UMEM Educational Pearls

Background:

Multisystem inflammatory syndrome in children (MIS-C) as defined by CDC Health Advisory in May 2020 is:

1) An individual aged <21 years presenting with fever*, laboratory evidence of inflammation**, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND

2) No alternative plausible diagnoses; AND

3) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.

*Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours

**Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin

As of January 31^st, 2022 the CDC reports the following statistics related to MIS-C in the United States:

·         Total MIS-C patients meeting case definition= 6,851

·         Total MIS-C deaths meeting case definition = 59

·         The median age of patients with MIS-C was 9 years. Half of children with MIS-C were between the ages of 5 and 13 years.

·         59% of the reported patients with race/ethnicity information available occurred in children who are Hispanic/Latino (1,746 patients) or Black, Non-Hispanic (2,050 patients).

·         98% of patients had a positive test result for SARS CoV-2, the virus that causes COVID-19. The remaining 2% of patients had contact with someone with COVID-19.

·         60% of reported patients were male.

 

Management:

First-Line Treatment:

·         IVIG 2 g/kg dosed based on ideal body weight with a maximum of 100 grams (1000 mL)  

o   For patients with significant myocardial dysfunction and concern for fluid overload, the infusion can be given in divided doses over 2 days (1g/kg q12 x 2 doses)

PLUS

·         Methylprednisolone 1 mg/kg (max of 30 mg/dose) IV twice daily and switch to PO and taper when clinically appropriate

Upon Consultation with Pediatric Hematology/Cardiology will consider adding the following therapies to IVIG and steroids:

·         Enoxaparin treatment versus prophylactic dosing depending on D-dimer elevation and whether or not being admitted to PICU

·         Aspirin 3-5 mg/kg (max 81 mg/dose) daily unless platelet count < 80 K/mcl

Second-Line Treatment (refractory to IVIG defined by symptoms and fever persisting >36 hours)*:

·         Methylprednisolone pulse dosing- 30 mg/kg (max of 1000 mg/dose) x 3-5 days

OR

·         High dose anakinra

OR

·         Infliximab 5-10 mg/kg IV x1  

*All second-line treatment options require peds infectious diseases and PICU attending approval

UMMS COVID/MIS-C Pathway: https://intra.umms.org/-/media/intranets/umms/pdfs/dept/pharmacy-and-therapeutics/guidelines/umms-pediatric-covid-pathway.pdf?upd=20220125144550

References

References:

1. Belhadjer Z, Meot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic external icon. Circulation 2020.

2. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic external icon. Lancet 2020.

3. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study external icon. Lancet 2020.

 

4. CDC COVID Data Tracker: Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. https://covid.cdc.gov/covid-data-tracker/#mis-national-surveillance. February 1, 2022.

 

5. Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3. Arthritis and Rheumatology 2022.