Table 5.

Immunomodulatory treatment in MIS-C^*

Guidance statement	Level of consensus
Patients under investigation for MIS-C without life-threatening manifestations should undergo diagnostic evaluation for MIS-C as well as other possible infections and non-infection-related conditions before immunomodulatory treatment is initiated.	Moderate
Patients “under investigation” for MIS-C with life-threatening manifestations may require immunomodulatory treatment for MIS-C before the full diagnostic evaluation can be completed.	High
After evaluation by specialists with expertise in MIS-C, some patients with mild symptoms may only require close monitoring without immunomodulatory treatment. The panel noted uncertainty around the empiric use of IVIG to prevent CAAs in this setting.	Moderate
A stepwise progression of immunomodulatory therapies should be used to treat MIS-C with IVIG considered first-tier therapy. Glucocorticoids should be used as adjunctive therapy in patients with severe disease or as intensification therapy in patients with refractory disease.	High
IVIG should be given to MIS-C patients who are hospitalized and/or fulfill KD criteria.	High
High-dose IVIG (typically 2 gm/kg, based on ideal body weight) should be used for treatment of MIS-C.	High
Cardiac function and fluid status should be assessed in MIS-C patients before IVIG treatment is provided. Patients with depressed cardiac function may require close monitoring and diuretics with IVIG administration.	High
In some patients with cardiac dysfunction, IVIG may be given in divided doses (1 gm/kg daily over 2 days).	Moderate
Low-to-moderate-dose glucocorticoids (1–2 mg/kg/day) should be given with IVIG as adjunctive therapy for treatment of MIS-C patients with shock and/or organ-threatening disease.	Moderate
In patients who do not respond to IVIG and low-to-moderate-dose glucocorticoids, high-dose, IV pulse glucocorticoids (10–30 mg/kg/day) may be considered, especially if a patient requires high-dose or multiple inotropes and/or vasopressors.	Moderate
In patients with refractory MIS-C despite a single dose of IVIG, a second dose of IVIG is not recommended, given the risk of volume overload and hemolytic anemia associated with large doses of IVIG.	High
Low-to-moderate-dose steroids (1–2 mg/kg/day) may also be considered in patients with milder forms of MIS-C who are persistently febrile and symptomatic despite a single dose of IVIG.	Moderate
Anakinra (>4 mg/kg/day IV or SC) may be considered for treatment of MIS-C refractory to IVIG and glucocorticoids in patients with MIS-C and features of macrophage activation syndrome or in patients with contraindications to long-term use of glucocorticoids.	Moderate
Serial laboratory testing and cardiac assessment should guide immunomodulatory treatment response and tapering. Patients may require a 2–3-week, or even longer, taper of immunomodulatory medications.	High

^*MIS-C = multisystem inflammatory syndrome in children; IVIG = intravenous immunoglobulin; CAAs = coronary artery aneurysms; SC = subcutaneous.