What are the principles of management of Kawasaki disease?

Management Principles of Kawasaki Disease

The cornerstone of Kawasaki disease management is prompt administration of intravenous immunoglobulin (IVIG) at a dose of 2 g/kg as a single infusion, along with aspirin therapy, to reduce the risk of coronary artery abnormalities. 1, 2

Initial Treatment

First-Line Therapy

• IVIG administration: 2 g/kg as a single infusion over 10-12 hours
  • Should be given as soon as diagnosis is established
  • Ideally within the first 10 days of illness
  • Reduces risk of coronary artery abnormalities from 20-25% to <5% 2

Aspirin Therapy

• Acute phase: High-dose aspirin (80-100 mg/kg/day divided into four doses)
  • Continue until patient is afebrile for 48-72 hours
• Convalescent phase: Low-dose aspirin (3-5 mg/kg/day as a single dose)
  • Continue for antiplatelet effect until 6-8 weeks after disease onset if no coronary abnormalities develop 2

Note: Recent evidence from a 2025 randomized clinical trial suggests that IVIG alone without high-dose aspirin may be non-inferior for preventing coronary artery lesions 3. However, current guidelines still recommend the combined approach.

Management of IVIG-Resistant Kawasaki Disease

IVIG resistance occurs in approximately 10-20% of patients, defined as persistent or recrudescent fever at least 36 hours after completion of initial IVIG infusion 1, 2.

Treatment Options for IVIG Resistance (in order of preference):

1. Second dose of IVIG (2 g/kg as a single infusion)

   • Recommended as first-line treatment for IVIG resistance 1

2. Corticosteroid therapy options:

   • Methylprednisolone pulse therapy: 20-30 mg/kg IV daily for 3 days
   • Prednisolone/prednisone: 2 mg/kg/day with taper over 2-3 weeks after CRP normalizes 1

3. Infliximab (TNF-α inhibitor)

   • Dose: 5 mg/kg IV as a single infusion over 2 hours
   • May be considered as an alternative to second IVIG dose
   • Particularly effective at preventing IVIG infusion reactions 1

4. Cyclosporine

   • For highly refractory cases (failure of second IVIG, steroids, or infliximab)
   • Oral: 4-8 mg/kg/day divided every 12 hours
   • IV: 3 mg/kg/day divided every 12 hours
   • Adjust dose to achieve trough 50-150 ng/mL; 2-hour peak level 300-600 ng/mL 1

5. Other options for highly refractory cases:

   • Anakinra (IL-1 receptor antagonist): 2-6 mg/kg/day subcutaneously
   • Plasma exchange (for extremely resistant cases)
   • Cyclophosphamide (rarely used): 2 mg/kg/day IV 1

Anticoagulation Management for Coronary Artery Involvement

Management depends on the severity and extent of coronary involvement 1:

Mild-to-Moderate Coronary Disease

• Low-dose aspirin (3-5 mg/kg/day)
• Consider adding clopidogrel or dipyridamole for more extensive disease

Rapidly Expanding Coronary Aneurysms

• Combination of heparin and aspirin during acute expansion phase
• Long-term anticoagulation with warfarin plus aspirin for large or giant aneurysms

Monitoring and Follow-up

• Echocardiography:

  • At diagnosis
  • 1-2 weeks after treatment
  • 4-6 weeks after treatment for uncomplicated cases
  • More frequent monitoring for patients with coronary abnormalities 2

• Long-term management:

  • Based on degree of coronary involvement
  • Annual influenza vaccination for children on long-term aspirin therapy to reduce risk of Reye syndrome 2

Important Clinical Considerations

1. Timing is critical: Treatment within the first 10 days of illness significantly reduces the risk of coronary artery complications 4

2. Risk stratification: Japanese scoring systems to predict IVIG resistance are not accurate in North American populations 1

3. Thromboembolism risk: IVIG therapy can increase blood viscosity, potentially increasing thromboembolism risk, particularly in patients with endothelial impairment 5

4. Incomplete Kawasaki disease: Consider diagnosis in children with prolonged unexplained fever and fewer than 4 principal clinical findings if laboratory or echocardiographic findings are compatible 2

5. Infants under 6 months: May present atypically with prolonged fever and irritability as the only clinical manifestations, leading to delayed diagnosis 2

By following these management principles and being vigilant for IVIG resistance, clinicians can significantly reduce the risk of coronary artery complications and improve outcomes in children with Kawasaki disease.