Multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C), or paediatric inflammatory multisystem syndrome (PIMS / PIMS-TS), or systemic inflammatory syndrome in COVID-19 (SISCoV), is a rare systemic illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2, the virus responsible for COVID-19.^[7] Studies suggest that MIS-C occurred in 31.6 out of 100,000 people under 21 who were infected with COVID-19.^[8][9] MIS-C has also been monitored as a potential, rare^[10] pediatric adverse event following COVID-19 vaccination.^[11] Research suggests that COVID-19 vaccination lowers the risk of MIS-C, and in cases where symptoms develop after vaccine, is likely extremely rare or related to factors like recent exposure to COVID-19.^[12] It can rapidly lead to medical emergencies such as insufficient blood flow around the body (a condition known as shock).^[7] Failure of one or more organs can occur.^[13] A warning sign is unexplained persistent fever with severe symptoms following exposure to COVID-19.^[14] Prompt referral to pediatric specialists is essential, and families need to seek urgent medical assistance.^[7] Most affected children will need intensive care.^[7]

All affected children have persistent fever.^[7] Other clinical features vary.^[14] The first symptoms often include acute abdominal pain with diarrhea or vomiting.^[7] Muscle pain and general fatigue are frequent,^[7] and low blood pressure is also common.^[15] Symptoms can also include pink eye, rashes, enlarged lymph nodes, swollen hands and feet, and "strawberry tongue".^[6] Various mental disturbances are possible.^[6] A cytokine storm may take place,^[16] in which the child's innate immune system stages an excessive and uncontrolled inflammatory response.^[17] Heart failure is common.^[15] Clinical complications can include damage to the heart muscle, respiratory distress, acute kidney injury, and increased blood coagulation.^[18] Coronary artery abnormalities can develop (ranging from dilatation to aneurysms).^[6]

This life-threatening disease has proved fatal in under 2% of reported cases.^[7] Early recognition and prompt specialist attention are essential.^[19] Anti-inflammatory treatments have been used, with good responses being recorded for intravenous immunoglobulin (IVIG), with or without corticosteroids.^[20] Oxygen is often needed.^[7] Supportive care is key for treating clinical complications.^[18] Most children who receive expert hospital care survive.^[7]

Knowledge of this newly described syndrome is evolving rapidly.^[21] Its clinical features may appear somewhat similar to Kawasaki disease, a rare disease of unknown origin that typically affects young children, in which blood vessels become inflamed throughout the body.^[15] It can also show features of other serious inflammatory conditions of childhood, including toxic shock and macrophage activation syndromes.^[15] Nevertheless, it appears to be a separate syndrome.^[22] Older children tend to be affected.^[23]

This emerging condition has been defined slightly differently (using different names), by the World Health Organization (WHO),^[24] the Royal College of Paediatrics and Child Health (RCPCH),^[13] and the Centers for Disease Control and Prevention (CDC).^[1] Although the condition is thought to follow SARS-CoV-2 viral infection, antigen or antibody tests are not always positive.^[3] Exclusion of alternative causes, including bacterial and other infections, is essential for differential diagnosis.^[3] Some general clinical guidance has been provided by the RCPCH,^[13] the National Institutes of Health,^[23] the American College of Rheumatology,^[25] and the American Academy of Pediatrics.^[26]

Clusters of new cases have been reported two to six weeks after local peaks in viral transmission.^[6] The disease is thought to be driven by a delayed biological mechanism in certain predisposed children.^[20] The European Centre for Disease Prevention and Control (ECDC) has rated risk to children in Europe as being 'low' overall, based on a 'very low' likelihood of a child developing this 'high impact' disease.^[3] Regarding ethnicity, the condition seems to affect more children of African, Afro-Caribbean, and Hispanic descent, whereas Kawasaki disease affects more of East Asian ancestry.^[19] Initial reports regarded children in various parts of Europe and the United States, and it was unclear to what extent the condition had gone unrecognized elsewhere.^[24] Reports have since emerged of cases in various other countries around the world.^[27][28] In adults, a similar condition has occasionally been reported, which has been called multisystem inflammatory syndrome in adults (MIS-A).^[29]