Initial Treatment for Small Vessel Vasculitis
For new-onset small vessel vasculitis (ANCA-associated vasculitis), initiate combination therapy with glucocorticoids plus either rituximab or cyclophosphamide immediately—do not delay treatment while waiting for biopsy results in patients with positive ANCA serology and compatible clinical presentation, especially if rapidly deteriorating. 1
Immediate Treatment Initiation
Start immunosuppressive therapy immediately in patients with clinical presentation compatible with small vessel vasculitis and positive MPO- or PR3-ANCA serology, without waiting for kidney biopsy results, particularly in rapidly deteriorating patients 1
Treatment should be initiated at centers with experience in ANCA-associated vasculitis management 1
First-Line Induction Regimen
The standard induction therapy consists of:
Glucocorticoids (prednisolone 1 mg/kg/day, maximum 60 mg/day) combined with either rituximab OR cyclophosphamide 1, 2
Cyclophosphamide dosing: 2 mg/kg/day orally (maximum 200 mg/day) or IV pulsed regimen 2
Choosing Between Rituximab and Cyclophosphamide
Cyclophosphamide is preferred when:
- Severe glomerulonephritis with serum creatinine >4 mg/dl (>354 μmol/l) 1
- Markedly reduced or rapidly declining GFR—limited data support rituximab alone in this setting 1
- Consider combination of 2 IV pulses of cyclophosphamide with rituximab for severe renal disease 1
Rituximab is preferred when:
- Younger patients concerned about fertility 4, 2
- Relapsing disease (67% vs 42% remission rate compared to cyclophosphamide) 4
- PR3-ANCA positive disease 1
Glucocorticoid Dosing Strategy
Initial high-dose phase:
- Prednisolone 1 mg/kg/day (maximum 60 mg/day) for the first month 1, 2
- Consider 3 doses of IV methylprednisolone (30 mg/kg/day, not exceeding 1g/day) prior to first rituximab infusion in severe cases 3
Tapering schedule:
- Maintain high dose for 1 month, then taper gradually to 15 mg/day or less during the first 3 months 2
- Continue at 5-7.5 mg/day for 2 years, then reduce by 1 mg every 2 months 4, 2
Important consideration: A reduced-dose glucocorticoid regimen (0.5 mg/kg/day) plus rituximab demonstrated noninferiority to high-dose glucocorticoids (1 mg/kg/day) plus rituximab for remission induction in patients without severe glomerulonephritis or alveolar hemorrhage, with significantly fewer serious adverse events (18.8% vs 36.9%) and serious infections (7.2% vs 20.0%) 5. However, this applies only to patients without severe renal involvement or life-threatening manifestations.
Route of Cyclophosphamide Administration
Intravenous cyclophosphamide preferred for:
- Patients with moderate cumulative cyclophosphamide exposure 1
- Lower white blood cell counts 1
- Ready access to infusion center 1
- Concerns about oral medication adherence 1
Oral cyclophosphamide preferred for:
- Cost considerations 1
- Limited access to infusion centers 1
- Patient preference for self-administered regimen 1
Essential Supportive Care
Pneumocystis jiroveci prophylaxis: Trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide 2
Mesna administration to prevent hemorrhagic cystitis in patients on cyclophosphamide 2
Bone protection therapy according to local guidelines for patients on long-term glucocorticoids 2
Critical Pitfalls to Avoid
Never delay treatment while waiting for biopsy results in rapidly deteriorating patients with positive ANCA serology 1
Avoid inadequate initial immunosuppression in severe disease—this compromises outcomes 4
Do not use alternate-day glucocorticoid therapy—this increases relapse risk 4
Monitor closely for infections—62% of rituximab-treated patients experience infections, with serious infections occurring in 11% 3