Kawasaki Disease: What Is, Symptoms, Diagnosis, and Treatment

What Is Kawasaki Disease?

Kawasaki Disease is a febrile disease involving an acute inflammation of the arteries. When arteries become inflamed, they can weaken and stretch out. This puts them at risk of tearing or narrowing, limiting blood flow to nourish tissues and organs.

Kawasaki disease is a condition that predominantly affects children below the age of five. Fortunately, this illness typically resolves within 12 days without any lasting complications. While most children fully recover, there are instances where severe cardiac complications may arise, so it is essential to provide prompt treatment to prevent severe cardiovascular issues. Notably, Kawasaki disease was first identified by Tomisaku Kawasaki in Japan in 1967. In developed countries, it is the leading cause of acquired heart disease among children.

How Common Is It?

Kawasaki disease can be observed globally, although its prevalence varies greatly depending on the geographical location and ethnic community. The highest incidence occurs in children of Asian origin (75-85% of cases), especially in Japanese.

In the United States, the CDC estimates that the incidence of the disease is 9 to 20 per 100,000 children under five years of age.

Who Is Most At Risk?

Kawasaki disease mainly affects children aged six months to five years. The peak incidence occurs at the age of 12-18 months. In infants, the course of the disease may be atypical, which makes it more challenging to recognize and usually more severe than in older children. The disease affects boys slightly more often. Kawasaki disease in adults and children over 13 years of age occurs very rarely.

Causes

The causes of the disease are still unknown. It is assumed that in genetically predisposed people, there is an abnormal response of the immune system to antigens of infectious agents (e.g., bacteria or viruses, but also to environmental factors).

This causes infiltration of the blood vessel walls by inflammatory immune system cells, which may destroy the vessel walls. The disease process may affect any tissue or organ. Often, the patient is diagnosed with a recent upper respiratory tract infection before symptoms appear.

Is Kawasaki Disease Contagious?

Kawasaki disease is not contagious because bacteria, viruses, or parasites do not cause it. Although the symptoms of the disease may resemble those of infectious diseases, it certainly cannot infect others.

Risk Factors

Three known factors increase the risk of developing Kawasaki disease:

• Age – children under five years of age
• Gender – boys are more likely to become ill than girls
• Ethnicity – children of Asian origin or living in Japan or Korea are more likely to suffer from Kawasaki disease

Symptoms

Kawasaki disease can be divided into several phases:

• Acute phase
• Subacute phase
• Convalescent phase

Acute Phase

The acute phase lasts 1 to 2 weeks. The main symptoms include:

• Fever – usually begins with a high fever of up to 40 degrees Celsius. The fever recurs after antipyretic drugs and does not respond to antibiotics. Without appropriate therapy, it lasts on average 11 days but may last up to 3-4 weeks.
• Conjunctival injection – The fever may be accompanied by conjunctival redness in both eyes and eyelid swelling, which is usually mild and does not cause pain.
• Pharyngitis – The symptoms of pharyngitis are particularly unpleasant for a child – the mucous membrane of the throat is red and swollen.
• “Strawberry tongue” – The tongue can appear bright red, enlarged, and dotted with small bumps, often referred to as a “strawberry” tongue, similar to scarlet fever. The lips may also be swollen, red, and possibly bleeding.
• Rash – A skin irritation typically shows up on the body within 3-5 days after the fever starts. The hands and feet may be affected by erythema, and in younger children, the diaper area may also be affected. Swelling and pain of the fingers and toes may occur, making it difficult for your child to walk or crawl.
• Lymph node enlargement – Enlargement of the anterior cervical lymph nodes, usually on one side, may also be characteristic.

Inflammatory changes can affect various organs, causing symptoms of:

• Heart
• Joints (swelling, pain)
• Digestive system (diarrhea, vomiting, abdominal pain)
• Urinary system (inflammation of the urethra, testicle swelling)
• Respiratory system (cough, runny nose, pneumonia)
• Nervous system (irritability, behavioral changes, convulsions)

Subacute Phase

The subacute phase of the disease begins after the fever and other symptoms subside. Lasts approximately 2-4 weeks.

Your child may still experience symptoms such as:

• Conjunctivitis
• Abdominal pain
• Gastrointestinal symptoms (diarrhea, vomiting)
• Pus in urine
• Lack of energy and lethargy
• Joint pain
• Irritability
• Yellowing of the skin and the whites of the eyes may appear (jaundice)
• The skin on the fingers begins to peel in patches

Convalescent Phase

The recovery phase lasts approximately two weeks. During this time, the child’s well-being improves, inflammatory markers normalize, and symptoms disappear.

Patients with Kawasaki disease require long-term observation, heart tests, and assessment for the risk of developing atherosclerosis (lipid panel control).

It may be necessary to perform imaging tests to exclude disease complications. The risk of recurrence is estimated at approximately 2%, often with a similar course.

Diagnosis

The basis for diagnosing the disease is its characteristic symptoms. According to The National Institute for Health and Care Excellence (NICE), a child may be suspected of having the disease if they have a fever lasting at least five days and one additional symptom from the list:

• Conjunctival injection – the red and bloodshot whites of the eye. Inflammation and dilatation of the conjunctival blood vessels cause this symptom
• Mouth and throat symptoms – these symptoms include red, cracked, dry lips, a red tongue with white spots, the so-called “strawberry” tongue, a red and swollen throat
• Changes in hands and feet – red and swollen hands and feet, peeling of the skin of the hands and soles of the feet
• A rash that may cover different parts of the body
• Enlarged lymph nodes in the neck area

In infants, the picture of the disease may be different, without a large part of the main symptoms, compared to older children. Some symptoms might come and go through the illness duration, so it is necessary to tell the doctor if your child has experienced a sign that is not present anymore.

Tests

Symptoms of Kawasaki disease may resemble other diseases such as scarlet fever, measles, Stevens-Johnson syndrome, toxic shock syndrome, lupus, viral meningitis, and glandular fever. Therefore, doctors may need to rule them out to confirm the diagnosis.

Some tests may help confirm the diagnosis. These include:

• Blood tests – white blood cells and platelet count
• Urine test – this can show whether there is a presence of white blood cells in the urine
• Cerebrospinal fluid test – a lumbar puncture makes it possible to collect cerebrospinal fluid for testing

Heart Tests

During the acute phase of the disease, several heart symptoms may appear, such as tachycardia (when the heart beats too fast), heart inflammation (myocarditis), fluid accumulation around the heart, or coronary artery aneurysm. Also, because the most common complications of the disease involve the heart, children who have had Kawasaki disease must undergo tests to check whether the heart is functioning correctly. These tests include:

• ECG (electrocardiogram) –During an ECG examination, a unique device allows recording of the heart’s electrical activity thanks to electrodes placed on the chest and limbs. It is a non-invasive and completely painless test. The recorded information enables doctors to evaluate how the heart works and identify potential issues, such as ischemic heart disease or cardiac overgrowth.
• Echocardiogram – An echocardiogram is a medical procedure that allows doctors to examine the structures of the heart and evaluate the blood flow in the heart and large blood vessels. It is a safe and non-invasive test that can be performed multiple times without any restrictions or risks. An ultrasound examination uses high-frequency sound waves emitted by an ultrasound probe.

What Other Diseases May Resemble Kawasaki Disease?

The conditions whose symptoms are similar to Kawasaki Disease and hence might be mistaken for it include:

• Scarlet fever
• Measles
• Covid-19
• Lupus
• Toxic Shock Syndrome
• Viral meningitis
• Stevens-Johnson Syndrome
• Glandular fever

Covid-19

A multisystem inflammatory syndrome similar to Kawasaki disease has been observed in children infected with SARS-Cov-2. However, there are significant differences between these two diseases. The disorders usually occur in children of different ages. Severe gastrointestinal symptoms appear in the case of COVID-19, and there are also differences in laboratory parameters – in SARS-CoV-2, there is thrombocytopenia (low number of platelets) and a reduced number of white blood cells in blood.

Scarlet Fever

Scarlet fever is caused by a bacteria – group A Strep. Mainly, children are affected, although the disease occurs sporadically in adults. The source of the condition is the sick person.

Scarlet fever has symptoms similar to Kawasaki disease. The disease begins abruptly. Fever usually appears first and can reach up to 40 degrees Celsius. Chills and severe sore throat accompany it. Other symptoms of scarlet fever that resemble Kawasaki disease include:

• Enlarged cervical lymph nodes
• Rash
• Throat redness
• Weakness and apathy
• White coating on the tongue followed by redness (so-called strawberry tongue)

However, the diseases differ in etiology – in scarlet fever, the cause of the disease is a bacterium. In contrast, the cause of Kawasaki disease is not fully known. Also, some symptoms allow the doctors to distinguish the two conditions from each other (lesions in the hands and feet in Kawasaki disease, characteristic lack of rash around the mouth in scarlet fever).

Measles

Measles and Kawasaki disease have many shared features, such as high fever, rash, conjunctivitis, and enlarged lymph nodes. However, in the case of measles, the fever usually subsides after a few days, and there is no skin peeling on the hands and feet.

Treatment

The condition needs to be treated in the hospital because it poses a risk of serious complications. Treating Kawasaki disease quickly after its onset can significantly reduce the risk of complications – changes in arteries, as well as other severe cardiac complications that are the leading cause of death.

Treatment mainly involves:

• Immunoglobulins (proteins involved in fighting inflammation)
• Acetylsalicylic acid (aspirin)

Aspirin

Aspirin (acetylsalicylic acid) is prescribed to children with Kawasaki disease. This is a rare occasion when this medication is used in children under 16 years as using it may cause a dangerous complication – Reye’s syndrome. For this reason, you should never give your child aspirin unless the doctor specifically recommends it.

Aspirin lowers fever, reduces pain and discomfort, reduces swelling and inflammation (in large doses), and prevents the formation of clots through its antiplatelet effect (in small amounts).

In Kawasaki disease, aspirin protects the vessels supplying blood to the heart against clot formation.

Immunoglobulins

IVIG, short for Intravenous Immunoglobulins, is a therapy that involves injecting antibodies obtained from healthy individuals directly into a vein. These antibodies, known as immunoglobulins, are proteins produced by the immune system to combat harmful microorganisms like bacteria and viruses. Specifically, the treatment utilizes a subtype of immunoglobulins called gamma globulins.

In Kawasaki disease, immunoglobulins reduce fever and the risk of heart complications. After administration of immunoglobulins, the child’s condition should improve within 36 hours.

Complications

The most severe complications of the disease are changes in the cardiovascular system, such as:

• Inflammation of blood vessels, usually the coronary arteries that supply blood to the heart
• Coronary artery aneurysms
• Decreased heart contractility and arrhythmias
• Myocarditis (inflammation of the heart)
• Peripheral artery obstruction

Each of the complications can damage the child’s heart. Inflammation of the coronary arteries can weaken and bulge the artery wall, causing aneurysm. Aneurysms can raise the chances of developing blood clots, which in turn can result in a heart attack or dangerous internal bleeding.

About 25% of children with Kawasaki disease develop complications if left untreated. Children under the age of one are more susceptible to experiencing severe complications.

In a small percentage of children with coronary artery problems, Kawasaki disease can cause death, even with treatment.

Kawasaki disease is the main reason for acquired heart disease in kids. However, with effective treatment, only a few children have permanent heart damage.

Prevention

Since the disease has no known cause, it cannot be prevented. Bacteria, viruses, or parasites do not cause Kawasaki disease, so there is no way to avoid getting it.

When Should You See a Doctor?

You should consult a pediatrician if you notice symptoms that may indicate Kawasaki disease in your child, such as prolonged fever accompanied by skin lesions, conjunctivitis, or strawberry tongue.

Kawasaki disease is a rare illness that can be difficult to diagnose because its symptoms, such as fever, sore throat, and rash, are not specific and can also occur in more common conditions like the common cold or pharyngitis. However, if these symptoms are severe, last for a long time, or if the child’s condition worsens, it is important to seek immediate medical advice.

Sources

• Centers for Disease Controle and Prevention (CDC) About Kawasaki Disease (2020) https://www.cdc.gov/kawasaki/about.html
• National Health Service (NHS) Kawasaki disease (2021) https://www.nhs.uk/conditions/kawasaki-disease/
• National Library of Medicine (NIH) Angeline M. Owens; Michael C. Plewa. Kawasaki Disease (2023) https://www.ncbi.nlm.nih.gov/books/NBK537163
• Mărginean CO, Meliţ LE, Mărginean MO. The peculiarities of Kawasaki disease at the extremes of age: Two case reports. Medicine (Baltimore). 2019 Oct;98(42):e17595. doi: 10.1097/MD.0000000000017595. PMID: 31626134; PMCID: PMC6824635. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824635/
• Goswami N, Marzan K, De Oliveira E, Wagner-Lees S, Szmuszkovicz J. Recurrent Kawasaki Disease: A Case Report of Three Separate Episodes at >4-Year Intervals. Children (Basel). 2018 Nov 21;5(11):155. doi: 10.3390/children5110155. PMID: 30469337; PMCID: PMC6262567. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262567/
• Maconochie IK KAWASAKI DISEASE Archives of Disease in Childhood – Education and Practice 2004;89:ep3-ep8. https://ep.bmj.com/content/89/1/ep3