What is the management of vasculitis?

Management of Vasculitis

Vasculitis management is determined by vessel size and disease severity: for severe ANCA-associated small/medium vessel vasculitis, use cyclophosphamide or rituximab combined with high-dose glucocorticoids for remission induction, followed by azathioprine, leflunomide, or methotrexate for maintenance; for large vessel vasculitis (giant cell arteritis/Takayasu arteritis), initiate high-dose glucocorticoids with adjunctive immunosuppression. 1, 2

Initial Assessment and Disease Categorization

• Refer patients to centers of expertise for management of primary small, medium, and large vessel vasculitis 1
• Perform ANCA testing (indirect immunofluorescence and ELISA) in appropriate clinical context for suspected ANCA-associated vasculitis 1
• Obtain tissue biopsy to confirm diagnosis—temporal artery biopsy for giant cell arteritis (do not delay treatment while awaiting biopsy), skin/kidney/other affected organ biopsy for small/medium vessel vasculitis 1
• Categorize ANCA-associated vasculitis by severity to guide treatment intensity 1:
  • Localized: Upper/lower respiratory tract disease without systemic involvement
  • Early systemic: Any manifestation without organ-threatening disease
  • Generalized: Renal or organ-threatening disease, creatinine <500 μmol/L
  • Severe: Vital organ failure, creatinine >500 μmol/L
  • Refractory: Progressive disease unresponsive to glucocorticoids and cyclophosphamide

Small and Medium Vessel Vasculitis (ANCA-Associated)

Remission Induction for Generalized/Severe Disease

• Use cyclophosphamide (2 mg/kg/day oral, max 200 mg/day, OR intravenous pulses) plus prednisolone (1 mg/kg/day, max 60 mg/day) for Wegener granulomatosis (granulomatosis with polyangiitis) and microscopic polyangiitis 1
• Rituximab 375 mg/m² weekly for 4 weeks is equally effective as cyclophosphamide and is preferred for patients with fertility concerns or relapsing disease, achieving 64% complete remission at 6 months 2, 3
• Administer pulse IV methylprednisolone (1000 mg/day for 1-3 days) before initial treatment in severe cases 3
• Provide Pneumocystis jiroveci prophylaxis (co-trimoxazole) during cyclophosphamide therapy 1
• Use Mesna as uroprotective agent with cyclophosphamide to reduce bladder toxicity risk, though it does not eliminate risk entirely 1

Remission Induction for Non-Organ Threatening Disease

• Use methotrexate (oral or parenteral) plus glucocorticoids as a less toxic alternative for early systemic, non-life threatening ANCA-associated vasculitis 1, 2
• Do not use methotrexate if patient develops organ-threatening manifestations—switch to cyclophosphamide 1

Plasma Exchange

• Add plasma exchange for patients with rapidly progressive severe renal disease (creatinine >500 μmol/L) to improve renal survival 1

Remission Maintenance

• Transition to maintenance therapy after remission induction (typically 3-6 months of cyclophosphamide) 1, 4
• Use azathioprine (2 mg/kg/day) as first-line maintenance combined with low-dose glucocorticoids 1
• Alternative maintenance agents include leflunomide or methotrexate if azathioprine is contraindicated 1
• Continue maintenance therapy for at least 18 months (12 months for polyarteritis nodosa/Churg-Strauss syndrome, longer for Wegener granulomatosis) 5

Refractory or Relapsing Disease

• Refer to expert centers for patients who fail standard therapy 1
• Consider rituximab for refractory disease—91% (42/46) of patients achieved remission within 6 months in open-label trials 1
• IVIG at 2 g/kg can be used as adjunctive therapy for short-term control in refractory disease 2
• Measure serum immunoglobulin levels before IVIG due to anaphylaxis risk in IgA deficiency and hyperviscosity risk with pre-existing hypergammaglobulinemia 1, 2
• Alternative options include mycophenolate mofetil, infliximab, or anti-thymocyte globulin 1

Large Vessel Vasculitis (Giant Cell Arteritis/Takayasu Arteritis)

Remission Induction

• Initiate high-dose glucocorticoids immediately (prednisolone 1 mg/kg/day, typically 40-60 mg/day) for giant cell arteritis or Takayasu arteritis 1
• Do not delay treatment while awaiting temporal artery biopsy results 1

Adjunctive Immunosuppression

• Add methotrexate (10-15 mg/week for giant cell arteritis, 20-25 mg/week for Takayasu arteritis) to reduce relapse rate and cumulative glucocorticoid dose 1
• Consider azathioprine (2 mg/kg/day) as alternative adjunctive agent for Takayasu arteritis 1
• Do not use infliximab for giant cell arteritis—it does not reduce relapse risk compared to glucocorticoid monotherapy 1
• Use cyclophosphamide only for Takayasu arteritis resistant to glucocorticoids 1

Cardiovascular Protection

• Prescribe low-dose aspirin (75-150 mg/day) for all giant cell arteritis patients to prevent cardiovascular and cerebrovascular events 1
• Provide gastroduodenal protection when initiating aspirin 1

Special Situations

Hepatitis C-Associated Cryoglobulinemic Vasculitis

• Use antiviral therapy as primary treatment 1

Hepatitis B-Associated Polyarteritis Nodosa

• Combine antiviral therapy, plasma exchange, and glucocorticoids 1

Non-Viral Mixed Essential Cryoglobulinemic Vasculitis

• Use immunosuppressive therapy and manage in conjunction with hepatologist 1

Monitoring and Follow-Up

• Perform structured clinical assessment, urinalysis, and basic laboratory tests at each visit 1
• Monitor with clinical assessment and inflammatory markers (ESR, CRP) for large vessel vasculitis 1
• Consider periodic MRI or PET imaging for Takayasu arteritis disease activity assessment 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 1
• Monitor blood counts and renal function regularly during immunosuppressive therapy 1
• Check blood glucose periodically while on glucocorticoid therapy 1

Critical Pitfalls to Avoid

• Never delay proven immunosuppressive therapy—untreated systemic vasculitis carries 40-46% five-year mortality in patients with poor prognostic factors 2
• Tobacco smokers on cyclophosphamide are particularly susceptible to bladder cancer at lower doses and earlier than non-smokers 1
• Pulsed cyclophosphamide may have higher relapse risk than continuous oral therapy despite lower toxicity 1
• Rituximab 500 mg courses showed lesser efficacy for radiographic outcomes compared to 1000 mg courses in some studies 3