What is the recommended treatment for vasculitis in children?

Treatment of Vasculitis in Children

For children with vasculitis, treatment must be tailored to the specific vasculitis type and disease severity, with Kawasaki disease requiring immediate high-dose IVIG (2 g/kg) plus aspirin, ANCA-associated vasculitis requiring combination glucocorticoids with cyclophosphamide or rituximab, and polyarteritis nodosa requiring cyclophosphamide plus high-dose glucocorticoids for severe disease. 1, 2, 3

Kawasaki Disease

Kawasaki disease is the most common vasculitis in children and requires urgent treatment to prevent coronary artery complications. 1, 4

Primary Treatment

• Administer IVIG 2 g/kg as a single infusion within 10 days of fever onset to reduce coronary artery aneurysm risk from 25% to 5% 1
• Combine with high-dose aspirin 80-100 mg/kg/day divided into 4 doses until fever resolves for 48-72 hours 1
• After fever resolution, reduce aspirin to 3-5 mg/kg/day (antiplatelet dose) and continue for 6-8 weeks if no coronary abnormalities are present 1
• If coronary aneurysms develop, continue low-dose aspirin indefinitely 1

Adjunctive Corticosteroids for High-Risk Patients

• Consider adding intravenous methylprednisolone 30 mg/kg/day (maximum 1,000 mg/day) for patients at high risk for IVIG resistance 1
• High-risk patients include those with elevated inflammatory markers or specific risk scores predicting IVIG failure 1
• Corticosteroids have shown shorter fever duration and potentially lower coronary artery abnormality rates in high-risk populations 1

Refractory Disease

• For persistent fever 36 hours after completing IVIG, administer a second dose of IVIG 2 g/kg 1
• For patients failing two IVIG infusions, restrict corticosteroid treatment to this population 1

ANCA-Associated Vasculitis (Granulomatosis with Polyangiitis, Microscopic Polyangiitis)

ANCA-associated vasculitis in children requires aggressive immunosuppression to prevent organ damage and mortality. 2, 3, 5

Induction Therapy for Severe Disease

• Initiate combination therapy with glucocorticoids plus either rituximab or cyclophosphamide immediately 2, 3
• Administer intravenous methylprednisolone 30 mg/kg/day (maximum 1,000 mg/day) for 3 doses prior to rituximab 3
• Follow with oral prednisone 1-2 mg/kg/day (maximum 60 mg/day) and taper to 0.2 mg/kg/day (maximum 10 mg/day) by month 6 1, 3

Rituximab Dosing in Children

• Give rituximab 375 mg/m² BSA intravenously once weekly for 4 consecutive weeks (days 1,8,15,22) 3
• After remission induction, administer subsequent rituximab infusions at or after month 6 to maintain remission 3
• Rituximab achieved 100% remission rate by month 18 in pediatric studies 3
• Favor rituximab in younger patients concerned about fertility and those with relapsing disease 2

Cyclophosphamide Alternative

• Use oral cyclophosphamide 2 mg/kg/day for patients with severe renal disease or rapidly declining renal function 2
• Consider combination of rituximab plus cyclophosphamide for severe disease with pulmonary hemorrhage or rapidly progressive renal disease 2

Maintenance Therapy

• After achieving remission, continue maintenance immunosuppression for at least 18 months 3
• Options include continued rituximab every 6 months or transition to azathioprine 3

Polyarteritis Nodosa

Systemic polyarteritis nodosa requires aggressive treatment based on disease severity. 1

Severe Disease (Life- or Organ-Threatening)

• Initiate IV pulse glucocorticoids: methylprednisolone 30 mg/kg/day (maximum 1,000 mg/day) for 3-5 days 1
• Combine with cyclophosphamide plus high-dose oral glucocorticoids (prednisone 1-2 mg/kg/day, maximum 60 mg/day) over glucocorticoids alone 1
• Prefer cyclophosphamide plus glucocorticoids over rituximab plus glucocorticoids for initial treatment 1

Nonsevere Disease

• Use moderate-dose oral glucocorticoids (prednisone ~0.5 mg/kg/day, generally 10-30 mg/day) 1
• May not require additional immunosuppression if no organ-threatening manifestations 1

Alternative Immunosuppression

• For patients unable to tolerate cyclophosphamide, use other non-glucocorticoid immunosuppressive agents including azathioprine, methotrexate, or mycophenolate mofetil 1

Takayasu Arteritis

All pediatric patients with Takayasu arteritis require glucocorticoid-sparing agents from diagnosis. 1, 2

• Initiate high-dose oral glucocorticoids (prednisone 1-2 mg/kg/day, maximum 60 mg/day) over IV pulse glucocorticoids 1
• Combine glucocorticoids with non-biological glucocorticoid-sparing agents such as methotrexate or azathioprine from the start 1, 2
• In children, consider alternate steroid dosing regimens (IV pulse with low daily oral dosing) to improve compliance and reduce growth impact 1

Henoch-Schönlein Purpura

Henoch-Schönlein purpura is typically self-limited and requires supportive care in most cases. 4, 6

• Manage with leg elevation, avoidance of prolonged standing, and NSAIDs for mild disease 7
• Reserve glucocorticoids for severe abdominal pain, gastrointestinal bleeding, or significant renal involvement 7
• Most cases resolve spontaneously without immunosuppression 4, 6

Critical Monitoring and Pitfalls

Diagnostic Considerations

• For suspected polyarteritis nodosa, obtain abdominal vascular imaging to establish diagnosis and extent of disease 1
• For suspected polyarteritis nodosa with skin involvement, obtain deep-skin biopsy reaching medium-sized vessels over superficial punch biopsy 1
• For suspected polyarteritis nodosa with peripheral neuropathy, obtain combined nerve and muscle biopsy over nerve biopsy alone 1

Treatment Monitoring

• Do not delay treatment in ANCA-associated vasculitis while waiting for biopsy results in rapidly deteriorating patients 2
• Monitor ANCA levels during treatment, as persistence or increase may predict future relapse 2, 8
• Assess disease activity using validated tools such as Pediatric Vasculitis Activity Score (PVAS) 3, 5
• Provide prophylaxis against Pneumocystis jiroveci for all patients on cyclophosphamide or rituximab 2

Kawasaki Disease-Specific Precautions

• Defer measles and varicella immunizations for 11 months after high-dose IVIG 1
• Avoid ibuprofen in children with coronary aneurysms taking aspirin for antiplatelet effect, as it antagonizes aspirin's irreversible platelet inhibition 1
• Administer annual inactivated influenza vaccine to all children on chronic aspirin therapy to prevent Reye syndrome risk 1

Long-Term Outcomes

• Recognize that 63% of children with ANCA-associated vasculitis develop organ damage within 12 months despite treatment 5
• Only 42% of pediatric ANCA-associated vasculitis patients achieve complete remission by 12 months, though 92% show significant improvement 5
• Lifelong cardiovascular monitoring is required for Kawasaki disease patients with coronary involvement 1