The two emergencies of Kawasaki syndrome and the implications for the developing world.

Kawasaki syndrome (KS) is the most common cause of acquired pediatric heart disease in the developed world. There have been 2 distinctive patterns for the emergence of KS that are likely related to several factors including exposure to the causative agent(s) and host genetics. In Europe and North America where we presume the genetic susceptibility seems to be low, KS has existed in the pediatric population for more than a century and is associated with relatively low incidence. In Japan where genetic susceptibility is presumed to be high, KS seems not to have existed before the early 1950s. This relatively recent exposure has resulted in 3 nationwide epidemics and a high current endemic rate of 200 per 100,000 in children less than 5 years. If our history of alternative patterns of the emergence of KS is valid, it may prove useful as a predictive tool for countries including India, where clusters of KS cases have been recently reported. This article examines the historical evidence in support of a 2-tiered emergence of KS in Euro-America and Japan and then returns briefly to discuss its implications for the pediatric populations of India and the health care delivery systems in the developing world.

Delayed diagnosis by physicians contributes to the development of coronary artery aneurysms in children with Kawasaki syndrome.

BACKGROUND: A diagnosis of Kawasaki syndrome is based on clinical criteria with nonspecific laboratory findings, and there is a substantial risk of coronary artery aneurysms if treatment with intravenous immunoglobulin is delayed. In this study, we examined the contributions of sociodemographic factors and parent and physician behavior to the development of coronary artery aneurysms in children with Kawasaki syndrome. METHODS: We performed a retrospective, case-control chart review of Kawasaki syndrome patients treated at our institution during an 11-year period (1991-2002). Of 324 patients, 21 patients had coronary artery aneurysms and were matched with 81 Kawasaki syndrome control patients without coronary artery aneurysms. RESULTS: Patients who developed coronary artery aneurysms were more likely to have had their diagnosis established after 10 days of fever as a result of a delay in physician recognition of Kawasaki syndrome. In addition, these patients were also more likely to have been hospitalized at an outside facility with an erroneous diagnosis, to have had a greater number of healthcare visits before diagnosis, to have sought medical care in Mexico, to lack medical insurance and to speak Spanish as a primary language. Independent predictors of delayed diagnosis included incomplete clinical signs of Kawasaki syndrome, seeking health care in Mexico, and being hospitalized at an outside facility with a different diagnosis. CONCLUSIONS: Increased risk of coronary artery aneurysms is associated with a delay in diagnosis by physicians and not with a delay in seeking medical consultation by parents. Sociodemographic factors influence the likelihood that patients will have a delayed diagnosis.

Seasonality and temporal clustering of Kawasaki syndrome.

BACKGROUND: The distribution of a syndrome in space and time may suggest clues to its etiology. The cause of Kawasaki syndrome, a systemic vasculitis of infants and children, is unknown, but an infectious etiology is suspected. METHODS: Seasonality and clustering of Kawasaki syndrome cases were studied in Japanese children with Kawasaki syndrome reported in nationwide surveys in Japan. Excluding the years that contained the 3 major nationwide epidemics, 84,829 cases during a 14-year period (1987-2000) were analyzed. To assess seasonality, we calculated mean monthly incidence during the study period for eastern and western Japan and for each of the 47 prefectures. To assess clustering, we compared the number of cases per day (daily incidence) with a simulated distribution (Monte Carlo analysis). RESULTS: Marked spatial and temporal patterns were noted in both the seasonality and deviations from the average number of Kawasaki syndrome cases in Japan. Seasonality was bimodal with peaks in January and June/July and a nadir in October. This pattern was consistent throughout Japan and during the entire 14-year period. Some years produced very high or low numbers of cases, but the overall variability was consistent throughout the entire country. Temporal clustering of Kawasaki syndrome cases was detected with nationwide outbreaks. CONCLUSIONS: Kawasaki syndrome has a pronounced seasonality in Japan that is consistent throughout the length of the Japanese archipelago. Temporal clustering of cases combined with marked seasonality suggests an environmental trigger for this clinical syndrome.

Failure to diagnose Kawasaki disease at the extremes of the pediatric age range.

To learn about physician practices in diagnosing Kawasaki disease, we surveyed general pediatricians and pediatric infectious disease physicians by questionnaire. A high proportion of general pediatricians (>50%) and infectious disease subspecialists (25%) did not consider the diagnosis of Kawasaki disease in children younger than 6 months and older than 8 years. Failure to consider the diagnosis at the extremes of the pediatric age range puts children at risk because coronary artery abnormalities occur more often in young infants and adolescents with Kawasaki disease.

The narratives of Kawasaki disease.

Kawasaki disease 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 its etiology and pathophysiology are unknown and no diagnostic laboratory test exists, diagnosis is made via a list of clinical signs; however, a significant number of children fail to meet the clinical criteria and go on to develop CAA. We suspected a connection between these missed cases and the continuing difficulty in identifying the etiological agent(s) and mechanisms for CAA. In search of that connection, we launched a historical investigation into the institutionalization of the clinical criteria, and explored how this process influenced the framing of research questions. Our findings suggest that the canonization of the Kawasaki disease case definition was as much due to the enshrinement of the historical narrative as to compelling scientific findings. The Kawasaki disease narrative encompasses interrelated issues of definition, discovery, and naming; these, in turn, have profoundly influenced diagnosis, treatment, and research. "Atypical" cases, despite being at risk for CAA, often fail to receive prompt diagnosis and treatment; consequently, research has been limited to the population that meets the diagnostic criteria for Kawasaki disease, rather than including 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 novel approaches. Equally important, it demonstrates how historians can make unique contributions as collaborators in clinical care and medical research.