Multisystem Inflammatory Syndrome in Children

As the world struggles to find ways for a reverse surge from coronavirus, we are focused on numerous things. This includes a plateauing numbers of cases, declining deaths, reopening society and increasing knowledge about the disease.

We as a nation have been able to flatten the curve to ensure that we provided excellent care to those who needed it and did not have to ration any type of treatment. Although our nation's health care system has been criticized for its expense for decades, when the chips were down, with the help of society sheltering in place, it functioned preeminently, ensuring that we cared for all those who needed help.

In this next phase, however, we continue to be confronted with an almost staggering impact on the economy, along with the clinical aspects of a virus that seems to keep evolving. For example, although children were spared a bit of a direct hit in the first presentation of the disease, it seems they may not be so fortunate in the next phase.

[See: Coronavirus Prevention Steps That Do or Do Not Work. ]

A newly recognized diagnosis of multisystem inflammatory syndrome in children (MIS-C) is now taking its toll on the pediatric patients in our nation. There are more than 140 cases in New York City alone, which for weeks was the epicenter of COVID-19 activity in our country. However, MIS-C has also been recognized in about half of the states, and numbers continue to grow. The international stage hasn't been spared, either, with multiple other nations reporting the same phenomenon.

MIS-C looks somewhat familiar to our pediatric infectious disease doctors and rheumatologists. It very closely resembles an illness known as Kawasaki disease that was first described by Dr. Tomisaku Kawasaki in 1974. Although the exact cause is unknown, it's suspected to be related to an infection of some kind -- but in more than four decades, no obvious germ has been identified. Whatever is the trigger, a hyper-exaggerated immune response is kicked off in the body, causing inflammation of blood vessels and organs, and making children extremely ill. The disease has been an enigma, sickening about 20,000 kids in total across the country each year.

Recently, however, pediatricians started reporting an increase in Kawasaki-like cases across the country. On further review, despite several shared features, this has been determined to likely be related to COVID-19 infection in some way. Although the majority of children have shown positive tests for the virus or its antibodies, the rate has not been 100%, and many of those kids had no COVID-19 history that they were aware of. This is not unusual, as many children have had COVID-19 without symptoms overt enough to be recognized.

The features of MIS-C include signs that the blood vessels and organs are irritated or inflamed. These include:

-- Prolonged fever, which is defined as a temperature of at least 100.4 degrees Fahrenheit or more daily.

-- Rash over the body.

-- Red eyes without pus draining, which is known as non-purulent conjunctivitis.

-- Swollen glands or lymph nodes in the neck.

-- Red cracked lips.

-- GI symptoms.

-- Swollen hands and feet.

Not everyone will have all the symptoms or have them all at the same time, making the diagnosis slightly difficult. A good review of fever history and timeline of symptoms can be helpful. Plus, some patients might have one or two of these symptoms without meeting the definition of MIS-C. Many viral illnesses, for example, will cause a rash known as a viral exanthem, but not the extreme inflammatory response.

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Internally, organs and blood vessels are also inflamed with MIS-C. These can cause more serious complications, including changes to the muscle of the heart and arteries. This can lead to weakening in the walls, allowing aneurysms or outpouching of the blood vessels, as well as weakness in the heart muscle that makes it harder to pump the necessary blood flow. These complications have been well-described with Kawasaki disease, and are seen in selected cases of MIS-C. Laboratory tests will show increased levels of inflammation in various organs of the body, not directly confirming a diagnosis but adding supportive data to the obvious symptoms.

There are very effective treatments for Kawasaki disease that can reverse the heart disease that used to be common in these patients. Treatment can also be applied to MIS-C -- something to celebrate in the world of medicine.

The MIS-C definition only applies to children who are under 21 years of age. We don't diagnose Kawasaki disease much outside grade school-age, so this fits with the theory that these two diseases are related. The illness may also be on a spectrum of disease and related to some of the sickest presentations of COVID-19 in adults. Many older patients have shown a hyper-exaggerated inflammatory response in their lungs and heart failure. Could it be that these are related to what we're now seeing in children?

MIS-C may be a direct effect of COVID-19, but it's possible that it represents a post-viral event, which is a well-described phenomenon in the child patient. There are many symptom complexes that may show up in a child two to even 12 weeks after a seemingly mild viral illness. Most resolve with therapy, leaving little injury behind. This might mean we are just beginning to see the effects of COVID-19 in children.

[See: What Are the Symptoms of Coronavirus?]

While we prepare for reverse surge, we need to include vigilance not only for the presentations of COVID-19 that have already been seen, but for different symptoms or associated post-viral illnesses. If recognized early and treated, we can minimize their long-term impact on children's health. Is MIS-C merely the first of such aftershocks from the initial surge? Is it just one more mystery of this pandemic? Add this speculation to the still unknowns about how the human body fights disease and infection, and you realize just how much we don't know in health care. And yet, we fight on -- and so far at least, we have fared as well as possible in the face of battle.

In this next phase, we may need to bring different battle plans and weapons, and they may be expensive. But perhaps that's the price for a premiere health care system that functions when we need it.

Dr. Elaine Cox is the Chief Medical Officer of Riley Children's Health in Indianapolis. She is also the Riley clinical safety officer. Dr. Cox practices as a pediatric infectious disease specialist and also instructs students as a professor of clinical pediatrics at the Indiana University School of Medicine. The former director of the pediatric HIV and AIDS program, Ryan White Center for Pediatric Infectious Diseases at Riley, Dr. Cox helped lead the effort to change Indiana law to provide universal HIV testing for expectant mothers.