What are the treatment approaches for small, medium, and large vessel vasculitis?

Treatment Approaches for Small, Medium, and Large Vessel Vasculitis

For optimal outcomes in terms of morbidity and mortality, treatment of vasculitis should be tailored to vessel size classification, with rituximab plus glucocorticoids as first-line therapy for most forms of ANCA-associated small vessel vasculitis, cyclophosphamide plus glucocorticoids for severe renal disease, and methotrexate plus glucocorticoids for non-severe disease. 1

Small Vessel Vasculitis Treatment

Remission Induction

• ANCA-associated vasculitis (GPA, MPA, EGPA):

  • First-line: Rituximab 375 mg/m² IV weekly for 4 weeks + glucocorticoids 1
  • Alternative: Cyclophosphamide (oral 2 mg/kg/day or IV pulse) + glucocorticoids 2
  • Non-severe disease: Methotrexate (20-25 mg/week) + glucocorticoids 2, 1

• Severe renal involvement (creatinine >500 μmol/L):

  • Add plasma exchange to improve renal survival 2, 1
  • Consider combination of cyclophosphamide and rituximab 1

• Glucocorticoid regimen:

  • Initial: IV methylprednisolone 500-1000 mg/day for 3-5 days 1
  • Followed by: Oral prednisone 1 mg/kg/day (max 60 mg/day) 2
  • Taper: According to clinical response, aim for 10 mg/day or less during remission 2

Maintenance Therapy

• First-line maintenance:

  • Azathioprine 1.5-2 mg/kg/day for 18-24 months, then decrease to 1 mg/kg/day until 4 years after diagnosis 2, 1
  • Low-dose glucocorticoids (5-7.5 mg/day) for 2 years, then gradual taper 2

• Alternative maintenance options:

  • Rituximab 500 mg IV every 6 months 2, 1
  • Methotrexate 20-25 mg/week (if creatinine <130 μmol/L) 2
  • Leflunomide 20-30 mg/day (more effective but more adverse effects) 2
  • Mycophenolate mofetil up to 2 g/day 2, 1

• Duration: Minimum 18-24 months, with British Society for Rheumatology recommending 24 months 2

Medium Vessel Vasculitis Treatment

Polyarteritis Nodosa (PAN)

• Induction therapy:

  • Cyclophosphamide + glucocorticoids 2, 1
  • For hepatitis B-associated PAN: Antiviral therapy + glucocorticoids 2

• Maintenance therapy:

  • Azathioprine 2 mg/kg/day 2, 3
  • Duration: 12 months for PAN 4

Kawasaki Disease

• Acute phase:
  • Intravenous immunoglobulin 2 g/kg as single dose 1
  • Aspirin (high-dose initially, then low-dose) 1

Large Vessel Vasculitis Treatment

Giant Cell Arteritis (GCA)

• Induction therapy:

  • High-dose glucocorticoids (prednisone 1 mg/kg/day, max 60 mg/day) 1, 5
  • Consider tocilizumab for newly diagnosed or relapsing disease 5

• Maintenance therapy:

  • Gradual prednisone taper
  • Methotrexate or azathioprine as steroid-sparing agents 6, 5

Takayasu Arteritis

• Induction therapy:
  • High-dose glucocorticoids + conventional DMARDs (methotrexate or azathioprine) 5
  • Consider TNF-alpha inhibitors or tocilizumab for refractory disease 5

Treatment of Refractory or Relapsing Disease

• For small vessel vasculitis:

  • Switch from cyclophosphamide to rituximab or vice versa 2, 1
  • Consider plasma exchange 2, 1
  • For persistent low activity: Intravenous immunoglobulin 2 g/kg over 5 days 2

• For medium/large vessel vasculitis:

  • Increase immunosuppression intensity 1
  • Consider biologic agents (tocilizumab for GCA, TNF inhibitors for Takayasu) 5

Monitoring and Supportive Care

• Infection prophylaxis:

  • Trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients on cyclophosphamide 2, 1
  • For Wegener's granulomatosis: Consider trimethoprim/sulfamethoxazole to reduce relapse risk 2

• Monitoring:

  • Regular assessment of disease activity, complete blood counts, renal function, and urinalysis 1
  • Monitor for cyclophosphamide toxicity with dose adjustments based on age and renal function 2
  • Serial ANCA testing has controversial utility in guiding therapy 2

Common Pitfalls and Caveats

• Dose adjustments: Cyclophosphamide dosing must be adjusted for age and renal function to minimize toxicity 2
• Treatment duration: Early cessation of therapy increases relapse risk 2
• Renal function: Methotrexate should be avoided if creatinine >130 μmol/L 2
• Pregnancy: Cyclophosphamide is contraindicated; consider alternative treatments 1
• Elderly patients: Require careful monitoring and dose adjustment with cyclophosphamide 1
• Cutaneous-limited vasculitis: May respond to less aggressive therapy like colchicine or dapsone 7

By following these evidence-based treatment approaches according to vessel size classification and disease severity, clinicians can optimize outcomes and minimize treatment-related complications in patients with vasculitis.