International Kawasaki Disease Research Articles

A Tale of a Trail on How It Takes 5 Days of Kawasaki Disease to Initiate Coronary Artery Injury and Change the Lives of Children.

Many articles written on Kawasaki disease explain the disease and the history of an acute inflammatory dysregulation that typically affects preschool children and does not spare older ones. Six decades have passed since the discovery of the disease in Japan, yet there are parts of the world where the disease passes unacknowledged, diagnosis is delayed, or basic treatments are not readily available. The burden of Kawasaki disease is on every health-care provider who attends to children's health. It takes 5 days for the disease to initiate coronary artery injury in a child's heart, compared to 5 decades of lifetime atherosclerosis. Challenges facing patients, families, and physicians may not be overcome unless we advocate for the disease recognition and seek support for affordable, timely treatment, impactful research, and dissemination of knowledge. The purpose of this review is to provide a comprehensive review of the history of Kawasaki disease and how it has affected children's health worldwide over the last 6 decades. The review also raises current challenges facing the fight against Kawasaki disease. In an effort to bring Kawasaki disease advocates together in a landing zone, an internet hub for Kawasaki disease experts and enthusiasts has been created: the International Kawasaki Disease Society (presently a concept idea) and a dedicated website, www.ikds-org.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500ng/L) and TnI (≥ 20ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

Obesity and Outcomes of Kawasaki Disease and COVID-19–Related Multisystem Inflammatory Syndrome in Children

Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C. In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with KD who had evidence of a recent COVID-19 infection or missing or unknown COVID-19 status were excluded. Patient demographic characteristics, clinical features, disease course, and outcome variables were collected from the IKDR data set. Using body mass index (BMI)/weight z score percentile equivalents, patient weight was categorized as normal weight (BMI <85th percentile), overweight (BMI ≥85th to <95th percentile), and obese (BMI ≥95th percentile). The association between adiposity category and clinical features and outcomes was determined separately for KD and MIS-C patient groups. Of 1767 children, 338 with KD (median age, 2.5 [IQR, 1.2-5.0] years; 60.4% male) and 1429 with MIS-C (median age, 8.7 [IQR, 5.3-12.4] years; 61.4% male) were contemporaneously included in the study. For patients with MIS-C vs KD, the prevalence of overweight (17.1% vs 11.5%) and obesity (23.7% vs 11.5%) was significantly higher (P < .001), with significantly higher adiposity z scores, even after adjustment for age, sex, and race and ethnicity. For patients with KD, apart from intensive care unit admission rate, adiposity category was not associated with laboratory test features or outcomes. For patients with MIS-C, higher adiposity category was associated with worse laboratory test values and outcomes, including a greater likelihood of shock, intensive care unit admission and inotrope requirement, and increased inflammatory markers, creatinine levels, and alanine aminotransferase levels. Adiposity category was not associated with coronary artery abnormalities for either MIS-C or KD. In this international cohort study, obesity was more prevalent for patients with MIS-C vs KD, and associated with more severe presentation, laboratory test features, and outcomes. These findings suggest that obesity as a comorbid factor should be considered at the clinical presentation in children with MIS-C.

Kawasaki Disease in the Time of COVID-19 and MIS-C: The International Kawasaki Disease Registry

BackgroundPatients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection. MethodsThe International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). ResultsOf 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities. ConclusionsThere appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Management of Multisystem Inflammatory Syndrome in Children: Decision-Making Regarding a New Condition in the Absence of Clinical Trial Data.

Multisystem inflammatory syndrome in children (MIS-C) is a new illness that evolved during the COVID-19 pandemic with initial reports of severe disease including use of extracorporeal membrane oxygenation and death. Institutions rapidly assembled task forces to develop treatment algorithms. At the national/international levels, collaboratives and associations assembled consensus writing groups to draft guidelines. These guidelines and algorithms were initially on the basis of expert opinion and small case series. Some groups used the Delphi approach, and the resultant guidelines often mimicked those for other conditions that resembled MIS-C, like Kawasaki disease (KD). For instance, intravenous immunoglobulin (IVIG), a known effective treatment for KD, was recommended for MIS-C. Early in the pandemic many favoured IVIG over steroids as first-line therapy. As evidence evolved so did some guidelines, which now endorse the dual use of IVIG with steroids as first-line therapy. In contrast, withholding immunotherapy became an option for some MIS-C patients with mild symptoms. Herein, we review guidelines and discuss the evidence informing early recommendations, how this has evolved, the role and limitations of expert opinion and observational data, and the importance of leveraging existing research infrastructures, such as the intensive care unit collaborative (Overcoming COVID-19 surveillance registry), and the International Kawasaki Disease Registry. Finally, we discuss strategies to rapidly develop, deploy, and adapt clinical trials evaluating the treatment of such rare conditions in children, which might include alternatives to conventional clinical trial design. The emergence of MIS-C during the COVID-19 pandemic has highlighted unmet needs regarding research of a new condition.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Association between Fc-Gamma Receptor Polymorphisms and Autoimmune Neutropenia in Early Childhood in Danish Patients

Background Copy number variation (CNV) in the genome is difficult to analyze with standard genotyping methods. CNV in the Fcγ receptor region (FCGR) is associated with risk of autoimmune disease. Genetic variation in Fc-gamma coding genes is also abundant, and several functional polymorphisms are described. Autoimmune neutropenia (AIN) primarily affects children under the age of five but can also affect adults. The disease is caused by autoantibodies reactive to neutrophil surface antigens, primarily the FCGR3B receptor. We investigated the association between common SNPs and CNV in Fcγ receptors and AIN. Aims Establish the association between CNV and genetic variation in Fc-gamma receptor coding genes in Danish patients. Methods 127 Danish AIN cases were compared with 610 healthy and unrelated Danish blood donors for FCGR2A-H166R, and with 919 Caucasians (1) for FCGR3A-V158F, FCGR2B-B2.4, FCGR2B-I232T and CNV. Molecular determination of copy number and genotypes was determined using Multiplex Ligation Probe Assay (MLPA) with the following SALSA MLPA probemixes: P110-C1 FCGR mix 1 and P111-C1 FCGR mix 2. Statistical analysis was performed with Fisher Exact test. Results The polymorphisms FCGR2A-166H, FCGR3A-158F, FCGR2B-232I were statistically significantly associated with a higher risk of AIN (Table 1). The presence of a FCGR2B-2B.4 promoter haplotype was associated with a significantly lower risk of AIN (OR=0.5). There was not observed a difference in the distribution of CNV for the Fc-gamma receptor genes (data not shown). Summary/Conclusion In our Danish cohort, we report an association between AIN and polymorphisms in Fc-gamma receptor 2A, 3A and 2B, indicating a significance of other Fc-gamma receptors than FCGR3B. We do not observe a difference in the distribution of CNV of the Fc-gamma receptor genes. 1) Nagelkerke SQ, Tacke CE, Breunis WB, Tanck MWT, Geissler J, Png E, Hoang LT, van der Heijden J, Naim ANM, Yeung RSM, Levin ML, Wright VJ, Burgner DP, Ponsonby A-L, Ellis JA, Cimaz R, Shimizu C, Burns JC, Fijnvandraat K, van der Schoot CE, van den Berg TK, de Boer M, Davila S, Hibberd ML,Kuijpers TW and the International Kawasaki Disease Genetics Consortium (2019) Extensive Ethnic Variation and Linkage Disequilibrium at the CGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease. Front. Immunol. 10:185. doi: 10.3389/fimmu.2019.00185 Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Physicians' Self-reported Exercise Testing and Physical Activity Recommendations in Kawasaki Patients.

Recommendations for management of patients with Kawasaki disease (KD) and coronary artery aneurysms (CAA) include physical activity (PA) promotion. This study aimed to characterize self-reported practices of KD providers to evaluate practice variation in use of cardiopulmonary exercise testing (CPET) and PA recommendations. We developed a REDCap survey with different clinical scenarios of KD patients. It was completed by members of the International Kawasaki Disease Registry (IKDR) and community pediatric cardiologists. Twenty-eight physicians responded; 63% practiced in the US, 63% practiced in an academic setting, 48% were general pediatric cardiologists, and 55% were IKDR members. Most respondents (69%) followed < 50 KD patients. The great majority (93%) agreed that patients with no CAA do not require CPET and could be cleared for all PA. For patients with small CAA, 43% of respondents recommended CPET and 75% cleared for all PA if CAAs regressed completely, but only 32% cleared if CAA persisted. For patients with medium CAA, 66% respondents cleared for PA if CAA regressed, and only 7% if CAA persisted; with 66% and 75% recommending CPET, respectively. For patients with large/giant CAA, 81% of respondents recommended CPET. No respondents felt comfortable clearing their patients with persistent large/giant CAA for PA and 19% would restrict from the entire physical education program. There is practice variation in use of CPET in KD patients with CAAs. Providers are hesitant to promote PA in KD patients with CAA despite known benefits and current guidelines.

Variation in Pharmacologic Management of Patients with Kawasaki Disease with Coronary Artery Aneurysms

To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in <10% of their patients, and 3 centers used it in >20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

Obituary for Dr Tomisaku Kawasaki (February 7, 1925–June 5, 2020)

Dr Tomisaku Kawasaki (1925–2020) Dr Tomisaku Kawasaki, the Former Chairman of the Japan Kawasaki Disease Research Foundation, passed away on June 5, 2020, aged 95 years. After graduating from Chiba Medical College in 1948, he started working at Japan Red Cross Central Hospital in Tokyo in 1950. He wrote, modestly, that his good fortune started from this hospital. Dr Kawasaki's first article was about his first patient having pertussis with encephalopathy, and this was found to be Pelger's familial anomaly of the leukocyte nucleus. His head, Dr. Jushichirou Naito, and the assistant chief, Dr. Yutaka Kokubo guided Dr. Kawasaki with their experienced clinical skill, and his splendid observational ability gradually flowered. During his busy days, with many experiences at the Red Cross Hospital, in January 1961, he encountered a 4-year-old patient with impressive facial appearance, but the symptoms were so strange that he could not diagnose this patient. One year later, on his night duty in February 1962, he noticed identical clinical symptoms in another patient. His concern became a conviction. He accumulated 50 similar cases until 1967 and published a historical article in Arerugi1, and an English version in Pediatrics in 19742. Although some authorities criticized his presentations in meetings of the early era that this disease was not a new disease but a subtype of Stevens–Johnson syndrome or Still disease. However, his speeches and article were convincing and broadly agreed for clinicians worldwide, and the reprints were quickly out of stock. Born in Asakusa, a historical area of Tokyo, he was a very frank and friendly person. His splendid observational eyes and devotion to patients came to fruition in this distinguished case-series article1, 2. Although Dr Kawasaki and his mentor Dr Kousaki named this condition mucocutaneous lymph node syndrome, most colleagues gradually came to call it “Kawasaki disease” out of respect for the discoverer. In 1972, the first nationwide surveillance made him fear that sudden deaths were occurring in children with this disease, and their autopsies revealed a large aneurysm of the coronary artery and an acute myocardial infarction with thrombus inside. This life-threatening complication presented a novel problem for pediatric cardiologists. From the 1970s, opportunities for ultrasonography, catheterization of the coronary artery, and treatment of ischemic heart disease increased markedly. The first autopsied case was reported in Pediatrics 1974 by the late professor Masayoshi Yanagisawa3. And the prognosis of coronary artery aneurysm was studied and published in the Journal of Pediatrics (1975)4, The Lancet (1992)5, and Circulation (1996)6 by Professor Hirohisa Kato. Those articles attracted pediatricians and cardiologists worldwide. Drs Kawasaki and Kato were invited to many international meetings to lecture, and received standing ovations. Dr Kawasaki was always with Mrs Reiko Kawasaki, who was also a pediatrician. For the first article, he hesitated to attach impressive color photographs, which were expensive because they were experiencing a hard time financially; however, Mrs Kawasaki persuaded him that color photos are indispensable for his article; then, she managed their home budget. Dr and Mrs Kawasaki participated in almost all the meetings together. It was very easy to find Dr and Mrs Kawasaki because they were always together and sitting in the front row of the venue. Whenever young doctors gather around him, he welcomed them by taking pictures together and shaking hands. The 12th International Kawasaki Disease Symposium in June 2018 was his last participation in the conference. After Mrs. Kawasaki passed away in June 2019, he was repeatedly hospitalized and quietly passed away, surrounded by his family at his bedside, also in June, in 2020. He was given many commendations, including the first Japan Pediatric Society Award (2006). He encouraged young doctors warmly and rigorously, with the motto “Be Strict to Study Medicine, Be Warm-hearted to Care for Patients.” Now we need to be back from deep sorrow and must investigate the cause of his namesake disease.

Management of Multisystem Inflammatory Syndrome in Children Associated With COVID-19: A Survey From the International Kawasaki Disease Registry

BackgroundSince April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation. MethodsWe surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries. ResultsAmong the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). Acetylsalicylic acid was frequently used among respondents (91%), including anti-inflammatory and/or antiplatelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms. ConclusionsThere is variation in management of MIS-C patients, with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies.

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From the International Kawasaki Disease Registry.

BackgroundCoronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD.Methods and ResultsA 34‐institution international registry of 1651 patients with KD who had CAAs (maximum CAA Z score ≥2.5) was used. Time‐to‐event analyses were performed using the Kaplan–Meier method and Cox proportional hazard models for risk factor analysis. In patients with CAA Z scores ≥10, the cumulative incidence of luminal narrowing (>50% of lumen diameter), coronary artery thrombosis, and composite major adverse cardiovascular complications at 10 years was 20±3%, 18±2%, and 14±2%, respectively. No complications were observed in patients with a CAA Z score <10. Higher CAA Z score and a greater number of coronary artery branches affected were associated with increased risk of all types of complications. At 10 years, normalization of luminal diameter was noted in 99±4% of patients with small (2.5≤Z<5.0), 92±1% with medium (5.0≤Z<10), and 57±3% with large CAAs (Z≥10). CAAs in the left anterior descending and circumflex coronary artery branches were more likely to normalize. Risk factor analysis of coronary artery branch level outcomes was performed with a total of 893 affected branches with Z score ≥10 in 440 patients. In multivariable regression models, hazards of luminal narrowing and thrombosis were higher for patients with CAAs of the right coronary artery and left anterior descending branches, those with CAAs that had complex architecture (other than isolated aneurysms), and those with CAAs with Z scores ≥20.ConclusionsFor patients with CAA after KD, medium‐term risk of complications is confined to those with maximum CAA Z scores ≥10. Further risk stratification and close follow‐up, including advanced imaging, in patients with large CAAs is warranted.

Guidelines for medical treatment of acute Kawasaki disease: report of the Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version).

Guidelines for medical treatment of acute Kawasaki disease: report of the Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version).

189 Kawasaki Disease- A Prospective Clinical Appraisal

INTRODUCTION Kawasaki disease is replacing rheumatic fever as the most common cause of acquired heart disease. The clinical appraisal of Kawasaki disease in Indian scenario is being recently recognized. We are reporting eight typical cases of Kawasaki disease.AIMS to study the clinical spectrum of Kawasaki disease to study the utility of investigatory tools. To study the efficacy of Intravenous Immunoglobulins vs methylprednisolone.MATERIALS AND METHODS: Children with fever and rash were screened for Kawasaki diseases per the guidelines of International Kawasaki disease criteria. All children of suspected Kawasaki disease were subjected to 2D-COLOUR DOPPLER and ECG for cardiac involvement and those with cardiac involvement were followed for coronary aneurysms irrespective of nature of treatment. The children were divided into two groups, first group were treated with 2gm/kg Immunoglobulin as a single dose infusion over a period of 12 hrs and aspirin therapy whereas the second group received Methyl prednisolone 30mg/kg /day for 5 days and aspirin. Aspirin is used initially in the dose of 30–50mg/kg/day in 4 divided doses for 2 weeks followed by 2–5mg/kg/day as a single dose until the platelet count returned to normal. All the data is analysed and tabulated.RESULTS A total of 8 cases were reported in 2 year period, 7 were females and 1 was male. All the cases were younger than 6 years of age. Cardiac involvement was seen in 50% of cases. Response to intravenous immunoglobulins is dramatic and complete within 2 days, whereas response to methylprednisolone is incomplete and prolonged. Coronary aneurysm was seen in one child who was treated with methylprednisolone. Time taken for platelet count to come to normal is unaffected by nature of therapy.

Summary and abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan.

Summary and Abstracts of the Seventh International Kawasaki Disease Symposium: December 4–7, 2001, Hakone, Japan

Summary and Abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan

Summary and Abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan

Summary and Abstracts of the Sixth International Kawasaki Disease Symposium

Summary and Abstracts of the Sixth International Kawasaki Disease Symposium

Kawasaki disease.

The 5th International Kawasaki Disease Symposium was held in May 1995 in Fukuoka, Japan. No one infectious agent has been found to initiate the syndrome, although the occurrence of Kawasaki disease in epidemics and its resemblance to toxic-shock syndrome make an infectious etiology seem most likely.

Effects of immunoglobulin (Ig) and gamma-interferon (INF-γ) on the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by the peripheral blood monocytes (PBM) in the acute phase of Kawasaki disease (KD)

In the third international KD symposium, we reported a significant increase in serum TNF-e was observed only after high dose intravenous immunoglobulin (IVIG) therapy in KD. In this paper, we studied the effects of intact Ig and INF-u on the production of TNF-u and IL-I8 by PBM obtained both before and after IVIG therapy in the acute phase of twenty patients suffering from KD. We also examined the effects of intact Ig in PBM obtained from five healthy children. Peripheral blood leukocytes were isolated from heparinized peripheral blood by Ficoll-Hypaque density gradient centrifugation. After these cells were incubated at 37~ in 5% carbon dioxide for 45 min, adhesive cells were treated as PBM. Intact Ig (I0 mg/ml, Organon Teknika Co.) markedly enhanced the production of TNF-u and IL-18 both before and after IVIG therapy compared with the spont@neous production (P<O.OI). On the other hand, intact Ig enhanced the production of IL-I8 (P<0.OI) but not TNF-e in healthy children. Neither beforelnor after IVIG therapy, INF-y (500 U/ml, Shionogi~Co.) enhanced the production of the two cytokines significantly. These results indicate that intact Ig enhances the production of TNF-e and IL-18 by PBM of patients in KD and the changes of these cytokines may be related to the clinical effects of high dose IVIG.