What is Kawasaki Disease?

In the 1960’s, in the Red Cross Hospital, Tokyo, Japan, paediatrician, Tomisaku Kawasaki came to a startling realisation that the number of children with unexplained fevers that were resistant to the usual antibiotics were infact victims of an alarming new disease. The disease presented itself with a unique set of signs: high fever, red lips, red eyes strawberry tongue, a bumpy rash, red palms and soles, swollen hands and feet, aching joints, swelling of the glands in the neck and loss of appetite.

The body responds with inflammation that can damage the blood vessels that supply blood to the child’s heart. The result is weakening to these arterial walls that can balloon and form aneurysms where clots can build up and this results in heart attacks and possibly even death.

The three stages of Kawasaki Disease

Kawasaki disease is selves–limited illness, which means the symptoms go away on their own. However it may take 6-8 weeks for the symptoms to resolve and the laboratory results to return to normal, and the effects on the coronary arteries can last a lifetime. The illness can be divided into three stages: acute, subacute, and convalescent phases.

The acute phase starts with fever, which lasts for at least 5 days (average of 11 days without treatment). Over the first week, the symptoms that comprise Kawasaki disease reveal themselves, but often one symptom appears as another disappears, making the diagnosis challenging, especially for children who see different physicians during the early days of their illness. An ultrasound of the heart (echocardiography or ECHO) is done at the time of diagnosis to look at the way the heart squeezes, and to get baseline measurements of the coronary arteries. Some children may have mild or moderately decreased heart output due to poor contraction of inflamed heart muscle; some may have a small amount of fluid around the heart (pericardial effusion). Very rarely, cardiac rhythm (electrical) disturbances may occur.

The subacute phase begins when the fever stops. However, many parts of the body are still affected by the disease. During this stage one of the most characteristic symptoms of the disease may be seen, peeling of the skin of the palms and soles beginning under the fingertips and toes (periungual desquamation). Joint inflammation, may also be present, usually affecting the larger weight-bearing joints in this phase. Laboratory studies reveal a high platelet count (one of the cells in the blood that helps clotting) and an increase in blood proteins that promote clotting. The sedimentation rate, a blood test that shows the overall degree of inflammation, continues to be high and anaemia (fewer red blood cells than usual) is common. Widening (dilation) or bubble formation (aneurysm) in the coronary arteries can be seen by echocardiogram in this phase.

Third is a convalescent phase: the child continues to recover and labs return to normal. Although the child is usually feeling better, coronary aneurysms may continue to enlarge, reaching their biggest size 4-6 weeks from the first day of fever.

What causes Kawasaki Disease?  

The cause of Kawasaki disease is unknown. Many believe it is related to an infection, for several reasons. First, Kawasaki disease is almost only seen in children; suggesting adults have developed an immunity to something that may be important in causing the disease. Second, outbreaks are seen in certain geographic regions, and more cases happen in the late winter and early spring. Lastly, children with acute Kawasaki disease have an appearance that is similar in some ways to children with other infectious diseases like scarlet fever, and some viruses.

However, Kawasaki disease does not spread from person to person or “catching.” No bacteria or virus has ever been proven to cause Kawasaki disease, so some experts wonder whether there might be several infections at fault.

Genes may also play a role in Kawasaki disease: 1) individuals of Japanese origin, no matter where in the world they live, are more likely to get Kawasaki disease; 2) brothers and sisters of children with Kawasaki disease are more likely than other neighbourhood children to get Kawasaki disease; and 3) some children of parents who had Kawasaki disease later have come down with the illness. Some studies have found associations between Kawasaki disease and recent carpet cleaning, and living near a body of stagnant water; but cause and effect have not been established. Kawasaki disease is also seen more commonly in children from higher socio-economic groups.

Who gets Kawasaki Disease?

 The first cases of Kawasaki disease in the United States were described in the early 1970s. Japanese children have the highest risk of this illness, but Kawasaki disease occurs in all races. Blacks have the second highest rate of occurrence, and white children follow. Eighty–five percent of cases occur in children under age 5 years, mostly in toddlers (1– to 2–year–olds). Infants often have atypical symptoms, without fulfilling diagnostic criteria; however, this age group (especially infant males) has the highest risk of developing severe coronary artery disease. Recent research has also shown more coronary artery aneurysms in children older than 6 years. Males are more likely to get the disease than females.  In Japan every year there are between 6000-7000 new cases of KD, in the USA it is estimated that the figure is between 5000-10000 and in South Africa the figures are still unknown although there are increasing number of cases reported, annually. 0.3% of children with Kawasaki disease die; almost all deaths are related to its effects on the heart.  

DIAGNOSES

What does Kawasaki Disease look like and is it diagnosed?

There is no laboratory test that can diagnose Kawasaki disease with 100% surety. Instead, we use a collection of criteria developed by Dr. Kawasaki and described by the Centres for Disease Control
(Table 1).

A child must have fever for more than 5 days plus four of five findings from the criteria on physical exam, without evidence of another disease. Lips and mouth are often bright red, as are both eyes, usually without fluid or crusting. The top layer of the tongue peels off, creating the appearance of “strawberry tongue,” which is red and glossy. Hands may be swollen and red. Kawasaki disease typically produces a rash as well, which is often worse in the groin area. There can be swollen glands (lymphadenopathy), usually one gland in the neck measuring at least 1.5 cm (normally glands are less than 0.5 cm).

There are other clinical and laboratory findings that can support the diagnosis (Table 2). Children are often extremely irritable over the course of the entire illness. Occasionally the diagnosis of Kawasaki disease is unclear and a spinal tap is done to evaluate for causes of fever; this can show mild inflammation of the spinal fluid (aseptic meningitis). One-third of patients have a temporary joint pain (arthritis), usually in the small joints initially (fingers and toes), with progression to the large weight-bearing joints (knees, wrists, elbows, hips). Many children have diarrhoea, nausea, and vomiting. The gall bladder may be large and children may have abdominal pain. The diagnostic criteria in Table 1 should be viewed only as a guideline, since some children develop coronary artery changes without meeting diagnostic criteria, referred to as “atypical Kawasaki disease”. A typical disease is more common in infants, who often present with subtle or incomplete findings.

How Is Kawasaki Disease Treated?

Treatment must be administered soon at the onset of the fever to prevent permanent damage of the arteries.

Gamma Globulin: The use of intravenous immunoglobulin (IVIG) shortens the acute phase of Kawasaki disease somewhat and prevents much of the coronary damage. This treatment is currently the standard of care in Kawasaki disease, in a dose of 2 g/kg through the vein over 8 to 12 hours. In an NIH study, gamma globulin decreased the number of aneurysms by 3-5 times, when given in the first ten days of illness. For children who are diagnosed after the 10th day and continue to have fever, IVIG still may be helpful. Children who still have fever two days after IVIG may benefit from further treatments with IVIG. Careful monitoring is necessary during the administration of gamma globulin because it rarely can cause an allergic-like reaction.

Aspirin: In the past, aspirin was used for Kawasaki disease because it decreases inflammation and lowers fever, as well as prevents blood clots. Aspirin has never been shown in a study to decrease the risk of aneurysms. High doses of aspirin (20–25 mg/kg/dose every 6 hours) are used in the first few days to control fever.

After a child has no fever for 2 or 3 days, the dose is decreased to one that makes the blood “slippery” and less likely to clot, an "antiplatelet" dose (3–5 mg/kg/day). Children continue to take low–dose aspirin through the convalescent phase and then stop unless they have coronary damage.

Treating children with aneurysms

Children with coronary aneurysms require long-term therapy to decrease the chance of clotting in the aneurysm. The chance of having a clot in the coronary arteries is greatest after the acute phase, when the platelet count is high and there continues to be inflammation of the blood vessels.

Aspirin therapy is the most common treatment for children with aneurysms. If a patient has "giant aneurysms”, other medicines are used to thin the blood. Heparin or warfarin (Coumadin) effect proteins in the blood that promote clotting. Treatment with Coumadin requires monitoring with blood tests every month. Many children with giant aneurysms are treated with both Coumadin and aspirin. Low molecular weight heparin is occasionally used instead of Coumadin; this treatment requires injections twice a day under the skin but does not require frequent blood testing. Newer drugs that affect the platelets, such as clopidogrel or Plavix, can also be used together with aspirin, though experience in children is still limited. The medicines used to prevent clotting will depend on the cardiologist’s opinions about the risks and benefits of different treatment regimens for the individual child.

Because aspirin is associated with Reye’s syndrome, children who take daily aspirin should have yearly influenza vaccines. If the child develops influenza or chickenpox, two viral illnesses especially associated with Reye’s syndrome and aspirin, aspirin must be stopped temporarily. Aspirin therapy also should not be given during the six weeks after a chicken pox vaccine. For children with especially large aneurysms for whom aspirin therapy must be interrupted, we can use other anti-platelet agents in the short-term. When there is a blood clot in a coronary aneurysm, either as detected by echocardiography or by symptoms of a heart attack, special treatments are used to prevent further clotting, to dissolve the clot, and to protect the heart muscle. These treatments are identical to those used in adults who have heart attacks.  
 
For more information contact:

KAWASAKI DISEASE FOUNDATION OF SOUTH AFRICA
79 ROCKHOPPER CLOSE
ROCKFORD
PHOENIX
4068

TEL. 031-539 3023
FAX. 031-328 3003

Email. kdfsa@webmail.co.za
Website: www.kawasakidiseasefoundation.co.za