Dermatomyositis

Dermatomyositis is a systemic autoimmune inflammatory myopathy with characteristic cutaneous findings, typically with proximal muscle weakness. Incidence is about 1 to 10 per million per year, with a female predominance (2 to 3:1) and a bimodal age distribution (juvenile onset 5 to 15 years, adult onset 40 to 60 years). Amyopathic dermatomyositis (clinically amyopathic, without weakness for 6 months or more) accounts for 10 to 20%.

Pathogenesis

• Type I interferon-driven complement-mediated microangiopathy, with capillary loss, perifascicular atrophy, and plasmacytoid dendritic cell and B-cell infiltration. Genetic risk (HLA-DRB1*0301) and environmental triggers (UV light, viral infection, drugs such as statins, hydroxyurea, penicillamine, checkpoint inhibitors).
• Myositis-specific autoantibodies define clinical subsets and prognosis.

Myositis-specific antibodies and associations

• Anti-Mi-2: classic skin disease, V-sign and shawl sign, good response, low cancer risk.
• Anti-TIF1 gamma (p155/140): strong cancer association in adults (up to 40 to 60%), severe cutaneous disease (palmar hyperkeratosis, hypopigmented and telangiectatic "salt and pepper" lesions, ulcerations), and in children severe skin disease with lipodystrophy.
• Anti-NXP2: juvenile disease with calcinosis, dysphagia, and adult cancer association.
• Anti-MDA5 (CADM-140): clinically amyopathic disease with skin ulceration, palmar papules (Gottron papules on palms), arthritis, and rapidly progressive interstitial lung disease (RP-ILD) with high mortality, particularly in East Asian populations.
• Anti-SAE: dysphagia, severe skin disease, later myopathy.
• Antisynthetase antibodies (anti-Jo-1): overlap with antisynthetase syndrome (ILD, arthritis, mechanic's hands, Raynaud, fever).
• Anti-HMGCR is immune-mediated necrotising myopathy rather than dermatomyositis.
• Cancer-associated myositis: risk is highest within 3 years before or after diagnosis (standardised incidence ratio about 3 to 6). Common cancers: ovarian, lung, pancreatic, stomach, colorectal, breast, lymphoma and nasopharyngeal (in Asian populations).
• Complications: interstitial lung disease (20 to 40%), dysphagia and aspiration, cardiac involvement (conduction block, myocarditis), calcinosis cutis (particularly juvenile), skin ulceration, steroid myopathy, osteoporosis, infection, and respiratory muscle weakness.

Cutaneous

• Heliotrope rash: violaceous erythema and oedema of the upper eyelids.
• Gottron papules: violaceous flat-topped papules over the metacarpophalangeal and interphalangeal joints. Gottron sign: macular erythema over elbows, knees and malleoli.
• Shawl sign (upper back and shoulders), V sign (anterior neck and chest), holster sign (lateral thighs), and photosensitive facial erythema involving the nasolabial folds (unlike lupus, which spares them).
• Periungual telangiectasia and cuticular overgrowth (ragged cuticles), mechanic's hands (fissured hyperkeratotic radial fingers), scalp involvement (violaceous scaly itchy scalp, nonscarring alopecia), poikiloderma, calcinosis cutis, ulcerations, panniculitis, and oral lesions.
• Pruritus is prominent and helps distinguish from lupus.

Muscle

• Symmetric proximal weakness (shoulder and hip girdle): difficulty rising from a chair, climbing stairs, raising arms, combing hair. Neck flexor weakness (head drop). Myalgia and tenderness in a minority. Distal weakness and sparing of eye muscles. Reflexes preserved until late.
• Dysphagia (oropharyngeal and oesophageal), dysphonia, and respiratory muscle weakness.

Extramuscular

• Interstitial lung disease (dry cough, dyspnoea, fine crackles), arthralgia or non-erosive arthritis, Raynaud phenomenon, fever, weight loss, cardiac arrhythmias and conduction defects, and gastrointestinal dysmotility.
• Juvenile dermatomyositis: calcinosis, lipodystrophy, vasculopathy with gastrointestinal ulceration and perforation, and Gower sign.
• Differential diagnosis: systemic lupus erythematosus, polymyositis and other myopathies (inclusion body myositis, immune-mediated necrotising myopathy, muscular dystrophy, metabolic myopathy), statin myopathy, hypothyroid myopathy, steroid myopathy, mixed connective tissue disease, scleroderma, eosinophilia-myalgia syndrome, psoriasis, atopic dermatitis, and drug eruption.
• Red flags: rapidly progressive dyspnoea (anti-MDA5), dysphagia with aspiration, ulcerating skin disease, age over 40 with new onset (screen for cancer), cardiac symptoms, respiratory failure, and skin necrosis.

Diagnosis combines the characteristic rash, proximal weakness, raised muscle enzymes, and histology or imaging (2017 EULAR/ACR classification criteria scoring).

Laboratory

• Creatine kinase (raised up to 50 times normal, may be normal in amyopathic and some anti-TIF1 gamma, anti-MDA5 disease), aldolase, AST, ALT, LDH (muscle origin), myoglobin, ESR and CRP (often normal), ferritin (very high in anti-MDA5 RP-ILD).
• Myositis antibody panel (ANA, Mi-2, TIF1 gamma, NXP2, MDA5, SAE, Jo-1 and other antisynthetase antibodies, SRP, HMGCR), and extractable nuclear antigens (Ro52, PM/Scl, Ku).
• CBC, creatinine, electrolytes, TSH, vitamin D, HIV, hepatitis B and C screening before immunosuppression.

Neuromuscular studies

• EMG: myopathic units (small, short, polyphasic), fibrillations and positive sharp waves, complex repetitive discharges.
• MRI of thighs (STIR sequences) shows muscle and fascial oedema, guiding biopsy site.
• Muscle biopsy (open from MRI-guided oedematous muscle): perifascicular atrophy (pathognomonic), perivascular and perimysial inflammation, capillary loss, MxA upregulation, and membrane attack complex deposition on capillaries. Skin biopsy shows interface dermatitis with mucin, similar to lupus (immunofluorescence differs).

Systemic assessment

• High resolution CT chest (ground glass, consolidation, reticulation, nonspecific interstitial pneumonia and organising pneumonia patterns), pulmonary function tests with DLCO, 6 minute walk test.
• ECG, troponin, NT-proBNP, echocardiography (cardiac MRI if indicated).
• Swallow assessment: videofluoroscopy or barium swallow, speech therapy review.
• Cancer screening: thorough history and examination, CT chest, abdomen and pelvis (and PET CT in high-risk antibody groups), mammography, cervical screening, colonoscopy as age appropriate, pelvic ultrasound or CA-125 in women, PSA, and nasopharyngeal examination in endemic regions. Repeat screening annually for 3 years after diagnosis (anti-TIF1 gamma and anti-NXP2).
• Juvenile disease: capillaroscopy, MRI, and screening for lipodystrophy and calcinosis.

Skin and general measures

• Strict photoprotection: broad-spectrum sunscreen SPF 50+ (including UVA), protective clothing, avoid sun between peak hours, window film.
• Topical therapy: potent topical corticosteroids to trunk and limbs (clobetasol 0.05%), calcineurin inhibitors (tacrolimus 0.1%) to face and eyelids, topical JAK inhibitor in selected cases. Antihistamines and sedating agents for itch (hydroxyzine 10 to 25 mg at night).
• Hydroxychloroquine 200 mg twice daily (maximum 5 mg/kg/day, retinal screening) for cutaneous disease, often with partial response (about 30%), and risk of rash with HCQ in dermatomyositis. Quinacrine 100 mg daily is an alternative. Smoking cessation reduces treatment resistance.

Systemic immunosuppression (all patients with muscle weakness, severe skin, or ILD)

• Glucocorticoids first line: prednisolone 1 mg/kg/day (maximum 60 to 80 mg) for 4 to 6 weeks, then slow taper over 6 to 12 months guided by strength and CK. Methylprednisolone 500 to 1000 mg IV daily for 3 days for severe weakness, dysphagia, or ILD.
• Steroid-sparing agents started early (at diagnosis or within weeks):
  • Methotrexate 15 to 25 mg weekly (oral or SC) with folic acid 5 mg weekly (avoid with ILD risk and hepatic or renal disease).
  • Azathioprine 2 to 3 mg/kg/day (check TPMT).
  • Mycophenolate mofetil 1 to 1.5 g twice daily (preferred with ILD or skin disease).
  • Tacrolimus 0.1 mg/kg/day (trough 5 to 10 ng/mL) or ciclosporin 3 to 5 mg/kg/day, particularly for ILD.
• Intravenous immunoglobulin 2 g/kg monthly (divided over 2 to 5 days): effective for refractory skin and muscle disease, dysphagia, and as bridging. Evidence from a randomised trial (ProDERM) supports use in dermatomyositis, with benefit in about 70%.
• Rituximab 1 g IV on days 1 and 15 (or 375 mg/m2 weekly for 4 doses) for refractory disease, antisynthetase syndrome and ILD.
• JAK inhibitors (tofacitinib 5 mg twice daily, baricitinib 2 to 4 mg daily) for refractory skin and muscle disease, and for anti-MDA5 disease, with monitoring for infection and thrombosis. Evidence is growing from case series and trials.
• Cyclophosphamide 500 to 1000 mg/m2 IV monthly (or 0.5 to 1 g every 2 to 4 weeks) for severe ILD.

Rapidly progressive ILD (especially anti-MDA5)

• Triple immunosuppression early: high-dose methylprednisolone 500 to 1000 mg IV for 3 days, then prednisolone 1 mg/kg, plus tacrolimus (target trough 8 to 12 ng/mL) or ciclosporin, plus IV cyclophosphamide 500 to 750 mg/m2 every 2 to 4 weeks. Add tofacitinib 5 to 10 mg twice daily, rituximab, or IVIG. Plasma exchange and ECMO as salvage. Mortality remains 30 to 50%. Pneumocystis prophylaxis with co-trimoxazole 960 mg three times weekly.

Calcinosis cutis

• Early aggressive immunosuppression to prevent. Treatments (limited evidence): diltiazem 120 to 480 mg daily, sodium thiosulfate (intralesional or IV 25 g three times weekly), minocycline 100 mg twice daily, bisphosphonates, probenecid, colchicine, IVIG, warfarin low dose, and surgical excision of symptomatic deposits.

Cancer-associated disease: treat the malignancy (muscle and skin may improve with tumour control), together with immunosuppression. Return of disease signals recurrence.

Supportive care

• Dysphagia: speech therapy, modified diet, PEG feeding if aspiration, and IVIG. Cricopharyngeal myotomy or botulinum injection in refractory cases.
• Rehabilitation: physiotherapy begun early, with gentle strengthening exercise safely in active disease and resistance training in remission. Vitamin D 800 to 2000 IU and calcium 1000 to 1200 mg, bone protection with bisphosphonate if on prolonged steroids (alendronate 70 mg weekly), and gastric protection.
• Monitoring and prophylaxis: Pneumocystis prophylaxis during combination immunosuppression, glucose, blood pressure, lipids, vaccination (inactivated influenza, pneumococcal, COVID-19, recombinant zoster), and avoidance of live vaccines on immunosuppression.
• Statins should be reviewed if myopathy persists (check anti-HMGCR).

Juvenile dermatomyositis

• Prednisolone 2 mg/kg/day (maximum 60 mg) with methotrexate 15 mg/m2 weekly from diagnosis, IV methylprednisolone 30 mg/kg (maximum 1 g) for severe cases, IVIG, and biologics for refractory disease. Early treatment reduces calcinosis. Monitor growth and bone health.

Follow-up

• Review every 4 to 8 weeks initially with strength testing (Manual Muscle Testing, CMAS), CK, skin scores (CDASI), and ILD surveillance (PFTs and chest imaging every 3 to 6 months in the first year). Relapse occurs in about 40 to 50% on tapering. Repeat cancer screening