Kawasaki disease

Summary

• Kawasaki disease is an acute systemic illness that causes fever and is characterised by inflammation of the blood vessels.
• If untreated, the disease can result in damage to large arteries, particularly the coronary vessels of the heart.
• The cause is unknown, but the disease does not appear to be contagious.
• Symptoms include a sustained high fever, inflammation of the eye area (conjunctivitis), red lips and tongue, sore throat, rash, and reddening and peeling of the palms and soles.
• The disease usually affects children aged five or younger.
• Gamma globulin therapy is used in the treatment of the disease. Aspirin is also used under careful supervision.

Alternative name

Mucocutaneous lymph node syndrome

Definition

Kawasaki disease, a fever-causing condition that mostly affects children, was first described in Japan in 1967. The disease is named after Dr Tomisaku Kawasaki who developed a set of diagnostic criteria for the disease.

Vasculitis - an inflammation of the walls of blood vessels - characterises the disease. Inflammation usually only involves the smallest arteries and veins. The vasculitis soon spreads to the larger arteries, normally including the arteries to the heart. Aneurysms (balloon-like swellings in the wall of an artery) may develop, leading to thrombosis of these vessels.

Up to 15 to 20% of children with untreated Kawasaki disease suffer damage to the coronary arteries, making the disease a leading cause of acquired heart disease in children. This complication is commoner in younger infants, and in boys. About 2% of cases are fatal and aneurysms usually recover spontaneously but slowly.

Cause

The exact cause of Kawasaki is still not known.

Several factors indicate, however, that an infectious agent may cause the disease. The disease almost exclusively occurs in children and infants, suggesting the development of passive immunity by adulthood. Geographic outbreaks occur during certain times of the year, also supporting this theory. There is some evidence to incriminate infection by certain strains of bacteria called staphylococci, but this has not yet been verified.

Even if an infectious agent plays a part, it is likely that constitutional or genetic factors in the individual also have a role in determining susceptibility to the disease, as the incidence is very high amongst individuals of Japanese origin, geographic factors aside.

Prevalence

Kawasaki disease usually occurs in children under the age of five. The peak age is 18 to 24 months of age.

Although the disease was first reported in Japan, it now occurs throughout the world. One survey in South Africa indicated that it was commonest in white children and those of mixed race, but relatively rare in black children. The disease has a greater incidence in males than females.

Symptoms

• Fever: The main initial symptom of Kawasaki disease is a sustained high fever, generally higher than 39°C. The fever usually persists for at least five days, but on average eleven days, and is unresponsive to antibiotic treatment.
• Conjunctivitis: Inflammation of the conjunctiva – usually in both eyes, without pus-like discharge – may occur. The eyes may become red and swollen. This condition doesn't usually affect vision, but may cause discomfort.
• Swollen glands: One or several lymph glands may be swollen, measuring at least 1.5 cm or larger.
• Inflammation of the lips, mouth and tongue: The mouth cavity, tongue and throat become inflamed and sore. Characteristically, the lips are red, and later become dry and cracked.
• Rash: A generalised rash is usual in Kawasaki Disease and may take different forms, starting on the trunk and then spreading to the limbs. It is usually accentuated in the groin area. The region between the anus and the urethral (males) or vaginal opening (females) may become red and peel during the first week of the illness.
• Reddening and peeling of the palms and soles: After several days, the hands and feet usually become swollen and puffy. The skin on the fingertips, toes, palms, soles and other parts of the body may start to peel during the second week of the illness.
• Irritability: The patient can become highly irritable and some patients can even have altered mental states. This may persist over the entire course of the illness.
• Arthritis: Arthritis occurs in one third of the patients, generally coming on in the second week and lasting for a few weeks. The small joints are usually targeted, with progression to the larger, weight-bearing joints. Arthritis tends to affect older children.

Other possible symptoms: Because the disorder is a widespread vasculitis, many organs can be affected. A mild (aseptic) meningitis is quite common. There may also be troublesome cough, or stomach cramps, vomiting and diarrhoea. Abdominal pain due to enlargement of the gallbladder may occur.

Course

The disease generally takes six to eight weeks to run its full course. Recovery is usually complete if vasculitis of the coronary arteries did not develop.

Acute phase

• The first sign of illness is usually the onset of a very high fever (higher than 39°) that lasts for a minimum of five days, associated with extreme irritability.
• Red eyes, intensely red tongue, dry fissured lips, rash, swollen hands and feet, poor appetite and enlarged lymph nodes in the neck, also characterise the acute phase.
• Small joint arthritis may occur during this phase.
• The above-mentioned symptoms usually start to appear during the first week of illness, but not all at once. This makes the diagnosis challenging.
• During the acute phase, at least some degree of myocarditis (inflammation of the heart muscle) is present.

Subacute phase

• The second phase is characterised by resolution of the fever, rash and enlarged lymph nodes, but the irritability and poor appetite may persist.
• Arthritis, if present, now generally affects the larger joints.
• The skin of the fingers and toes may begin to peel. Heart problems may develop during this phase that lasts from day 10 until day 21.
• The heart problems are characterised by the development of weak areas (aneurysms) in the coronary arteries. These weak areas may eventually lead to thrombosis of a coronary vessel.

Convalescent phase

During this phase, the child's wellbeing will start to return. Laboratory values will also return to normal.

Although the child may be feeling better during the convalescent phase, there is still a chance that there has been damage to the coronary vessels, and this must be monitored carefully.

Apart from this risk, recovery is usually complete and second attacks are rare.

Atypical cases

It is now well-established that Kawasaki disease may occur in milder forms without the full picture described earlier, and yet still give rise to coronary vessel problems.

Diagnosis

There is no specific lab test that definitively diagnoses Kawasaki disease. The diagnosis is established by meeting certain criteria, as follows:

• A fever lasting for at least five days

At least four of the following symptoms should also be present:

• Conjunctivitis of the eyes without a pus-like discharge
• Redness and inflammation of the lips and tongue
• Swelling, redness and peeling of the hands and feet
• Generalised rash, accentuated in the groin area
• Swollen lymph glands in the neck

A doctor makes the diagnosis from these symptoms. However, certain laboratory findings are characteristic of Kawasaki disease:

• a high white cell count with preponderance of polymorphonuclear leukocytes
• after five days, a very high sedimentation rate
• in the second and subsequent weeks, a high platelet count

Cardiac studies such as electrocardiogram and echocardiograms (an ultrasound of the heart) are essential in all patients with Kawasaki disease.

Treatment

Kawasaki disease can be successfully treated with intravenous immunoglobulin (also called gammaglobulin) - proteins which are normally present in the blood and form part of the immune system. This treatment shortens the acute phase of the disease and decreases the risk of coronary heart damage. It should be administered during the fever phase.

Aspirin has a positive effect on inflammation and fever. It is also prescribed during the convalescent phase to prevent blood clots from forming. The use of aspirin should, however, be monitored carefully.

When to see your doctor

Consult your doctor if a child has unexplained fever for more than two or three days or if a skin rash persists.

Reviewed by Prof M. Kibel, Emeritus Professor of Child Health