Multisystem Inflammatory Syndrome in Children
Recent reports from Europe and North America have described clusters of children and adolescents requiring admission to intensive care units with Pediatric Inflammatory Multisystem Syndrome (PIMS) that is associated with SARS-CoV-2 infection. On May 14, the Centers for Disease Control and Prevention (CDC) issued a national health advisory on COVID19 patients with a syndrome that it called multisystem inflammatory syndrome in children (MIS-C).
Common clinical findings include:
- Shock
- Myocardial dysfunction
- Arrhythmia
- Acute respiratory failure
- Acute kidney injury
- Serositis (small pleural, pericardial, and ascitic effusions)
- Hepatitis or hepatomegaly
- Encephalopathy, seizures, coma, or meningoencephalitis
Hematologic findings include: lymphopenia, neutrophilia, anemia, and thrombocytopenia. Elevated markers of inflammation include C-reactive protein, D-Dimer, fibrinogen, ferritin, procalcitonin and interleukin-6. Troponin and BNP may also be elevated. Chemistry abnormalities include hypoalbuminemia, elevated transaminases, elevated LDH and hypertriglyceridemia.
The clinical findings in approximately 50% of children overlap those found in Kawasaki disease (KD). However, some key differences have been described:
- MIS-C commonly affects older children and adolescents, whereas classic KD typically affects infants and young children.
- MIS-C disproportionally affects black and Hispanic children, whereas classic KD has a higher incidence in East Asia and in children of Asian descent
- Gastrointestinal symptoms (particularly abdominal pain) are very common in MIS-C, but not in classic KD.
- Myocardial dysfunction and shock occur more commonly in MIS-C compared with classic KD
- Inflammatory markers (especially C-reactive protein, ferritin, and D-dimer) are more elevated in MIS-C compared with KD. Absolute lymphocyte and platelet counts tend to be lower in MIS-C compared with classic KD
These clinical features can help distinguish MIS-C from KD, but ultimately, the designation of MIS-C versus KD is based on SARS-CoV-2 testing and exposure history. Both COVID19 PCR and serology should be performed. Approximately 50 to 60 percent of patients have positive serology with negative PCR, 25 to 30 percent are positive on both tests, and 10 to 15 percent are negative for both tests. In the latter scenario, diagnosis requires evidence of an exposure to a known COVID19 individual within the past weeks prior to onset of symptoms.
Patients with positive SARS-CoV-2 testing (or with an exposure to an individual with COVID-19) who also fulfill criteria for complete or incomplete KD should be considered to have MIS-C and should receive standard treatment for KD.
Both CDC and WHO have published case definitions. Both definitions require fever, elevated inflammatory markers, at least two signs of multisystem involvement, evidence of SARS-CoV-2 infection or exposure, and exclusion of other potential causes. The CDC case definition requires that the child have severe symptoms requiring hospitalization, whereas the WHO case definition does not.
Between March 2 and July 18, CDC received reports of 570 young people, ranging from infancy to 20 years of age, that met the definition of MIS-C. The reports came from health departments in 40 states, as well as New York City and Washington D.C. Children of color were more disproportionately affected. About 40 percent were Hispanic or Latino, 33 percent Black and 13 percent white. Two thirds of the patients had no previous underlying medical conditions, but 25 percent were obese. Nearly two thirds were admitted to the ICU for a median of five days and ten died.
References
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020. Epub 2020/05/11.
DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region. J Pediatr. 2020
Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Bradley Segal J, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020. Epub 2020/04/09
WHO, Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19, May 15, 2020, WHO/2019 -nCoV/Sci_Brief/Multisystem_Syndrome_Children/2020.1
Center for Disease Control and Prevention, Center for Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), Clinician Outreach and Communication (COCA) Webinar. Available at: https://emergency.cdc.gov/coca/calls/2020/callinfo_051920.asp?deliveryName=USCDC_1052-DM28623.
Whittaker E, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, JAMA, June 8, 2020, doi:10.1001/jama.2020.10369
Godfred-Cato S, Bryant B, Leung J, et al. COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020. MMWR Morb Mortal Wkly Rep. ePub: 7 August 2020. DOI:http://dx.doi.org/10.15585/mmwr.mm6932e2
