Necrotizing myopathy, inclusion body myositis and polymyositis
- Lesion
Some muscle autoimmunity kills fibres with little inflammation, sometimes after statins; inclusion body myositis slowly weakens thighs and fingers in old age.
What it is
Beyond dermatomyositis, three inflammatory myopathies matter. Immune-mediated necrotizing myopathy causes subacute, severe proximal weakness with very high CK; the biopsy shows many necrotic and regenerating fibres with little inflammation, and antibodies target SRP or HMG-CoA reductase (HMGCR), the latter often after statin exposure. Sporadic inclusion body myositis is the commonest myopathy after 50: slowly progressive, asymmetric weakness of quadriceps and finger flexors with dysphagia, rimmed vacuoles, protein aggregates and CD8 T cells invading fibres, and poor response to immunosuppression. Polymyositis, once common, is now rare and a diagnosis of exclusion: endomysial CD8 T cells attacking MHC class I-expressing fibres without skin disease.
Structure
- IMNM: scattered necrotic fibres at different stages with macrophages, regenerating fibres, MAC on the sarcolemma and few lymphocytes.
- sIBM: rimmed vacuoles lined by basophilic granules, cytoplasmic inclusions, invading CD8 cells, COX-negative fibres.
- Polymyositis: endomysial lymphocytes, mostly CD8, surrounding and invading non-necrotic fibres; widespread MHC class I upregulation.
Step by step
- Statin exposure raises HMGCR expression in muscle and may break tolerance in susceptible people (HLA-DRB1*11:01).
- Anti-HMGCR or anti-SRP antibodies bind regenerating fibres and fix complement, causing necrosis.
- In sIBM, cytotoxic CD8 T cells and degenerative protein aggregation act together in aging muscle.
- Aggregates of misfolded proteins and failed autophagy produce rimmed vacuoles.
- The degenerative component explains why sIBM does not respond to immunosuppression.
The inflammatory myopathies compared
| Feature | Dermatomyositis | IMNM | Inclusion body myositis | Polymyositis |
|---|---|---|---|---|
| Age | Children and adults | Adults | Over 50 | Adults |
| Weakness | Proximal, symmetric; skin rash | Proximal, severe, subacute | Quadriceps, finger flexors; asymmetric; slow | Proximal, symmetric |
| CK | Raised | Very high | Normal or mildly raised | Raised |
| Inflammation | Perimysial, perivascular | Scant | Endomysial CD8 | Endomysial CD8 |
| Key biopsy finding | Perifascicular atrophy | Necrotic fibres | Rimmed vacuoles, inclusions | CD8 cells invading non-necrotic fibres |
| Response to immunosuppression | Good | Usually, sometimes hard | Poor | Good |
Clinical notes
- Weakness after starting a statin that keeps worsening after the drug is stopped: test for anti-HMGCR.
- An older man who trips on his knees and cannot grip well, with steroid-resistant 'polymyositis': reconsider inclusion body myositis.
- Dysphagia in sIBM can cause aspiration.
Test yourself
Think of the answer, then tap the question to see it.
Which autoantibody links statins to immune-mediated necrotizing myopathy?
Anti-HMG-CoA reductase (anti-HMGCR).
Which muscles are typically weak in inclusion body myositis?
Quadriceps and deep finger flexors, often asymmetrically.
What are rimmed vacuoles?
Vacuoles lined by basophilic granular material in muscle fibres, typical of inclusion body myositis.
Why is polymyositis now a diagnosis of exclusion?
Many cases once called polymyositis are IBM, IMNM, antisynthetase syndrome or dystrophies with inflammation.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Myositis | Polymyositis | Dermatomyositis | MedlinePlus (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.