Multisystem inflammatory syndrome in children, or MIS-C, is associated with COVID-19 but has a clinical presentation similar to that of Kawasaki disease, with symptoms like high fever and high inflammatory markers.
“The body starts to respond in a typical way, developing anti-inflammatory cells to eradicate the coronavirus,” says Children’s Hospital Colorado pediatric cardiologist Pei-Ni Jone, MD. “But then the immune system goes hyperactive and a cytokine storm develops in which the immune cells start to harm the normal cells in addition to the virus. So these patients get sicker and faster than those with Kawasaki disease.”
That’s why it’s crucial that doctors diagnose MIS-C quickly, accurately differentiating it from Kawasaki disease and other more common conditions. At Children’s Colorado, Dr. Jone and a multidisciplinary team of infectious disease specialists, rheumatologists and critical care experts have developed a treatment pathway that helps them take a standardized approach.
Like in most hospitals across the country, the MIS-C pathway combines recommendations from the Centers for Disease Control and Prevention, World Health Organization and European Centre for Disease Prevention and Control. But there are several intentional differences.
A comprehensive echo is essential
According to the pathway, a patient with suspected MIS-C must have a fever for more than three days and at least two criteria consistent with the clinical case definition, such as rash; hypotension or shock; features of myocardial dysfunction, pericarditis, valvulitis; or evidence of coagulopathy. If the patient is also hemodynamically unstable and has evidence of multi-organ dysfunction, the next step is a myriad of labs.
“Heart inflammation will often cause damage to the heart cells,” says Dr. Jone. “That sets off a marker called troponin, which can be elevated in patients with MIS-C. Additional tests reveal these patients have low lymphocyte counts, meaning that these cells are fighting the virus and depleting the lymphocytes. That’s really what makes MIS-C a totally different entity from Kawasaki disease.”
Those characteristics trigger steps including a comprehensive echocardiogram with coronary imaging and a function assessment of the heart. That’s one of the most important protocols they wrote into the pathway, says Dr. Jone, and something that’s unique to Children’s Colorado.
“It’s very sophisticated imaging. These are 1- or 2-millimeter measurements,” she says. “If you wait to do that kind of assessment until the next day, you’re likely already too late. We need to know immediately if the coronary is dilated so we can be very aggressive with treatment.”
IVIG therapy, or intravenous immunoglobulin therapy, is an anti-inflammatory medication that gives a patient the antibodies they need to fight an infection. It’s often used in patients with Kawasaki disease who, because of coronary artery dilation, are at increased risk of clotting and heart attack. MIS-C is the same in that respect, so delaying IVIG is dangerous. Depending on symptoms, coronary involvement and their severity, Dr. Jone and her team may combine IVIG with a chimeric monoclonal antibody drug called infliximab.
The multidisciplinary team then monitors the patient throughout recovery, repeating labs and other steps along the pathway as necessary.
Information sharing and research
Since May, the pathway has helped Dr. Jone and the multidisciplinary team successfully treat more than 14 patients who’ve been diagnosed with MIS-C. They continue to adjust the pathway for efficiency, removing excess labs as they learn more. The comprehensive guidelines are so effective, in fact, that institutions across the country have asked for them.
“I love sharing our protocols,” says Dr. Jone. “I’ll send them to anyone who wants to take a look. The more doctors who know about how to effectively care for MIS-C, the better it is for the patients.” Boston Children’s Hospital took note of the approach and asked Children’s Colorado to join a study called Long-Term Outcomes after the Multisystem Inflammatory Syndrome in Children: MUSIC that looks at heart function and long-term outcomes of MIS-C patients. Children’s Colorado is participating in several other research initiatives related to MIS-C and COVID-19. One is with Rady Children’s Hospital called Characterization of Multisystem Inflammatory Syndrome in Children (CHARMS) and its relationship to Kawasaki disease. That study will compare bloodwork in KD and MIS-C patients for biomarker differences. The other is a multi-center study funded by the National Institutes of Health called Overcoming COVID-19.
Find our clinical pathway for MIS-C
Note: Use the Google Chrome browser to access the file via Agile MD.
Additionally, Dr. Jone is the primary author of and is in the process of writing a guideline paper for the American Heart Association on COVID-19 and the cardiovascular complications in pediatric congenital heart disease patients. She and the paper’s other authors hope to publish in the next three months.