Autopsy report of a sudden infant death that was strongly suspicious of Kawasaki disease.

We conducted an autopsy on a 3-month-old boy in whom Kawasaki disease (KD) was strongly suspected based on the autopsy findings. The infant had a fever and was brought to a nearby clinic, where he was prescribed antipyretics and kept under observation. However, 15 days after onset of the fever, he suddenly died in bed. He exhibited no obvious redness of the lips, tongue, or conjunctiva. Membranous desquamation was present on his distal fingers. Vasculitis was observed in the coronary arteries, renal artery, splenic artery, and pulmonary vein. In addition, coronary artery aneurysms were present in the right coronary artery and left anterior descending artery. Thrombotic occlusion was observed in one aneurysm in the right coronary artery, resulting in acute myocardial infarction. The coronary artery wall showed infiltration of numerous macrophages and neutrophils. This case was classified as incomplete KD because the coronary artery aneurysm could not be demonstrated before death and was only recognized at autopsy. Pathologists and forensic scientists need to be aware that there are cases in which KD goes undiagnosed and untreated, leading to coronary artery aneurysm formation and sudden death.

Thirty-year overview of Japanese autopsy cases of Takayasu arteritis - Results of analysis of Japanese autopsy reports.

OBJECTIVE: The objective of the study was to analyse the trends in Takayasu arteritis (TAK) in Japan during three recent decades based on autopsy reports. METHODS: We extracted TAK cases from the Japanese Pathological Autopsy Reports published during three decades (1991-2000, 2001-10, and 2011-20) and compared the data for the number of cases, age, gender, malignant tumour complication rate, and cause of death. RESULTS: 322 TAK cases were reported during the 30 years. They represented 0.04-0.06% of the total autopsies, with little variation among the three decades. The peak age at autopsy increased: from the 60s for 1991-2010 to the 70s for 2011-20. The malignant tumour complication rate increased to 12.2%, 18.5%, and 22.7% during the three decades. However, about half of those cases had no metastases, and malignant tumours were rarely directly involved in a TAK patient's death. TAK-associated cardiovascular lesions accounted for most deaths. CONCLUSIONS: Although the age at TAK onset showed little change during the 30 years, the age at autopsy has increased, suggesting that the long-term prognosis has improved. Although the malignant tumour complication rate increased with age, the most common causes of death were cardiovascular lesions.

A pathological study on the efficacy of Syk inhibitors in a Candida albicans-induced aortic root vasculitis murine model.

BACKGROUND: The activation of innate immunity may be involved in the development of Candida albicans-induced murine vasculitis, which resembles Kawasaki disease (KD) vasculitis. This study aimed to histologically clarify the time course of the development of vasculitis in this model in detail and to estimate the potential role of spleen tyrosine kinase (Syk) inhibitors in KD vasculitis. METHODS AND RESULTS: DBA/2 male mice were intraperitoneally injected with a vasculitis-inducing substance and treated with a Syk inhibitor (R788 or GS-9973). Systemic vasculitis, especially in the aortic annulus area, was histologically evaluated. Regarding lesions in the aortic annulus area, some mice in the untreated control group already showed initiation of vasculitis 1 day after the final injection of a vasculitis-inducing substance. The vasculitis expanded over time. Inflammation occurred more frequently at the aortic root than at the coronary artery. The distribution of inflammatory cells was limited to the intima, intima plus adventitia, or all layers. In the Syk inhibitor-treated groups, only one mouse had vasculitis at all observation periods. The severity and area of the vasculitis were reduced by both Syk inhibitors. CONCLUSION: Candida albicans-induced murine vasculitis may occur within 1 day after the injection of a vasculitis-inducing substance. Additionally, Syk inhibitors suppress murine vasculitis.

Histological studies shed new light on the initiation and characteristics of calcification of coronary artery aneurysms in Kawasaki disease.

BACKGROUND: Calcification of coronary artery aneurysms (CAAs) is common in the remote phase of Kawasaki disease (KD), but the detailed features of its development remain unclear. This study aimed to elucidate the histological characteristics of calcification in KD CAAs. MATERIALS AND METHODS: The study materials consisted of 24 coronary artery branches with aneurysms that were obtained from 14 Japanese patients who died during the period from 40 days to 3 years after the onset of KD. We first examined the CAAs for the presence of thrombi and calcification. When calcifications were observed, we determined their location and shape, and investigated the time-course of the changes based on the time-interval from KD onset until death. Then we measured the area of each calcification and examined for correlations between the calcified area, and (1) the disease duration, and (2) the aneurysm diameter. RESULTS: Calcification was observed in 14 of 24 CAAs (in 7 of 13 LCA and 7 of 11 RCA). Thrombi were also seen in 13 of 14 CAAs with calcification. Calcification showed two localizations: in the organized portion of the thrombus (seen in 12 CAAs) and deep in the thickened tunica of the intima (3 CAAs). The earliest observation of calcification was in an infant who died on the 49th disease day: it was a small, band-shaped calcified lesion in granulation tissue that had formed at the boundary between the thrombus and the blood vessel wall. As the duration of KD increased, the calcified lesion increased in size, and nodular shapes were formed. Moreover, the calcified area tended to increase as the diameter of the aneurysm increased. CONCLUSION: Histologically, CAA calcification starts early in the remote phase of KD, and it is closely related to organization of thrombi.

The pathology of Kawasaki disease aortitis: a study of 37 cases.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis syndrome that occurs most frequently in children. Most clinical and pathological studies have focused on its coronary artery lesions. To date, no detailed studies of the aorta have been conducted. We studied KD autopsy cases with the aims of clarifying the time-course of changes in aortic lesions, the differences in the inflammatory cells and degree of inflammation at various aortic sites, and the progression of the inflammation. MATERIALS AND METHODS: The study materials were aortic specimens taken from 37 KD autopsy cases (acute phase: 19; remote phase: 18). Twenty-seven of the cases also had coronary aneurysms. We chose 3 aortic sites, i.e., the thoracic aorta, aortic root and aortic bifurcation, and we histologically observed and compared those sites in regard to the changes with time, the kinds of infiltrating cells and the number of inflammatory cells. We also observed the relationship between the vasa vasorum and inflammatory cell localization in the tunica media, and examined the progression of inflammation in the tunica media. RESULTS: Destruction of the vascular architecture was not seen in any of the 37 cases, but inflammatory cell infiltration was observed in 90% of the acute-phase cases. The inflammatory cell infiltration involved the tunica intima and tunica adventitia of the aorta on the 6th disease-day, and all layers of the aorta on the 13th disease-day; the infiltration peaked on the 18th disease-day. The infiltration gradually disappeared thereafter, and no significant infiltration was seen in the remote phase. The infiltrating inflammatory cells consisted mainly of CD163-positive macrophages. Comparison of the 3 sites of the aorta showed that the inflammatory cell infiltration was more severe in the aortic root and aortic bifurcation than in the thoracic aorta. The progression of inflammation to the aortic tunica media from the adventitia showed 2 patterns: 1 in which macrophages were aggregated around the vasa vasorum; and a second in which there was no such aggregation around the vasa vasorum, but there was diffuse inflammatory cell infiltration of the tunica media. In addition to this, there were findings of direct infiltration of cells from the tunica intima into the tunica media. CONCLUSION: Inflammation in KD occurs in the aorta. The changes with time and the kinds of infiltrating cells were the same as reported to date for coronary arteries in KD. There were differences in the degree of inflammation among the 3 aortic sites. It can be thought that the inflammation from the adventitia to the media progresses via the vas vasorum, and also, there is a possibility of spreading directly. From the intima to the media, inflammation spreads directly. However, formation of aneurysms and destruction of the vascular architecture of the aorta were absent in this study, unlike in coronary arteries.

Giant coronary artery aneurysm associated with Kawasaki disease showing progressive dilation over 30 years.

A 33-year-old pregnant woman with a history of a giant coronary artery aneurysm (CAA) of the right coronary artery owing to Kawasaki disease (KD) was referred to our hospital for the management of pregnancy and delivery. The CAA was detected when she was 10 months old on the 24th day from the onset of KD and showed transient regression followed by progressive dilation and reached a size of 25 mm when she was 30 years old. The baby was delivered at 38 weeks of gestational age. Resection of the CAA and coronary artery bypass grafting were performed 5 months after the delivery. Pathological results suggest that progressive dilation of the CAA was owing to a reduction in elastic recoiling force caused by partial destruction of the internal elastic lamina and degenerated tunica media against an increase in blood pressure that accompanied the growth of the patient. The pathophysiology of CAAs with atypical clinical course may be different from that of typical CAAs owing to KD. .