What is Multisystem Inflammatory Syndrome in Children (MIS-C)?

Multisystem Inflammatory Syndrome in Children (MIS-C) was first seen in Europe in March 2020 and thereafter in the Eastern United States in April of 2020. It has now been reported in many states across the U.S. but remains relatively uncommon. MIS-C has been associated with a variety of signs and symptoms that include multiple organ system involvement and clinical and laboratory evidence of systemic inflammation. It is important to note that there have been several names for this syndrome put forth by different organizations and include: Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) and Pediatric Multisystem Inflammatory Syndrome (PMIS). The term put forth by the U.S. Centers for Disease Control and Prevention (CDC) is “MIS-C” and will be the term used hereafter to describe this syndrome.

Is MIS-C caused by SARS-CoV-2?

We are not completely certain however many of the children with MIS-C presented several weeks (roughly 4 weeks) after the SARS-CoV-2 peak illness in the regions where cases have occurred. Additionally, many of the children have been found to have a history of exposure to someone with COVID-19 illness and/or are positive for SARS-CoV-2 by PCR and/or antibody testing at the time of MIS-C diagnosis, regardless as to whether they had symptoms of COVID-19 infection. Fortunately MIS-C appears to be a rare disorder with only a few hundred cases around the world, a small fraction of the estimated tens of thousands of pediatric cases (>50,000 confirmed COVID-19 cases in children in the U.S.).

Are MIS-C and Kawasaki Disease the same thing?

No. When MIS-C was first discovered in the United Kingdom, some of the children had symptoms very similar to Kawasaki Disease (a medium vessel vasculitis) such as fever, conjunctivitis, mucous membrane changes (e.g. red, cracked lips) and swollen hands and feet. Additional overlap has been described in that some children with MIS-C have been found to have coronary artery aneurysms. However, MIS-C can have many different appearances depending on which areas of the body have the associated inflammatory response and MIS-C has commonly been associated with myocardial dysfunction and shock. While there is a shock syndrome associated with Kawasaki Disease, it is relatively an uncommon presentation (approximately 5% of the time). Children with MIS-C often have complaints of severe belly pain, vomiting or diarrhea which is not typical in children with Kawasaki Disease. Additionally, children with Kawasaki Disease are typically younger (less than 5 years old) whereas children with MIS-C tend to be school age children (including adolescents).

What are the symptoms of MIS-C?

Not all children with MIS-C have the same symptoms. Some MIS-C symptoms include: persistent fever, abdominal pain, vomiting, diarrhea has been commonly reported as has shock with hypotension and myocardial dysfunction. Other symptoms include neck pain or stiffness, rash, conjunctivitis, swelling of the hands and feet, irritability, altered mental status or fatigue. Children require hospital admission and several have required care in the pediatric intensive care unit.

When do children need to be referred to the ED and/or further workup for MIS-C?

MIS-C may resemble other common febrile childhood illnesses such as Kawasaki Disease, gastroenteritis and viral exanthems. Well appearing children with short-lived fevers (<24 hours) and only one clinical feature involved (e.g. isolated rash) are unlikely to have this disorder, particularly if there has not been any known history or contact with SARS-CoV-2. A child with persistent fevers should be frequently monitored for clinical symptoms and laboratory evaluation considered (see below). Any child with hypotension, severe abdominal pain, shortness of breath, pain or pressure in the chest, altered mental status, poor perfusion or cyanosis should be referred to the ED immediately.

What are the laboratory abnormalities in MIS-C?

MIS-C has been universally associated with elevated inflammatory markers (including C-reactive protein and erythrocyte sedimentation rate) but there is no specific laboratory study that is diagnostic of MIS-C. Other common lab findings in patients with MIS-C include high procalcitonin, high ferritin, lymphopenia, thrombocytopenia, hyponatremia, elevated creatinine, elevated ALT, low albumin, high D-dimer, elevated troponin, and high brain type natriuretic peptide (BNP and pro-BNP).

Can a patient have MIS-C and another infection?

Although we are still learning about this syndrome, guidance issued by the CDC states that the diagnosis of MIS-C requires the exclusion of alternative plausible diagnoses. If an alternative source is identified such as a viral or bacterial infection that explains the child’s illness no further workup for MIS-C is necessary.

Do children with MIS-C who are SARS-CoV-2 positive require isolation precautions?

While MIS-C is thought to primarily be an immune-mediated disorder, some of the children have been found to be positive by PCR on nasal swab. However, many of these are weakly positive and often children are antibody positive suggesting infection most likely occurred weeks before presentation. However, hospitalized patients who are exhibiting COVID or flu-like symptoms or those with a pending or positive PCR for COVID-19 will be maintained in precautions as per our Rush University Medical Center COVID-19 isolation protocols.

Is MIS-C treatable?

Yes. While optimal treatment is not yet known, most children with MIS-C have done well with good supportive care typically in the intensive care unit. Other medications being given include those used in other hyper inflammatory syndromes such as IVIG, aspirin, steroids, anticoagulants and immunomodulators for refractory patients.

What is Rush University Medical Center doing to help?

Rush University Medical Center is working with state and local health departments, professional societies, scientists and other hospitals nationally and across the Chicagoland area to collect data on children with MIS-C to help understand which children are most at risk for this rare disorder, the best therapies, and the best ways to provide care for children in the hospital and long-term. Rush has formed a multi-disciplinary team of pediatric specialists such as infectious diseases, cardiology, immunology, gastroenterology, hematology, pharmacy, intensive care and other front line health-care providers that will be immediately ready and available to treat children with MIS-C. This multi-disciplinary team has already been successful in treating cases of MIS-C. Rush has been a leader in providing COVID-19 care throughout the pandemic and has already cared for several hundred children with COVID-19 illness.

For more information, please visit the CDC's website.