Management and Treatment of Vasculitis

Immediate Management Priorities

All patients with suspected vasculitis should be managed at or in close collaboration with centers of expertise, as these are rare, heterogeneous, and potentially life-threatening diseases requiring multidisciplinary care. 1

Critical First Steps

Do not delay treatment while awaiting biopsy results in patients with rapidly deteriorating clinical status, particularly those with positive ANCA serology and typical clinical presentation 1, 2
Obtain tissue biopsy whenever feasible to confirm diagnosis—histopathological evidence remains the gold standard, with renal biopsy yielding up to 91.5% diagnostic sensitivity in GPA with renal involvement 1
Categorize disease severity immediately to guide treatment intensity: severe/organ-threatening versus non-severe/non-organ-threatening disease 1

Treatment by Disease Severity

Severe or Organ-Threatening ANCA-Associated Vasculitis

For new-onset severe AAV (rapidly progressive glomerulonephritis, pulmonary hemorrhage, or other life/organ-threatening manifestations), initiate combination therapy with high-dose glucocorticoids PLUS either rituximab OR cyclophosphamide. 1, 2

Induction Regimen Options:

Option 1: Rituximab-based (preferred for specific populations)

Rituximab 375 mg/m² IV weekly for 4 weeks OR 1,000 mg IV on days 1 and 15 1, 3
PLUS glucocorticoids: 1 mg/kg/day oral prednisone (maximum 60-80 mg/day) 1, 2
Consider IV methylprednisolone 500-1,000 mg/day for 1-3 days before oral therapy 1, 3
Rituximab is specifically favored for: younger patients concerned about fertility, relapsing disease (67% vs 42% remission rate compared to cyclophosphamide), and patients with prior cyclophosphamide exposure 1, 2

Option 2: Cyclophosphamide-based

Cyclophosphamide 2 mg/kg/day oral (maximum 200 mg/day) for 3-6 months OR IV 15 mg/kg every 2 weeks for 3 doses, then every 3 weeks 1, 2
PLUS glucocorticoids: same dosing as above 1
Cyclophosphamide is specifically favored for: severe renal disease with markedly reduced or rapidly declining function 2

For the most severe presentations (dialysis-dependent, rapidly progressive renal failure, or diffuse alveolar hemorrhage with hypoxemia):

Consider combination of rituximab PLUS cyclophosphamide 2
Add plasma exchange for serum creatinine ≥500 μmol/L (5.7 mg/dL) or severe pulmonary hemorrhage 1

Evidence Quality:

The 2024 EULAR guidelines provide Level 1A evidence for cyclophosphamide and Level 1B for rituximab in GPA/MPA 1. The FDA label confirms 64% complete remission rate with rituximab at 6 months, demonstrating non-inferiority to cyclophosphamide 3.

Non-Severe, Non-Organ-Threatening AAV

For limited disease without life or organ-threatening manifestations, use methotrexate OR mycophenolate mofetil PLUS glucocorticoids. 1, 2

Methotrexate up to 25 mg/week (oral or subcutaneous) 1
OR Mycophenolate mofetil up to 1,500 mg twice daily 1
PLUS glucocorticoids: 1 mg/kg/day with tapering 1
Critical caveat: Do not use methotrexate if GFR <60 mL/min per 1.73 m² 2

Glucocorticoid Tapering Protocol

Maintain high-dose glucocorticoids (1 mg/kg/day) for approximately one month, then taper gradually. 1, 2

Reduce to 5-7.5 mg/day by 6 months and maintain at this dose for remission maintenance 2
Continue low-dose glucocorticoids (5-7.5 mg/day) for minimum 2 years, then reduce by 1 mg every 2 months 2
Avoid alternate-day glucocorticoid therapy—this significantly increases relapse risk 2

Remission Maintenance Therapy

Once remission is achieved (typically by 3-6 months), transition to maintenance therapy for a minimum of 18-24 months, preferably extending to 4 years to reduce relapse risk. 1, 2

Maintenance Options (in order of evidence strength):

Azathioprine up to 2 mg/kg/day (strongest evidence, first-line choice) 1, 2
Rituximab 500 mg IV every 6 months 1
Methotrexate up to 25 mg/week (if GFR ≥60 mL/min) 1, 2
Mycophenolate mofetil up to 1,500 mg twice daily 1

All maintenance regimens should include low-dose glucocorticoids (5-7.5 mg/day) 1, 2

Management of Refractory or Relapsing Disease

For patients failing standard induction therapy or experiencing major relapse, switch immunosuppressive agents: cyclophosphamide to rituximab or rituximab to cyclophosphamide. 1

Rituximab achieves 91% remission rate in refractory AAV across multiple open-label trials 1, 2
For major relapse with organ-threatening disease, treat as new disease with full induction regimen 1
Refer immediately to expert centers for enrollment in clinical trials 1

Additional Options for Refractory Disease:

IVIG 2 g/kg for short-term control (check serum immunoglobulin levels first—risk of anaphylaxis in IgA deficiency) 1, 2
Consider mycophenolate mofetil, 15-deoxyspergualin, or anti-thymocyte globulin 1

Mandatory Monitoring Requirements

At Every Clinical Visit:

Structured clinical assessment using Birmingham Vasculitis Activity Score (BVAS) 2, 4
Urinalysis with microscopy and proteinuria quantification 1, 2
Comprehensive metabolic panel, ESR, and CRP 2
Monitor for drug toxicity: CBC for leukopenia, renal function 1, 2

Long-Term Surveillance:

Investigate all persistent unexplained hematuria in patients with prior cyclophosphamide exposure—bladder cancer risk persists indefinitely, with tobacco smokers developing cancer at lower doses and earlier than non-smokers 1, 2
Test serum immunoglobulin levels before each rituximab course and in patients with recurrent infections (27% develop low IgA, 58% low IgG at 6 months) 3
Screen for cardiovascular risk factors periodically—AAV patients have increased cardiovascular events related to disease activity burden 1
Assess for osteoporosis, chronic kidney disease, diabetes, and hypertension 1

ANCA Testing:

Do not use ANCA levels alone to guide treatment changes—structured clinical assessment should inform decisions 1
However, ANCA persistence, rising levels, or conversion from negative to positive may predict future relapse and should be considered alongside clinical assessment 2

Critical Pitfalls to Avoid

Never delay treatment in rapidly deteriorating patients while awaiting biopsy confirmation 1, 2
Never use alternate-day glucocorticoid regimens—significantly increases relapse risk 2
Never use methotrexate if GFR <60 mL/min per 1.73 m² 2
Never provide inadequate initial immunosuppression in severe disease—combination therapy is mandatory, not optional 2
Never stop monitoring for bladder cancer in cyclophosphamide-exposed patients—risk persists indefinitely with periodic urinalysis required throughout follow-up 1, 2
Never ignore recurrent infections in rituximab-treated patients—check immunoglobulin levels 1, 3

Special Populations

Eosinophilic Granulomatosis with Polyangiitis (EGPA):

Evidence for cyclophosphamide and rituximab is lower quality (Level 3-4) compared to GPA/MPA 1
Consider mepolizumab 300 mg SC every 4 weeks as adjunctive or steroid-sparing therapy 1

Pediatric Patients (6-17 years):

Rituximab dosing: 375 mg/m² IV weekly for 4 weeks OR 575 mg/m² (BSA ≤1.5 m²) or 750 mg/m² (BSA >1.5 m²) on days 1 and 15 1
Safety profile consistent with adults 3

Hepatitis B-Associated Polyarteritis Nodosa:

Combination of antiviral therapy, plasma exchange, and glucocorticoids 1

Hepatitis C-Associated Cryoglobulinemic Vasculitis:

Antiviral therapy is primary treatment 1

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