Risk Of Coronary Artery Aneurysms Research Articles

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.

Thrombocytopenia in Kawasaki Disease: A Risk Factor for the Development of Coronary Artery Aneurysms

The authors report on a 2-year-old boy with atypical Kawasaki disease (KD) and thrombocytopenia who developed 3 coronary artery aneurysms. The mechanism of thrombocytopenia in KD seems to be consumption coagulopathy. Review of the 30 reported cases of KD and thrombocytopenia revealed that this combination is more common in girls and in young age groups, and is associated with an increased risk of coronary artery aneurysm and myocardial infarction.

Safety from thromboembolism using intravenous immunoglobulin therapy in Kawasaki disease: Study of whole-blood viscosity.

High-dose intravenous infusions of immunoglobulin (IVIG) are well established as a standard therapy for Kawasaki disease (KD) for reducing the risk of coronary artery aneurysms. IVIG therapy might increase the blood viscosity both in vitro and in vivo, which has been reported as a risk factor for cardiovascular or cerebrovascular thromboembolism in adults. We measured the whole-blood viscosity in vitro, serum IgG and albumin, and blood hematocrit in 10 patients with KD and 10 with non-KD (five with acute encephalitis, one with sepsis, one with idiopathic thrombocytopenic purpura, one with Guillain-Barré syndrome, one with insulin-dependent diabetes mellitus, and one with Evans syndrome) before and after IVIG therapy. The blood viscosity increased significantly after IVIG therapy in the patients with non-KD, but did not increase in those with KD. The results of the present study suggest that the use of IVIG therapy for KD might be relatively safe, with no risk of thromboembolism due to hyperviscosity.

Rethinking the Boundaries of Kawasaki Disease: Toward a Revised Case Definition

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.

Thrombocytopenia in Kawasaki Disease: A Risk Factor for the Development of Coronary Artery Aneurysms

The authors report on a 2-year-old boy with atypical Kawasaki disease (KD) and thrombocytopenia who developed 3 coronary artery aneurysms. The mechanism of thrombocytopenia in KD seems to be consumption coagulopathy. Review of the 30 reported cases of KD and thrombocytopenia revealed that this combination is more common in girls and in young age groups, and is associated with an increased risk of coronary artery aneurysm and myocardial infarction.

Reply

Reply We thank Dr Bose and Professor Booy for their letter. They are correct, and we should have reported that we excluded Group A streptococcal infection by throat swab culture and serology. We agree that there is a wide differential diagnosis of Kawasaki Disease (KD). The associations between coronary aneurysms and various organisms, toxin-producing and otherwise, which they quote, however, are merely associations and have not been proven to be causes of KD. There is no single diagnostic test for KD. There are two major reasons to make the diagnosis, clinical and epidemiological. We believe that Bose and Booy are confusing the two and so are missing the reason for reporting this ‘instructive case’. The CDC criteria are epidemiological, so that when researches report data such as the incidence or the outcome of KD, say in different countries, they are comparing similar diseases. The importance of early clinical diagnosis is to initiate early treatment with intravenous immunoglobulin, which has been proven to reduce the risk of coronary artery aneurysms.1 We reported a child who developed giant aneurysms despite not meeting the epidemiological ‘diagnostic’ criteria of KD in order to heighten awareness and suspicion, in the hope that earlier diagnosis and treatment might prevent some children developing coronary aneurysms.

Scoring method for identifying patients with Kawasaki disease at high risk of coronary artery aneurysms

The beneficial effect of immunoglobulin in preventing coronary artery aneurysms in patients with Kawasaki disease is recognized, but immunoglobulin should be selectively given to patients at high risk for coronary lesions. The present study was designed to present a scoring method to evaluate the severity of Kawasaki disease in terms of coronary artery disease based on clinical and early laboratory findings. Seventy-eight patients who were admitted at 4 to 7 days of illness and who had received aspirin alone during the acute febrile period were separated into 2 groups according to significant coronary artery involvement, and possible related factors to the discrimination of the 2 groups were studied using multivariate analysis. Age at onset, C-reactive protein and platelet count contributed significantly to the discrimination, and from these 3 items a simple scoring system was devised to predict patients at high risk for coronary lesions. Retrospective study using this scoring method indicated that significant coronary artery disease was more often seen in patients predicted to be at high risk treated with aspirin, while no patients who received immunoglobulin had coronary lesions of moderate or severe degree. Thus, the present scoring method provides simple but clinically useful criteria for predicting patients at high risk of coronary artery disease, and immunoglobulin therapy for selected patients may reduce the significant coronary artery complications of Kawasaki disease.