Inflammatory Myopathies

The idiopathic inflammatory myopathies (IIM) are a group of acquired autoimmune diseases characterised by chronic muscle inflammation, progressive skeletal muscle weakness, and multi-organ involvement. The principal adult subtypes — dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), and immune-mediated necrotising myopathy (IMNM) — differ in pathogenesis, clinical phenotype, cancer association, and treatment responsiveness.

In Australia, population-based data from the Australian Institute of Health and Welfare (AIHW) and state-based registries estimate the overall prevalence of IIM at approximately 10–15 per 100,000 persons. Dermatomyositis has an annual incidence of approximately 5–9 per million, with a bimodal age distribution peaking in childhood (5–15 years) and adulthood (45–60 years). PM is rarer and increasingly recognised to overlap with other autoimmune conditions (overlap myositis). IBM is the most common acquired myopathy in patients over 50 years, with an estimated prevalence of 45–70 per million in those aged ≥50, and a male-to-female ratio of approximately 3:1.

IMNM has gained increasing recognition since the association of anti-HMGCR antibodies with statin exposure was described in 2010. With Australia's high rates of statin use (approximately 2.5 million PBS prescriptions annually), statin-associated IMNM is an important consideration in any patient presenting with unexplained myalgia and markedly elevated creatine kinase (CK).

The overlap of DM and PM with systemic autoimmune features — interstitial lung disease (ILD), arthritis, Raynaud phenomenon, and mechanic's hands — is collectively termed antisynthetase syndrome when associated with anti-aminoacyl-tRNA synthetase antibodies. Australian rheumatology referral pathways emphasise early recognition and MSA testing to guide cancer screening urgency and therapeutic decisions.

Dermatomyositis is an autoimmune inflammatory myopathy with distinctive cutaneous manifestations and a well-established association with malignancy in adults. It is mediated by complement-driven microangiopathy affecting intramuscular blood vessels and skin.

Clinical Features

• Muscle: Symmetrical, progressive proximal weakness (difficulty rising from chairs, climbing stairs, lifting arms above head). Dysphagia occurs in 20–30%.
• Skin (pathognomonic): Heliotrope rash (violaceous periorbital oedema), Gottron papules (erythematous papules over MCP/PIP/DIP joints), shawl sign, V-sign, mechanic's hands, periungual erythema, and calcinosis (more common in juvenile DM).
• Systemic: Interstitial lung disease (especially anti-MDA5 and anti-synthetase), dysphagia, cardiac involvement (arrhythmia, myocarditis), arthralgia, constitutional symptoms.

Diagnosis

Diagnosis follows the 2017 EULAR/ACR classification criteria. Characteristic skin findings plus proximal weakness, elevated CK, and myopathic EMG or MRI signal abnormality strongly suggest DM. Muscle biopsy shows perifascicular atrophy — the histopathological hallmark.

Treatment

Cutaneous Management

• Sun protection (SPF 50+, protective clothing) — essential; UV exposure exacerbates skin disease.
• Topical corticosteroids (moderate potency, e.g., mometasone furoate 0.1%) for localised Gottron papules and rash.
• Hydroxychloroquine 200–400 mg/day PO — PBS General Benefit — for refractory skin disease.
• For calcinosis: no proven pharmacotherapy; surgical excision for symptomatic lesions. Trials of diltiazem, colchicine, and sodium thiosulfate with limited evidence.

Polymyositis is an autoimmune myopathy characterised by subacute proximal muscle weakness without the cutaneous features of dermatomyositis. It is mediated by direct CD8+ cytotoxic T-cell attack on muscle fibres. PM is increasingly recognised as an entity that frequently overlaps with other connective tissue diseases (antisynthetase syndrome, scleroderma-overlap, mixed connective tissue disease).

Clinical Features

• Symmetrical proximal weakness developing over weeks to months.
• Dysphagia in 30–40% — may be presenting feature.
• No skin involvement (distinguishes from DM).
• May overlap with ILD, arthritis, Raynaud, mechanic's hands — screen for antisynthetase antibodies.
• Cardiac involvement (arrhythmia, conduction defects, myocarditis) in 10–30%.

Diagnosis

Requires: (1) proximal weakness, (2) elevated CK, (3) myopathic EMG with fibrillation potentials and short-duration polyphasic motor unit potentials, (4) muscle biopsy showing endomysial CD8+ T-cell infiltrate invading non-necrotic muscle fibres, and (5) absence of skin findings. Anti-Jo-1 (anti-histidyl-tRNA synthetase) is the most common associated antibody.

Treatment

Treatment mirrors dermatomyositis — high-dose prednisolone with early addition of steroid-sparing agent:

• First-line: Prednisolone 1 mg/kg/day + methotrexate (preferred) or azathioprine.
• Second-line: Mycophenolate mofetil, tacrolimus (especially for ILD), rituximab (refractory disease; PBS Authority Required for rheumatoid — off-label use).
• IVIg: 2 g/kg divided over 2–5 days for severe or refractory disease; PBS Authority Required via Specialist Drug Programs.

Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients over 50 years and the most common inflammatory myopathy in men. It is characterised by a combination of inflammatory and degenerative pathological features (rimmed vacuoles, amyloid deposits, TDP-43 aggregates). IBM is largely resistant to immunosuppressive therapy.

Clinical Features

• Insidious onset: Slowly progressive over years; often misdiagnosed as PM or age-related weakness.
• Finger flexor weakness: Weakness of flexor digitorum profundus (FDP) — cannot grip objects, turn keys, open jars. This pattern is highly characteristic.
• Quadriceps weakness: Early knee extensor weakness leading to falls and difficulty rising from seated position.
• Asymmetric involvement: Unlike DM/PM, IBM may be notably asymmetric.
• Dysphagia: Present in up to 60%; can be severe and life-threatening (aspiration risk).
• CK: Normal or only mildly elevated (typically <10× ULN).

Diagnosis

2011 ENMC criteria require: (1) duration >12 months, (2) age >45 years, (3) weakness of finger flexors and/or quadriceps, (4) CK <15× ULN, (5) EMG with myopathic or mixed pattern, and (6) muscle biopsy with endomysial inflammatory infiltrate AND rimmed vacuoles.

Management

• Physiotherapy: Supervised, progressive resistance training — maintains function, does not exacerbate disease.
• IVIg: May provide modest benefit in swallowing function; 2 g/kg over 2–5 days every 4 weeks for selected patients with significant dysphagia.
• Dysphagia: Speech pathology assessment, modified diet textures, oesophageal dilatation for cricopharyngeal dysfunction; consider botulinum toxin injection to upper oesophageal sphincter.
• Fall prevention: Home modifications, walking aids, quadriceps strengthening.
• Clinical trials: Emerging therapies — arimoclomol (heat shock protein co-inducer), sirolimus, rapamycin; refer to tertiary centres for trial access.

Immune-mediated necrotising myopathy (IMNM), also termed necrotising autoimmune myopathy (NAM), is characterised by prominent myofibre necrosis with minimal inflammatory infiltrate on muscle biopsy. Two major autoantibody-defined forms exist: anti-HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and anti-SRP (signal recognition particle).

Anti-HMGCR Myopathy

• Strongly associated with statin exposure (atorvastatin, rosuvastatin most commonly in Australia), but also occurs statin-naïve, particularly in younger patients.
• Presents with severe proximal weakness and very high CK (often >10× ULN, frequently >3,000 U/L).
• Weakness persists and may worsen after statin cessation — distinguishes from self-limiting statin myopathy.
• Treatment: Immunosuppression as per DM/PM; often requires IVIg for refractory disease.
• Antibody titres correlate with disease activity — useful for monitoring.

Anti-SRP Myopathy

• Not associated with statins; presents with severe, rapidly progressive proximal weakness.
• Very high CK levels (often >5,000 U/L).
• Higher rates of cardiac involvement (arrhythmia, heart failure) — baseline ECG and echocardiogram recommended.
• Treatment: Often requires combination therapy — prednisolone + steroid-sparing agent + IVIg or rituximab.
• Generally more treatment-resistant than anti-HMGCR IMNM.

Myositis-specific antibodies (MSA) define distinct clinical phenotypes, predict cancer risk, inform screening urgency, and guide treatment. Testing is available at major Australian reference laboratories (including Royal Prince Alfred Hospital immunology, SA Pathology, and interstate referral centres).

Testing in Australia

• MSA panels available via line immunoassay (Euroline) or addressable laser bead immunoassay (ALBIA) at reference laboratories.
• MBS item: Not directly MBS-rebated as a panel; individual antibody tests may be billed under extended serology. Specialist referral required.
• Myositis-associated antibodies (MAA) — anti-PM-Scl, anti-Ku, anti-U1-RNP, anti-Ro52 — indicate overlap syndromes and should be tested in conjunction with MSA.

Adult-onset dermatomyositis carries a 4–7-fold increased risk of malignancy, with the highest risk in the first 3 years after diagnosis. Approximately 20–30% of adult DM patients will be diagnosed with cancer, most commonly within the first year. Cancer screening is therefore mandatory at diagnosis and must continue for at least 3–5 years.

Recommended Screening Protocol (Australian Practice)

Cancers Most Commonly Associated with DM

Severity assessment guides treatment intensity and monitoring frequency. Stratify patients at diagnosis based on functional impairment, organ involvement, antibody profile, and cancer risk.

Validated Outcome Measures

• MDAAT (Myositis Disease Activity Assessment Tool): Physician global activity (0–10 VAS), muscle VAS, extramuscular VAS.
• CMAS (Childhood Myositis Assessment Scale): 14-item functional scale; validated for children and useful in adults.
• MMT-8 (Manual Muscle Testing 8): Quantitative strength testing of 8 proximal muscle groups.
• HAQ-DI (Health Assessment Questionnaire — Disability Index): Patient-reported functional status.

First-Line Therapy (DM, PM, IMNM)

Second-Line & Refractory Disease

Allergy / Intolerance Alternatives

• Methotrexate intolerance (GI or hepatotoxicity): Switch to azathioprine or mycophenolate mofetil. Consider SC methotrexate to reduce GI side effects.
• Azathioprine (low TPMT): Switch to methotrexate or mycophenolate mofetil.
• Myositis-ILD (refractory to MMF): Add or switch to tacrolimus; consider rituximab.
• Corticosteroid-sparing in pregnancy: Azathioprine (safe), hydroxychloroquine (safe). Avoid methotrexate and mycophenolate (teratogenic).

1. 1. Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Arthritis Rheumatol. 2017;69(12):2271–2282.
2. 2. Allenbach Y, Mammen AL, Benveniste O, Stenzel W. 224th ENMC International Workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies, Naarden, The Netherlands, 14–16 October 2016. Neuromuscul Disord. 2018;28(1):87–99.
3. 3. Rose MR. 188th ENMC International Workshop: Inclusion body myositis, 2–4 December 2011, Naarden, The Netherlands. Neuromuscul Disord. 2013;23(12):1044–1055.
4. 4. Tiniakou E,