Overview
Definition:
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but serious condition associated with SARS-CoV-2 infection, characterized by inflammation of various organs, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs.
Epidemiology:
Typically affects children and adolescents aged 6 months to 19 years, with a median age of around 8-9 years
It has a peak incidence weeks after a surge in community SARS-CoV-2 transmission
Boys are slightly more commonly affected
It is most prevalent in the post-COVID-19 pandemic era.
Clinical Significance:
MIS-C poses a significant risk of severe morbidity, including acute cardiac dysfunction, shock, and death, making prompt recognition and appropriate management crucial for improving patient outcomes
Understanding escalation strategies is vital for DNB and NEET SS preparation.
Clinical Presentation
Symptoms:
Fever lasting at least 4 days
Rash involving the trunk, extremities, or both
Conjunctivitis
Oral mucosal changes such as red lips or cracked lips, strawberry tongue, or pharyngeal erythema
Limb changes including edema or erythema of hands or feet, or desquamation of hands or feet
Gastrointestinal symptoms like abdominal pain, vomiting, or diarrhea
Neurological symptoms such as headache or altered mental status
Hypotension or shock.
Signs:
Persistent fever (>38°C or 100.4°F)
Bilateral non-exudative conjunctivitis
Oral mucosal changes
Peripheral edema or erythema
later desquamation
Diffuse maculopapular rash
Evidence of shock (e.g., hypotension, poor perfusion, elevated lactate)
Cardiac involvement evidenced by myocarditis, pericarditis, valvulitis, or coronary artery abnormalities
Signs of inflammation: elevated CRP, ESR, or neutrophilia
Cytopenias: anemia, lymphopenia, or thrombocytopenia.
Diagnostic Criteria:
CDC and WHO criteria include: age <18 years, fever >38°C for at least 4 days, laboratory evidence of inflammation, illness onset within 4 weeks of SARS-CoV-2 infection or exposure, evidence of severe illness requiring hospitalization, and no other plausible diagnosis
Key inflammatory markers include elevated CRP, ESR, and ferritin
Cardiac involvement is assessed via echocardiogram and troponin levels.
Diagnostic Approach
History Taking:
Detailed history of fever duration and characteristics
Inquiry about exposure to COVID-19 or recent infections
Assessment of specific symptoms including rash, conjunctivitis, oral findings, gastrointestinal complaints, neurological symptoms, and limb changes
Past medical history, especially cardiac conditions, and medication use.
Physical Examination:
Comprehensive assessment including vital signs (temperature, heart rate, blood pressure, respiratory rate, oxygen saturation)
Thorough skin examination for rash characteristics and distribution
Ophthalmic examination for conjunctivitis
Oral cavity examination
Examination of extremities for edema, erythema, or desquamation
Cardiac auscultation and assessment for signs of shock
Neurological assessment.
Investigations:
Complete blood count (CBC) with differential to assess for anemia, lymphopenia, and neutrophilia
Inflammatory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, procalcitonin
Liver function tests (LFTs) and renal function tests (RFTs)
Cardiac assessment: Electrocardiogram (ECG), echocardiogram (to assess for myocarditis, pericardial effusion, and coronary artery dilation/aneurysm), cardiac enzymes (troponin I/T, BNP)
Coagulation profile (PT, aPTT, D-dimer)
SARS-CoV-2 testing (RT-PCR or serology)
Blood cultures to rule out bacterial sepsis
Urinalysis
Chest X-ray or CT chest if respiratory symptoms are prominent.
Differential Diagnosis:
Kawasaki disease (KD) is the closest differential, especially for younger children
MIS-C typically presents with more severe systemic inflammation and cardiac involvement
Bacterial sepsis
Other viral exanthems
Macrophage activation syndrome (MAS)
Acute rheumatic fever
Toxic shock syndrome
Stevens-Johnson syndrome.
Management
Initial Management:
Immediate hospitalization, typically in a pediatric intensive care unit (PICU) for critically ill patients
Hemodynamic support with intravenous fluids
Vasopressor support if in shock
Oxygen therapy as needed.
Medical Management:
Intravenous immunoglobulin (IVIG) is the cornerstone of initial therapy, typically 2 g/kg infused over 10-12 hours
Corticosteroids are frequently used, often as a second-line therapy or in conjunction with IVIG for severe cases
common regimens include methylprednisolone IV (10-30 mg/kg/day) or oral prednisolone (1-2 mg/kg/day)
Aspirin is usually initiated at an anti-inflammatory dose (3-5 mg/kg/day) for coronary artery abnormality risk, and then changed to an antiplatelet dose (1-3 mg/kg/day) if no abnormalities are present, or continued at antiplatelet dose if coronary artery aneurysms develop.
Escalation Pathways:
If patients do not respond to IVIG and corticosteroids (persistent fever or ongoing inflammation), escalation to biologic agents is considered
Tocilizumab (an IL-6 receptor antagonist) is a key biologic, typically given as a single IV dose (8-10 mg/kg)
Other biologics like anakinra (IL-1 receptor antagonist) or infliximab (TNF-alpha inhibitor) may be used in refractory cases
The choice of escalation depends on the specific inflammatory profile and clinical response.
Supportive Care:
Close monitoring of vital signs, fluid balance, and cardiac function
Pain management and fever control
Nutritional support
Anticoagulation may be considered in patients with coronary artery aneurysms or hypercoagulable states
Prophylactic antibiotics may be indicated based on infection risk.
Complications
Early Complications:
Cardiogenic shock
Myocarditis leading to heart failure
Coronary artery aneurysms and thrombosis
Acute kidney injury
Neurological complications (e.g., encephalitis, seizures)
Gastrointestinal complications (e.g., intussusception, appendicitis)
Hemophagocytic lymphohistiocytosis (HLH).
Late Complications:
Coronary artery aneurysms leading to myocardial infarction
Chronic heart failure
Arrhythmias
Long-term neurological deficits
Persistent inflammation.
Prevention Strategies:
Early recognition and prompt initiation of appropriate therapy (IVIG, corticosteroids) are crucial
Careful monitoring for cardiac involvement
Aggressive management of shock and inflammation
Consideration of antiplatelet or anticoagulant therapy in cases of coronary artery abnormalities.
Prognosis
Factors Affecting Prognosis:
Timeliness of diagnosis and treatment
Severity of initial presentation (e.g., presence of shock, degree of cardiac dysfunction)
Development of coronary artery aneurysms
Response to initial therapy and escalation strategies
Underlying comorbidities.
Outcomes:
Most children with MIS-C recover fully with appropriate treatment
However, a significant proportion may develop long-term cardiac complications
Mortality rates are low but present, emphasizing the severity of the condition
Long-term follow-up is essential for all survivors.
Follow Up:
Regular clinical review with a cardiologist
Serial echocardiograms to monitor for coronary artery abnormalities
ECG monitoring
Assessment for neurological and developmental sequelae
Patients with coronary artery aneurysms require lifelong cardiology follow-up and potentially antiplatelet/anticoagulant therapy.
Key Points
Exam Focus:
MIS-C is a post-infectious hyperinflammatory syndrome
Differentiate from Kawasaki disease
IVIG is first-line
steroids are often second-line or adjuvant
Escalation to biologics like tocilizumab is for refractory cases
Cardiac involvement is a major concern.
Clinical Pearls:
Maintain a high index of suspicion in febrile children with multi-system involvement following a viral illness
Echocardiography is vital for assessing cardiac status and coronary arteries
Escalation pathways are guided by clinical response and inflammatory markers.
Common Mistakes:
Delaying diagnosis due to atypical presentation
Underestimating cardiac involvement
Inappropriate escalation of therapy without considering standard first-line treatments
Failing to follow up long-term cardiac sequelae.