CLASSIFICATION AND TREATMENT OF THE JUVENILE IDIOPATHIC INFLAMMATORY MYOPATHIES

https://doi.org/10.1016/S0889-857X(05)70350-1Get rights and content

The idiopathic inflammatory myopathies (IIMs) of childhood are a rare group of disorders characterized by chronic skeletal muscle inflammation of unknown cause, with onset at less than 18 years of age. The first pediatric case of dermatomyositis was reported by Potain in 1875, 240 and the early history of adult and juvenile dermatomyositis was thoroughly reviewed by Steiner in 1903.295 Research in this century has concentrated on the epidemiology, etiology, pathogenesis, and clinical characteristics of juvenile dermatomyositis (JDM), the most common of the juvenile IIMs. This article highlights other aspects of the juvenile IIMs: first, the classification of juvenile myositis and the placement of JDM into a broader context of illnesses that share idiopathic chronic muscle inflammation and often meet the same clinical diagnostic criteria 26 and second, the clinical management of these disorders.

Section snippets

CLASSIFICATION OF THE JUVENILE IDIOPATHIC INFLAMMATORY MYOPATHIES

Clinical and histopathologic features have been useful in defining different groups of myositis patients that share similar disease courses, responses to therapy, and prognosis. A clinicopathologic classification of myositis subsets has long been recognized in adults with IIMs. * Recent studies suggest that children with myositis share similar clinical characteristics, histopathologic features and disease courses as adults within these distinct subgroups,

TREATMENT APPROACHES FOR JUVENILE DERMATOMYOSITIS AND JUVENILE POLYMYOSITIS

The published experiences with treatment of juvenile IIMs, in large part focused on JDM, are few, and our ability to draw conclusions is limited. The rarity of these diseases has resulted in a lack of randomized, controlled studies; thus, conclusions regarding treatment consist of an accumulation of possibly biased, open-label observations. Treatment reports are usually drawn from the experience of a single referral center and are often retrospective. With the small number of patients, studies

AGENTS FOR SEVERE OR LIFE-THREATENING DISEASE

Successful experience with daily oral cyclophosphamide has been reported in four JDM patients whose disease was refractory to steroids and methotrexate; all improved with a daily regimen of 50 to 75 mg/m 2, with remission induced in three. Hemorrhagic cystitis and herpes zoster infections required discontinuation in two patients.209 Reports of pulse intravenous cyclophosphamide and chlorambucil have been limited to adult IIM patients. Results with pulse cyclophosphamide in treating adult

EXTRASKELETAL MUSCLE DISEASE: CUTANEOUS DISEASE, CALCINOSIS, AND OSTEOPOROSIS

A thorough review of the therapy of extramuscular disease, including cardiopulmonary disease, gastrointestinal involvement, and arthritis, has recently been published 3; most experience in these areas has been derived from adults. For this reason, only the treatment of cutaneous disease, new approaches in treating calcinosis, and treatment of osteoporosis will be addressed.

Cutaneous disease is often neglected in the treatment of JDM. Although the histopathology of skin lesions may resemble that

PERSONAL VIEWPOINT ON TREATMENT OF JUVENILE DERMATOMYOSITIS

It is clear from published data that there are many different approaches to treat JDM. Although certain general therapeutic approaches for JDM have been suggested (Table 7), therapy in each patient must be individualized, taking into account disease severity, prognostic risk factors, and risks for and history of adverse events from medications.

Currently available data suggest that morbidity from juvenile and adult IIM remains high, 47, 73, 314 resulting from delay of treatment of disease, 30,

CONCLUSION

Although JDM is the most common of the juvenile IIMs, a number of other distinct clinicopathologic entities, serologic subsets, and environmentally triggered myositis syndromes are being recognized in children. These subsets seem to parallel their counterparts in adults in defining relatively homogeneous groups of patients sharing similar clinical features, responses to therapy, and prognoses. Additional serologic and environmentally associated myositis subsets are likely to be recognized,

ACKNOWLEDGMENTS

We thank Elizabeth Adams, MD, and Karyl Barron, MD, for critical reading of the manuscript, Ira Targoff, MD, for his immunologic expertise, Paul Plotz, MD, and John Klippel, MD, of NIAMS for support of our research studies on the natural history and disease activity of juvenile myositis, and the patients and physicians who have participated in the Childhood Myositis Heterogeneity Study for helping to better define the classification of the juvenile idiopathic inflammatory myopathies.

References (330)

  • J.A. Cotterill et al.

    Dermatomyositis after immunisation

    Lancet

    (1978)
  • J.M. Crennan et al.

    Echovirus polymyositis in patients with hypogammaglobulinemia: Failure of high–dose intravenous gammaglobulin therapy and review of the literature

    Am J Med

    (1986)
  • A.N. Crowson et al.

    The role of microvascular injury in the pathogenesis of cutaneous lesions of dermatomyositis

    Hum Pathol

    (1996)
  • P. Dantzig

    Juvenile dermatomyositis treated with cyclosporine

    J Am Acad Dermatol

    (1990)
  • P.C. Dau et al.

    Plasmapheresis in childhood dermatomyositis

    J Pediatr

    (1981)
  • W. Ehrengut

    Dermatomyositis and vaccination

    Lancet

    (1978)
  • G.L. Ellis et al.

    Focal myositis of the perioral musculature

    Oral Surg

    (1979)
  • L.R. Espinoza et al.

    Characteristics and pathogenesis of myositis in human immunodeficiency virus infection: Distinction from azidothymidine-induced myopathy

    Rheum Dis Clin North Am

    (1991)
  • T.H. Finkel et al.

    Chronic parvovirus B19 infection and systemic necrotising vasculitis: Opportunistic infection or aetiological agent?

    Lancet

    (1994)
  • C. Gama et al.

    Myositis in Kawasaki disease

    Pediatr Neurol

    (1990)
  • M. Abinun et al.

    Failure of first-line therapy with intravenous immunoglobulin in a child with scleromyositis

    Br J Rheumatol

    (1996)
  • B.L. Agrawal et al.

    Eosinophilic myositis: An unusual cause of pseudotumor and eosinophilia

    JAMA

    (1981)
  • M. Al-Janadi et al.

    Cyclophosphamide treatment of interstitial pulmonary fibrosis in polymyositis/dermatomyositis

    J Rheumatol

    (1989)
  • J.N. Alpert et al.

    Acute polymyositis caused by sarcoidosis: Report of a case and review of the literature

    Mt Sinai J Med

    (1979)
  • American College of Rheumatology Taskforce on Osteoporosis Guidelines

    Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis

    Arthritis Rheum

    (1996)
  • B.A. Anderson et al.

    Polymyositis in chronic graft vs host disease: A case report

    Arch Neurol

    (1982)
  • S. Ando et al.

    [Successful combination therapy of cyclosporine and steroids in two cases with interstitial pneumonitis associated with polymyositis]

    Ryumachi

    (1995)
  • K. Arahata et al.

    Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells

    Ann Neurol

    (1984)
  • K. Arahata et al.

    Monoclonal antibody analysis of mononuclear cells in myopathies. IV: Cell-mediated cytotoxicity and muscle fiber necrosis

    Ann Neurol

    (1988)
  • S. Arase et al.

    Eosinophilic polymyositis induced by tranilast

    J Dermatol

    (1990)
  • B.Q. Banker et al.

    Dermatomyositis (systemic angiopathy) of childhood

    Medicine

    (1966)
  • K.S. Barron et al.

    Intravenous immunoglobulin therapy: Magic or black magic

    J Rheumatol

    (1992)
  • M. Basta et al.

    High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments

    J Clin Invest

    (1994)
  • J. Benbassat et al.

    Epidemiology of polymyositis-dermatomyositis in Israel, 1960–1976

    Isr J Med Sci

    (1980)
  • M.D. Benson et al.

    Azathioprine therapy in polymyositis

    Arch Intern Med

    (1973)
  • N. Birdi et al.

    Localized scleroderma progressing to systemic disease

    Arthritis Rheum

    (1993)
  • B. Bittar et al.

    Early development of Hodgkin's lymphoma in association with the use of methotrexate for the treatment of dermatomyositis

    Ann Rheum Dis

    (1995)
  • M. Blaszczyk et al.

    Childhood scleromyositis: An overlap syndrome associated with polymyositis-Scl antibody

    Pediatr Dermatol

    (1991)
  • B.J. Bloom et al.

    Worsening of the rash of juvenile dermatomyositis with hydroxychloroquine therapy

    J Rheumatol

    (1994)
  • C. Bodemer et al.

    Efficacy of intravenous immunoglobulins in sclerodermatomyositis

    Br J Dermatol

    (1990)
  • A. Bohan et al.

    Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis

    Medicine

    (1977)
  • K.E. Bove et al.

    Infantile myositis with leukoencephalopathy

    Pediatr Pathol

    (1992)
  • I.M. Braverman

    Connective tissue (rheumatic) diseases

  • D.A. Breems et al.

    [Intravenously administered immunoglobulin first-choice remedy in autoimmune diseases?]

    Ned Tijdschr Geneeskd

    (1993)
  • J.S. Bresee et al.

    Hepatitis C virus infection associated with administration of intravenous immune globulin: A cohort study

    JAMA

    (1996)
  • BrewerE.J. et al.

    Plasma exchange therapy of a childhood onset dermatomyositis patient

    Arthritis Rheum

    (1980)
  • C.L. Bullen et al.

    Chronic orbital myositis

    Arch Ophthalmol

    (1982)
  • T.W. Bunch

    Prednisone and azathioprine for polymyositis: Long-term follow-up

    Arthritis Rheum

    (1981)
  • T.W. Bunch et al.

    Azathioprine with prednisone for polymyositis: A controlled, clinical trial

    Ann Intern Med

    (1980)
  • G. Cambridge et al.

    Juvenile dermatomyositis: Serial studies of circulating autoantibodies to a 56kD nuclear protein

    Clin Exp Rheumatol

    (1994)
  • Cited by (131)

    • Medications received by patients with juvenile dermatomyositis

      2018, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      Since high doses of daily oral prednisone of longer duration reportedly have led to better functional outcomes and less frequent calcinosis [5], patients with JDM have been treated primarily with high doses of oral prednisone. Based on open-label and retrospective studies, methotrexate (MTX), intravenous pulse methylprednisolone (IVMP), intravenous immunoglobulin (IVIG), cyclosporine and cyclophosphamide were later introduced to decrease the exposure to daily oral prednisone, as well as the duration of active disease [6–10]. In recent years, additional therapeutic options for treatment-refractory patients that were often supported by open-label trials and retrospective case series have included mycophenolate mofetil (MMF), tacrolimus, anti-TNF therapy, and rituximab, among others [3,11–13].

    • Critical review of the role of intravenous immunoglobulins in idiopathic inflammatory myopathies

      2017, Seminars in Arthritis and Rheumatism
      Citation Excerpt :

      This study found that despite greater initial disease activity, subjects in the IVIg group maintained similar or even lower disease activity than controls, from 30 days to 4 years after diagnosis, particularly in the steroid-resistant subjects, suggesting a beneficial effect of early IVIg in controlling short- and long-term disease activity in severe or refractory JDM. Several other uncontrolled studies have reported improvement in steroid-resistant, steroid-dependent or with severe myopathic involvement in 63–86% of juvenile IIM subjects treated with monthly IVIg of varying duration (Table 5) [47–49]. However, relapse was reported in 14–67% of initially responsive subjects when IVIg was discontinued [47,48,50].

    • Pediatric Systemic Lupus Erythematosus, Juvenile Dermatomyositis, Scleroderma, and Vasculitis

      2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth Edition
    View all citing articles on Scopus

    Address reprint requests to Lisa G. Rider, MD, Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Building 29B, Room 2G11, HFM-561, 8800 Rockville Pike, Bethesda, MD 20892

    This work was supported by the intramural programs of CBER, FDA and NIAMS, NIH. The opinions expressed herein are the authors' and do not necessarily represent the positions of the US Food and Drug Administration or the Center for Biologics Evaluation and Research.

    *

    From the Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland

    View full text