Pediatric Rheumatologists Lead the Way in Treating a New Inflammatory Illness in Children

News reports have spiked in recent days about a new mystery illness affecting children that may be related to the COVID-19 virus. Because this illness is often compared to Kawasaki disease, a condition related to childhood arthritis, parents are understandably concerned. The Arthritis Foundation is working to understand any connection between the new illness and juvenile arthritis, and to help parents get information they need. Here is what we have learned from the leading pediatric rheumatologists treating and studying these diseases.

By Marcy O'Koon

Until this mystery illness emerged, it had been assumed that children were much less likely than adults to contract or have serious complications of COVID-19. However, in recent weeks doctors – in Italy, the U.K., and more recently in the U.S. – have seen a burst of cases of a previously unrecognized severe illness occurring in some children that may be related to COVID-19. To pediatric rheumatologists it looks very similar to, but not quite the same as, Kawasaki disease (KD), a rheumatic disease that most commonly occurs in infants and very young children. Pediatric rheumatologists and adult rheumatologists around the world are being called in by other specialist physicians to consult on this previously unseen diagnosis and advise on its treatment.

“We are the experts on inflammation, and so we are in a good position to help understand how to diagnose and treat this condition,” says Peter A. Nigrovic, MD, a rheumatologist who treats both adults and children at Brigham and Women's Hospital in Boston as well as Boston Children’s Hospital, and an associate professor of medicine at Harvard Medical School.

This new, sometimes fatal syndrome goes by several names, but is termed multisystem inflammatory syndrome in children (MIS-C) by the Centers for Disease Control and Prevention (CDC). Some of these cases would previously have been considered atypical KD, but now are recognized as a unique syndrome that is both similar and different from KD.

Kawasaki disease is a rheumatic disease, one of the most common types of pediatric vasculitis, or blood vessel disease, found mostly in infants and preschool-age children. KD begins with fevers for five days or longer. Other signs include rash, red eyes, red cracked lips and a red swollen tongu, joint pain, an enlarged lymph node on the neck and swelling of the hands and feet, sometimes with joint pain. Most children recover well with treatment, but some children develop heart dysfunction as well as long-term damage to the blood vessels of the heart caused by the high levels of inflammation.

Most children who get COVID-19 recover well, too, but a small subset experience this new syndrome. Parents of children who have a history of KD, juvenile arthritis, including systemic juvenile idiopathic arthritis, or those who are immunosuppressed due to drug treatment can rest easy for now; their children are not at increased risk for MIS-C, but more research is needed.

Some MIS-C symptoms overlap with those of KD, but patients with MIS-C can experience problems in diverse organs, including the stomach and intestines, kidney and brain. The effects differ, too. MIS-C presents more commonly with signs of cardiac inflammation. KD most frequently affects the coronary vessels, whereas MIS-C more commonly presents with a weakened heart muscle.

There are other key differences. Sivi Lapidus, MD, a pediatric rheumatologist at the Joseph M. Sanzari Children’s Hospital in Hackensack, New Jersey, has seen multiple patients with MIS-C. Unlike KD, MIS-C patients include children of all ages, up to 21 years old, says Dr. Lapidus, who leads the medical center’s MIS-C task force.

Dr. Nigrovic describes what is perhaps the most notable difference. “It’s surprising that in MIS-C, otherwise healthy children experience a hyperinflammatory syndrome sometimes called a cytokine storm,” he says. Cytokines are chemicals that communicate with the immune system. A cytokine storm occurs when those chemicals flood the system, leading to a general immune overactivation. In KD, only some children experience a cytokine storm – a serious, potentially fatal medical state that can lead to shock – but it’s more common in MIS-C.

He adds that children with MIS-C often – but not always – test positive for COVID-19 antibodies, indicating previous infection, sometimes four to six weeks prior.

Dr. Lapidus, an assistant professor of pediatrics at Hackensack Meridian School of Medicine at Seton Hall University in New Jersey, says that may explain the sudden and dramatic increase in cases of MIS-C right now. COVID-19 was spreading rapidly in Italy, the U.S. and the U.K. about that long ago.

Dr. Nigrovic adds that a nasal swab test does not always show that children with MIS-C are positive for the COVID-19 virus. In fact, many test positive only for COVID-19 antibodies, indicating an infection in the recent past. As a result, one theory is that MIS-C is not triggered by the virus itself but by the body’s reaction to the virus.

A successful recovery from MIS-C begins with early recognition. All parents, regardless of their child’s KD or COVID-19 history, should be vigilant for signs of MIS-C, such as a high fever for more than a few days, poor eating or drinking, reduced urine output, difficulty breathing, fatigue and/or general appearance of illness. Parents should immediately seek emergency evaluation. Specialists in the evaluation of sick children are now on high alert for MIS-C as a cause.  

Doctors are working quickly to sort out the similarities and differences between MIS-C and KD to find effective treatment. Doctors world-wide are recording cases of COVID-19 and MIS-C in registries, both local and global. Dr. Nigrovic is working with international colleagues to share and discuss cases in search of insights. The Arthritis Foundation is the major sponsor of the Childhood Arthritis Research and Rheumatology Alliance (CARRA), which has initiated its own registry to understand the impact off COVID-19 in children with juvenile arthritis and other rheumatic diseases.

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