Dermatomyositis and antisynthetase syndrome
- Lesion
In dermatomyositis, immune injury to small vessels causes skin rash and weakness at the edges of muscle bundles; some cases signal a hidden cancer.
What it is
Dermatomyositis is an autoimmune disease of skin and muscle in children and adults. Type I interferon signaling, complement deposition on endomysial capillaries and capillary loss injure the edges of muscle fascicles, producing perifascicular atrophy. Patients have proximal weakness with characteristic skin signs. Myositis-specific autoantibodies define subgroups: anti-Mi-2 (classic skin and muscle disease), anti-MDA5 (rapid interstitial lung disease, little myositis), anti-TIF1-γ and anti-NXP2 (cancer in adults). Antisynthetase syndrome, with antibodies against aminoacyl-tRNA synthetases such as Jo-1, combines myositis with interstitial lung disease, arthritis, Raynaud phenomenon, fever and 'mechanic's hands'.
Structure
- Perifascicular atrophy: small, degenerating fibres along the edges of fascicles where capillary loss is greatest.
- Inflammation is perimysial and perivascular rather than inside fascicles.
- Membrane attack complex deposited on endomysial capillaries; reduced capillary density.
- Type I interferon-induced proteins such as MxA in perifascicular fibres.
- Skin: interface dermatitis with mucin, similar to lupus.
Step by step
- Genetic risk and triggers (UV light, infections, tumour antigens) start an autoimmune response.
- Plasmacytoid dendritic cells produce type I interferon, which induces interferon-stimulated genes in muscle and vessels.
- Antibody and complement damage endomysial capillaries, which drop out.
- Fibres at the edges of fascicles, farthest from surviving vessels, become ischaemic and atrophic.
- In antisynthetase syndrome, immunity against tRNA synthetases injures lung and muscle together.
Autoantibodies of dermatomyositis and related myositis
| Antibody | Phenotype | Note |
|---|---|---|
| Anti-Mi-2 | Classic skin and muscle disease | Good response to treatment |
| Anti-MDA5 | Little myositis, rapid ILD, skin ulcers | High mortality from lung disease |
| Anti-TIF1-γ | Severe skin disease | Strong cancer association in adults |
| Anti-NXP2 | Calcinosis, juvenile disease | Cancer link in adults |
| Anti-Jo-1 and other synthetases | Antisynthetase syndrome | ILD, arthritis, mechanic's hands |
Clinical notes
- A new diagnosis of adult dermatomyositis calls for age-appropriate cancer screening, repeated over the first years.
- Lung function and chest CT screen for interstitial lung disease, the main cause of death in antisynthetase and anti-MDA5 disease.
- Treatment is immunosuppression with glucocorticoids and steroid-sparing agents.
Test yourself
Think of the answer, then tap the question to see it.
What is perifascicular atrophy?
Atrophy of fibres at the edges of muscle fascicles, the biopsy hallmark of dermatomyositis.
Which skin signs are typical of dermatomyositis?
Heliotrope rash of the eyelids, Gottron papules over the knuckles, shawl and V signs.
Which antibody is linked to cancer-associated dermatomyositis?
Anti-TIF1-γ (also anti-NXP2).
What features define antisynthetase syndrome?
Antisynthetase antibodies such as anti-Jo-1 with myositis, interstitial lung disease, arthritis, Raynaud and mechanic's hands.
Elsewhere in DurgiPedia
- Type I interferons (α, β)
- Autoantibodies: the table to know
- Complement: three pathways, MAC, regulators
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Myositis | Polymyositis | Dermatomyositis | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.