Juvenile Dermatomyositis

Juvenile dermatomyositis (JDM) is an autoinflammatory systemic small-vessel vasculopathy that primarily affects the skin and muscle, leading to characteristic rashes and proximal muscle weakness. It is the most common idiopathic inflammatory myopathy in children. Other kinds of inflammatory myopathy include polymyositis (PM) and inclusion body myositis, which will not be discussed in this chapter as they are rare in children.

Epidemiology

The incidence is estimated to be 3 in 1,000,000 children per year with a peak age of onset of 5 to 14 years. As with many other autoimmune/autoinflammatory diseases, prevalence is higher in females than males (approximate ratio of 2:1).

Pathogenesis

The etiology of JDM is not completely understood, but it is likely due to a combination of environmental triggers in a genetically susceptible host that leads to immune dysfunction and an inflammatory tissue response. Geographic and seasonal clustering of cases has been described, lending support to environmental contributors. Additionally, preceding respiratory tract or gastrointestinal (GI) infections and ultraviolet (UV) light exposure are potential JDM triggers. Predisposing genetic factors include certain HLA loci (namely HLA-B, DRB1, and DQA1). Both innate and adaptive immunity are implicated in the pathogenesis of JDM, with humoral and cell-mediated pathways causing vascular and muscular damage.

Clinical Features

Focus primarily on skin and muscle involvement while keeping in mind that many other organ systems can be affected, as detailed below:

Constitutional Features

• low-grade fevers

• fatigue due to muscle weakness, malaise, anorexia, and weight loss

• motor developmental delays or regression of motor milestones

Mucocutaneous Manifestations

Images of mucocutaneous manifestations can be found here and here.

• characteristic rashes

  • malar rash: often involves nasolabial folds, in contrast with malar rash in systemic lupus erythematosus (SLE)

  • heliotrope rash: classically a violaceous hue to the upper eyelids

  • Gottrön papules: erythematous papules on extensor surfaces of metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints; elbows; and knees. Inverse Gottrön papules on palmar surface may be associated with anti-MDA-5 antibody and higher risk of interstitial lung disease (ILD)

• nail-fold capillary changes: nail-fold capillary dilation, giant loops, arborization, and dropout; changes correlate with disease activity

• cutaneous ulcerations: sign of more severe disease

• calcinosis: calcium deposition in the skin, subcutaneous tissue, muscles and/or visceral organs; typically occurs later in the disease course and can lead to cellulitis, joint contractures, pain (entrapped nerves), and exoskeleton (extensive subcutaneous calcification)

• lipodystrophy: slow loss of subcutaneous and visceral fat in a generalized or focal pattern; associated with metabolic derangements (hypertriglyceridemia, insulin resistance, hypertension)

• oral ulcers and gingival inflammation

Muscle Involvement

• symmetric weakness of proximal skeletal muscles: shoulders and pelvic girdle, neck, back, abdomen

• pharyngeal, hypopharyngeal, palatal weakness; can lead to dysphagia, aspiration, and vocal changes

• deep-tendon reflexes are preserved

• may not have muscle pain or tenderness

• typically, insidious onset over 3-6 months, but one third of cases are acute

• cutaneous features without clinical or laboratory evidence of muscle disease is characteristic of amyopathic dermatomyositis, an uncommon variant of JDM

Joint Involvement

• arthritis can be transient or persistent

• tenosynovitis and flexor nodules can develop

• joint contractures due to myofascial inflammation or calcinosis

Gastrointestinal Involvement

• visceral vasculopathy: severe, progressive abdominal pain with GI ulceration and bleeding (melena, hematemesis); risk of intestinal perforation associated with high mortality

• prolonged transit time: leading to constipation

Cardiopulmonary Involvement

• restrictive lung disease: due to diaphragmatic and intercostal muscle weakness or ILD

• interstitial pneumonitis: associated with poor prognosis, antisynthetase antibodies (e.g., anti-Jo-1), and anti-MDA-5 antibodies

• glucocorticoid-induced hypertension

• sinus tachycardia: the most common cardiac abnormality; serious cardiac involvement is rare but has been reported (including myocarditis, pericarditis, and conduction defects)

Diagnosis

Bohan and Peter Diagnostic Criteria for Dermatomyositis

• dermatologic features: heliotrope rash, malar rash, V-sign, shawl sign, Gottrön papules

• plus at least two of the following features for probable JDM or more than three for definite JDM:

  • progressive, symmetric weakness of limb-girdle muscles and anterior neck flexors

  • elevation of serum skeletal-muscle enzymes

  • muscle-biopsy evidence*

  • electromyographic (EMG) findings*

*If diagnosis is uncertain, MRI is often performed instead of muscle biopsy and/or EMG (although not included in diagnostic criteria).

History and Physical Exam

• Assess for failure to thrive and symptoms of aspiration (choking, coughing with oral intake); may be indications for inpatient hospitalization

• Careful skin exam for rashes, calcinosis, abnormal nailbeds, lipodystrophy

• Strength/functional assessment includes five-point strength scale and manual muscle testing using the Childhood Myositis Assessment Scale (CMAS).

• Review respiratory symptoms/chronic cough, oxygen saturation, lung exam due to risk of ILD in certain autoantibody-positive types of JDM

Laboratory Evaluation

• complete blood count (CBC) with differential: Lymphopenia and anemia of chronic inflammation may be present. Iron deficiency anemia should raise concern for gastrointestinal blood loss.

• inflammatory markers: Erythrocyte sedimentation rate (ESR) is usually mildly elevated, and C-reactive protein (CRP) is usually normal.

• muscle enzymes: Check all muscle enzymes (creatine kinase [CK], aldolase, aspartate transaminase [AST], alanine transaminase [ALT], lactate dehydrogenase [LDH]) because CK is not always elevated.

• antinuclear antibody (ANA): This is not a routine test because it does not help with diagnosis or prognosis in JDM (positive in 41%-72% of cases).

• myositis-specific autoantibodies: These autoantibodies are associated with certain disease phenotypes and can help with prognostication and comorbidity monitoring as follows:

  • anti-Mi-2: mild myositis with classic skin rashes

  • anti-Jo-1: ILD and high mortality

  • anti-p155/140 (aka anti-TIF1-gamma): severe cutaneous involvement, lipodystrophy

  • anti-MJ (aka anti-NXP2): more-severe disease, joint contractures, calcinosis, GI ulceration

  • anti-MDA-5: associated with skin and oral ulceration, arthritis, milder muscle disease, and rapid evolution of ILD (19%)

Imaging and Other Studies

• pelvic or thigh MRI without contrast: with T2- or short tau inversion recovery [STIR]-weighted images of muscles; localizes active disease sites; only needed if diagnosis is uncertain

• pulmonary function testing: in children old enough to cooperate, can identify restrictive pattern due to muscle weakness or low diffusion capacity of the lung for carbon monoxide (DLCO) due to ILD

• high-resolution chest CT: to evaluate for ILD if there is clinical concern from abnormal pulmonary function tests or reported symptoms

• electrocardiogram (ECG) and echocardiogram: baseline assessment of arrhythmias or cardiac dysfunction

• modified barium swallow: if clinical concern for dysphagia or aspiration

• muscle biopsy: if diagnosis is uncertain; classic pathology findings include perifascicular atrophy with degenerating and regenerating fibers and perivascular inflammation

• electromyography (EMG): if needed to confirm diagnosis or guide muscle biopsy; not routinely performed

Treatment

• mild disease

  • oral glucocorticoids

  • methotrexate

  • hydroxychloroquine (particularly for cutaneous disease)

• moderate-to-severe disease: severe disability (inability to get out of bed due to weakness), presence of aspiration or dysphagia, GI vasculitis, myocarditis, parenchymal lung disease, central nervous system (CNS) disease, skin ulceration

  • pulse glucocorticoids (intravenous [IV] methylprednisolone for 3 to 5 days followed by prolonged oral administration)

    • Intermittent pulses of methylprednisolone (30 mg/kg, max 1g) are utilized to help wean from daily oral steroids more quickly and prevent subsequent side effects.

  • intravenous immune globulin (IVIG) every 2-4 weeks

  • methotrexate

  • hydroxychloroquine

  • increasing consideration for early cyclophosphamide or rituximab in severe disease, particularly in the setting of ILD

• refractory disease

  • consider other agents, including cyclophosphamide, mycophenolate mofetil, rituximab, calcineurin inhibitors (cyclosporine A, tacrolimus), intermittent pulse methylprednisolone, tumor necrosis factor inhibitors, JAK-STAT inhibitors

• interstitial lung disease

  • evidence is inconclusive regarding treatment efficacy (but cyclophosphamide, rituximab, tacrolimus, and pulse glucocorticoids are commonly used options)

• sunscreen

  • minimum SPF 30 with UVA and UVB protection to prevent disease flares triggered by UV light

• vitamin D and calcium supplementation

• physical and occupational rehabilitation