What is the appropriate treatment approach for a patient diagnosed with vasculitis?

Treatment Approach for Vasculitis

Immediate Management Priority

Vasculitis requires immediate initiation of combination immunosuppressive therapy with high-dose glucocorticoids plus either rituximab or cyclophosphamide, with treatment decisions guided by disease severity, organ involvement, and vasculitis type. 1, 2

Disease Classification and Severity Assessment

• Categorize patients by vessel size and disease severity before initiating treatment: localized, early systemic, generalized, severe (organ-threatening), or refractory disease 1
• Obtain tissue biopsy when feasible to confirm diagnosis, but do not delay treatment while awaiting histological confirmation in rapidly deteriorating patients 1, 2
• Perform ANCA testing (indirect immunofluorescence and ELISA) in appropriate clinical contexts, with sensitivity of 80-90% for ANCA-associated vasculitis (AAV) 1, 2
• Conduct structured clinical assessment including urinalysis with microscopy, comprehensive metabolic panel, ESR, and CRP at baseline 1, 2

Induction Therapy for ANCA-Associated Vasculitis

Severe/Generalized Disease

For severe or generalized AAV, initiate prednisolone 1 mg/kg/day (maximum 60 mg/day) combined with either:

• Cyclophosphamide 2 mg/kg/day orally (maximum 200 mg/day) OR intravenous pulses 1, 2
• Rituximab 375 mg/m² weekly for 4 weeks 2, 3

Choosing Between Cyclophosphamide and Rituximab

Favor cyclophosphamide for: 2

• Markedly reduced or rapidly declining renal function
• Severe renal disease requiring dialysis
• Diffuse alveolar hemorrhage with hypoxemia

Favor rituximab for: 2, 3

• Younger patients with fertility concerns
• Relapsing disease (67% vs 42% remission rate compared to cyclophosphamide)
• Patients who have previously received cyclophosphamide

Non-Organ Threatening Disease

• For non-organ threatening or non-life threatening AAV, use methotrexate (oral or parenteral) plus glucocorticoids as a less toxic alternative 1
• Do not use methotrexate in patients with GFR <60 mL/min per 1.73 m² 2

Adjunctive Therapies

• Add plasma exchange for patients with dialysis requirement, rapidly progressive renal failure, or diffuse alveolar hemorrhage with hypoxemia 1, 2
• Initiate Pneumocystis jiroveci prophylaxis with sulfamethoxazole-trimethoprim (800 mg-160 mg on alternate days or 400 mg-80 mg daily) in all patients receiving cyclophosphamide and/or rituximab 1, 2
• Provide bone protection therapy (calcium, vitamin D, bisphosphonates) for all patients on glucocorticoids 1, 2
• Consider intravenous methylprednisolone 1,000 mg daily for 1-3 days before oral glucocorticoids in severe disease 3

Glucocorticoid Tapering

• Maintain high-dose glucocorticoids (1 mg/kg/day) for one month minimum before initiating gradual taper 2
• Never use alternate-day glucocorticoid therapy, as this significantly increases relapse risk 2
• Taper to 5-7.5 mg/day for maintenance therapy over 2 years, then reduce by 1 mg every 2 months 2

Maintenance Therapy After Remission

Once remission is achieved (typically after 3-6 months), transition to maintenance therapy with low-dose glucocorticoids (5-7.5 mg/day) PLUS one of the following: 1, 2

• Azathioprine 1-2 mg/kg/day (first-line choice with strongest evidence) 1, 2
• Rituximab (for patients with relapsing disease or who achieved remission with rituximab) 2, 3
• Mycophenolate mofetil 1, 2
• Leflunomide 1
• Methotrexate (if GFR ≥60 mL/min per 1.73 m²) 1, 2

Continue maintenance therapy for minimum 18-24 months, with extended therapy to 4 years reducing relapse risk 1, 2

Refractory or Relapsing Disease

• For patients failing standard therapy or experiencing relapse, rituximab achieves 91% remission rate in refractory AAV 1, 2
• Consider intravenous immunoglobulin (IVIG) 2 g/kg for short-term control, but measure serum immunoglobulin levels first due to anaphylaxis risk in IgA deficiency 1, 2
• Alternative options include mycophenolate mofetil, 15-deoxyspergualin, anti-thymocyte globulin, or infliximab 1
• Refer refractory patients to expert vasculitis centers for enrollment in clinical trials 1

Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis)

• Initiate high-dose glucocorticoids immediately (prednisolone 1 mg/kg/day, maximum 60 mg/day) for large vessel vasculitis 2
• For Giant Cell Arteritis with symptoms, immediate glucocorticoid initiation reduces recurrent stroke risk 2
• Consider adjunctive immunosuppressive therapy (methotrexate or tocilizumab) as steroid-sparing agents for Giant Cell Arteritis 2
• For Takayasu Arteritis, all patients should receive non-biological glucocorticoid-sparing agents in combination with glucocorticoids 2

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• Treatment follows similar principles to other AAV with glucocorticoids plus cyclophosphamide or rituximab for severe disease 1
• Screen for hepatitis B virus and HIV before initiating cyclophosphamide or rituximab 1
• Monitor quantitative IgG serum concentrations due to risk of secondary hypogammaglobulinemia 1
• Consider anti-histaminic treatment for allergic patients to control ENT symptoms 1

Monitoring and Follow-Up

• Perform structured clinical assessment, urinalysis, and basic laboratory tests at every clinical visit 1
• Monitor ANCA levels, as persistence, increase, or change from negative to positive may predict future relapse 2
• Investigate all persistent unexplained hematuria in patients with prior cyclophosphamide exposure due to bladder cancer risk 1, 2
• Conduct periodic urinalysis for duration of follow-up in all cyclophosphamide-treated patients 1
• Screen for and manage cardiovascular risk factors, osteoporosis, and chronic kidney disease 1
• Perform age-appropriate cancer screening; cyclophosphamide-treated patients require additional screening for bladder cancer, myeloid leukemia, and skin cancer 1

Multidisciplinary Management

• Manage all vasculitis patients at centers with specific vasculitis expertise or with ready access to such centers 1
• Ensure access to multidisciplinary diagnostic evaluation including nephrology, pulmonology, otorhinolaryngology, and ophthalmology as needed 1
• Provide patient education through appropriately trained nurses and healthcare providers experienced in AAV 1

Critical Pitfalls to Avoid

• Delaying treatment while awaiting biopsy results in rapidly deteriorating patients 1, 2
• Using alternate-day glucocorticoid therapy, which increases relapse risk 2
• Inadequate initial immunosuppression in severe disease 2
• Tobacco smokers on cyclophosphamide develop bladder cancer at lower doses and earlier than non-smokers 2
• Failing to provide Pneumocystis prophylaxis in patients receiving cyclophosphamide or rituximab 1
• Using methotrexate in patients with impaired renal function (GFR <60 mL/min per 1.73 m²) 2
• Stopping maintenance therapy prematurely (before 18-24 months minimum) 1, 2