Immune-Mediated Necrotizing Myopathy
🧪 Anti-signal recognition particle (SRP) and anti-HMG-CoA reductase (HMGCR) autoantibodies are strongly linked with immune-mediated necrotizing myopathy (IMNM), a rare but severe autoimmune myopathy.
🌍 About
- IMNM is a subgroup of idiopathic inflammatory myopathies characterised by profound muscle fibre necrosis with relatively little inflammation.
- Unlike polymyositis or dermatomyositis, the pathology is driven more by antibody-mediated muscle injury than by cellular infiltration.
🧬 Aetiology & Pathophysiology
- Histology shows myofibre necrosis and regeneration, but minimal inflammatory cell infiltrate.
- Anti-SRP antibodies: thought to cause direct immune-mediated muscle injury via complement activation.
- Anti-HMGCR antibodies: associated with prior statin exposure (though can occur without). Antibodies persist even after statin withdrawal → ongoing myopathy.
- Genetic predisposition: HLA-DRB1*11:01 increases risk of anti-HMGCR IMNM.
🧾 Types of IMNM
- 🔴 Anti-SRP myopathy: severe, rapidly progressive weakness, often treatment-resistant.
- 🟣 Anti-HMGCR myopathy: linked to statins, but not always statin-induced.
- ⚪ Antibody-negative IMNM: diagnosis relies on biopsy + clinical features.
🩺 Clinical Features
- 💪 Severe proximal weakness (difficulty rising from chairs, climbing stairs, lifting arms).
- 🫁 Interstitial lung disease (ILD) may occur, particularly with anti-SRP.
- ⚡ Muscle pain and fatigue are common.
- 🧏 Dysphagia in advanced cases (bulbar involvement).
🔬 Investigations
- 🧪 Autoantibodies: anti-SRP or anti-HMGCR (ELISA, immunoblot).
- 📈 Creatine kinase (CK): typically very high (often >10,000 IU/L).
- 🧫 Muscle biopsy: necrosis + regeneration with little lymphocytic infiltrate.
- ⚡ EMG: myopathic pattern, helps exclude mimics such as myasthenia gravis.
- 🖥️ MRI: detects muscle oedema and fatty replacement, guides biopsy site.
💊 Management
- ⚠️ Prognosis is often worse than polymyositis or dermatomyositis - relapses are common.
- 🟠 Corticosteroids (first-line) → high-dose oral or IV methylprednisolone.
- 🟢 Steroid-sparing immunosuppressants: methotrexate, azathioprine, mycophenolate.
- 💉 Rituximab or IVIG may be required in resistant disease.
- 🚫 In statin-associated disease: withdraw statin immediately.
⚠️ Complications
- 🚶 Chronic disability due to persistent muscle weakness and atrophy.
- 🫁 Interstitial lung disease → monitor with lung function tests and imaging.
- ⚡ Rhabdomyolysis (rare but possible in severe cases).
📚 Teaching Pearls
- High CK (>10,000 IU/L) + proximal weakness + anti-SRP/HMGCR antibodies = classic exam combination 📝.
- IMNM can mimic polymyositis - but biopsy shows necrosis with minimal inflammation.
- Think of it in patients with progressive weakness despite statin withdrawal.
- Early, aggressive immunosuppression is key to preserving mobility and lung function.
🔗 References
