Then and Now: What do we still not know about Kawasaki Disease?

Review of an article written 25 years ago about KD with a discussion of symptoms, research yet the cause still goes unanswered.

In the September 1985 issue of Contemporary Pediatrics, David M. Bell, MD wrote an article entitled "Kawasaki update: More answers, fewer questions." Bell reviewed the epidemiology, clinical and laboratory features, differential diagnosis, and contemporary management of Kawasaki disease (KD).

It is 2009 and we have even more answers about KD than we did in 1985, but the critical question of its etiology remains unanswered. The additional answers have come through careful observation by individuals and meticulous multi-center cooperative studies that have been designed to provide incremental progress in our understanding of this perplexing condition.

In 1967, Dr. Tomisaku Kawasaki described 50 Japanese children who had a collection of clinical findings he termed mucocutaneous lymph node syndrome (MCLS).1 By 1970, the Japanese MCLS Study Group had established diagnostic criteria for the condition; those criteria are now used throughout the world. In 1976, the first US cases of KD were described,2 and by the time Bell's article appeared in Contemporary Pediatrics, outbreaks of the disease had been described across this country.3

In addition, reports began to accumulate of children, usually infants, who developed coronary artery aneurisms in association with an illness that did not meet all of the diagnostic criteria for KD. These reports led to recognition of "incomplete KD."

In 2009, there are no more specific laboratory findings known to be associated with KD than were recognized in 1985. Non-specific elevations in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), WBC count, and platelet count are seen in nearly all patients, and anemia is often seen. Various scoring systems have used laboratory studies to predict the likelihood of development of coronary artery aneurisms. One such scoring system, proposed in the early 1990s by Japanese investigators, combines a WBC >12,000/mm3, a platelet count of <350,000/mm3, elevated CRP, hematocrit <35%, albumin <3.5 g/dL, age more than 12 months, and male sex to predict which children with KD will be most likely to benefit from treatment with intravenous immune globulin (IVIG).4

Evaluation of the heart and the coronary arteries in children suspected of having KD is both more accurate and better standardized in 2009 than it was in 1985. Coronary artery size is now compared to the body surface area, for more accurate detection of enlarged arteries. Pulsed and color Doppler techniques allow for more accurate assessment of valvular dysfunction than is possible with simple 2D echocardiographic technique. Angiography is still needed in some patients with complicated disease, but cardiac magnetic resonance imaging and angiography, intravascular ultrasound, transesophageal echocardiography, and ultrafast computed tomography are all available as non-invasive tests now, for when visualization using conventional echocardiography is not adequate.

In August 1986, just one year after publication of Bell's article, Newburger and colleagues published the results of a multi-center, collaborative study demonstrating that IVIG in a dose of 400 mg/kg/day for four days reduced the likelihood of coronary artery aneurisms in children with KD from 18% (treated with high-dose aspirin alone) to 4% (treated with IVIG plus high-dose aspirin) when assessed seven weeks following diagnosis.5 Five years later a similar collaboration, also led by Newburger, demonstrated that a single infusion of 2 grams/kg given once reduced the incidence of aneurisms even further.6