Kawasaki rash or Kawasaki disease causes heart diseases in young children. Kawasaki disease in adults may also be fatal if not treated in time.

Kawasaki Disease

Humza Khizer

Overview

Acute febrile illness with no known etiology, Kawasaki disease (KD), often known as Kawasaki syndrome, predominantly affects children under five. 
&nbsp;

Tomisaku Kawasaki first identified the disease in Japan in 1967 and the first instances outside Japan were noted in Hawaii

The illness certainly isn&#39;t contagious, but it can occasionally occur in a community in clusters. Children are more prone to developing the disease in the winter and spring. Small to medium-sized arteries (e.g.,&nbsp;<a href="https://www.merisehat.pk/disease/coronary-artery-disease" target="_blank">coronary arteries</a>) that transport blood throughout the body become swollen (inflamed) in children with Kawasaki disease.&nbsp;

A population-based study reported an incidence rate of 67.3 in the age groups of less than 5 years<a href="#accordion">[1]</a>. Interestingly the incidence rates of KD were low in age groups above 5 (5.75-0.26/per 100,000 for age groups between 5-20 years)<a href="#accordion">[1]</a>. Future projections for 2030 suggest an annual incidence of 725 new KD patients with a KD population of 35,00<a href="#accordion">[6]</a>. It has also been predicted that in 2030, 1,469 of these KD patients will need medical care for coronary complications.

It is also important to note that boys are affected more than girls by a ratio of 1.5:12. 
&nbsp;

There are two main types - complete Kawasaki disease and incomplete Kawasaki disease.

&nbsp;

<ul>
	<li>
	<h5>Complete Kawasaki Disease</h5>
	</li>
</ul>

A complete case of Kawasaki disease is defined as the presence of a fever for at least five days along with at least 4 of the 5 following symptoms:

<ol>
	<li>Changes in the extremities</li>
	<li>Conjunctival injection</li>
	<li>Erythema of oral mucosa and lips</li>
	<li>Exanthem</li>
	<li>Cervical lymphadenopathy, with at least one node of 1.5 cm diameter or more</li>
</ol>

&nbsp;

<ul>
	<li>
	<h5>Incomplete Kawasaki Disease</h5>
	</li>
</ul>

Incomplete Kawasaki disease (KD) affects patients with a five-day or more extended fever and 2-3 of the 5 characteristic symptoms (exanthem, conjunctival injection, changes in the extremities, erythema of oral mucosa and lips, cervical lymphadenopathy). 
&nbsp;

Challenges In Incomplete Kawasaki Disease

In a clinical setting diagnosing incomplete KD can be quite challenging and the search for additional criteria or consideration of additional symptoms is still ongoing. For e.g., a French study compared certain clinical ( including echocardiographic coronary artery abnormalities) and laboratory features of patients with complete and incomplete KD to assess additional criteria that support a suspicion of KD.&nbsp;

Pediatric patients with complete KD displayed significantly higher rates of changes in the extremities, conjunctival injection, exanthem, and higher serum levels of alanine aminotransferase and gamma-glutamyl transferase compared to the incomplete KD group<a href="#accordion">[3]</a>. However, the most interesting finding was the significantly lower rate of coronary artery dilation in the complete KD group (48.7%) compared to the incomplete KD group (90%).&nbsp;

Furthermore, the incomplete KD group displayed certain other features such as acute anterior uveitis or unexplained pyuria<a href="#accordion">[3]</a>.&nbsp;

The findings of the study indicate that both types of KD carry a risk of coronary artery disease, while also highlighting the need to consider additional features to the principal criteria of diagnosing incomplete KD. The challenging nature of incomplete KD may be made easy by consideration of other symptoms such as uveitis and unexplained pyuria<a href="#accordion">[3]</a>.&nbsp; 
&nbsp;

<h5>Phases Of Kawasaki Disease</h5>

Three clinical phases comprise Kawasaki disease&#39;s course: acute, subacute, and convalescent.

&nbsp;

<ul>
	<li>
	Acute Phase: The acute febrile period typically lasts seven to fourteen days. Conjunctival injection, mouth and lip alterations, swelling and erythema of the hands and feet, rash, and cervical lymphadenopathy are the main features of this phase. The acute phase typically ends when the fever goes away.
	</li>
</ul>

&nbsp;

<ul>
	<li>
	Sub-Acute Phase:&nbsp;The sub-acute phase lasts from when the fever stops until around day 25. During this phase, patients may experience thrombocytosis, <a href="https://www.merisehat.pk/disease/arthritis" target="_blank">arthritis</a>, desquamation of the fingers and toes, and arthralgia.
	</li>
</ul>

&nbsp;

<ul>
	<li>
	Convalescent Phase:&nbsp;The convalescent phase begins six to eight weeks after the onset of the illness. It typically starts when the clinical symptoms go away, and lasts until the erythrocyte sedimentation rate returns to normal.
	</li>
</ul>

<div>&nbsp;</div>

Signs And Symptoms

&nbsp;

<ul>
	<li>
	<h5>Early Stages</h5>
	</li>
</ul>

A child typically needs at least four of the following symptoms plus a temperature of 102.2&deg;F (39&deg;C) for at least five or more days in order to be diagnosed with Kawasaki disease. They are:

<ol>
	<li>A rash across the body or near the genitalia</li>
	<li>An enlarged neck lymph node&nbsp;</li>
	<li>Extremely Red eyes without any thick discharge</li>
	<li>Red and swollen tongue (strawberry tongue)&nbsp;</li>
	<li>Cracked, red, dry lips</li>
	<li>The skin on the palms of the hands and the bottoms of the feet are swollen&nbsp;and red, and subsequently begin to peel</li>
</ol>

&nbsp;

<ul>
	<li>
	<h5>Late Stages</h5>
	</li>
</ul>

Late-stage symptoms start to appear, mainly within 2 weeks. A child&#39;s hands and feet may peel and flake off in sheets.&nbsp;

&nbsp;

Other indications and symptoms are

<ol>
	<li>Abdominal pain</li>
	<li>Vomiting</li>
	<li>Diarrhea</li>
	<li>Irritability</li>
	<li>Joint pain</li>
</ol>

&nbsp;

The third phase of symptoms usually involves delayed remission. It might persist for as long as eight weeks.

&nbsp;

Note: Call your doctor if your kid exhibits any of these signs, including a fever of 101-103&deg;F that continues for more than four days. Early intervention can reduce the likelihood of long-term consequences. 
&nbsp;

Causes

Although the exact cause of Kawasaki disease is unknown, specific genes inherited from their parents may increase a child&rsquo;s risk of developing the condition.

&nbsp;

<ul>
	<li>
	<h5>Infection</h5>
	</li>
</ul>

Kawasaki disease&#39;s symptoms resemble a bacterial or viral infection, however, no bacterial or viral cause has been found thus far. Also, the non-contagious nature of the disease is indicative of the lack of viral causative factors. Children of any age can develop Kawasaki disease. However, children under the age of one may experience more severity.

&nbsp;

<ul>
	<li>
	<h5>Genes Inherited From Parents</h5>
	</li>
</ul>

A genetic predisposition to Kawasaki illness may exist in children who acquire the condition. They are usually more likely to develop the disease due to the genes they receive from their parents.

According to one theory, Kawasaki disease may not be caused by a single gene, but rather by several genes, each of which slightly increases the likelihood that a kid would be affected.

Children from northeast Asia, particularly Japan, and Korea, are more likely to have Kawasaki disease, which adds to the possibility of genetic causes. 
&nbsp;

Diagnosis

A thorough clinical examination, a thorough patient history, and the identification of characteristic symptoms (described earlier e.g. strawberry tongue) are used to diagnose Kawasaki syndrome.

Kawasaki disease has no specific test to date and since the disease resembles many others in symptoms, doctors usually run tests to rule out other conditions listed below:&nbsp;

&nbsp;

<ul>
	<li>Scarlet Fever&nbsp;- A&nbsp;bacterial infection characterized by a pink rash along with fever, chills, and sore throat</li>
	<li>Rocky Mountain Spotted Fever&nbsp;- A disease spread by ticks&nbsp;</li>
	<li>Glandular Fever -&nbsp;Viral infection with fever and swollen lymph nodes</li>
	<li>Toxic Shock Syndrome - A rare but life-threatening bacterial infection</li>
	<li>Juvenile <a href="https://merisehat.pk/disease/rheumatoid-arthritis">Rheumatoid Arthritis</a>&nbsp;- A&nbsp;chronic condition that damages joints and produces pain and swelling</li>
	<li>Measles -&nbsp;An infectious viral disease with distinct spots that are usually red-brown in color</li>
	<li>Idiopathic Juvenile <a href="https://www.merisehat.pk/disease/arthritis">Arthritis</a></li>
	<li>Juvenile Mercury Poisoning - Indicated by some case reports</li>
	<li>Stevens-Johnson Syndrome -&nbsp;Severe allergic reaction to medications</li>
	<li><a href="https://www.merisehat.pk/disease/viral-meningitis" target="_blank">Viral Meningitis</a>&nbsp;- A viral infection of the spinal cord or brain&rsquo;s protective membranes&nbsp;</li>
	<li>Lupus -&nbsp;An autoimmune disease that can cause fatigue, joint discomfort, and a rash</li>
</ul>

&nbsp;

The following tests can be performed to support the diagnosis of Kawasaki disease:

<ul>
	<li>Urine Sample - To check for the presence of white blood cells</li>
	<li>Lumbar Puncture - This involves the insertion of a needle between the lower spine&#39;s vertebrae to get a sample of the cerebrospinal fluid</li>
	<li>Blood Tests - To check for anemia (decreased red blood cell count), increased white blood cell count and markers of inflammation These can all occur with KD.</li>
</ul>

&nbsp;

A pediatrician may request additional tests to form a definitive diagnosis and also to examine the disease&#39;s impact on the heart. These may consist of:

&nbsp;

<ul>
	<li>
	Echocardiography -&nbsp;&nbsp;An echocardiograph produces images of the heart as well as its arteries. Since the coronary arteries are impacted in KD, an echo is done to see the damage to the vessels. This test needs to be repeated over time to see if the damage has worsened. This test can also help identify any structural or functional issues in the heart as well.&nbsp;
	</li>
	<li>
	Blood Tests -&nbsp;&nbsp;To rule out other illnesses, additional blood testing may be required.
	</li>
	<li>
	Electrocardiogram -&nbsp;&nbsp;KD can cause heart rhythm problems, hence an electrocardiogram or ECG which captures the heart&#39;s electrical activity, can easily reveal any abnormalities in rhythm.&nbsp;
	</li>
	<li>
	Chest X-ray -&nbsp;&nbsp;A chest X-ray can help doctors check for inflammation and heart failure symptoms.
	</li>
</ul>

<div>&nbsp;</div>

Treatment

KD is treated in hospitals due to the possibility of serious complications associated with the disease. It is advisable to commence treatment promptly and preferably when the child still has a fever.&nbsp;Delayed treatment increases the risk of long-term complications and also lengthens the recovery time.&nbsp;

&nbsp;

The two primary Kawasaki disease therapies are intravenous immunoglobulin and aspirin.

&nbsp;

<h5>1. Aspirin</h5>

Aspirin belongs to the class of non-steroidal anti-inflammatory drugs (NSAID). It&#39;s the choice of drug to treat Kawasaki disease because

<ul>
	<li>It can reduce discomfort and pain</li>
	<li>It can assist in lowering fever</li>
	<li>It has an anti-inflammatory effect when used in large amounts (it reduces swelling)</li>
	<li>At small doses, it acts as an ant-platelet agent (prevents blood clotting)</li>
</ul>

&nbsp;

Depending on your child&#39;s symptoms, a doctor will advise you on the dosage and duration of aspirin treatment. They&#39;ll probably receive aspirin at a high dosage until their temperature drops. After that, for up to 6 to 8 weeks following the onset of their symptoms, low-dose aspirin may be recommended. This will lessen the risk of blood clots in the vessels supplying blood to the heart.

Note: Treating KD is one of the few times doctors will prescribe aspirin to children under 16 years. Due to the risk of Reye&rsquo;s syndrome, aspirin should not be offered to any child unless a doctor recommends it.

&nbsp;

<h5>2. Intravenous Immunoglobulin (IVIG)</h5>

The immune system creates antibodies, which are proteins, to combat pathogen-carrying organisms. IVIG refers to a mixture of antibodies obtained from healthy donors and is administered intravenously.&nbsp;

According to research, IVIG lowers the risk of coronary artery issues and reduces inflammation of the vessels. Within 36 hours of receiving IVIG, your child&#39;s symptoms ought to start to get better. They might receive a second IVIG dosage if their elevated temperature doesn&#39;t subside after 36 hours.

Gamma globulin is the immunoglobulin used to treat Kawasaki disease.

&nbsp;

<h5>3. Corticosteroids</h5>

Corticosteroids might be suggested if IVIG treatment hasn&#39;t been effective or if it&#39;s determined that your child has a higher risk of developing heart issues. 
&nbsp;

<h5>After Your Child Goes Home</h5>

A child may experience fatigue and irritability for several weeks before returning to normal. Recovery usually takes six to eight weeks or longer. The physician will advise you:

&nbsp;

<ul>
	<li>Take your child&#39;s temperature every day for three days after being discharged from the hospital.</li>
	<li>Give the aspirin as directed. Your child must continue taking aspirin for at least six weeks after returning home. Aspirin isn&rsquo;t typically administered to kids, but it is necessary and beneficial in this situation.&nbsp;</li>
	<li>Taking aspirin with meals or a glass of milk could help prevent aspirin side effects, including a stomach ache or burning sensation.</li>
	<li>Without first seeing a doctor, avoid giving your child any more medications.</li>
	<li>Ensure your child drinks enough water (at least three glasses a day).</li>
	<li>Apply Vaseline&nbsp;to dry lips, and odorless lotions or creams to dry skin.</li>
	<li>Please schedule appointments with a cardiologist as cardiac-related complications are common in children with KD.&nbsp;</li>
	<li>Additional activities are typically permitted after the initial follow-up visit i.e. two weeks after being discharged from the hospital.&nbsp;</li>
	<li>In some cases, a week after being released from the hospital, your child may be allowed to return to school or daycare.</li>
</ul>

&nbsp;

<h5>Important!</h5>

<ul>
	<li>If your child develops flu or chickenpox during treatment, please contact your healthcare provider immediately as it is likely that aspirin treatment will be stopped.&nbsp;</li>
	<li>Please wait 11 months to get a live vaccine ( e.g. chicken pox, <a href="https://merisehat.pk/disease/measles">measles</a>,&nbsp;etc.) administered to your child after treatment with gamma globulin.&nbsp;</li>
	<li>Aspirin Side Effects - Since aspirin in children (under 16 ) can cause <a href="https://www.merisehat.pk/disease/reyes-syndrome" target="_blank">Reye&#39;s syndrome</a>, it is generally not recommended for treatment in young children. Reye&#39;s syndrome is a rare side effect but it can cause severe liver and brain damage. It can also cause death in some cases. It is characterized by continuous vomiting and low energy and if your child exhibits any of these symptoms, get medical attention immediately.</li>
</ul>

<div>&nbsp;</div>

The majority of kids with Kawasaki disease recuperate entirely with proper treatment. But problems can occasionally arise. Heart-related issues make up the majority of Kawasaki disease consequences. They occur due to the condition&#39;s inflammatory action on the blood vessels. Sometimes, this can impact vessels outside the heart.

&nbsp;

<h5><a href="https://www.merisehat.pk/disease/aortic-aneurysm" target="_blank">Aneurysm</a></h5>

Inflammation in the blood vessels that supply the heart (coronary arteries) can cause a portion or portions of the arterial walls to weaken. As the blood travels through the vessels, the blood pressure causes the artery wall&#39;s weak spot to swell outward. This is known as an aneurysm.

&nbsp;

This may result in:

<ul>
	<li>A <a href="https://www.merisehat.pk/disease/myocardial-infarction" target="_blank">heart attack</a>, where a portion of the heart muscle dies from oxygen deprivation</li>
	<li>A heart disease due to blocked or interrupted blood supply to the heart</li>
</ul>

&nbsp;

Rarely, the aneurysm may rupture, leading to severe internal bleeding, which requires immediate medical attention.

It&#39;s also likely that other significant arteries, for example, the femoral artery in the upper thigh or even the brachial artery in the upper arm, will be impacted.&nbsp;

Some aneurysms gradually disappear on their own. However, some kids can develop some additional complications necessitating specialist follow-ups and interventions.&nbsp; 
&nbsp;

<h5>Risk Of Complications</h5>

Heart-related complications occur for 1 in 4 children with Kawasaki disease. This is likely attributable to misdiagnosis and hence lack of treatment. These heart-related complications can be fatal in 2-3% of cases that go untreated and this risk is higher for children under age<a href="#accordion">[1]</a>.&nbsp;&nbsp;

IVIG treatment is hence essential as it has been seen that children who receive intravenous immunoglobulin treatment have less chance of developing complications.&nbsp; 
&nbsp;

<h5>Treatment Of Complications</h5>

If your kid develops a significant cardiac condition due to KD, they might need medication or surgery.&nbsp;Treatment options include:

<ul>
	<li>If your child&#39;s arteries are highly inflamed, anticoagulant and antiplatelet medications can help them avoid a heart attack by preventing blood clots.</li>
	<li>Heart artery bypass graft: a procedure to reroute blood around constrictions in the arteries. This helps ensure a healthy supply of blood and oxygen to the heart.</li>
	<li>Coronary angioplasty is a technique to open up restricted or blocked coronary arteries, improving blood flow to the heart. Occasionally, a stent is placed into the obstructed artery to keep it open.</li>
</ul>

Note: Children with severe complications may have permanent damage to their heart muscles or valves, and hence require frequent cardiology consultations.&nbsp; 
&nbsp;

<h5>Complications In Later Life</h5>

Your child is more likely to experience cardiovascular problems later in life if they have experienced heart-related issues (heart failure and/or heart diseases) due to Kawasaki disease.

It&#39;s crucial to schedule follow-up sessions with a cardiologist. They will provide you with advice regarding the likelihood of your child experiencing other heart-related issues in the future. 
&nbsp;

Although the illness is most likely not contagious, it occasionally occurs in communities in clusters. It affects children more frequently in the winter and spring. In addition, the following factors can increase a child&#39;s risk of Kawasaki disease:

<ul>
	<li>Age - Kids who are 5 years old or younger are typically affected.</li>
	<li>Sex - It affects boys 1.5 times more frequently than it does girls<a href="#accordion">[4]</a>.</li>
	<li>Ethnicity&nbsp; -&nbsp;&nbsp;Asian children are especially susceptible to developing Kawasaki disease.</li>
</ul>

&nbsp;

Currently, there are no recommended preventable measures against KD. 
&nbsp;

&nbsp;

<h5>1. A New Diagnostic Model To Distinguish Kawasaki Disease From Other</h5>

Cardiovascular problems can result from KD. For instance, 15&ndash;25% of children who have not received KD treatment develop coronary artery aneurysms (CAAs). These CAAs are mostly linked to myocardial ischemia and <a href="https://www.merisehat.pk/disease/coronary-artery-disease" target="_blank">coronary artery blockage</a>, which can elevate morbidity and fatality.

Management with high-dose intravenous immunoglobulin has considerably reduced the frequency of CAA formation in KD and associated morbidity and mortality (IVIG). The key to attaining the best therapy results is early diagnosis.

However, it takes a while to distinguish KD from other febrile infections, which causes delays in IVIG medication and KD diagnosis. It has been hypothesized that diagnosis after 10 days of fever will increase the prevalence of CAAs by 2.8 to 7.1 times. Patients with &quot;incomplete KD&quot; can develop CAAs.

Many other frequent pediatric infections, such as <a href="https://merisehat.pk/disease/measles" target="_blank">measles</a>, infection by echoviruses, adenoviruses, and Epstein-Barr virus (EBV), share clinical characteristics with KD. These viral infections resemble KD and exhibit many of the same mucocutaneous inflammatory symptoms.

As per the study, age, AST: ALT ratio, GGT&ndash;gamma-glutamyl transferase, PLT&ndash;platelet count test, pre-albumin, urinalysis, phosphorus, globulin, and globulin levels were independent determinants for the diagnosis of KD. In order to effectively diagnose KD and provide a foundation for a diagnostic test, the researchers created a new model, using these parameters, with high sensitivity and accuracy for the early detection of KD. Further studies are required prior to the incorporation of these parameters in routine clinical testing<a href="#accordion">[5]</a>.

&nbsp;

<h5>2. Kawasaki Disease And<a href="https://www.merisehat.pk/disease/covid-19" target="_blank"> COVID-19</a></h5>

Throughout the early months of the <a href="https://www.merisehat.pk/disease/covid-19" target="_blank">COVID-19</a> pandemic, incidences of a disease that resembled KD sharply increased.

For instance, in 2020 the United Kingdom reported eight kids who spent a total of 10 days in the hospital for symptoms resembling Kawasaki disease or other disorders. This amount was deemed &quot;unprecedented&quot; by researchers<a href="#accordion">[6]</a>.

A further 2020 French study analyzed Kawasaki disease cases on a monthly basis from December 2005 to mid-May 2020. Scientists found that hospital admissions rose by 497% in April 2020, relative to the prior months, coinciding with the<a href="https://www.merisehat.pk/disease/covid-19" target="_blank"> COVID-19</a> pandemic&#39;s peak<a href="#accordion">[7]</a>. Furthermore, coronavirus infections were found in 80% of hospitalized individuals<a href="#accordion">[7]</a>.&nbsp;

An increase in instances of a severe type of Kawasaki illness during the early months of the COVID-19 pandemic was also reported in a 2020 study from Italy. However, according to other studies, hospital admission rates for Kawasaki disease throughout the COVID-19 era were either steady or declining<a href="#accordion">[8]</a>.

&nbsp;

<h5>3. NT-proBNP As A Biomarker For Early Detection For Predicting Coronary Artery Lesion Of Kawasaki Disease</h5>

Till date, there is no single useful biomarker for detecting Coronary artery lesion (CAL) caused by Kawasaki disease (KD). CAL&nbsp; is currently the most common acquired heart disease in children in many countries. and recently some studies have highlighted the utility of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a biomarker to predict CAL. Further studies are needed to establish its diagnostic value 
&nbsp;

Key Points

<ul>
	<li>KD is a well-known autoinflammatory pediatric illness that has recently been receiving more attention, especially in Asia. It is characterized by an inflammation of small to medium-sized arteries, with coronary arteries being most frequently affected</li>
	<li>There are 2 types: incomplete and complete KD</li>
	<li>There are 3 phases of the disease: acute, subacute and convalescent</li>
	<li>KD is more common in children under 5.</li>
	<li>The disease affects boys more than girls&nbsp;</li>
	<li>The most feared complication includes heart related issues, hence prompt treatment is recommended.&nbsp;</li>
	<li>Treatment includes aspirin and intravenous immunoglobulin (IVIG)</li>
	<li>Early administration of IVIG can lower morbidity and death</li>
	<li>Children with severe complications may have permanent damage to their heart muscles or valves, and hence will require frequent cardiology consultations</li>
	<li>Some studies have highlighted the utility of NT-proBNP as a biomarker for early detection for predicting coronary artery lesion of Kawasaki disease</li>
</ul>

<div>&nbsp;</div>

[1] Huang S-K, Lin M-T, Chen H-C, Huang S-C, Wu M-H. Epidemiology of Kawasaki disease: prevalence from national database and future trends projection by system dynamics modeling. J Pediatr. 2013;163(1):126–31.

[2] Diagnostic guidelines for kawasaki disease. Circulation. 2001;103(2):335-336.

[3] Perrin L, Letierce A, Guitton C, Tran TA, Lambert V, Koné-Paut I. Comparative study of complete versus incomplete Kawasaki disease in 59 pediatric patients. Joint Bone Spine. 2009;76(5):481-485.

[4] Kawasaki Disease. NHS choices.

[5] Huang Z, Tan X-H, Wang H, Pan B, Lv T-W, Tian J. A New Diagnostic Model to Distinguish Kawasaki Disease From Other Febrile Illnesses in Chongqing: A Retrospective Study on 10,367 Patients. Front Pediatr. 2020;8:533759

[6] Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395(10237):1607–8.

[7] Ouldali N, Pouletty M, Mariani P, Beyler C, Blachier A, Bonacorsi S, et al. Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of  the French COVID-19 epidemic: a time-series analysis. Lancet Child Adolesc Heal. 2020 Sep;4(9):662–8.

[8] Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the  SARS-CoV-2 epidemic: an observational cohort study. Lancet (London, England). 2020 Jun;395(10239):1771–8