Juvenile Dermatomyositis

Disease/Disorder

Definition

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. It also differs from juvenile polymyositis, a rare form of IIM that lacks skin disease.

Etiology

JDM occurs in genetically susceptible individuals in response to environmental or infectious triggers. Environmental factors, including a preceding respiratory or gastrointestinal infection,¹ medications,² and ultraviolet light,³ may trigger onset or alter the course of disease in JDM.

Genetic predisposition to JDM has been associated with certain human leukocyte antigens (HLA), particularly HLA-DR3.⁴ There are also non-HLA associated genes that have been identified as risk factors for JDM development and severity of presentation.⁵  

Environmental risks include sun exposure, medications (including NSAIDS), and inhaled air pollutants (including tobacco smoke, silica, and traffic pollution).^4,5

Multiple infectious agents have been identified as triggers for onset of JDM including coxsackie B virus, group A streptococcus, enteroviruses, parvovirus B19, EBV, and varicella.^4,5 There is a seasonal variation in JDM disease onset, with higher incidence in nonwinter months, correlating with infectious patterns of some of the above agents.  

Epidemiology including risk factors

Juvenile dermatomyositis has an incidence of 1.9-4 per million children per year. The median age of onset is roughly 5.7-6.9 years, with median diagnosis occurring around 7.5 years. Approximately 25% of children present before age 4 years.⁶ Females are affected more than twice as often as males.^6,7 There does not appear to be a propensity for certain racial or ethnic groups.⁶ Seasonal birth patterns may show an increased role of perinatal exposure to infection in the development of certain subgroups of JDM.⁸

Patho-anatomy/physiology

Juvenile dermatomyositis is an autoimmune disorder associated with systemic vasculopathy that can include occlusive arteriopathy and capillary necrosis. These vascular changes lead to tissue ischemia and perifascicular muscle atrophy. Degeneration and necrosis of both type 1 and type 2 muscle fibers are histopathologic features.⁵

The widespread tissue inflammation that occurs in JDM predominantly affects skeletal muscle and skin, leading to the hallmark features of symmetric proximal muscle weakness and characteristic cutaneous findings.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Patients typically present with heliotrope rash, proximal muscle weakness, and constitutional symptoms. Symptom onset is frequently insidious,and the heliotrope rash may precede proximal muscle weakness by months.⁵ Additional common cutaneous findings at diagnosis include nailfold capillary abnormalities, Gottron papules, malar/facial rash, and calcinosis.⁹

Proximal muscle weakness may manifest as difficulty reaching overhead, navigating stairs, and transitioning from sit to stand, as well as decreased endurance.⁶ Muscle weakness is typically progressive, and can include bulbar symptoms, which are a frequent cause of hospitalization in later stages.⁶ Over time, the chronic inflammation can lead to fibrosis and contracture of affected muscles, which further limits function. Approximately 5 percent of patients have clinically amyopathic JDM (CAJDM), where they do not develop noticeable muscle weakness despite having characteristic skin findings for greater than 6 months and not receiving systemic treatment.

The clinical course of JDM follows one of the following patterns

• Monocyclic: (1/3 of children) A single episode of disease with good response to standard therapy and remission occurring within 2 years.
• Chronic Continuous: (Up to 2/3 of children) Following disease development, chronic presence of symptoms, without remissions, despite adequate treatment for greater than 2 years. This pattern requires more aggressive, longer-term treatment regimens, and has a higher risk of complication.
• Polycyclic: (Rare) Following disease development, multiple remissions/relapses occur within two years when not treated with corticosteroids. It is postulated that these children may have underlying subclinical disease present during the “remission” periods and thus may represent a subset of the chronic continuous pattern.

Cutaneous symptoms are more resistant to treatment than muscle disease. The major causes of death related to JDM are severe muscle weakness, infection, bowel perforation, myocardial failure, and respiratory distress.⁴ However, with standard treatment, the 5-year survival rate of JDM is greater than 95%.^6,10 

Specific secondary or associated conditions and complications

 Associated conditions include the following

• Calcinosis: (seen in 17-44%) Abnormal calcification in the skin or subcutaneous tissue (usually around the knee and elbow joints or at fingertips) with extension into muscles, and may be painful leading to joint contractures, nerve entrapment, and ulceration. It is more common with delayed diagnosis, younger age of onset, specific autoantibodies, high disease activity, cardiac involvement, or inadequate treatment.⁶
• Gottron’s papules: (seen in 80%) erythematous papulosquamous lesions over the extensor surfaces of joints, most commonly the finger joints (MCP, PIP, DIP), elbow, and knee joints.
• Nailfold capillary changes: (83%) Dilated or tortuous nailfold capillaries, with dropout. Typically present at time of diagnosis but may only be apparent with magnification.⁹
• Skin ulceration: (seen in up to 20%) Vasculopathy of the skin can lead to ulceration and is a potentially life-threatening complication. Skin ulceration can signal vasculopathy in other organs such as the lungs or GI tract and is associated with a more severe course of disease with worse prognosis.
• Lipodystrophy: (seen in 8-14%) Leads to progressive loss of subcutaneous and visceral fat and can be associated with dyslipidemia and diabetes. Lipodystrophy can be associated with a more severe and chronic disease course.
• Interstitial lung disease: (rare) May be rapidly progressive and life threatening.
• Gastrointestinal Vasculopathy: (rare) May present with abdominal pain, GI bleeding, or perforation, and can be life threatening.
• Osteoporosis: Increased risk regardless of whether steroids are used in treatment of JDM.  
• Arthritis: (23-61%)Non-erosive, can cause arthralgia. Contractures are rarely due to arthritis and are more commonly present due to muscle inflammation and fibrosis.¹⁰
• Anasarca: (rare) A poor prognostic sign and can indicate severe disease that is unlikely to respond to monotherapy with glucocorticoids.
• Dysphagia and dysphonia: (30%)

Essentials of Assessment

History

Patients present with slow onset of fatigue, muscle pain, and symmetric proximal 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 a thorough history 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. Patients should also be asked about any preceding illnesses or family history of autoimmune or rheumatologic disorders.

Physical examination

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 of joints, most commonly the finger joints (MCP, PIP, DIP), elbow, and knee joints
  • 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

In 2017, the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) published classification criteria for idiopathic inflammatory myopathies (IIM), including JDM. The EULAR/ACR criteria uses a scoring system to determine the probability of an IIM diagnosis, with points given for presence of proximal muscle weakness, skin findings (heliotrope rash or Gottron’s papules), dysphagia or esophageal dysmotility, in addition to laboratory studies described below.¹³

Functional assessment

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), a quantitative tool for evaluation of muscle function, and Manual Muscle Test-8 (MMT8) can be used to assess strength and muscle function in JDM.¹¹ Cognition, behavior, and affective state can be assessed using tools such as the Child Health Questionnaire.¹²

Laboratory studies

Elevated levels of muscle enzymes including creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) are common in JDM. The elevation of any one of these markers adding to the likelihood of JDM diagnosis based on EUALR/ACR criteria. Muscle enzyme levels can be normal or slightly elevated at the time of diagnosis or during periods of clinical remission, thus a diagnosis of JDM should still be considered and can be made based on EULAR/ACR criteria even in the absence of muscle enzyme elevation.¹³   

The presence of anti-Jo-1 autoantibody is an additional laboratory study that can aid in the diagnosis of JDM based on the EULAR/ACR criteria. ¹³

Elevation in erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) are nonspecific findings that may help gauge JDM disease activity during treatment but are not included in criteria for diagnosis.  

Imaging

Although magnetic resonance imaging (MRI) is not included in any diagnostic criteria for JDM, it is commonly used to identify muscle involvement (seen as muscle edema, perifascicular edema, and honeycomb appearance of affected muscles) and monitor for disease progression or response to therapy.^5,14 MRI can be used to select muscles for muscle biopsy or EMG testing when needed.

Supplemental assessment tools

• Electromyography and Nerve Conduction Studies are recommended only when diagnosis is uncertain. Motor and sensory nerve conduction studies are typically normal. EMG typically shows:
  • Acute phase:
    • Prominent spontaneous activity (positive sharp waves and fibrillations)
    • Increased insertional activity
    • Low-amplitude, short duration polyphasic motor unit action potentials with rapid recruitment
  • Chronic phase:
    • Complex repetitive discharges develop
    • Insertional activity may decrease
    • A mix of small and larger MUAPs may be present, reflecting both active inflammation and muscle fiber atrophy.¹⁵ 
• Muscle biopsy should be done in all cases where presentation is atypical. When biopsy is obtained at diagnosis, the histologic findings can be used to predict outcome. Muscle biopsy shows:
  • Perivascular lymphocytic infiltration
  • Muscle fiber regeneration and atrophy
  • Endothelial and small vessel abnormalities
  • Centralization of nuclei in muscle fibers

EMG and muscle biopsy have historically been used in making or confirming the diagnosis of JDM but are more invasive and less well tolerated in children. These tests now are reserved for instances where the diagnosis remains in question after physical exam, lab testing, and MRI. It is notable that based on the EULAR/ACR diagnostic criteria, a diagnosis of JDM can be made in the absence of muscle biopsy, EMG, or imaging.

• Swallow assessment: 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 there is concern for interstitial lung disease.
• Electrocardiogram, echocardiogram, or cardiac MRI: for evaluation of those with suspected cardiac problems.

Early predictions of outcomes

Disease outcome is influenced by time from disease onset, time of initiation of treatment, lab values, and pathophysiology.¹⁶

• Prognosis is poorer in patients with:
  • Chronic continuous or polycyclic disease
  • Delay in diagnosis or treatment
  • Younger age (especially before age 5y) at diagnosis
  • Presence of calcinosis, skin ulceration, GI vasculopathy, lipodystrophy, or anasarca
  • Presence of nailfold involvement after more than 6 months of treatment
  • Certain specific myositis-specific autoantibodies (MSAs) or HLA types
• Differing myositis-specific autoantibodies (MSAs) can be associated with specific disease courses, response to treatment, or complication.^6,14

Environmental

It is important to get information on the patient’s home and school environment including the following:

• Stairs, availability of handrails, and elevator/or stair lift for use.
• Seating heights for chairs, school desks, and workstations.
• 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:

• 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.

Professional issues

Because of a frequently nonspecific and insidious onset, diagnosis and thus treatment is often delayed, which may lead to poorer prognosis.

Many patients present with weakness; thus, it is important to address functional impairments early in their treatment course to promote positive social and community engagement.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Patients who receive early aggressive treatment have better overall outcomes and fewer disease complications.¹⁶ The initial treatment plan is based upon the severity of presenting symptoms.

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.¹⁷ These protocols are intended to guide clinicians, but treatment is individually tailored. Based on treatment, gastrointestinal prophylaxis and calcium and/or Vitamin D replacement may be recommended. Sunscreen is recommended because the JDM rash is photosensitive.

There are no published rehabilitation guidelines, but early rehabilitation interventions should include

• 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, range of motion activities, and strength training.
• Directed therapy for transfer training and promotion of weight bearing activities.

At different disease stages

Resistance and aerobic training are recommended at all stages of disease. It is suggested that exercise may attenuate chronic low-grade systemic inflammation, showing direct effect on the pathogenesis of the disease.¹⁸ There can be improvement in strength, aerobic conditioning, function, bone density, and health-related quality of life without disease exacerbation with a guided training program.^19,20,21 Progressive aerobic and resistance training programs that are structured to avoid fatigue are beneficial. ^18,19,22 Aquatic programs are often useful.

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 Juvenile Myositis Foundation (http://www.curejm.org/).

Emerging/unique interventions

Rituximab and TNF-inhibitors are the most commonly used biologic agents for treatment of refractory JDM. Two additional biologics, Abatacept, and Janus Kinase (JAK) inhibitors are emerging as treatment of refractory JDM.^23,24 Multiple other biologics are also under investigation, but further studies are needed to provide higher level evidence and to aid in development of expert consensus for the use of biologics in the treatment of JDM.²⁵

Hydroxychloroquine has been used in patients with skin-predominant JDM or refractory disease, but newer studies are showing possibility of adverse cutaneous reactions.^5,26 Further investigation is needed.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

• JDM is a rare autoimmune myositis associated with multi-systemic vasculitis.
• JDM typically presents with characteristic cutaneous findings and symmetric proximal muscle weakness.
• JDM is diagnosed primarily on clinic findings using EULAR/ACR diagnostic criteria.
• Early use of corticosteroids and methotrexate are mainstay treatments.
• The use of biologics in treatment of refractory disease should be considered however there is no consensus recommendation on specific agent.
• Early introduction to guided aerobic and resistance training can improve strength and reduce disease activity, and thus should be recommended for all patients with JDM.

Cutting Edge/Emerging and Unique Concepts and Practice

Blood flow restriction therapy is being assessed in adults with myositis and may have implications for strength training in JDM.²⁷

There is emerging research into the role of mitochondrial function relating to development of skeletal muscle calcinosis in JDM. Identification of antimitochondrial autoantibodies may highlight patients at risk for developing calcinosis, and allow for earlier targeted treatment of mitochondrial dysfunction, reducing the risk of calcinosis-related complications in those individuals.²⁸

Gaps in the Evidence-Based Knowledge

There are multiple gaps in knowledge about JDM ranging from pathophysiology to diagnostic criteria to best treatments. Additional research is needed to identify biomarkers that predict disease course and treatment response.

A key unmet need is to develop individualized therapeutic approaches to optimize the early treatment regimen to avoid unnecessary adverse effects from immunosuppressive medications and to allow administration of more aggressive treatment to those with anticipated severe or refractory disease.

References

1. 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.
2. 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.
3. 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.
4. Gara S, Jamil RT, Muse ME, Litaiem N. Juvenile Dermatomyositis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 16, 2023.
5. Leung AKC, Lam JM, Alobaida S, Leong KF, Wong AHC. Juvenile Dermatomyositis: Advances in Pathogenesis, Assessment, and Management. Curr Pediatr Rev. 2021;17(4):273-287.
6. Wu JQ, Lu MP, Reed AM. Juvenile dermatomyositis: advances in clinical presentation, myositis-specific antibodies and treatment. World J Pediatr. 2020 Feb;16(1):31-43.5.
7. Wedderburn LR, Rider LG. Juvenile dermatomyositis. New development in pathogenesis, assessment, and treatment. Best Pract Res Clin Rheumatol. 2009;23:665-678.
8. Opinc-Rosiak AH, Makowska JS. Environmental exposures as risk factors for idiopathic inflammatory myopathies. J Autoimmun. 2023;140:103095.
9. Cancarini P, Nozawa T, Whitney K, et al. The clinical features of juvenile dermatomyositis: A single-centre inception cohort. Semin Arthritis Rheum. 2022;57:152104
10. Robinson AB, Reed AM. Clinical features, pathogenesis and treatment of juvenile and adult dermatomyositis. Nat Rev Rheumatol. 2011;7:664-675.
11. Wu Q, Wedderburn LR, McCann LJ. Juvenile dermatomyositis: Latest advances. Best Pract Res Clin Rheumatol. 2017 Aug;31(4):535-557.
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13. Lundberg IE, Tjärnlund A, Bottai 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 [published correction appears in Ann Rheum Dis. 2018 Sep;77(9):e64.
14. Kim H, Huber AM, Kim S. Updates on Juvenile Dermatomyositis from the Last Decade: Classification to Outcomes. Rheum Dis Clin North Am. 2021;47(4):669-690.
15. Paganoni S, Amato A. Electrodiagnostic evaluation of myopathies. Phys Med Rehabil Clin N Am. 2013 Feb;24(1):193-20.
16. 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.
17. 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.
18. Gualano B, SaPinto AL, Perondi B, et al. Evidence for prescribing exercise as treatment in pediatric rheumatic diseases. Automimmune Rev. 2010;9:569-573.
19. 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.
20. Reed AM, Lopez M. Juvenile dermatomyositis: recognition and treatment. Paediatr Drugs.2002:4:315-321.
21. Omori CH, Silva CAA, Sallum AME, Rodrigues Pereira RM et al. Exercise training in juvenile dermatomyositis. Arthritis Care Res. 2012;64(8):1186-1194.
22. Alexanderson H, Lundberg IE. Exercise as a therapeutic modality in patients with idiopathic inflammatory myopathies. Curr Opin Rheumatol. 2012;24:201-207.
23. Curiel RV, Nguyen W, Mamyrova G, Jones D, Ehrlich A, Brindle KA, Haji-Momenian S, Sheets R, Kim H, Jones OY, Rider LG; Abatacept in Dermatomyositis (AID) Trial Investigators. Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy. Arthritis Rheumatol. 2023 Jul;75(7):1229-1237.
24. Sener S, Cam V, Ozen S, Batu ED. Treatment with Janus kinase inhibitors in juvenile dermatomyositis: A review of the literature. Semin Arthritis Rheum. 2024 Jun;66:152426.
25. Sener S, Cam V, Ozen S, Batu ED. Biologic drugs in the treatment of juvenile dermatomyositis: a literature review. Clin Rheumatol. 2024 Feb;43(2):591-602
26. Allenzara A, Hollis A, Álvarez C, Lovelace H, Maczuga S, Helm M, Olsen N, Nelson A, Foulke G. Higher Odds of Adverse Cutaneous Reactions in Patients With Dermatomyositis Treated With Hydroxychloroquine Compared With Methotrexate. ACR Open Rheumatol. 2023 Nov;5(11):594-599.
27. Minniti MC, Statkevich AP, Kelly RL, et al. The safety of blood flow restriction training as a therapeutic intervention for patients with musculoskeletal disorders: A systematic review. Am J Sports Med. 2020 Jun;48(7):1773-1785.
28. Duvvuri B, Pachman LM, Hermanson P, et al. Role of mitochondria in the myopathy of juvenile dermatomyositis and implications for skeletal muscle calcinosis. J Autoimmun. 2023;138:103061.

Original Version of the Topic

Galen Joe, MD. Dermatomyositis. Original Publication Date. 2/12/2014

Previous Revision(s) of the Topic

Kimberly C Hartman, MD. Juvenile Dermatomyositis. 9/7/2018

Kimberly Hartman, MD, Angela C Nwankwo, BA. Juvenile Dermatomyositis. 9/23/2021

Author Disclosure

Sara Liegel, MD
Nothing to Disclose

Deanna Jewell, DO
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