What are the diagnostic criteria and treatment for Kawasaki disease?

Kawasaki Disease Diagnosis and Treatment

Kawasaki disease is diagnosed based on fever persisting for at least 5 days plus at least 4 of 5 principal clinical features, and treatment with intravenous immunoglobulin (IVIG) and aspirin should be initiated as soon as the diagnosis is established to reduce the risk of coronary artery abnormalities from 20-25% to less than 5%. 1, 2

Diagnostic Criteria

Principal Clinical Findings

Fever persisting at least 5 days plus at least 4 of the following 5 principal features:

1. Changes in extremities

   • Acute phase: Erythema and edema of hands and feet with sharp demarcation at wrists and ankles
   • Convalescent phase: Periungual desquamation of fingers and toes

2. Polymorphous exanthema/rash

   • Usually appears within first 5 days
   • Primarily truncal with accentuation in the groin
   • Most commonly maculopapular

3. Bilateral bulbar conjunctival injection

   • Non-purulent/non-exudative
   • Often spares the limbus
   • Not typically associated with photophobia or eye pain

4. Changes in lips and oral cavity

   • Erythema and cracking of lips
   • Strawberry tongue
   • Diffuse erythema of oral and pharyngeal mucosa
   • No focal lesions, ulcerations, or exudates

5. Cervical lymphadenopathy

   • Usually unilateral
   • ≥1.5 cm in diameter
   • Confined to the anterior cervical triangle 1, 2

Important Diagnostic Considerations

• The diagnosis can be made before day 5 of fever by experienced clinicians if classic features are present 1, 2
• Kawasaki disease can be diagnosed with only 3 clinical features if coronary artery abnormalities are detected on echocardiography 1, 2
• Not all clinical features are present simultaneously; a careful history is necessary 1
• Incomplete (atypical) Kawasaki disease should be considered in children with unexplained fever for ≥5 days and 2-3 principal clinical features 3

Supporting Laboratory Findings

• Elevated ESR and CRP
• Leukocytosis with neutrophil predominance
• Hypoalbuminemia
• Mild anemia in acute phase
• Thrombocytosis (typically in the second week)
• Sterile pyuria
• Elevated liver enzymes 1, 2

Treatment Protocol

Initial Treatment

1. IVIG: 2 g/kg as a single infusion over 10-12 hours

   • Should be administered as soon as diagnosis is established
   • Ideally within the first 10 days of illness 2

2. Aspirin: Dual-phase approach

   • Acute phase: High-dose (80-100 mg/kg/day divided into four doses) until patient is afebrile for 48-72 hours
   • Convalescent phase: Low-dose (3-5 mg/kg/day as a single dose) for antiplatelet effect 2

Treatment for IVIG Resistance

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

1. Second IVIG dose: 2 g/kg if fever persists or recurs within 36 hours after initial IVIG

2. Consider corticosteroids for patients who fail to respond to a second IVIG dose:

   • 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)

3. Consider infliximab (5 mg/kg IV as a single infusion) after failure of a second IVIG dose 2

Cardiac Monitoring

• Initial echocardiography: At diagnosis
• Follow-up echocardiography:
  • Within 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

• Continue low-dose aspirin until 6-8 weeks after disease onset if no coronary abnormalities develop
• Long-term aspirin therapy for patients who develop coronary artery abnormalities
• Annual influenza vaccination for children on long-term aspirin therapy to reduce the risk of Reye syndrome
• Defer measles and varicella immunizations for 11 months after high-dose IVIG administration 2

Pitfalls and Caveats

1. Delayed diagnosis: Kawasaki disease is the leading cause of acquired heart disease in children in developed countries. Missing the diagnosis can lead to serious coronary complications 1, 2

2. Incomplete presentation: Children with incomplete Kawasaki disease have the same risk of coronary artery abnormalities as those with complete presentation 3

3. Early diagnosis challenges: Patients diagnosed before the fifth day of illness may have a higher risk of coronary artery aneurysm and may respond poorly to IVIG 4

4. Differential diagnosis: Many conditions can mimic Kawasaki disease, including viral infections (measles, adenovirus, enterovirus), scarlet fever, toxic shock syndrome, and drug hypersensitivity reactions 1

5. Lymphadenopathy misdiagnosis: Cervical lymphadenopathy may be the most notable initial finding in some patients, leading to misdiagnosis as bacterial lymphadenitis and delaying proper treatment 1

By following these diagnostic criteria and treatment protocols, the risk of coronary artery abnormalities can be significantly reduced, improving long-term outcomes for children with Kawasaki disease.