Overview/Definition
Definition:
• Kawasaki Disease (KD) is an acute febrile multisystem vasculitis primarily affecting medium-sized arteries, particularly coronary arteries in children
Previously known as mucocutaneous lymph node syndrome, it is the leading cause of acquired heart disease in children in developed countries
Early recognition and treatment crucial to prevent cardiac complications.
Epidemiology:
• Incidence varies globally with highest rates in Japan (240-350 per 100,000 children <5 years), intermediate in Korea and Taiwan, and lower rates in Western countries (8-25 per 100,000)
In India, reported incidence ranges from 4.5-45.1 per 100,000 children <5 years with increasing recognition and diagnosis.
Age Distribution:
• Peak incidence at 9-11 months with 80% of cases occurring before age 5 years
Male predominance with male:female ratio of 1.5-1.7:1
Seasonal variation noted with winter-spring peaks in temperate climates
Recurrence rare (1-3%) but associated with higher risk of coronary complications.
Clinical Significance:
• Critical high-yield topic for DNB Pediatrics and NEET SS focusing on diagnostic criteria, IVIG treatment protocols, and coronary artery complications
Essential for understanding systemic vasculitis, immune-mediated disease mechanisms, and long-term cardiac surveillance requirements
Major cause of pediatric acquired heart disease globally.
Age-Specific Considerations
Newborn:
• KD in infants <6 months is rare but associated with higher risk of incomplete presentation and coronary artery abnormalities (up to 25%)
Lower fever response may mask diagnosis
Increased difficulty meeting classic diagnostic criteria due to less prominent mucocutaneous manifestations
Higher IVIG resistance rates in this age group.
Infant:
• Peak age group (6 months-2 years) with highest incidence and most typical presentations
Classic fever pattern and mucocutaneous signs usually prominent
Risk of coronary artery aneurysms highest in this age group, especially males <12 months
Irritability and feeding difficulties common presenting features.
Child:
• School-age children (2-12 years) often present with more complete diagnostic criteria
Joint involvement more common in older children
Abdominal pain and gallbladder hydrops more frequent
Lower risk of coronary complications but still require same urgency in treatment
Better cooperation with echocardiographic assessment.
Adolescent:
• KD rare in adolescents but when it occurs, often incomplete presentation with atypical features
Higher risk of shock syndrome and myocarditis
Joint involvement very common
May mimic other systemic inflammatory conditions
Require specialized transition planning for long-term cardiac follow-up into adulthood.
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Clinical Presentation
Symptoms:
• Classic presentation: fever >5 days with at least 4 of 5 principal criteria: bilateral conjunctival injection, oral mucosal changes, peripheral extremity changes, polymorphous rash, cervical lymphadenopathy >1.5cm
Incomplete KD: fever with <4 criteria but evidence of coronary artery involvement
Associated features: irritability, abdominal pain, diarrhea, vomiting.
Physical Signs:
• Fever typically high (>39°C), prolonged, and antibiotic-resistant
Bilateral non-purulent conjunctivitis with limbal sparing
"Strawberry tongue," lip fissuring, oral erythema
Polymorphous rash (not vesicular/bullous)
Palmar-plantar erythema and edema, followed by periungual desquamation
Unilateral cervical lymphadenopathy >1.5cm diameter.
Severity Assessment:
• Standard KD: fever with ≥4 principal criteria
Incomplete KD: fever with <4 criteria plus laboratory/echocardiographic abnormalities
IVIG-resistant KD: persistent fever >36 hours after initial IVIG infusion
KD shock syndrome: associated with hemodynamic compromise requiring intensive care support.
Differential Diagnosis:
• Differential includes viral infections (EBV, CMV, adenovirus), streptococcal/staphylococcal infections, measles, drug hypersensitivity reactions, juvenile idiopathic arthritis, and other systemic vasculitides
Stevens-Johnson syndrome, toxic shock syndrome, and scarlet fever important to exclude
Post-infectious glomerulonephritis may share some features.
Diagnostic Approach
History Taking:
• Detailed fever history including onset, duration, pattern, and response to antipyretics/antibiotics
Review of systems for principal criteria features and associated symptoms
Recent travel, sick contacts, medication exposures
Family history of autoimmune diseases or Kawasaki disease
Immunization history and recent infections.
Investigations:
• Laboratory findings: elevated ESR (>40mm/hr), CRP (>3mg/dL), leukocytosis with neutrophil predominance, thrombocytosis (often >450,000/μL after week 1), hypoalbuminemia (<3g/dL), elevated ALT
Echocardiography essential to assess coronary arteries, performed at diagnosis, 2 weeks, and 6-8 weeks.
Normal Values:
• Normal coronary artery dimensions age-dependent: LAD and RCA z-scores should be <2.5 (mild dilation 2.5-5, moderate 5-10, severe >10)
Normal ESR varies by age: <2 years <30mm/hr, 2-8 years <40mm/hr
Normal CRP <0.3mg/dL in healthy children
Normal platelet count 150,000-450,000/μL.
Interpretation:
• Coronary artery z-scores calculated using body surface area-adjusted nomograms
Small aneurysms (z-score 2.5-5) have good prognosis, medium aneurysms (z-score 5-10) require anticoagulation, giant aneurysms (z-score >10 or absolute dimension ≥8mm) have highest complication risk requiring intensive management.
Management/Treatment
Acute Management:
• First-line treatment: high-dose IVIG 2g/kg as single infusion over 10-12 hours within 10 days of fever onset (ideally within 7 days)
Concurrent high-dose aspirin 80-100mg/kg/day divided QID until fever resolves for 48-72 hours
IVIG resistance predictors: age <12 months, male sex, elevated CRP, low albumin, elevated ALT.
Chronic Management:
• Post-acute phase: transition to low-dose aspirin 3-5mg/kg/day (anti-platelet dose) continued until normal coronary arteries confirmed at 6-8 weeks
If coronary abnormalities persist, continue aspirin indefinitely
IVIG-resistant cases: second IVIG dose, corticosteroids (methylprednisolone 30mg/kg/day × 3 days), or infliximab 5mg/kg.
Lifestyle Modifications:
• Activity restriction during acute phase with gradual return to normal activities as inflammation resolves
Avoid contact sports in patients with coronary aneurysms
Regular cardiology follow-up for coronary assessment
Influenza vaccination recommended annually
Avoid aspirin during viral infections due to Reye syndrome risk.
Follow Up:
• Acute phase: daily monitoring of fever, clinical status, and laboratory parameters
Echocardiography at diagnosis, 2 weeks, 6-8 weeks
Long-term follow-up based on coronary involvement: normal arteries may discontinue cardiology follow-up after 1 year, persistent abnormalities require lifelong surveillance with stress testing after age 10-12 years.
Age-Specific Dosing
Medications:
• IVIG: 2g/kg as single dose (maximum 100g per dose) infused over 10-12 hours
High-dose aspirin: 80-100mg/kg/day divided q6h (maximum 4g/day), then low-dose 3-5mg/kg/day once daily
Methylprednisolone: 30mg/kg/day (maximum 1g/day) for IVIG-resistant cases
Infliximab: 5mg/kg IV for refractory cases.
Formulations:
• IVIG available as 5% and 10% solutions for IV infusion requiring slow administration with premedication
Aspirin available as 81mg chewable tablets, 325mg regular tablets that can be crushed and suspended
Methylprednisolone 40mg, 125mg, 500mg, 1g vials for IV administration.
Safety Considerations:
• IVIG monitoring for infusion reactions (fever, chills, rash), hemolytic anemia, renal dysfunction, and thrombotic events
Aspirin monitoring for GI upset, tinnitus, and Reye syndrome risk with viral infections
Steroid side effects include hyperglycemia, hypertension, and increased infection risk
Pre-infusion vital signs and post-infusion monitoring essential.
Monitoring:
• Daily fever monitoring and clinical assessment during acute treatment phase
Complete blood count, comprehensive metabolic panel, liver function tests every 2-3 days initially
Echocardiography performed by pediatric cardiologist at specified intervals
Long-term monitoring includes annual ECG, echocardiography, and stress testing when indicated.
Prevention & Follow-up
Prevention Strategies:
• Primary prevention not possible as etiology remains unknown, though infectious triggers and genetic susceptibility are proposed
Secondary prevention focuses on early recognition and prompt treatment to prevent coronary complications
Community education for parents and healthcare providers about classic signs and symptoms important for timely diagnosis.
Vaccination Considerations:
• Standard immunization schedule should be maintained with consideration for timing around acute illness
Live vaccines should be delayed 11 months after IVIG administration due to potential interference with vaccine response
Annual influenza vaccine especially important given aspirin therapy and Reye syndrome risk
COVID-19 vaccination recommended.
Follow Up Schedule:
• Acute phase: daily assessment until fever-free for 48 hours
Week 1-2: clinical and laboratory monitoring
Week 2: first follow-up echocardiogram
Week 6-8: repeat echocardiogram to assess coronary evolution
Long-term: frequency based on coronary involvement from annually (normal) to every 6 months (severe abnormalities).
Monitoring Parameters:
• Clinical parameters: fever resolution, improvement in mucocutaneous signs, resolution of irritability
Laboratory: normalization of inflammatory markers (ESR, CRP), platelet count evolution, liver function improvement
Cardiac: coronary artery dimensions and z-scores, ventricular function, valvular regurgitation assessment, rhythm monitoring.
Complications
Acute Complications:
• Coronary artery aneurysms develop in 15-25% of untreated patients and 3-5% of appropriately treated patients
KD shock syndrome occurs in 1-2% with hemodynamic instability requiring ICU support
Myocarditis, pericarditis, and valvular regurgitation can occur during acute phase
Aseptic meningitis, hydrops of gallbladder, and arthritis are associated complications.
Chronic Complications:
• Long-term coronary complications include stenosis, thrombosis, and myocardial infarction, particularly in patients with giant aneurysms (>8mm)
Sudden cardiac death rare but possible
Accelerated atherosclerosis may occur in patients with coronary involvement
Some patients develop chronic inflammatory arthritis or other autoimmune conditions.
Warning Signs:
• Signs requiring immediate attention: persistent fever >48 hours after IVIG, signs of shock (hypotension, poor perfusion), chest pain or ECG changes, signs of heart failure, neurological symptoms, or signs of thrombosis
Any child with known coronary aneurysms developing chest pain requires urgent evaluation.
Emergency Referral:
• Immediate referral indicated for: suspected KD with fever >5 days, KD shock syndrome, chest pain in patient with known coronary aneurysms, signs of myocardial infarction or heart failure
IVIG-resistant cases require prompt pediatric rheumatology or cardiology consultation for alternative therapies.
Parent Education Points
Counseling Points:
• Explain KD as inflammatory condition affecting blood vessels, particularly around the heart, with excellent prognosis when treated promptly
Emphasize importance of completing full aspirin course and follow-up appointments even when child feels well
Discuss long-term outlook: most children with normal coronary arteries have no restrictions
Address concerns about recurrence (very rare).
Home Care:
• Monitor for fever recurrence and provide comfort measures during recovery phase
Ensure adequate fluid intake and nutrition
Observe for skin peeling on fingers and toes (normal part of recovery)
Maintain good hygiene and avoid exposure to ill contacts during recovery period
Continue prescribed medications as directed.
Medication Administration:
• Give IVIG only in hospital setting under medical supervision
Administer aspirin with food to minimize GI upset, use measuring devices for accurate liquid dosing
Never give aspirin during viral illnesses due to Reye syndrome risk - contact doctor for fever management alternatives
Store medications safely away from children.
When To Seek Help:
• Seek immediate medical attention for: fever recurrence >48 hours after treatment, chest pain, severe abdominal pain, difficulty breathing, severe irritability or lethargy, signs of bleeding or bruising
Contact cardiologist promptly for: any cardiac symptoms, missed follow-up appointments, concerns about activity restrictions, or medication side effects.