Incidence rate of recurrent Kawasaki disease in Japan

To calculate the incidence of recurrent Kawasaki disease and to discuss some potential risk factors for its recurrence, we observed a cohort consisting of those followed-up since the first episode of the disease. A total of 4560 persons, with 16 500.4 person-years were observed from the second month after the first episode of the disease to the end of 1989. The mean observation period was 3.62 years. The overall incidence rate was 5.21 per 1000 person-years, with a higher incidence within the 2 years from the first episode; although not statistically significant, the incidence was higher among males and those who experienced the first episode at ± 2 years of age. The possibility of i.v. gamma globulin therapy being one of the risk factors was negated by a stratified analysis to control confounding factors but supported by univariate analysis.     

Kawasaki disease in parents and children

Aim: To estimate the probability that the parents of patients with Kawasaki disease also had a history of the same disease. Methods: Self-reported parents' histories of Kawasaki disease were collected from data of the 16th nationwide survey of the disease conducted in Japan from January 1999 to December 2000. The incidence of Kawasaki disease was calculated by using data reported in all 16 nationwide surveys and live births in the Japanese vital statistics. The expected number of parents with a history of Kawasaki disease in the general population, which was calculated by using the assumed number of parents in the vital statistics and the incidence of this disease, was compared with the observed number. Results: Among 14 163 parent pairs of patients with Kawasaki disease, 33 parents (25 mothers and 8 fathers) had a history of the disease. The number of parents expected to have a history of Kawasaki disease was 16.1 (8.4 mothers and 7.7 fathers). From a Poisson distribution, the probability of the observed number was less than 0.001 among parents or mothers. The prevalence of a recurrence of Kawasaki disease and incidences involving siblings of patients whose parents had a history of the disease were five or six times higher than those of all patients who were reported in the 16th survey.

Conclusion: When compared with parents in the general population, the probability of a history of Kawasaki disease was significantly higher in those parents whose children suffered from the same disease. This suggests that, epidemiologically, a genetic predisposition to Kawasaki disease may be implicated in its occurrence.     

A case-control study of recurrent Kawasaki disease using the database of the nationwide surveys in Japan

Abstract In spite of many reports of recurrent Kawasaki disease, little information about the risk factors associated with recurrence is available. We conducted a case-control study on 150 cases of recurrent Kawasaki disease and 1173 pair-matched controls selected from the database of nationwide surveys of the same disease in Japan. Items observed were: sex, age, use of intravenous gamma globulin, and cardiac sequelae at the first episode. Sex and cardiac sequenlae did not affect the risk of recurrence. One- to 2-year-old chilren were more likely to be affected again than infants (odds ratio [OR]=1.42; 95% confidence interval [CI], 0.94–2.13), and children who were 3 years of age or older were less likely to experience a recurrence than infants (OR=0.59; 95% CI, 0.34–1.02). Intravenous gamma globulin therapy at the first episode increased the risk for recurrence of Kawasaki disease within 12 months (OR=2.66, 95% CI, 1.06–6.66). However, it did not affect recurrences 12 months after the first episode (OR=1.02; 95% CI, 0.53–1.97).Conclusion Patients with Kawasaki disease treated with intravenous gamma globulin are 2.66 times as likely to be affected by the disease again within 12 months as those treated without intravenous gamma globulin.     

Clinical features of recurrent Kawasaki disease and its risk factors

The clinical features and risk factors for recurrence of Kawasaki disease (KD) remain unclear. In order to summarize clinical features of recurrent KD and identify risk factors associated with recurrence, we conducted a retrospective review of the medical records of consecutive cases of KD from January 2002 to December 2010. Demographic, clinical, laboratory, and echocardiographic data were analyzed. The maximum coronary artery Z score normalized against body surface area was assessed using coronary artery diameters. At the first onset of recurrent KD, children had longer durations of fever before intravenous immunoglobulin (IVIG) treatment and higher levels of alanine aminotransferase, serum aspartate aminotransferase (AST), and lower hemoglobin levels than those with a single episode of KD. Multivariate logistic regression analysis showed that long durations of fever before IVIG treatment, high AST levels, and reduced hemoglobin levels were significantly associated with recurrent KD. Ten of the 22 recurrent KD children had coronary artery complications during the first onset episode, and six (60 %) of these also had coronary artery complications during the recurrence. Children with longer durations of fever, lower hemoglobin levels, and higher AST levels may be at increased risk for KD and coronary artery complications are more likely to occur in children with recurrent KD if they were present during the first episode.     

Recurrent Kawasaki disease

Summary This case report describes a boy who had Kawasaki disease (KD) at age 12 months and had a recurrence one year later. The coronary arteries were normal following the initial episode; however, during the second episode he developed coronary aneurysms. Gallium-67 radionuclide imaging, echocardiography, and angiography were used to diagnose the coronary abnormalities.This work was supported in part by grant RR-00188 from the General Clinical Research Branch of the National Institutes of Health, Bethesda, Maryland.     

Rate,associated factors and outcomes of recurrence of Kawasaki disease in Ontario,Canada

Background: Previous studies on recurrence of Kawasaki disease (KD) have mostly been limited to Japan, which has an incidence of KD 8–10‐fold higher than North America. The aim of the present study was to determine the rate of KD recurrence for patients in Ontario, to identify factors potentially associated with increased odds of recurrence, and to compare the clinical course and outcomes of index and recurrent KD episodes. Methods: Review was undertaken of all patients with recurrence of KD identified in Ontario, Canada, from 1995 to 2006. All patients with recurrence of KD (defined as at least three clinical signs of KD in addition to fever ≥5 days), presenting ≥14 days after the return to baseline from the index episode were included. Results: A total of 1010 patients were followed for 5786 patient‐years. During this period a total of 17 recurrent episodes in 16 patients were identified at a median of 1.5 years after the initial episode (2 weeks–5 years). Rate of recurrence of KD was 2.9 episodes/1000 patient‐years, which is higher than the expected annual incidence of KD in the same age group (26.2/100 000 per year). No factors associated with increased risk of recurrence were identified, perhaps due to the small number of events. Clinical course and outcomes of the index and recurrent KD episodes were similar. Conclusions: A previous history of KD should increase the index of suspicion for future episodes of KD to allow for rapid recognition, treatment and to achieve optimal outcomes.     

Kawasaki disease in families

The rate of second-case Kawasaki disease occurring among 1788 siblings of children with the disease was derived from data obtained from questionnaires mailed to the members of the Japanese Association of Parents of Children With Kawasaki Disease. Within 1 year after the onset of the first case in a family, the overall second-case rate was 2.1% for siblings, as compared to an overall incidence of approximately 0.19% in the general population of children 0 to 4 years of age in Japan in the epidemic year 1982. For siblings younger than 1 year of age, it was 8.4%, and for those between 1 and 2 years of age, it was 9.3%. More than half (54.1%) of the second cases developed 10 days or less after the first cases occurred.     

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目的探讨川崎病(KD)患儿合并冠状动脉损伤的危险因素。方法按照KD诊断标准,对北京儿童医院2000-01-01—2004-12-31收治的644例KD患儿临床资料、治疗方法以及实验室资料进行分析。结果Pear-son卡方检验显示,患儿性别、发热持续时间、丙种球蛋白使用时间、丙种球蛋白使用剂量、血沉及C反应蛋白与KD合并冠状动脉损伤有关(P<0·05);进一步多因素Logistic回归分析显示,性别、发热持续时间、丙种球蛋白使用剂量与冠状动脉扩张显著独立相关(P<0·05)。结论对男性、发热持续时间长的KD患儿应予足够重视,早期足量使用丙种球蛋白以减少或减轻冠状动脉并发症。     

Recurrent skin peeling following Kawasaki disease

Long term follow up of 259 cases of Kawasaki disease led to the observation that 11% of children have episodes of recurrent peeling of the skin for several years after their recovery. These events were usually associated with an upper respiratory tract infection and were distinct from a recurrence of Kawasaki disease. Repeeling was significantly less frequent in children who had suffered coronary artery dilatation and was more frequently seen in those with nasal staphylococcal colonisation. The mechanism for this phenomenon is unclear, but it has been observed in a number of other conditions caused by infectious agents and their toxins. Paediatricians need to be aware of this phenomenon which is distinct from recurrence of Kawasaki disease.     

Clinical features of patients with Kawasaki disease whose parents had the same disease

OBJECTIVE: To observe the clinical characteristics of patients with Kawasaki disease whose parent also had the same disorder. DESIGN: Cross-sectional study using the data from nationwide surveys of Kawasaki disease in Japan. SETTING: All hospitals with a bed capacity of 100 or more and pediatric departments in Japan. PATIENTS: All patients described on the 16th and 17th surveys covering the 4-year period from January 1, 1999, through December 31, 2002. MAIN OUTCOME MEASURES: We compared clinical details, including sibling case, recurrence, diagnosis, administration of intravenous immunoglobulin, and coronary abnormalities, between patients whose parents had Kawasaki disease and patients with no parental history of Kawasaki disease. We also observed age at onset and sex of affected parent-offspring pairs with Kawasaki disease confirmed by using the data of previous nationwide surveys. RESULTS: The odds for having sibling cases were significantly increased among patients whose parents also had Kawasaki disease (odds ratio, 6.94; 95% confidence interval, 2.77-17.38). Patients with parental Kawasaki disease were more likely to experience recurrent Kawasaki disease, receive additional administration of intravenous immunoglobulin, and experience coronary abnormalities at 1 month after onset. Among confirmed parent-offspring pairs with Kawasaki disease, the mean age at onset of offspring was younger than that of their parents (25.6 vs 41.8 months), despite the lack of statistical significance. CONCLUSIONS: Some cases of Kawasaki disease show familial susceptibility to the disorder. Family history, especially parental history of Kawasaki disease, may be an indicator of disease severity.     

Management of Kawasaki disease in the British Isles.

Kawasaki disease in the British Isles was surveyed by an active reporting scheme, based on all cases reported to the British Paediatric Surveillance Unit that were diagnosed between 1 January and 31 December 1990. The study was prompted by the need to investigate the high case fatality rate of Kawasaki disease of 2% observed in 1988. One hundred and sixty three patients were identified of whom six (3.7%) died. Forty five children (28%) suffered cardiac complications of which 39 (24%) were coronary artery abnormalities; five children were diagnosed at postmortem examination, and coronary artery abnormalities were detected by echocardiography in 34. One hundred and forty nine children (93%) had echocardiography. High thrombocytosis, leucocytosis, duration of fever, and younger age were associated with the presence of coronary artery abnormalities. Erythrocyte sedimentation rate, sex, and the number of diagnostic criteria were not. One hundred and thirty three children (87%) received aspirin. Ninety three children (61%) received intravenous gammaglobulin (IVGG). Children were more likely to receive IVGG if they had thrombocytosis or typical Kawasaki disease. The incidence of coronary artery abnormalities was found to be similar in those treated with IVGG (29%) and those untreated (20%), including those treated within 10 days of onset. This may have reflected selection of the more serious cases to receive IVGG or that Kawasaki disease in the British Isles is a different illness to that experienced elsewhere. It amy be, however, that IVGG is less effective in the treatment of British patients with Kawasaki disease than has been the experience in the United States and Japan. These observations emphasise the need for a therapeutic trial of treatment modalities for Kawasaki disease in the UK and the Republic of Ireland.     

Recurrent skin peeling following Kawasaki disease.

Long term follow up of 259 cases of Kawasaki disease led to the observation that 11% of children have episodes of recurrent peeling of the skin for several years after their recovery. These events were usually associated with an upper respiratory tract infection and were distinct from a recurrence of Kawasaki disease. Repeeling was significantly less frequent in children who had suffered coronary artery dilatation and was more frequently seen in those with nasal staphylococcal colonisation. The mechanism for this phenomenon is unclear, but it has been observed in a number of other conditions caused by infectious agents and their toxins. Paediatricians need to be aware of this phenomenon which is distinct from recurrence of Kawasaki disease.     

Febrile convulsion during the acute phase of Kawasaki disease

BACKGROUND: Although seizures occur in association with meningitis or encephalitis in Kawasaki disease, febrile convulsions in Kawasaki disease are considered to be extremely rare. The aim of the present study is to elucidate the incidence of febrile convulsion in the acute phase of Kawasaki disease, in Niigata City General Hospital, Niigata, Japan. METHODS: The study included 177 patients with Kawasaki disease. Patients ranged in age from 2 months to 10 years (mean age 26.89 +/- 22.44 months). The study included 105 males and 72 females. The clinical records of Kawasaki disease patients were examined retrospectively. RESULTS: Febrile convulsions were not recognized in these 177 patients throughout the course of the disease, despite the presence of a high grade fever and their young age. However, eight of the 177 patients had experienced simple febrile convulsions during other febrile illness except for those with Kawasaki disease. In the acute phase of Kawasaki disease, only two patients showed generalized convulsion associated with prolonged consciousness disturbance and pleocytosis in the cerebrospinal fluid. CONCLUSION: The incidence of febrile convulsions in the acute phase of Kawasaki disease might be extremely low, confirming the results of previous reports. Kawasaki disease is characterized by systemic vasculitis and is sometimes complicated by intracranial vasculitis. The incidence of electroencephalographic abnormalities and pleocytosis in the cerebrospinal fluid is higher in patients with Kawasaki disease. However, the reason why febrile convulsions did not occur in the acute phase of Kawasaki disease remains unknown, despite the presence of central nervous system involvement.     

2002-2010年北京儿童医院川崎病住院患儿临床分析

目的总结川崎病的临床特征,以指导临床治疗。方法回顾性分析2002年1月-2010年12月1 484例北京儿童医院川崎病住院患儿临床资料,总结分析其临床特征。结果北京儿童医院川崎病患儿年龄分布为2个月～14.7岁,高峰年龄为1岁;男女=1.821,复发率1.7%。6种主要临床表现中,发热为最常见临床表现,皮疹发生率最低。1 484例川崎病患儿中行2 g.kg-1IVIG初次治疗者占92.4%,其中IVIG无反应型川崎病发生率为16.9%。实验室检查中CRP升高、ESR升高、白细胞升高、贫血、血浆清蛋白降低、低钠血症、肝功能异常、心肌酶异常发生率分别为94.5%、96.4%、89.2%、72.3%、81.8%、37.9%、56.9%、27.4%。其中贫血及心肌酶升高婴幼儿发生率较高,且除贫血和肝功能异常外,其他化验指标在冠状动脉扩张发生率方面无统计学差异。冠状动脉扩张发生率为36.1%,非冠状动脉心血管并发症中,心电图异常最常见,发生率为32.3%。结论本组90%以上的川崎病患儿CRP及ESR升高,提示CRP及ESR可作为川崎病尤其是不完全川崎病的参考诊断指标,除贫血和肝功能异常外其他化验指标在冠状动脉扩张发生率方面无统计学差异,提示这2项指标在一定程度上可反映病情的轻重。     

儿童 2 年内川崎病多次复发 1 例报告#br#

目的：探讨儿童川崎病（KD）多次复发情况。方法回顾分析1例多次复发KD患儿2年的临床资料。结果患儿,男,4岁。于2岁时第1次患典型KD,无冠状动脉损伤,以后2年内又患不完全KD共4次,均表现为发热伴颈部淋巴结肿痛、双侧球结膜充血、唇红、皲裂、杨梅舌,无咽痛、咽炎、口腔溃疡,血常规白细胞计数、C反应蛋白、红细胞沉降率均升高,颈部淋巴结超声均未见化脓性改变,大剂量丙种球蛋白静脉输注后均退热,每次发热持续时间为6~8 d,相邻2次发热之间的无热间隔期约为2.5、1.5、4.5、13.5个月,临床表现和基因检测结果均不符合周期性发热、口疮性口炎、咽炎及颈淋巴结炎综合征（PFAPA）。结论儿童2年内患5次KD罕见,需要长期随访。     

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目的分析儿童静脉注射免疫球蛋白(IVIG)不敏感川崎病的临床特点。方法对2005-01—2005-12在重庆医科大学儿童医院住院的233例川崎病的患儿进行病例回顾性分析。结果IVIG不敏感川崎病共31例(占13.3%)。IVIG不敏感川崎病中男女性别比为4.17∶1,明显高于IVIG敏感川崎病1.43∶1(P<0.05)。两组川崎病年龄构成差异无显著性(P>0.05)。IVIG不敏感川崎病中有中度以上冠状动脉扩张或冠状动脉瘤者6例(6/31,19.4%),明显高于IVIG敏感川崎病(5/202,2.4%)(P<0.05)。川崎病患儿发生IVIG耐药的可能危险因素有外周血白细胞、中性粒细胞比例、血红蛋白、C反应蛋白、血沉、血浆白蛋白、乳酸脱氢酶等,分析结果提示血浆白蛋白降低及男性可能与IVIG不敏感川崎病有关,但仅此两项指标尚不能预测IVIG不敏感川崎病的发生。IVIG不敏感川崎病冠脉病变发生危险因素无阳性发现。IVIG不敏感川崎病患儿中14例通过复用IVIG后临床症状得以缓解,仅8例在复用IVIG后症状仍不能控制而加用激素治疗。结论IVIG不敏感川崎病并不少见且较IVIG敏感川崎病更易发生较严重冠状动脉病变,川崎病患儿发生IVIG耐药及IVIG不敏感川崎病冠脉病变发生的危险因素不肯定。复用IVIG及必要时在抗凝基础上加用激素对IVIG不敏感川崎病治疗有较好疗效。     

Kawasaki disease: A brief history

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 distinct clinical entity. Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide surveys in Japan. These have indicated that: 1) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; 2) there are approximately 5,000 to 6,000 new cases each year; 3) current estimates of incidence rates are 120 to 150 cases per 100,000 children <5 years old; 4) KD is 1.5 times more common in males and 85% of cases occur in children <5 years old; and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for Disease Control and Prevention published a case definition based on Kawasaki's original criteria. The Centers for Disease Control and Prevention developed a computerized database in 1984, and a passive reporting system currently exists in 22 states. Regional investigations and national surveys suggest an annual incidence of 4 to 15 cases per 100 000 children <5 years o     

Analysis of Kawasaki disease showing elevated antibody titres of Yersinia pseudotuberculosis

AIM: To elucidate a clinical difference between patients with Kawasaki disease documented with Yersinia pseudotuberculosis infection and patients with Kawasaki disease without Yersinia pseudotuberculosis infection. PATIENTS AND METHODS: From January 1985 to July 2004, 452 patients were diagnosed with Kawasaki disease. Forty-two patients had elevated antibody titres of Yersinia pseudotuberculosis and/or positive stool culture (Yersinia-positive group). Three hundred and thirty patients had no elevated antibody titres (Yersinia-negative group). We compared the clinical characteristics retrospectively. RESULTS: The age of onset in the Yersinia-positive group (3.05+/-2.20 y) was significantly higher than that in the Yersinia-negative group (2.31+/-2.05 y) (p=0.03). The age-adjusted statistical analysis demonstrated that the incidence of coronary artery lesions (dilatations plus aneurysms) in the Yersinia-positive group (22/42, 52.4%) was significantly higher than in the Yersinia-negative group (105/330, 31.8%) (p=0.001), and the incidence of additional administration of immunoglobulin in the Yersinia-positive group (13/36, 36.1%) was significantly higher than in the Yersinia-negative group (41/256, 16.0%) (p=0.004). CONCLUSION: Our data suggest that Yersinia pseudotuberculosis infection might play a role in the developing mechanism of poor response to therapy and the tendency to develop coronary artery lesions in Kawasaki disease patients.     

An adolescent with Kawasaki disease

Kawasaki disease is an acute vasculitis of unknown etiology that predominantly affects children <5 years of age. The incidence and the severity of myocarditis in this disease is variable and depends upon the stage of the disease, acute or chronic. Acute-stage Kawasaki disease shows relatively high incidence of myocarditis, but almost all cases are clinically mild. We describe teenage boy presenting with atypical/incomplete manifestations of Kawasaki disease and developing fulminant myocarditis within a week of illness resulting in death. The case underscores the importance of suspecting Kawasaki disease in a young child presenting with features of myocardial ischemia.     

Facial nerve palsy complicating Kawasaki disease

The diagnosis of Kawasaki disease, the most common cause of pediatric acquired heart disease, is difficult and often delayed for children whose age falls outside the typical range of 6 months to 5 years, especially in those with incomplete Kawasaki disease and atypical features. Delayed diagnosis is associated with an increased incidence of coronary artery pathology. Here we describe 2 cases of lower motor neuron facial nerve palsy complicating Kawasaki disease. In both cases the diagnosis of Kawasaki disease was not made acutely, and both patients developed extensive coronary artery lesions. These cases highlight the importance of considering Kawasaki disease in children with unexplained prolonged fever at any age, particularly those without full diagnostic criteria and with unusual features.