What is the treatment for multisystem inflammatory syndrome in children (MIS-C) after influenza?

Multisystem Inflammatory Syndrome in Children After Influenza

Critical Clarification

The evidence provided exclusively addresses MIS-C associated with SARS-CoV-2 (COVID-19), not influenza. There is no established multisystem inflammatory syndrome specifically linked to influenza in the medical literature provided. MIS-C is a post-infectious hyperinflammatory condition that occurs 2-6 weeks after SARS-CoV-2 infection, not influenza 1, 2.

If you are asking about a child with hyperinflammatory symptoms following influenza, this would require evaluation for other conditions (such as influenza-associated complications, bacterial superinfection, or other inflammatory syndromes), not MIS-C treatment protocols.

Treatment Approach for MIS-C (SARS-CoV-2 Associated)

First-Line Immunomodulatory Therapy

For confirmed MIS-C, initiate combination therapy with IVIG 2 gm/kg AND methylprednisolone 1-2 mg/kg/day as first-line treatment. 1

Treatment Algorithm:

Mild Cases Without Life-Threatening Features:

• Complete diagnostic evaluation before initiating immunomodulatory treatment 1
• Some well-appearing patients with mild symptoms may only require close monitoring without immediate treatment 1
• However, early combination therapy with both IVIG and glucocorticoids is associated with shorter hospital length of stay 3

Moderate-to-Severe Cases or Life-Threatening Manifestations:

• Initiate treatment before full diagnostic evaluation is completed if life-threatening features present 1

• IVIG dosing: 2 gm/kg based on ideal body weight 1

  • Assess cardiac function and fluid status before administration 1
  • In patients with cardiac dysfunction, may divide dose (1 gm/kg daily over 2 days) 1
  • Administer when cardiac function is restored in shock patients 1

• Glucocorticoid dosing: Methylprednisolone 1-2 mg/kg/day IV 1

  • For patients with concerning features (ill appearance, highly elevated BNP, unexplained tachycardia) who have not yet developed shock 1
  • High-dose IV pulse glucocorticoids (10-30 mg/kg/day) for life-threatening complications including shock, especially if requiring high-dose or multiple inotropes/vasopressors 1

Intensification Therapy for Refractory Disease

Refractory disease is defined as persistent fevers and/or ongoing significant end-organ involvement despite first-line therapy. 1

Options for intensification:

1. High-dose methylprednisolone 10-30 mg/kg/day IV 1
2. High-dose anakinra (>4 mg/kg/day IV or SC) 1

• Anakinra should be considered for MIS-C refractory to IVIG and glucocorticoids or in patients with contraindications to these treatments 1

Antiplatelet and Anticoagulation Therapy

Low-dose aspirin (3-5 mg/kg/day; maximum 81 mg/day):

• Use in patients with Kawasaki disease-like features and/or thrombocytosis (platelet count ≥450,000/μl) 1
• Continue until platelet count normalizes and normal coronary arteries confirmed at ≥4 weeks after diagnosis 1
• Avoid aspirin if platelet count ≤80,000/μl 1

Therapeutic anticoagulation with enoxaparin:

• Required for documented thrombosis or ejection fraction <35% until at least 2 weeks after hospital discharge 1
• For 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
• For z-score 2.5-10.0: low-dose aspirin alone 1

Treatment Duration and Tapering

Serial laboratory testing and cardiac assessment should guide immunomodulatory treatment response and tapering. 1

• Patients typically require a 2-3 week taper of immunomodulatory medications 1

Cardiac Monitoring Requirements

Echocardiogram schedule:

• At diagnosis with evaluation of ventricular/valvular function, pericardial effusion, and coronary artery dimensions with z-scores 1
• Repeat at minimum 7-14 days and 4-6 weeks after presentation 1
• Consider at 1 year for patients with acute phase cardiac abnormalities 1
• More frequent monitoring required for LV dysfunction and/or coronary artery aneurysms 1

EKG monitoring:

• Every 48 hours minimum while hospitalized and during follow-up 1
• Continuous telemetry if conduction abnormalities present 1

Cardiac biomarkers:

• Trend BNP and troponin T until normalization 1

Common Pitfalls to Avoid

• Do not delay treatment in life-threatening cases waiting for complete diagnostic workup 1
• Do not administer IVIG before assessing cardiac function in shock patients 1
• Do not use aspirin with severe thrombocytopenia (platelet count ≤80,000/μl) 1
• Do not assume mild presentation will remain mild—68% of MIS-C cases require ICU admission 4
• Early combination therapy (IVIG + glucocorticoids) is superior to monotherapy or delayed treatment 3