Etiology Of Kawasaki Disease Research Articles

Abstract 17: Environmental Epidemiology of Kawasaki Disease

Background: The etiology of Kawasaki disease (KD) is commonly described as an exaggerated immune response to an environmental or infectious trigger in developmentally, immunologically and genetically susceptible children. The trigger for KD has not yet been identified. Methods: Patients with newly diagnosed KD (n=73) were enrolled within 6 weeks of KD diagnosis. Control subjects (n=65) were enrolled during pediatric annual visits and from friends of enrolled KD patients. All participants completed an extensive questionnaire about medical history, family and environment. Geographic localisation software characterized the participants’ neighborhoods. A hypothetical scenario was used for control patients to simulate similar recall bias to that of the KD patients. Results: There were no differences in age, gender, allergies, child and family medical history or recent vaccination. Children with KD were more likely to be unwell prior to KD symptom onset than controls, including fever, stomach pain, lethargy, jaundice, loss of appetite and irritability, but not infectious disease symptoms (16% vs. 21%, p=0.49). Infectious symptomatology developed concurrently to classic KD symptoms. Children with KD had less exposure to environmental allergens and were more likely to be exposed to chemical irritants. Conclusions: The presence of symptoms for up to 1 month before onset of KD may suggest that a preceding illness/environmental agents may alter barriers to entry/exposure or prime an immunologic reaction to an etiologic trigger. Children with fewer allergen/infectious exposures and chronic chemical exposure may be immunologically more susceptible.

Abstract 49: Kawasaki Disease With Tsutsugamushi Disease: A Case Report

Background : Clinical and epidemiologic features suggest infectious agents as a possible cause of Kawasaki disease; however, the etiology of Kawasaki disease still remains unknown. A number of microorganisms were hypothesized as an etiology of the illness. This is the first reported case of Kawasaki disease with tsutsugamushi disease. Case presentation: We report the case of a 4-year-old boy who presented with fever of 7 days duration and skin rash and bilateral conjunctival injection. He had a history of visiting a rural area with his grandmother. On admission, he had fever of 39.4 °C. His heart rate was 90/minute and his blood pressure was 90/60 mmHg. His pharynx was slightly injected and there was red lip. His neck was swollen with cervical lymphadenitis. He had erythematous macular rash on her trunk. Examination of his skin revealed an eschar on penile base of right scrotum. His laboratory results showed WBC 4,720/mm 3 , 42% polymorphonuclear leucocytes, 39% lymphocytes, hemoglobin 10.3 gm/dL, platelet count 148,000/mm 3 , CRP 3.23mg/dl, pro-BNP 316.5 pg/ml. The respiratory viruses using a multiplex real-time-PCR kit (Adenovirus, Influenza A, Influenza B, Metapneumovirus, Rhino A virus, Respiratory syncytiai virus, Parainfluenza ) were all negative. Mycoplasma pneumonia IgM was negative. R.tsutsugamushi Ab was positive. Echocardiographic findings 1 day after admission was mild dilatation of LCA (RCA=1.8mm, LCA=3mm). He was treated on oral roxithromycin for presumptive diagnosis of tsutsugamushi disease along with clinical features of Kawasaki disease which resolved after therapy with intravenous immune globulin and aspirin. Over the next 48 hours, he became afebrile and his rash improved. He was placed on low-dose aspirin for 8 weeks. His echocardiogram were within normal limit (RCA= 1.9mm, LCA= 2.7mm) at 2 months after the onset of his illness. Conclusion: This case report suggests that Kawasaki disease can rarely occur concurrently or immediately after a rickettsial illness such as tsutsugamushi disease.

Abstract 67: Peroral Administration Of Extract Of Candida Albicans Induce Kawasaki Disease-like Vasculitis In Mice

Background: The cause of Kawasaki disease (KD) has been still unknown though the intestinal flora was reported as one of the candidate etiology of KD. Candida is known as one of the intestinal flora. Intraperitoneal injection of Candida albicans water-soluble fractions (CAWS) that compose of polysaccharide of cell wall of the yeast can induce systemic vasculitis in mice. It is evaluated as animal model of Kawasaki disease vasculitis because this experimental vasculitis is similar to those observed in KD patients. However it is uncertain whether or not oral administration of CAWS can induce vasculitis in mice. Aim: The present study aimed to elucidate whether or not oral administration of CAWS can induce vasculitis. Materials and methods: Mice, DBA/2, male, 4 weeks of age were used. CAWS suspended in PBS was administered perorally to mice for 28 consecutive days. As a priming agent, 20 micrograms of LPS was injected to mice intraperitoneally before administration of CAWS. Experimental groups are as follows. Group-I : Peroral administration of 800 micrograms of CAWS with LPS, Group-II: Peroral administration of 800 micrograms of CAWS without LPS, Group-III : Peroral administration of 250 micrograms of CAWS with LPS. Mice injected CAWS intraperitoneally (conventional procedure) were used as control group. Vasculitis was evaluated by routine histological techniques. This study conformed with regulations of position of the American Heart Association on research animal use and Toho University’s Animal Ethics Committee. Result: The incidence of vasculitis in each group were as follows : Group-I : 1/6, Group-II:0/6, Group-III:1/6, Control : 3/3. Dense infiltration of neutrophils and macrophages was observed in coronary artery and/or aortic root. Severity of inflammatory cell infiltration and extent of the lesion in Group-I and Group-III were milder and smaller than those of control. Conclusion: Present study revealed that peroral administration of CAWS could induce vasculitis in mice though the incidence of vasculitis was lower than that of control. This model is considered to be useful to clarify the relation between intestinal immunity and vasculitis. We should clarify the mechanism that oral administration of CAWS induced vasculitis.

Imputation of class I and II HLA loci using high-density SNPs from ImmunoChip and their associations with Kawasaki disease in family-based study.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children in most developed countries including the United States. The etiology of KD is not known; however, epidemiological and immunological data suggest infectious or immune-related factors in the manifestation of the disease. Further, KD has several hereditary features that strongly suggest a genetic component to disease pathogenesis. Human leucocyte antigen (HLA) loci have also been reported to be associated with KD, but results have been inconsistent, in part, because of small study samples and varying linkage disequilibrium (LD) patterns observed across different ethnic groups. To maximize the informativeness of single nucleotide polymorphism (SNP) genotypes in the major histocompatibility (MHC) region, we imputed classical HLA I (A, B, C) and HLA II (DRB1, DQA1, DQB1) alleles using SNP2HLA method from genotypes of 6700 SNPs within the extended MHC region contained in the ImmunoChip among 112 White patients with KD and their biological parents from North America and tested their association with KD susceptibility using the transmission disequilibrium test. Mendelian consistency in the trios suggested high accuracy and reliability of the imputed alleles (class I = 97.5%, class II = 96.6%). While several SNPs in the MHC region were individually associated with KD susceptibility, we report over-transmission of HLA-C*15 (z = +2.19, P = 0.03) and under-transmission of HLA-B*44 (z = -2.49, P = 0.01) alleles from parents to patients with KD. HLA-B*44 has been associated with KD in other smaller studies, and both HLA-C*15 and HLA-B*44 have biological mechanisms that could potentially be involved in KD pathogenesis. Overall, inferring HLA loci within the same ethnic group, using family-based information is a powerful approach. However, studies with larger sample sizes are warranted to evaluate the correlations of the strength and directions between the SNPs in MHC region and the imputed HLA alleles with KD.

History of Kawasaki disease

We describe a short history of Kawasaki disease. In 1967, we published a paper entitled 'Infantile acute febrile mucocutaneous lymph node syndrome with specific desquamation of the fingers and toes. Clinical observation of 50 cases'; this was the first report on what is now called Kawasaki disease. Since then, many reports on cardiology, treatment, epidemiology, pathology and etiology of Kawasaki disease have been published. Furthermore, a recent Chapel Hill Consensus Statement on Kawasaki disease in the classification of vasculitis is given, along with a figure on the relationship and classification of childhood vasculitis by autopsy material.

Development of Kawasaki disease in a patient with PFAPA

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA) is one of the autoinflammatory diseases of unknown etiology characterized by regularly recurrent fever episodes with attacks lasting 3-6 days every 3-8 weeks associated with at least one of the three cardinal clinical signs: aphthous stomatitis, pharyngitis, and cervical adenitis. Kawasaki disease (KD) is an acute, self-limited systemic vasculitis that occurs predominantly in infants and young children. In most KD patients, i.v. immunoglobulin leads to a rapid amelioration of clinical symptoms and significantly decreases the risk of coronary artery aneurysms. Although the etiology of KD is still unknown, it was reported that innate immunity was activated in the patients. Described herein is a patient with PFAPA who developed KD. This is the first report of KD development in a PFAPA patient. The association between KD and PFAPA may represent a genetic predisposition to dysregulated innate immune response.

Kawasaki Disease

To the Editors: Previous studies have shown that 4.6% of patients with Kawasaki disease (KD) present with acute surgical abdomen.1 Although the etiology of KD is likely cytokine-associated disease, previous studies have not confirmed the cytokine characteristics in patients with acute surgical abdomen and KD. We describe the relationship between acute surgical abdomen and cytokine profile in a patient with KD. A 5-year-old boy was referred for suspected peritonitis on day 6 of treatment for persistent high fever, frequent diarrhea and abdominal pain. He was pyrexic (39.2°C) and dehydrated with diffuse abdominal tenderness and rigidity. At admission, a complete blood count revealed hemoglobin of 129 g/L, white blood cell count of 20.0 × 109/L with neutrophilia and platelet count of 153 × 109/L. Biochemical laboratory findings included hyponatremia (123 mEq/L), hypoalbuminemia (2.3 g/dL) and high C-reactive protein concentration (12.4 mg/dL). Chest radiographs and a computed tomography scan revealed ascites, ileus of the small bowel and colonic mucosal thickening. The patient received intravenous administration of albumin and intravenous antimicrobial treatment without improvement. Because the patient was suffering from severe abdominal pain, increased white blood cell count (15.9 × 109/L) and C-reactive protein (15.5 mg/dL), exploratory laparotomy was performed on day 8 that revealed marked serous ascites, mesenteric adenopathy and no bowel perforation. Because our surgeon chose a minimally invasive approach, lymph node biopsy was not performed. The appendix was removed, and pathological examination of the resected specimen confirmed a focal peritonitis. Cytology of the ascites showed increased cellularity (0.6 × 109/L, 50% neutrophils and 50% lymphocytes without malignant cells) consistent with exudative ascites and a total protein content of 28 g/L consistent with exudative and transudative ascites. Bacterial cultures of the ascitic fluid, blood and stool were negative. Serologic tests for antinuclear antibodies, antineutrophil cytoplasmic antibodies, C3, C4, Mycoplasma and Yersinia enterocolitica were negative. Polymerase chain reaction did not detect Epstein-Barr virus DNA in the blood, and cytomegalovirus antigen was not increased. On day 9, polymorphous exanthema developed on the patient’s hand which lasted for 1 day. The patient then developed oliguria, leg and palpebral edema and a gallop rhythm. Cardiomegaly with pleural effusion was seen on chest radiographs, and decreased ejection fraction of 51% with moderate mitral regurgitation and mild pericardial effusion was seen on echocardiography. We started anticongestive therapy with furosemide (0.5 mg/kg, 3 times daily), carperitide (0.05–0.2 μg/kg/min) and olprinone (0.3 μg/kg/min), and contractility improved (ejection fraction 56%). Intravenous methylprednisolone pulse therapy was instituted at 30 mg/kg/d on days 9, 10 and 11 to counteract abdominal pain and high grade fever, and these symptoms improved promptly. Echocardiography showed increased echo intensity in the coronary arterial wall and increased pericardial effusion. Intravenous immunoglobulin was begun (day 10, 1 g/kg; day 12, 2 g/kg) because of suspected atypical KD, and all effusions resolved. The patient developed desquamation of the fingers and toes on day 11. One month later, the patient’s mother reported that he had transient conjunctival congestion and reddening of the lips. Therefore, 5 of 6 principal symptoms and signs were satisfied for a diagnosis of KD. The patient had no cardiac deficits after 10 months. Elevated cytokines included serum interleukin (IL)-6 (day 9, 484 pg/mL; day 17, <1.6 pg/mL; normal, <4 pg/mL), IL-8 (day 9, 35.5 pg/mL; day 17, 16 pg/mL; normal, <2 pg/mL) and tumor necrosis factor (TNF)-α (day 9, 8.5 pg/mL; day 17, 2.4 pg/mL; normal, 0.6–2.8 pg/mL). Serum vascular endothelial growth factor also increased (day 9, 413 pg/mL; day 17, 911 pg/mL; normal, <459 pg/mL).2 In our patient with acute surgical abdomen and KD, a significantly increased IL-6 in the acute phase and later increased vascular endothelial growth factor were similar to previously reported elevations of these cytokines in KD resistant to initial intravenous immunoglobulin.3,4 Many reports have indicated that indurative edema develops by exudative mechanisms, caused by vasculitis in KD. Yasukawa et al2 showed that the exudative mechanism in KD was the direct result of increased serum vascular endothelial growth factor associated with cytokines (ie, IL-6) and reflected the severity of vascular hyperpermeability. In general, serum TNF-α is elevated in KD, with the highest values observed in patients who develop coronary artery aneurysm.5 Zulian et al1 reported that half of KD patients with acute surgical abdomen developed coronary artery aneurysm with cardiac involvement, whereas TNF-α with KD was not confirmed. In our patient, KD with cardiac involvement occurred with slightly increased serum TNF-α without coronary artery aneurysm. Kenji Miyamoto, MD Yuzuru Yamazaki, MD Department of Pediatrics, Dokkyo Medical University Kentaro Okamoto, MD Department of Pediatric surgery, Dokkyo Medical University Tatsuo Tsuboi, MD Jun-ichi Hirao, MD Osamu Arisaka, MD Department of Pediatrics, Dokkyo Medical University, Tochigi, Japan

Manejo anestésico del paciente con enfermedad de Kawasaki durante la cirugía de revascularización coronaria: informe de un caso

Kawasaki disease is a self-limited vasculitis that occurs predominantly in infants and young children, that is characterized by coronary artery lesions (especially aneurysms). It is one of the leading causes of acquired heart disease in children. The etiology of Kawasaki disease still remains unknown. A hypothesis is that an infectious agent produces clinically apparent disease only in certain genetically predisposed individuals. It also is possible that the disease results from an immunologic response and is triggered by different microbial agents. For unknown reason it dominates in Asians. Treatment is directed to prevent coronary thrombosis and reduce inflammation; it is based on high-dose intravenous immunoglobulin and acetyl salicylic acid, which significantly reduce the risk of coronary artery aneurysms from 25 to 4%. In order to reduce myocardial ischemia, percutaneous coronary interventions and coronary artery bypass graft can be used. There is a lot of information about surgical techniques for coronary artery complications linked to Kawasaki disease, but minimal information about anesthetic techniques; for this reason, we describe the anesthetic management of a patient who required coronary artery bypass graft, and we present a literature review on the topic.

Decreasing Fertility Rate Correlates with the Chronological Increase and Geographical Variation in Incidence of Kawasaki Disease in Japan

BackgroundKawasaki disease (KD) is a common cause of acquired paediatric heart disease in developed countries. KD was first identified in the 1960s in Japan, and has been steadily increasing since it was first reported. The aetiology of KD has not been defined, but is assumed to be infection-related. The present study sought to identify the factor(s) that mediate the geographical variation and chronological increase of KD in Japan.Methods and FindingsBased upon data reported between 1979 and 2010 from all 47 prefectures in Japan, the incidence and mean patient age at the onset of KD were estimated. Using spatial and time-series analyses, incidence and mean age were regressed against climatic/socioeconomic variables. Both incidence and mean age of KD were inversely correlated with the total fertility rate (TFR; i.e., the number of children that would be born to one woman). The extrapolation of a time-series regressive model suggested that KD emerged in the 1960s because of a dramatic decrease in TFR in the 1940s through the 1950s.ConclusionsMean patient age is an inverse surrogate for the hazard of contracting the aetiologic agent. Therefore, the observed negative correlation between mean patient age and TFR suggests that a higher TFR is associated with KD transmission. This relationship may be because a higher TFR facilitates sibling-to-sibling transmission. Additionally, the observed inverse correlation between incidence and TFR implies a paradoxical “negative” correlation between the incidence and the hazard of contracting the aetiologic agent. It was hypothesized that a decreasing TFR resulted in a reduced hazard of contracting the agent for KD, thereby increasing KD incidence.

Comorbidity of Kawasaki disease and group A streptococcal pleural effusion in a healthy child: a case report

BackgroundKawasaki disease is an acute self-limiting vasculitis that affects children. The most dreaded complication of Kawasaki disease reported in the literature over the years is coronary artery disease, which is considered as the main cause of acquired heart disease. However, pulmonary associations with Kawasaki disease have been overlooked. We present a rare, if not unique, case of Kawasaki disease associated with group A streptococcus pleural effusion in the English language literature. A search of the PubMed database was carried out, using a combination of the terms “Kawasaki disease”, “pneumonia”, and “group A streptococcus”. The majority of studies conducted in children with Kawasaki disease have concentrated on the coronary artery implications. Kawasaki disease is considered a self-limiting illness, but can have detrimental consequences if not diagnosed early. When there is a prolonged inflammatory reaction, with no infectious agent identified or remittent fever unresponsive to antibiotics, Kawasaki disease should be taken into consideration. Elevated Vβ2+ T cells compared with healthy controls suggest possible involvement of a superantigen in the etiology of Kawasaki disease, so it is wise that the health care provider concentrates not only on the cardiac consequences, but also on pulmonary associations.

Kawasaki disease: basic and pathological findings

Kawasaki disease (KD) is considered to be a kind of systemic vasculitis syndrome. It most frequently affects infants and young children and primarily invades medium-sized muscular arteries, including the coronary arteries. The etiology of KD is unknown, but epidemiological data suggest involvement of infectious agents, such as bacteria and viruses, in the onset of KD. In addition, host genetics underlie the disease's pathogenesis. Histologically, coronary arteritis begins 6-8days after KD onset, and inflammation of all layers of the artery rapidly ensues. The inflammation spreads completely around the artery, resulting in severe damage to structural components. Then, the artery begins to dilate. KD arteritis is characterized by inflammation consisting of marked accumulation of monocytes/macrophages. Aberrant activation of monocytes/macrophages is thought to be involved in the formation of vascular lesions. Inflammatory-cell infiltration persists until about the 25th day of the disease, after which the inflammatory cells gradually decrease in number. Lesions in all arteries are relatively synchronous, as they evolve from acute to chronic injury. If a giant aneurysm remains or vessel recanalization occurs after thrombotic occlusion of an aneurysm, remodeling of the vascular structure, sometimes including even reocclusion, continues even in the remote stage.

Maladie de Kawasaki : ce qu’il faut savoir

Kawasaki disease (KD) is an acute systemic vasculitis syndrome occurring mostly in children younger than 5 years of age. Especially young infants (<1 year) have an increased risk of coronary artery lesions (CAL). Whereas the etiology of KD is still unknown, progress in treatment during its acute phase has decreased the incidence of CAL from 25-30% to 3-5%. In "atypical KD", the clinical picture is dominated by an unusual symptom as seizure, bloody diarrhea, compressive cervical adenopathy, nephrotic syndrome or hyponatremia. To make a diagnosis in case of "incomplete KD", the supplementary criteria (clinical and biological) suggested by the American Heart Association can be helpful. Once the diagnosis established, the treatment of choice is the intravenous administration of immunoglobulin associated to aspirin at anti-inflammatory dose. However, some patients remain feverish within 36 hours following the end of immunoglobulin administration. This treatment resistance seems increasing in some regions of the globe and can touch up 20% of patients. The unsatisfactory answer to the initial treatment is associated to a higher risk of CAL. Predictive criteria of resistance have been identified and allow to strengthen the medical treatment with a second administration of immunoglobulins. Moreover, methylprednisolone pulse therapy and tumor necrosis factor-alpha blockade (infliximab) appear to be interesting therapeutic options in the future. At last, other treatments have not been the object of controlled studies yet but are alternatives in refractory forms e.g. cytotoxic agents (cyclosporine A, cyclophosphamide, methotrexate), plasmapheresis, plasma exchange or abciximab, especially in patients with aneurysms. Sclerotic vascular changes are often observed in post-Kawasaki disease patients, including those without coronary lesions during the acute phase. Indeed, endothelial dysfunction and risk factors for the development of atherosclerosis, such as dyslipidemia, decreased vascular elasticity, increased C-reactive protein, oxidative stress, and inflammatory cytokines, are known to be present in the late phase of KD. However, it is not clearly established that the survivors of KD carry a higher risk of coronary disease. The epidemiological studies of the next decade should give clearer answers as far as these patients henceforth achieved the age of the atherosclerosis. In conclusion, the diagnosis of KD imposes a strict supervision by a pediatric cardiologist initially. The follow-up is organized according to the existence or non-existence of coronary artery lesions. Late complications as stenosis or coronary thrombosis can occur but remain rare. Thus, it is necessary to be reassuring with the parents, especially for those whose children had no or regressive CAL, while recommending a prevention of the cardiovascular risk factors in the adulthood.

Can Kawasaki Disease Be Managed?

Kawasaki Disease (KD) is the leading cause of acquired cardiovascular disease among children, but management of KD has received relatively little attention. In the US alone, about 5500 cases were estimated in 2009. KD is most common among Asian and Pacific Islander children but can affect all ethnicities and races. Timely and accurate diagnosis remains critical, but difficult: the etiology of KD is unknown, and no accurate diagnostic laboratory test has been developed. Continuing medical education can help physicians, clinicians, and nurse practitioners accurately diagnose and treat KD. A registry specific to KD or a surveillance system may be necessary to increase awareness among health care professionals and to decrease complications related to misdiagnosis.

A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p<1×10(-5)). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR]=2.90, 95% confidence interval [CI]=1.85-4.54, P (combined)=1.46×10(-6)); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR=2.70, 95% CI=1.77-4.12, P (combined)=2.00×10(-6)). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.

Kawasaki disease : A Clinical Update

The etiology of Kawasaki disease (KD) remains unknown, although a number of epidemiological and clinical observations may suggest that it is triggered by a single or more possibly multiple infectious agents, each of which can result in the clinical manifestation of the disease. Advances have been made in the management of the disease with the introduction of aspirin and IVIG that have had a significant impact on lowering the rate of coronary artery aneurysms and death from the disease. Questions remain regarding the management of those patients who fail to respond to IVIG. It appears that some patients with severe KD who are resistant to IVIG may benefit from IV pulse steroids therapy or infliximab infusion. However, a recent multi-center, randomized-controlled trial do not support for the addition of a pulsed dose of intravenous methylprednisolone to the conventional IVIG therapy for the primary treatment of KD. It still remains to be seen whether other anti-inflammatory agents such as immunosuppressive therapies, or new biologics play a role in the management of patients with KD.

Association between Kawasaki disease and acute respiratory viral infections

Purpose:The etiology of Kawasaki disease (KD) is still unknown. Recently, an association between human coronavirus NL63 (HCoV-NL63) and KD was implicated. Hence, we attempted to determine the association between KD and acute respiratory viral infections. Methods:Nasopharyngeal aspirate samples were obtained from 54 patients diagnosed with KD at the Seoul National University (SNU) Children’s Hospital and SNU-Bundang Hospital between October 2003 and September 2006. Viral diagnoses of 11 respiratory viruses were made using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR): respiratory syncytial virus (RSV), adenovirus, rhinovirus (RV), parainfluenza viruses (PIVs) 1 and 3, influenza viruses (IFVs) A and B, human metapneumovirus (HMPV), human bocavirus (HBoV), HCoV OC43/229E, and HCoV-NL63. Clinical data were reviewed retrospectively. Results:The median age was 32 months (6 months-10.4 years). Respiratory symptoms were observed in 37 patients (69%). The following respiratory viruses were identified in 12 patients (22%): RV (n=4), PIV-3 (n=2), HBoV (n=2), and adenovirus, RSV, PIV-1, IFV-A, and HCoV-NL63 (n=1). Co-infection with PIV-3 and RV was observed in one patient. Respiratory symptoms were observed in 7 (58.3%) and 30 (71.4%) patients of the virus-positive and virus-negative groups (P> 0.05). Response rate to intravenous immunoglobulin administration was 67% (n=8) and 86% (n=36) in the virus- positive and virus-negative groups (P>0.05). Conclusion:Respiratory symptoms were commonly observed in KD patients but the association between respiratory viruses and KD were not found. Large multicenter-based investigations are required to confirm the association between acute respiratory viral infections and KD.

Characterization of CD4+ T helper cells in patients with Kawasaki disease (KD): preferential production of tumour necrosis factor-alpha (TNF-alpha) by V beta 2- or V beta 8- CD4+ T helper cells.

KD is an acute febrile illness in children characterized by coronary arteritis accompanied by aneurysm and thrombotic occlusion. The etiology of KD is unknown. It has been recently reported that KD is associated with the selective expansion of V beta 2+ and V beta 8.1+ T cells in peripheral blood lymphocytes (PBL), by studying the T cell receptor (TCR) repertoire of in vitro activated T cells. KD may therefore be caused by a superantigen [1-3]. To understand better the immunopathology of KD, we investigated TCR V beta 2 and V beta 8.1 expression on both the T cells of freshly isolated PBL and T cell clones (TCC) from patients with KD. Cytokine production by TCC was also studied. Blood samples were obtained from patients with acute (n = 20) and convalescent (n = 20) KD, age-matched children with non-infectious diseases (n = 18), and healthy adults (n = 20). Among these four groups, there were no significant differences in the percentages of either V beta 2+ or V beta 8.1+ T cells of freshly isolated PBL. The same was true for the CD4+ or CD8+ T cell subsets. One hundred and five TCC (98 CD3+ CD4+ CD8- and seven CD3+ CD4- CD8+) established from the affected skin, lymph node or PBL of six patients with KD were also negative for either V beta 2 or V beta 8.1 TCR. Sixty-eight of 105 TCC (65%) produced detectable levels (> 5 pg/ml) of TNF-alpha (6-1016 pg/ml), in the absence of any stimuli. In contrast, only 11 (10%) of 105 TCC or 7 (7%) of 97 TCC produced detectable levels of IL-2 or IL-6, respectively, in the absence of any stimuli. Stimulation with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) induced most TCC to produce higher amounts of TNF-alpha, IL-2 and IL-6. These results suggest that CD4+ T helper cells expressing TCR-beta other than V beta 2 or V beta 8 receptor, primarily through TNF-alpha production, are involved in the immunopathology of KD.

Cardiovascular complications after Kawasaki disease and its management

Kawasaki disease is a systemic vasculitis of unknown etiology usually occurring in infants and young children. Although the etiology of Kawasaki disease remains uncertain its serious complicationssuch as giant aneurysm formation coronary arterial stenotic lesions and thrombotic occlusionhave been proven to cause myocardial ischemia or infarction in patients with Kawasaki disease. To prevent and treat these complications several modes of therapyincluding long-term anticoagulation interventional catheterization and surgical treatmenthave been gradually developed. In this article we review the cardiovascular complications following Kawasaki disease and the management thereof which includes thrombolytic therapy catheter intervention and coronary artery bypass graft. (Korean J Pediatr 2008;51:462-467

Interview with a Quality Leader: Wilbert H. Mason on Pediatric Healthcare Quality

: Wilbert H. Mason, MD MPH, is professor of clinical pediatrics at the Keck School of Medicine of the University of Southern California and a member of the research faculty of the Saban Research Institute of Childrens Hospital Los Angeles (CHLA). His specialty is pediatric infectious disease, and his research interest includes pediatric health outcomes, epidemiology, and etiology of Kawasaki disease, on which he has numerous publications. He attended medical school at the University of California-Irvine and obtained an MPH in epidemiology from the University of California-Los Angeles. He is a member of the American Academy of Pediatrics and the Infectious Disease Society of America. He has twice received the Philip E. Rothman Memorial Award for Outstanding Teaching at CHLA as well as the Victor E. Stork Award and the Affiliates and Associates Award. Currently he is leading a research project on patient safety in pediatrics funded by the Agency for Healthcare Research and Quality. He provides leadership to the hospital and faculty in quality and performance improvement through his role as medical director for quality systems management. Activities in the areas of medication safety, clinical guideline development, and cost effectiveness have contributed greatly to the quality of clinical care and efficiency at CHLA.

Influence of vascular endothelial growth factor (VEGF) and endostatin on coronary artery lesions in Kawasaki disease

Purpose : Recently, there has been several studies to clarify the pathogenesis of Kawasaki disease (KD) and the relations of VEGF and endostatin that act on vascular endothelial cells to the coronary artery complications. In this report, we measured serum levels of VEGF and endostatin in acute and subacute phases of KD to assess the change of these levels and the relations to the development of coronary artery lesions (CAL). Methods : Twenty six patients were diagnosed and treated for KD between January, 2001 and July, 2005 at Kangnam St. Mary's Hospital, the Catholic University of Korea. They were divided into those with and without CAL. Serum levels of VEGF and endostatin were measured during acute and subacute phases and compared to those measured in healthy and disease control groups. Results : Serum levels of VEGF were increased in KD but no differences were noted in KD with and without CAL. Serum levels of endostatin were decreased in the acute phase of KD, however they were recovered in the subacute phase of KD, regardless of CAL. The VEGF/endostatin ratio was increased in KD. KD without CAL showed a relative decrease in this ratio during the subacute phase. Significant positive correlations were found between serum VEGF and WBC count, VEGF and ESR, VEGF/endostatin ratio and ESR in the acute phase of KD. Conclusion : Analysis of factors influencing the vascular endothelium such as VEGF and endostatin will help to clarify the etiology of KD and the pathogenesis of CAL.