Kawasaki syndrome

Toddlers with fevers? Only about as common as sand on the beach. But for toddlers with Kawasald syndrome, fever is just one of the early signs of a very serious illness.

Kawasaki disease, or Kawasaki syndrome, is an infectious inflammatory disease that affects mainly infants and young children. At first, the symptoms--fever, rash, watery eyes, swollen lymph nodes--look like those seen with many of the bugs kids pick up all the time.

But this is no simple bug. It affects many systems in youngsters' bodies, but damage to the heart and surrounding tissue is of the greatest concern. Left untreated, Kawasaki syndrome can damage the coronary arteries that feed the hem-t, possibly causing a massive heart attack. Recently, the Food and Drug Administration approved use of a previously licensed biologic, intravenous immune globulin--Immune Globulin Intravenous (Human)to help minimize the complications of Kawasaki syndrome.

Although there have been rare reports of Kawasald syndrome in adults, the disease primarily affects children under 5 years old, with most cases affecting 1- to 2-year-olds. The disease affects boys about 50 percent more often than girls, and seems to affect children of Asian descent at a much higher rate than children of African or European descent. "The typical patient would be a 2-year-old boy with high fever," says Stanford Shulman, M.D., Chief of Infectious Diseases at Children's Memorial Hospital in Chicago.

There have been three epidemics of the disease in Japan: in 1979, 1982 and 1986. According to surveys of those epidemics, 1 in 250 Japanese children with the disease died from it, and 15 to 20 percent developed heart aneurysms. These abnormal enlargements of blood vessels cause a weakening of the vessel that could burst at any time, threatening the patient' s life.

Kawasaki syndrome is not considered contagious, although outbreaks tend to occur in certain geographic regions. The disease is most common in Asia, particularly in Japan and Korea. In the United States, the incidence in children of Japanese or Korean background is four times greater than in children of European background. This link puzzles researchers. The disease is more prevalent even in Asian children with little or no exposure to the foods or customs of Asian culture.

In Hawaii, the disease is far more common among Japanese-American children. While Japanese-Americans compose onethird of Hawaii's population, JapaneseAmerican children account for 85 to 90 percent of the cases of Kawasaki syndrome in that state. Most of these children are third- or fourth-generation Americans with little or no Japanese cultural influence in their daily lives. These statistics appear to indicate a genetic factor that researchers are not yet able to explain.

The disease was first described by Tomisaku Kawasaki, M.D., a Tokyo pediatrician, in 1967, but wasn't reported in English literature until 1974. Fever develops within the first few days of onset of the disease. Many Kawasaki patients experience abrupt spikes in temperature-- several spikes a day for five or more days--as the disease begins. Left untreated, the spiking can continue for as long as four weeks.

A measles-like rash usually accompanies the fever, and lymph nodes in the neck swell. Conjunctivitis, characterized by red eyes and swollen eyelids, may also develop in the first few days. The lips, tongue and throat may become red and swollen. One of the most distinguishing symptoms of Kawasald disease is the redness and swelling of palms and soles within a few days of onset. After a couple of weeks, the skin of the hands and feet begins to peel.

Diagnosis Critical

Early and accurate diagnosis is critical to successful treatment, as the disease can start to damage the heart after just one week of illness.

But diagnosis is difficult. One problem is that the symptoms don't always appear together. Some patients experience all of the symptoms, and some have only a few. Infants are less likely than toddlers to have all symptoms.

Fever and swollen glands are a source of concern for any parent, but "cardiac involvement is the only long-term issue in Kawasaki disease," says Shulman. "It's the only thing of real importance."

The acute phase of Kawasaki syndrome is followed by a convalescent stage, which can be misleading. Often patients' families see improvement, even without treatment. Fever is reduced--sometimes temperature even returns to normal--skin redness subsides, and skin begins to peel. "The worrisome thing [during this stage]," says Shulman, "is that in those children who are destined to develop heart involvement, this is the period of time it begins to show up."

According to a study by the Division of Pediatric Cardiology of Columbia Unlversity's College of Physicians and Surgeons, 25 percent of Kawasald patients show some signs of heart inflammation-- such as fast or irregular heartbeat-during this stage. Heart inflammation is a waming sign indicating the possibility of damage to the carrdiovascular system. Although heart inflammation may subside over time, aneurysms, permanent and sometimes life-threatening dilations of blood vessels, may occur.

The peak size of an aneurysm is typically reached three to four weeks after the onset of fever," says Jane Newburger, M.D., a pediatric cardiologist with Children' s Hospital in Boston. This makes it important to monitor Kawasaki patients carefully. Once an aneurysm has formed, there is no guarantee that the damage can be reversed. However, treatment is aimed at preventing the formation of aneurysms.

The damage from Kawasaki disease is thought to start with an inappropriate immune response. Children with the disease produce an unusually large number of immune cells. The immune cells go haywire and begin to attack artery walls.

Once the artery wall is damaged, it becomes a dam where platelets can form a blood clot. This clot, combined with the damage to the artery wall, further enlarges the artery, causing an aneurysm. Once this happens, blood flow is severely restricted, and a heart attack is possible. (See "Aneurysms Difficult to Diagnose, Complex to Cure" in the October 1992 FDA Consumer.)

Aspirin and IGIV

Early diagnosis and treatment helps minimize the danger from Kawasaki syndrome. Although the cause is unknown, it can be treated effectively, says Mary Glode, M.D., an infectious disease specialist with the Department of Pediatrics of the University of Colorado in Denver.

Researchers have found that a combination of aspirin and intravenous immune globulin (often abbreviated IGIV) is highly effective in preventing long-term coronary artery problems from Kawasald syndrome. Initially, patients were given aspirin alone, but the findings of researchers prompted FDA to recently approve the addition of IGIV to the treatment of Kawasald patients.

The role of IGIV is unclear. IGIV is a product made by purifying the naturally occuring antibodies in human blood plasma. Several pharmaceutical companies produce IGIV, but only one product, produced by Oesterreichisches Institut ruer Haemodenzate (OIH), a pharmaceutical company based in Austria, has been approved by FDA for use in treatment of Kawasaki disease.

According to John Finlayson, Ph.D., a protein specialist with FDA, "We don't really understand why immune globulin works, but the major benefit is in minimizing coronary aneurysms."

The immune globulin is given intravenously in either a single large dose of 2 grams per kilogram of body weight over 12 hours, or four smaller daily doses of 400 milligrams per kilogram (1 kilogram is about 2.2 pounds).

Besides minimizing the potential for cardiac damage, this treatment regimen seems to work to "turn off' the disease. If treatment starts within 24 hours of the onset of the disease, the child is usually feeling much better by the next day.

According to Newburger, aspirin provides both an anti-inflammatory and antiplatelet effect. The anti-inflammatory effect keeps the arteries from swelling, and the anti-platelet effect prevents clots from forming in arteries.

Aspirin is given is fairly high daily doses--from 30 to 180 milligrams per kilogram (for example, 405 to 2,430 milligrams per day for a 30-pound child) of the patient' s body weight--for the first two weeks of the disease. (For comparison, one regular aspirin is 325 milligrams.) The dose is then lowered to 3 to 5 milligrams per kilogram for an additional six to eight weeks.

Patients who have some heart damage may be given low doses of aspirin for several months; those with more severe damage, for years.

Aspirin use in the treatment regimen for children is somewhat controversial. The association between aspirin and Reye syndrome in children with flu and chickenpox has made parents and doctors wary of using aspirin to treat children with any acute illness.

However, no association has been reported between Reye syndrome and the use of aspirin in children with Kawasaki syndrome. Therefore, the benefits of its use in this instance, under a doctor's direction, outweigh its risks. Children who need to continue low doses of aspirin for long periods after the acute stage of the disease are monitored closely for signs of chickenpox or flu, and the aspirin can be stopped for a few days if a child develops symptoms of these illnesses.

Inexplicably, a possible connection has been made by some studies between children contracting Kawasaki syndrome and recently cleaned carpets. Researchers at Comeil University Medical Center were the first to find the apparent association in a survey of the families of Kawasaki patients and a separate control group.

Researchers asked questions about other family members with the disease, the type of foods the patient had been eating, and whether or not the child was breast-fed.

The only factor that clearly differed between the two groups is that children with Kawasald disease were more likely to have been exposed to carpets and rugs that had been shampooed, beaten, or vigorously cleaned within a month of the onset of illness. Most cases of Kawasaki syndrome occur between December and May, prompting some experts to recommend that families with infants and toddlers not clean carpets during winter and early spring.

Since the Cornell study, 13 additional studies have tested the connection. "Four studies have found an association between exposure to shampooed carpets and development of Kawasaki," says Shulman. "Nine of the studies failed to find an association."

Shulman explains that while the association is generally unproved, it may be valid in certain geographic locations. To be on the safe side, he recommends keeping children away from just-shampooed carpets for 24 to 48 hours.

Long-Term Outlook

According to Newburger, a Kawasaki patient' s long-term outlook depends on how much damage is done to the heart. Patients who receive treatment early will likely suffer no damage to the arteries. More than haft the children who do develop aneurysms recover within a year.

Patients who don't fare as well are those who don't receive treatment and develop extremely large aneurysms. "The most [severely affected] patients--those with aneurysms of at least 8 millimeters--those patients will probably not return to normal," says Newburger.

Because the disease was so recently identified, doctors don't yet know if there are any long-term effects that aren't apparent when the acute phase of the disease ends.

While most childhood fevers, sniffles, and watery eyes are no reason for alarm, parents should be aware that accompanied by other symptoms, the illness may require immediate medical attention. Recognized and treated early, Kawasaki syndrome can be stopped before it becomes a life-threatening problem.

COPYRIGHT 1992 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group