What is vasculitic neuropathy?

Vasculitic Neuropathy: Definition and Clinical Approach

Vasculitic neuropathy is an inflammatory disorder of peripheral nerve blood vessels causing ischemic nerve damage, typically presenting as painful, asymmetric sensorimotor deficits that can progress from mononeuritis multiplex to polyneuropathy if untreated.

Pathophysiology and Classification

Vasculitic neuropathy results from inflammation of blood vessels supplying peripheral nerves, leading to:

• Vessel wall inflammation and damage
• Ischemic injury to nerve fibers
• Wallerian degeneration of affected axons

Classification based on distribution:

• Systemic vasculitic neuropathy: Part of a systemic vasculitis affecting multiple organs
• Non-systemic vasculitic neuropathy (NSVN): Limited to peripheral nerves without other organ involvement 1

Classification based on vessel size:

• Large arteriole vasculitis: More severe, often part of systemic disease
• Microvasculitis: May be limited to peripheral nerves 2

Clinical Presentation

Typical Features

• Acute to subacute onset of painful sensory and motor deficits 2
• Asymmetric or multifocal pattern (mononeuritis multiplex)
• Can progress to distal-predominant sensorimotor polyneuropathy 3
• Lower limb predominance
• Pain is present in most cases

Associated Conditions

• Primary systemic vasculitides:

  • ANCA-associated: Granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis 4, 5
  • Polyarteritis nodosa
  • Cryoglobulinemic vasculitis (often HCV-associated) 6

• Secondary vasculitides:

  • Rheumatoid vasculitis
  • Infection-related (HCV, VZV)
  • Connective tissue disorders
  • Medication-induced
  • Malignancy-associated 7

Diagnostic Approach

Clinical Evaluation

• Look for sensory or sensorimotor deficits with asymmetric/multifocal pattern
• Assess for pain, which is common and often prominent
• Evaluate for signs of systemic vasculitis (skin lesions, joint involvement, etc.)

Laboratory Testing

• Inflammatory markers: ESR, CRP
• Autoantibodies: ANCA, cryoglobulins, rheumatoid factor
• Viral serology: HCV, HIV
• Complete blood count, renal and liver function tests 4

Electrodiagnostic Studies

• Shows axonal neuropathy pattern
• Reduced amplitude of motor or sensory potentials
• Asymmetric findings
• Pseudo-conduction block (acute stage) or temporal dispersion (chronic stage) 3

Definitive Diagnosis

• Nerve biopsy: Gold standard for diagnosis

  • Pathologically definite vasculitic neuropathy requires:
    • Vessel wall inflammation with vascular damage
    • Supporting features: IgM/C3/fibrinogen deposits, hemosiderin, asymmetric nerve fiber loss, active axonal degeneration 1

• Combined nerve and muscle biopsy (sural nerve and peroneus brevis) increases diagnostic yield 3

Treatment

First-Line Therapy

• Corticosteroid monotherapy for at least 6 months in non-severe cases 1
  • Typically oral prednisone 1 mg/kg/day (maximum 60-80 mg/day)
  • For severe cases: IV methylprednisolone 1g/day for 3-5 days initially 4

For Severe or Progressive Disease

• Combination therapy with corticosteroids plus immunosuppressants:

  • Cyclophosphamide (first choice for severe disease)
    • IV pulse: 15 mg/kg every 2-4 weeks, or
    • Oral: 2 mg/kg/day 4

• Alternative agents for those intolerant to cyclophosphamide:

  • Azathioprine (2 mg/kg/day)
  • Methotrexate (15-25 mg/week)
  • Mycophenolate mofetil (2-3 g/day)
  • Rituximab (particularly effective in ANCA-associated and cryoglobulinemic vasculitis) 5

Maintenance Therapy

• After achieving remission (typically 3-6 months), transition from cyclophosphamide to less toxic agents
• Continue maintenance therapy for 18-24 months 1
• Gradually taper corticosteroids

Prognosis and Monitoring

• Recovery from axonal degeneration is slow and sometimes incomplete 3
• Regular clinical assessment for neurological improvement
• Laboratory monitoring: complete blood count, renal and liver function tests
• Poor prognostic factors:
  • Delayed diagnosis and treatment
  • Severe axonal damage
  • Older age
  • Systemic involvement

Special Considerations

• For HCV-associated cryoglobulinemic vasculitis with neuropathy, consider rituximab 4
• For VZV-associated vasculitis, IV acyclovir plus corticosteroids 4
• Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim/sulfamethoxazole for patients on cyclophosphamide 4

Early recognition and prompt treatment are essential to prevent permanent neurological damage and improve quality of life outcomes.