Idiopathic Inflammatory Myopathies

Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle diseases. They are characterised by inflammatory infiltration of skeletal muscle producing symmetrical proximal muscle weakness. Several distinct clinical and histopathological subtypes carry different associations and treatment approaches.

Classification

Dermatomyositis is characterised by distinctive skin findings accompanying muscle weakness, with a perivascular and perifascicular pattern of muscle inflammation reflecting a complement mediated microangiopathy, and a notable association with underlying malignancy, particularly around the time of diagnosis in adults.

Polymyositis presents with muscle weakness without the characteristic skin findings, with a direct cytotoxic T cell mediated attack on muscle fibres, and is a less common and somewhat controversial diagnosis given overlap with other myopathies once modern diagnostic criteria and antibody testing are applied.

Immune mediated necrotising myopathy presents with severe, often rapidly progressive weakness and markedly elevated creatine kinase, associated with anti signal recognition particle or anti HMG CoA reductase antibodies, the latter sometimes triggered by statin exposure and persisting after drug withdrawal.

Inclusion body myositis is distinct from the other subtypes, occurring predominantly in older men, with a characteristically slow, asymmetrical pattern of weakness affecting distal as well as proximal muscles (notably finger flexors and quadriceps), poor response to immunosuppression, and specific histological findings (rimmed vacuoles, inclusion bodies) reflecting a combined inflammatory and degenerative process.

Myositis associated with connective tissue disease overlap and antisynthetase syndrome represent important recognisable phenotypes with specific management implications, particularly regarding pulmonary surveillance. Antisynthetase syndrome is characterised by myositis, interstitial lung disease, arthritis, mechanic's hands, Raynaud phenomenon and fever, associated with anti Jo 1 and related antisynthetase antibodies.

Symmetrical proximal muscle weakness developing over weeks to months is the core feature across most subtypes, manifesting as difficulty rising from a chair, climbing stairs, raising the arms overhead, and, in severe cases, neck flexor weakness and dysphagia from pharyngeal muscle involvement.

Dermatomyositis specific cutaneous features include:

• Heliotrope rash (violaceous discolouration of the upper eyelids, often with periorbital oedema).
• Gottron papules (scaly erythematous or violaceous papules over the extensor surfaces of the metacarpophalangeal and interphalangeal joints, pathognomonic when present).
• Gottron sign (similar erythema over extensor surfaces without discrete papules).
• Shawl sign (erythema over the upper back and shoulders).
• Mechanic's hands (rough, cracked skin over the finger pads and lateral fingers).

Antisynthetase syndrome features (mechanic's hands, arthritis, Raynaud phenomenon, fever and interstitial lung disease) may dominate the presentation, sometimes with interstitial lung disease preceding or occurring independent of overt myositis.

Dysphagia from pharyngeal and oesophageal muscle involvement carries aspiration risk and requires active assessment.

Cardiac involvement (myocarditis, conduction abnormalities) and interstitial lung disease contribute significantly to morbidity and mortality across the inflammatory myopathies.

Inclusion body myositis presents distinctively with slowly progressive, often asymmetrical weakness, prominent early quadriceps and finger flexor involvement, frequent falls from knee buckling, and a notably poor response to standard immunosuppressive therapy.

Constitutional symptoms and, in dermatomyositis particularly, features of an underlying occult malignancy should be actively sought, especially in adults over forty at diagnosis or with atypical or refractory disease.

Creatine kinase is markedly elevated in most subtypes (though can be normal in dermatomyositis, particularly with predominant skin disease, and in inclusion body myositis it is typically only mildly elevated), with aldolase, lactate dehydrogenase, alanine aminotransferase and aspartate aminotransferase also frequently elevated reflecting muscle breakdown.

Myositis specific and myositis associated autoantibody panel identifies clinically important subgroups with specific prognostic and management implications:

• anti Jo 1 and other antisynthetase antibodies (interstitial lung disease risk)
• anti Mi 2 (classical dermatomyositis, good prognosis)
• anti TIF1 gamma and anti NXP2 (strong malignancy association in adult dermatomyositis)
• anti MDA5 (characteristic skin ulceration and rapidly progressive interstitial lung disease, a recognised cause of severe respiratory failure requiring urgent recognition)
• anti SRP and anti HMG CoA reductase (necrotising myopathy)

Electromyography shows characteristic myopathic changes (short duration, low amplitude polyphasic motor unit potentials, fibrillation potentials, complex repetitive discharges) and helps exclude a neurogenic cause of weakness.

Muscle magnetic resonance imaging identifies areas of active inflammation (useful for guiding biopsy site and for monitoring treatment response) and, in inclusion body myositis, characteristic patterns of muscle atrophy and fatty replacement.

Muscle biopsy remains important for definitive subtype classification, particularly to distinguish inclusion body myositis (with its characteristic rimmed vacuoles and inclusions, which fundamentally changes the management approach) from the other inflammatory myopathies, and in cases where the diagnosis remains uncertain after serological and clinical assessment.

Malignancy screening (age and sex appropriate cancer screening, with a lower threshold for full investigation including computed tomography of the chest, abdomen and pelvis) is essential in adult onset dermatomyositis, particularly with anti TIF1 gamma or anti NXP2 positivity. The malignancy risk is substantially elevated, clustering around the time of diagnosis.

Pulmonary function testing and high resolution computed tomography of the chest screen for interstitial lung disease, particularly important and urgent in antisynthetase syndrome and with anti MDA5 positivity given the risk of rapidly progressive, life threatening lung disease.

High dose corticosteroids (prednisolone 1 mg per kg daily, or intravenous methylprednisolone for severe disease) are first line induction therapy across the inflammatory myopathies excluding inclusion body myositis, with gradual tapering guided by clinical strength and creatine kinase response.

Steroid sparing immunosuppression is introduced early given the near universal need for prolonged treatment. Methotrexate or azathioprine are first line agents. Mycophenolate mofetil, ciclosporin, tacrolimus, rituximab or intravenous immunoglobulin are used for refractory disease or where interstitial lung disease is prominent (mycophenolate and tacrolimus in particular are favoured with significant pulmonary involvement).

Intravenous immunoglobulin is particularly effective and often used early in necrotising myopathy (especially anti HMG CoA reductase associated disease) and in severe, refractory or rapidly progressive dermatomyositis, including anti MDA5 associated disease.

Anti MDA5 associated rapidly progressive interstitial lung disease requires aggressive combination immunosuppression (typically corticosteroids, a calcineurin inhibitor and either cyclophosphamide or rituximab, sometimes with plasma exchange) initiated urgently given the high mortality of untreated disease.

Statin discontinuation is required in suspected statin associated anti HMG CoA reductase myopathy, though immunosuppression is typically still required given the autoimmune nature of the persisting disease even after drug withdrawal.

Physiotherapy is essential throughout, both during the acute phase (gentle range of motion to prevent contracture) and recovery phase (progressive strengthening as inflammation settles), and speech and language therapy assessment for dysphagia with aspiration precautions where indicated.

Sun protection and topical therapy (corticosteroids, calcineurin inhibitors) for the cutaneous manifestations of dermatomyositis, with hydroxychloroquine commonly added for refractory skin disease.

Inclusion body myositis management differs fundamentally given poor immunosuppressive response: physiotherapy, occupational therapy, mobility aids and fall prevention form the mainstay, with a trial of immunosuppression sometimes attempted but expectations set appropriately given the generally disappointing response and progressive natural history of this condition.

Cardiac assessment (electrocardiogram, echocardiography) given the risk of myocarditis and conduction disease, and ongoing malignancy vigilance in dermatomyositis beyond the initial screening period, particularly with refractory or relapsing disease.