Kawasaki Disease: A Brief History

Abstract

Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause of acquired heart disease among children in North America and Japan. Although an infectious agent is suspected, the cause 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 before that time is currently under study. The most significant controversy in the 1960s in Japan was whether 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 the early assertion of Kawasaki that KD was a self-limited illness with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases of sudden cardiac death after KD. By the time of the first English-language publication by Kawasaki in 1974, the link between KD and coronary artery vasculitis was well-established. KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles Children's Hospital, 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 factors responsible for KD were introduced into Japan after the World War II 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 distinc...

Kawasaki Disease: The Coronary Affection Perspective

“…Less than 2% of cases has recurrences. There have been great advances in the treatment of KD with the employment of intravenous immunoglobulins [IVIG] and high-dose aspirin [ASA]; [5], however, the lack of a diagnostic test can result in significant delays in treatment, often resulting in cardiovascular sequelae ranging from asymptomatic coronary artery ectasis or aneurysm formation to giant coronary artery aneurysms with thrombosis, myocardial infarction [MI], and sudden death in 20-25% of untreated children [6,7].…”

“…In 1967, Kawasaki published his first report in Japan describing the cluster of symptoms he observed in 50 patients seen since 1961, which he presented as an emergent disease called "mucocutaneous ocular syndrome" (MCOS) or mucocutaneuos lymph node syndrome [9]. Kawasaki's claim that MCOS was indeed a novel disease was met with a great deal of controversy [6]. A more highly debated topic was the proposed association between the symptoms of MCOS and a series of cardiac complications, which was first recognized by Dr. Noboru Tanaka, a Japanese pathologist, following the autopsy of a child diagnosed with MCOS [6].…”

“…Kawasaki's claim that MCOS was indeed a novel disease was met with a great deal of controversy [6]. A more highly debated topic was the proposed association between the symptoms of MCOS and a series of cardiac complications, which was first recognized by Dr. Noboru Tanaka, a Japanese pathologist, following the autopsy of a child diagnosed with MCOS [6]. The cardiac sequelae were first observed clinically and subsequently presented to the public in a report by Dr. Takajiro Yamamoto [10].…”

“…The cardiac sequelae were first observed clinically and subsequently presented to the public in a report by Dr. Takajiro Yamamoto [10]. A nationwide epidemiologic survey of MCOS in Japan released in 1970 confirmed the claims of Tanaka and Yamamoto and established the association between MCOS and cardiac complications caused by severe vasculitis [6,11].…”

“…However, KD was independently recognized as a distinct disease in Hawaii in the early 1970's by Dr. Marian Melish, a specialist in pediatric infectious disease, and Dr. Raquel Hicks, a pediatric rheumatologist [6]. The pair documented the disease in Hawaiian children, who were mostly Japanese Americans, and in 1973, after seeing photographs of children with KD from Japan and contacting Kawasaki, they concluded the syndrome they had encountered was the same as that recently documented in Japan [6]. In addition, in 1971, Eunice Larson, a pediatric pathologist in Honolulu, observed the cardiac sequelae of a child [later recognized as having KD] and after further investigation made the connection with the Japanese KD [6].…”