Key Facts

The concept of polymyositis has evolved significantly. True PM (excluding IBM and IMNM) is now thought to be uncommon. The antisynthetase syndrome is the most important subgroup.

Epidemiology

• Incidence: 2-10 per million/year (including IMNM)
• F:M 2:1; peak onset 30-60 years
• Rare in children (unlike DM)

Aetiology

• Autoimmune: CD8+ T-cell-mediated myofibre destruction
• Genetic: HLA-DRB1*0301
• Viral triggers (HIV, HTLV-1, coxsackie)
• Drug-induced: statins (IMNM with anti-HMGCR), D-penicillamine

Pathophysiology

• CD8+ cytotoxic T cells directly invade and destroy MHC class I-expressing myofibres
• Endomysial inflammation (within fascicles) – distinct from DM (perivascular/perifascicular)
• ILD driven by antisynthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12)
• IMNM: macrophage-mediated with minimal lymphocytic infiltrate; anti-SRP or anti-HMGCR positive

Muscle

• Symmetric proximal weakness: gradual onset over weeks to months
• Hip flexors and shoulder abductors most affected
• Difficulty: rising from chairs, climbing stairs, lifting arms, combing hair
• Neck flexor weakness (head drop) in severe cases
• Myalgia in ~50%
• Dysphagia: pharyngeal/oesophageal weakness (20-30%)
• Respiratory muscle weakness: dyspnoea, reduced MIP/MEP

Antisynthetase Syndrome

• ILD: NSIP most common; may be presenting feature
• Mechanic's hands: rough, cracked, hyperkeratotic lateral finger skin
• Raynaud phenomenon: 60%
• Arthritis: symmetrical, non-erosive
• Fever: often low-grade
• Anti-Jo-1 most common antisynthetase antibody (20% of PM)

Red Flags

• Rapidly progressive weakness → consider IMNM (anti-SRP)
• Distal weakness + finger flexor/knee extensor weakness in >50 year old → consider IBM
• ILD with myositis → antisynthetase syndrome
• Failure to respond to steroids → reconsider diagnosis (IBM, IMNM)

Bloods

• CK: elevated (often 10-50× ULN)
• Myositis antibodies: anti-Jo-1, anti-PL-7, anti-PL-12 (antisynthetase); anti-SRP, anti-HMGCR (IMNM)
• ANA: positive in ~40%
• LDH, AST, ALT: elevated (muscle origin)
• ESR/CRP: may be elevated

Imaging

• MRI: muscle oedema (guides biopsy)
• HRCT chest: ILD (especially antisynthetase)
• PFTs: FVC and DLCO

EMG

• Myopathic pattern: short-duration, low-amplitude polyphasic motor units

Biopsy

• Muscle biopsy: endomysial CD8+ T-cell infiltrate, myofibre necrosis, MHC class I upregulation
• Distinguishes from DM (perifascicular) and IMNM (necrosis with minimal inflammation)

Malignancy Screening

• CT CAP at diagnosis; age-appropriate cancer screening
• Less strongly associated than DM but still elevated risk (~5-10%)

Pharmacological

• Prednisolone 1mg/kg/day: taper over months guided by CK and strength
• Methotrexate 15-25mg weekly or azathioprine 2-3mg/kg/day: steroid-sparing
• IVIg: for refractory disease (2g/kg over 2-5 days)
• Rituximab: for refractory PM (off-label; RIM trial data)
• Mycophenolate: for ILD
• Cyclophosphamide: for severe ILD

Non-pharmacological

• Physiotherapy: graduated exercise once CK improving
• SLT assessment: if dysphagia
• Pulmonary rehabilitation: if ILD

Monitoring

• CK levels every 2-4 weeks initially; guide treatment response
• PFTs 3-6 monthly if ILD
• Muscle strength assessment (MMT-8 score)

Referral Criteria

• Suspected inflammatory myopathy → rheumatology
• ILD → respiratory
• Dysphagia → gastroenterology

• 5-year survival: ~85-90% with treatment
• Antisynthetase syndrome with ILD: poorer prognosis; 5-year survival ~70-80%
• Anti-SRP IMNM: severe, often refractory; may require aggressive treatment
• Response to treatment: most patients improve significantly on prednisolone + DMARD
• IBM: important differential as it does NOT respond to immunosuppression
• CK normalisation usually precedes strength improvement by weeks-months

Inflammatory Myopathy Classification (Updated)

Antisynthetase Syndrome Features