Vasculitic Neuropathy

Vasculitic neuropathy is nerve ischaemia from inflammation of the vasa nervorum, presenting as painful, asymmetric, stepwise mononeuropathy multiplex or distal symmetric neuropathy. It occurs in systemic vasculitis (polyarteritis nodosa, ANCA-associated vasculitis, eosinophilic granulomatosis with polyangiitis, cryoglobulinaemia, rheumatoid arthritis, lupus) or as a non-systemic vasculitic neuropathy limited to nerves.

Pathophysiology. Immune mediated transmural inflammation of epineurial small and medium vessels causes ischaemic axonal infarction, especially in watershed zones of nerves.

Acute or subacute painful sensory and motor deficits in the distribution of individual nerves (peroneal, ulnar, median, radial), with new nerves added over days to weeks. Fever, weight loss, malaise, skin lesions (purpura, livedo, ulcers), kidney or lung involvement, and hypertension suggest systemic disease.

Red flags.

• Acute foot or wrist drop with severe pain.
• Haematuria, haemoptysis or rash.
• Rapidly progressive multifocal deficit.

Nerve conduction studies show asymmetric axonal sensorimotor neuropathy. Check inflammatory markers, ANCA, antinuclear antibodies, complement, cryoglobulins, rheumatoid factor, hepatitis B and C, HIV, urinalysis, creatinine and chest imaging. Combined nerve and muscle biopsy (sural nerve with peroneus brevis) shows vasculitis and is the diagnostic test. MRI or ultrasound of nerves can guide biopsy.

Differential diagnosis.

• Diabetic neuropathy, multifocal motor neuropathy, and multifocal CIDP.
• Hereditary neuropathy with pressure palsies, infection (leprosy, Lyme disease) and lymphoma.
• Amyloid neuropathy and compressive mononeuropathies.

Start immediately, since delay leads to permanent axonal loss.

Induction.

• Methylprednisolone 1 g IV daily for 3 days, then prednisolone 1 mg/kg daily (maximum 60 mg) tapered over months.
• Plus cyclophosphamide 15 mg/kg IV every 2 to 3 weeks for 6 pulses (or 2 mg/kg orally daily) for systemic or severe disease, or rituximab 375 mg/m2 weekly for 4 weeks (or 1 g twice, 2 weeks apart).
• Non-systemic vasculitic neuropathy: corticosteroids with cyclophosphamide or methotrexate.

Maintenance. Azathioprine 2 mg/kg daily, methotrexate 15 to 25 mg weekly (with folic acid), mycophenolate mofetil 1 g twice daily, or rituximab, for 18 to 24 months.

Infection related. Treat the cause (hepatitis B or C antiviral therapy).

Supportive. Neuropathic pain (gabapentin, amitriptyline), physiotherapy, splints and foot care. Pneumocystis prophylaxis (co-trimoxazole 480 mg daily) and bone protection during steroids.

Monitoring. Full blood count, renal and liver function, ESR, and relapse (about 20 to 30%).

Referral and escalation. Refer urgently to neurology and rheumatology.

Special groups. In pregnancy, avoid cyclophosphamide, methotrexate and mycophenolate, and use azathioprine with steroids.