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Potentially life-threatening emergency
Multisystem inflammatory syndrome in children in Child
Other Resources UpToDate PubMed
Potentially life-threatening emergency

Multisystem inflammatory syndrome in children in Child

Contributors: Eric Ingerowski MD, FAAP, Paritosh Prasad MD
Other Resources UpToDate PubMed

Synopsis

Although pediatric patients with primary coronavirus disease 2019 (COVID-19) usually are asymptomatic or have a very mild illness and rarely require medical attention, a new serious and potentially life-threatening syndrome associated with COVID-19 is becoming recognized and is known as multisystem inflammatory syndrome in children (MIS-C) (also known as multisystem inflammatory syndrome in children and adolescents temporally associated with COVID-19). This syndrome was first reported in the United Kingdom and has subsequently been described elsewhere in Europe, Asia, and the United States. It occurs in individuals younger than 21 years and presents with symptoms that overlap with toxic shock syndrome, Kawasaki disease, bacterial sepsis, and macrophage activation syndrome. While the etiology of this syndrome has yet to be proven, it is thought to be a postinfectious immune response to infection with the SARS-CoV-2 virus involving a possible cytokine storm. Although it is thought to be rare, the true incidence is unknown.

Median age is 8 years of age, and obesity is the most common underlying medical condition, identified in 25.6% of cases. Patients typically present with persistent fevers, elevated inflammatory markers (increased C-reactive protein [CRP], neutrophilia, or lymphopenia), and evidence of single or multisystem end organ dysfunction. The individual features of each patient case may be variable and include a wide range of possible symptoms. Gastrointestinal symptoms including diarrhea and vomiting are common. Gastrointestinal imaging may reveal ileitis, ascites, and bowel wall thickening. Several of these patients have shown signs of shock (cardiogenic or vasogenic) with hypotension and supplemental O2 requirements and have had single or multisystem end organ dysfunction requiring admission to the intensive care unit (ICU).

Cardiac symptoms are present in over 50% of cases and include myocarditis; decreased cardiac output and features of shock; coronary artery inflammation, dilatation, or aneurysm; and pericardial effusions. Other features such as lymphadenopathy, mucous membrane changes, rash, swelling of the hands and feet, conjunctivitis, pharyngitis, headache, and/or neck pain may be present. A cough is present in less than one-third of all patients. Neurologic manifestations resulting from involvement of the central and peripheral nervous systems may include hyporeflexia, generalized weakness, meningeal signs, mental status changes, and encephalopathic symptoms.

Based on a case series of 570 MIS-C patients published by the CDC, 86% of patients will have 4 or more organ systems involved; 40.6% had cardiac dysfunction, 35.4% had shock, 22.8% had myocarditis, 18.6% had coronary artery dilation or aneurysm, and 18.4% had acute kidney injury. In this cohort, 99.1% had positive testing for COVID (either RT-PCR or serology), and only 0.9% did not have any testing or epidemiologic link to COVID. The majority of these patients (63.9%) were admitted to the ICU with a median length of stay of 5 days and a mortality rate of 1.8%. This case series went further, using latent class analysis, and described 3 classes of disease.
  • Class 1 (total 203 patients; 35.6%): Mean age of 9 years old. Patients had the highest number of involved organ systems, with 48.8% having 6 or more organ systems involved, most commonly the cardiovascular (100%) and gastrointestinal systems (97.5%). These patients had significantly higher rates of abdominal pain, lymphopenia, shock, and myocarditis as well as elevation in serum inflammatory markers such as CRP and ferritin and markers of cardiac injury including troponin and brain natriuretic peptide (BNP). Almost all (98%) had positive SARS-CoV-2 serology testing with or without positive SARS-CoV-2 RT-PCR. Mortality rate in this group was 0.5%.
  • Class 2 (total 169 patients; 29.6%): Mean age of 10 years old. The majority of these patients (76.3%) had respiratory involvement. These patients were more likely to have pneumonia, cough and shortness of breath, and some had progression to acute respiratory distress syndrome (ARDS). The majority (84%) of these patients had positive SARS-CoV-2 RT-PCR but negative serology, with a case fatality rate of 5.3%, higher than either class 1 or 3. These patients may represent primarily acute COVID-19 or a combination of acute COVID-19 and MIS-C.
  • Class 3 (total 198 patients; 34.7%): These patients were younger (mean age 6 years old) and had the highest prevalence of rash (62.6%) and mucocutaneous lesions (44.9%). These patients were more likely to meet criteria for Kawasaki disease (6.6%) compared with the other classes. They also had the lowest prevalence of underlying medical conditions and organ system involvement or complications and elevation of inflammatory markers. The majority of these patients had positive SARS-CoV-2 serology only (63.1%), and 33.8% had both positive serologic and positive RT-PCR results.
Laboratory findings show evidence of inflammation and end organ dysfunction and frequently include abnormal fibrinogen, high D-dimers, lactic acid dehydrogenase (LDH), interleukin (IL)-6 and ferritin, elevated CRP, hypoalbuminemia, neutrophilia, and lymphopenia. Laboratory signs of acute kidney injury, coagulopathy, and transaminitis have been described as well as elevated troponin, proBNP, anemia, and thrombocytopenia.

Many of the patients have positive serologic testing for SARS-CoV-2, indicating that this is a later manifestation of COVID-19. A small minority of patients, however, have had positive reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, while others were negative on all tests. Other microbiologic causes of the above symptoms as well as other diagnoses that could explain the patient's symptoms must be ruled out.

Because this is newly described syndrome, the case definition is likely still evolving. On May 14, 2020, the US Centers for Disease Control and Prevention (CDC) published its case definition (see Look For).

Codes

ICD10CM:
U07.1 – COVID-19

SNOMEDCT:
840539006 – Disease caused by severe acute respiratory syndrome coronavirus 2

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Last Reviewed:06/03/2020
Last Updated:09/14/2020
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Potentially life-threatening emergency
Multisystem inflammatory syndrome in children in Child
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Copyright © 2021 VisualDx®. All rights reserved.