Dermatomyositis

Much of the etiology is unknown. It is proposed from clinical observation, disease models, and experimental studies that DM may result from interplay between genetic susceptibility and environmental factors.[13]

Genetic and immunologic: a genetic predisposition is suggested by the occurrence in monozygotic twins, familial cases, and familial association with other autoimmune diseases.[14][15][16] There appears to be an association between certain human leukocyte antigen (HLA) subtypes and increased risk of developing DM.[17][18] Additionally, there is a stronger association between HLA genotypes and specific myositis-associated antibodies.[18][19][20][21]
Environmental: attempts to identify environmental triggers have found only weak associations. The strongest evidence exists for the role of ultraviolet radiation intensity in the development of DM associated with anti-Mi-2 antibodies.[22][23][24]
Infection: although numerous viral and bacterial agents have been shown to directly cause localized myositis, the association between infectious agents and the development of the disorder is less clear. There are some reports of DM/polymyositis developing in patients with antibodies to Borrelia burgdorferi and Toxoplasma gondii.[25][26] Other studies describe findings of viral antibodies, viral particles, and viral nucleic acids in patients with inflammatory myopathies.[27][28][29][30][31][32][33][34][35] Despite this, definitive evidence of an infectious etiology is yet to be found.
Drug-induced: drugs that have been implicated in causing DM include D-penicillamine, hydroxyurea, statins, phenylbutazone, and terbinafine.[36][37][38][39][40][41][42][43][44]

DM is widely accepted to be of autoimmune origin. Factors supporting this include:

the presence of autoantibodies
association with other autoimmune disorders
evidence of T-cell mediated muscle injury
complement-mediated vascular damage
response to immunosuppression.

Although autoantibodies are found in most patients, their role in the pathogenesis is uncertain. Autoantibodies are, however, associated with certain clinical presentations.[3][45][46][47][48][49][50]

Much about the pathogenesis is unclear, but it is postulated that DM is predominantly humorally mediated and that the endothelium of endomysial capillaries is the primary antigenic target.[3]

Complement-mediated vascular damage occurs, but it is unknown whether this is due to activation of complement C3 or deposition of complement proteins and other immune complexes.[51][52] This results in endothelial cell damage, capillary necrosis, perivascular inflammation, ischemia, and destruction of muscle fibers.[53][54] Complement activation also leads to the production of cytokines and chemokines that facilitate movement of activated T cells into the perimysial and endomysial spaces. Cardinal features on muscle biopsy are perifascicular atrophy, capillary loss, and a cellular infiltrate of B cells and CD4-positive T cells in keeping with a humorally mediated process.[55]

Interferon (IFN) -alfa and -beta may also have a role in the pathogenesis. Several genes known to be regulated by IFN-alfa and IFN-beta are up-regulated in the capillaries and perifascicular muscle fibers.[56]

Studies focusing on adult and juvenile DM skin biopsies support the role of vasculopathy in skin lesions, as has been demonstrated in muscle.[57]

Classification of dermatomyositis based on skin and/or muscle involvement at presentation[2]

1. Classic dermatomyositis (CDM): hallmark dermatomyositis (DM) skin manifestations, proximal muscle weakness, and laboratory evidence of myositis.

Adult-onset CDM
Juvenile-onset CDM.

2. Clinically amyopathic dermatomyositis (CADM): skin disease present and no clinical muscle weakness at the time of diagnosis. Amyopathic patients require continued follow-up to screen for the development of muscle disease.

Amyopathic dermatomyositis (ADM): biopsy-confirmed typical skin DM lesions (for ≥6 months) but no clinical muscle weakness or laboratory, radiologic, or histopathologic evidence of myositis.
Hypomyopathic dermatomyositis (HDM): biopsy-confirmed typical skin DM lesions (for ≥6 months) and no clinical muscle weakness, but elevated (or normal) muscle enzymes and electrophysiologic, radiologic, or histopathologic evidence of myositis.

3. Premyopathic dermatomyositis (PRMDM): hallmark DM skin lesions present for <6 months with no evidence of muscle weakness.

4. Adermatopathic dermatomyositis: typical pattern of muscle weakness with typical histology on muscle biopsy but no skin involvement.[3]

Etiology

Pathophysiology

Classification