What is the treatment for Kawasaki disease?

Treatment of Kawasaki Disease

The standard treatment for Kawasaki disease consists of intravenous immunoglobulin (IVIG) 2 g/kg as a single infusion, along with high-dose aspirin (80-100 mg/kg/day divided into four doses), which should be administered as soon as the diagnosis is established and ideally within the first 10 days of illness. 1

Initial Treatment

Primary Therapy

1. IVIG Administration:

   • Dose: 2 g/kg as a single infusion (Level A evidence)
   • Timing: As soon as diagnosis is established, ideally within first 10 days of illness
   • Administration: Usually given over 10-12 hours
   • Purpose: Reduces risk of coronary artery abnormalities from 20-25% to <5% 1, 2

2. Aspirin Therapy:

   • Acute phase: High-dose aspirin (80-100 mg/kg/day divided into four doses)
   • Duration: Until patient is afebrile for 48-72 hours
   • Transition: Reduce to low-dose aspirin (3-5 mg/kg/day as a single dose) for antiplatelet effect 1
   • Maintenance: Continue low-dose aspirin until 6-8 weeks after disease onset if no coronary abnormalities develop 1, 2

Note: Recent research suggests IVIG alone without high-dose aspirin may be equally effective in preventing coronary artery lesions, though this approach has not yet been incorporated into guidelines 3.

Management of IVIG Resistance

Approximately 10-20% of patients develop recrudescent or persistent fever at least 36 hours after IVIG infusion (IVIG resistance) 1.

Treatment Options for IVIG Resistance:

1. Second IVIG dose:

   • Administer 2 g/kg if fever persists or recurs within 36 hours after initial IVIG 1

2. Corticosteroids:

   • Consider in patients who fail to respond to second IVIG dose
   • Options include:
     • IVIG + prednisolone (2 mg/kg/day IV divided every 8 hours until afebrile, then oral prednisone until CRP normalizes, followed by taper over 2-3 weeks) 1
     • Intravenous pulse methylprednisolone (30 mg/kg once daily for 1-3 days) 1

3. Biological agents:

   • Infliximab (monoclonal antibody against TNF-α): 5 mg/kg IV as a single infusion 1
   • May be considered after failure of second IVIG dose

Special Considerations

Timing of Treatment

• Treatment should ideally begin within the first 10 days of illness
• Patients presenting after day 10 should still receive IVIG if they have:
  • Persistent fever without other explanation
  • Elevated inflammatory markers (CRP >3.0 mg/dL)
  • Coronary artery abnormalities 1, 2

Aspirin Precautions

• Avoid ibuprofen in children taking aspirin as it may antagonize aspirin's antiplatelet effect 1
• Risk of Reye syndrome with aspirin during influenza or varicella infection:
  • Annual influenza vaccination recommended for children on long-term aspirin therapy
  • Consider alternative antiplatelet agents if varicella exposure occurs 1

Immunization Considerations

• Defer measles and varicella immunizations for 11 months after high-dose IVIG administration 1

Follow-up Monitoring

• Echocardiography should be performed at diagnosis, within 1-2 weeks, and 4-6 weeks after treatment for uncomplicated cases
• More frequent imaging (at least twice weekly) for patients with coronary abnormalities until dimensions stabilize 2
• Long-term aspirin therapy (indefinitely) for patients who develop coronary artery abnormalities 1

Emerging Therapies

Recent research is investigating the addition of corticosteroids to standard IVIG and aspirin therapy as primary treatment to further reduce coronary artery aneurysm rates, particularly in European populations where higher complication rates have been observed 4.

For IVIG-resistant cases that fail to respond to second-line therapies, alternative treatments such as cyclosporine, anakinra (IL-1β receptor antagonist), cyclophosphamide, or methotrexate may be considered in consultation with specialists, though evidence for these approaches is limited 1, 5.