What is the initial treatment for vasculitis?

Initial Treatment for Vasculitis

The initial treatment for vasculitis requires immediate combination therapy with high-dose glucocorticoids (prednisolone 1 mg/kg/day, maximum 60-80 mg/day) plus either rituximab (375 mg/m² weekly for 4 weeks) or cyclophosphamide (2 mg/kg/day oral or 15 mg/kg IV every 2-3 weeks), with the specific regimen determined by vasculitis type, disease severity, and organ involvement. 1, 2, 3

Classification-Based Treatment Algorithm

ANCA-Associated Vasculitis (GPA, MPA, EGPA)

For severe/generalized disease (alveolar hemorrhage, glomerulonephritis, CNS vasculitis, mononeuritis multiplex):

• Glucocorticoids: Start with IV methylprednisolone 500-1,000 mg/day for 3-5 days, followed by oral prednisone 1 mg/kg/day (maximum 80 mg/day for adults, 60 mg/day for children) 1, 2
• Plus either:
  • Cyclophosphamide: 2 mg/kg/day oral (maximum 200 mg/day) for 3-6 months, OR 15 mg/kg IV every 2 weeks for 3 doses, then every 3 weeks for at least 3 additional doses 1, 2
  • Rituximab: 375 mg/m² IV weekly for 4 weeks OR 1,000 mg IV on days 1 and 15 1, 4

Choosing between cyclophosphamide and rituximab: 3

• Favor cyclophosphamide: Severe renal disease with rapidly declining function, dialysis requirement, or diffuse alveolar hemorrhage with hypoxemia
• Favor rituximab: Younger patients concerned about fertility, relapsing disease (67% vs 42% remission rate compared to cyclophosphamide), or when cyclophosphamide is contraindicated 3, 4

For nonsevere disease (rhinosinusitis, asthma, mild systemic symptoms, uncomplicated cutaneous disease):

• High-dose oral glucocorticoids plus methotrexate (up to 25 mg/week) or rituximab 1, 2

Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis)

Giant Cell Arteritis:

• Immediate high-dose glucocorticoids (prednisone 1 mg/kg/day, maximum 60 mg/day) to prevent vision loss and stroke 2, 3
• Add adjunctive immunosuppressive therapy (methotrexate or tocilizumab) as steroid-sparing agents from the outset 2, 3

Takayasu Arteritis:

• All patients should receive glucocorticoids PLUS non-biological glucocorticoid-sparing agents (methotrexate, azathioprine, or mycophenolate mofetil) in combination from the start 3

Critical Adjunctive Therapies for Severe Disease

Plasmapheresis should be added for: 2, 3

• Rapidly increasing serum creatinine or dialysis requirement
• Diffuse pulmonary hemorrhage with hypoxemia
• Overlap syndrome of ANCA vasculitis and anti-GBM glomerulonephritis

Glucocorticoid Tapering Strategy

• Maintain high-dose glucocorticoids for 1 month 1, 2
• Begin gradual taper after 1 month, reducing by approximately 10 mg every 2 weeks until reaching 20 mg/day 2
• Then taper more slowly by 2.5-5 mg every 2-4 weeks to reach 5-7.5 mg/day by 6 months 2
• Never use alternate-day glucocorticoid therapy as this increases relapse risk 3

Mandatory Supportive Care

All patients on cyclophosphamide require: 2

• Trimethoprim-sulfamethoxazole prophylaxis against Pneumocystis jiroveci
• Mesna to prevent hemorrhagic cystitis (for IV cyclophosphamide)
• Bone protection therapy (calcium, vitamin D, bisphosphonates)
• Regular monitoring: CBC, renal function, urinalysis every 2-4 weeks

Cyclophosphamide dose adjustments: 1, 2

• Reduce dose by 25% if age >60 years
• Reduce dose by 25-50% if GFR <30 mL/min
• Discontinue if white blood cell count <3,000/mm³

Transition to Maintenance Therapy

After achieving remission (typically 3-6 months): 1, 2

• Discontinue cyclophosphamide and switch to maintenance therapy

• Maintenance options (in order of preference based on evidence):

  • Rituximab: 500 mg IV every 6 months OR 1,000 mg IV every 4 months 1, 4
  • Azathioprine: up to 2 mg/kg/day 1
  • Mycophenolate mofetil: up to 1,500 mg twice daily 1
  • Methotrexate: up to 25 mg/week (avoid if GFR <60 mL/min) 1, 3

• Duration: Continue maintenance therapy for at least 18-24 months, with extended therapy to 4 years reducing relapse risk 3

• Glucocorticoids: Taper to 5-7.5 mg/day and maintain for 2 years, then reduce by 1 mg every 2 months 3

Critical Pitfalls to Avoid

• Never delay treatment while waiting for biopsy results in rapidly deteriorating patients with positive ANCA serology 2, 3
• Do not change immunosuppression based solely on ANCA titer changes without clinical disease activity 2
• Avoid inadequate initial immunosuppression in severe disease—this is not the time for conservative dosing 3
• Do not use methotrexate as maintenance therapy if GFR <60 mL/min 3
• Never abruptly stop glucocorticoids or taper too rapidly in the first 6 months 2

Monitoring During Induction

• Weekly CBC for first month, then every 2 weeks 2
• Serum creatinine and urinalysis every 2-4 weeks 2
• Clinical assessment of disease activity using Birmingham Vasculitis Activity Score (BVAS) 3
• ANCA titers may predict relapse but should not guide treatment changes alone 3