Makindo Medical Notes

🧪 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

• Immune-Mediated Necrotizing Myopathy – Review (NCBI)