ABSTRACT, “The Narratives of Kawasaki Disease”

Howard I. Kushner, Christena H. Turner, John F. Bastian, & Jane C. Burns. “The Narratives of Kawasaki Disease” Bulletin of the History of Medicine, July, 2004, 78: 410-439. Click here to view the entire article.

Kawasaki disease (KD) is 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. Because the etiology and patho-physiology of KD are unknown, and no diagnostic laboratory test exists, diagnosis is made by relying on a list of clinical signs. However, a significant number of children fail to meet the clinical criteria, receive delayed treatment, and develop CAA. We hypothesized that the there might be a connection between these missed cases and the continuing frustration of researchers to identify the etiological agent(s)and mechanisms responsible for CAA. In order to determine what that connection might be, we launched a historical investigation into the construction of the clinical criteria and the process of their canonization. We explored how this construction and reification influenced the framing of research questions.
Our exploration suggested that the canonization of the KD case definition was due as much to the enshrinement of the historical narrative as it was informed by compelling scientific findings. The KD narrative encompasses distinct but interrelated issues of definition, discovery, and naming. These, in turn, have profoundly influenced diagnosis, treatment, and research. One result is that “atypical” cases, despite being at risk for CAA, often fail to receive prompt diagnosis and treatment . Consequently, research on the etiology and mechanisms of CAA has been limited to the population that meets the KD diagnostic criteria, rather than to those who are at risk of CAA. Although clinical concerns prompted this investigation, it nevertheless, has important implications for the history of medicine. It provides an illustration of how a historical interrogation of a syndrome’s construction can free medical researchers to pursue alternative and novel approaches. As important, it demonstrates how historians can make unique contributions as collaborators in clinical care and medical research.

 

ABSTRACT, "Rethinking the Boundaries of Kawasaki Disease: Toward the Next Case Definition"

Howard I. Kushner, John F. Bastian, Christena H. Turner,& Jane C. Burns. "Rethinking the Boundaries of Kawasaki Disease: Toward the Next Case Definition", Perspectives in Biology & Medicine, 46, (Spring) 2003, 216-233. Click here to view the entire article.

This paper describes the historical evolution of the Kawasaki disease (KD) case definition and its limitations for identification and treatment of children at risk for coronary artery aneurysms (CAA). The dominant view of pathogenesis is that an unknown agent infects infants and children, who then develop the signs of KD. Some of the infected infants and children then develop CAA, and a few die from myocardial infarction. Because the etiologic agent remains unknown, diagnosis of KD relies on observation and recognition of the clinical signs that comprise the KD case definition criteria. This approach has been successful in identifying and treating many children at risk for CAA. Unfortunately, however, it has delayed the effective treatment of children who fail to meet the KD case definition criteria but who, nevertheless, develop CAA. The original case definition was developed before the general acceptance of CAA as sequelae of KD, the availability of the echocardiogram, and effective treatment with intravenous immunoglobulin. Despite an evolution in awareness, detection, and treatment of possible CAA sequela, the case definition has not been altered so as to incorporate this knowledge. Our investigation explores the transformation of the case definition from an epidemiological instrument to a diagnostic tool. We urge the construction of a more sensitive KD case definition that includes signs and laboratory findings associated with CAA.

 

ABSTRACT, “Kawasaki Disease: A Brief History”

Jane C. Burns, Howard. I. Kushner, John. F. Bastian, Hiroko Shike, Chisato Shimizu, Tomoyo Matsubara, Christena L. Turner, “Kawasaki Disease: A Brief History,” Pediatrics 2000, 106: e27-e34. Click here to view the entire article.

Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki Disease (KD) in 1974. Since that time, KD has been reported in North American and Japanese children and is now the leading cause of acquired heart disease in children. Although an infectious agent is suspected, the etiology remains unknown. However, significant progress has been made toward understanding the natural history of the disease and therapeutic interventions have been developed that halt the immune-mediated destruction of the arterial wall. We present a brief history of KD, review progress in research on the disease, and suggest avenues for future study.
Kawasaki saw his first case of KD in January 1961 and published his first report in Japanese in 1967. Whether cases existed in Japan prior to that time is currently under study by the authors of this article as part of the Kawasaki Disease History Project. The most significant controversy in the 1960s in Japan was over whether the the rash and fever sign/symptom complex described by Kawasaki was connected to subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka and pediatrician Takajiro Yamamoto disputed Kawasaki's early assertion that KD was exclusively self-limiting with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented cardiac involvement as a sequela in about 25% of cases. By the time of Kawasaki's first English language publication in 1974, the link between KD and coronary artery vasculitis had been well established.
KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks in Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson in consultation with Benjamin Landing retrospectively diagnosed a 1971 autopsy case as KD. The similarity between KD and Infantile Periarteritis Nodosa (IPN) was apparent to these pathologists, as it had been to Tanaka earlier.
What remains unknown is the reason for the simultaneous recognition of this disease around the world in the 1960s and 1970s. There are several possible explanations. KD may have been a new disease that emerged in Japan and emanated to the Western World through Hawaii, where the disease is prevalent among Asian children. Alternatively, KD and IPN may be part of the spectrum of the same disease and clinically mild KD masqueraded as other diseases such as scarlet fever in the preantibiotic era. Case reports of IPN from Western Europe extend back to at least the 19th century but, thus far, cases of IPN have not been discovered in Japan before World War II. Perhaps the factor(s) responsible for KD was (were) introduced into Japan after the Second World War and then reemerged in a more virulent form that subsequently spread through the industrialized Western world. It is also possible that improvements in health care and, in particular, the use of antibiotics to treat infections caused by organisms including toxin-producing bacteria reduced the burden of rash/fever illness and allowed KD to be recognized as a distinct clinical entity.
Itsuro Shigematsu, Hiroshi Yanagawa and colleagues conducted fourteen nationwide surveys in Japan. These have indicated that (a) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; (b) there are approximately 5,000-6,000 new cases a year; (c) current estimates of incidence rates are 120-150 cases/100,000 in children < 5 year old; (d) KD is 1.5 times more common in males and 85% of cases occur in children < 5 year of age; and (e) the recurrence rate is low (4%). In 1978 David Morens at the Centers for Disease Control (CDC) published a case definition based on Kawasaki's original criteria. CDC developed a computerized data base and currently a passive reporting system exists in 22 states in 1984. Regional investigations and national surveys suggest an annual incidence of 4-15/100,000 children < 5 years of age in the U.S.
The natural history of KD reveals that coronary artery aneurysms occur as a sequela of the vasculitis in 20% to 25% of untreated children. Echocardiography can be successfully used to detect coronary artery dilatation and aneurysms in virtually all patients. Patients with no acute phase coronary artery changes detected by echocardiogram are clinically asymptomatic at least 10 years later. The Japanese Ministry of Health has established a registry of 6,500 children for longitudinal evaluation to determine long-term outcomes. No similar registry of patients exists in the United States.
Studies of KD pathogenesis show a progression of arterial lesions accompanying KD vasculitis and a number of immunoregulatory changes, including the deficiency of circulating CD8+ suppressor/cytotoxic T cells and the abundance of circulating B cells spontaneously producting immunoglobulins and activated monocytes. Biochemical and immunologic evidence suggests endothelial cell activation and injury. While the cause of KD remains unknown, clinical trials have established effective therapies, despite the absence of a proven etiology. Intravenous Immunoglobulin (IVIG) plus aspirin lowers the rate of coronary artery aneurysms from 20% to 3-5%. In 1988, the Committee on Infectious Diseases of the American Academy of Pediatrics endorsed IVIG treatment as recommended therapy for KD. Questions remain regarding treatment of patients who fail to respond to an initial dose of IVIG. The role of steroids or other anti-inflammatory agents in the treatment of KD is controversial.
Areas for further research include: a) a revised case definition reflecting clinical experience and including laboratory and echocardiographic criteria; b) development of a diagnostic test based on the biology of inflammation and acute endothelial cell damage that, in the absence of the etiologic agent, could be used to identify children with KD; c) studies of index cases and their families to identify relevant genetic factors; and d) long-term follow-up of patients into their third and fourth decades monitoring for late cardiovascular sequelae.