What is the recommended treatment for Kawasaki disease?

Treatment of Kawasaki Disease

The recommended first-line treatment for Kawasaki disease is intravenous immunoglobulin (IVIG) at a dose of 2 g/kg given as a single infusion, combined with high-dose aspirin (80-100 mg/kg/day divided into four doses) until the patient is afebrile for at least 48 hours. 1

Diagnosis

Before initiating treatment, diagnosis must be established based on:

• Fever for at least 5 days plus 4 or more of the following clinical features 1:

  • Bilateral non-purulent conjunctival injection
  • Oral mucosal changes (red/cracked lips, strawberry tongue, diffuse erythema)
  • Polymorphous rash (typically truncal, erythematous and maculopapular)
  • Swelling or redness of extremities with sharp demarcation at ankles/wrists
  • Cervical lymphadenopathy (≥1.5 cm diameter)

• Incomplete Kawasaki disease can be diagnosed with fewer criteria if coronary artery abnormalities are present on echocardiography 1

• For patients with fever >5 days and only 2-3 classic symptoms, laboratory testing should include CRP and ESR; if elevated, additional testing (serum albumin, transaminases, CBC, urinalysis) should be performed 1

Initial Treatment Protocol

1. IVIG Administration:

   • Dose: 2 g/kg as a single infusion 1
   • Timing: Within first 10 days of illness, preferably within 7 days 1
   • Infusion rate: Administer over 10-12 hours to reduce risk of coronary aneurysms 2

2. Aspirin Therapy:

   • Initial high-dose: 80-100 mg/kg/day divided into 4 doses 1
   • Duration of high-dose: Until patient is afebrile for at least 48 hours 1
   • Transition to low-dose: 3-5 mg/kg/day as a single daily dose 1
   • Duration of low-dose: 6-8 weeks if no coronary abnormalities; indefinitely if coronary abnormalities persist 1

3. Important considerations:

   • High-dose aspirin may be associated with better outcomes, as low-dose aspirin is associated with 3 times higher odds of requiring IVIG retreatment 3
   • Avoid ibuprofen in patients on aspirin therapy as it antagonizes aspirin's antiplatelet effect 1
   • Discontinue aspirin during influenza or varicella infection due to risk of Reye syndrome; consider alternative antiplatelet therapy during these periods 1
   • Annual influenza vaccination is recommended for children on long-term aspirin therapy 1

Management of IVIG-Resistant Disease

Approximately 10-20% of patients develop recrudescent or persistent fever at least 36 hours after IVIG infusion 1. These patients are at increased risk for coronary artery abnormalities 4.

Options for IVIG-resistant cases (in order of preference):

1. Second dose of IVIG:

   • 2 g/kg as a single infusion 1
   • Consider this as first option for IVIG resistance 1

2. Infliximab:

   • 5 mg/kg IV given over 2 hours 1
   • Recent evidence shows infliximab may be more effective than second IVIG for resistant cases, with shorter fever duration, reduced need for additional therapy, and shorter hospitalization 5

3. Corticosteroids:

   • High-dose pulse methylprednisolone (20-30 mg/kg IV for 3 days) 1
   • OR prednisolone/prednisone (2 mg/kg/day) until afebrile, then oral prednisone until CRP normalizes with 2-3 week taper 1

4. Alternative therapies for highly refractory cases:

   • Cyclosporine: 4-8 mg/kg/day PO divided every 12 hours or 3 mg/kg/day IV divided every 12 hours 1
   • Anakinra: 2-6 mg/kg/day subcutaneously 1
   • Cyclophosphamide: 2 mg/kg/day IV (for exceptional cases) 1
   • Plasma exchange (for patients who have failed all other therapies) 1

Long-term Antiplatelet/Anticoagulation Management

Management depends on the degree of coronary artery involvement 1:

1. No coronary abnormalities:

   • Low-dose aspirin (3-5 mg/kg/day) for 6-8 weeks after disease onset 1

2. Small coronary aneurysms:

   • Long-term low-dose aspirin indefinitely 1

3. Moderate-sized aneurysms (4-6 mm):

   • Aspirin plus a second antiplatelet agent that antagonizes adenosine diphosphate (e.g., clopidogrel) 1

4. Giant aneurysms (≥8 mm):

   • Low-dose aspirin plus warfarin (target INR 2.0-3.0) 1
   • For infants or children where warfarin is difficult to regulate, consider aspirin plus therapeutic doses of low-molecular-weight heparin 1

5. Extraordinary risk cases (giant aneurysms with recent coronary thrombosis):

   • Consider triple therapy with aspirin, a second antiplatelet agent, and anticoagulation 1

Monitoring

• Frequent echocardiography and ECG evaluation during the first 3 months after diagnosis, especially for patients with giant coronary aneurysms 1
• The highest risk for coronary artery thrombosis occurs within the first 3 months, with peak incidence in the first 15-45 days 1

Common Pitfalls and Caveats

• Delaying treatment beyond 10 days increases risk of coronary artery abnormalities 1
• Incomplete Kawasaki disease is more common in children under 1 year, who paradoxically have higher rates of coronary aneurysms if not treated 1
• Kawasaki disease can mimic common childhood illnesses (adenovirus, scarlet fever) and drug reactions, leading to missed diagnoses 1
• Measles and varicella immunizations should be deferred for 11 months after high-dose IVIG administration 1
• Peeling of fingers and toes typically occurs 2-3 weeks after onset of symptoms, when fever has usually resolved 1