Treatment of Primary CNS Vasculitis
Primary CNS vasculitis should be treated with high-dose glucocorticoids (prednisolone 1 mg/kg/day, maximum 60 mg/day) combined with 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, 2, 3
Initial Treatment Approach
First-Line Induction Therapy
Initiate combination therapy immediately with high-dose glucocorticoids plus cyclophosphamide, as this regimen achieves favorable responses in most patients and can prevent serious outcomes when started early 2, 3
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 4
Cyclophosphamide can be administered either orally at 2 mg/kg/day (maximum 200 mg/day) or as intravenous pulses 5, 4
Provide Mesna as uroprotective agent with cyclophosphamide to reduce bladder toxicity risk, though this does not eliminate the risk entirely 5, 1
Prescribe Pneumocystis jiroveci prophylaxis with trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) for all patients receiving cyclophosphamide 1, 4
Alternative First-Line Option
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, 6
Rituximab achieved 64% complete remission at 6 months in ANCA-associated vasculitis trials and has shown favorable response in PCNSV case reports 1, 6
Maintenance Therapy
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) 5, 4
Alternative maintenance agents include methotrexate or leflunomide if azathioprine is not tolerated 5
For patients initially treated with rituximab, consider rituximab maintenance dosing at 500 mg at remission and at months 6,12, and 18 4
Refractory or Relapsing Disease
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, 2
These patients should be referred to expert centers for further management and enrollment in clinical trials 5
For relapsing disease, reinduction therapy is recommended, preferably with rituximab 4
Critical Monitoring and Safety Considerations
Perform structured clinical assessment, urinalysis, and basic laboratory tests at each visit to monitor disease activity and treatment toxicity 5, 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 5, 1
Tobacco smokers are particularly susceptible to cyclophosphamide-related bladder cancer at lower doses and earlier than non-smokers 5
Monitor blood counts and renal function regularly during treatment 4
Provide bone protection therapy according to local guidelines for patients on long-term glucocorticoids 4
Prognostic Factors
Diagnostic delay is associated with worse outcomes, with median diagnostic delays of 23 months reported in cohort studies 3
Presence of myelitis and longer duration of illness before diagnosis are associated with poorer functional outcomes 3
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
Treatment with steroids plus another immunosuppressant reduces relapse rates, with 65.2% of patients achieving good functional outcome (mRS 0-2) at 2 years in recent cohorts 3