Juvenile dermatomyositis (JDM) causes symmetric, proximal muscle weakness (myopathy) and classic skin changes in children and teenagers. It is thought to be an autoimmune disease, primarily a capillary vasculopathy, and the most common form of idiopathic inflammatory myopathy (IIM) in children. It differs from adult dermatomyositis (ADM), an IIM of unknown etiology related to connective tissue disease, which has a higher association with malignancy and interstitial lung disease.
JDM is hypothesized to be the result of an autoimmune response in genetically susceptible individuals, probably in response to environmental triggers. Some of the triggers reported include a preceding respiratory or gastrointestinal infection,1 medications,2 and ultraviolet light.3 There is an association of increased risk with some human leukocyte antigens (HLAs), and others which are protective alleles.
Epidemiology including risk factors
JDM has an annual incidence of 2 to 4 cases per million children. The peak age of onset is 4 to 10 years (mean, 7y), with approximately 25% presenting before age 5 years. There is a predominance of girls affected in North America with the ratio of girls to boys at 2.3:1.4 Seasonal birth patterns may show an increased role of perinatal exposures in the development of certain subgroups of JDM.5
JDM pathophysiology is not well understood but may develop as a response to infection in genetically susceptible individuals. Allelic variants (HLA-B*o8, DRB1*0301, DQA1*0501, DQA1*0301) are part of a haplotype that confer risk for JDM and suggest that autoreactive B cells may be involved in the early pathologic process.6 Prolonged disease course, increased risk for calcinosis, and ulcerative disease have been associated with the tumor necrosis factor (TNF)-alpha variant, TNF-alpha 308A. High levels of major histocompatibility complex class I proteins in susceptible muscle cells can lead to a pro-inflammatory stress response resulting in muscle damage.7
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
Patients present with symmetric proximal muscle weakness (82-100%), rash (66-95%), and fever (50%) with one of the disease course patterns subsequently noted. Calcinosis (5-30%), dysphagia (18-44%), dyspnea (5-43%), and arthritis (23-61%) can be seen at disease presentation.9 The 5-year survival rate is greater than 95%.10
- Monocyclic: approximately one-third of children have 1 episode of weakness and rash with resolution.
- Polycyclic: approximately one-third of children have 1 episode of weakness and rash, and the next episode is within 2 years but most commonly within 1 year.
- Chronic: the remaining one-third have a chronic course without remissions, require more aggressive, longer-term treatment regimens, and have a higher risk of complication.
Specific secondary or associated conditions and complications
Associated conditions include the following:
- Calcinosis: abnormal calcification in the limbs occurs in approximately 20% and may be painful leading to joint contractures, nerve entrapment, and ulceration. It is more common with delayed diagnosis, younger age of onset, or inadequate treatment and has no specific treatment.
- Lipodystrophy: seen in up to 40% of patients with insulin resistance and hyperlipidemia.
- Interstitial lung disease: (rare) may be life threatening.
- Intestinal perforation: (rare) seen with gastrointestinal vasculopathy.
- Osteoporosis: may lead to increased fracture risk.
Of note, the risk of malignancy (common in ADM) is rare in JDM.
2. ESSENTIALS OF ASSESSMENT
Patients present with slow onset of fatigue, muscle pain, and weakness limiting their ability to keep up with their peers when performing routine activities, such as climbing stairs, getting up from the floor, brushing hair, or getting dressed. It is essential to elicit any historical information including fatigue, weakness, rash, pain, fever, anorexia, weight loss, abdominal pain, nail changes, irritability, joint and muscle aches, and/or difficulty with self-care, swallowing, or speaking.
Evaluation for strength and skin changes must be performed. Key findings on physical examination are as follows:
- Symmetric proximal weakness, muscle fatigue, and/or muscle tenderness
- Rash (3 patterns)
- Heliotrope rash: a reddish purple rash of the upper eyelids, which may include edema.
- Gottron’s papule: erythematous papules over extensor surfaces and the metacarpophalangeal joints (may involve elbows, knees, medial malleolus).
- Malar or facial rash
- Joint changes: arthritis and/or contractures
- Nail capillary changes with increased vascularity
- Calcinosis: white nodules (nonpainful) usually around the knee and elbow joints or fingertips
Functional assessment includes measures of mobility, self-care, swallow, and social function. Tools, such as the Pediatric Evaluation of Disability Inventory, are often used. The Childhood Myositis Assessment Survey (CMAS) and Manual Muscle Test 8 (MMT8) may be used as well (to be subsequently discussed). Cognition/behavior and affective state may also be assessed using tools such as the Child Health Questionnaire.11
Creatine kinase, lactate dehydrogenase, aldolase, alanine aminotransferase, and aspartate aminotransferase are relatively insensitive markers of disease and progression. Most patients will have at least 1 of these enzymes elevated, but they may normalize as the disease progresses. Erythrocyte sedimentation rate and C-reactive protein, are nonspecific, but may help gauge disease activity during treatment. Serologic indicators include neopterin, CD19+ B lymphocytes, and von Willebrand factor.12Proinflammatory cytokine levels, including whole-blood type I interferon gene and chemokine scores, may be more reliable indicators, but they are not yet commonly used.13
As EMG and muscle biopsy are considered more invasive, magnetic resonance imaging (MRI) now plays a greater role in diagnosis and monitoring. Increased signal intensity on fat suppressed weighted and short tau inversion recovery images in affected muscle (most typically the thigh musculature) may indicate active disease.14,15 This improves as muscle recovers. Whole-body MRI and magnetic resonance (MR) spectroscopy are being evaluated in some research settings.
Supplemental assessment tools
- Electromyography may help to define a clinically active area for muscle biopsy.
- High-frequency repetitive discharges.
- Positive sharp waves and fibrillations.
- Polyphasic motor unit potentials.
- Muscle biopsy findings may correlate with disease severity and clinical course.
- Perivascular lymphocytic infiltration.
- Muscle fiber regeneration and atrophy.
- Endothelial and small vessel abnormalities.
- Centralization of nuclei in muscle fibers.
Of note, muscular dystrophies such as Limb-Girdle Muscular Dystrophy (LGMD2b) may demonstrate similar findings of inflammation and should be considered in the differential diagnosis.
- Swallow assesssment: to determine safety for eating and drinking and to direct treatment of dysphagia.
- Pulmonary function tests: useful in evaluating those with respiratory involvement. May also consider high resolution CT scan of chest if suspected respiratory problems
- Electrocardiogram and echocardiogram: for evaluation of those with suspected cardiac problems.
Early predictions of outcomes
Factors, such as time from disease onset, time of initiation of treatment, lab values, and pathophysiology, all have an effect on disease outcomes.8
- Skin ulceration may indicate the following:
- Organ vasculopathy.
- More severe course.
- Worse outcome.
- Younger age (especially before age 5y) at diagnosis predicts worse outcome, particularly with calcinosis.
- Poorer prognosis is found with later diagnosis, delay in treatment, undertreatment, disease chronicity, and persistent rash with nailfold involvement at more than 6 months of treatment.
- Poorer outcomes are associated with the following:
- Myositis-specific antibodies
- Certain unique HLA types
- TNF-polymorphism 308.9
It is important to get information on the patient’s home and school environment including the following:
- Stairs, availability of hand rails, and elevator/or stair lift for use.
- Seating heights for chairs, school desks, and home work stations.
- Heights for storage of items that the patient will need to have frequent access to.
- Bathroom setup, including physical space, toilet height, and adaptive equipment available.
Social role and social support system
Thought should be given to the patient’s social role and support system including the following:
- Activities performed in school, employment, household, and social contexts.
- Any adaptive equipment or strategies available to the patient (current or past use).
- Comfort level with use of adaptive equipment.
- Availability of psychosocial support.
Because of a frequently nonspecific and insidious onset, diagnosis is often delayed and may lead to medical or legal issues.
Options for management of recurrent or refractory disease are unclear, and the roles of bone marrow and stem cell transplantation are points of debate.
3. REHABILITATION MANAGEMENT AND TREATMENTS
Available or current treatment guidelines
Patients who receive early aggressive treatment have better overall outcomes and fewer disease complications.8 There are no published rehabilitation guidelines, but early use of rehabilitation interventions include the following:
- Early patient education on disease impact and sequelae of the disease.
- Early use of energy conservation techniques.
- Teaching joint and muscle protective techniques for patient’s specific activities (school/work).
- Education on adaptive strategies and equipment use for performing activities of daily living.
- Home-based activity/exercise program for mobility maintenance, which may include active exercise and range of motion activities.
- Progressive resistance exercise and aerobic endurance exercise in those with stable disease.16-18
The Children’s Arthritis and Rheumatology Research Alliance (CARRA) developed clinical protocols for treatment of moderate/severe JDM. Each protocol involves prednisone or intravenous methylprednisolone along with methotrexate. Methotrexate can shorten treatment time and decrease the total dose of steroids, minimizing the risk of side effects. Intravenous immune globulin (IVIG) is common as a second line agent in addition to mycophenolate mofetil and cyclosporine A, cyclophosphamide, tacrolimus, infliximab, and rituximab.9 These protocols are intended to guide clinicians and additional research is necessary. Based on treatment, gastrointestinal prophylaxis and calcium and/or Vitamin D replacement may be recommended. Sunscreen is recommended because the JDM rash is photosensitive.
At different disease stages
Recent reports indicate that there can be improvement in strength, aerobic conditioning, function, bone density, and health-related quality of life without disease exacerbation with a supervised training program.17,19,22 It is suggested that exercise may attenuate chronic low-grade systemic infection, showing direct effect on the pathogenesis of the disease.16 Exercise programs with some benefit are aerobic and resistance training programs that are structured to avoid fatigue. Physical and occupational therapy are recommended to work on range of motion, transfer and weight-bearing, adaptive activities of daily living, and energy conservation techniques in those with all stages of disease. Aquatic programs are often useful. In chronic cases, treatment focus is on preventing further loss in strength and range of motion and compensating for disabilities. Interventions are limited in the acute phases of the disease and should focus on range of motion maintenance and adaptive strategies for activity maintenance in performing activities of daily living. Active strengthening without resistance and low-level aerobic exercise may be started in the subacute phases. Progressive resistance exercises and sustained aerobic activities are recommended as tolerated in stable disease or remission states.
Coordination of care
A multidisciplinary team approach with pediatric rheumatology, physiatry, physical and occupational therapy, and vocational rehabilitation is important in managing these patients during developmental years. Pediatric orthopedics is valuable for those with limitations because of calcinosis or contracture. Pediatric surgery, gastroenterology, endocrinology, pulmonology, and dermatology are included when relevant conditions are present.
Patient & family education
Because of a high potential of severe complications with JDM and its treatments, early education on the signs, symptoms, and sequelae of the disease process is important in guiding self-management. Parents should be prepared to assist with treatments and exercise programs. Families may benefit from support organizations, such as the Cure JM Foundation (http://www.curejm.org/).
The Paediatric Rheumatology International Trials Organization developed core measures of disease activity, muscle strength, physical function, global activity assessment, and a health-related quality of life measure. The CMAS is used to measure muscle function.20 The Childhood Health Assessment Questionnaire evaluates health and disability related function and quality of life.21 Use of tools, such as the Disease Activity Score, to assess skin and muscle involvement along with rash have been used.11,15
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
Aquatic therapy programs are ideal for strengthening, improving endurance, range of motion maintenance, and mobility training in an environment that minimizes pain and protects joints.
4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE
Cutting edge concepts and practice
Whole-body MRI and MR spectroscopy are current areas of imaging research. Stem cell transplantation is being evaluated for use in severe cases.
5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE
Gaps in the evidence-based knowledge
The cause of JDM is not specifically known. There are some gaps in knowledge ranging from pathophysiology to diagnosis and to best treatments. Treatment plans begin with corticosteroids and methotrexate, but none are curative. The options for management of refractory disease are unclear, and the role of bone marrow and stem cell transplantation are points of debate. The approach to exercise for this group also has particularly dramatic gaps in knowledge.
- Pachman LM, Lipton R, Ramsey-Goldman R, 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;53:166-172.
- Magro CM, Schaefer JT, Waldman J, Knight D, Seilstad K, Hearne D. Terbinafine-induced dermatomyositis: a case report and literature review of drug-induced dermatomyositis. J Cutan Pathol. 2008:35:74-81.
- Okada S, Weatherhead E, Targoff IN, Wesley R, Miller FW; International Myositis Collaborative Study Group. Global surface ultraviolet radiation intensity may modulate the clinical and immunologic expression of autoimmune muscle disease. Arthritis Rheum. 2003;48:2285-2293.
- Wedderburn LR, Rider LG. Juvenile dermatomyositis. New development in pathogenesis, assessment, and treatment. Best Pract Res Clin Rheumatol. 2009;23:665-678.
- Vegosen LJ, Weinberg CR, O’Hanlon TP, et al. Seasonal birth patterns in myositis subgroups suggest an etiologic role of early environmental exposures. Arthritis Rheum. 2007:56:2719-2728.
- Martin N, Li CK, Wedderburn LR. Juvenile dermatomyosotis: new insights and new treatment strategies. Ther Adv Musculoskelet Dis.2012;4:41-50.
- Li CK, Knopp P, Moncrieffe H, et al. Over expresion of MHC class I heavychan protein in young skeletal muscle leads to myositis: implications for juvenile myositis. Am J Pathol. 2009; 175:1030-1040.
- Kim S, El-Hallak M, Dedeoglu F, et al. Complete and sustained remission of juvenile dermatomyositis resulting from aggressive treatment. Arthritis Rheum. 2009;60:1825-1830.
- Laxer RM, Benseler SM. Pediatric systemic lupus erythematosus, dermatomyositis, scleroderma, and vascultiis. In: Firestein GS, et al, eds. Kelley’s Textbook of Rheumatology. 9th ed. Philadelphia, Pa: Elsevier; 2010:1781-1782.
- Robinson AB, Reed AM. Clinical features, pathogenesis and treatment of juvenile and adult dermatomyositis. Nat Rev Rheumatol. 2011;7:664-675.
- Rider LG, Werth VP, Huber AM, et al. Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: 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). Arthritis Care Res(Hoboken). 2011;63 Suppl 11:S118-S157.
- Pachman LM. Juvenile dermatomyositis (JDMS): new clues to diagnosis and pathogenesis. Clin Exp Rheumatol. 1994;12 Suppl 10:S69-S73.
- Reed AM, Peterson E, Bilgic H, et al. Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course. Arthritis Rheum. 2012;64:4078-4086.
- Gardner-Medwin JM, Irwin G, Johnson K. MRI in juvenile idiopathicarthritis and juvenile dermatomyositis. Ann N Y Acad Sci. 2009;1154:52-83.
- Martin N, Li CK, Wedderburn LR. Juvenile dermatomyositis: new insights and treatment strategies. Ther Adv Musculoskeletal Dis.2012;4:41-50.
- Gualano B, SaPinto AL, Perondi B, et al. Evidence for prescribing exercise as treatment in pediatric rheumatic diseases. Automimmune Rev. 2010;9:569-573.
- Omori C, Prado DM, Gualano B, et al. Responsiveness to exercise training in juvenile dermatomyositis: a twin case study. BMC Musculoskelet Disord.2010;11:1471-1474.
- Alexanderson H, Lundberg IE. Exercise as a therapeutic modality in patients with idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2012;24:201-207.
- Reed AM, Lopez M. Juvenile dermatomyositis: recognition and treatment. Paediatr Drugs.2002:4:315-321.
- Huber AM, Feldman BM, Rennebohm RM, 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;50:1595-1603.
- Feldman BM, Ayling-Campos A, Luy L, et al. Measuring disability in juvenile dermatomyositis: validity of the childhood health assessment questionnaire. J Rheumatol. 1995;22:326-331.
- Omori CH, Silva CAA, Sallum AME, Rodrigues Pereira RM et al. Exercise training in juvenile dermatomyositis. Arthritis Care Res. 2012;64(8):1186-1194.
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Ravelli A, Ruperto N, Trail L, et al. Clinical assessment in juvenile dermatomyositis. Autoimmunity. 2006;39:197-203.Author Disclosure
Original Version of the Topic
Galen Joe, MD. Dermatomyositis. Original Publication Date. 02/12/2014.
Kimberly Hartman, MD
Nothing to Disclose