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Dermatomyositis/Polymyositis, Pediatric

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Dermatomyositis/Polymyositis, Pediatric

Basics

Description

Epidemiology

Juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) are inflammatory myopathies in which inflammation of capillary endothelium of muscle, skin, and other tissues causes vascular and tissue damage. JDM patients present with characteristic rashes and muscle weakness. JPM patients have inflammatory myopathy but lack skin findings. Both disorders have a wide range of severity and presenting findings.

- Genetic factors, including the following: - HLA alleles: B8, DRB10301, DQA10501, DQA1*0301 - Cytokine polymorphisms: TNFα-308A promoter, various IL1 genes, interferon regulatory factor 5, and others, all resulting in upregulated inflammation - Polymorphisms of immunoglobulin constant regions

Bohan and Peter criteria (1975): not validated in children but nonetheless used. Definite JDM requires rash plus three other criteria; probable JDM requires rash plus two other criteria:

  • The average age of onset is 7 years, but 25% of cases are diagnosed by 4 years of age.
  • Male-to-female ratio in the United States is 1:2.3.
  • JDM incidence is 3.2 new cases per 1 million children per year; JPM is extremely rare.

Risk Factors

  • Underlying genetic susceptibility
  • Environmental triggersUltraviolet light exposureInfectious triggers are inconsistently reported, including group A β-hemolytic streptococci, coxsackievirus B, toxoplasma, enterovirus, and parvovirus.Reports of drug exposure, vaccination, and psychological stress prior to diagnosis, but no causation has been found
  • Ultraviolet light exposure
  • Infectious triggers are inconsistently reported, including group A β-hemolytic streptococci, coxsackievirus B, toxoplasma, enterovirus, and parvovirus.
  • Reports of drug exposure, vaccination, and psychological stress prior to diagnosis, but no causation has been found
  • Genetic factors, including the following:HLA alleles: B8, DRB1*0301, DQA1*0501, DQA1*0301Cytokine polymorphisms: TNFα-308A promoter, various IL1 genes, interferon regulatory factor 5, and others, all resulting in upregulated inflammationPolymorphisms of immunoglobulin constant regions
  • Epigenetic factors likely exist: Monozygotic twin studies show low concordance.
  • HLA alleles: B8, DRB1*0301, DQA1*0501, DQA1*0301
  • Cytokine polymorphisms: TNFα-308A promoter, various IL1 genes, interferon regulatory factor 5, and others, all resulting in upregulated inflammation
  • Polymorphisms of immunoglobulin constant regions

Pathophysiology

  • Vasculopathy in patients with underlying inflammatory genetic susceptibility, triggered by environmental factors
  • JDM: immune attack on muscle capillary endothelium with infiltration of plasmacytoid dendritic cells causing a type I interferon response and upregulation of myofiber MHC class I expressionImmune complex deposition and complement activation drive vasculopathyUpregulation of ICAM-1 and von Willebrand factor antigen indicates endothelial injury.After vasculopathy and MHC class I upregulation, plasmacytoid dendritic and other immune cells infiltrate perivascular and perimysial tissue, resulting in upregulated type I interferon response which perpetuates inflammatory processes including increased production of proinflammatory cytokines
  • JPM: CD8 T cell and myeloid dendritic cell-mediated attack on myofibers causing myonecrosis; no increased interferon response
  • Myositis-specific and associated autoantibodies directed against vascular and muscle antigens implicated in pathogenesis of JDM and JPM
  • Maternal cell chimerism reported in peripheral blood T cells and muscle tissue of JDM patients may be autoreactive toward host cells.
  • Immune complex deposition and complement activation drive vasculopathy
  • Upregulation of ICAM-1 and von Willebrand factor antigen indicates endothelial injury.
  • After vasculopathy and MHC class I upregulation, plasmacytoid dendritic and other immune cells infiltrate perivascular and perimysial tissue, resulting in upregulated type I interferon response which perpetuates inflammatory processes including increased production of proinflammatory cytokines

Commonly Associated Conditions

  • Dermatomyositis in children is not associated with presence of malignancy as seen in adults.
  • Celiac disease is rarely associated with JDM.

Diagnosis

  • Characteristic rashes: heliotrope discoloration of eyelids and/or erythematous papules over extensor surfaces of joints (Gottron papules)
  • Symmetric proximal muscle weakness
  • Elevated serum skeletal muscle enzymes
  • Electromyographic (EMG) findings of myopathy and denervation; characteristic MRI findings are often substituted to fulfill EMG criteria in children, although are not specific.
  • Muscle biopsy with characteristic abnormalities

History

  • Onset is often insidious but can be rapid.
  • ConstitutionalFever and adenopathy in some childrenAnorexia, weight lossFatigue is a sign of muscle weakness and immune activation.
  • Skin: characteristic rashes, ulceration, mouth sores, sun sensitivity, limb edema, calcinosis cutis; Raynaud phenomenon and erythema around fingernails due to vasculopathy
  • Weakness (e.g, difficulty rising, climbing stairs, getting out of bed or chair, combing hair)
  • Gastrointestinal (GI)Dysphonia, dysphagia, choking, and regurgitation of liquids through nose indicate pharyngeal muscle weakness.Constipation, early satiety from muscle weakness, and gut vasculopathyAbdominal pain and hematochezia from gut vasculopathy
  • Musculoskeletal: myalgia, arthralgia, arthritis, joint contractures
  • Often strong family history of various autoimmune diseases
  • Fever and adenopathy in some children
  • Anorexia, weight loss
  • Fatigue is a sign of muscle weakness and immune activation.
  • Dysphonia, dysphagia, choking, and regurgitation of liquids through nose indicate pharyngeal muscle weakness.
  • Constipation, early satiety from muscle weakness, and gut vasculopathy
  • Abdominal pain and hematochezia from gut vasculopathy

Physical Exam

  • Classic rashes in JDM:Heliotrope rash: violaceous discoloration of upper eyelids; can be accompanied by lid swelling, capillary telangiectasia, discoloration below eyesGottron papules: scaly, erythematous, symmetric, usually hypertrophic but sometimes atrophic papules over extensor surfaces of joints, especially fingers, elbows, knees, and ankles
  • Other cutaneous findings in JDM:Malar rashV-sign: erythema of upper chest; shawl-sign includes erythema of shouldersNailfold capillary telangiectasiaOvergrown, ragged cuticlesEdema of skin overlying inflamed musclesErythema, dilated vessels, ulcerations of hard palate and buccal mucosaDermatitis of scalpUlcerations of skin especially of inner canthi, elbows, or at sites of calcinosisCalcinosis cutis is a late finding:Tumorlike calcium deposits at pressure points: elbows, scapulae, ischiaSheetlike or nodular calcification around joints, axillae
  • MusculoskeletalCore weakness: neck, abdominal musclesProximal weakness: symmetric weakness of shoulder abductors, hip flexorsDistal muscle weakness in severe casesMuscle tendernessWaddling (Trendelenburg), wide-based or marching gait due to weak hip flexorsArthritis and joint contracturesGI: diffuse abdominal tenderness, distension, palpable stoolCV: tachycardia, murmurs, tachypneaPhysical exam tipsGower sign: inability to rise from floor without using handsLying supine on flat exam table without a pillow, patients with neck and abdominal weakness will have difficulty lifting head (chin to chest) or shoulders off bed.Objective measure of strength: duration of straight-leg raise (normal = 20 seconds)Use ophthalmoscope or otoscope to examine nailfolds for telangiectasia.Evaluate for dysphonia by asking child to say "Nancy" or "jug"-listen for a nasal quality to voice.
  • Heliotrope rash: violaceous discoloration of upper eyelids; can be accompanied by lid swelling, capillary telangiectasia, discoloration below eyes
  • Gottron papules: scaly, erythematous, symmetric, usually hypertrophic but sometimes atrophic papules over extensor surfaces of joints, especially fingers, elbows, knees, and ankles
  • Malar rash
  • V-sign: erythema of upper chest; shawl-sign includes erythema of shoulders
  • Nailfold capillary telangiectasia
  • Overgrown, ragged cuticles
  • Edema of skin overlying inflamed muscles
  • Erythema, dilated vessels, ulcerations of hard palate and buccal mucosa
  • Dermatitis of scalp
  • Ulcerations of skin especially of inner canthi, elbows, or at sites of calcinosis
  • Calcinosis cutis is a late finding:Tumorlike calcium deposits at pressure points: elbows, scapulae, ischiaSheetlike or nodular calcification around joints, axillae
  • Tumorlike calcium deposits at pressure points: elbows, scapulae, ischia
  • Sheetlike or nodular calcification around joints, axillae
  • Core weakness: neck, abdominal muscles
  • Proximal weakness: symmetric weakness of shoulder abductors, hip flexors
  • Distal muscle weakness in severe cases
  • Muscle tenderness
  • Waddling (Trendelenburg), wide-based or marching gait due to weak hip flexors
  • Arthritis and joint contractures
  • GI: diffuse abdominal tenderness, distension, palpable stool
  • CV: tachycardia, murmurs, tachypnea
  • Physical exam tipsGower sign: inability to rise from floor without using handsLying supine on flat exam table without a pillow, patients with neck and abdominal weakness will have difficulty lifting head (chin to chest) or shoulders off bed.Objective measure of strength: duration of straight-leg raise (normal = 20 seconds)Use ophthalmoscope or otoscope to examine nailfolds for telangiectasia.Evaluate for dysphonia by asking child to say "Nancy" or "jug"-listen for a nasal quality to voice.
  • Gower sign: inability to rise from floor without using hands
  • Lying supine on flat exam table without a pillow, patients with neck and abdominal weakness will have difficulty lifting head (chin to chest) or shoulders off bed.
  • Objective measure of strength: duration of straight-leg raise (normal = 20 seconds)
  • Use ophthalmoscope or otoscope to examine nailfolds for telangiectasia.
  • Evaluate for dysphonia by asking child to say "Nancy" or "jug"-listen for a nasal quality to voice.
  • Findings requiring immediate evaluation: tachycardia, dyspnea, dysphagia, hematochezia, severe abdominal pain, and inability to stand up from the floor or walk
  • Some JDM patients have little to no muscle weakness (amyopathic/hypomyopathic JDM). Patients seemingly without weakness with facial, hand, and/or other vasculopathic rashes can be misdiagnosed with eczema or psoriasis.
  • Rarely, patients may have myositis and vasculopathic skin findings but lack heliotrope changes and Gottron papules.

Diagnostic Tests & Interpretation

  • Muscle enzymes: creatine kinase, aldolase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferaseOne or more is elevated in most cases
  • Markers of immune activationESR and C-reactive protein often normalInflammatory findings in complete blood count often not presentElevated neopterin: secreted by activated macrophages and dendritic cellsElevated von Willebrand factor antigen: marker of endothelial activationComplement generally normal; if low, consider overlap syndrome
  • AutoantibodiesAntinuclear antibodies with various antigen specificities may be present.~63% of JDM/JPM patients have a myositis-specific antibody (MSA). Anti-p-155 and MJ antibodies most common; anti-synthetase antibodies (i.e., Jo-1), anti-Mi-2, and anti-signal recognition particle are rare in childhood-onset disease.Myositis-associated antibodies (MAAs) are seen in ~16% of JDM/JPM patients, including anti-Ro, anti-U1RNP, and anti-PM-Scl.MSAs and MAAs should be tested by immunoprecipitation using validated assays.Rheumatoid factor and double-stranded DNA antibodies are usually negative; if positive, consider overlap syndrome.Consider celiac disease testing if with GI symptoms, anemia, and weight loss.
  • Occult blood in stool; anemia if blood loss
  • One or more is elevated in most cases
  • ESR and C-reactive protein often normal
  • Inflammatory findings in complete blood count often not present
  • Elevated neopterin: secreted by activated macrophages and dendritic cells
  • Elevated von Willebrand factor antigen: marker of endothelial activation
  • Complement generally normal; if low, consider overlap syndrome
  • Antinuclear antibodies with various antigen specificities may be present.
  • ~63% of JDM/JPM patients have a myositis-specific antibody (MSA). Anti-p-155 and MJ antibodies most common; anti-synthetase antibodies (i.e., Jo-1), anti-Mi-2, and anti-signal recognition particle are rare in childhood-onset disease.
  • Myositis-associated antibodies (MAAs) are seen in ~16% of JDM/JPM patients, including anti-Ro, anti-U1RNP, and anti-PM-Scl.
  • MSAs and MAAs should be tested by immunoprecipitation using validated assays.
  • Rheumatoid factor and double-stranded DNA antibodies are usually negative; if positive, consider overlap syndrome.
  • Consider celiac disease testing if with GI symptoms, anemia, and weight loss.
  • MRI: Inflamed muscles are identified by signal enhancement on short T1 inversion recovery (STIR) or fat-suppressed T2 sequences; useful to locate site for biopsy
  • Video swallow study to identify palatal or proximal esophageal weakness, aspiration
  • PFTs to evaluate for respiratory musculature weakness and interstitial lung disease
  • EKG and possibly ECHO to evaluate for myocarditis, myocardial dysfunction
  • Muscle biopsy
  • Skin biopsy
  • EMG is rarely used in children but can help support diagnosis.
  • Skeletal muscle: perifascicular atrophy; variation in fiber size due to degeneration and regeneration; focal necrosis; lymphocytic and mononuclear infiltrates in the perimysium and perivascular spaces (perifascicular), overexpression of MHC class I
  • Skin: epidermal atrophy, dermal and perivascular lymphocytic infiltrates

Differential Diagnosis

  • Infectious/postinfectious: influenza A and B, coxsackievirus B, schistosomiasis, trypanosomiasis; bacterial/pyomyositis if focal
  • Trauma (physical, toxic, or drug-induced)
  • Myositis with other connective tissue diseasesSystemic lupus erythematosusSystemic sclerosisOverlap syndromes including mixed or undifferentiated connective tissue diseaseOther forms of idiopathic inflammatory myopathy (extremely rare in children): inclusion body myositis, cancer-associated myositis, eosinophilic myositis/fasciitis
  • Childhood neuromuscular diseasesMuscular dystrophiesCongenital myopathies (nemaline rod)Myotonic disordersMetabolic myopathies (glycogen metabolism disorders, mitochondrial myopathies, familial periodic paralysis, lipid myopathies [carnitine deficiencies], myoadenylate deaminase deficiency, myopathy secondary to endocrinopathy)Neurogenic atrophies (spinal muscular atrophy and anterior horn cell dysfunction, peripheral nerve dysfunction, neuromuscular transmission disorders)
  • The differential diagnosis for JPM is broader than JDM due to lack of skin findings.
  • Systemic lupus erythematosus
  • Systemic sclerosis
  • Overlap syndromes including mixed or undifferentiated connective tissue disease
  • Other forms of idiopathic inflammatory myopathy (extremely rare in children): inclusion body myositis, cancer-associated myositis, eosinophilic myositis/fasciitis
  • Muscular dystrophies
  • Congenital myopathies (nemaline rod)
  • Myotonic disorders
  • Metabolic myopathies (glycogen metabolism disorders, mitochondrial myopathies, familial periodic paralysis, lipid myopathies [carnitine deficiencies], myoadenylate deaminase deficiency, myopathy secondary to endocrinopathy)
  • Neurogenic atrophies (spinal muscular atrophy and anterior horn cell dysfunction, peripheral nerve dysfunction, neuromuscular transmission disorders)

Treatment

Medication

  • Early aggressive therapy improves overall outcome and reduces frequency of calcinosis.
  • Prednisone 1-2 mg/kg/24 h PO (maximum 60 mg) for 1 month, taper over months to years
  • IV methylprednisolone 30 mg/kg/24 h (maximum 1,000 mg) for 3 infusions at treatment onset; may also be given weekly
  • Methotrexate, usually 15 mg/m2 (maximum generally 25 mg) weekly; SC or IV preferred-PO absorption is poor due to gut vasculopathy
  • IV gammaglobulin, especially helpful for rash
  • Hydroxychloroquine, especially useful for rash
  • 2nd-line immunosuppressants: cyclosporine, mycophenolate mofetil
  • Biologic agents for refractory disease including rituximab and abatacept under investigation
  • Topical calcineurin inhibitors for rash
  • Aggressive broad-spectrum photoprotection with physical blockers (i.e., titanium dioxide) and chemical blockers (i.e., avobenzone)
  • Calcium and vitamin D supplementation
  • Treatment of calcinosis may include sodium thiosulfate, diltiazem, and bisphosphonates.

Issues for Referral

  • Pediatric rheumatologist for diagnosis and management
  • Speech therapist for dysphagia
  • Gastroenterology, cardiology, or pulmonary referral depending on involved organ system
  • Plastic surgery referral may be indicated for excision of severe calcifications, but there is risk of recurrence and infection.

Additional Therapies

  • Physical and occupational therapyInitially to maintain range of movementStrengthening after acute inflammation resolvesDepending on disease severity, patients may require extensive, long-term therapy.
  • Initially to maintain range of movement
  • Strengthening after acute inflammation resolves
  • Depending on disease severity, patients may require extensive, long-term therapy.

Inpatient Considerations

  • Respiratory compromise occasionally requires mechanical ventilation.

Ongoing Care

Follow-up Recommendations

  • Serial evaluation of muscle strength and function using validated measures such as the Childhood Myositis Assessment Scale or Manual Muscle Testing
  • Muscle enzyme levels to monitor treatment efficacy and flare of inflammation
  • Joint range of motion
  • Skin exams to check for ulceration, calcinosis
  • Steroid-induced myopathy is possible; consider if weakness worsens or does not improve during treatment

Patient Education

  • Lifelong sun avoidance and sun protection
  • Steroid side effects and warnings about physiologic dependence

Prognosis

  • Presence of myositis-specific or associated antibodies can predict disease course.
  • Normal to good functional outcome: 65-80%
  • Minimal atrophy or joint contractures: 24%
  • Calcinosis cutis: 12-40%
  • Wheelchair dependent: 5%
  • Death: 1-3% (sepsis, GI bleeding or perforation, respiratory failure, myocarditis)

Complications

  • Infections, sepsis due to immunosuppression
  • Ulcerative rash and scarring
  • Calcinosis cutis
  • Skin infections at sites of ulceration, calcinosis
  • Lipoatrophy, lipodystrophy
  • Muscle fibrosis or arthritis causing joint contractures
  • Restrictive, interstitial lung disease
  • Aspiration pneumonia due to respiratory weakness and swallowing dysfunction
  • Myocarditis (rare)
  • GI tract vasculitis causing ulcerations, perforation
  • Osteoporosis due to inflammation and glucocorticoids

Additional Reading

  • Feldman BM, Rider LG, Reed AM, et al. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet. 2008;371(9631):2201-2212. [View Abstract]
  • Khanna S, Reed AM. Immunopathogenesis of juvenile dermatomyositis. Muscle Nerve. 2010;41(5):581-592. [View Abstract]
  • Ravelli A, Trail L, Ferrari C, et al. Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients. Arthritis Care Res. 2010;62(1):63-72. [View Abstract]
  • Rider LG, Lindsley CB, Cassidy JT. Juvenile dermatomyositis. In: Cassidy JT, Petty RE, Laxer RM, et al, eds. Textbook of Pediatric Rheumatology. 6th ed. Philadelphia, PA: Elsevier; 2011:375-413.
  • Rider LG, Pachman LM, Miller FW, et al, eds. Myositis and You: A Guide to Juvenile Dermatomyositis for Patients, Families, and Healthcare Providers. Washington, DC: The Myositis Association; 2007.
  • Rider LG, Shah M, Mamyrova G, et al. The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine. 2013;92(4):223-243. [View Abstract]
  • Wedderburn LR, Rider LG. Juvenile dermatomyositis: new developments in pathogenesis, assessment and treatment. Best Pract Res Clin Rheumatol. 2009;23(5):665-678. [View Abstract]

Codes

ICD09

  • 710.3 Dermatomyositis
  • 710.4 Polymyositis

ICD10

  • M33.00 Juvenile dermatopolymyositis, organ involvement unspecified
  • M33.02 Juvenile dermatopolymyositis with myopathy

SNOMED

  • 1212005 Childhood type dermatomyositis (disorder)
  • 31384009 Polymyositis (disorder)

FAQ

  • Q: Is it mandatory to perform a muscle biopsy to confirm the diagnosis?
  • A: Biopsy is indicated if diagnosis is in any way uncertain. In patients with classic rash, weakness, and elevated muscle enzymes, MRI may suffice. However, biopsy results potentially provide prognostic information.