What is the treatment for small vessel vasculitis?

Treatment for Small Vessel Vasculitis

The treatment of small vessel vasculitis requires a combination of high-dose glucocorticoids and immunosuppressive therapy, with rituximab or cyclophosphamide being the preferred agents for induction therapy in severe disease. 1

Disease Classification and Initial Assessment

• Small vessel vasculitis should be categorized according to severity to guide appropriate treatment decisions: localized, early systemic, generalized, severe, or refractory 1
• ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) 1
• Disease severity assessment should include evaluation of organ involvement, particularly renal function and pulmonary status 1

Induction Therapy

For Severe/Generalized Disease:

• First-line therapy: High-dose glucocorticoids (prednisolone 1 mg/kg/day, maximum 60 mg/day) combined with either:

  • Cyclophosphamide (oral 2 mg/kg/day, maximum 200 mg/day or IV pulsed) 1
  • Rituximab (375 mg/m² weekly for 4 weeks) 2, 3

• Rituximab has demonstrated non-inferiority to cyclophosphamide for induction of remission and may be superior in relapsing disease 2, 3

• Initial high-dose glucocorticoids should be maintained for 1 month, then tapered gradually to 15 mg/day or less during the first 3 months 1

For Non-Organ Threatening Disease:

• Methotrexate (15-25 mg/week, oral or parenteral) combined with glucocorticoids is recommended as a less toxic alternative to cyclophosphamide 1
• Methotrexate should be started at 15 mg/week and escalated to 20-25 mg/week over 1-2 months if tolerated 1

For Severe Renal Disease:

• Plasma exchange is recommended for patients with rapidly progressive severe renal disease (serum creatinine >500 μmol/L or 5.65 mg/dL) to improve renal survival 1
• In diffuse alveolar hemorrhage with hypoxemia, plasma exchange can be considered in addition to standard therapy 1

Maintenance Therapy

• After achieving remission, transition to maintenance therapy with:
  • Rituximab (using either the MAINRITSAN scheme: 500 mg at remission and at months 6,12, and 18; or the RITAZAREM scheme: 1000 mg at remission and months 4,8,12, and 16) 1
  • Azathioprine (1.5-2 mg/kg/day) for 18-24 months, then decrease to 1 mg/kg/day until 4 years after diagnosis 1
  • Mycophenolate mofetil (2000 mg/day in divided doses) for 2 years 1
• Glucocorticoids should be continued at 5-7.5 mg/day for 2 years and then slowly reduced by 1 mg every 2 months 1

Management of Refractory or Relapsing Disease

• For refractory disease, consider:
  • Increasing glucocorticoid dose (IV or oral) 1
  • Switching from cyclophosphamide to rituximab or vice versa 1
  • Plasma exchange as an additional therapy 1
• For relapsing disease, reinduction therapy is recommended, preferably with rituximab 1, 4
• Early intensive treatment with cyclophosphamide has been associated with shorter time to remission in CNS vasculitis 4

Supportive Care and Monitoring

• Prophylaxis against Pneumocystis jiroveci with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) is recommended for all patients on cyclophosphamide 1, 5
• Patients receiving cyclophosphamide should be given Mesna to prevent hemorrhagic cystitis 1
• Regular monitoring of blood counts, renal function, and urinalysis is essential 5
• Bone protection therapy should be provided according to local guidelines for patients on long-term glucocorticoids 1

Special Considerations

• Dose adjustments for cyclophosphamide are necessary based on age and renal function 1
• In hepatitis C-associated cryoglobulinemic vasculitis, antiviral therapy is recommended 1
• For non-viral mixed essential cryoglobulinemic vasculitis, immunosuppressive therapy is recommended 1

The treatment approach should be guided by disease severity, organ involvement, and patient factors, with close monitoring for treatment response and adverse effects.