenesis, role of myositis-specific autoantibodies, and review of rituximab use. Pediatr Dermatol. 2011;28:357–67.

    PubMed  Google Scholar 

  111. Bader-Meunier B, Decaluwe H, Barnerias C, Gherardi R, Quartier P, Faye A, et al. Safety and efficacy of rituximab in severe juvenile dermatomyositis: results from 9 patients from the French Autoimmunity and Rituximab registry. J Rheumatol. 2011;38:1436–40.

    CAS  PubMed  Google Scholar 

  112. Mahler EA, Blom M, Voermans NC, van Engelen BG, van Riel PL, Vonk MC. Rituximab treatment in patients with refractory inflammatory myopathies. Rheumatology (Oxford). 2011;50:2206–13.

    CAS  Google Scholar 

  113. Rios-Fernandez R, Callejas-Rubio JL, Sanchez-Cano D, Saez-Moreno JA, Ortego-Centeno N. Rituximab in the treatment of dermatomyositis and other inflammatory myopathies: a report of 4 cases and review of the literature. Clin Exp Rheumatol. 2009;27:1009–166.

    CAS  PubMed  Google Scholar 

  114. Valiyil R, Casciola-Rosen L, Hong G, Mammen A, Christopher-Stine L. Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: a case series. Arthritis Care Res (Hoboken). 2010;62:1328–34.

    CAS  Google Scholar 

  115. Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65:314–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Aggarwal R, Loganathan P, Koontz D, Qi Z, Reed AM, Oddis CV. Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab. Rheumatology (Oxford). 2017;56:247–54.

    CAS  Google Scholar 

  117. Riley P, McCann LJ, Maillard SM, Woo P, Murray KJ, Pilkington CA. Effectiveness of infliximab in the treatment of refractory juvenile dermatomyositis with calcinosis. Rheumatology (Oxford). 2008;47:877–80.

    CAS  Google Scholar 

  118. Wang CR. Successful treatment of refractory juvenile dermatomyositis with adalimumab. J Clin Rheumatol. 2017;23:174–5.

    CAS  PubMed  Google Scholar 

  119. Martin N, Krol P, Smith S, Murray K, Pilkington CA, Davidson JE, et al. A national registry for juvenile dermatomyositis and other paediatric idiopathic inflammatory myopathies: 10 years' experience; the Juvenile Dermatomyositis National (UK and Ireland) Cohort Biomarker Study and repository for idiopathic inflammatory myopathies. Rheumatology (Oxford). 2011;50:137–45.

    Google Scholar 

  120. Yamada-Kanazawa S, Kajihara I, Kobayashi A, Watanabe C, Ihn H. Infliximab improved the refractory cutaneous involvement in a patient with dermatomyositis. Dermatol Ther. 2019;32:e12859.

    PubMed  Google Scholar 

  121. Schiffenbauer A, Garg M, Castro C, Pokrovnichka A, Joe G, Shrader J, et al. A randomized, double-blind, placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis. Semin Arthritis Rheum. 2018;47:858–64.

    CAS  PubMed  Google Scholar 

  122. Campanilho-Marques R, Deakin C, Simou S, Wedderburn LR, Pilkington C. OP0221 efficacy and safety of tumour necrosis factor-alpha antagonists in a large cohort of juvenile dermatomyositis patients. Ann Rheum Dis. 2016;75:140.

    Google Scholar 

  123. Iannone F, Scioscia C, Falappone PCF, Covelli M, Lapadula G. Use of etanercept in the treatment of dermatomyositis: a case series. J Rheumatol. 2006;33:1802–4.

    CAS  PubMed  Google Scholar 

  124. Rouster-Stevens KA, Ferguson L, Morgan G, Huang CC, Pachman LM. Pilot study of etanercept in patients with refractory juvenile dermatomyositis. Arthritis Care Res (Hoboken). 2014;66:783–7.

    CAS  Google Scholar 

  125. Arabshahi B, Silverman RA, Jones OY, Rider LG. Abatacept and sodium thiosulfate for treatment of recalcitrant juvenile dermatomyositis complicated by ulceration and calcinosis. J Pediatr. 2012;160:520–2.

    PubMed  PubMed Central  Google Scholar 

  126. Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, Tawil R, et al. Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis. Ann Neurol. 2005;57:664–78.

    CAS  PubMed  Google Scholar 

  127. Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, et al. An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Mol Med. 2007;13:59–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Walsh RJ, Kong SW, Yao Y, Jallal B, Kiener PA, Pinkus JL, et al. Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum. 2007;56:3784–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Niewold TB, Kariuki SN, Morgan GA, Shrestha S, Pachman LM. Elevated serum interferon-alpha activity in juvenile dermatomyositis: associations with disease activity at diagnosis and after thirty-six months of therapy. Arthritis Rheum. 2009;60:1815–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Salajegheh M, Kong SW, Pinkus JL, Walsh RJ, Liao A, Nazareno R, et al. Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy. Ann Neurol. 2010;67:53–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Cappelletti C, Baggi F, Zolezzi F, Biancolini D, Beretta O, Severa M, et al. Type I interferon and Toll-like receptor expression characterizes inflammatory myopathies. Neurology. 2011;76:2079–88.

    CAS  PubMed  Google Scholar 

  132. Suárez-Calvet X, Gallardo E, Nogales-Gadea G, Querol L, Navas M, Díaz-Manera J, et al. Altered RIG-I/DDX58-mediated innate immunity in dermatomyositis. J Pathol. 2014;233:258–68.

    PubMed  Google Scholar 

  133. Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, et al. Interleukin-6 and type I interferon–regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum. 2009;60:3436–46.

    CAS  PubMed  Google Scholar 

  134. Moneta GM, Pires Marafon D, Marasco E, Rosina S, Verardo M, Fiorillo C, et al. Muscle expression of type I and type II interferons is increased in juvenile dermatomyositis and related to clinical and histologic features. Arthritis Rheumatol. 2019;71:1011–21.

    CAS  PubMed  Google Scholar 

  135. Ladislau L, Suarez-Calvet X, Toquet S, Landon-Cardinal O, Amelin D, Depp M, et al. JAK inhibitor improves type I interferon induced damage: proof of concept in dermatomyositis. Brain. 2018;141:1609–21.

    PubMed  Google Scholar 

  136. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Papadopoulou C, Wedderburn LR. Treatment of juvenile dermatomyositis: an update. Pediatr Drugs. 2017;19:423–34.

    Google Scholar 

  138. Kurtzman DJ, Wright NA, Lin J, Femia AN, Merola JF, Patel M, et al. Tofacitinib citrate for refractory cutaneous dermatomyositis: an alternative treatment. JAMA Dermatol. 2016;152:944–5.

    PubMed  Google Scholar 

  139. Hornung T, Janzen V, Heidgen FJ, Wolf D, Bieber T, Wenzel J. Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med. 2014;371:2537–8.

    PubMed  Google Scholar 

  140. Moghadam-Kia S, Charlton D, Aggarwal R, Oddis CV. Management of refractory cutaneous dermatomyositis: potential role of Janus kinase inhibition with tofacitinib. Rheumatology (Oxford). 2019;58:1011–5.

    Google Scholar 

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Wu, JQ., Lu, MP. & Reed, A.M. Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment. World J Pediatr 16, 31–43 (2020). https://doi.org/10.1007/s12519-019-00313-8

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