What is the treatment for vasculitis-induced neuropathy?

Treatment of Vasculitis-Induced Neuropathy

For severe vasculitis-induced neuropathy, initiate high-dose glucocorticoids combined with cyclophosphamide as first-line therapy, followed by transition to maintenance immunosuppression with azathioprine, methotrexate, or mycophenolate mofetil for approximately 18 months. 1, 2

Initial Assessment and Diagnosis

Before initiating treatment, establish the diagnosis and severity:

• Obtain combined nerve and muscle biopsy (not nerve biopsy alone) to confirm vasculitic neuropathy, sampling clinically affected tissue—preferably a purely sensory nerve like the sural nerve to avoid motor deficits 1, 2
• Test for ANCA when ANCA-associated vasculitis (GPA, MPA, EGPA) is suspected, as this guides specific treatment decisions 1, 2
• Perform nerve conduction studies and electromyography to identify multiple mononeuropathies and differentiate from polyneuropathy 2
• Assess for systemic involvement through laboratory markers (ESR, CRP), imaging, and organ-specific evaluation to distinguish systemic from nonsystemic vasculitic neuropathy 1, 3

Treatment Algorithm by Disease Severity

Severe Disease (Life-Threatening or Organ-Threatening)

Remission Induction (0-6 months):

• Intravenous pulse methylprednisolone (1000 mg/day for 1-3 days) is preferred over high-dose oral glucocorticoids for active, severe disease 1
• Follow with oral prednisone 1 mg/kg/day (maximum 60-80 mg/day) with pre-specified tapering 1
• Add cyclophosphamide using either:
  • Intravenous pulse: 15 mg/kg every 2-4 weeks, OR
  • Oral daily: 2 mg/kg/day (maximum 200 mg/day) 1, 3
• Continue cyclophosphamide for 3-6 months until remission is achieved 1, 3, 4

Remission Maintenance (6-24 months):

• Transition to azathioprine, methotrexate, or mycophenolate mofetil after achieving remission with cyclophosphamide 1, 2
• Continue maintenance therapy for approximately 18 months total 1, 2
• Azathioprine can be safely substituted for cyclophosphamide after 3 months without increased relapse rates 4

Non-Severe Disease (No Organ-Threatening Features)

• Glucocorticoids combined with non-cyclophosphamide immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil) as first-line treatment 1, 2
• Reserve cyclophosphamide for patients who fail to respond or relapse during glucocorticoid tapering 1, 3, 4

Disease-Specific Considerations

ANCA-Associated Vasculitis (GPA/MPA)

• Rituximab 375 mg/m² weekly for 4 weeks is an alternative to cyclophosphamide for remission induction in severe disease, demonstrating non-inferiority with 64% achieving complete remission at 6 months 1, 5
• Rituximab is particularly effective in ANCA-positive cases and can be considered for maintenance therapy at 500 mg every 6 months 1, 2, 5
• For follow-up treatment after achieving disease control, rituximab 500 mg every 6 months for 18 months is effective 5

EGPA-Associated Neuropathy

• Consider mepolizumab (anti-IL-5) with glucocorticoids as an alternative approach for EGPA-associated mononeuritis multiplex 1, 2
• Standard immunosuppression with glucocorticoids and cyclophosphamide remains first-line for severe cases 1

Hepatitis C-Associated Cryoglobulinemic Vasculitis

• Antiviral therapy for HCV eradication should be considered first-line for mild-moderate disease without major contraindications 1
• Rituximab has shown efficacy in 90% of glomerulonephritis cases and 75% of peripheral neuropathy cases, with improvement typically within 1-5 months 1
• For severe manifestations, combine antiviral therapy with immunosuppression 1

Nonsystemic Vasculitic Neuropathy (NSVN)

• High-dose prednisone is the initial therapy, but recent data suggest better outcomes when cyclophosphamide is added from the outset rather than waiting for prednisone failure 3, 4
• If prednisone monotherapy is used initially, add cyclophosphamide if no improvement after several months or if relapse occurs during tapering 3, 4

Alternative and Adjunctive Therapies

For Cyclophosphamide-Intolerant Patients

• Intravenous immunoglobulin (IVIG) can be considered in severe or treatment-resistant cases 2, 3, 4
• Plasma exchange may be added for severe cases, particularly with rapidly progressive disease 1, 2, 4
• Mycophenolate mofetil has demonstrated efficacy in systemic manifestations with a favorable side-effect profile compared to cyclophosphamide 1, 2

Supportive Care

• Physical therapy is strongly recommended for all patients with nerve and/or muscle involvement to optimize functional recovery 2
• Prophylaxis against Pneumocystis jiroveci should be provided during cyclophosphamide therapy 1
• Osteoporosis prophylaxis is essential given prolonged glucocorticoid use 1

Monitoring and Follow-Up

• Serial neurologic examinations are preferred over repeated electromyography every 6 months for monitoring stable disease activity 1, 2
• Repeat electromyography/nerve conduction studies only if uncertainty exists about new or worsening neurological processes 1
• Monitor for clinical improvement in neurological symptoms and function, though nerve conduction parameters may remain unchanged in most patients over time 2
• Follow immunoglobulin levels during rituximab therapy, as hypogammaglobulinemia (IgG <5 g/L) develops in approximately 21% of patients receiving long-term treatment 1, 5

Critical Pitfalls to Avoid

• Do not delay treatment initiation, as delay is associated with severe, irreversible neurological deficits 2
• Avoid superficial skin punch biopsies when polyarteritis nodosa is suspected; obtain deep-skin biopsies reaching medium-sized vessels 1
• Do not perform "blind" biopsies of tissue that does not appear clinically affected 1
• Be aware that peripheral neuropathy may worsen during antiviral therapy for HCV-associated vasculitis; carefully evaluate before starting treatment 1
• Intravenous pulse cyclophosphamide likely offers similar efficacy to oral therapy but with lower risk of complications, particularly bladder toxicity 1, 4