Overview
Definition:
Kawasaki disease (KD) is an acute, self-limiting vasculitis of medium-sized arteries, primarily affecting children under 5 years
It is the leading cause of acquired heart disease in children in developed countries
Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious hyperinflammatory syndrome associated with SARS-CoV-2 infection, characterized by fever, inflammation of multiple organ systems, and often cardiac involvement, typically seen weeks after infection.
Epidemiology:
Kawasaki disease: Incidence varies geographically, highest in Japan and other East Asian countries
Affects approximately 10-20 per 100,000 children annually in the US and Europe
Predominantly affects infants and young children (<5 years), with a male predominance
MIS-C: Emerged during the COVID-19 pandemic, predominantly affecting school-aged children and adolescents (median age ~9-10 years), with a higher incidence in certain ethnic groups
Often presents 2-6 weeks after SARS-CoV-2 infection.
Clinical Significance:
Accurate and timely differentiation is crucial as both conditions can lead to severe cardiac complications, including coronary artery aneurysms (in KD) and myocarditis, pericarditis, and coronary artery abnormalities (in MIS-C)
Prompt treatment can prevent long-term sequelae
Understanding the subtle yet important distinctions is vital for pediatricians and residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Kawasaki Disease: Prolonged fever (>5 days) is the hallmark
Bilateral non-exudative conjunctivitis
Oral mucosal changes (erythema of lips, fissuring, strawberry tongue, diffuse redness of oral mucosa)
Rash (polymorphous, often erythematous)
Extremity changes (erythema and edema of hands and feet, later desquamation of fingertips)
Cervical lymphadenopathy (>1.5 cm, unilateral, non-purulent)
MIS-C: Fever (often >5 days)
Signs of inflammation in at least two organ systems (e.g., gastrointestinal: abdominal pain, vomiting, diarrhea
cardiovascular: myocarditis, pericarditis, valvular dysfunction, coronary artery dilation/aneurysm
dermatologic: rash, conjunctivitis
neurologic: headache, lethargy
respiratory: cough, shortness of breath
hematologic: cytopenias)
Severe illness with signs of shock and cardiac dysfunction can occur.
Signs:
Kawasaki Disease: Conjunctival injection
Erythematous lips, strawberry tongue
Polymorphous rash
Edematous hands/feet, later peeling
Enlarged cervical lymph node
MIS-C: Fever
Hypotension or shock
Tachycardia
Tachypnea
Signs of specific organ involvement (e.g., conjunctivitis, abdominal tenderness, erythematous rash, altered mental status, signs of heart failure).
Diagnostic Criteria:
Kawasaki Disease: Fever for ≥5 days PLUS ≥4 of the 5 cardinal clinical features (conjunctivitis, oral changes, rash, extremity changes, cervical lymphadenopathy)
Atypical KD requires fever plus <4 features but with evidence of coronary artery abnormality on echocardiography
MIS-C: Meets criteria for a case definition (e.g., CDC definition): Age <21 years with fever ≥4 days, laboratory evidence of inflammation, AND evidence of severe clinical illness requiring hospitalization in which clinical management was directed at MIS-C AND alternative diagnoses have been reasonably excluded
Importantly, MIS-C is linked to SARS-CoV-2 infection (current or recent infection, or presumed exposure).
Diagnostic Approach
History Taking:
For KD: Duration and pattern of fever, presence of any cardinal signs, recent infections, family history of cardiac conditions
For MIS-C: History of recent SARS-CoV-2 infection (symptomatic or asymptomatic), symptom onset relative to infection, presence and severity of multi-organ system involvement, contact with COVID-19 cases.
Physical Examination:
Thorough systemic examination focusing on eyes (conjunctivitis), oropharynx (mucosal changes), skin (rash, desquamation), extremities (edema, erythema, peeling), lymph nodes (cervical), and cardiovascular system (murmurs, gallops, signs of shock or heart failure)
Assess for signs of inflammation in other organ systems for MIS-C.
Investigations:
Kawasaki Disease: Laboratory findings are supportive, not diagnostic
Mild anemia, thrombocytosis (after 1 week), elevated ESR and CRP, sterile pyuria
Echocardiography is crucial to assess for coronary artery abnormalities (ectasia, aneurysms)
MIS-C: Laboratory findings indicate systemic inflammation: elevated CRP, ESR, ferritin, D-dimer, troponin, BNP, lymphopenia, thrombocytopenia
Cardiac biomarkers and ECG are essential
Echocardiography is vital for assessing cardiac function, valvular involvement, and coronary artery dimensions
SARS-CoV-2 testing (PCR, antibody) is often positive or suggestive of recent infection
Differential diagnosis includes sepsis, toxic shock syndrome, other viral exanthems, and rheumatologic conditions.
Differential Diagnosis:
Differentiating KD from MIS-C hinges on the clinical context and timeline relative to SARS-CoV-2 infection
KD is a primary vasculitis
MIS-C is a post-infectious hyperinflammatory syndrome
MIS-C often presents with more severe cardiac dysfunction and shock, and a broader spectrum of organ involvement beyond the typical KD features
Sepsis, other viral infections (adenovirus, enterovirus, Epstein-Barr virus), Scarlet fever, Stevens-Johnson syndrome, and other rheumatologic conditions like Juvenile Idiopathic Arthritis should also be considered.
Management
Initial Management:
Both conditions require hospitalization and close monitoring, especially for cardiac involvement
Initial management focuses on hemodynamic stabilization if in shock, and prompt initiation of anti-inflammatory therapy
Early diagnosis and treatment are paramount for preventing cardiac sequelae.
Medical Management:
Kawasaki Disease: Intravenous Immune Globulin (IVIG) 2 g/kg as a single infusion over 10-12 hours is the cornerstone of therapy, ideally administered within 10 days of fever onset
Aspirin: Started at a high dose (80-100 mg/kg/day) divided into 4 doses until afebrile for 48-72 hours, then continued at a low dose (3-5 mg/kg/day) for 6-8 weeks
MIS-C: IVIG (2 g/kg) is also a primary treatment
Corticosteroids (e.g., methylprednisolone or oral prednisone) are often used, especially in more severe cases or those unresponsive to IVIG
Aspirin may be used for its antiplatelet effect, but its role is less clearly defined than in KD
often reserved for patients with coronary involvement
Immunomodulatory agents like anakinra or biologics may be considered for refractory cases.
Surgical Management:
Rarely, surgical intervention may be required in cases of severe coronary artery aneurysms leading to thrombosis or stenosis, or for management of complications like myocardial infarction or valve rupture in advanced stages of both diseases
However, this is a late-stage consideration and not part of initial management.
Supportive Care:
Continuous cardiac monitoring (ECG, echocardiography)
Fluid management, especially in patients with shock or dehydration
Antipyretics for symptomatic relief
Monitoring for medication side effects (e.g., aseptic meningitis with IVIG, gastrointestinal upset with aspirin)
Close follow-up for cardiac complications.
Complications
Early Complications:
Kawasaki Disease: Myocarditis, pericarditis, valvulitis, coronary artery aneurysms/ectasia, arrhythmias, heart failure, myocardial infarction (rare)
MIS-C: Myocarditis, pericarditis, valvulitis, coronary artery dilation/aneurysms, heart failure, cardiogenic shock, arrhythmias, myocardial infarction, multi-organ dysfunction (e.g., renal failure, hepatic dysfunction, encephalitis).
Late Complications:
Kawasaki Disease: Persistent coronary artery aneurysms (increased risk of thrombosis, stenosis, myocardial infarction, sudden death)
Calcification of coronary arteries
MIS-C: Similar to late KD complications related to coronary arteries
Also, potential long-term effects on other affected organ systems.
Prevention Strategies:
Early diagnosis and prompt treatment with IVIG within the first 10 days of fever onset significantly reduce the risk of coronary artery aneurysms in KD
For MIS-C, timely recognition and appropriate immunosuppressive therapy are key to mitigating cardiac and systemic complications.
Prognosis
Factors Affecting Prognosis:
Kawasaki Disease: Delayed treatment (onset of IVIG >10 days), incomplete response to initial IVIG, presence of coronary artery abnormalities at diagnosis, younger age at onset, certain genetic factors
MIS-C: Severity of cardiac involvement, degree of inflammation, promptness of treatment, presence of shock, and response to therapy
For both, the development and size of coronary artery aneurysms are critical prognostic indicators.
Outcomes:
With timely and appropriate treatment, the majority of children with KD recover fully with minimal long-term sequelae
However, a significant minority develop coronary artery abnormalities that require lifelong monitoring and management
MIS-C outcomes are variable
while many recover, some may experience persistent cardiac dysfunction or long-term sequelae related to systemic inflammation.
Follow Up:
Kawasaki Disease: Children treated successfully without coronary abnormalities typically have follow-up echocardiograms at 6-8 weeks post-illness
Those with coronary abnormalities require lifelong cardiology follow-up, including serial echocardiograms, stress tests, and potentially antiplatelet/anticoagulant therapy
MIS-C: Requires diligent cardiology follow-up, especially if coronary arteries are involved, with serial echocardiograms, ECGs, and potentially further cardiac investigations
Monitoring for recurrence or long-term organ system dysfunction may also be necessary.
Key Points
Exam Focus:
Differentiating KD and MIS-C based on clinical presentation, timeline of symptoms, and association with SARS-CoV-2 is crucial
Remember the cardinal signs of KD and the diagnostic criteria
Recognize that MIS-C is a post-infectious syndrome with broader multi-organ involvement and often severe cardiac manifestations
IVIG is the mainstay for both, often supplemented with steroids in MIS-C.
Clinical Pearls:
Always consider KD in a child with prolonged fever and rash, even without all cardinal signs (atypical KD)
Think MIS-C in a child with fever and multi-organ system inflammation, especially in the context of a COVID-19 pandemic, even if the initial SARS-CoV-2 test was negative
Echocardiography is your best friend for assessing cardiac involvement in both conditions.
Common Mistakes:
Delaying treatment for KD beyond 10 days of fever onset
Mistaking MIS-C for a simple viral illness or sepsis without considering the hyperinflammatory post-infectious nature
Underestimating the cardiac risk in both conditions
Inadequate follow-up for patients with coronary abnormalities.