Applied History of Medicine


Kawasaki Disease Research Project

Kawasaki disease (KD) is named after the Japanese pediatrician Tomisaku Kawasaki who in 1967 described 50 cases of infants with persistent fever, accompanied by rash, lymphadenopathy, edema, conjunctival injection, redness and cracking of the lips, "strawberry tongue," and convalescent desquamation. Today KD is understood as a rash/fever illness of early childhood in which coronary artery aneurysms (CAA), sometimes fatal, may develop in up to 25 percent of untreated children.

The incidence is highest in Japan with an annual rate of 130-140/100,000 children under 5 years of age. In comparison, incidence for the continental U.S. varies between 9 and 20/100,000 children under 5 years of age and for Japanese Americans living in Hawaii between 120 and130/100,000 in children under 5 years of age. Because its etiologic agent(s) and patho-physiological mechanisms remain unknown, and because there is no diagnostic laboratory test for KD, diagnosis relies on the observation and recognition of clinical signs that comprise the KD case definition. With the establishment of intravenous immunoglobulin (IVIG) as an effective therapy, prompt diagnosis has become essential for timely therapy to ensure a good cardiac outcome.

Although researchers have attempted to uncover the etiology of KD since the 1960s, we appear to be no closer to an answer. Among those who assume there is an infectious agent, disagreement continues over whether the agent is bacterial or viral and whether or not it acts as a super-antigen. Immune response remains a crucial arena of investigation; yet no robust hypothesis has convincingly linked the sign complex and immune cascade with the development of CAA. For more information visit the Kawasaki Disease Foundation.

The Kawasaki Disease Research Project
In an effort to widen research questions related to the etiology of KD, the Kawasaki Disease Research Program at the University of California, San Diego (UCSD) School of Medicine initiated a medical historical investigation of KD in the spring of 1998. We hoped that such an investigation might uncover useful clues in the search for an etiology of Kawasaki disease.

Investigators collected a variety of data including historical records of clinical cases and autopsy reports. Because KD was only recently recognized, first-hand accounts are available from those involved in its "discovery." We conducted a series of KD-focused interviews with pediatricians, pathologists, and medical researchers from Japan, North America, and Europe. Topics covered in these open-ended interviews included a recollection of the person's earliest clinical observations, their histories of research into the characteristics and the etiology of the syndrome, and their professional conversations about it. To gain a context for the interview data, we also observed practicing physicians, including members of our team, as they considered and eliminated KD and possible alternative diagnoses. In addition, the observational data were triangulated with our historical understanding derived from the review of existing written sources.

In 2003, the investigators and the Kawasaki Disease Foundation, a national parents group led by Greg Chin in Massachusetts, applied for and were awarded a three-year National Library of Medicine Grant (National Institutes of Health) to develop a website and produce a film on the history of Kawasaki Disease. This website will include transcriptions of these interviews and our publications to date.