What is the treatment for Kawasaki disease?

Treatment of Kawasaki Disease

The standard treatment for Kawasaki disease consists of intravenous immunoglobulin (IVIG) at a dose of 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

First-Line Treatment

IVIG Administration

• Dose: 2 g/kg as a single infusion
• Timing: As soon as diagnosis is established, ideally within first 10 days of illness
• Administration: Usually given over 10-12 hours
• Efficacy: Reduces risk of coronary artery abnormalities from 20-25% to <5% 1
• Note: Shorter infusion times (<10 hours) may be associated with higher risk of coronary artery aneurysms 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 1
  • High-dose aspirin is associated with lower odds of IVIG resistance compared to starting with low-dose aspirin 3

Management of IVIG Resistance

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

1. Second IVIG dose:

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

2. Corticosteroids (for patients who fail to respond to a second IVIG dose):

   • Option: 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
   • Evidence suggests that adding corticosteroids to standard therapy lowers the prevalence of coronary artery abnormalities, duration of fever, and inflammation in high-risk patients 4

3. Infliximab:

   • Consider after failure of a second IVIG dose
   • Dose: 5 mg/kg IV as a single infusion 1
   • Acts by binding to TNF-α, which is elevated in acute KD 4

Special Considerations

• Late presentation: 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), or coronary artery abnormalities 1

• Medication interactions:

  • Avoid ibuprofen in children taking aspirin as it may antagonize aspirin's antiplatelet effect
  • Annual influenza vaccination is recommended for children on long-term aspirin therapy to reduce the risk of Reye syndrome 1

• Immunizations:

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

Monitoring and Follow-up

• Echocardiography should be performed:

  • At diagnosis
  • Within 1-2 weeks after treatment
  • 4-6 weeks after treatment for uncomplicated cases 1

• For patients with coronary abnormalities:

  • More frequent imaging (at least twice weekly) until dimensions stabilize
  • Long-term aspirin therapy (indefinitely) 1

Alternative Treatments for Refractory Cases

For cases resistant to standard therapies, alternative treatments may be considered:

• Cyclosporine
• Anakinra (IL-1β receptor antagonist)
• Cyclophosphamide
• Methotrexate 1, 5

Emerging Evidence

Recent European studies have shown higher coronary complications despite IVIG treatment, leading to ongoing trials like KD-CAAP that are investigating whether immediate adjunctive corticosteroid treatment with standard IVIG and aspirin will reduce coronary artery aneurysm rates in unselected KD patients 6.