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We conducted an autopsy on a 3‐month‐old boy in whom Kawasaki disease (KD) was strongly suspected based on the autopsy findings. The infant had a fever and was brought to a nearby clinic, where he was prescribed antipyretics and kept under observation. However, 15 days after onset of the fever, he suddenly died in bed. He exhibited no obvious redness of the lips, tongue, or conjunctiva. Membranous desquamation was present on his distal fingers. Vasculitis was observed in the coronary arteries, renal artery, splenic artery, and pulmonary vein. In addition, coronary artery aneurysms were present in the right coronary artery and left anterior descending artery. Thrombotic occlusion was observed in one aneurysm in the right coronary artery, resulting in acute myocardial infarction. The coronary artery wall showed infiltration of numerous macrophages and neutrophils. This case was classified as incomplete KD because the coronary artery aneurysm could not be demonstrated before death and was only recognized at autopsy. Pathologists and forensic scientists need to be aware that there are cases in which KD goes undiagnosed and untreated, leading to coronary artery aneurysm formation and sudden death. [ABSTRACT FROM AUTHOR]

Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute systemic vasculitis involving small and medium-sized vessels. It can be complicated by varying degrees of cardiac damage, especially coronary artery disease. The disease mainly occurs in children aged < 5 years, with rarer cases in older children and adults. Intravenous immunoglobulin combined with aspirin is the widely accepted treatment regimen in the acute phase, but the dosage recommended by the American Heart Association guidelines is not suitable for heavier children. This article reports the successful management of an overweight 14-year-old child with Kawasaki disease. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a systemic inflammatory disease characterized by vasculitis. In South Korea, some pediatric doctors empirically prescribe steroids to control febrile pediatric patients. This study aimed to evaluate the clinical characteristics of patients with KD after steroid exposure. This was a single-center, retrospective, observational study. This study included patients (aged ≤15 years) between January 2020 and July 2022. We compared two groups, one group exposed to steroids and the other group who were not, using the Student's t-test or analysis of variance; otherwise, the Mann–Whitney U test or Kruskal–Wallis test was conducted. Statistical significance was set at p < 0.05. In total, 190 patients with KD were enrolled; of these, 64 (33.7 %) had a history of steroid exposure, and 126 (66.3 %) had no history of steroid exposure. In the steroid exposure group, prolonged fever duration (6.72 ± 1.72 versus 5.61 ± 1.19, p-value = <0.001), a lower proportion of complete KD (29.69 % vs. 88.10 %, p-value = <0.001), and a significantly lower level of C-reactive protein were observed. However, no significant correlations were observed between the Transthoracic Echocardiography (TTE) results (coronary artery aneurysm, existence of pericardial effusion) and prognostic factors (days of hospitalization, the number of intravenous immunoglobulin administrations, and Kobayashi score) between the two groups. Patients with KD and previous steroid exposure may exhibit an incomplete KD phenotype with prolonged fever. Although previous steroid exposure does not affect the prognosis of KD, including coronary artery aneurysms, it may mask the classic features of KD, resulting in a delayed diagnosis. [ABSTRACT FROM AUTHOR]

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BackgroundKawasaki disease (KD), an acute self-limiting vasculitis, is the main cause of acquired heart disease. Timely diagnosis and treatment can mitigate the occurrence of complications and improve patient prognosis. Facial nerve paralysis (FNP) and ptosis are rare complications of KD and are rarely reported, but FNP is considered a high risk factor for coronary aneurysms. If giant coronary artery aneurysms are formed, clinicians should be vigilant when diagnosing the formation of systemic artery aneurysms (SAAs).Patient presentationA 10-month-old girl with fever, diffuse rash, and conjunctival congestion was hospitalized locally, diagnosed with KD, and treated with intravenous infusion of gamma globulin (IVIG). She had fever again after 1 week of temperature stability, accompanied by conjunctival congestion, and was treated with a second dose of IVIG, but she still experienced recurrent fever. The day prior to admission, she developed facial asymmetry, left FNP, diffuse erythema and membranous peeling of the fingers of both hands. The patient's body temperature normalized after treatment with 20 mg/kg methylprednisolone, but cardiac ultrasound revealed progressive enlargement of the coronary artery aneurysms. On day 37of the illness, transient eyelid ptosis developed; fortunately, the left FNP and eyelid ptosis finally resolved, leaving no sequelae. Two years and eight months after onset, the patient developed bilateral humeral aneurysm.ConclusionThis is the first KD patient involving two neurological complications combined with giant coronary artery aneurysms and SAAs. KD needs to be considered in infants with unexplained recurrent fever who present with FNP or ptosis. FNP secondary to KD is a high risk factor for coronary artery aneurysms, so it is necessary to perform cardiac ultrasound for accurate diagnosis. KDs combined with giant coronary aneurysms require careful physical examination and noninvasive angiography during follow-up to detect SAA formation.

Kawasaki disease (KD) is an acute systemic vasculitis that affects medium-sized vessels, particularly the coronary arteries. KD predominantly affects children under 5 years of age. Main symptoms include fever, bilateral conjunctivitis, polymorphous exanthema, oropharyngeal mucous membranes changes, palmar and/or plantar erythema and edema, and cervical lymphadenopathy. KD can present with a few clinical features, which might lead to a delayed diagnosis, particularly in infants. When the therapy is delayed, the diagnosis is missed or in refractory cases, there is a higher risk of coronary artery aneurysms to be formed. We report a clinical case of a 3-month-old male who presented initially with fever and cervical lymphadenopathy in whom a bacterial infection was suspected and treatment with antibiotics was started. In the course of the disease erythema of the palms and soles and generalized erythematous rash developed. The diagnosis of KD was made on the 11th day of onset of symptoms and despite the treatment with two doses of intravenous immunoglobulin, high-doses corticosteroids and infliximab, during follow-up the infant developed giant coronary artery aneurysms. A comprehensive review of the literature concerning KD in infants is included. Clinical suspicion is required to diagnose KD in the youngest patients, as they are more likely to present with few features of the disease.

Kawasaki disease, extremely rare vasculitis of unknown etiology characterized by inflammation of small to medium sized arteries of multiple systems. This case report enhances the knowledge and management skills of rare clinical conditions. Here we report a case of a 3- month-old infant presented with acute onset fever, rash, non-exudative conjunctivitis and swellings of hands and legs with blood culture positive sepsis and right coronary artery dilatation. The child didn’t respond to treatment with the first dose of intravenous immunoglobulin. Therefore, the immunoglobulin resistant Kawasaki disease in infants needs further evaluation and clinical management at tertiary level hospitals.

Kawasaki disease (KD), an acute systemic vasculitis that primarily affects children under 5 years of age, is the leading cause of acquired heart disease in this age group. Recent studies propose a novel perspective on KD’s etiology, emphasizing the gastrointestinal (GI) tract, particularly the role of gut permeability. This review delves into how disruptions in gut barrier function trigger systemic inflammatory responses, exacerbate vascular inflammation, and contribute to coronary artery aneurysms. Evidence suggests that children with KD often exhibit increased gut permeability, leading to an imbalance in gut immunity and subsequent gut barrier damage. These changes impact vascular endothelial cells, promoting platelet aggregation and activation, thereby advancing severe vascular complications, including aneurysms. Additionally, this review highlights the correlation between GI symptoms and increased resistance to standard treatments like intravenous immunoglobulin (IVIG), indicating that GI involvement may predict therapeutic outcomes. Advocating for a new paradigm, this review calls for integrated research across gastroenterology, immunology, and cardiology to examine KD through the lens of GI health. The goal is to develop innovative therapeutic interventions targeting the intestinal barrier, potentially revolutionizing KD management and significantly improving patient outcomes.

Background Patients with Kawasaki disease (KD) with coronary artery involvement require long‐term cardiac care. Although respective evidence‐based recommendations are missing, cardiac catheterization is still considered the gold standard for diagnosing detailed coronary pathology. Therefore, to better understand coronary artery pathology development, we conducted a survey to document and evaluate cardiac catheterization data in a European population. Methods and Results We retrospectively analyzed cardiac catheterization data from KD children from the year 2010 until April 2023. This registry covers basic acute‐phase clinical data, and more importantly, detailed information on morphology, distribution, and the development of coronary artery pathologies. A total of 164 mainly White patients (65% boys) were included. A relevant number of patients had no coronary artery aneurysm (CAA) at the cardiac catheterization, indicating that distal CAAs were almost exclusively detected alongside proximal CAAs. Patients with multiple CAAs revealed a significant positive correlation between the number of CAAs and their dimensions in diameter and in length. Location of the CAA within the coronary artery, age at onset of KD, or natal sex did not significantly influence CAA diameters, but CAAs were longer in older children and in boys. Conclusions That distal CAAs were only present together with proximal ones will hopefully reduce diagnostic CCs in patients with KD without echocardiographically detected proximal CAAs. Furthermore, this study gives valuable insights into dimensional specifics of CAAs in patients with KD. As an ongoing registry, future analyses will further explore long‐term outcomes and performed treatments, helping to refine clinical long‐term strategies for patients with KD. REGISTRATION URL: https://drks.de/; Unique Identifier: DRKS00031022.

ObjectivesTo investigate the relationship between recent antibiotic exposure and the development of coronary artery lesions (CALs) during the clinical course of Kawasaki disease (KD).DesignData were obtained from the 25th nationwide epidemiological survey of KD conducted in Japan from 2017 to 2018. Baseline characteristics and clinical course were compared between Antibiotics (+) and Antibiotics (–) groups.SettingNationwide survey of KD in Japan.ParticipantsKD patients were enrolled by response to a questionnaire sent to physicians working in pediatrics at hospitals with >100 beds.ExposureAntibiotic exposure within one week before the first hospital visit as KD patients.Main outcome measuresThe relationship between recent antibiotic exposure and the development of coronary artery lesions (CALs).ResultsOut of 28,265 KD patients, 12,918 (45.7%) received antibiotics. In KD patients who received antibiotics in the week before KD diagnosis, the frequency of coronary artery lesions (CALs) at each phase were significantly higher compared to those who did not receive antibiotics. In further analysis using propensity score matching, recent antibiotic exposure and the initial IVIG resistance were associated with CALs at the acute and the sequelae phase. After adjusting for the status of initial IVIG resistance, recent antibiotic exposure remained associated with CALs during the acute phase (adjusted OR 1.29, 95%CI 1.16, 1.43) and the sequelae phase (1.26, 95%CI 1.04, 1.52).ConclusionsThese observations suggest that recent antibiotic exposure might be associated with higher frequency of CAL development in KD patients, possibly by altering the gut microbiota and diminishing beneficial bacteria.

Abstract Kawasaki disease (KD) causes vascular injury and lifelong remodeling. Excessive intimal proliferation has been observed, resulting in coronary artery lesions (CALs). However, the mechanisms underlying vascular remodeling in CAL and statin treatment have not been comprehensively elucidated. This study aimed to investigate the effects of statins on vascular remodeling using a KD mouse model. Candida albicans water‐soluble substance (CAWS) was intraperitoneally injected in 5‐week‐old male apolipoprotein‐E‐deficient mice. They were categorized as follows (n = 4): control, CAWS, CAWS+statin, and late‐statin groups. The mice were euthanized at 6 or 10 weeks after injection. Statins (atorvastatin) were initiated after CAWS injection, except for the late‐statin group, for which statins were internally administered 6 weeks after injection. Elastica van Gieson staining and immunostaining were performed for evaluation. Statins substantially suppressed the marked neointimal hyperplasia induced by CAWS. Additionally, CAWS induced TGFβ receptor II and MAC‐2 expression around the coronary arteries, which was suppressed by the statins. KD‐like vasculitis might promote the formation of aneurysm by destroying elastic laminae and inducing vascular stenosis by neointimal proliferation. The anti‐inflammatory effects of statins might inhibit neointimal proliferation. Therefore, statin therapy might be effective in adult patients with KD with CAL by inhibiting vascular remodeling.

IntroductionIntravenous immunoglobulin (IVIG) plus methylprednisolone as initial intensive therapy or additional therapy in Kawasaki disease (KD) has been used in clinical practice. However, its molecular and cellular mechanism is unclear.MethodsWe performed single-cell analysis on 14 peripheral blood mononuclear cell (PBMC) samples obtained from 7 KD patients who received either IVIG monotherapy or IVIG plus methylprednisolone therapy. This encompassed 4 samples from KD patients collected before and after IVIG treatment, as well as 3 samples from KD patients before and after IVIG plus methylprednisolone therapy.ResultsBoth IVIG monotherapy and IVIG plus methylprednisolone therapy can increase lymphocyte counts (e.g. CD4+T, CD8+T, and gdT cells) to address lymphopenia. They can also decrease monocyte counts and repress the expression of S100A12, NLRP3, and genes associated with immune-cell migration in monocytes. IVIG combined with methylprednisolone downregulates more monocyte-driven inflammatory pathways than IVIG alone. Additionally, this combination uniquely enhances NK cell cytotoxicity by modulating receptor homeostasis, while significantly upregulating interferon-related genes in CD4+ T cells, CD8+ T cells, and B cells, particularly type I interferons.ConclusionThe combination of IVIG with methylprednisolone attenuated monocyte-driven inflammation and improved NK cell cytotoxicity which might provide clues for pediatricians to consider treatment options for children with KD. Whether the monocyte-driven hyperinflammatory state and NK cell function can be indicators for the clinical choice of IVIG with methylprednisolone therapy in KD needs further investigation.

BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy.MethodsWe performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients.ResultsOverall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment.ConclusionOur results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients.

This issue of the Biomedical Journal features a special section on extracellular vesicles (EVs), covering their role in neurological diseases, viral infections, trogocytosis, allogeneic organ rejection and tolerance, as well as EV biodistribution. Two articles explore the mechanisms of Parkinson's disease, focusing on white matter and exosomes. This journal issue also examines polyomavirus-induced damage in renal transplant grafts, proposes a miRNA signature as a diagnostic biomarker for Kawasaki disease, discusses neural gating and associated brain wave alterations, and further clarifies the relationship between gut microbiota and immune checkpoint inhibitors. Additionally, the importance of therapeutic drug monitoring is reaffirmed.

Summary: Background: Only limited information exists regarding the epidemiology of Kawasaki disease (KD) in low-income and middle-income countries. The present study provides the incidence of KD during 2015–2019 in Chandigarh, north India. Our centre follows the largest KD cohort in India. Methods: Children with KD at Chandigarh diagnosed during January 2015–December 2019 were enrolled in the study. Annual incidence rates were determined using decadal growth rates of the National Census 2011. We computed the incidence of KD in children aged

Summary: Background: Transthoracic echocardiography (TTE) has traditionally been the primary method for coronary imaging in children with Kawasaki disease (KD). We aimed to evaluate coronary artery lesions (CALs) of the left circumflex artery (LCx) in KD on computed tomography coronary angiography (CTCA). Methods: Over a 9-year period (November 2013–December 2022), 225 children with KD underwent radiation-optimized CTCA on a 128-slice dual-source platform. TTE was performed on the same day, or a day prior or after CTCA. Findings: On CTCA, LCx CALs were seen in 41/225 (18.2%) patients. However, TTE detected CALs in only one third of these patients [15/41 (36.6%)]. CTCA showed 47 LCx CALs in 41 patients–aneurysms in 39 patients (40 fusiform, 2 saccular; 7 giant aneurysms), stenoses in 3, and thrombosis in 2. Thromboses and stenoses were both missed on TTE. Proximal LCx aneurysms were seen in 39 patients–of these, 12 had distal extension. Six patients had distal LCx aneurysms without proximal involvement and 2 non-contiguous multiple aneurysms. Four (9.75%) patients had isolated LCx involvement. Based on CTCA findings, treatment protocols had to be modified in 3/41 (7.3%) patients. Interpretation: This study highlights anatomical findings of LCx involvement in KD. Isolated LCx CALs were noted in 4/41 (9.75%) patients. TTE alone proved inadequate for LCx assessment in children with KD. With abnormalities detected in 18.2% of cases, including those missed by TTE, CTCA emerges as an essential imaging modality. The findings have implications for treatment planning and follow-up strategies in children with KD. Funding: None.

Objective: To explore the effect of intravenous immunoglobulin combined with aspirin drugs on the levels of lymphocyte subsets and related factors in children with Kawasaki disease. Methods: 105 children with Kawasaki disease admitted from March 2023 to February 2024 were selected and divided into 45 children in the control group with aspirin alone, and 60 children in the observation group were treated with intravenous immunoglobulin combined with aspirin. Compare the two groups of related indicators. Results: The total response rate was significantly higher than the observation group (P < 0.05) the values of CD4+, CD3+, CD4+ and CD4+/ CD8+ increased in the observation group (P < 0.05) IFN-γ, TNF-α, IL-2, IL-4, were lower than the observation group (P < 0.05) the incidence of adverse reactions between the two groups (P > 0.05) Conclusion: Intravenous immunoglobulin combined with aspirin in the treatment of Kawasaki disease has a remarkable effect, which can improve the level of lymphocyte subsets and related factors, then improve immune function, reduce inflammatory response, and have high safety. [ABSTRACT FROM AUTHOR]

Introduction. Kawasaki disease (KD) and pediatric inflammatory multisystem syndrome (PIMS) are similar vasculitis conditions affecting medium and small vessels, particularly the coronary arteries. This study aimed to highlight diagnostic and treatment challenges in a case initially diagnosed as PIMS, which evolved into atypical KD. Materials and methods. A 2-year-10-month-old male was admitted with a high fever persisting for 6 days, unresponsive to antipyretics. Results. On admission, the patient exhibited a poor general condition, pale skin, non-pruritic erythematous rash, and enlarged, non-painful lymph nodes. Laboratory tests showed elevated inflammatory markers, leukocytosis with neutrophilia, hypoalbuminemia, liver enzyme abnormalities, altered cardiac markers, and elevated D-dimers, but no initial echocardiographic changes. Positive SARS-CoV-2 antibodies led to an initial PIMS diagnosis, and treatment with intravenous methylprednisolone, antiplatelet, anticoagulant therapy, and hepatoprotective agents was started. The patient’s condition initially improved but then worsened with febrile spikes, rash, neutropenia, thrombocytopenia, anemia, and coronary artery dilation on echocardiography. This led to a diagnosis of KD with atypical onset, and treatment with immunoglobulin, antiplatelet, and anticoagulant therapy was initiated. The patient’s condition improved slowly. Conclusions. KD and PIMS share overlapping characteristics, making them difficult to distinguish. There is no definitive criterion to differentiate KD and PIMS, leading to potential diagnostic errors.

Abstract Background Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease. Case presentation We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy. Conclusions We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities.

Abstract Background Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. Methods We measured mtDNA and 2’3’-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. Results KD patient serum exhibited increased mtDNA and 2’3’-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. Conclusion These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.

Abstract Background Kawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan. Methods Through the national health insurance database, we identified KD during 2001–2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity. Results The KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity. Conclusions This study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants.

Abstract We present a case of a 21‐year‐old woman with fever (>38.0°C) for 5 days, mucocutaneous lesions and refractory hypotension requiring dual inotropic support. The only significant past medical history was an episode of COVID infection 4 months before admission. She was diagnosed to have multisystem inflammatory syndrome in adult (MIS‐A)—a relatively new entity which occurs as a severe complication in patients post‐COVID‐19 infection. This condition can present remarkably similarly to Kawasaki disease. Although the paediatric counterpart of MIS‐A typically occurs within 2–6 weeks post COVID‐19 infection, MIS‐A may occur up to 4 months post‐COVID‐19 infection. We wish to raise awareness of this rare entity, their similarities with Kawasaki disease and the importance of early initiation of intravenous immunoglobulin and high‐dose aspirin.

Abstract Background Macrophage activation syndrome (MAS), an example of secondary hemophagocytic lymphohistiocytosis, is a potentially fatal complication of rheumatic diseases. We aimed to study the clinical and laboratory characteristics, treatment schemes, and outcomes of different rheumatic disorders associated with MAS in children. Early warning indicators of MAS have also been investigated to enable clinicians to make a prompt and accurate diagnosis. Methods Fifty-five patients with rheumatic diseases complicated by MAS were enrolled between January 2017 and December 2022. Clinical and laboratory data were collected before disease onset, at diagnosis, and after treatment with MAS, and data were compared between patients with systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and systemic lupus erythematosus (SLE). A random forest model was established to show the importance score of each variable with a significant difference. Results Most (81.8%) instances of MAS occurred during the initial diagnosis of the underlying disease. Compared to the active stage of sJIA, the platelet count, erythrocyte sedimentation rate, and fibrinogen level in sJIA-MAS were significantly decreased, whereas ferritin, ferritin/erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and D-dimer levels were significantly increased. Ferritin level, ferritin/erythrocyte sedimentation rate, and platelet count had the greatest predictive value for sJIA-MAS. The level of IL-18 in the sJIA-MAS group was significantly higher than in the active sJIA group, whereas IL-6 levels were significantly lower. Most patients with MAS were treated with methylprednisolone pulse combined with cyclosporine, and no deaths occurred. Conclusions Thrombocytopenia, ferritin levels, the ferritin/erythrocyte sedimentation rate, and elevated aspartate aminotransferase levels can predict the occurrence of MAS in patients with sJIA. Additionally, our analysis indicates that IL-18 plays an important role in the pathogenesis of MAS in sJIA-MAS.

Abstract Background Kawasaki disease is an acute febrile vasculitis of childhood mainly affecting children under 4 years of age. In the acute stage of the disease, heart function decreases and gradually returns to normal after treatment. However, subendocardial involvement may persist, which cannot be assessed by M-mode echocardiography. Strain echocardiography is a recently developed technique to assess subendocardial involvement of myocardial deformation. We aimed to study the stratified strain of left ventricular function in a Kawasaki patient at least 6 months after the acute stage of the disease with special conditions for entering the study using two-dimensional speckle-tracking imaging. Between September 2020 and October 2022, 27 healthy children and 27 children with a history of Kawasaki disease more than 6 months ago were evaluated using two-dimensional global longitudinal peak systolic strain with automated function imaging technology. Results The mean age of patients was 5.6 years. With M-mode echocardiography, ejection fraction of each group was in the normal range. Mean (± standard deviation) global longitudinal peak strain in four-chamber view of girls with Kawasaki disease was − 23.74 ± 2.77, and that in boys with Kawasaki disease was − 20.93 ± 2.06 (P value = 0.008). GLPS (global longitudinal peak strain) was compared as an overall average and as in a separate segment, which showed significant difference in two comparisons. In our study, a decrease in the function of some cardiac segments is reported. Global longitudinal peak strain in four-chamber view was significantly lower in boys. Comparing different segments, a difference in global left ventricular long-axis strain was found between the two groups. On the other hand, there was a major difference between the two groups in the basal inferolateral, basal anterolateral, and mid-inferolateral, which receives blood from Left Circumflex artery. Conclusion Using stain echocardiography to detect continued subendocardial involvement in asymptomatic children with a history of Kawasaki disease for a better understanding of the condition, effective management and follow-up is recommended.

Abstract Background This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. Methods We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. Results The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. Conclusion Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) shows a significant overlap of symptoms with other hyper-inflammatory diseases such as Kawasaki disease (KD), but the real difference of the two conditions is still matter of debate. Coronary artery lesions (CAL) are the most relevant complication in KD. Nonetheless, CAL, myocarditis, pericarditis, arrhythmia are the main cardiovascular complications in MIS-C. A close clinical assessment is mandatory, both at the diagnosis and during the follow-up, by ECG and echocardiography. Cardiac magnetic resonance (MRI) adds important data to ultrasound findings. However, cardiac MRI studies in MIS-C are limited to a small number of cohorts. Methods We enrolled 20 children (age:1–16 years; 11 F; 9 M) with cardiac involvement secondary to MIS-C, all evaluated by cardiac MRI. Results 8 children showed pathological cardiac MRI: 2 showed pericardial effusion; 2 showed myocardial oedema; 1 showed aortic insufficiency; 3 showed delayed enhancement (one for acute myocarditis with oedema; 2 for myocardial fibrosis). Delayed enhancement was reduced significantly 5.6-9 months after the first MRI evaluation. 25% of patients with pathological MRI had CAL associated with valvular insufficiency of 2 valves. 17% of patients with normal MRI had CAL, associated with valvular insufficiency of 1 valve in 1 patient. The correlations between haematological, clinical, cardiologic parameters, treatment, did not reach the statistical significance. 4 patients were treated with anakinra. Among those, 2 patients showed a normal cardiac MRI. Cardiac lesions resolved in all the patients during the follow-up. Some patients with pathological cardiac MRI could not underwent a control with MRI, for the low compliance. However, echocardiography and ECG, documented the resolution of the pathological data in these cases. Conclusions A higher risk of CAL was documented in patients with an association of other cardiac lesions. Cardiac MRI is difficult to perform routinely; however, it is useful for evaluating the acute myocardial damage and the outcome of patients with MIS-C.

Objective: Reliably prediction models for coronary artery abnormalities (CAA) in children aged >5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting CAA at 4 to 8 weeks of illness in children with KD older than 5 years. Methods: A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance. Results: Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model. Conclusions: A novel nomogram model was established to accurately assess the risk of CAA at 4–8 weeks of onset among KD children older than 5 years, which may aid clinical decision-making.

Objective: This study investigates electrocardiographic (ECG) findings in pediatric patients diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) during the coronavirus disease-2019 pandemic, offering valuable insights into the diagnostic process. Method: Demographic, clinical, and laboratory data of 71 MIS-C cases and 27 Kawasaki disease cases between January 2019 and December 2021 were retrospectively collected from hospital records, following ethics committee approval. MIS-C diagnosis adhered to World Health Organization criteria, and Kawasaki disease diagnosis followed American Heart Association guidelines. Results: Seventy one MIS-C cases and 27 Kawasaki disease cases were included. MIS-C patients exhibited a significantly shorter duration of fever, higher C-reactive protein levels, and elevated serum cardiac troponin T troponin values compared to Kawasaki disease cases. Transthoracic echocardiographic evaluation revealed specific cardiac abnormalities in MIS-C patients, including mitral regurgitation and aortic regurgitation. ST segment changes, T-wave negativity, and QRS changes were observed significantly in MIS-C patients. Conclusion: Results provide crucial information about the ECG profile of MIS-C cases. Particularly, indicators such as ST segment changes and T-wave negativity play a critical role in distinguishing MIS-C from other similar conditions and understanding its cardiac effects. These data offer valuable clinical markers that can be utilized in the diagnosis and treatment of MIS-C.

Kawasaki disease (KD) is a mucocutaneous lymphonodular syndrome, a vasculitis of unknown etiology that mainly affects children under the age of 5 years. Today, KD is the most common cause of acquired heart disease in children in developed countries. Given the absence of pathognomonic diagnosis of the disease, the diagnosis is based solely on the identification of clinical signs and the exclusion of other clinically similar diseases. Timely therapy with intravenous immunoglobulin has significantly reduced the incidence of complications, such as coronary artery aneurysms, from 25 to ≈ 4 %. The long-term prognosis of the disease depends on the initial and current level of coronary artery damage. Patients with coronary artery aneurysms remain at high risk of developing myocardial ischaemia due to thrombosis and stenosis of the coronary arteries, which can occur in case of untimely treatment for KD. Therefore, the life of these patients depends on lifelong thromboprophylaxis and timely diagnosis of stenosis. The article presents a clinical case of incomplete Kawasaki disease, which was complica­ted by the development of giant coronary artery aneurysms.

Abstract Aim The relationship between vitamin D status and Kawasaki Disease (KD), as well as coronary artery lesion (CAL), has yet to be established. Methods A meta-analysis was conducted to assess the correlation between vitamin D status and KD, as well as the impact of vitamin D status on the progression of KD into CAL. Results The meta-analysis revealed a consistent and significant association between serum 25(OH)D level and the occurrence KD (studies N = 22; z = -3.51, P

Abstract Background Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions. Methods Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1β, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran. Results The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin β1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin β1-dependent manner, while both plexin C1 and integrin β1 contributed to Sema7A-induced HCAEC hyperpermeability. Conclusions Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin β1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.

Robert J Petrella1– 6 1Harvard Medical School, Boston, MA, USA; 2Department of Chemistry & Chemical Biology, Harvard University, Cambridge, MA, USA; 3Emergency Departments, CharterCARE Health Partners, Providence and North Providence, RI, USA; 4Emergency Department, Boston VA Medical Center, Boston, MA, USA; 5Emergency Departments, Steward Health Care Systems, Boston and Methuen, MA, USA; 6Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USACorrespondence: Robert J Petrella, Email robertjpetrella@yahoo.comAbstract: Sixth Disease (roseola infantum) and its primary causative agent, HHV-6, share names that numerically concur. This article examines and answers the question of whether that correspondence is by design or coincidental by briefly reviewing the history and nomenclature of the HHV viruses and the classic febrile rashes of childhood while highlighting some clinical and microbiologic features of HHV-6 infection.Keywords: HHV-6, HHV-7, human herpesviruses, roseola infantum, sixth disease, Kawasaki disease, viral taxonomy, nomenclature, emergency medicine, historical coincidence

Abstract Background Kawasaki disease has been described across the globe, although publications from Africa are limited. To our knowledge, there are no publications on Kawasaki disease from Kenya, which triggered this report. Methods A retrospective cross-sectional study was undertaken to identify in-patients with a discharge diagnosis of Kawasaki disease, over 2 different 5-year periods, at two pediatric hospitals in Nairobi, Kenya. We reviewed the medical records of all patients and report their clinical findings, diagnostic workup and treatment. In addition, we undertook a detailed review of the literature. Results Twenty-three patients with Kawasaki disease were identified, of those 12 (52.2%) had incomplete disease. The mean age was 2.3 years (SD+/-2.2) (range 0.3–10.3) with a male to female ratio of 1:1. The mean duration of fever at diagnosis was 8.3 days (SD+/-4.7) (range 2–20). Oral changes were the most common clinical feature and conjunctivitis the least common. Thrombocytosis at diagnosis was seen in 52% (12/23). Twenty-one patients (91.3%) were treated with intravenous immunoglobulin and all except 1 received aspirin. Baseline echocardiograms were performed in 95.7% (22/23) and found to be abnormal in 3 (13.6%). Follow-up data was limited. Our literature review identified 79 publications with documented cases of Kawasaki disease in children from 22 countries across the African continent with a total of 1115 patients including those from this report. Only 153 reported cases, or 13.7%, are from sub-Saharan Africa. Conclusions This is the first publication on Kawasaki disease from Kenya and one of the largest reports from sub-Saharan Africa. It is the first to have a complete review of the number of published cases from the African continent. Challenges in the diagnosis and management of Kawasaki disease in many African countries include disease awareness, infectious confounders, access and cost of intravenous immunoglobulin, access to pediatric echocardiography and follow-up. Increasing awareness and health care resources are important for improving outcomes of Kawasaki disease in Africa.

Abstract Background Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10–20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. Methods Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. Results Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58–0.72), specificity as 0.71 (95% CI 0.57–0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66–0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35–3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35–0.69), and the diagnostic odds ratio was 5 (95% CI 2–10). Conclusion CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

Background: To investigate whether two brands of intravenous immunoglobulin (IVIG) from the same manufacturer lead to varied effects when administered to patients with Kawasaki disease. (KD) Methods: Clinical characteristics, laboratory data, IVIG response, and coronary arteries change were analyzed between two groups. Results: We included 158 KD cases. The mean age at KD diagnosis was 23 ± 1.39 (range, 2–95) months. In the first IVIG course, 18 (11.4 %) patients were unresponsive. TBSF (brand T) and Privigen (brand P) were administered to 94 and 64 patients, respectively. The brand P group had a significantly longer fever (P

Although Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share some clinical manifestations, their cardiovascular outcomes are different, and this may be reflected at the level of the endothelial cell (EC). We performed RNA-seq on cultured ECs incubated with pre-treatment sera from KD (n = 5), MIS-C (n = 7), and healthy controls (n = 3). We conducted a weighted gene co-expression network analysis (WGCNA) using 935 transcripts differentially expressed between MIS-C and KD using relaxed filtering (unadjusted p < 0.05, >1.1-fold difference). We found seven gene modules in MIS-C, annotated as an increased TNFα/NFκB pathway, decreased EC homeostasis, anti-inflammation and immune response, translation, and glucocorticoid responsive genes and endothelial-mesenchymal transition (EndoMT). To further understand the difference in the EC response between MIS-C and KD, stringent filtering was applied to identify 41 differentially expressed genes (DEGs) between MIS-C and KD (adjusted p < 0.05, >2-fold-difference). Again, in MIS-C, NFκB pathway genes, including nine pro-survival genes, were upregulated. The expression levels were higher in the genes influencing autophagy (UBD, EBI3, and SQSTM1). Other DEGs also supported the finding by WGCNA. Compared to KD, ECs in MIS-C had increased pro-survival transcripts but reduced transcripts related to EndoMT and EC homeostasis. These differences in the EC response may influence the different cardiovascular outcomes in these two diseases.

Background: Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease. Case presentation: We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy. Conclusions: We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is the most important acquired heart disease in children. This study investigated annual incidence, seasonality, secular trend and the correlation of KD incidence with viral activity in Taiwan. Methods: Through the national health insurance database, we identified KD during 2001–2020. The viral activity was obtained from nationwide surveillance database. We analyzed KD age-specific annual incidence, secular trends, seasonality and the correlation between KD incidence and common enteric or respiratory viral activity. Results: The KD incidence of subjects younger than 18 years significantly increased from 2001 to 2020 (11.78 and 22.40 per 100,000 person-years, respectively), and substantially decreased with age. Infants younger than 1 year presented the highest KD annual incidence at 105.82 to 164.34 per 100,000 person-years from 2001 to 2020. For all KD patients, the most frequently occurring season was summer followed by autumn. The KD incidence of infants younger than 1 year had significantly positive correlation with enteric (r = 0.14) and respiratory (r = 0.18) viral activity. Conclusions: This study demonstrates the increasing trend of KD annual incidence and seasonality (more in summer and autumn) in Taiwan. The activity of common respiratory and enteric viruses was significantly correlated with KD incidence in infants. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. Methods: We measured mtDNA and 2'3'-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. Results: KD patient serum exhibited increased mtDNA and 2'3'-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. Conclusion: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management. [ABSTRACT FROM AUTHOR]