Kawasaki syndrome and Covid-19: what we really know

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Philippe Gloaguen
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In the last few days we have been hearing a lot about a possible association between syndrome in Kawasaki (but many experts prefer to simply call it Kawasaki disease) and infection with SARS-CoV-2. And there was also talk of a possible association between the infection and the so-called pediatric multisystem inflammatory syndrome. But what do we really know about the relationship between the virus and Kawasaki disease? And what is the relationship between this disease and the inflammatory syndrome?

We asked the professor Angelo Ravelli, head of the pediatric clinic and rheumatology unit of the Gaslini Institute of Genoa and secretary of the rheumatology study group of the Del Paesena Society of pediatrics - the first to notice in Del Paese an anomalous increase in cases of manifestations similar to those of the disease Kawasaki - to help us shed some light on the matter.

In this article

  • what is Kawasaki syndrome
  • who it affects and how frequent it is
  • what are the symptoms
  • the possible risks
  • how to diagnose
  • how do you care
  • the causes
  • link between Kawasaki disease and coronavirus
  • relationship between Kawasaki syndrome and multisystem inflammatory syndrome
  • how much do we have to worry about
  • when to call the pediatrician
  • how to protect children

Kawasaki syndrome, what it is

"It is an acute disease characterized by systemic vasculitis, that is, from inflammation of blood vessels of the organism and in particular of the coronary arteries that supply the heart "explains Ravelli. It is a disease described for the first time in 1967 in Japan by the doctor Tomisaku Kawasaki.

Who it affects and how frequent it is

"It's a rare disease that exists only in children and typically affects children of age under five and more often under the age of two, even infants "explains Ravelli.

It is estimated that it affects one child under five for every 6500-20500 children (the differences depend on the area of ​​the world considered: in Japan and Korea it is probably more widespread due to a genetic susceptibility of the population). Ravelli indicates that in our country they occur approximately 250-400 cases each year of illness. 

What are the symptoms

"The first symptom of Kawasaki syndrome is one persistent high fever, which tends not to pass with the municipalities antifebriles such as paracetamol and ibuprofen and lasts more than four to five days ". The fever is accompanied by a series of other signs which, although not specific to the disease (that is, they can also be present in other conditions) are nonetheless characteristic. These are:

  • bilateral redness of the eyes (bilateral conjunctivitis);
  • enlarged lymph nodes on the sides of the jaw (often one-sided);
  • marked chapping of the lips;
  • redness of the oral cavity, pharynx and throat, with raspberry or strawberry tongue (very red and with small swellings);
  • edema (swelling) of the hands and feet;
  • skin rash on the trunk and limbs, similar to that of measles.

"While it's not a major symptom, it can also be there mood change, with generally quiet children becoming a lot nervous and irritable"Ravelli said.

Read also: Fever of unknown origin: what it is, how to behave

Kawasaki syndrome, the possible risks

"Kawasaki syndrome can heal on its own within two to three weeks but if not treated promptly and adequately there is a risk that it leads to the development of coronary aneurysms, which could cause myocardial infarctions, "says Ravelli.

How is the diagnosis made

The diagnosis is made based on symptoms (which may not even be present all at the same time). "In cases that clearly express all the symptoms described, the diagnosis is quite simple for any pediatrician" says Ravelli, underlining that there may be some more difficulties if the manifestations are incomplete, which often happens in very young children, under six months. . "In these cases there may be only fever and skin rash, or fever and conjunctivitis."

If Kawasaki disease is diagnosed, aechocardiography to diagnose the main complications affecting the coronary arteries.

How to cure

Kawasaki disease therapy is performed in the hospital and provides intravenous infusion of immunoglobulins at high dosage. "These are human nonspecific antibodies derived from a pool of donors that exert a protective role against the arteries" explains the specialist. Immunoglobulins are associated withaspirin initially at full dosage, which has an adjuvant effect in relieving symptoms such as fever and general inflammation. "Once the acute phase is over, the aspirin is continued at a low dose, antiplatelet, as long as any aneurysms persist".

The aneurysms that can be caused by the disease tend to resolve on their own over time, if they are small in size, but waiting for this to happen and if they are larger in size it is necessary to continue with the antiplatelet therapy with aspirin.

Without therapy, the risk of aneurysms forming is 15-25%, while with therapy it drops below 5%. 

What do we know about the causes

The precise cause remains unknown. "It is thought that it may have an infectious origin, both because the typical symptoms closely resemble those of known infections such as measles, rubella and scarlet fever, and because in the past they have been possible relationships with some infections by bacteria and viruses identified, including a coronavirus (different from the Sars-Cov-2 in circulation today), even if there has never been a definitive confirmation "explains Ravelli.

This is why there is so much interest in the possible association between Kawasaki disease - and its atypical forms that have occurred around this time - and the coronavirus responsible for Covid-19.

"In any case, the most accredited hypothesis at the moment is that it is not so much an infectious agent that causes the disease in itself, but a abnormal immune reaction to infection by the organism, which would occur in children with a genetic predisposition to react in that way. "The cause, therefore, could be a combination of genetic and infectious factors.

Read also: Exanthematous diseases, symptoms and treatments

Kawasaki and coronavirus: what's the link?

On 29 April, a press release from the Gaslini Institute reported, first in Del Paese, that in the areas of the country most affected by the Sars-Cov-2 epidemic, a increased frequency of children with Kawasaki disease. "In our hospital, one of the most important Del Paeseni pediatric polyclinics, we see approximately 7-8 cases a year, while we had only observed 5 in the previous three weeks", Ravelli said. Similar reports have arrived at the rheumatology study group of the Del Paesena Society of Pediatrics, but also from abroad (in particular from the United Kingdom).

Of course, the anomaly could depend on a simple statistical effect, given that it is a rare disease, but given the ongoing pandemic, it is inevitable to ask, how the international medical and scientific community is doing, if there is a link with the coronavirus . And Ravelli is quite convinced that the link exists. "For example it has been observed that a proportion of the affected children had had a positive swab for the virus or contact with affected patients, while others have turned out positive in serological tests despite the swabs being negative ". 

At the moment, however, the topic is still under study, above all because it is not yet clear whether it is precisely Kawasaki disease or a different inflammatory syndrome. "With the second wave of coronavirus infection, as might be expected, they are emerging new cases of this multisystem syndrome very similar to Kawasaki disease"- explains Dr. Ravelli, who adds" compared to the first wave, half of the cases we record show typical manifestations of Kawasaki syndrome, while the other half have symptoms similar to Kawasaki, but with hyper-inflammatory forms that tend to involve above all the heart and which are accompanied by important gastrointestinal symptoms such as diarrhea and vomiting ".

Kawasaki syndrome and pediatric multisystem inflammatory syndrome: what is the relationship

Another point still to be clarified therefore concerns whether the one observed in children is really one real Kawasaki disease. Unfortunately, in the latter period the cases of children with Covid-19 developing one are increasing severe inflammatory condition that the World Health Organization defines PIMS-TS, while other institutions such as the American Center for Disease Control call MIS-C. The name changes, but in essence it is a pediatric multisystem inflammatory syndrome.

This multisystem inflammation that occurs following Covid-19 is causing debate in the scientific community. In fact, some scientists believe that although there is a similarity in symptoms, it would not be Kawasaki disease, while others believe that this inflammatory syndrome falls within the spectrum of Kawasaki disease.

"My hypothesis - explains Ravelli - is that it is still the same disease that in some children manifests itself with the classic form of Kawasaki syndrome, while in other children it manifests itself in a much more aggressive form. In my interpretation, however, it is a distorted Kawasaki syndrome made more aggressive by the Sars-Cov-2 virus ".

On the other hand, the researchers of the Bambino Gesù Children's Hospital of the city and the Karolinska Institute in Stockholm have a different opinion, who recently published a study in which they affirm that the mysterious disease is precisely the pediatric multisystem inflammatory syndrome (MIS-C) and not the Kawasaki disease, although i symptoms are similar.

In fact, in some centers - both in the country and abroad - it has been seen that a part of the affected children present a clinical picture that is not typical of Kawasaki disease.

For example they are affected children and young people even over the age of six, which may also present abdominal pain, vomiting and diarrhea, while the characteristic raspberry tongue, conjunctivitis and swollen lymph nodes in the neck may be absent. Also, there may be an evolutionary trend towards one toxic shock syndrome, which in some rare cases required hospitalization in intensive care. 

We will therefore have to wait for more in-depth studies to better understand the link between the new coronavirus and these two pathologies, but in the meantime Ravelli reassures "also in more severe cases all the children have been treated and are now well. There nucleoside used - continues Ravelli - is the standard one for Kawasaki disease which consists in the administration of high dosages of immunoglobulins. If the syndrome occurs in more severe form it can be dealt with cortisone at high doses and possibly with drugs with inhibitory action of interleukin 1 if the situation is serious ".

How much do we need to worry about?

The alarm in parents is natural, but Ravelli is reassuring: "In the first place I still remember that it is a rare disease. We are not talking about an outbreak of Kawasaki disease or hyper-inflammatory syndrome, but of a few more cases than we usually observe in this time. However, the absolute numbers remain very low. Secondly there are effective therapies: none of the children affected so far have had fatal complications ".

What to do if we suspect that the child may have the syndrome

The symptoms to watch out for are the ones we talked about:

  • high fever (above 38,5 ° C) for more than four to five days, which does not respond to classical therapies;
  • conjunctivitis;
  • swollen lymph nodes in the neck;
  • swelling of the hands or feet;
  • significant cracking of the lips and raspberry or strawberry tongue;
  • abdominal pain with vomiting and diarrhea

"In the presence of any of these symptoms, as always, the first thing to do is to contact the family pediatrician, what stability to do. In case of diagnosis - or suspicion - of Kawasaki disease or hyper-inflammatory syndrome, the pediatrician will indicate admission to a specialist center, where the child will receive adequate therapy ".

How to protect children

"The measure to be implemented is to strictly follow the recommendations issued by the authorities and scientific societies for the prevention of coronavirus infection. social distancing, use of masks, hand washing", Ravelli recommends." And if abnormal symptoms occur, don't be afraid to take the baby to the hospital. Some parents fear this step for fear of getting infected, but if the condition is serious it can expose the child to even greater risks. "   

Read also: How and when to use masks in children

- Updated on 30.11.2022

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