Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research

This article proposes a clinical guideline for the diagnosis and treatment of Kawasaki disease in the UK based on the best available evidence to date, and highlights areas of practice where evidence is anecdotal or based on retrospective data. Future research as proposed by the London Kawasaki Disease Research Group is outlined, and clinicians are invited to prospectively enroll their suspected cases into this collaborative research project.     

An update on Kawasaki disease II: Clinical features,diagnosis, treatment and outcomes

This is the second of two updates on Kawasaki disease. The first review focused on epidemiology and aetio‐pathogenesis. Here, we review the clinical features and diagnosis of Kawasaki disease, as well as recent evidence on treatment, follow‐up and cardiovascular outcomes.     

Adenovirus, adeno-associated virus and Kawasaki disease

Clinical similarities and shared seasonality suggested a relationship between adenovirus infection and Kawasaki disease. We performed adenovirus serology and quantitative polymerase chain reaction for both adenovirus and adeno-associated virus in patients with acute Kawasaki disease. No evidence was found to suggest a link between either virus and Kawasaki disease.     

静脉输注免疫球蛋白在儿童川崎病中应用的专家共识

川崎病是一种好发于5岁以下儿童的急性自限性血管炎性疾病。静脉输注免疫球蛋白（intravenous immunoglobulin,IVIG）已经成为一种有效的治疗方案,可以有效减少心血管并发症的发生率,但目前国内外尚无儿童川崎病IVIG应用共识或临床指南。该共识是基于目前国内外关于儿童川崎病中IVIG应用的研究进展,同时参考国内外川崎病的诊疗指南,并经过制定专家充分讨论而形成。该共识对IVIG在儿童川崎病中的临床应用策略及其不良反应的防治提出了具体建议。 引用格式:     

Kawasaki disease fact check: Myths,misconceptions and mysteries

Kawasaki disease (KD) is an important cause of childhood vasculitis and a common cause of acquired heart disease in children world‐wide. The emergence of Paediatric Multisystem Inflammatory Syndrome‐Temporally Associated with SARS‐CoV‐2, a KD‐like hyperinflammatory syndrome and the recent death of Dr Tomisaku Kawasaki make this a timely review. Although KD was described by Dr Kawasaki over 50 years ago, there is still no specific diagnostic test and the aetiology remains elusive. This article summarises the latest evidence, highlights important myths and misconceptions and discusses some of the mysteries that surround this disease.     

Kawasaki disease: infection, immunity and genetics

Kawasaki disease is an acute multisystem vasculitic syndrome of unknown etiology occurring mostly in infants and children younger than 5 years of age. In developed countries, Kawasaki disease is currently the leading cause of acquired heart diseases in children. However, it is still a mysterious disease. In this article, we reviewed and summarized from the aspects based on infection agents, host immune dysregulation and genetic background intended to establish a feasible infection-immunogenetic pathogenesis for this mysterious disease and also provided the rational strategy to explore optimal treatment of this disease.     

川崎病冠状动脉损伤机制及治疗新进展

川崎病也称为皮肤黏膜淋巴结综合征,是一种具有自限性、由免疫介导的全身中小血管的炎性综合征,其中冠状动脉最易受累。目前川崎病已逐渐成为发达国家儿童冠状动脉损伤的首位病因。冠状动脉的损伤机制及治疗是目前川崎病研究的热点。该文就川崎病引起冠状动脉损伤的机制及治疗最新进展作一综述。     

Kawasaki disease

PURPOSE OF REVIEW: Kawasaki disease is an acute, self-limited vasculitis of childhood characterized by fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develop in approximately 15 to 25% of untreated children with the disease and may lead to myocardial infarction, sudden death, or ischemic heart disease. RECENT FINDINGS: In the United States, Kawasaki disease has now surpassed acute rheumatic fever as the leading cause of acquired heart disease in children. The cause of Kawasaki disease remains unknown, but fortunately intravenous immune globulin therapy has proved to be effective at reducing the prevalence of coronary aneurysms in most children treated in the acute phase. Therapy for Kawasaki disease resistant to intravenous immune globulin therapy is an area of research and controversy. The long-term treatment of children with Kawasaki disease is dependent on coronary artery status. SUMMARY: This review covers key data on the etiology, pathogenesis, treatment, and long-term outcomes of Kawasaki disease, highlighting recent publications.     

他汀类药物在川崎病治疗中的研究进展

川崎病是一种自身免疫性血管炎性疾病,主要累及中小动脉,尤其是冠状动脉,冠状动脉损伤程度与川崎病的预后密切相关。他汀类药物在心血管疾病中的治疗作用已被证实,近年来研究发现其在川崎病的治疗中也发挥重要作用,对川崎病急性期及恢复期阻止冠脉动脉瘤形成具有潜在价值。现就他汀类药物在川崎病治疗中的研究进展作一综述。     

静脉人免疫球蛋白无反应型川崎病患儿的循证治疗

目的：针对近期收治的1例IVIG无反应型川崎病的患儿,我们进行了证据检索和评价,以期找到更有效的治疗方法。方法：通过计算机检索UpToDate(2012.10)、Cochrane图书馆（Issue 10,2012）、PubMed（1978~2012.10）、CNKI（1978~2012.10）等数据库,查找免疫球蛋白或糖皮质激素治疗IVIG无反应型川崎病及病情缓解有关的系统评价、临床随机对照试验等,并对所获证据进行GRADE评价。结果：高质量的临床证据表明,小剂量激素联合IVIG治疗IVIG无反应型川崎病,其在退热效果及减少冠状动脉扩张方面,均优于单纯IVIG治疗。根据此临床证据,结合医生经验及家属意愿对该患儿实施甲强龙（2mg/kg,ivd）联合第三剂IVIG（1g/kg）治疗,激素逐渐减量维持,并继续采用阿司匹林、双嘧达莫等治疗。经治疗后,患儿体温及各实验室指标逐渐恢复正常,心脏彩超随访半年未见有冠状动脉进一步损伤。结论：小剂量激素联合IVIG治疗IVIG无反应型川崎病可有效退热及减少冠脉扩张,长期效果需待进一步观察。     

Antiendothelial cell antibodies detected by a cellular based ELISA in Kawasaki disease.

Kawasaki disease is an acute vasculitic illness of childhood associated with significant morbidity and mortality. A cellular based enzyme linked immunosorbent assay (ELISA) was used to demonstrate the presence of antiendothelial cell antibodies in sera from children with Kawasaki disease. Twenty one of 32 patients with Kawasaki disease had raised IgM antibody titres and four had raised IgG antiendothelial antibody titres. There was a significant difference in the IgM antiendothelial cell antibody titres when comparing the patients with normals and febrile controls. The antibody titre paralleled the disease activity in patients studied serially. There was no relative increase in binding of antiendothelial cell antibodies after cytokine stimulation. These findings may be of importance in further research into the understanding of mechanisms involved in this and other forms of vasculitis in man.     

Kawasaki disease in India–Lessons learnt over the last 20 years

Over the last 20 years, Kawasaki disease is being increasingly recognized in India and it may soon replace acute rheumatic fever to become the commonest cause of acquired heart disease amongst children. However, the vast majority of children with Kawasaki disease in India are still not being diagnosed. Diagnosis of Kawasaki disease is based on a constellation of clinical findings which have a typical temporal sequence. All pediatricians must we familiar with the nuances involved in arriving at a diagnosis of Kawasaki disease. With early diagnosis and prompt treatment, the risk of coronary artery abnormalities can be significantly reduced.     

川崎病休克综合征早期识别与诊治研究进展

川崎病(KD)是儿童常见的急性血管炎,而川崎病休克综合征(KDSS)是KD少见而又严重的表现形式,近年来逐渐引起临床医师的关注,因其可出现在疾病早期,病情进展迅速,并伴有多系统器官受累,早期诊断困难,极易漏诊和误诊.本文综述了近年来KDSS诊断、早期识别、发病机制及治疗和预后等的研究进展.     

Small bowel obstruction as a complication of Kawasaki disease

A case of small bowel obstruction in an 8-month-old infant with Kawasaki disease is described. At laparotomy a discrete area of jejunal stricture with adhesions was noted. Microscopic examination revealed evidence of small artery thrombosis. Kawasaki disease results in a diffuse vasculitis, which may produce significant abnormalities in multiple organ systems. Serious abdominal complications can occur and should be considered when gastrointestinal symptoms develop in a patient with Kawasaki disease.     

Doppler detection of tricuspid regurgitation following Kawasaki disease

Between June 1984 and April 1985, five patients (4.2%) had tricuspid regurgitation detected on pulsed Doppler echocardiography among 119 patients with Kawasaki disease. The grade of tricuspid regurgitation was moderate in three and mild in two patients; conventional cardiac examinations revealed no evidence of this complication. All patients had associated coronary artery aneurysms except one, but no patients developed subsequent myocardial infarction. The occurrence of tricuspid regurgitation following Kawasaki disease has been considered to be causally related to the carditis, a frequent complication during the acute febrile period of the illness. The present data indicate that tricuspid regurgitation is an additional cardiovascular complication of Kawasaki disease and that Doppler echocardiography is useful in detecting this disorder.     

Kawasaki Disease and Epstein-Barr Virus

We report the results of virological (serological and molecular biological) studies of Epstein-Barr virus (EBV) in patients with Kawasaki disease (KD). Forty-nine (86%) of 57 Kawasaki disease patients and 15 (68%) of 22 patients with recurrent Kawasaki disease had serological evidence of primary Epstein-Barr virus infection during the first month after the onset of their disease based on the results of a sensitive method of detecting antibody to viral capsid antigen (VCA). The serological response to EBV was significantly low and transient. EBV sequences were identified directly in peripheral blood mononuclear cell (PBMC) DNA samples from 23 (56%) of 41 KD patients within 2 weeks after onset by means of the polymerase chain reaction (PCR). EBV sequences were also detected in 10 (83%) of 12 repeatedly tested KD patients within 3 months after onset. In contrast, only 7 (18%) of 40 control DNA samples were PCR-positive. These virological studies indicate that an unusual EBV-cell interaction may occur in KD.     

Update on Kawasaki disease: Epidemiology,aetiology and pathogenesis

Kawasaki disease is an acute systemic vasculitis predominantly affecting young children. It is due to an abnormal host response to as yet unidentified infectious trigger(s). Kawasaki disease may cause coronary artery damage, long‐term cardiovascular morbidity and occasionally mortality, especially if the diagnosis is missed or timely treatment is not given. This is the first of two updates on Kawasaki disease. Here we review recent advances in epidemiology, possible aetiologies, host susceptibility and pathogenesis of this fascinating condition.     

川崎病患者易早发动脉粥样硬化

川崎病是一种急性自限性全身性血管炎,其心血管并发症,尤其是冠状动脉损害(冠状动脉扩张、冠状动脉瘤形成、冠状动脉狭窄甚至闭塞等)使其受到了临床医师,尤其是儿科临床医师的广泛关注.川崎病首次被认识至今已经40余年,随着那些最早的川崎病患者逐渐迈入中年,关于川崎病长期预后的研究引起了临床工作者的极大兴趣.虽然动脉粥样硬化性心血管疾病临床表现多出现在中老年期,但近年来其被认为是一种病变始于儿童时期,并在各种危险因素的作用下逐渐进展的疾病.越来越多的研究发现,川崎病尤其是伴有冠状动脉损害的川崎病可能是早发动脉粥样硬化的危险因素.     

CASP3基因一个新的功能性SNP rs72689236与川崎病相关性的Meta分析

目的：综合分析半胱氨酸蛋白酶3基因 (CASP3)一个新的功能性单核苷酸多态位点（SNP） rs72689236与川崎病发生发展的相关性。方法：国内外数据库中检索川崎病与CASP3基因相关性研究的文献,根据纳入与排除标准筛选文献,获取2012年11月以前公开发表的病例-对照研究与家系传递不平衡研究（TDT）的资料,结合作者的相关研究结果,评价质量后采用RevMan 5.1软件进行Meta分析。结果：川崎病患者中rs72689236的A等位基因频率显著增高（P<0.001,OR=1.34,95% CI：1.24~1.46)。rs72689236风险等位基因A的携带者（AG+AA）相较于GG个体,患病风险增加约44% （P<0.001, OR=1.44,95% CI：1.27~1.65）。该SNP的风险等位基因A增加了川崎病并发冠状动脉损伤的风险（P=0.01, OR=1.51,95% CI：1.10~2.07）,携带风险等位基因A的川崎病患者相比于非携带者,并发冠状动脉损伤的风险增加约59%（P=0.05, OR=1.59,95% CI：1.00~2.53）。未发现该SNP与川崎病患者静脉注射免疫球蛋白（IVIG）疗效相关联的证据。结论：CASP3基因功能性SNP rs72689236的A等位基因增加了川崎病的发生风险,该SNP的风险等位基因有可能作为川崎病并发冠状动脉损伤的易感遗传标记。目前还没有足够的证据提示该SNP对川崎病的重要治疗手段IVIG的疗效存在影响,需要更多的相关研究以进一步评价其应用于临床个体化治疗方案选择的可行性。