Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder with fatigable weakness.

• Prevalence is 20 per 100,000; bimodal onset (women under 40, men over 60).

• Antibodies: acetylcholine receptor (85%), MuSK (5 to 8%), LRP4, seronegative.

• Thymic hyperplasia in 65%, thymoma in 10 to 15%.

• Myasthenic crisis (respiratory failure) occurs in 15 to 20%, often triggered by infection, surgery, drugs (aminoglycosides, fluoroquinolones, macrolides, magnesium, beta blockers, checkpoint inhibitors).

• Fatigable ptosis and diplopia, worse at the end of the day; ocular onset in 50%, with 50 to 60% generalising within 2 years.

• Bulbar weakness (dysarthria, dysphagia, nasal speech, chewing fatigue), neck extensor and proximal limb weakness.

• Respiratory failure with orthopnoea and rapid shallow breathing.

• MuSK: prominent bulbar, neck and respiratory weakness, muscle atrophy.

• AChR antibodies, then MuSK if negative; ice pack test, edrophonium test (rarely).

• Repetitive nerve stimulation (decrement over 10%), single fibre EMG (most sensitive).

• CT chest for thymoma. Thyroid function, ANA, hepatitis and TB screen.

• Forced vital capacity and negative inspiratory force in crisis (intubate if FVC under 15 to 20 mL/kg).

• Pyridostigmine 30 to 60 mg three to four times daily (maximum 120 mg every 3 hours); cholinergic effects, glycopyrronium for diarrhoea.

• Prednisolone starting 10 to 20 mg alternate day, raised by 5 mg to 1 mg/kg; steroid dip risk at start. Add azathioprine 2 to 3 mg/kg (check TPMT) or mycophenolate for sparing.

• Thymectomy for thymoma and for AChR positive generalised disease aged under 50 to 65.

• Refractory or severe: rituximab (especially MuSK) 375 mg/m2 weekly for 4 doses; eculizumab 900 mg weekly for 4 doses then 1200 mg every 2 weeks, ravulizumab; efgartigimod 10 mg/kg weekly for 4 doses (FcRn), rozanolixizumab, zilucoplan 0.3 mg/kg SC daily.

• Crisis: ICU, IVIG 2 g/kg over 5 days or plasma exchange (5 exchanges), hold pyridostigmine while ventilated.

• Avoid precipitating drugs. Pregnancy: avoid mycophenolate and methotrexate; neonatal transient MG.