Inflammatory Myopathies

The idiopathic inflammatory myopathies (IIM) are acquired, immune-mediated diseases of skeletal muscle producing symmetrical proximal muscle weakness with muscle inflammation, raised muscle enzymes and extramuscular involvement.

Pathy's classifies acquired myopathies into idiopathic inflammatory myopathies — dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM) — alongside alcohol-related, drug-induced, endocrine and metabolic, and paraneoplastic myopathies.

Modern classification adds immune-mediated necrotising myopathy (IMNM) and antisynthetase syndrome, and regards "polymyositis" as a shrinking diagnosis of exclusion.

Geriatric significance: inclusion body myositis is the commonest acquired myopathy after 50 years, and dermatomyositis in an older adult carries a high risk of underlying malignancy. IIM must always be separated from the far commoner statin myopathy, hypothyroid myopathy, PMR and sarcopenia.

Dermatomyositis is a humoral, complement-mediated microangiopathy: antibody and complement deposition (membrane attack complex) on endomysial capillaries causes capillary dropout, muscle ischaemia and the characteristic perifascicular atrophy. Interferon type I signature is prominent.

Polymyositis is a cell-mediated disease: CD8+ cytotoxic T cells invade non-necrotic muscle fibres expressing MHC class I — the histological hallmark of endomysial inflammation.

Inclusion body myositis combines autoimmune (CD8+ T-cell) inflammation with a degenerative process — rimmed vacuoles, congophilic amyloid, tau and TDP-43 aggregates, and mitochondrial abnormalities (ragged red, COX-negative fibres). This dual pathology explains its poor response to immunosuppression.

Immune-mediated necrotising myopathy shows scattered necrotic and regenerating fibres with sparse inflammation, and is associated with anti-SRP and anti-HMGCR antibodies — the latter typically statin-triggered and persisting after statin withdrawal.

Core presentation: painless, symmetrical, proximal weakness — difficulty rising from a chair or toilet, climbing stairs, and lifting the arms above the head. Myalgia is present in only about a third; pain-free weakness is the rule.

Cutaneous features of dermatomyositis: heliotrope rash (violaceous periorbital discolouration with oedema), Gottron's papules over the metacarpophalangeal and interphalangeal joints and Gottron's sign over elbows and knees, shawl sign and V-sign photodistributed erythema, mechanic's hands, periungual telangiectasia with ragged cuticles, calcinosis cutis and poikiloderma. Skin disease may precede muscle disease (amyopathic dermatomyositis).

Extramuscular: dysphagia from pharyngeal and upper oesophageal muscle involvement (also the commonest cause of aspiration in IBM), respiratory muscle weakness, interstitial lung disease (especially with antisynthetase antibodies and anti-MDA5), non-erosive arthritis, Raynaud's phenomenon, myocarditis and arrhythmia.

Antisynthetase syndrome: myositis, interstitial lung disease, arthritis, Raynaud's, fever and mechanic's hands, with anti-Jo-1 or other anti-tRNA synthetase antibodies.

Malignancy association — a key geriatric point: dermatomyositis, particularly with anti-TIF1-γ or anti-NXP2 antibodies, carries a markedly increased risk of occult cancer (ovary, lung, breast, colorectal, stomach, pancreas, and nasopharyngeal carcinoma in Asian populations). Risk is highest in the first 1–3 years around diagnosis. Pathy's separately recognises paraneoplastic myopathies as a category.

Red flags for IBM: a man over 50 with slowly progressive, asymmetrical weakness of the quadriceps (causing falls and knee buckling) and long finger flexors (causing loss of grip), early dysphagia, and a CK that is normal or only mildly elevated, who has "failed steroids".

Clinical assessment of the pattern, distribution and tempo of weakness — the first step in Pathy's myopathy chapter.

Biochemical studies: creatine kinase (the key screening test), aldolase, lactate dehydrogenase and transaminases (a raised ALT/AST from muscle is often mistaken for liver disease); also TSH, calcium, phosphate, vitamin D, potassium, renal function and ESR/CRP.

Electrophysiology (EMG): shows a myopathic pattern — small-amplitude, short-duration polyphasic motor unit potentials with early recruitment, plus spontaneous activity (fibrillations, positive sharp waves) indicating active inflammation. In IBM, mixed myopathic and neurogenic units are seen.

Muscle biopsy is the definitive test: perifascicular atrophy with perimysial and perivascular CD4/B-cell infiltrate in DM; endomysial CD8+ invasion of non-necrotic MHC-I expressing fibres in PM; rimmed vacuoles with congophilic inclusions and ragged red fibres in IBM; necrosis without inflammation in IMNM.

Myositis-specific and myositis-associated antibodies: anti-Jo-1 and other synthetases, anti-Mi-2 (classic DM, good prognosis), anti-TIF1-γ and anti-NXP2 (malignancy), anti-MDA5 (clinically amyopathic DM with rapidly progressive ILD, high mortality), anti-SAE, anti-SRP and anti-HMGCR (necrotising myopathy), anti-cN1A (IBM).

MRI of thigh muscles with STIR sequences shows oedema and guides the biopsy site while excluding fatty replacement; useful when biopsy is difficult in a frail patient.

Screening for complications and associations: high-resolution CT chest and pulmonary function tests with DLCO for ILD, video-fluoroscopic swallow, ECG and echocardiography, and age-appropriate malignancy screening — CT chest/abdomen/pelvis, mammography, PSA, colonoscopy and pelvic ultrasound, repeated annually for 3 years in high-risk DM.

Classification criteria: the 2017 ACR/EULAR classification criteria for adult and juvenile IIM have replaced the older Bohan and Peter criteria; the 2016 ACR/EULAR Myositis Response Criteria Total Improvement Score (TIS) is the standard outcome measure in trials.

Drug-induced myopathies — Pathy's classifies these as painful myopathy, painless myopathy, focal myopathy, periodic weakness and acute rhabdomyolysis; statin-induced myopathy is dealt with separately and is the single commonest mimic. Also gold-induced myopathy, colchicine, amiodarone, chloroquine, zidovudine, and alcohol-related myopathy.

Endocrine and metabolic myopathies: hypothyroidism, hyperthyroidism, Graves' ophthalmopathy, pituitary– adrenal axis disorders (Cushing's and steroid myopathy), primary hyperparathyroidism, osteomalacia and disorders of vitamin D metabolism.

Others: polymyalgia rheumatica (normal CK, normal EMG, normal biopsy), myasthenia gravis (fatigable, ocular/bulbar, normal CK), motor neurone disease, muscular dystrophies presenting late (facioscapulohumeral, oculopharyngeal, myotonic), sarcopenia and disuse atrophy, and electrolyte disturbance.

Corticosteroids are first-line for DM, PM and IMNM: prednisolone 0.75–1 mg/kg/day (or pulse methylprednisolone in severe disease), continued until strength improves and CK falls, then tapered slowly over 9–12 months.

Steroid-sparing agents from the outset in older adults, given the certainty of steroid toxicity: methotrexate, azathioprine, or mycophenolate mofetil — Pathy's specifically lists mycophenolate mofetil for dermatomyositis. Ciclosporin and tacrolimus are alternatives, particularly with interstitial lung disease.

Intravenous immunoglobulin for refractory or severe disease, dysphagia, or when immunosuppression is hazardous — it is now licensed for dermatomyositis. Rituximab is used in refractory disease and antisynthetase syndrome; cyclophosphamide for rapidly progressive ILD, often with tacrolimus.

Cutaneous disease: strict photoprotection, topical corticosteroids and calcineurin inhibitors, and hydroxychloroquine. Pruritus can be severe and disabling.

Inclusion body myositis: no immunosuppressive therapy has been shown to alter the natural history — management is supportive with resistance and aerobic exercise, occupational therapy, ankle-foot orthoses, walking aids, dysphagia assessment with diet modification, and cricopharyngeal dilatation or myotomy for severe dysphagia.

Universal supportive care in the elderly: physiotherapy and graded exercise (safe and beneficial even in active myositis), speech and language therapy for dysphagia with aspiration precautions, nutrition, osteoporosis prophylaxis with calcium, vitamin D and a bisphosphonate from day one, gastroprotection, glucose monitoring, screening for latent tuberculosis before immunosuppression, vaccination, and Pneumocystis prophylaxis on high-dose combined immunosuppression.

Prognosis: DM and PM generally respond well, with 5-year survival above 75–80%; adverse prognostic factors are older age, dysphagia, interstitial lung disease (especially anti-MDA5), cardiac involvement and underlying malignancy. IBM is relentlessly progressive, with most patients needing a walking aid within 5–10 years, though it does not markedly shorten life expectancy.