What are the guidelines for managing Multisystem Inflammatory Syndrome in Children (MIS-C)?

Management of Multisystem Inflammatory Syndrome in Children (MIS-C)

All hospitalized MIS-C patients should receive high-dose IVIG (2 gm/kg based on ideal body weight) as first-line therapy, with adjunctive low-to-moderate-dose glucocorticoids (1-2 mg/kg/day methylprednisolone) added upfront for patients presenting with shock or organ-threatening disease. 1

Initial Assessment and Treatment Timing

Before initiating immunomodulatory therapy:

• Patients without life-threatening manifestations should undergo complete diagnostic evaluation for MIS-C and rule out other infections before treatment 1
• Patients with life-threatening manifestations (shock, severe cardiac dysfunction, respiratory failure) require immediate immunomodulatory treatment before completing full diagnostic workup 1
• Assess cardiac function and fluid status before IVIG administration, as patients with depressed cardiac function may require close monitoring, diuretics, and divided IVIG dosing (1 gm/kg daily over 2 days) 1

Mild cases:

• Some patients with mild symptoms may only require close monitoring without immunomodulatory treatment after evaluation by specialists with MIS-C expertise 1
• The American College of Rheumatology notes uncertainty around empiric IVIG use to prevent coronary artery aneurysms in this setting 1

Stepwise Immunomodulatory Treatment Algorithm

First-line therapy:

• IVIG 2 gm/kg (based on ideal body weight) for all hospitalized patients and/or those fulfilling Kawasaki disease criteria 1, 2
• Add low-to-moderate-dose glucocorticoids (1-2 mg/kg/day methylprednisolone) as adjunctive therapy for patients with shock and/or organ-threatening disease 1, 2

Second-line therapy for refractory disease:

• For patients not responding to IVIG and low-to-moderate-dose glucocorticoids, escalate to high-dose IV pulse glucocorticoids (10-30 mg/kg/day methylprednisolone), especially if requiring high-dose or multiple inotropes/vasopressors 1
• Low-to-moderate-dose steroids (1-2 mg/kg/day) may be added for milder MIS-C cases with persistent fever and symptoms despite single IVIG dose 1
• Do NOT give a second dose of IVIG for refractory disease due to risks of volume overload and hemolytic anemia 1

Third-line therapy:

• Anakinra (>4 mg/kg/day IV or SC) for MIS-C refractory to IVIG and glucocorticoids, particularly in patients with macrophage activation syndrome features or contraindications to prolonged glucocorticoid use 1, 2

Treatment duration and tapering:

• Serial laboratory testing and cardiac assessment should guide treatment response and tapering 1
• Patients typically require 2-3 weeks or longer taper of immunomodulatory medications 1

Antiplatelet and Anticoagulation Management

Low-dose aspirin:

• Give 3-5 mg/kg/day (maximum 81 mg/day) to all MIS-C patients 1
• Continue until platelet count normalizes AND normal coronary arteries confirmed at >4 weeks after diagnosis 1
• Avoid aspirin if: active bleeding, significant bleeding risk, or platelet count ≤80,000/µl 1

Therapeutic anticoagulation indications:

• Coronary artery aneurysms with z-score ≥10.0: low-dose aspirin PLUS therapeutic anticoagulation with enoxaparin (factor Xa level 0.5-1.0) or warfarin 1
• Documented thrombosis OR ejection fraction <35%: therapeutic enoxaparin until at least 2 weeks after hospital discharge 1, 2

Long-term anticoagulation:

• Coronary artery aneurysms with z-score >10.0: indefinite therapeutic enoxaparin 1
• Documented thrombosis: therapeutic anticoagulation for ≥3 months pending thrombus resolution 1
• Ongoing moderate-to-severe left ventricular dysfunction: continue therapeutic enoxaparin 1

Coronary artery aneurysms with z-score 2.5-10.0:

• Treat with low-dose aspirin only 1

Cardiac Monitoring Protocol

During hospitalization:

• Continuous telemetry if conduction abnormalities present 2
• EKG every 48 hours minimum while hospitalized 2
• Trend cardiac biomarkers (BNP, troponin T) until normalization 2

Follow-up echocardiography schedule:

• At diagnosis, 7-14 days, and 4-6 weeks after presentation 2
• More frequent echocardiograms required for patients with left ventricular dysfunction and/or coronary artery aneurysms 1, 2

Advanced cardiac imaging:

• Cardiac MRI indicated 2-6 months after diagnosis for patients with significant transient left ventricular dysfunction (ejection fraction <50%) or persistent dysfunction 1
• Cardiac MRI should include functional assessment, T1/T2-weighted imaging, T1 mapping, extracellular volume quantification, and late gadolinium enhancement 1
• Cardiac CT for suspected distal coronary artery aneurysms not well visualized on echocardiogram 1

Critical Pitfalls to Avoid

Volume overload risk:

• Always assess cardiac function and fluid status before IVIG administration 1
• Consider divided IVIG dosing (1 gm/kg over 2 days) in patients with cardiac dysfunction 1
• Never give second IVIG dose for refractory disease 1

Delayed glucocorticoid administration:

• Recent multicenter data demonstrates that early glucocorticoid administration (within 48 hours) is independently associated with shorter hospital length of stay 3
• Do not delay glucocorticoids in patients with shock or organ-threatening disease 1, 2

Inadequate cardiac follow-up:

• All MIS-C patients require cardiology follow-up regardless of initial cardiac involvement 4
• Long-term cardiac sequelae remain incompletely characterized, necessitating structured follow-up protocols 5