Kawasaki Disease

Kawasaki disease is an acute vasculitis of childhood that primarily affects medium-sized arteries, particularly the coronary arteries. It is the leading cause of acquired heart disease in children in developed countries. Without treatment, about 25% of children develop coronary artery aneurysms, but with prompt treatment, this risk drops to less than 5%. Early recognition and treatment within the first 10 days of illness are crucial for preventing cardiac complications.

⚠️ Time-Critical Treatment

Seek immediate medical attention for: fever lasting 5+ days in a child with rash, red eyes, swollen hands/feet, or other Kawasaki symptoms. Treatment within 10 days of fever onset is critical to prevent coronary artery damage. Do not delay evaluation.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition.

Understanding Kawasaki Disease

First described by Dr. Tomisaku Kawasaki in 1967, this acute febrile illness causes inflammation of blood vessels throughout the body. The exact cause remains unknown, but it's believed to result from an abnormal immune response to an infection in genetically predisposed children.

Key Characteristics

  • Most common in children under 5 years (80%)
  • Peak age: 18-24 months
  • Rare after age 8
  • More common in boys (1.5:1)
  • Higher incidence in Asian populations
  • Seasonal peaks in winter and spring
  • Not contagious between people

Three Clinical Phases

  1. Acute phase (Days 1-11): Fever and acute symptoms
  2. Subacute phase (Days 11-21): Resolution of fever, risk of coronary aneurysms
  3. Convalescent phase (Day 21-60): Clinical signs resolve, labs normalize

Clinical Features and Diagnosis

Classic Diagnostic Criteria

Diagnosis requires fever ≥5 days PLUS 4 of 5 principal features:

  1. Bilateral conjunctival injection
    • Non-purulent (no discharge)
    • Bulbar conjunctiva affected
    • Limbic sparing (clear ring around iris)
  2. Oral mucosal changes
    • Red, cracked lips
    • Strawberry tongue
    • Diffuse oral/pharyngeal erythema
  3. Peripheral extremity changes
    • Acute: Erythema and edema of hands/feet
    • Subacute: Periungual desquamation (peeling)
  4. Polymorphous rash
    • Usually trunk and extremities
    • Can be maculopapular, diffuse, or targetoid
    • NOT vesicular or bullous
  5. Cervical lymphadenopathy
    • Usually unilateral
    • >1.5 cm diameter
    • Non-purulent

Incomplete Kawasaki Disease

Consider when fever ≥5 days with only 2-3 principal features, especially in infants <6 months:

  • Check laboratory markers (CRP, ESR)
  • Look for supplemental criteria
  • Perform echocardiogram
  • Higher risk of coronary complications if treatment delayed

Other Clinical Features

  • Extreme irritability: Out of proportion to fever
  • GI symptoms: Abdominal pain, vomiting, diarrhea
  • Respiratory: Cough, rhinorrhea
  • Joint: Arthritis or arthralgia
  • Neurologic: Aseptic meningitis, facial palsy
  • Genitourinary: Urethritis, meatitis
  • Cardiac: Myocarditis, pericarditis, valvulitis

Age-Specific Presentations

Infants <6 months

  • Often incomplete presentation
  • Prolonged fever may be only sign
  • Higher risk of coronary aneurysms
  • May lack classic features

Older children >5 years

  • More likely to have complete criteria
  • May have more joint involvement
  • Still at risk for cardiac complications

Laboratory Findings

Acute Phase

  • Inflammatory markers:
    • Elevated CRP (>3.0 mg/dL)
    • Elevated ESR (>40 mm/hr)
  • CBC:
    • Leukocytosis with left shift
    • Normocytic anemia
    • Thrombocytosis (after day 7)
  • Chemistry:
    • Hypoalbuminemia
    • Elevated ALT
    • Hyponatremia
  • Urinalysis:
    • Sterile pyuria (WBCs without bacteria)

Subacute Phase

  • Thrombocytosis peaks (often >1,000,000/μL)
  • ESR remains elevated
  • Anemia persists
  • Lipid abnormalities appear

Cardiac Complications

Coronary Artery Abnormalities

  • Timing: Usually develop days 10-25
  • Classification by Z-score:
    • Dilation: Z-score 2.0-2.5
    • Small aneurysm: Z-score ≥2.5 to <5
    • Medium aneurysm: Z-score ≥5 to <10
    • Giant aneurysm: Z-score ≥10

Risk Factors for Coronary Complications

  • Male gender
  • Age <1 year or >5 years
  • Prolonged fever
  • Delayed treatment (>day 10)
  • IVIG resistance
  • Low albumin
  • High CRP
  • Low hemoglobin
  • High neutrophil count

Other Cardiac Manifestations

  • Myocarditis (50-70%)
  • Pericardial effusion
  • Valvular regurgitation
  • Conduction abnormalities
  • Ventricular dysfunction
  • Rare: MI, arrhythmias, sudden death

Treatment

Initial Therapy

IVIG (Intravenous Immunoglobulin)

  • Dose: 2 g/kg as single infusion over 10-12 hours
  • Timing: Within 10 days of fever onset (ideally days 5-7)
  • Mechanism: Anti-inflammatory, immunomodulatory
  • Effect: Reduces coronary aneurysm risk from 25% to <5%
  • Monitor: Vital signs, fluid overload, hemolysis

Aspirin

  • High dose (acute): 80-100 mg/kg/day divided q6h
  • Duration: Until afebrile 48-72 hours
  • Low dose (antiplatelet): 3-5 mg/kg/day
  • Continue: 6-8 weeks if no coronary changes
  • Longer: If coronary abnormalities present

IVIG-Resistant Disease (10-20%)

Defined as persistent or recrudescent fever ≥36 hours after IVIG completion:

  • Second IVIG dose: 2 g/kg
  • Corticosteroids:
    • Pulse methylprednisolone 30 mg/kg x 3 days
    • Consider as initial adjunct in high-risk patients
  • Infliximab: 5 mg/kg IV
  • Anakinra: IL-1 receptor antagonist
  • Cyclosporine: For refractory cases

Adjunctive Therapy for High-Risk Patients

  • Consider primary adjunctive corticosteroids
  • Scoring systems (Kobayashi, Egami) to identify high risk
  • More aggressive initial therapy may prevent IVIG resistance

Long-term Management

Cardiac Follow-up Schedule

Risk Level Coronary Status Follow-up
I (No involvement) Always normal None after 1 year
II (Transient dilation) Resolved by 8 weeks Every 1-2 years
III (Small aneurysm) Z-score 2.5-5 Annual
IV (Medium aneurysm) Z-score 5-10 Every 6 months
V (Giant aneurysm) Z-score ≥10 Every 3-6 months

Antiplatelet/Anticoagulation

  • No coronary changes: Low-dose ASA x 6-8 weeks
  • Coronary dilation: Low-dose ASA until normalized
  • Aneurysms:
    • Small: Low-dose ASA indefinitely
    • Large/Giant: ASA + clopidogrel or warfarin

Activity Restrictions

  • No coronary involvement: No restrictions after 6-8 weeks
  • Coronary aneurysms:
    • Avoid contact sports if on anticoagulation
    • Stress testing before competitive sports
    • Individualized recommendations

Additional Monitoring

  • Lipid profile
  • Blood pressure monitoring
  • Cardiovascular risk factor modification
  • Stress echocardiography
  • Cardiac MRI or CT angiography as indicated

Special Considerations

Immunizations

  • Defer live vaccines for 11 months after IVIG
  • Give inactivated vaccines on schedule
  • Annual influenza vaccine recommended
  • Varicella/measles titers before live vaccines

Aspirin and Viral Illnesses

  • Risk of Reye syndrome with influenza/varicella
  • Options during viral illness:
    • Continue aspirin (most common)
    • Temporary switch to dipyridamole
    • Brief discontinuation (if low risk)

Recurrence

  • Rate: 1-3% in Japan, <1% in North America
  • Usually within 2 years
  • Treat as new episode
  • Increased risk of coronary complications

Adult Survivors

  • Transition to adult cardiology care
  • Lifelong monitoring if coronary involvement
  • Pregnancy counseling for women
  • Aggressive cardiovascular risk reduction

Differential Diagnosis

Infectious Causes

  • Viral: Adenovirus, enterovirus, EBV, measles
  • Bacterial: Scarlet fever, toxic shock syndrome
  • Rickettsial: Rocky Mountain spotted fever
  • Other: Leptospirosis

Inflammatory Conditions

  • Systemic juvenile idiopathic arthritis
  • Polyarteritis nodosa
  • Drug hypersensitivity reactions
  • Stevens-Johnson syndrome
  • Serum sickness

Other

  • Mercury hypersensitivity (acrodynia)
  • Multiple daily fever spikes suggest alternative diagnosis
  • Response to antibiotics suggests bacterial infection

Prognosis

Overall Outcomes

  • Mortality <0.1% in treated patients
  • Full recovery in most without coronary involvement
  • 50% of aneurysms regress within 1-2 years
  • Giant aneurysms rarely regress completely
  • Long-term cardiac sequelae possible

Prognostic Factors

  • Favorable:
    • Treatment within 10 days
    • Good response to IVIG
    • No coronary involvement
    • Age 1-5 years
  • Unfavorable:
    • Giant coronary aneurysms
    • IVIG resistance
    • Age <1 year
    • Delayed diagnosis

With prompt recognition and treatment, most children with Kawasaki disease recover completely without cardiac sequelae. However, lifelong follow-up is essential for those with coronary involvement to monitor for late complications including stenosis, thrombosis, and premature atherosclerosis.