Pediatricians seeing children with prolonged fever should rule out other explanations before screening for multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, according to pediatric specialists with Norton Children’s.

The Centers for Disease Control and Prevention (CDC) issued a health advisory May 14 defining the syndrome, which had previously been described as an illness with Kawasaki disease-like features.

“The CDC definition emphasizes multisystem organ involvement, so two or more organ systems involved, along with fever and no alternative plausible diagnosis,” said Kristina A. Bryant, M.D., pediatric infectious disease specialist with Norton Children’s Infectious Diseases, affiliated with the UofL School of Medicine. Dr. Bryant spoke during a livestreamed continuing medical education activity presented by Norton Children’s.

The CDC case definition also requires fever, laboratory evidence of inflammation, and positive SARS-CoV-2 infection by RT-PCR, or antibody test, or known COVID-19 exposure within four weeks prior to the onset of symptoms. Respiratory symptoms were not always present with MIS-C.

MIS-C also appears to hit four to six weeks after acute illness, even if it was minor or asymptomatic, according to Brian J. Holland, M.D., chief of pediatric cardiology with Norton Children’s Heart Institute, affiliated with the UofL School of Medicine.

There are important distinctions between MIS-C and Kawasaki disease.

MIS-C has been seen in school-aged children and adolescents, while Kawasaki disease generally affects children under five.

Another difference: MIS-C seems to more frequently involve the heart, with abnormalities of the coronaries or cardiac dysfunction. As many as half of the patients in Italy presenting with Kawasaki disease-like features had some cardiac dysfunction and poor cardiac output.

Patients who are unstable, poorly perfused, with low blood pressure, who develop shock, need to have their coronaries imaged right away, according to Dr. Holland. Patients with fever who develop signs of inflammation also may need to have their coronaries imaged.

“If you get to the point where you think this patient needs to have their coronaries evaluated, I think they need to come to the children’s hospital.,” Dr. Holland said.

At Norton Children’s Hospital, three children have been treated for MIS-C. Two of them came in with primary gastrointestinal symptoms, which could be the result of GI inflammation. MIS-C can also cause vasculitic rashes, although there are many potential causes for these rashes in children.

According to Dr. Holland, Norton Children’s has a multidisciplinary team of cardiology, rheumatology, infectious disease and other specialists as needed to treat patients with MIS-C. Norton Children’s will follow up with these children after discharge in a multidisciplinary clinic with these subspecialists to learn as much as possible about the syndrome, which then can be shared with providers.

Dr. Bryant’s advice to pediatricians was to first rule out common explanations for fever — as they always have.

“I think common things are going to be common. If the fever persists, then we’ll pursue additional workup,” she said. “You are seeing this on the news, and it’s scary. This can make kids really sick, but really and truly, it is a very rare disorder.”

According to Dr. Bryant, pediatricians should advise parents that a small number of children who test positive for COVID-19 infection go on to develop MIS-C. Pediatricians should give parents the signs and symptoms of hyperinflammation so they can watch for them.

Pediatricians with questions can call Norton Children’s pediatric COVID-19 helpline: (800) 722-5725.