What are the causes and treatment approaches for vasculitis in children?

Causes and Treatment Approaches for Vasculitis in Children

Vasculitis in children is caused by various inflammatory processes affecting blood vessel walls, with the most common forms being Kawasaki disease and Henoch-Schönlein purpura, requiring prompt diagnosis and targeted immunosuppressive therapy to prevent serious organ damage and mortality. 1

Common Causes of Pediatric Vasculitis

Primary Vasculitides

• Henoch-Schönlein purpura (HSP):

  • Most common pediatric vasculitis 2
  • Characterized by palpable purpura, abdominal pain, arthritis, and potential renal involvement
  • IgA-mediated small vessel vasculitis

• Kawasaki disease:

  • Acute, self-limited vasculitis predominantly affecting infants and young children 1
  • Leading cause of acquired heart disease in children in developed countries
  • Characterized by fever, bilateral nonexudative conjunctivitis, erythema of lips/oral mucosa, extremity changes, rash, and cervical lymphadenopathy
  • Coronary artery aneurysms develop in 15-25% of untreated cases 1

• ANCA-associated vasculitides:

  • Granulomatosis with polyangiitis (formerly Wegener's)
  • Microscopic polyangiitis
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
  • More aggressive in children than adults with higher rates of renal involvement 2

• Primary CNS angiitis/vasculitis:

  • Inflammatory process only affecting intracranial vessels 1
  • Subcategorized into:
    • Large-to-medium-vessel vasculitis (angiography positive)
    • Small vessel vasculitis (requires brain biopsy for diagnosis) 1

• Takayasu's arteritis:

  • Rare in children, more common in adolescent girls and young adult women 2
  • Affects large vessels, particularly the aorta and its major branches

Secondary Vasculitides

• Infection-associated:

  • Post-streptococcal, mycoplasma, viral infections
  • Mycotic infections in immunocompromised hosts 1
  • Other infectious causes: aspergillosis, Coxsackie-9 virus, California encephalitis virus, mumps, paramyxovirus, Borrelia burgdorferi, cat-scratch disease, brucellosis, and neurocystercercosis 1

• Connective tissue disease-associated:

  • Systemic lupus erythematosus
  • Juvenile idiopathic arthritis
  • Dermatomyositis

• Drug-induced vasculitis

• Malignancy-associated vasculitis (rare in children)

Diagnostic Approach

Clinical Evaluation

• Assess for organ-specific symptoms:
  • Skin: palpable purpura, nodules, ulcers
  • Renal: hematuria, proteinuria, hypertension
  • Neurological: headache, altered consciousness, focal deficits
  • Pulmonary: cough, hemoptysis, shortness of breath
  • Gastrointestinal: abdominal pain, bleeding
  • Cardiovascular: chest pain, heart failure signs

Laboratory Testing

• Complete blood count with differential
• Inflammatory markers (ESR, CRP)
• Renal function tests (creatinine, BUN)
• Urinalysis
• Autoantibodies:
  • ANCA (PR3-ANCA, MPO-ANCA)
  • ANA
  • Anti-dsDNA
• Complement levels (C3, C4)
• Immunoglobulin levels including IgA for HSP

Imaging Studies

• For CNS vasculitis:

  • MRI brain (shows progressive multifocal parenchymal lesions on T2-weighted imaging) 1
  • MRA or CTA (for large-medium vessel vasculitis) 1
  • Conventional angiography (most sensitive for cerebral vasculitis but negative in small-vessel disease) 1

• For Kawasaki disease:

  • Echocardiography to assess coronary arteries

• For systemic vasculitis:

  • Chest radiography
  • CT or MRI of affected organs

Tissue Biopsy

• Gold standard for diagnosis of many vasculitides
• Skin, kidney, nerve, or affected organ biopsy as indicated
• For CNS small-vessel vasculitis, brain biopsy may be required 1

Treatment Approaches

Kawasaki Disease

• First-line treatment:

  • Intravenous immunoglobulin (IVIG) 2g/kg as a single infusion within 10 days of fever onset 1
  • Aspirin (high-dose initially, then low-dose for antiplatelet effect)
  • Early treatment reduces coronary artery aneurysm risk from 25% to <5% 3

• For IVIG-resistant cases (10-20% of patients):

  • Second IVIG dose
  • Corticosteroids
  • Consider TNF-α antagonists (infliximab) in selected cases 1

ANCA-Associated Vasculitis

• Induction therapy for pediatric GPA and MPA:

  • Methylprednisolone pulse therapy (30 mg/kg/day, not exceeding 1g/day) 4
  • Rituximab: 375 mg/m² BSA weekly for 4 weeks 4
  • Oral prednisone/prednisolone (1 mg/kg/day, max 60 mg/day) with taper to 0.2 mg/kg/day 4
  • Alternative: Cyclophosphamide with corticosteroids

• Maintenance therapy:

  • Rituximab infusions every 6 months 4
  • Alternative: Azathioprine, methotrexate, or mycophenolate mofetil

Henoch-Schönlein Purpura

• Mild disease: Supportive care, NSAIDs for joint pain
• For significant renal involvement: Corticosteroids
• Severe nephritis: Consider cyclophosphamide, azathioprine, or mycophenolate mofetil

Primary CNS Vasculitis

• Induction therapy: Glucocorticoids with or without immunosuppressants 1
• Maintenance therapy: Steroid-sparing immunosuppressants 1

Takayasu's Arteritis

• Corticosteroids as initial therapy
• Steroid-sparing agents: Methotrexate, azathioprine, or leflunomide 1
• Biological agents (anti-TNF) for refractory cases

Important Considerations and Pitfalls

• Early diagnosis is critical: Delayed treatment of Kawasaki disease beyond 10 days significantly increases risk of coronary artery aneurysms 1

• Incomplete Kawasaki disease: Consider in infants with prolonged fever even if full criteria aren't met; treat promptly to prevent coronary complications 2

• Monitor for disease relapse: Particularly in ANCA-associated vasculitis, where relapse rates are high

• Long-term follow-up: Patients with aneurysms from Kawasaki disease require lifelong cardiology follow-up 1

• Growth and development: Consider impact of chronic steroid therapy on growth in children and use steroid-sparing agents when possible

• Vaccination considerations: Live vaccines should be avoided during immunosuppressive therapy

• Transition to adult care: Develop transition plans for adolescents with chronic vasculitis

By understanding the specific causes and implementing appropriate treatment approaches, outcomes for children with vasculitis can be significantly improved, reducing morbidity and mortality associated with these complex inflammatory conditions.