Dermatomyositis/Polymyositis

Basics

DESCRIPTION

Juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) are inflammatory myopathies in which inflammation within tissues and capillary endothelium of muscle, skin, and other organs 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.

EPIDEMIOLOGY

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 triggers
- 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

GENETICS

Genetic factors, including the following:
- HLA alleles: B8, DRB1*0301, DQA1*0501, DQA1*0301
- Cytokine polymorphisms: TNFα-308A promoter, various IL-1 genes, interferon regulatory factor 5, and others, all resulting in upregulated inflammation
- Polymorphisms of immunoglobulin constant regions
Epigenetic factors likely exist: Monozygotic twin studies show low concordance.

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 expression
- 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
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.

ASSOCIATED-CONDITIONS

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

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