What is the recommended treatment regimen for systemic vasculitis, including induction and maintenance therapies for ANCA-associated vasculitis, giant cell arteritis, Takayasu arteritis, Kawasaki disease, and IgA vasculitis?

Treatment of Systemic Vasculitis

For ANCA-associated vasculitis, initiate remission induction with glucocorticoids combined with rituximab or cyclophosphamide, followed by maintenance therapy with rituximab or azathioprine plus low-dose glucocorticoids for 18 months to 4 years 1.

ANCA-Associated Vasculitis (GPA, MPA, EGPA)

Induction Therapy (Remission Induction)

Initiate treatment immediately when clinical presentation is compatible with small-vessel vasculitis and ANCA serology is positive—do not delay for biopsy results in rapidly deteriorating patients 1.

Standard induction regimen:

• Glucocorticoids PLUS rituximab OR cyclophosphamide 1

Glucocorticoid dosing:

• Start: 1 mg/kg/day (maximum 80 mg/day)
• Reduce for age: ≥60 years use 1.5 mg/kg/day; ≥70 years use 1.0 mg/kg/day
• Taper to 10-15 mg/day by 3 months 1

Rituximab dosing:

• 375 mg/m² weekly × 4 weeks 1
• Preferred for relapsing disease 1

Cyclophosphamide dosing:

• Intravenous: 15 mg/kg every 2-4 weeks (reduce for age ≥60 years to 12.5 mg/kg; ≥70 years to 10 mg/kg)
• Oral: 2 mg/kg/day (maximum 200 mg/day)
• Reduce by 2.5 mg/kg for GFR <30 ml/min/1.73 m² 1
• Consider cyclophosphamide for severe renal disease (SCr >4 mg/dl or >354 μmol/l) 1

Plasma exchange considerations:

• Consider for SCr >3.4 mg/dl (>300 mmol/l), dialysis-dependent patients, or diffuse alveolar hemorrhage with hypoxemia 1

Maintenance Therapy

After achieving remission, transition to maintenance therapy with:

• Rituximab (preferred) OR azathioprine plus low-dose glucocorticoids 1

Rituximab maintenance dosing (choose one protocol):

1. MAINRITSAN scheme: 500 mg × 2 at remission, then 500 mg at months 6,12, and 18
2. RITAZAREM scheme: 1000 mg at remission, then at months 4,8,12, and 16 1

Azathioprine maintenance dosing:

• 1.5-2 mg/kg/day at complete remission
• Continue for 1 year, then decrease by 25 mg every 3 months
• For extended therapy: maintain 1.5-2 mg/kg/day for 18-24 months, then reduce to 1 mg/kg/day until 4 years, then taper by 25 mg every 3 months 1

Glucocorticoid maintenance:

• Continue 5-7.5 mg/day for 2 years
• Then reduce by 1 mg every 2 months 1

Alternative maintenance agents:

• Mycophenolate mofetil: 2000 mg/day (divided doses) for patients intolerant of azathioprine 1
• Methotrexate: Alternative to azathioprine, but contraindicated if GFR <60 ml/min/1.73 m² 1

Duration of maintenance: 18 months to 4 years after induction of remission 1

Relapsing Disease

Severe relapse (life- or organ-threatening):

• Re-induce with same regimen as initial therapy
• Rituximab is preferred over cyclophosphamide for relapsing disease 1

Non-severe relapse:

• Increase glucocorticoids and/or intensify immunosuppression
• Avoid cyclophosphamide to minimize cumulative exposure 2

Refractory Disease

• Increase glucocorticoids (IV or oral)
• Switch between rituximab and cyclophosphamide (add rituximab if cyclophosphamide was used initially, or vice versa)
• Consider plasma exchange 1

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Giant Cell Arteritis (GCA)

Initiate high-dose glucocorticoids immediately upon clinical suspicion—do not delay for temporal artery biopsy 3.

Induction Therapy

Glucocorticoid regimen:

• High-dose glucocorticoids (specific dosing per local protocols)
• Early tapering recommended to reduce cumulative dose and toxicity 3

Glucocorticoid-sparing agents:

• Tocilizumab (IL-6 inhibitor): Now established as standard therapy in GCA 4, 5
• Methotrexate: 10-15 mg/week as adjunctive therapy to reduce relapse rate and lower cumulative glucocorticoid dose (level of evidence 1A, grade B) 3
• Upadacitinib (JAK inhibitor): Recently approved for GCA based on phase 3 trial results 5

Low-dose aspirin:

• Recommend 75-150 mg/day for all patients to protect against cardiovascular and cerebrovascular events (unless contraindicated) 3
• Consider gastroduodenal mucosal protection when starting aspirin 3

Monitoring

• Clinical monitoring supported by inflammatory markers (ESR, CRP)
• Relapse typically associated with rising ESR 3
• Duration of glucocorticoid therapy is variable and may extend to several years 3

Common pitfall: 86% of patients on glucocorticoid monotherapy suffer glucocorticoid-related adverse events at 10-year follow-up, emphasizing the importance of early glucocorticoid-sparing agents 3.

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Takayasu Arteritis (TAK)

Initiate high-dose glucocorticoids combined with immunosuppressive agents as initial therapy 3, 4.

Initial Therapy

Glucocorticoids PLUS immunosuppressive agent:

• Azathioprine: 2 mg/kg/day
• Methotrexate: 20-25 mg/week
• These agents improve disease control and facilitate glucocorticoid dose reduction 3

For glucocorticoid-resistant disease:

• Cyclophosphamide has been used in small open-label studies 3

Biologic therapy for relapsing/refractory disease:

• TNF-α inhibitors or IL-6 blockade (tocilizumab) can be considered 5

Monitoring

• Clinical monitoring with inflammatory markers
• Periodic MRI imaging may assist assessment of disease activity
• PET scanning may be valuable for monitoring
• Limited evidence for carotid/subclavian ultrasonography 3
• All patients require long-term monitoring 3

Surgical Considerations

• Reconstructive surgery should be performed in the quiescent phase of disease at expert centers
• Angioplasty and stent insertion have higher restenosis rates than surgical reconstruction but may be appropriate for selected patients
• Elective procedures should be performed when disease is in remission 3

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Kawasaki Disease

Intravenous immunoglobulin (IVIG) is standard therapy.

For IVIG-resistant disease:

• Infliximab (TNF-α inhibitor) is an option 6

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IgA Vasculitis (Henoch-Schönlein Purpura)

Treatment depends on severity and organ involvement 7.

Cutaneous Disease

Mild disease:

• Symptomatic treatment usually sufficient due to favorable course
• If triggers identified, avoid them 8

Hemorrhagic blisters suggesting skin necrosis:

• Glucocorticoids indicated 8

Chronic or relapsing disease:

• Colchicine or dapsone 8

Severe Glomerulonephritis in Adults

• Insufficient evidence for glucocorticoid efficacy
• ACE inhibitors can be helpful depending on symptoms 8
• Treatment should be individualized based on severity of renal involvement 7

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Key Clinical Considerations

Prophylaxis during treatment:

• Pneumocystis jiroveci prophylaxis with trimethoprim-sulfamethoxazole during cyclophosphamide or rituximab therapy 2, 9
• Bone protection therapy for all patients on glucocorticoids (unless contraindicated) 3
• Bladder protection with MESNA for patients receiving cyclophosphamide to prevent hemorrhagic cystitis 9

Treatment at expert centers:

• Patients with ANCA-associated vasculitis should be treated at centers with AAV management experience 1
• Takayasu arteritis surgical procedures should be performed at expert centers 3

Monitoring for drug toxicity:

• Regular monitoring of blood counts, renal function, and liver function during immunosuppressive therapy
• Cyclophosphamide carries long-term risks of hemorrhagic cystitis and malignancy 9