Treatment of Primary CNS Vasculitis

Initial Treatment Approach

The American College of Rheumatology recommends initiating combination therapy immediately with high-dose glucocorticoids (prednisolone 1 mg/kg/day, maximum 60 mg/day) plus cyclophosphamide (2 mg/kg/day oral, maximum 200 mg/day, or intravenous pulses) as first-line therapy, with early initiation critical to prevent permanent neurological damage and death 1
Glucocorticoid dosing should be prednisolone 1 mg/kg/day (maximum 60 mg/day), maintained at high dose for 1 month, then tapered gradually to 15 mg/day or less during the first 3 months 2
Cyclophosphamide can be administered either orally at 2 mg/kg/day (maximum 200 mg/day) or as intravenous pulses, with Mesna as a uroprotective agent to reduce bladder toxicity risk 3, 2
The European League Against Rheumatism recommends prescribing Pneumocystis jiroveci prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide 1, 2
Rituximab (375 mg/m² weekly for 4 weeks) is an equally effective alternative to cyclophosphamide and should be preferred for patients with fertility concerns, relapsing disease, or cyclophosphamide intolerance 1

After achieving remission, transition to maintenance therapy with low-dose glucocorticoids (5-7.5 mg/day for 2 years) plus azathioprine (1.5-2 mg/kg/day for 18-24 months, then decrease to 1 mg/kg/day until 4 years after diagnosis) 3, 2
Alternative maintenance agents include methotrexate or leflunomide if azathioprine is not tolerated 3
For patients initially treated with rituximab, consider rituximab maintenance dosing at 500 mg at remission and at months 6, 12, and 18 2

For patients who fail to achieve remission or relapse on standard therapy, consider rituximab if not already used, mycophenolate mofetil, intravenous immunoglobulin (2 gm/kg), or tumor necrosis factor-α blockers 1
These patients should be referred to expert centers for further management and enrollment in clinical trials 3

Perform structured clinical assessment, urinalysis, and basic laboratory tests at each visit to monitor disease activity and treatment toxicity 3, 1
Investigate persistent unexplained hematuria in all patients with prior cyclophosphamide exposure due to bladder cancer risk, which can occur months to years after treatment 3, 1
Monitor blood counts and renal function regularly during treatment 2
Provide bone protection therapy according to local guidelines for patients on long-term glucocorticoids 2

Delaying proven immunosuppressive therapy risks permanent organ damage or death, as untreated systemic vasculitis carries 40-46% five-year mortality in patients with poor prognostic factors 1