加载中

    logo
    Prognostic nutrition index as a predictor of coronary artery aneurysm in Kawasaki Disease. Tai I-Hsin,Wu Pei-Lin,Guo Mindy Ming-Huey,Lee Jessica,Chu Chi-Hsiang,Hsieh Kai-Sheng,Kuo Ho-Chang BMC pediatrics BACKGROUND:Kawasaki Disease (KD) is considered a major acquired heart disease in children under the age of 5. Coronary artery aneurysm (CAA) can occur in serious cases despite extreme therapy efforts. Previous studies have reported low serum albumin level was associated with disease outcome, but no further investigation was addressed yet. METHOD:This retrospective (case-control) study randomly included children with KD who were admitted and underwent laboratory tests before undergoing IVIG treatment in this institution, the largest tertiary medical center in southern Taiwan from 2012 to 2016. Prognostic nutrition index (PNI), an albumin-based formula product, was evaluated as a predictor of CAA the first time. The progression of CAA was monitored using serial echocardiography for six months. We performed multivariable logistic regression analysis on the laboratory test and PNI with the disease outcome of the KD patients. RESULT:Of the 275 children, 149 had CAA, including transient dilatation, while the other 126 did not develop CAA during the 6-month follow-up period. A multivariate logistic regression model revealed that PNI, gender, IVIG non-responder, and platelet count are significant predictors of CAA with a 95% confidence interval estimator of 1.999, 3.058, 3.864 and 1.004, respectively. Using PNI to predict CAA presence gave an area under the receiver-operating-characteristics (ROC) curve of 0.596. For a cutoff of 0.5 in the logistic regression model and the PNI cut-off point is taken as 55 together with IVIG non-responder, boy gender, and platelet count take into account, sensitivity and specificity were 65.7 and 70.4%. CONCLUSION:PNI could be a candidate of adjunctive predictor of coronary artery aneurysm in addition to IVIG non-responder. Together with low PNI, IVIG non-responder, male gender and platelet count will give high odds to predict coronary artery aneurysm within 6 months of illness. 10.1186/s12887-020-02111-y
    Interleukin-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive Kawasaki disease rather than coronary artery aneurysm. Wu Yue,Liu Fei Fei,Xu Yao,Wang Jing Jing,Samadli Sama,Wu Yang Fang,Liu Hui Hui,Chen Wei Xia,Luo Huang Huang,Zhang Dong Dong,Wei Wei,Hu Peng Clinical and experimental medicine Kawasaki disease (KD) is an acute, systemic vasculitis and occurs mainly in childhood. Interleukin-6 (IL-6) is a pleiotropic cytokine synthesized predominantly by neutrophils and monocytes/macrophages and plays an important role in systemic inflammatory disease. However, a little information is currently available on the relationship of serum IL-6 with conventional inflammatory mediators, clinical classification, IVIG response and coronary artery aneurysm (CAA). 165 Chinese children with KD were enrolled and divided into six subgroups, including complete KD, incomplete KD, IVIG-responsive KD, IVIG-nonresponsive KD, coronary artery noninvolvement KD and coronary artery involvement KD. Blood samples were collected from all subjects within 24-h pre- and 48-h post-IVIG therapy, respectively. Serum IL-6 and conventional inflammatory mediators were detected. (1) Serum IL-6 markedly increased in the acute phase of KD, whereas declined to normal after IVIG therapy; it was positively correlated with C-reactive protein and erythrocyte sedimentation rate. (2) Serum IL-6 was significantly elevated in patients with incomplete KD when compared with their complete counterparts. The area under receiver operating characteristic curve (AUC) value for serum IL-6 in prediction of incomplete KD was 0.596, and the estimated sensitivity and specificity were 77.80% and 54.40% with a cutoff of IL-6 > 13.25 pg/ml, respectively. (3) Serum IL-6 was significantly elevated in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts; the AUC value for serum IL-6 in prediction of IVIG-nonresponsive KD was 0.580, and the estimated sensitivity and specificity were 60.00% and 66.30% with a cutoff of IL-6 > 26.40 pg/ml, respectively. (4) No significant differences in IL-6 were found between KD patients with and without CAA. IL-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive KD rather than CAA. 10.1007/s10238-018-00544-5
    The elevated serum levels of calcineurin and nuclear factor of activated T-cells 1 in children with Kawasaki disease. Sun Yameng,Liu Jingjing,Geng Zhimin,Tao Yijing,Zheng Fenglei,Wang Ying,Fu Songling,Wang Wei,Xie Chunhong,Zhang Yiying,Gong Fangqi Pediatric rheumatology online journal BACKGROUND:The calcineurin and nuclear factor of activated T-cells (CaN-NFAT) signaling pathway had been found to be associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysm formation as a contributor. To evaluate serum calcineurin (CaN) and nuclear factor of activated T-cells 1(NFAT1) levels in patients with Kawasaki disease (KD). METHODS:Serum levels of CaN and NFAT1 were measured by enzyme-linked immunosorbent assay method in 66 healthy children and 74 KD patients at acute, afebrile and subacute stage. RESULTS:The serum levels of CaN and NFAT1 increased significantly in the acute stage, and decreased progressively in the afebrile and subacute stage, along with the reduction of C-reactive protein, white blood cells and neutrophil counts. And in the acute stage, the afebrile stage and the subacute stage, the expression of CaN and NFAT1 was upregulated significantly in KD patients compared to that in the healthy control. After the IVIG treatment, the serum levels of CaN and NFAT1 declined significantly in IVIG responders. However, the CaN and NTAT1 levels in the IVIG non-responders declined slowly. And in the afebrile stage, the NFAT1 levels were lower in KD patients with coronary artery lesions (CALs) (268.82 ± 11.96 ng/ml) than those without CALs (285.84 ± 25.13 ng/ml). However, the serum levels of CaN in KD patients with CALs had no significant difference with those in KD patients without CALs. CONCLUSIONS:The specific regulation of CaN and NFAT1 serum levels in the course of KD was suggested that both of them were related in the development of KD. 10.1186/s12969-020-0420-8
    Overweight, obesity and coronary artery lesions among Kawasaki disease patients. Shi Hongying,Weng Fengfeng,Li Chen,Jin Zengyou,Hu Junyong,Chu Maoping,Qiu Huixian Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIMS:Overweight is associated with increased cardiovascular disease in general populations. However, a similar relationship among Kawasaki Disease (KD) patients was unclear. The study aimed to investigate the relation between weight-for-height and coronary artery lesions (CAL) among KD patients, and whether laboratory indices modified this relation. METHODS AND RESULTS:All consecutive KD patients from January 2009 to December 2014 in a city in China were reviewed, and classified into overweight/obese and control groups. All patients were followed to assess the occurrence of CAL by echocardiography for two months from disease onset. The independent effect of overweight/obesity on CAL was evaluated after adjustment for confounders. The interaction effect between overweight and laboratory indices was examined. The prevalence of overweight/obesity among KD patients was 18.5% (95%CI: 16.0%, 21.0%). The proportion of male patients and the proportion of non-standard IVIG treatment were significantly higher in overweight/obese children in comparison with their counterparts. Overweight/obesity was associated with increased odds of total CAL (aOR = 1.69, 95%CI: 1.16, 2.45) and also increased odds of CAL after treatment (aOR = 1.96, 95%CI: 1.09, 3.51); after adjustment for age, gender, KD type, change of medical departments, number of days before admission, treatment regimen and laboratory index. Similar results were found using stratification analysis. In addition, patients at risk of overweight were also associated with significantly increased risk of CAL. There was interaction between weight-for-height and platelet, WBC, and albumin. CONCLUSIONS:Overweight/obesity may be an independent risk factor for CAL among KD patients. Some laboratory indicators may modify this association. 10.1016/j.numecd.2021.01.015
    Z-score is a possible predictor of the risk of coronary artery lesion development in patients with Kawasaki disease in Japan. Suzuki Takayuki,Kakimoto Nobuyuki,Tsuchihashi Tomoya,Suenaga Tomohiro,Takeuchi Takashi,Shibuta Shoichi,Kitano Naomi,Suzuki Hiroyuki European journal of pediatrics Risk factors for coronary artery lesion (CAL) development in patients with Kawasaki disease (KD) include male sex, age < 12 months, intravenous immunoglobulin (IVIG) resistance, and delayed diagnosis.. We aimed to explore the relationship between CAL development and Z-score. We enrolled 281 patients with KD who were treated with our protocol. Echocardiography was performed in three phases: pre-treatment (P1), post-treatment (P2), and 4 weeks after onset (P3). The highest Z-score of the right, left main, left anterior descending, and left circumflex coronary arteries was expressed as Zmax at each phase. P3-Zmax ≥ 2.5 represented CAL development. Clinical parameters, such as laboratory data and Z-scores, were retrospectively compared between patients with and without CAL development. Sixty-seven patients (23.8%) showed a P1-Zmax ≥ 2.0, and CAL development occurred in 21 patients (7.5%). Independent risk factors associated with CAL development were P1-Zmax, a ΔZmax (P2-Zmax - P1-Zmax) ≥ 1, male sex, < 12 months of age, and resistant to the first intravenous immunoglobulin (IVIG) administration (adjusted odds ratio [95% confidence interval]: 198 [1.01-3.92], 4.04 [1.11-14.7], 6.62 [1.33-33.04], 4.71 [1.51-14.68], 5.26 [1.62-17.13], respectively). Using receiver operating characteristic curve analysis, a P1-Zmax ≥ 1.43 detected CAL development with an area under the curve of 0.64 (sensitivity = 81.0%; specificity = 48.1%).Conclusion: Our results suggest that P1-Zmax and a ΔZmax (P2-Zmax - P1-Zmax) ≥ 1 may predict CAL development. What is Known: • KD is an acute vasculitis predominantly affecting the coronary artery of young children. • Although P1 Z-max ≥ 2.0 has been a predictor of CAL development, it has not yet been shown in Japan. What is New: • P1-Zmax and a ΔZmax ≥ 1 are presumably associated with CAL development. • In the ROC curve analysis, P1-Zmax ≥ 1.43 detected CAL development, a sensitivity (81%) and a specificity (48%). We need to consider intensified initial therapy for patients with these risk factors. 10.1007/s00431-021-04006-1
    Risk Model Development and Validation for Prediction of Coronary Artery Aneurysms in Kawasaki Disease in a North American Population. Son Mary Beth F,Gauvreau Kimberlee,Tremoulet Adriana H,Lo Mindy,Baker Annette L,de Ferranti Sarah,Dedeoglu Fatma,Sundel Robert P,Friedman Kevin G,Burns Jane C,Newburger Jane W Journal of the American Heart Association Background Accurate prediction of coronary artery aneurysms ( CAAs ) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score ≥2.5 at 2 to 8 weeks after fever onset in a development cohort (n=903) and a validation cohort (n=185) of patients with Kawasaki disease. Associations of baseline clinical, laboratory, and echocardiographic variables with later CAA were assessed in the development cohort using logistic regression. Discrimination (c statistic) and calibration (Hosmer-Lemeshow) of the final model were evaluated. A practical risk score assigning points to each variable in the final model was created based on model coefficients from the development cohort. Predictors of CAAs at 2 to 8 weeks were baseline Z score of left anterior descending or right coronary artery ≥2.0, age <6 months, Asian race, and C-reactive protein ≥13 mg/ dL (c=0.82 in the development cohort, c=0.93 in the validation cohort). The CAA risk score assigned 2 points for baseline Z score of left anterior descending or right coronary artery ≥2.0 and 1 point for each of the other variables, with creation of low- (0-1), moderate- (2), and high- (3-5) risk groups. The odds of CAA s were 16-fold greater in the high- versus the low-risk groups in the development cohort (odds ratio, 16.4; 95% CI , 9.71-27.7 [ P<0.001]), and >40-fold greater in the validation cohort (odds ratio, 44.0; 95% CI, 10.8-180 [ P<0.001]). Conclusions Our risk model for CAA in Kawasaki disease consisting of baseline demographic, laboratory, and echocardiographic variables had excellent predictive utility and should undergo prospective testing. 10.1161/JAHA.118.011319
    Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial. Hamada Hiromichi,Suzuki Hiroyuki,Onouchi Yoshihiro,Ebata Ryota,Terai Masaru,Fuse Shigeto,Okajima Yoshitomo,Kurotobi Shunji,Hirai Katsuki,Soga Takashi,Ishiguchi Yukiko,Okuma Yoshiaki,Takada Nobuyuki,Yanai Masaaki,Sato Junichi,Nakayashiro Mami,Ayusawa Mamoru,Yamamoto Eiichi,Nomura Yuichi,Hashimura Yuya,Ouchi Kazunobu,Masuda Hiroshi,Takatsuki Shinichi,Hirono Keiichi,Ariga Tadashi,Higaki Takashi,Otsuki Akio,Terauchi Moe,Aoyagi Reiko,Sato Takatoshi,Fujii Yasuhisa,Fujiwara Tadami,Hanaoka Hideki,Hata Akira, Lancet (London, England) BACKGROUND:Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. METHODS:We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. FINDINGS:We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78). INTERPRETATION:Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. FUNDING:Japan Agency for Medical Research and Development (grant CCT-B-2503). 10.1016/S0140-6736(18)32003-8
    Up-regulation of miR-27a promotes monocyte-mediated inflammatory responses in Kawasaki disease by inhibiting function of B10 cells. Luo Ying,Yang Jun,Zhang Chi,Jin Yan,Pan Hong,Liu Lanlan,Gong Yifeng,Xia Yu,Wang Guobing,Zhang Jiaosheng,Li Chengrong,Li Qiu Journal of leukocyte biology Kawasaki disease (KD) is an acute systemic vasculitis and activation of monocytes plays a central role in the pathogenesis of it. B10 cells, a B cell subset with negative regulatory properties, are functionally identified by their ability to express cytoplasmic IL-10 after ex vivo stimulation. Here, we aimed to explore the functional role of B10 cells during monocyte-mediated inflammatory responses in KD, as well as elucidate the underlying microRNA (miRNA)-mediated regulatory mechanisms. Expression of IL-10 by each group of B cells (total B cells, transitional B cells, naïve B cells, and memory B cells) and inhibition of monocyte-derived TNF-α by activated B cells were measured by flow cytometry. Expression of miRNAs (miR-21-3p, miR-98-5p/3p, miR-27a-3p, let7b-5p, and miR-1423p/5p) that affect IL-10 levels in B cells was quantitated by real-time PCR. The relationship between IL-10 and these miRNAs was examined by multivariate analysis. MiR-mediated RNA interference in B cells was performed to investigate the role of miR-27a on expression of IL-10. The results showed expression of cytoplasmic IL-10 in B cell subsets from patients with KD was down-regulated. The inhibitory effect of B10 cells on production of TNF-α by monocytes from patients with KD was also compromised. The miR-27a-3p expression was markedly up-regulated during the acute phrase of KD, and it promoted monocyte-mediated TNF-α release by negatively regulating expression of cytoplasmic IL-10 within B cells in vitro. The data suggest up-regulated miR-27a in B cells from patients with KD may promote monocyte-mediated inflammatory responses by inhibiting the regulatory function of B10 cells. 10.1002/JLB.5A0919-075RR
    Clinical aspects for differential diagnosis of Kawasaki disease shock syndrome: a case control study. Park Woo Young,Lee Sang Yun,Kim Gi Beom,Song Mi Kyoung,Kwon Hye Won,Bae Eun Jung,Choi Eun Hwa,Park June Dong BMC pediatrics BACKGROUND:Because of the absence of a specific diagnostic test and pathognomonic clinical features, physicians must rely on the presence of specific clinical criteria and laboratory data that support the diagnosis of KD. To help clinicians distinguish KD, KDSS, septic shock, and TSS earlier, we suggest differential diagnosis and treatment guideline. METHODS:Medical records of immunocompetent patients who were admitted to the pediatric department with a diagnosis of KDSS, septic shock or TSS (SS group) were retrospectively reviewed. In addition, KD patients were selected by seasonal matching to each case of KDSS patient by date of admission (± 2 weeks). RESULTS:There were 13 patients with KDSS, 35 patients with SS group, and 91 patients with KD. In comparison between KDSS and septic shock group, KDSS group had significantly higher rate of coronary aneurysm incidence, and higher left ventricle dysfunction rate. In comparison between KDSS and TSS, patients with KDSS had a significantly higher erythrocyte sedimentation rate (ESR) and significantly lower creatinine. Receiver operation characteristic curve revealed that the optimal ESR cut off value for determining the KDSS was 56.0 (sensitivity 75.0%, specificity of 100.0%) and the optimal creatinine cut off value for determining the TSS was 0.695 (sensitivity 76.9%, specificity 84.6%). CONCLUSIONS:Clinical symptoms, laboratory finding, echocardiography, and culture studies can be used to differentiate KD, KDSS, septic shock and TSS. 10.1186/s12887-020-02488-w
    Kawasaki disease in infants less than one year of age: an Italian cohort from a single center. Mastrangelo Greta,Cimaz Rolando,Calabri Giovani Battista,Simonini Gabriele,Lasagni Donatella,Resti Massimo,Trapani Sandra BMC pediatrics BACKGROUND AND AIMS:Few data are currently available for Kawasaki disease (KD) below 12 months especially in Caucasians. This study aims to analyze clinical and laboratory features of KD among an Italian cohort of infants. METHODS:A retrospective chart review of KD children aged less than 1 year at time of disease onset between January 2008-December 2017 was performed. Clinical data, laboratory parameters, instrumental findings, treatment and outcome were collected in a customized database. RESULTS:Among 113 KD patients, 32 (28.3%) were younger than 1 year. Nineteen patients aged below 6 months, and three below 3 months. The median age was 5.7 ± 2.7 months. The mean time to diagnosis was 7 ± 3 days and was longer in the incomplete forms (8 ± 4 vs 6 ± 1 days). Conjunctival injection was present in 26 patients (81.2%); rash in 25 (78.1%); extremity changes in 18 (56.2%); mucosal changes in 13 (40.6%,) and lymphadenopathy only in 7 (21.8%). Mucosal changes were the least common features in incomplete forms (18.2%). Twenty-two patients (68.7%) had incomplete KD. Nineteen (59.4%) had cardiac involvement, of whom 13 (59.0%) had incomplete form. ESR, PCR and platelet values were higher in complete KD; especially, ESR resulted significantly higher in complete forms (80 ± 25.7 mm/h vs 50 ± 28.6 mm/h; p = 0.01). Conversely, AST level was statistically significant higher in patients with incomplete forms (95.4 ± 132.7 UI/L vs 29.8 ± 13.2 UI/L; p = 0.03). All patients received IVIG. Response was reported in 26/32 patients; 6 cases needed a second dose of IVIG and one required a dose of anakinra. CONCLUSION:In our cohort, incomplete disease was commonly found, resulting in delayed diagnoses and poor cardiac prognosis. Infants with incomplete KD seem to have a more severe disease and a greater predilection for coronary involvement than those with complete KD. AST was significantly higher in incomplete forms, thus AST levels might be a new finding in incomplete forms' diagnosis. Eventually, we highlight a higher resistance to IVIG treatment. To our knowledge this is the first study involving an Italian cohort of patients with KD below 12 months. 10.1186/s12887-019-1695-0
    Kawasaki disease: Shedding light on a mysterious diagnosis. Galuppo Jana,Kowker Alexandra,Rolfs Jenna,Nicholas Joyce,Schmidt Eric JAAPA : official journal of the American Academy of Physician Assistants Kawasaki disease is an acute systemic febrile vasculitis of medium and small arteries, most often occurring in children under age 5 years. This condition is the most common cause of acquired heart disease in children in the developed world. The cause is unclear but is thought to be a hyperimmune reaction to an infectious agent. Diagnosis is clinical; the classic presentation includes persistent fever, lymphadenopathy, oral mucosal changes, conjunctivitis, and rash. Although the disease technically is self-limiting, treatment with IV immunoglobulin (IVIG) and high-dose aspirin is necessary to prevent cardiac complications, such as coronary artery aneurysm, pericarditis, or myocarditis. This article reviews the pathophysiology, clinical presentation, diagnosis, and treatment of Kawasaki disease. 10.1097/01.JAA.0000668792.41976.f2
    Clinical observation of noncoronary cardiac abnormalities in Chinese children with Kawasaki disease. Liu Fei Fei,Liu Hui Hui,Qiu Zhen,Wang Jing Jing,Samadli Sama,Wu Yue,Wu Yang Fang,Xu Yao,Luo Huang Huang,Chen Wei Xia,Zhang Dong Dong,Hu Peng European journal of clinical investigation BACKGROUND:Kawasaki disease (KD) is an acute, self-limited vasculitis. Coronary artery aneurysm (CAA) serves as a major contributor to the long-term prognosis of KD. In addition, acute KD usually also leads to several kinds of noncoronary cardiac abnormalities (NCA) involving the pericardium, myocardium and endocardium. MATERIALS AND METHODS:A total of 142 Chinese children with KD were recruited from July 2015 to April 2018. Blood samples were collected at 24 hours pre-intravenous immunoglobulin (IVIG) therapy. Several inflammatory mediators and biomarkers for acute myocardial infarction were detected. Echocardiography and electrocardiography (ECG) were performed. RESULTS:Plasma white blood cell counts (WBC) were significantly increased in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts. A total of 106 children (74.65%) suffered from NCA, including 8 patients (5.63%) with pericardial effusion, 23 patients (16.20%) with acute myocarditis, 101 patients (71.13%) with valvular regurgitation and 8 patients (5.63%) with abnormal ECG. No significant differences were observed in the distribution of clinical classification and the response to IVIG therapy regardless of NCA exhibited or not. CONCLUSIONS:Noncoronary cardiac abnormalities is almost universal in acute KD and mainly manifests as valvular regurgitation. However, it has no influence on clinical classification and the response to IVIG therapy. 10.1111/eci.13210
    Maternal Autoimmune Disorders and Risk of Kawasaki Disease in Offspring. Belkaibech Sabrina,Potter Brian J,Kang Harb,Lee Ga Eun,Bilodeau-Bertrand Marianne,Auger Nathalie The Journal of pediatrics We assessed the association between maternal autoimmune disorders and offspring risk of Kawasaki disease in a longitudinal cohort of 792 108 newborns. We found that maternal autoimmune disorders, especially autoimmune thyroiditis, may be risk factors for Kawasaki disease in children, particularly young children. 10.1016/j.jpeds.2020.02.016
    Kawasaki disease in an infant after administration of hexavalent vaccine. Almeshary Meshal Z,Alanazi Saud A,Almoosa Khalid M,Bassrawi Rolan K Saudi medical journal Kawasaki disease is a vascular disorder of unknown etiology that affects children. Kawasaki disease mainly involves medium-sized blood vessels and may cause cardiovascular complications, particularly coronary artery aneurysms. Concern has been raised against various types of vaccines becoming potential risk factors for Kawasaki disease. Here, we describe a case of a 4-month-old Saudi infant who presented with incomplete Kawasaki disease a few hours after receiving his hexavalent vaccine and there was a significant dilatation of all coronary arteries. Although a relationship between vaccinations and Kawasaki disease has been suggested, there is no strong evidence of an increased risk or causal association. This possibility of adverse effects is rare but should be observed and further investigated. 10.15537/smj.2021.42.7.20210061
    Hepatic predominant presentation of Kawasaki disease in adolescence case report and review of literature. Pratap Krishan,Gardner Logan S,Gillis David,Newman Martin,Wainwright Dana,Prentice Roger BMC gastroenterology BACKGROUND:Kawasaki Disease (KD) is the most common paediatric vasculitis affecting small to medium arteries. Although the average age of diagnosis is 3.4 years with a well-defined clinical presentation, older patients with KD including adolescent and adult patients demonstrate a less classical presentation with prominent findings including hepatitis, cervical lymphadenopathy, and arthralgia. We describe a case of an adolescent presentation of Kawasaki Disease presenting with a predominantly cholestatic hepatic picture. CASE PRESENTATION:We describe a case of KD in a 16-year-old Caucasian female with predominately hepatic disease that showed resistance to intravenous immunoglobulin (IVIG). The formal diagnosis of KD was made on her 8th day of symptoms. She displayed classical symptoms commencing with fever, followed by peripheral desquamation, strawberry tongue, cervical lymphadenopathy. She became clinically jaundiced with evidence of hepatic artery narrowing on ultrasound that resolved with treatment. Her disease was biphasic and required further IVIG for non-hepatic symptoms. She did not develop coronary aneurysms. CONCLUSION:Significant hepatic dysfunction with clinical jaundice is rare in KD without associated gall bladder hydrops and tends to occur in older patients. We describe such a case and review the five described cases in the literature. Diagnostic delay is more common in adolescent patients and given that the prognosis of KD is closely correlated to diagnostic timing and provision of care, it is important to consider Kawasaki Disease in older demographics especially with undiagnosed hepatic disease. 10.1186/s12876-020-01461-2
    A machine learning approach to predict intravenous immunoglobulin resistance in Kawasaki disease patients: A study based on a Southeast China population. Wang Tengyang,Liu Guanghua,Lin Hongye PloS one Kawasaki disease is the leading cause of pediatric acquired heart disease. Coronary artery abnormalities are the main complication of Kawasaki disease. Kawasaki disease patients with intravenous immunoglobulin resistance are at a greater risk of developing coronary artery abnormalities. Several scoring models have been established to predict resistance to intravenous immunoglobulin, but clinicians usually do not apply those models in patients because of their poor performance. To find a better model, we retrospectively collected data including 753 observations and 82 variables. A total of 644 observations were included in the analysis, and 124 of the patients observed were intravenous immunoglobulin resistant (19.25%). We considered 7 different linear and nonlinear machine learning algorithms, including logistic regression (L1 and L1 regularized), decision tree, random forest, AdaBoost, gradient boosting machine (GBM), and lightGBM, to predict the class of intravenous immunoglobulin resistance (binary classification). Data from patients who were discharged before Sep 2018 were included in the training set (n = 497), while all the data collected after 9/1/2018 were included in the test set (n = 147). We used the area under the ROC curve, accuracy, sensitivity, and specificity to evaluate the performances of each model. The gradient GBM had the best performance (area under the ROC curve 0.7423, accuracy 0.8844, sensitivity 0.3043, specificity 0.9919). Additionally, the feature importance was evaluated with SHapley Additive exPlanation (SHAP) values, and the clinical utility was assessed with decision curve analysis. We also compared our model with the Kobayashi score, Egami score, Formosa score and Kawamura score. Our machine learning model outperformed all of the aforementioned four scoring models. Our study demonstrates a novel and robust machine learning method to predict intravenous immunoglobulin resistance in Kawasaki disease patients. We believe this approach could be implemented in an electronic health record system as a form of clinical decision support in the near future. 10.1371/journal.pone.0237321
    HLA-B*54:01 Is Associated With Susceptibility to Kawasaki Disease. Kwon Young-Chang,Sim Bo Kyung,Yu Jeong Jin,Yun Sin Weon,Yoon Kyung Lim,Lee Kyung-Yil,Kil Hong-Ryang,Kim Gi Beom,Han Myung-Ki,Song Min Seob,Lee Hyoung Doo,Jang Gi Young,Hong Young Mi,Kwon Oh-Joong,Oh Heung-Bum,Lee Jong-Keuk, , Circulation. Genomic and precision medicine 10.1161/CIRCGEN.118.002365
    A framework for understanding Kawasaki disease pathogenesis. Lo Mindy S Clinical immunology (Orlando, Fla.) Kawasaki disease (KD) is a common vasculitis of childhood, typically affecting children under the age of five. Despite many aspects of its presentation that bear resemblence to acute infection, no causative infectious agent has been identified despite years of intense scrutiny. Unlike most infections, however, there are significant differences in racial predilection that suggest a strong genetic influence. The inflammatory response in KD specifically targets the coronary arteries, also unusual for an infectious condition. In this review, we discuss recent hypotheses on KD pathogenesis as well as new insights into the innate immune response and mechanisms behind vascular damage. The pathogenesis is complex, however, and remains inadequately understood. 10.1016/j.clim.2020.108385
    Multisystem inflammatory syndrome in children: Is there a linkage to Kawasaki disease? Loke Yue-Hin,Berul Charles I,Harahsheh Ashraf S Trends in cardiovascular medicine Since 1967, researches have hunted for an etiology for Kawasaki Disease (KD). Meanwhile, the 2019 Coronavirus Disease (COVID-19) pandemic has produced a strange new illness termed multisystem inflammatory syndrome in children (MIS-C) and raised hopes that a cause for KD may be identified. This current review paper discusses KD and its potential connection to pediatric COVID-19 and MIS-C illness. 10.1016/j.tcm.2020.07.004
    Oxidised Low-Density Lipoprotein and Its Receptor-Mediated Endothelial Dysfunction Are Associated with Coronary Artery Lesions in Kawasaki Disease. He Yue-E,Qiu Hui-Xian,Wu Rong-Zhou,Rong Xing,Xu Hai-Tang,Xiang Ru-Lian,Chu Mao-Ping Journal of cardiovascular translational research The study aimed to investigate the role of oxidised low-density lipoprotein (oxLDL)/lectin-like-oxLDL receptor-1 (LOX-1) in coronary artery lesions (CALs) in Kawasaki disease (KD) and of plasma oxLDL concentration in the early prediction of CALs in KD. This prospective study included 80 KD patients, 20 febrile and 20 healthy children. oxLDL, LOX-1 and other parameters were analysed in the acute phase. Plasma oxLDL concentration and LOX-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) were significantly increased in KD patients compared with febrile and healthy children (P < 0.001 and P = 0.022, respectively), particularly in the group with CALs (P < 0.001 and P = 0.027, respectively). Coronary Z-score was significantly correlated with plasma oxLDL concentration and LOX-1 mRNA expression (r = 0.739 and 0.637, respectively; P < 0.01). The sensitivity and specificity of predicting CALs were 71.4% and 77.2%, respectively, at plasma oxLDL concentration ≥ 12.38 mU/L. oxLDL/LOX-1 may be involved in CAL development. The plasma oxLDL concentration in the acute phase is a potentially useful biological indicator for predicting CAL in KD patients. 10.1007/s12265-019-09908-y
    Increased Interleukin-35 suppresses peripheral CD14 monocytes function in patients with Kawasaki disease. Xing Haijian,Tian Gang BMC immunology BACKGROUND:Interleukin-35 (IL-35) is a newly identified IL-12 cytokine family member, which regulates the activity of immune cells in infectious diseases and autoimmune disorders. However, the regulatory function of IL-35 in Kawasaki disease is not well elucidated. METHODS:Thirty-three patients with Kawasaki disease and seventeen healthy controls were studied. Peripheral IL-35 concentration was measured by enzyme linked immunosorbent assay. CD14 monocytes were purified, and mRNA expression of IL-35 receptor (IL-12Rβ2 and gp130) was semi-quantified by real-time polymerase chain reaction. CD14 monocytes were stimulated with recombinant IL-35. The modulatory role of IL-35 treated CD14 monocytes to naïve CD4 T cell activation was investigated by flow cytometry. The influence of IL-35 to cytotoxicity of CD14 monocytes was assessed by measuring target cell death, cytokine and granzyme secretion. RESULTS:Plasma IL-35 concentration was elevated in patients with Kawasaki disease. There was no significant differences of either IL-12Rβ2 or gp130 mRNA expression in CD14 monocytes between Kawasaki disease patients and controls. IL-35 suppressed CD14 monocytes induced naïve CD4 T cell activation in Kawasaki disease, and this process required direct cell-to-cell contact. IL-35 also inhibited tumor necrosis factor-α and granzyme B secretion by CD14 monocytes from patients with Kawasaki disease, however, only granzyme B was responsible for the cytotoxicity of CD14 monocytes. CONCLUSIONS:IL-35 played an important immunosuppressive role to CD14 monocytes function in Kawasaki disease. 10.1186/s12865-020-00348-x
    DIAGNOSTIC VALUE OF THE REACTION AT THE BACILLUS CALMETTE-GUÉRIN VACCINATION SITE IN KAWASAKI DISEASE. Diniz Lilian Martins Oliveira,Castanheira Raquel Gomes,Giampietro Yala Gramigna,Silva Matheus Sewastjanow,Nogueira Flávia Duarte,Pessoa Priscila Duarte,Santos Thamires Marx da Silva,Coutinho Gislene Soares,Romanelli Roberta Maia de Castro Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo OBJECTIVE:To describe the case of an infant - diagnosed with incomplete Kawasaki disease - who developed BCG scar reactivation. CASE DESCRIPTION:A 6-month-old patient was admitted to hospital with fever associated with ocular hyperemia, cervical lymphadenopathy, and hyperemic lips, and remained hospitalized for 12 days. The physical examination revealed an inflammatory reaction at the site of the BCG scar, leading to the diagnosis of incomplete Kawasaki disease. The patient was treated with venous immunoglobulin, but presented recurrence of Kawasaki disease, with subsequent onset of coronary artery disease. COMMENTS:BCG scar reactivation is an important finding in countries where the vaccine is routinely given and may be a useful marker for early diagnosis of Kawasaki disease, especially in its incomplete form. 10.1590/1984-0462/2021/39/2019338
    Berberine protects Kawasaki disease-induced human coronary artery endothelial cells dysfunction by inhibiting of oxidative and endoplasmic reticulum stress. Xu Mingguo,Qi Qi,Men Lina,Wang Shushui,Li Meng,Xiao Min,Chen Xiaozhou,Wang Sheng,Wang Guobing,Jia Hongling,Liu Cong Vascular pharmacology Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis especially in coronary arteries. Berberine (BBR) shows several beneficial effects on cardiovascular system. The present study is to investigate whether BBR exerts protective effect against KD-induced damage of human coronary artery endothelial cell (HCAECs) and the underlying mechanisms. HCAECs exposed to medium with 15% serum from KD patients or healthy volunteers for 24 h. Stimulated HCAECs were treated with vehicle (without BBR) and BBR (20 μM) for 24 h, the cell apoptosis, cell cycle, induction of intracellular reactive oxygen species (ROS) and protein expression were examined by flow cytometry and western blot. The KD-induced differentially expressed proteins in HCAECs were determined by quantitative proteomics. BBR inhibited HCAECs from apoptosis and arrested cell cycle at G0/G1 stage. BBR protected HCAECs from injury by inhibiting expression of THBD, vWF and EDN1. Bioinformatics analysis suggested that the oxidative and ER stress were involved in KD-induced damage in HCAECs. ROS production and the protein expression of ATF4, p-EIF2α, p-PERK, XBP1, p-IRE1, HSP90B1, HSPG2, DNAJC3, P4HB and VCP were increased by serum from KD patients and decreased by BBR treatment. BBR exerts its protective effects on KD-induced damage of HCAECs through its inhibitory effects on oxidative and ER stress indicating BBR as a therapeutic candidate for KD. 10.1016/j.vph.2020.106660
    A Comprehensive Update on Kawasaki Disease Vasculitis and Myocarditis. Soni Priya R,Noval Rivas Magali,Arditi Moshe Current rheumatology reports PURPOSE OF THE REVIEW:Kawasaki disease (KD) is a childhood systemic vasculitis of unknown etiology that causes coronary artery aneurysms (CAA), and if left undiagnosed can result in long-term cardiovascular complications and adult cardiac disease. Up to 20% of KD children fail to respond to IVIG, the mainstay of therapy, highlighting the need for novel therapeutic strategies. Here we review the latest findings in the field regarding specific etiology, genetic associations, and advancements in treatment strategies to prevent coronary aneurysms. RECENT FINDINGS:Recent discoveries using the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model have accelerated the study of KD pathophysiology and have advanced treatment strategies including clinical trials for IL-1R antagonist, Anakinra. KD remains an elusive pediatric vasculitis syndrome and is the leading cause of acquired heart disease among children in the USA and developed countries. Advancements in combination treatment for refractory KD with further understanding of novel genetic risk factors serve as a solid foundation for future research endeavors in the field. 10.1007/s11926-020-0882-1
    Analysis of Exercise Capacity of Children with Kawasaki Disease by a Coronary Artery z Score Model (ZSP Version 4) Derived by the Lambda-Mu-Sigma Method. Tuan Sheng-Hui,Su Hung-Tzu,Chen Chia-Hsin,Liou I-Hsiu,Weng Tzu-Pin,Chen Guan-Bo,Lin Ko-Long The Journal of pediatrics OBJECTIVE:To compare exercise capacity measured by direct cardiopulmonary exercise testing (CPET) of children with Kawasaki disease with different coronary artery diameter z scores (CA z score). STUDY DESIGN:This was a retrospective study that recruited children with Kawasaki disease after the acute stage receiving CPETs determined by CPET with treadmill. CA z score was based on a model using the Lambda-Mu-Sigma method. Max-Z was defined as the maximum z score of the proximal left anterior descending CA (LCA) or right CA (RCA). Children with Kawasaki disease with a Max z <2.0 and ≥2.0 were defined as Kawasaki disease group 1 and Kawasaki disease group 2, respectively. RESULTS:We recruited 32 boys and 17 girls with a mean age of 12.39 ± 3.61 years. Kawasaki disease group 1 (n = 36) had significantly higher peak metabolic equivalent (peak-MET) and peak rate pressure product (PRPP) than Kawasaki disease group 2 (n-13) (P = .046, P < .001). Max-Z correlated with peak-MET moderately and negatively (P < .001, Spearman rho= - .506). Max-Z correlated with PRPP modestly and negatively (P = .011, Spearman rho= - .360). CONCLUSIONS:Children after Kawasaki disease with a coronary artery Max-Z ≥ 2.0 had significantly lower peak exercise capacity than those with a Max-Z < 2.0. Max-Z might be used as an indicator of CA reserve and exercise capacity during peak exercise after the acute stage of Kawasaki disease. 10.1016/j.jpeds.2018.05.036
    Neurological involvement in Kawasaki disease: a retrospective study. Liu Xiaoliang,Zhou Kaiyu,Hua Yimin,Wu Mei,Liu Lei,Shao Shuran,Wang Chuan Pediatric rheumatology online journal BACKGROUND:Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children. Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive. We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). METHODS:We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017. Profiles of patients with neurological symptoms (group A, n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B, n = 512). Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance. RESULTS:Neurological involvement was observed in 5.1% (80/1582) of patients with KD. The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%). Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD. The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B. However, neurological involvement was not an independent risk factor for IVIG resistance or CALs. CONCLUSION:Rates of neurological involvement were relatively low in patients with KD. Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden. Our results highlight the need for pediatricians to recognize KD with neurological involvement and the importance of standard IVIG therapy. TRIAL REGISTRATION:Retrospectively registered. 10.1186/s12969-020-00452-7
    Value of C-reactive protein/albumin ratio in predicting intravenous immunoglobulin-resistant Kawasaki disease- a data from multi-institutional study in China. Li Gang,Wang Ting,Gou Yongying,Zeng Rumeng,Liu Dong,Duan Yan,Liu Bin International immunopharmacology BACKGROUND:C-reactive protein/albumin ratio (CAR) is associated with inflammation. However, it prognostic value for intravenous immunoglobulin (IVIG) resistant Kawasaki disease (KD) has scarcely investigated. METHODS:A total of 957 patients with KD including 159 IVIG-resistant patients and 798 with IVIG-responsive patients between Jun 2013 and August 2019 were reviewed and the laboratory records were compared between IVIG-resistant patients and IVIG-responsive patients. Univariate and multivariate logistic analysis were performed to determine the independent predictors of IVIG resistance. A receiver operating characteristic curve analysis was conducted to compare the predictive accuracy between CAR and the combination of neutrophil-to-lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). RESULTS:High CAR was associated with high the incidence of IVIG-resistance, anemia and coronary artery lesions, and high levels of neutrophils, CRP, aspartate aminotransferase, NLR, PLR, and erythrocyte sedimentation rate, and associated with low levels hemoglobin, albumin and lymphocytes count (all p < 0.05). The CAR (OR: 1.33, CI: 1.09-1.57), NLR (OR: 1.02, CI: 1.002-1.039) and PLR (OR: 1.004, CI: 1.003-1.005) were independent predictors for IVIG-resistance. CAR has superior discriminatory ability for IVIG resistance when compared with combination of NLR and PLR (z = 2.575, p = 0.01). CONCLUSIONS:CAR prior to IVIG treatment could be a novel prognostic marker for IVIG resistant KD. CAR was superior to the combination of NLR and PLR for predicting IVIG resistant KD. 10.1016/j.intimp.2020.107037
    Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease. Kong Wei-Xing,Ma Fei-Yue,Fu Song-Ling,Wang Wei,Xie Chun-Hong,Zhang Yi-Ying,Gong Fang-Qi World journal of pediatrics : WJP BACKGROUND:Currently, there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease. METHODS:A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions. RESULTS:The intravenous immunoglobulin resistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions. CONCLUSIONS:Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions. 10.1007/s12519-019-00234-6
    Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition. Li Yandie,Zheng Qi,Zou Lixia,Wu Jianqiang,Guo Li,Teng Liping,Zheng Rongjun,Jung Lawrence Kwok Leung,Lu Meiping Pediatric rheumatology online journal BACKGROUND:As an acute febrile and inflammatory disease, Kawasaki disease (KD) could develop Kawasaki disease shock syndrome (KDSS) sometimes. However its pathogenesis was still not well known. This study was to learn more about the clinical features and evaluate the role of cytokines in the pathogenesis of KDSS. METHODS:We collected clinical and laboratory data retrospectively for all patients with KDSS(KDSS, n = 27)who were hospitalized at our hospital from Jan 2014 to Oct 2017. For patient with KDSS, we randomly identified 43 patients with KD as control subjects (KD, n = 43). Clinical features, laboratory evaluations were collected. Cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in serum were assayed using flow cytometric bead array. RESULTS:The patients with KDSS were older age (43.41 ± 31.42 vs 28.81 ± 21.51 months, P < 0.05), longer duration of fever (10.63 ± 5.12 vs 6.98 ± 2.45 days, P < 0.05), higher WBC count, neutrophils, CRP, ESR, PCT and D-dimer, and lower hemoglobin and albumin, more severe hyponatremia and hypokalemia, more refractory to IVIG therapy, more coronary artery abnormalities (CAAs), aseptic meningitis, and longer duration of hospitalization than patients with KD (all P < 0.05). The levels of serum IL-6 [184.1 (27.7-2577.3) vs 54.1 (4-425) pg/ml], IL-10 [42.6 (5-236.7) vs 9.4 (3-94) pg/ml], TNF-α [2.6 (1.0-23.4) vs 2.1 (1-6) pg/ml] and IFN-γ [18.3 (4.5-94.4) vs 6.7 (2-56) pg/ml] in KDSS patients were significant higher than KD patients (all P < 0.05). ROC curves showed that 66.7 pg/ml of IL-6, 20.85 pg/ml of IL-10 and 8.35 pg/ml of IFN-γ had sensitivity and specificity for identifying KDSS as 85.2 and 62.8%; 66.7 and 83.7%; 74.1 and 74.4% respectively. No fatality was recorded in this series. CONCLUSIONS:KDSS were characteristic as more cytokine production and prone to developing IVIG non-responsiveness and CAAs. KD patients with IL-6 above 66.7 pg/ml, IL-10 above 20.85 pg/ml, and IFN-γ above 8.35 pg/ml suggested higher risk for KDSS. 10.1186/s12969-018-0303-4
    Current pharmacological intervention and development of targeting IVIG resistance in Kawasaki disease. Zhang Rui Long,Lo Hang Hong,Lei Cheng,Ip Nikki,Chen Juan,Law Betty Yuen-Kwan Current opinion in pharmacology Kawasaki disease is an acute childhood self-limited vasculitis, causing the swelling or inflammation of medium-sized arteries, eventually leading to cardiovascular problems such as coronary artery aneurysms. Acetylsalicylic acid combined with intravenous immunoglobulin (IVIG) is the standard treatment of Kawasaki disease (KD). However, a rising number of IVIG resistant cases were reported with severe disease complications such as the KD Shock Syndrome or KD-Macrophage activation syndrome. Recent reports have depicted the overlapped number of children with SARS-CoV-2 and KD, which was called multisystem inflammatory syndrome. Simultaneously, the incidence rate of KD-like diseases are increased after the outbreak of COVID-19, suggesting the virus may be associated with KD. New intervention is important to overcome the problem of IVIG treatment resistance. This review aims to introduce the current pharmacological intervention and possible resistance genes for the discovery of new drug for IVIG resistant KD. 10.1016/j.coph.2020.08.008
    Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study. Miyata Koichi,Kaneko Tetsuji,Morikawa Yoshihiko,Sakakibara Hiroshi,Matsushima Takahiro,Misawa Masahiro,Takahashi Tsutomu,Nakazawa Maki,Tamame Takuya,Tsuchihashi Takatoshi,Yamashita Yukio,Obonai Toshimasa,Chiga Michiko,Hori Naoaki,Komiyama Osamu,Yamagishi Hiroyuki,Miura Masaru, The Lancet. Child & adolescent health BACKGROUND:The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVIG plus prednisolone. METHODS:We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratified patients using the Kobayashi score into predicted IVIG non-responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defined according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. FINDINGS:From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27·6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3-8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5-5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe inflammation from the Kawasaki disease itself. INTERPRETATION:Primary IVIG plus prednisolone therapy in this study had an effect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. FUNDING:Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center. 10.1016/S2352-4642(18)30293-1
    Retrospective study of the course, treatment and long-term follow-up of Kawasaki disease: a single-center experience from Poland. Stasiak Aleksandra,Smolewska Elżbieta Rheumatology international Kawasaki disease (KD) is an acute, self-limited, systemic vasculitis and the most common cause of acquired coronary artery disease in pediatric population in the developed countries. It occurs mostly in Asian countries; however, due to better access to diagnostic and imaging tests, it is more frequently diagnosed among pediatric patients in Poland. The aim of this study was to describe the clinical course with special interest in cardiac involvement, treatment and follow-up of Polish patients with KD. It is a single-center retrospective study. Clinical features (including coronary involvement), laboratory results and treatment were evaluated. In our study group, we observed elevated levels of indicators of inflammation: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocytosis, platelet count, fibrinogen, D-dimer and ferritin. We also noticed changes in lipid profile and liver enzymes. Twenty-four patients were diagnosed with coronary artery abnormalities. Mean day of treatment equaled 9th day of the disease. Kawasaki disease should be suspected in all pediatric patients who have fever lasting 5 days, or more particularly those under 5 years of age. It is very important to apply treatment within the first 10 days of disease due to the high risk of cardiovascular complications. Each child should have echocardiography on admission, around 14th day of the disease, after 4-6 weeks from the onset of symptoms, as well as long-term observation at least once a year due to the fact that the inflammatory process and changes in the lipid profile increase the risk of atherosclerosis. Children with coronary aneurysms should undergo check-ups every 6 months. 10.1007/s00296-019-04286-9
    Temporal Clusters of Kawasaki Disease Cases Share Distinct Phenotypes That Suggest Response to Diverse Triggers. Burns Jane C,DeHaan Laurel L,Shimizu Chisato,Bainto Emelia V,Tremoulet Adriana H,Cayan Daniel R,Burney Jennifer A The Journal of pediatrics OBJECTIVE:To test the hypothesis that cases of Kawasaki disease within a temporal cluster have a similar pattern of host response that is distinct from cases of Kawasaki disease in different observed clusters and randomly constructed clusters. STUDY DESIGN:We designed a case-control study to analyze 47 clusters derived from 1332 patients with Kawasaki disease over a 17-year period (2002-2019) from a single clinical site and compared the cluster characteristics with those of 2 control groups of synthetic Kawasaki disease clusters. We defined a "true" Kawasaki disease cluster as at least 5 patients within a 7-day moving window. The observed and synthetic Kawasaki disease clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, rotated empirical orthogonal function analysis. RESULTS:In a univariate analysis, the median values for age, coronary artery z-score, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and age-adjusted hemoglobin for several of the true Kawasaki disease clusters exceeded the 95th percentile for the 2 synthetic clusters. REOF analyses revealed distinct patterns of demographic and clinical measures within clusters. CONCLUSIONS:Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features and levels of inflammation than would be expected by chance. These observations suggest that different triggers and/or different intensities of exposures result in clusters of cases of Kawasaki disease that share a similar response pattern. Analyzing cases within clusters or cases who share demographic and clinical features may lead to new insights into the etiology of Kawasaki disease. 10.1016/j.jpeds.2020.09.043
    Early childhood exposure to maternal smoking and Kawasaki Disease: A longitudinal survey in Japan. Yorifuji Takashi,Tsukahara Hirokazu,Doi Hiroyuki The Science of the total environment Kawasaki disease is the leading cause of acquired childhood heart disease in most developed countries, but the etiology of the disease is unknown. An aberrant immune response to some environmental triggers may play a role and involuntary exposure to tobacco smoke can alter immune functions. We thus prospectively examined the association between early childhood exposure to maternal smoking and the incidence of Kawasaki disease. We used a large, nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 38,444 children for whom information on maternal smoking was available. Maternal smoking status was ascertained at 6months of age, and responses to questions about hospital admission for Kawasaki disease between the ages of 6 and 30months were used as outcome. We conducted binomial log-linear regression analyses adjusting for children's, parental, and residential factors with children of non-smoking mothers as our reference group. Maternal smoking increased the risk of admission, in particular for the period between 6 and 18months of age, in a dose-dependent manner. Compared with children of non-smoking mothers, the children of mothers who smoked had a risk ratio of 1.83 (95% confidence interval: 1.06, 3.35) for hospital admissions between 6 and 30months of age and a risk ratio of 2.69 (95% confidence interval: 1.56, 4.64) for hospital admissions between 6 and 18months of age. Early childhood exposure to maternal smoking may increase the risk of Kawasaki disease hospitalizations in childhood. 10.1016/j.scitotenv.2018.11.194
    A 10-year cross-sectional retrospective study on Kawasaki disease in Iranian children: incidence, clinical manifestations, complications, and treatment patterns. Sadeghi Payman,Izadi Anahita,Mojtahedi Sayed Yousef,Khedmat Leila,Jafari Mohsen,Afshin Azadeh,Yarahmadi Pourya,Hosseinali Beigi Effat BMC infectious diseases BACKGROUND:Kawasaki disease (KD) as an acute, systemic vasculitis is the leading cause of acquired heart disease in children under the age of 5 years. METHODS:A 10-year cross-sectional retrospective study was designed to assess 190 Iranian children with KD during 2008-2018. Demographic data, clinical and laboratory manifestations from the onset of symptoms to diagnosis, clinical signs and symptoms, and subsequent treatments were evaluated to predict hospitalization stay, complications, and response to treatment. RESULTS:Children with KD had a male-to-female ratio of 1.18:1 and an average age of 36 months. There was an insignificantly more incidence of KD in cold seasons. The most frequent symptoms were fever (92.6%), oral mucus membrane changes (75.8%), bilateral bulbar conjunctival injection (73.7%), polymorphous skin rash (73.2%), peripheral extremity changes (63.7%), and cervical lymphadenopathy (60.0%). The rate of gastrointestinal, cardiac, joint, and hepatic complications was determined to be 38.4, 27.9, 6.8, and 4.2%, respectively. 89.5% of patients received intravenous immunoglobulin (IVIG) plus aspirin as the first line of treatment, while, 16.3% of them needed an extra second line of treatment. Significantly low serum sodium levels and high platelet counts were detected in KD patients with cardiac complications. Cardiac complications often were more encountered in patients who did not respond to the first line of treatment. Higher platelet count, lower serum sodium amount, and C-reactive protein (CRP) level were significantly associated with a need for an additive second line of treatment. A significant relationship between hospitalization stay and hemoglobin level was found. CONCLUSION:As most of the clinical manifestations and complications were following other reports released over the past few years, such data can be confidently used to diagnose KD in Iran. Seasonal incidence and a positive history of recent infection in a notable number of patients may provide clues to understand possible etiologies of KD. Laboratory markers can successfully contribute to health practitioners with the clinical judgment of the need for additional treatments, possible complications, and hospitalization duration. 10.1186/s12879-021-06046-2
    A comparison of serum IL6 and CRP levels with respect to coronary changes and treatment response in Kawasaki disease patients: a prospective study. Nandi Alolika,Pal Priyankar,Basu Surupa Rheumatology international To evaluate serum levels of IL6 in patients with Kawasaki disease and compare it with CRP, and to assess the role of these biomarkers in predicting coronary changes and resistance to the first-line therapy of this disease in a subset of Indian population. A single centre prospective observational study was conducted amongst all Kawasaki disease patients for a period of 18 months from January 2017 at Institute of Child Health, Kolkata. Serum IL6 and CRP were compared at diagnosis and after 48 h of administering IVIG in patients who developed coronary changes with those who did not and also among the responders and non-responders to IVIG, the first-line therapy given to these patients. Out of total 72 patients of KD [mean age of presentation: 24 months, M:F = 1.22:1], 30% (n = 22) had coronary artery involvement (CALs), and 15% (n = 11) were IVIG non-responders. Mean IL6 prior to IVIG in those with CALs was 143.60 pg/ml, which was about three times higher than in those without CALs (mean = 52.90 pg/ml), the difference being significant (p < 0.01). Mean CRP values also were significantly raised in patients with CALs (p < 0.01) whereas post-IVIG levels of mean serum IL6 was found to be 108.15 pg/ml in non-responders which was about 17 times raised than that in the responders (mean IL6 = 6.22),the difference again was statistically significant (p < 0.001).Also, ROC analysis revealed a sensitivity and specificity of 81.0% and 82.0%, respectively, for IL6; 72% and 74%, respectively, for CRP for predicting CALs. This study also shows a sensitivity of 72% and specificity of 68% for IL6 in predicting IVIG resistance whereas that of CRP being 90% sensitive and 36% specific. These results suggest that higher levels of IL-6 and CRP at diagnosis are associated with occurrence of CALs and IVIG resistance in KD patients. Using the cutoff for IL6 and CRP from our study, chances of developing CALs and IVIG resistance can be predicted, which might prevent the development of future complications like aneurysms in such patients. 10.1007/s00296-019-04375-9
    Prognosis and Risk Factors of Coronary Artery Lesions before Immunoglobulin Therapy in Children with Kawasaki Disease Qiu Huixian,Jia Chang,Wang Zhenquan,He Yuee,Rong Xing,Wu Rongzhou,Chu Maoping,Shi Hongying Balkan medical journal Background:Many children with Kawasaki disease develop coronary artery lesions before intravenous immunoglobulin treatment. However, little data are available on the prognosis of children with Kawasaki disease who developed coronary artery lesions before intravenous immunoglobulin treatment. Aims:To explore the outcomes of coronary artery lesions before intravenous immunoglobulin treatment in children with Kawasaki disease and analyze the factors that influence the duration of coronary artery lesions. Study Design:Retrospective cohort study. Methods:All patients with Kawasaki disease who developed coronary artery lesions before intravenous immunoglobulin treatment in our hospital from January 2009 to December 2014 were reviewed. A Cox proportional hazards model was used to determine the factors influencing the prognosis of coronary artery lesions. Results:Among 182 patients included, 28.6% were male, 83.50% were younger than 36 months, and 181 exhibited resolution of coronary artery lesions 2 years after disease onset. The median duration of coronary artery lesions was 31 days, and the proportion of coronary artery lesions was 52% at 1 month, 35% at 2 months, 33% at 3 months, 25% at 6 months, 14% at 1 year, and 0.5% at 2 years. The univariate analysis showed that overweight status, higher platelet count, lower albumin level, and starting treatment more than 10 days after disease onset were factors that possibly affect the duration of coronary artery lesions in children. The multivariate Cox regression analysis showed that female sex (adjusted hazard ratio, 1.661; 95% confidence interval, 1.117-2.470) was an independent protective factor, and overweight status (adjusted hazard ratio, 0.469; 95% confidence interval, 0.298-0.737), higher platelet count (adjusted hazard ratio, 0.649; 95% confidence interval, 0.443-0.950), and starting treatment more than 10 days after disease onset (adjusted hazard ratio, 0.392; 95% confidence interval, 0.215-0.716) were independent risk factors for a longer duration of coronary artery lesions. Conclusion:The average duration of coronary artery lesions before intravenous immunoglobulin therapy in children with Kawasaki disease is approximately 1 month. Male gender, overweight status, higher platelet count, and initiation of treatment more than 10 days after the onset of the disease are independent risk factors for longer-lasting coronary artery lesions. 10.4274/balkanmedj.galenos.2020.2020.1.56
    [National consensus on the cardiological treatment and follow-up of Kawasaki disease]. Barrios Tascón Ana,Centeno Malfaz Fernando,Rojo Sombrero Henar,Fernández-Cooke Elisa,Sánchez-Manubens Judith,Pérez-Lescure Picarzo Javier, Anales de pediatria Kawasaki disease is a self-limiting acute vasculitis that affects small and medium-sized vessels, and is the most common cause of acquired heart disease in children in our environment. Up to 25% of untreated patients develop coronary aneurysms. It is suspected that an infectious agent may be the trigger of the disease, but the causative agent is still unknown. Based on the previous evidence, recommendations are proposed for the diagnosis, treatment of acute disease, and the long-term management of these patients, in order to unify criteria. The diagnosis must be quick, based on easy-to-use algorithms and with the support of complementary tests. This document includes the indication of available imaging techniques, as well as the planning of cardiological examinations based on the initial involvement. Intravenous immunoglobulin is the basis of the initial treatment. The role of corticosteroids is still controversial, but there are studies that support its use as adjuvant treatment. A multidisciplinary working group has developed a scheme with different treatment guidelines depending on the risk factors at diagnosis, the patient's clinical situation, and response to previous treatment, including indications for thromboprophylaxis in patients with coronary involvement. The stratification of risk for long-term treatment is essential, as well as the recommendations on the procedures based on the initial cardiological involvement and its progression. Patients with coronary aneurysms require continuous and uninterrupted cardiological monitoring for life. 10.1016/j.anpedi.2018.04.003
    Elevated Levels of Platelet Activating Factor and Its Acetylhydrolase Indicate High Risk of Kawasaki Disease. Yi Lunyu,Zhang Jing,Zhong Jiarong,Zheng Yuqiang Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research Kawasaki disease (KD) is a systemic vasculitis in children, which is related to inflammation and abnormal activation of immune system. Platelet activating factor (PAF) and its acetylhydrolase (PAF-AH) may play an important role in the pathogenesis of KD. This study aimed to investigate diagnosis and prognostic value of serum PAF and PAF-AH in KD. One hundred thirteen KD children were divided into coronary artery lesion (CAL) KD, noncoronary artery lesion (NCAL) KD, intravenous immunoglobulin (IVIG)-responsive KD, and IVIG-nonresponsive KD group. Seventy cases of fever control (F) group and 71 cases of normal control (N) group were set up. Peripheral venous blood was collected to detect serum PAF and PAF-AH levels, combined with other inflammatory mediators. Results showed that the serum levels of PAF and PAF-AH were significantly elevated in the KD group compared with F group and N group ( < 0.05). And the levels of conventional inflammatory mediators in KD group were significantly higher than those of F group ( < 0.05). In children with fever (KD group and F group), the area under the receiver operating characteristic curve (AUC) for PAF in prediction of KD was 0.804, and the estimated sensitivity and specificity were 79.6% and 74.3% with a cutoff of PAF >201.77 ng/mL, respectively; the AUC for PAF-AH in prediction of KD was 0.587, and the estimated sensitivity and specificity were 61.9% and 55.7% with a cutoff of PAF-AH >0.153 μmol/min/mL, respectively. Compared with NCAL group, PAF and C-reactive protein were higher in CAL group ( < 0.05). The AUC for PAF in prediction of CAL KD was 0.679, and the estimated sensitivity and specificity were 96.0% and 40.9% with a cutoff of PAF >225.52 ng/mL, respectively. Thus, serum levels of PAF and PAF-AH were significantly elevated in the acute phase of KD. Serum PAF and PAF-AH contributed to the diagnosis of KD, and serum PAF has a greater diagnostic value for KD. At the same time, elevated serum PAF has a certain predictive value for the occurrence of coronary artery lesions in Kawasaki disease rather than IVIG-nonresponsive KD. 10.1089/jir.2019.0141
    Prediction Model for the Differential Diagnosis of Kawasaki Disease and Acute Cervical Lymphadenitis in Patients Initially Presenting with Fever and Cervical Lymphadenitis. Kim Jae Min,Kim Jihye The Journal of pediatrics OBJECTIVES:To distinguish early-stage lymph node first presentation of Kawasaki disease from acute cervical lymphadenitis, we developed an algorithm using sequential laboratory marker levels and radiologic findings. STUDY DESIGN:Data were obtained from pediatric inpatients initially presenting with fever and cervical lymphadenopathy. Discriminative factors for the differential diagnosis of acute cervical lymphadenitis and lymph node first presentation of Kawasaki disease were identified from intergroup comparison or univariate logistic regression analysis. A model for differentiating between lymph node first presentation of Kawasaki disease and acute cervical lymphadenitis was constructed using decision-tree analysis. RESULTS:Patients were divided into 2 cohorts: training (206 patients) and validation (103 patients) cohorts. A decision-tree model developed from the data of the training cohort included 3 determinants: neck computed tomography- or ultrasonography-defined abscess, percentage change in C-reactive protein level, and percentage change in neutrophil count. The prediction power of our decision-tree model for the validation cohort was superior to that of previously known laboratory markers (sensitivity of 89.5%, specificity of 88.9%, positive predictive value of 95.8%, negative predictive value of 75.0%, overall accuracy of 89.3%, and a Youden index of 0.784). CONCLUSIONS:A decision-tree model could differentiate lymph node first presentation of Kawasaki disease from acute cervical lymphadenitis with an increased accuracy. External validation based on multicenter data is needed before clinical application. 10.1016/j.jpeds.2020.05.031
    Von Willebrand factor parameters as potential biomarkers for disease activity and coronary artery lesion in patients with Kawasaki disease. Jakob André,Schachinger Eva,Klau Simon,Lehner Anja,Ulrich Sarah,Stiller Brigitte,Zieger Barbara European journal of pediatrics Elevated von Willebrand factor (vWF):Antigen plasma levels have been observed in conjunction with cardiovascular diseases or vasculitis. The association of Kawasaki disease, a vascular inflammatory disease and vWF:Antigen, vWF:Collagen binding activity, and vWF multimers is unknown. We therefore investigated vWF parameters in 28 patients with acute Kawasaki disease in association with disease activity and coronary artery lesions. VWF:Antigen and vWF:Collagen binding activity were assessed via enzyme-linked immunoassay. The ratio of both (vWF:Collagen binding activity and VWF:Antigen) was calculated and vWF multimeric structure analysis performed. We analyzed the association between vWF parameters and our clinical data focusing on coronary artery outcome. VWF:Antigen and vWF:Collagen binding activity levels were significantly higher in the acute than in the disease's convalescence phase, and correlated positively with CRP levels. Neither variable was associated with coronary artery lesions. The vWF:Collagen binding activity/vWF:Antigen ratio, however, was significantly decreased in patients with a coronary artery lesion (z-score > 2; N = 10; mean ratio 0.96 vs. 0.64; p = 0.031) and even more so in those with a coronary artery aneurysm (z-score > 2.5; N = 8; mean ratio 0.94 vs. 0.55; p = 0.02). In a sub-analysis, those patients with a very low ratio in the acute phase presented a persistent coronary artery aneurysm at their 1-year follow-up.Conclusion: This study suggests that comprehensive analysis of vWF parameters may help to both monitor KD inflammation and facilitate the identification of those patients carrying an increased risk for coronary artery lesion.What is Known:• Von Willebrand factor (VWF)-parameters represent surrogate markers for vascular inflammation.• Kawasaki disease is a generalized vasculitis in children, which can be complicated by coronary artery lesions.What is New:• In those Kawasaki disease patients with coronary artery lesions, the vWF:CB/vWF:Ag ratio was significantly decreased.• VWF parameters may help to identify patients at risk for coronary artery lesions. 10.1007/s00431-019-03513-6
    Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015-2016. Makino Nobuko,Nakamura Yosikazu,Yashiro Mayumi,Kosami Koki,Matsubara Yuri,Ae Ryusuke,Aoyama Yasuko,Yanagawa Hiroshi Pediatrics international : official journal of the Japan Pediatric Society BACKGROUND:Approximately 50 years have passed since Kawasaki disease (KD) was first reported. The KD nationwide survey began in 1970. Although >360 000 cases have already been reported in Japan, the cause is still unknown. In Japan, the number of patients and incidence rate of KD has continued to increase. It is necessary to examine the trend of the occurrence in the surveillance of KD. METHODS:The nationwide survey of patient incidence in 2015 and 2016 was conducted in 2017, as the 24th nationwide survey of KD. A questionnaire was sent to pediatric departments in hospitals with >100 beds and specialized pediatric hospitals, and was responded to by the attending pediatricians. RESULTS:The total number of patients in 2 years was 31 595, and the sex ratio (male/female) was 1.34. The incidence rate (/100 000 children aged 0-4 years/year) was 330.2 (371.2 in boys, 287.3 in girls) in 2015, and 309.0 (343.2 in boys, 273.2 in girls) in 2016. The number of patients by month peaked in January. The age-specific incidence rate according to sex was highest in children between 9 and 11 months of age, after which the incidence rate gradually decreased with advancing age. CONCLUSIONS:We summarize the most recent nationwide survey of KD and consider the change in the epidemiologic picture. 10.1111/ped.13809
    Clinical Manifestations of Kawasaki Disease Shock Syndrome. Ma Le,Zhang Ya-Yuan,Yu Hai-Guo Clinical pediatrics A case-control study was performed to ascertain clinical features of children who had been diagnosed as Kawasaki disease shock syndrome (KDSS), a severe condition related to Kawasaki disease (KD). Hospitalized patients were selected in Nanjing Children's Hospital. Demographic characteristics, clinical presentation, laboratory data, cardiovascular findings, and therapies were analyzed. Compared with the control group, KDSS patients were older and had more serious skin rash. The proportions of leukocytosis, neutrophilia, and hypoalbuminemia was higher, as was the level of while blood cell count, C-reactive protein, brain natriuretic peptide, and ferroprotein. KDSS patients had higher incidence of arrhythmias and more severe coronary artery involvement. All case patients received aspirin, glucocorticoid, and intravenous immunoglobulin, 33.3% required albumin, and 90.4% needed vasoactive infusions. In conclusion, KDSS patients may have more serious inflammatory responses in the acute phase. Short-term use of glucocorticoid may be important in inhibiting the inflammatory response. Albumin and vasoactive drugs are useful to rescue shock. 10.1177/0009922817729483
    Kawasaki disease fact check: Myths, misconceptions and mysteries. Butters Coen,Curtis Nigel,Burgner David P Journal of paediatrics and child health 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. 10.1111/jpc.15101
    Australian hospitalisations for Kawasaki disease, 1993-1994 to 2017-2018. O'Brien Kathleen Journal of paediatrics and child health AIM:To estimate and describe trends in hospitalisations for Kawasaki disease in Australia. METHODS:Analysis of the National Hospital Morbidity Database for separations with a principal diagnosis of Kawasaki disease, 1993-1994 to 2017-2018. Limited to persons aged 0-19 years. RESULTS:Over the period 1993-1994 to 2017-2018, there were 6368 hospitalisations for Kawasaki disease among people aged 0-19 years; 433 same-day (6.8%) and 5935 overnight (93.2%). Among overnight separations, 15.8% were for children under the age of 1 year and 58.7% for those aged 1-4 years; 60.3% were for males. The hospitalisations rate has increased from 5.2 per 100 000 population in 1993-1994 to 12.4 per 100 000 in 2017-2018. The ratio of male to female hospitalisations was 1.5:1. CONCLUSIONS:Kawasaki disease is uncommon among Australia children, but its incidence is increasing. As there are no known preventable risk factors for the disease, prompt identification and treatment remain crucial to minimising the risk of cardiovascular sequelae. 10.1111/jpc.14847
    The relationship between Interleukin-27 gene polymorphisms and Kawasaki disease in a population of Chinese children. Si Feifei,Wu Yao,Wang Xianmin,Gao Fang,Yang Dan,Liu Ruixi,Yi Qijian Cardiology in the young BACKGROUND:Kawasaki disease is the leading cause of acquired heart disease in children from developed countries. The Interleukin-6/ Interleukin-12 cytokine family has many members, including the paradoxical anti- and pro-inflammatory Interleukin-27. Recent studies have demonstrated that Interleukin-27 plays a role in immune diseases. Given this, we sought to evaluate the association between Interleukin-27 genetic polymorphisms and Kawasaki disease in Chinese children.Methods and resultsInterleukin-27 was genotyped in 100 Kawasaki disease children and 98 healthy children (controls), resulting in the direct sequencing of eight Single-nucleotide Polymorphisms: rs17855750, rs40837, rs26528, rs428253, rs4740, rs4905, rs153109, and rs181206). There were no significant differences in Interleukin-27 genotypes between Kawasaki disease and control groups. Of the eight Single-nucleotide Polymorphisms, there was a significant increase in the risk of Kawasaki disease with coronary arterial lesions in children with the rs17855750 (T>G), rs40837 (A>G), rs4740 (G>A), rs4905 (A>G), rs153109 (T>C), and rs26528 (A>G) Single-nucleotide Polymorphisms. This was particularly true for rs17855750 (T>G), which had a greater frequency in Kawasaki disease children with coronary arterial aneurysm. CONCLUSION:These findings may be used as risk factors when assessing a child's likelihood of developing Kawasaki disease, as well as for the development of future therapeutic treatments for Kawasaki disease. 10.1017/S1047951118000914
    Association of MnSOD gene polymorphism with susceptibility to Kawasaki disease in Chinese children. Wu Jiping,Yu Meng,Huang Lihua,Qian Yujie,Kong Min,Kang Zhijuan,Yang Zuocheng Cardiology in the young BACKGROUND:Kawasaki disease is a type of acute febrile rash disease that is common in children and is characterised by primary lesions of systemic middle and small vasculitis, which can lead to coronary artery lesions. Manganese superoxide dismutase (MnSOD), one of the most important antioxidases in the human body, plays a key role in maintaining the balance of free radicals in the human body. Two single-nucleotide polymorphisms (SNPS) (rs4880 and rs5746136) in the MnSOD gene were related to oxidative stress disease. The purpose of this study is to explore the possible relationship between MnSOD gene polymorphisms and Kawasaki disease susceptibility. METHODS:This study included 100 Kawasaki disease children and 102 healthy children. Two single-nucleotide polymorphisms (rs4880 and rs5746136) were detected by polymerase chain reaction sequence-based typing. RESULTS:There was a significant difference in both the genotype frequency (χ2 = 10.805, p = 0.005) and the allele frequency (χ2 = 7.948, p = 0.005) of rs5746136 between the Kawasaki disease group and the control group. Children with the A allele had a 0.558 times lower risk of Kawasaki disease than those without the A allele (χ2 = 7.948, p = 0.005, odds ratio = 0.558, 95% confidence interval = 0.371-0.838). There was no significant difference in the genotype and gene frequencies of rs5746136 between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesion groups (p > 0.05), and there was no significant difference in the rs4880 genotype and allele frequencies between the Kawasaki disease and healthy control groups or between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesions groups (p > 0.05). CONCLUSION:This study provides evidence supporting an association between MnSOD gene polymorphisms and susceptibility to Kawasaki disease. The genotype AA and the allele A of the MnSOD gene locus rs5746136 were risk factors for Kawasaki disease. 10.1017/S104795112000356X
    The serum concentration of soluble interleukin-2 receptor in patients with Kawasaki disease. Teraura Hiroyuki,Kotani Kazuhiko,Minami Takaomi,Takeshima Taro,Shimooki Osamu,Kajii Eiji Annals of clinical biochemistry Kawasaki disease is a febrile disease of childhood that is associated with increased inflammatory cytokines and immunoregulatory abnormalities. While the serum concentrations of soluble IL-2 receptor can change under such pathologies, the relevance of the soluble IL-2 receptor concentration in patients with Kawasaki disease has not been specified. We aimed to summarize the existing studies that reported the soluble IL-2 receptor concentrations in patients with Kawasaki disease. Original articles that were published up to July 2016 were collected using a PubMed/Medline-based search engine. A total of nine articles that reported the serum soluble IL-2 receptor concentrations in acute-phase Kawasaki disease were eligible. All of the articles described a high soluble IL-2 receptor concentration in patients with Kawasaki disease relative to the level of controls or the reference range. Two of five articles on patients with coronary artery aneurysms described a significantly higher soluble IL-2 receptor concentration in patients with coronary artery aneurysms than patients without. Two articles on patients with intravenous immunoglobulin therapy described a significant decrease of the soluble IL-2 receptor concentration after the therapy. Accordingly, the serum soluble IL-2 receptor can be a potent marker of disease activity and therapeutic effects in patients with Kawasaki disease; further studies are thus warranted for its use in the clinical setting. 10.1177/0004563216677583
    Multiple Emergency Department Visits for a Diagnosis of Kawasaki Disease: An Examination of Risk Factors and Outcomes. Lo Jeffrey,Gauvreau Kimberlee,Baker Annette L,de Ferranti Sarah D,Friedman Kevin G,Lo Mindy S,Dedeoglu Fatma,Sundel Robert P,Newburger Jane W,Son Mary Beth F The Journal of pediatrics OBJECTIVES:To determine predictors of >1 emergency department (ED) visit for a Kawasaki disease diagnosis in a quaternary care pediatric hospital and compare outcomes between patients with 1 vs >1 visit for Kawasaki disease diagnosis. STUDY DESIGN:Medical records of patients evaluated for Kawasaki disease between January 2006 and August 2018 at Boston Children's Hospital were abstracted for demographic and clinical data. Predictors of >1 visit were explored using logistic regression and classification and regression tree analysis. RESULTS:Of 530 patients diagnosed with Kawasaki disease, 117 (22%) required multiple ED visits for Kawasaki disease diagnosis. Multivariable regression and classification and regression tree analysis identified ≤2 Kawasaki disease criteria (OR 33.9; 95% CI 18.1-63.6), <3 days of fever at the first visit (OR 3.47; 95% CI 1.77-6.84), and non-White race (OR 2.15; 95% CI 1.18-3.95) as predictors of >1 visit. There were no significant differences in duration of hospitalization, day of illness at initial Kawasaki disease treatment, intravenous immunoglobulin resistance, need for adjunctive therapies, or coronary artery outcomes between patients diagnosed with Kawasaki disease at initial visit vs subsequent visits. CONCLUSIONS:Incomplete Kawasaki disease criteria, fewer days of fever, and non-White race were significant predictors of multiple ED visits for Kawasaki disease diagnosis in this single institution study. Our findings underscore the importance of maintaining a high index of suspicion for Kawasaki disease in patients with <4 Kawasaki disease criteria. Further research is needed to determine causes for increased healthcare use in non-White patients to receive a Kawasaki disease diagnosis. 10.1016/j.jpeds.2021.01.007
    Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey. Cattalini Marco,Della Paolera Sara,Zunica Fiammetta,Bracaglia Claudia,Giangreco Manuela,Verdoni Lucio,Meini Antonella,Sottile Rita,Caorsi Roberta,Zuccotti Gianvincenzo,Fabi Marianna,Montin Davide,Meneghel Alessandra,Consolaro Alessandro,Dellepiane Rosa Maria,Maggio Maria Cristina,La Torre Francesco,Marchesi Alessandra,Simonini Gabriele,Villani Alberto,Cimaz Rolando,Ravelli Angelo,Taddio Andrea, Pediatric rheumatology online journal BACKGROUND:There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS:The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS:One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION:Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths. 10.1186/s12969-021-00511-7
    Kawasaki disease and 13-valent pneumococcal conjugate vaccination among young children: A self-controlled risk interval and cohort study with null results. Baker Meghan A,Baer Bethany,Kulldorff Martin,Zichittella Lauren,Reindel Rebecca,DeLuccia Sandra,Lipowicz Hana,Freitas Katherine,Jin Robert,Yih W Katherine PLoS medicine BACKGROUND:Kawasaki disease is an acute vasculitis that primarily affects children younger than 5 years of age. Its etiology is unknown. The United States Vaccine Safety Datalink conducted postlicensure safety surveillance for 13-valent pneumococcal conjugate vaccine (PCV13), comparing the risk of Kawasaki disease within 28 days of PCV13 vaccination with the historical risk after 7-valent PCV (PCV7) vaccination and using chart-validation. A relative risk (RR) of 2.38 (95% CI 0.92-6.38) was found. Concurrently, the Food and Drug Administration (FDA) conducted a postlicensure safety review that identified cases of Kawasaki disease through adverse event reporting. The FDA decided to initiate a larger study of Kawasaki disease risk following PCV13 vaccination in the claims-based Sentinel/Postlicensure Rapid Immunization Safety Monitoring (PRISM) surveillance system. The objective of this study was to determine the existence and magnitude of any increased risk of Kawasaki disease in the 28 days following PCV13 vaccination. METHODS AND FINDINGS:The study population included mostly commercially insured children from birth to <24 months of age in 2010 to 2015 from across the US. Using claims data of participating Sentinel/PRISM data-providing organizations, PCV13 vaccinations were identified by means of current procedural terminology (CPT), Healthcare Common Procedure Coding System (HCPCS), and National Drug Code (NDC) codes. Potential cases of Kawasaki disease were identified by first-in-365-days International Classification of Diseases 9th revision (ICD-9) code 446.1 or International Classification of Diseases 10th revision (ICD-10) code M30.3 in the inpatient setting. Medical records were sought for potential cases and adjudicated by board-certified pediatricians. The primary analysis used chart-confirmed cases with adjudicated symptom onset in a self-controlled risk interval (SCRI) design, which controls for time-invariant potential confounders. The prespecified risk interval was Days 1-28 after vaccination; a 28-day-long control interval followed this risk interval. A secondary analytic approach used a cohort design, with alternative potential risk intervals of Days 1-28 and Days 1-42. The varying background risk of Kawasaki disease by age was adjusted for in both designs. In the primary analysis, there were 43 confirmed cases of Kawasaki disease in the risk interval and 44 in the control interval. The age-adjusted risk estimate was 1.07 (95% CI 0.70-1.63; p = 0.76). In the secondary, cohort analyses, which included roughly 700 potential cases and more than 3 million person-years, the risk estimates of potential Kawasaki disease in the risk interval versus in unexposed person-time were 0.84 (95% CI 0.65-1.08; p = 0.18) for the Days 1-28 risk interval and 0.97 (95% CI 0.79-1.19; p = 0.80) for the Days 1-42 risk interval. The main limitation of the study was that we lacked the resources to conduct medical record review for all the potential cases of Kawasaki disease. As a result, potential cases rather than chart-confirmed cases were used in the cohort analyses. CONCLUSIONS:With more than 6 million doses of PCV13 administered, no evidence was found of an association between PCV13 vaccination and Kawasaki disease onset in the 4 weeks after vaccination nor of an elevated risk extending or concentrated somewhat beyond 4 weeks. These null results were consistent across alternative designs, age-adjustment methods, control intervals, and categories of Kawasaki disease case included. 10.1371/journal.pmed.1002844
    One year in review: Kawasaki disease. Tirelli Francesca,Marrani Edoardo,Giani Teresa,Cimaz Rolando Current opinion in rheumatology PURPOSE OF REVIEW:Kawasaki disease is a childhood vasculitis of unknown origin, whose major complication is the development of coronary artery aneurysms (CAA). The purpose of this review is to provide an overview on the most recent evidence on the pathogenesis, diagnosis and treatment options of Kawasaki disease summarizing the most relevant studies published in the last year. RECENT FINDINGS:Several genetic polymorphisms leading to Kawasaki disease susceptibility have been identified, mostly related to immune system regulation; potential external triggers are being investigated by environmental epidemiology studies. A new diagnostic test based on trascriptomics has been tested with promising preliminary results. With regards to first-line treatments, the real effectiveness of high-dose aspirin remains a matter of debate. For refractory cases, the ones at the highest risk for developing CAA, promising results come from the use of biologic agents, especially TNF and IL-1 blockers. SUMMARY:Recent literature has provided interesting insights on the various factors involved in the complex scenario behind the pathogenesis of Kawasaki disease, especially genetic ones. Novel diagnostic tests and new evidence on the use of biologic agents in Kawasaki disease are emerging, but further evidence is needed to permit early diagnosis and effective treatment of this condition. 10.1097/BOR.0000000000000671
    Kawasaki Disease Outcomes and Response to Therapy in a Multiethnic Community: A 10-Year Experience. Skochko Shannon M,Jain Sonia,Sun Xiaoying,Sivilay Nipha,Kanegaye John T,Pancheri Joan,Shimizu Chisato,Sheets Robert,Tremoulet Adriana H,Burns Jane C The Journal of pediatrics OBJECTIVES:To describe the epidemiology, response to therapy, and outcomes of Kawasaki disease in a multiethnic community with a large Hispanic and Asian population. STUDY DESIGN:We analyzed prospectively collected data from 788 unselected patients with Kawasaki disease diagnosed and treated at a single medical center over a 10-year period. RESULTS:The average incidence of Kawasaki disease in children <5 years in San Diego County over the 10 years from 2006 to 2015 was 25 per 100 000 children, with the greatest incidence (50 per 100 000) for Asian/Pacific Islanders. Compared with other race/ethnicities, Asian/Pacific Islander patients with Kawasaki disease were younger, were diagnosed earlier in the course of their fever, had higher levels of inflammatory markers, and were more likely to develop aneurysms. There was no difference across race/ethnicity groups in response to intravenous immunoglobulin therapy. Filipino children had the highest recurrence rates (9.1%; 95% CI, 3.0%-22.6%) and 12 of 788 patients (1.5%) had a first- or second-degree relative with a history of Kawasaki disease. After correcting for age of onset, sex, and illness day at diagnosis, Asian/Pacific Islander children had an increased risk of developing aneurysms (aOR, 2.37; 95% CI, 1.37-4.11; P  = .002). Overall, 180 of 788 patients (22.8%) had a maximal Z score of 2.5-10.0 and 14 of the 788 patients (1.8%) had a maximal Z score ≥10.0 despite 84% of these patients being treated within 10 days of fever onset. CONCLUSIONS:Our data provide new insights into the natural history of treated Kawasaki disease in a multiethnic population. Patient race/ethnicity influenced susceptibility to Kawasaki disease, timing of diagnosis, coronary artery outcome, and recurrence rates. 10.1016/j.jpeds.2018.07.090
    [Interpretation of the JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease]. Mu Zhi-Long,Jiao Fu-Yong,Xie Kai-Sheng Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics Kawasaki disease is the main cause of acquired heart disease in children. The cardiovascular sequelae of Kawasaki disease, such as coronary artery lesion and giant coronary aneurysm, have a great impact on children's physical and mental health. The Japanese Circulatory Society and the Japanese Society of Cardiac Surgery jointly released the JCS/JSCS 2020 guideline on diagnosis and management of cardiovascular sequelae in Kawasaki disease in July, 2020, which systematically introduces the advances in the diagnosis and management of cardiovascular sequelae of Kawasaki disease. The article gives an interpretation in the severity evaluation of Kawasaki disease and diagnosis, treatment and long-term management of cardiovascular sequelae in the guideline.
    Weather condition, air pollutants, and epidemics as factors that potentially influence the development of Kawasaki disease. Fujii Fumihiko,Egami Naoki,Inoue Masataka,Koga Hiroshi The Science of the total environment Environmental factors have been suspected to have effects on the development of Kawasaki disease. However, the associations have been conflicting. The aim of this study was to investigate the effects of air pollution, weather conditions, and epidemic infections on the risks for Kawasaki disease in Japan. The concentrations of air pollutants (nitric oxide, nitrogen dioxide, and sulfur dioxide); ambient weather conditions (temperature, atmospheric pressure, relative air humidity, precipitation, sunshine duration, and wind velocity); and the epidemic conditions of 14 infectious diseases in hospitalized patients with Kawasaki disease were monitored from 2011 to 2018 in Beppu, Japan. The overdispersed generalized additive model was used to evaluate the effects, and a combination model with a distributed lag nonlinear model was used to estimate the cumulative effects. The incidence of Kawasaki disease had positive associations with preceding hot temperature and increased concentrations of nitric oxide and sulfur dioxide and a negative association with epidemic herpangina. The cumulative relative risk of Kawasaki disease at 5 lagged days of increased temperature was 1.76 (95% confidence interval: 1.01-3.07). This city-level observational study suggested that the incidence of Kawasaki disease was associated with air pollution and increased temperature and may be indirectly influenced by epidemic herpangina. 10.1016/j.scitotenv.2020.140469
    A novel score system of blood tests for differentiating Kawasaki disease from febrile children. Tsai Chih-Min,Chu Chi-Hsiang,Liu Xi,Weng Ken-Pen,Liu Shih-Feng,Huang Ying-Hsien,Kuo Ho-Chang PloS one BACKGROUND:Kawasaki disease is the most common cause of acquired heart disease among febrile children under the age of 5 years old. It is also a clinically diagnosed disease. In this study, we developed and assessed a novel score system using objective parameters to differentiate Kawasaki disease from febrile children. METHODS:We analyzed 6,310 febrile children and 485 Kawasaki disease subjects in this study. We collected biological parameters of a routine blood test, including complete blood count with differential, C-reactive protein, aspartate aminotransferase, and alanine aminotransferase. Receiver operating characteristic curve, logistic regression, and Youden's index were all used to develop the prediction model. Two other independent cohorts from different hospitals were used for verification. RESULTS:We obtained eight independent predictors (platelets, eosinophil, alanine aminotransferase, C-reactive protein, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and monocyte) and found the top three scores to be eosinophil >1.5% (score: 7), alanine aminotransferase >30 U/L (score: 6), and C-reactive protein>25 mg/L (score: 6). A score of 14 represents the best sensitivity value plus specificity prediction rate for Kawasaki disease. The sensitivity, specificity, and accuracy for our cohort were 0.824, 0.839, and 0.838, respectively. The verification test of two independent cohorts of Kawasaki disease patients (N = 103 and 170) from two different institutes had a sensitivity of 0.780 (213/273). CONCLUSION:Our findings demonstrate a novel score system with good discriminatory ability for differentiating between children with Kawasaki disease and other febrile children, as well as highlight the importance of eosinophil in Kawasaki disease. Using this novel score system can help first-line physicians diagnose and then treat Kawasaki disease early. 10.1371/journal.pone.0244721
    Kawasaki Disease: an Update. Rife Eileen,Gedalia Abraham Current rheumatology reports PURPOSE OF REVIEW:Provide the most recent updates on the epidemiology, pathogenesis, and treatment advances in Kawasaki disease. RECENT FINDINGS:Treatment advances in complex, IVIG-refractory cases of Kawasaki disease. Multisystem inflammatory syndrome, a newly reported inflammatory condition with Kawasaki-like features and an association with the 2019 Coronavirus (COVID-19). Kawasaki disease (KD) is a rare systemic inflammatory disease that predominately affects children less than 5 years of age. Pathogenesis of KD remains unknown; the leading theory is that an unknown stimulus triggers an immune-mediated inflammatory cascade in a genetically susceptible child. Classic KD is a clinical diagnosis based on set criteria and excluding other similar clinical entities. Patients who do not fulfill complete diagnostic criteria for KD are often referred to as atypical (or incomplete) KD. The most feared complication of KD is coronary artery abnormality development, and patients with atypical KD are also at risk. Administration of intravenous immunoglobulin (IVIG) and aspirin has greatly reduced the incidence of coronary lesions in affected children. Several other immune-modulating therapies have recently been utilized in complex or refractory cases. 10.1007/s11926-020-00941-4
    [Giant coronary aneurysms in infant with Kawasaki disease shock syndrome]. García-Domínguez Miguel,Riviera-Navarro David,Quibrera José,Pérez-Gaxiola Giordano Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993) BACKGROUND:Kawasaki disease shock syndrome is a rare presentation of Kawasaki disease, in which cardiovascular manifestations associated with elevated inflammation biomarkers that develop hypotension are observed. It is preceded by gastrointestinal and neurological manifestations, with an increased risk of coronary lesions and resistance to intravenous immunoglobulin. CASE REPORT:A 5-month-old male patient with a fever that had developed in the last week, gastrointestinal and neurological symptoms with hypotensive shock, urticarial rash, BCG lymphadenitis, and edema of palms and soles. Giant coronary aneurysms were evident, so Kawasaki disease shock syndrome was diagnosed, which was treated with corticosteroid pulse and intravenous immunoglobulin. CONCLUSIONS:Clinicians must suspect Kawasaki disease shock syndrome when there is hypotensive shock, and the gastrointestinal, neurological and mucocutaneous symptoms that are characteristic of the disease, especially in infants under one year of age. The timely treatment of this disease reduces severe complications. 10.29262/ram.v67i2.737
    Adjuvant herbal therapy for targeting susceptibility genes to Kawasaki disease: An overview of epidemiology, pathogenesis, diagnosis and pharmacological treatment of Kawasaki disease. Tang Bin,Lo Hang Hong,Lei Cheng,U Ka In,Hsiao Wen-Luan Wendy,Guo Xiaoling,Bai Jun,Wong Vincent Kam-Wai,Law Betty Yuen-Kwan Phytomedicine : international journal of phytotherapy and phytopharmacology Background:Kawasaki disease (KD) is a self-limiting acute systemic vasculitis occur mainly in infants and young children under 5 years old. Although the use of acetylsalicylic acid (AAS) in combination with intravenous immunoglobulin (IVIG) remains the standard therapy to KD, the etiology, genetic susceptibility genes and pathogenic factors of KD are still un-elucidated. Purpose:Current obstacles in the treatment of KD include the lack of standard clinical and genetic markers for early diagnosis, possible severe side effect of AAS (Reye's syndrome), and the refractory KD cases with resistance to IVIG therapy, therefore, this review has focused on introducing the current advances in the identification of genetic susceptibility genes, environmental factors, diagnostic markers and adjuvant pharmacological intervention for KD. Results:With an overall update in the development of KD from different aspects, our current bioinformatics data has suggested CASP3, CD40 and TLR4 as the possible pathogenic factors or diagnostic markers of KD. Besides, a list of herbal medicines which may work as the adjunct therapy for KD via targeting different proposed molecular targets of KD have also been summarized. Conclusion:With the aid of modern pharmacological research and technology, it is anticipated that novel therapeutic remedies, especially active herbal chemicals targeting precise clinical markers of KD could be developed for accurate diagnosis and treatment of the disease. 10.1016/j.phymed.2020.153208
    Variation in the management of Kawasaki disease in Australia and New Zealand: A survey of paediatricians. Lucas Ryan,Dennington Peta,Wood Erica,Dionne Audrey,de Ferranti Sarah D,Newburger Jane W,Dahdah Nagib,Cheng Allen,Burgner David,Singh-Grewal Davinder Journal of paediatrics and child health AIM:This study aimed to describe the current management practices for Kawasaki disease (KD) in Australia and New Zealand. METHODS:We performed a secondary analysis on the Australian and New Zealand responses to a large international survey of clinicians' perspectives on KD diagnosis and management. RESULTS:There was general consensus among Australian and New Zealand clinicians regarding the indications for intravenous immunoglobulin and aspirin in the management of acute KD. There was less consensus on the dose of these agents, the definition and management of treatment-resistant KD and the approach to long-term thromboprophylaxis. CONCLUSION:Most clinicians use intravenous immunoglobulin for primary treatment of KD. There is variation regarding other aspects of KD diagnosis and important management issues. Future studies should confirm whether this reported variation occurs in real-world practice and assess potential impacts on patient outcome. 10.1111/jpc.15290
    Kawasaki disease shock syndrome complicated by coronary aneurysms: a case report. Rassas Ahmed,Guizani Rihab,Werdani Amina,Jammeli Nesrine,Mahjoub Bahri The Pan African medical journal Kawasaki disease is a generalized systemic vasculitis, which primarily affects medium-sized arteries. Kawasaki disease shock syndrome is a rare but severe presentation of this disease. This report describes a case of delayed diagnosis of Kawasaki disease shock syndrome in a 13-year-old boy who presented with cervical adenophlegmon, persistent fever, injected conjunctiva, rash, and hypotension. Echocardiography revealed the presence of bilateral coronary aneurysms. Early recognition of Kawasaki disease shock syndrome can be difficult; however, delay in diagnosis and treatment can increase the risk of coronary artery disease. 10.11604/pamj.2021.38.52.27599
    Kawasaki disease, autoimmune disorders, and cancer: a register-based study. Nielsen Troels Munck,Andersen Niels Holmark,Torp-Pedersen Christian,Søgaard Peter,Kragholm Kristian Hay European journal of pediatrics Kawasaki disease has well-described cardiovascular complications. However, the association to autoimmunity and cancer in the long term is not well described. We investigated theses associations using a registry-based matched cohort follow-up study of patients diagnosed with Kawasaki disease. Patients with Kawasaki disease were included and matched 1:5 to a population control group, matched by birth year, sex and incident month of the Kawasaki disease diagnosis. A total of 820 cases < 21 years of age were identified. Median age at diagnosis was 3 years. Median follow-up time was 12 years. Patients with KD were at higher risk of being diagnosed with ischaemic heart disease at 10 years (HR 39.94 (95% CI 5.00-319.28)) and 30 years (HR 8.33 (95% CI 3.03-22.91)). The 10-, 20- and 30-year risks of developing autoimmune disorders were HR 4.23 (95% CI 3.01-5.94), HR 3.23 (95% CI 2.44-4.29) and 2.83 (95% CI, 2.17-3.68), all p < 0.001. Cancer risk was increased after 30 years (HR 2.42 (95% CI, 1.09-5.34)). All-cause mortality after 35 years was also significantly increased (HR 3.14 (95% CI, 1.03-9.60)). Children with KD have increased long-term risks of ischaemic heart disease also of autoimmune disease and cancer, as well as an increased all-cause mortality. The surprisingly increased risk of autoimmunity must be investigated further. What is known: • Kawasaki disease is characterized by acute vasculitis and inflammation that can affect the coronary arteries. • Anti-inflammatory medicine is effective in the acute stages of the disease. What is new: • Children with Kawasaki disease have an increased risk of developing autoimmune disease in the long term. • Kawasaki disease is associated with a slightly increased mortality rate driven by non-cardiovascular causes. 10.1007/s00431-020-03768-4
    Association between breastfeeding and Kawasaki disease: a case-control study. Wang Shun,Xiang Dan,Fang Congcong,Yao Baozhen European journal of pediatrics The association between breastfeeding and Kawasaki disease is not fully understood. We performed a case-control study to examine the association between breastfeeding and Kawasaki disease. In this study, 389 children diagnosed with Kawasaki disease and 426 gender- and age-matched controls were identified at Renmin Hospital of Wuhan University between November 2013 and March 2019. Demographic and clinical data were collected from a structured telephone interview and medical record database. Odds ratio and 95% confidence interval for risk of Kawasaki disease were estimated. Children who were breastfed exclusively had a decrease in developing Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.53 (0.38-0.74). Although the risk reduction was not statistically different, partial breastfeeding also provided a protective effect (adjusted odds ratios and 95% confidence intervals 0.70 (0.48-1.01). In the stratified analysis, we still observed that exclusive breastfeeding was inversely associated with the development of complete Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.52 (0.31-0.88) and incomplete Kawasaki disease (adjusted odds ratios and 95% confidence intervals 0.54 (0.38-0.77). However, there was no significant association between exclusive breastfeeding and the intravenous immunoglobulin treatment response (adjusted odds ratios and 95% confidence intervals 0.69 (0.27-1.69) and the risk of coronary artery lesions (adjusted odds ratios and 95% confidence intervals 0.79 (0.49-1.31) in Kawasaki disease.Conclusion: Our analysis suggests that exclusive breastfeeding was inversely associated with the development of Kawasaki disease and that breastfeeding might be a potential protective factor against Kawasaki diseaseWhat is known• Previous studies have demonstrated that breastfeeding has been shown to potentially confer protection against several autoimmune disorders of childhood.• The association between breastfeeding and Kawasaki disease is not fully understood.What is newThe first study to evaluate the association between breastfeeding and the development of Kawasaki disease in China with a large sample size.• Exclusive breastfeeding was inversely associated with the development of Kawasaki disease and breastfeeding might be a potential protective factor against Kawasaki disease. 10.1007/s00431-019-03529-y
    Cardiac Valvular Lesions due to Kawasaki Disease: A Japanese Nationwide Survey. Tsuda Etsuko,Yashiro Mayumi,Nakamura Yosikazu The Journal of pediatrics OBJECTIVES:To clarify the characteristics of valvular lesions after Kawasaki disease with a Japanese nationwide survey. STUDY DESIGN:Among 137 026 patients in the nationwide Japanese surveys between 2007 and 2016, 290 (0.2%) with valvular sequelae were investigated by questionnaires. RESULTS:Among the 290 patients with valvular sequelae, mitral regurgitation (MR), tricuspid regurgitation, aortic regurgitation, and pulmonary regurgitation were present 1 month after the development of Kawasaki disease in 183 (63%), 112 (39%), 39 (13%), and 49 (17%) patients, respectively. The numbers of patients with MR during the acute phase and 1 year after developing Kawasaki disease were 208 (72%) and 95 (33%), respectively. MR improved significantly during the late period (P < .0001). Although aortic regurgitation and tricuspid regurgitation also improved significantly (P < .001), pulmonary regurgitation did not change. Ruptured mitral valves chordae tendineae occurred in 6 infants by 6 months of age, within 4 months after the onset of Kawasaki disease. Three patients needed mitral valve plasty, and 1 patient died of acute heart failure. Another 4-month-old girl died of an acute myocardial infarction with MR. In the acute phase, there was a significant difference in the MR severity between the intravenous immunoglobulin-responder group and the intravenous immunoglobulin-resistant group (P < .05). CONCLUSIONS:The inflammation caused by acute Kawasaki disease affects the function of the mitral valves. Most cases of MR improve with the alleviation of inflammation. Severe MR may have decreased with the development of treatment for acute vasculitis. However, ruptured mitral valves chordae tendineae rarely occurs in infants younger than 6 months old, within 4 months after Kawasaki disease. 10.1016/j.jpeds.2019.11.008
    Acute cholestasis as uncommon onset of Kawasaki disease: a case report. Gallerani Massimo,Pala Marco,Fabbian Fabio,De Giorgi Alfredo BMC gastroenterology BACKGROUND:Kawasaki disease (KD) or mucocutaneous lymph node syndrome is a vasculitis that mostly occurs in young children. Adult-onset KD (AKD) is rare and often misdiagnosed. Here we report a rare case of KD with cholestasis as principal symptom. CASE PRESENTATION:A 43-year-old caucasian man was admitted to our hospital for high fever, lack of appetite related to nausea and vomiting, headache and significant malaise. Physical examination highlighted fever, increasing jaundice, bilateral laterocervical lymph nodes, erythema of the palms, and strikingly red lips and conjunctiva. The clinical course was complicated by arterial hypotension, tachycardia, decreasing haemoglobin, increasing acute phase reactants tests, and multiorgan failure. Due to cardiovascular instability the patient was admitted to the local Intensive Care Unit. Chest X-ray, abdominal ultrasound, chest and abdominal CT and Colangio Magnetic Resonance were normal. Jaundice was investigated and infections, autoimmune diseases or drugs adverse reactions, were excluded. Also coronary artery computed tomography was carried out excluding coronary artery aneurysms. Broad-spectrum antibiotics were not effective. After exclusion other possible conditions, diagnosis of KD was set. He was treated with high doses of corticosteroids and acetylsalicylic acid and clinical conditions as well as laboratory exams improved. CONCLUSIONS:This report dealing with an adult onset of atypical KD may be of benefit to physicians of various specialties, including primary care doctors, hospital internists, intensivists and gastroenterologists due to its peculiarities. It demonstrates that a case of prolonged fever unresponsive to antibiotics and related to cholestatic jaundice, oedema or erythema of the extremity associated with desquamation of feet and hands, and red eyes, may suggest atypical form of KD. 10.1186/s12876-020-01495-6
    Association between left ventricular ejection fraction and Kawasaki disease shock syndrome. Qiu Huixian,Li Chen,He Yuee,Weng Fengfeng,Shi Hongying,Pan Lulu,Guo Yuping,Zhang Yuanhai,Wu Rongzhou,Chu Maoping Cardiology in the young OBJECTIVE:This study was performed to explore the clinical features of Kawasaki disease shock syndrome and analyse the association between the left ventricular ejection fraction and Kawasaki disease shock syndrome. METHODS:We retrospectively reviewed the medical records of all consecutive inpatients with Kawasaki disease at Wenzhou Medical University Second Affiliated Hospital and Yuying Children's Hospital in Wenzhou, China from January 2009 to December 2016. We compared the clinical characteristics, laboratory data, and left ventricular ejection fraction between patients with and without Kawasaki disease shock syndrome and analysed the effect of the left ventricular ejection fraction on Kawasaki disease shock syndrome under different clinical conditions of Kawasaki disease. RESULTS:In total, 1147 patients were diagnosed with Kawasaki disease. Of these 1147 patients, 17 were diagnosed with Kawasaki disease shock syndrome; 68 patients admitted to the hospital at the same time, ±2 weeks, with Kawasaki disease but without Kawasaki disease shock syndrome served as the control group. Compared with the control group, the Kawasaki disease shock syndrome group had a significantly higher incidence of coronary artery lesions, cardiac troponin I concentration, N-terminal prohormone of brain natriuretic peptide concentration, neutrophil count and ratio, alanine aminotransferase concentration, aspartate aminotransferase concentration, and C-reactive protein concentration and a significantly lower platelet count, serum albumin concentration, and left ventricular ejection fraction. A low left ventricular ejection fraction was associated with Kawasaki disease shock syndrome under different conditions of Kawasaki disease. CONCLUSION:Among patients with Kawasaki disease, cardiac injury is more likely in those with Kawasaki disease shock syndrome than without, and a low left ventricular ejection fraction may be associated with the development of Kawasaki disease shock syndrome. 10.1017/S1047951118002056
    Kawasaki Disease Shock Syndrome Versus Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles. Power Alyssa,Runeckles Kyle,Manlhiot Cedric,Dragulescu Andreea,Guerguerian Anne-Marie,McCrindle Brian W The Journal of pediatrics OBJECTIVES:To compare the clinical features and resuscitative measures of children with Kawasaki disease shock syndrome vs septic shock. STUDY DESIGN:In this retrospective case-control study, children with Kawasaki disease shock syndrome admitted to the intensive care unit from 2007 to 2017 were identified and compared with age-matched controls with septic shock. We studied 9 children with Kawasaki disease shock syndrome and 18 children with septic shock. Clinical characteristics were abstracted and between-group differences were compared. RESULTS:Compared with septic shock controls, children with Kawasaki disease shock syndrome were less likely to have an underlying comorbid illness (1/9 [11%] vs 11/18 [61%]; P = .02) and were more likely to have at least 1 of the 5 classic diagnostic signs of Kawasaki disease at presentation (9/9 [100%] vs 0/18 [0%]; P < .001), a longer duration of illness before admission (9 days [IQR, 7-14 days] vs 3 days [IQR, 1-5 days]; P = .004), and a lower platelet count at presentation (140 [IQR 73, 167]) vs 258 [IQR, 137-334]; P = .02). Among patients who underwent echocardiography, abnormalities such as ventricular dysfunction, valvulitis, and coronary artery dilation were more common in the Kawasaki disease shock syndrome cohort (5/9 [56%] vs 0/7 [0%]; P = .03). There were no differences in volume of fluid resuscitation, vasoactive-inotropic scores, duration of inotropic therapy, or biochemical markers of illness severity (other than platelet count) between the matched groups. CONCLUSIONS:A longer duration of illness before admission, lack of any significant underlying medical comorbidities, a lower platelet count, echocardiographic abnormalities, and the presence of classic diagnostic signs of Kawasaki disease at presentation may be useful early features to differentiate Kawasaki disease shock syndrome from septic shock. 10.1016/j.jpeds.2020.12.002
    Epidemiology, Treatments, and Cardiac Complications in Patients with Kawasaki Disease: The Nationwide Survey in Japan, 2017-2018. Ae Ryusuke,Makino Nobuko,Kosami Koki,Kuwabara Masanari,Matsubara Yuri,Nakamura Yosikazu The Journal of pediatrics OBJECTIVE:To report the epidemiologic characteristics, treatments, and cardiac complications of Kawasaki disease, using data from the nationwide survey in Japan. STUDY DESIGN:The nationwide Kawasaki disease survey in Japan has been conducted biennially since 1970. The most recent survey was completed in 2019, obtaining information for patients who developed Kawasaki disease during 2017-2018. Survey respondents were hospitals specializing in pediatrics and those with ≥100 beds and a pediatric department throughout Japan, where patients with Kawasaki disease were eventually hospitalized. RESULTS:The survey identified 32 528 patients with Kawasaki disease, which consisted of 15 164 (46.6%) in 2017 and 17 364 (53.4%) in 2018. The highest annual incidence rate was recorded in 2018 (359 per 100 000 children aged 0-4 years). After 1982, patients with ≤4 principal Kawasaki disease signs gradually increased, resulting in 6847 (21.1%) patients diagnosed during 2017-2018. Among the 30 784 patients receiving initial intravenous immunoglobulin administration, 6061 (19.7%) did not respond. Within 30 days of Kawasaki disease onset, 9.0% of patients were diagnosed with cardiac complications, and 2.6% of patients developed cardiac sequelae after the acute illness. CONCLUSIONS:The annual number of patients developing Kawasaki disease in Japan increased from 1970 through 2018, whereas the proportion of patients with Kawasaki disease with cardiac complications decreased in the most recent 2 decades. Early diagnosis of Kawasaki disease as well as advances in initial treatments could explain these findings. 10.1016/j.jpeds.2020.05.034