The secrets behind a rare but serious childhood illness that affects the heart are slowly unraveling because of ongoing research and clinical trials in Japan and the United States, including work at the UC San Diego Medical School and at Childrens Hospital in Los Angeles.
The use of intravenous gamma globulin--blood serum full of antibodies--is proving highly effective in preventing heart disease, which affects up to 30% of the children who contract Kawasaki Syndrome and is suspected of remaining with them for the rest of their lives. The medicine also quickly tames the high fever and inflammation indicative of the illness.
Just the name of the illness itself--Kawasaki Syndrome--conveys a sense of mystery. First recognized by a Japanese physician in 1967 despite a still-unknown cause, it strikes Japanese children between ages 1 and 5 about five times as often as it does Caucasian juveniles.
Yet outbreaks have occurred throughout the United States--an estimated 250 cases each year. Most affected is Hawaii, but there was an outbreak in the Boston area in 1980 and in Southern California last winter.
Traditionally, pediatricians have been able to treat the multifold symptoms--persistent high fever, cracked lips, strawberry tongue, swelling of hands and feet, major fatigue--only with aspirin, to reduce fever and try to prevent blood clots from developing in arterial walls of the heart. It is not contagious.
But in the last two years, the gamma globulin testing has developed from joint efforts between American and Japanese doctors. Under sponsorship of the federal National Institutes of Health (NIH), six U.S. medical centers have found that the incidence of coronary disease has been cut seven times--from about 30% to 4%--during the first year of trial use with about 200 patients. The comparisons were made between patients given gamma globulin over a four-day period and those patients only given aspirin.
"The results were so startling that NIH (officials) said it would be immoral not to give everyone in the program gamma globulin," Dr. Kyung Chung, director of the UCSD Kawasaki Disease Center and a physician at the medical center pediatric cardiology unit, said. "So as of last November, every child in the trials is given gamma globulin."
The centers are now testing whether a single massive dose can be as effective as the four-day regimen because a shorter period can save substantial costs by shortening hospital stays.
But the key to effective gamma globulin treatment is quick diagnosis within 10 days of onset of the first fever, Chung emphasized. If more time elapses, the gamma globulin apparently does not work as effectively. At present, victims must go to one of the six centers nationwide to get the treatment.
Because Kawasaki Syndrome is fairly uncommon in the United States--about two to three cases a month in the San Diego area, for example--many pediatricians do not recognize the symptoms readily.
"I'm sure that it has been around for a long time (before first recognized as a syndrome) and probably just labeled a viral disease," Chung said.
Chung said that researchers suspect the disease is racially related since it affects Japanese children much more often than those of other backgrounds.
"Initially, it was suspected that whatever causes the problem was in the environment," Chung said, noting that almost all Japanese houses contain straw "tatami," or sleeping, mats. Researchers surmised that mites in the mats could be responsible for the disease.
"But that wasn't the case. And later Dr. Marian E. Melish at the University of Hawaii, another of the test centers, showed that Japanese-American children had a higher incidence of Kawasaki Syndrome than Caucasian or other (Asian-American) children even though they were living (outside Japan)."
While there are several theories that the syndrome is viral-related, the agent that causes it has not been identified as yet. Chung said that many think the blood vessel wall of victims may somehow overreact to an antigen produced by the agent, resulting in an overproduction of antibodies and leading to the various symptoms of the syndrome.
"But it's still mysterious," Chung said.
In addition, new work by Japanese researchers indicates that once the syndrome affects the heart area, it remains with the victims indefinitely even though its signs may later seem to disappear. "The Japanese are saying that there could be lifelong coronary artery disease," Chung said. American doctors are now looking into the latest Japanese work, she said.
"Once an organ has a disease, it is difficult to say that it is ever cured," Chung said. Because of limited research until now, children who seemingly recover from heart-related problems with Kawasaki Syndrome will have to be checked for many years to determine whether cardiac disease remains.
The syndrome was discovered at the Tokyo Red Cross medical Center, where the first intravenous gamma globulin treatments began about three years ago. Chung said that it was theorized the gamma globulin could help suppress the apparent antibody reaction of the blood vessel wall.
The four-day regimen of gamma globulin given intravenously proves painful for children as well as expensive for the hospital and parents, Chung said, even though the drug has been donated by the Austrian pharmaceutical firm Immuno AG. The new study hopes to show that a single dose proves equally effective, cutting costs considerably, Chung said.
At that point, researchers will ask federal authorities to authorize use of the drug nationwide for the syndrome.