Overview/Definition
Definition:
• Multisystem Inflammatory Syndrome in Children (MIS-C) is rare but serious post-infectious inflammatory condition following COVID-19, while Kawasaki Disease (KD) is acute systemic vasculitis of unknown etiology affecting medium-sized arteries
Both conditions share overlapping features causing diagnostic challenges but require different management approaches.
Epidemiology:
• MIS-C: Rare complication of COVID-19 affecting 1:3000-4000 infected children, reported globally since April 2020
Peak age 8-12 years, slight male predominance
Kawasaki Disease: Annual incidence 10-20 per 100,000 children <5 years in India, peak age 1-5 years
Both conditions show seasonal variation and possible genetic predisposition.
Age Distribution:
• MIS-C: Broader age range (0-20 years), median age 8-10 years, can affect adolescents and young adults
Kawasaki Disease: Classic age group 6 months-5 years (80% cases), rare in neonates and adolescents
Atypical presentations more common in infants <6 months and children >8 years.
Clinical Significance:
• Essential differential diagnosis for DNB Pediatrics and NEET SS examinations given overlapping presentations and different treatment approaches
Understanding diagnostic criteria, cardiac complications, and treatment protocols crucial
Knowledge of IVIG response patterns and steroid indications important for board preparation.
Age-Specific Considerations
Newborn:
• Neonates (0-28 days): Kawasaki disease rare but reported, often incomplete presentation
MIS-C extremely rare in neonates, limited data available
Both conditions require high index of suspicion
Maternal COVID-19 history relevant for MIS-C consideration
Empirical treatment may be needed based on clinical presentation.
Infant:
• Infants (1-24 months): Kawasaki disease common, often presents as incomplete form lacking classic criteria
Fever, irritability, cervical lymphadenopathy prominent
MIS-C less common but reported, gastrointestinal symptoms prominent
Coronary artery complications risk higher in both conditions.
Child:
• Children (2-12 years): Both conditions present in this age group
Kawasaki disease shows classic pentad more commonly
MIS-C peak age group with multisystem involvement
Gastrointestinal symptoms more prominent in MIS-C
Cardiac involvement patterns differ between conditions.
Adolescent:
• Adolescents (12-18 years): Kawasaki disease rare, often incomplete or atypical presentation
MIS-C more commonly reported, severe cardiac involvement possible
Systemic inflammatory response more pronounced
Adult-like presentations with shock and multi-organ failure.
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Clinical Presentation
Symptoms:
• MIS-C: Persistent fever >38°C for ≥24 hours, gastrointestinal symptoms (abdominal pain, vomiting, diarrhea) in 80-90%
Kawasaki Disease: Fever >39°C for ≥5 days, conjunctival injection, oral mucosa changes, rash, extremity changes, cervical lymphadenopathy
Both: Irritability, fatigue, headache.
Physical Signs:
• MIS-C: Hypotension/shock in 50-60%, conjunctival injection, rash (variable), extremity swelling, lymphadenopathy
Cardiac: Myocarditis, pericarditis, valvular regurgitation
Kawasaki Disease: Classic pentad features, strawberry tongue, peeling of fingers/toes, polymorphous rash.
Severity Assessment:
• MIS-C severity: Shock requiring inotropic support (50-60%), myocardial dysfunction, multi-organ involvement
Laboratory markers: Elevated troponin, BNP, ferritin, CRP
Kawasaki Disease: Complete vs incomplete forms, risk stratification for coronary complications using age, laboratory parameters.
Differential Diagnosis:
• Toxic shock syndrome: Rapid onset, specific toxin-mediated
Sepsis: Positive cultures, different inflammatory pattern
Viral myocarditis: Usually single organ involvement
Drug reaction: DRESS syndrome, specific medication exposure
Other vasculitis: Different age groups, organ involvement patterns.
Diagnostic Approach
History Taking:
• MIS-C: COVID-19 exposure/infection history in preceding 2-6 weeks, close contact history, travel to COVID-19 endemic areas
Kawasaki Disease: No specific exposure history, family history of autoimmune diseases, recent illness or immunization
Both: Medication history, previous similar episodes.
Investigations:
• MIS-C: SARS-CoV-2 RT-PCR (often negative), serology (IgG positive), inflammatory markers (CRP, ESR, ferritin, D-dimer), cardiac biomarkers (troponin, BNP), echocardiography
Kawasaki Disease: No specific tests, diagnosis clinical, elevated acute phase reactants, echocardiography for coronary assessment.
Normal Values:
• Inflammatory markers: CRP <10 mg/L, ESR <20 mm/hr, ferritin 50-200 ng/ml, D-dimer <500 ng/ml
Cardiac biomarkers: Troponin <0.04 ng/ml, BNP <100 pg/ml
Complete blood count: Age-appropriate values
Liver enzymes: ALT/AST <40 IU/L.
Interpretation:
• MIS-C diagnostic criteria: Fever + multisystem involvement + elevated inflammatory markers + COVID-19 exposure/serology + exclusion of other causes
Kawasaki Disease: Clinical criteria-based diagnosis, laboratory tests supportive
Echocardiography essential in both for cardiac assessment.
Management/Treatment
Acute Management:
• MIS-C: IVIG 2 g/kg single dose + methylprednisolone 1-2 mg/kg/day, aspirin 3-5 mg/kg/day
Supportive care: Fluid management, inotropic support if shock
Kawasaki Disease: IVIG 2 g/kg single dose within 10 days of fever onset + high-dose aspirin 80-100 mg/kg/day until fever resolution.
Chronic Management:
• MIS-C: Gradual steroid taper over 2-4 weeks, low-dose aspirin until platelet count and cardiac function normalize
Kawasaki Disease: Low-dose aspirin 3-5 mg/kg/day until platelet count normal and no coronary changes
Both require cardiology follow-up.
Lifestyle Modifications:
• Activity restriction based on cardiac involvement severity
Gradual return to normal activities after clearance
Contact precautions for MIS-C patients
Family education about warning signs
Regular medication compliance important for both conditions.
Follow Up:
• MIS-C: Weekly initially, then monthly cardiology follow-up
Repeat echocardiography at 1-2 weeks, 4-6 weeks
Long-term cardiac surveillance needed
Kawasaki Disease: 2 weeks, 6-8 weeks, then based on coronary involvement
Annual cardiology follow-up if coronary changes present.
Age-Specific Dosing
Medications:
• IVIG: 2 g/kg IV over 8-12 hours for both conditions
Methylprednisolone (MIS-C): 1-2 mg/kg/day divided 8-12 hourly
Aspirin high-dose (KD): 80-100 mg/kg/day divided 6 hourly until fever resolution
Aspirin low-dose: 3-5 mg/kg/day once daily for cardioprotection.
Formulations:
• IVIG: Various brands 50-100 mg/ml concentrations for IV infusion
Methylprednisolone: Injectable 40 mg/ml, tablets 4 mg, 8 mg, 16 mg
Aspirin: Tablets 75 mg, 150 mg, dispersible formulations
Liquid aspirin preparations for young children.
Safety Considerations:
• IVIG adverse effects: Fever, headache, thrombosis risk, hemolytic anemia
Monitor renal function, blood viscosity
Steroid side effects: Hyperglycemia, hypertension, mood changes, infection risk
Aspirin: Reye syndrome risk with viral infections, bleeding risk.
Monitoring:
• Daily clinical assessment during acute phase
Complete blood count, inflammatory markers every 2-3 days
Liver function monitoring with high-dose aspirin
Cardiac monitoring: Daily ECG, echocardiography as indicated
Renal function with IVIG therapy.
Prevention & Follow-up
Prevention Strategies:
• MIS-C: COVID-19 prevention measures (vaccination when eligible, masks, social distancing)
No specific prevention available
Kawasaki Disease: No specific prevention, genetic counseling for family history
Early recognition and treatment prevent complications.
Vaccination Considerations:
• COVID-19 vaccination recommended for eligible children to prevent MIS-C
Live vaccines (MMR, varicella) contraindicated for 11 months after IVIG therapy
Routine immunization schedule may be delayed during acute illness
Influenza vaccine recommended annually.
Follow Up Schedule:
• MIS-C: 1-2 weeks, 1 month, 3 months, 6 months, then annually
Kawasaki Disease: 2 weeks, 6-8 weeks, 3-4 months, then annually if coronary involvement
Both require long-term cardiology surveillance if cardiac complications present.
Monitoring Parameters:
• Cardiac function: Serial echocardiography, ECG monitoring
Growth parameters, developmental assessment
Laboratory: Complete blood count, inflammatory markers normalization
Activity tolerance assessment
Quality of life evaluation.
Complications
Acute Complications:
• MIS-C: Cardiogenic shock (50-60%), myocarditis, coronary dilatation, valvular regurgitation, arrhythmias
Multi-organ failure: Respiratory, renal, neurological
Kawasaki Disease: Coronary artery aneurysms (20-25% untreated), myocarditis, pericardial effusion, valvular regurgitation.
Chronic Complications:
• MIS-C: Long-term cardiac sequelae under investigation, possible persistent myocardial dysfunction
Kawasaki Disease: Coronary stenosis, myocardial infarction, sudden death (rare with treatment)
Both may have long-term exercise intolerance, require cardiac surveillance.
Warning Signs:
• Cardiac: Chest pain, shortness of breath, palpitations, decreased exercise tolerance, syncope
Systemic: Recurrent fever, persistent fatigue, abdominal pain, neurological symptoms
Laboratory: Rising inflammatory markers, abnormal cardiac biomarkers.
Emergency Referral:
• Immediate referral for signs of shock, severe cardiac dysfunction, chest pain, respiratory distress
Cardiology consultation for any cardiac involvement
ICU referral for multi-organ dysfunction
Rheumatology consultation for treatment-resistant cases or atypical presentations.
Parent Education Points
Counseling Points:
• Both conditions are serious but treatable inflammatory diseases
MIS-C related to COVID-19, importance of prevention measures
Kawasaki disease cause unknown but early treatment prevents complications
Long-term cardiac follow-up essential
Prognosis generally good with appropriate treatment.
Home Care:
• Activity restriction as advised by cardiologist, gradual increase as tolerated
Regular medication administration especially aspirin for cardioprotection
Temperature monitoring, watch for recurrent fever
Adequate nutrition and hydration
Follow-up appointment compliance crucial.
Medication Administration:
• IVIG given in hospital setting only
Aspirin with food to reduce gastric irritation
Steroids with food, morning dosing to reduce sleep disturbance
Complete medication course as prescribed
Report side effects: Bleeding, stomach pain, mood changes.
When To Seek Help:
• Immediate medical attention for chest pain, difficulty breathing, severe abdominal pain
Recurrent fever, persistent fatigue, decreased activity tolerance
Signs of bleeding with aspirin therapy
Any concerning symptoms or changes in child's condition
Emergency contact information provided.