Kawasaki disease in Kenya and review of the African literature.

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.

C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

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.

Investigating the comparative effect of vitamin D level with the type of complications in Henoch Schönlein purpura and Kawasaki disease.

INTRODUCTION AND OBJECTIVES: Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. MATERIALS AND METHODS: The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients' electronic file, and then they were analyzed after collecting information of the patients. RESULTS: In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P=0.02), hematuria (P=0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P<0.001) were significant. DISCUSSION AND CONCLUSIONS: The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients.

Investigating the comparative effect of vitamin D level with the type of complications in Henoch Schönlein purpura and Kawasaki disease / Investigación del efecto comparativo del nivel de vitamina D con el tipo de complicaciones en la púrpura de Henoch-Schönlein y la enfermedad de Kawasaki

Introduction and objectives: Henoch Schönlein purpura (HSP) and Kawasaki disease (KD) are two main inflammatory diseases among childhood vasculitis. Considering the anti-inflammatory effects of 25-hydroxyvitamin D3, we decided to investigate the association of serum 25-hydroxy vitamin D3 level with the type and severity of these conditions. Materials and methods: The present study was performed as a historical cohort of 254 affected children with KD and HSP vasculitis. The required data were extracted, using a researcher-made questionnaire from patients’ electronic file, and then they were analyzed after collecting information of the patients. Results: In HSP group, 54% of participants were boys. Similarly, in KD group, boys were more affected than girls. The comparative 25-hydroxyvitamin vitamin D3 level in HSP patients with and without renal involvement (P=0.02), hematuria (P=0.14), and in two groups with and without heart disease, and also with and without coronary artery dilatation in KD patients (P<0.001) were significant. Discussion and conclusions: The findings showed that insufficient level of vitamin D3 were significantly associated with the exacerbation of complications of both diseases, and therefore it seems that vitamin D deficiency can be an effective predictive factor of severity in HSP and KD patients.(AU)

Introducción y objetivos: La púrpura de Henoch-Schönlein (HSP) y la enfermedad de Kawasaki (EK) son dos patologías inflamatorias principales entre las vasculitis infantiles. Teniendo en cuenta los efectos antiinflamatorios de la 25-hidroxivitamina D3, decidimos investigar la asociación del nivel sérico de esta con el tipo y la gravedad de dichas afecciones. Materiales y métodos: El presente estudio se realizó como una cohorte histórica de 254 niños afectados con vasculitis por EK y HSP. Los datos requeridos se extrajeron mediante un cuestionario elaborado por un investigador del expediente electrónico de los pacientes y se analizaron después de recopilar la información de los usuarios. Resultados: En el grupo HSP, 54 y 46% de los participantes eran niños y niñas, respectivamente. De manera similar, en el grupo KD, los varones se vieron más afectados. El nivel comparativo de 25-hidroxivitamina D3 en pacientes con HSP con y sin afectación renal (p = 0,02), hematuria (p = 0,14), y en dos grupos con y sin enfermedad cardiaca, y en dos con y sin dilatación de la arteria coronaria en usuarios con EK (p < 0,001) fueron significativos. Discusión y conclusiones: Los hallazgos mostraron que los niveles insuficientes de vitamina D se asociaron significativamente con la exacerbación de las complicaciones de ambas enfermedades, por lo que parece que la deficiencia de vitamina D puede ser un factor predictivo eficaz de la gravedad en pacientes con HSP y EK.(AU

The etiologies of Kawasaki disease.

Kawasaki disease (KD) is a systemic vasculitis that affects young children and can result in coronary artery aneurysms. The etiology is currently unknown, but new clues from the epidemiology of KD in Japan, the country of highest incidence, are beginning to shed light on what may trigger this acute inflammatory condition. Additional clues from the global changes in KD incidence during the COVID-19 pandemic, coupled with a new birth cohort study from Japan, point to the potential role of person-to-person transmission of an infectious agent. However, the rising incidence of KD in Japan, with coherent waves across the entire country, points to an increasing intensity of exposure that cannot be explained by person-to-person spread. This Review discusses new and historical observations that guide us toward a better understanding of KD etiology and explores hypotheses and interpretations that can provide direction for future investigations. Once the etiology of KD is determined, accurate diagnostic tests will become available, and new, less expensive, and more effective targeted therapies will likely be possible. Clearly, solving the mystery of the etiologies of KD remains a priority for pediatric research.

Involvement of IL-17 A/IL-17 Receptor A with Neutrophil Recruitment and the Severity of Coronary Arteritis in Kawasaki Disease.

PURPOSE: To assess the role of the interleukin (IL)-17 A/IL-17 receptor A (IL-17RA) in Kawasaki disease (KD)-related coronary arteritis (CA). METHODS: In human study, the plasma levels of IL-17 A and coronary arteries were concurrently examined in acute KD patients. In vitro responses of human coronary endothelial cells to plasma stimulation were investigated with and without IL-17RA neutralization. A murine model of Lactobacillus casei cell-wall extract (LCWE)-induced CA using wild-type Balb/c and Il17ra-deficient mice were also inspected. RESULTS: The plasma levels of IL-17 A were significantly higher in KD patients before intravenous immunoglobulin therapy, especially in those with coronary artery lesion. The pre-IVIG IL-17 A levels positively correlated with maximal z scores of coronary diameters and plasma-induced endothelial mRNA levels of chemokine (C-X-C motif) ligand-1, IL-8, and IL-17RA. IL-17RA blockade significantly reduced such endothelial upregulations of aforementioned three genes and inducible nitric oxide synthase, and neutrophil transmigration. IL-17RA expression was enhanced on peripheral blood mononuclear cells in pre-IVIG KD patients, and in the aortic rings and spleens of the LCWE-stimulated mice. LCWE-induced CA composed of dual-positive Ly6G- and IL-17 A-stained infiltrates. Il17ra-deficient mice showed reduced CA severity with the fewer number of neutrophils and lower early inducible nitric oxide synthase and chemokine (C-X-C motif) ligand-1 mRNA expressions than Il17ra+/+ littermates, and absent IL-17RA upregulation at aortic roots. CONCLUSION: IL-17 A/IL-17RA axis may play a role in mediating aortic neutrophil chemoattraction, thus contributory to the severity of CA in both humans and mice. These findings may help to develop a new therapeutic strategy toward ameliorating KD-related CA.

Adverse Events Following COVID-19 Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. METHODS: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization's global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12-17 years, ICSRs following any vaccines on adolescents aged 12-17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. RESULTS: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents; myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05-27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89-9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72-1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44-0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59-2.09) were not significantly higher following COVID-19 vaccination. CONCLUSION: In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

APDS patients with immune-complex vasculitis and resolution with leniolisib.

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity with heterogeneous clinical manifestations of infections, immune dysregulation, autoimmunity; lymphoproliferation; and malignancy. Immune complex-mediated vasculitides have not yet been described in APDS patients. Here we offer a case series of three patients with APDS who have refractory IgA vasculitis (also called Henoch-Schönlein purpura), a form of immune complex-mediated vasculitis that activates complement and attracts neutrophils, macrophages and eosinophils to cause local tissue injury. Leniolisib is an inhibitor of PI3K p110δ and an FDA-approved treatment for APDS. IgA vasculitis resolved upon treatment with leniolisib. Patients with immune dysregulation including IgA vasculitis should be screened for APDS.

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease.

Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

Knowledge, attitudes, and practices towards Kawasaki disease from caregivers of children with Kawasaki disease: a cross-sectional study.

PURPOSE: To examine the knowledge, attitudes, and practices (KAP) of caregivers of children with Kawasaki disease toward Kawasaki disease. METHODS: This cross-sectional study was conducted at four hospitals in China from March 2023 to June 2023. The KAP scores were evaluated using a self-designed questionnaire (Cronbach's α = 0.840; KMO = 0.7381). Correlations between dimension scores were evaluated by Pearson correlation analysis. A structural equation model (SEM) was used to examine the relationships among factors. RESULTS: Of 643 surveyed, 49.50% were male caregivers. The mean knowledge, attitude, and practice scores were 7.12 ± 2.34 (possible range, 0-11), 29.23 ± 5.67 (possible range, 12-60), and 21.57 ± 5.34 (possible range, 6-30). Knowledge correlated with attitude (r = 0.172, P < 0.001) and practice (r = 0.280, P < 0.001). Attitude was significantly related to practice (r = 0.598, P < 0.001). SEM showed knowledge had a positive effect on attitudes (ß = 0.581, P < 0.001) and practices (ß = 0.786, P < 0.001). In addition, attitudes also positively affected practices (ß = 0.554, P < 0.001). Occupation type (ß = 0.598, P = 0.025) and monthly per capita income (ß=-0.750, P = 0.020) had different effects on attitudes, while monthly per capita income also had negative effects on practices (ß=-0.410, P = 0.021). CONCLUSION: Caregivers of children with Kawasaki disease have moderate knowledge and unfavorable attitudes but proactive practices toward this disease. The results could help design an educational intervention to improve KAP, which could translate into better patient management and outcomes. TRIAL REGISTRATION: Not applicable.

Markers of Endothelial Dysfunction in Kawasaki Disease: An Update.

Kawasaki disease (KD) is a medium vessel vasculitis that has a special predilection for coronary arteries. Cardiovascular complications include the development of coronary artery abnormalities (CAAs) and myocarditis. Endothelial dysfunction (ED) is now recognized to be a key component in the pathogenesis of KD and is believed to contribute to the development of CAAs. ED has been evaluated by several clinical parameters. However, there is paucity of literature on laboratory markers for ED in KD. The evaluation of ED can be aided by the identification of biomarkers such as oxidative stress markers, circulating cells and their progenitors, angiogenesis factors, cytokines, chemokines, cell-adhesion molecules, and adipokines. If validated in multicentric studies, these biomarkers may be useful for monitoring the disease course of KD. They may also provide a useful predictive marker for the development of premature atherosclerosis that is often a concern during long-term follow-up of KD. This review provides insights into the current understanding of the significance of ED in KD.

Protective role of forsythoside B in Kawasaki disease-induced cardiac injury: Inhibition of pyroptosis via the SIRT1-NF-κB-p65 signaling pathway.

Kawasaki disease (KD), an acute exanthematous febrile pediatric illness involving systemic non-specific inflammatory reactions in small- and medium-sized arteries, poses a significant risk of coronary artery and myocardial inflammatory injury. Developing new KD treatments with improved safety and fewer side-effects is highly desirable. Forsythoside B (FTS-B), extracted from the Forsythia suspensa plant, exerts anti-inflammatory activity by inhibiting NF-κB, which is regulated by SIRT1, the reduced expression of which is strongly associated with cardiovascular disease. However, it has yet to be established whether FTS-B influences KD-related inflammatory damage. In this study, we investigated the effects of FTS-B on inflammation in cellular and murine models of KD. Our findings revealed that KD is associated with cardiac dysfunction and inflammatory injury to myocardial and human coronary artery endothelial cells (HCAECs), resulting in a pyroptosis-feedback loop. Both cellular and KD models were characterized by reduced SIRT1 expression and increased NF-κB p65 expression. Contrastingly, the rates of pyroptosis in both murine model myocardial tissues and HCAECs were significantly alleviated in response to FTS-B treatment. Also in both models, we detected an increase of SIRT1 expression and a decrease in the expression of p65. Further examination of the protective mechanism of FTS-B using the SIRT1-specific inhibitor, EX 527, revealed that this inhibitor blocked the palliative effects of FTS-B on inflammatory injury-induced pyroptosis. These results highlight the potential utility of the SIRT1-NF-κB-p65 pathway as a therapeutic target for KD treatment and demonstrate that FTS-B can alleviate KD-induced cardiac and HCAEC inflammatory injury via inhibition of pyroptosis.

NLRC4 methylation and its response to intravenous immunoglobulin therapy in Kawasaki disease: a case control study.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis accompanied by many systemic physiological and biochemical changes. Elucidating its molecular mechanisms is crucial for diagnosing and developing effective treatments. NLR Family CARD Domain Containing 4 (NLRC4) encodes the key components of inflammasomes that function as pattern recognition receptors. The purpose of this study was to investigate the potential of NLRC4 methylation as a biomarker for KD. METHODS: In this study, pyrosequencing was utilized to analyze NLRC4 promoter methylation in blood samples from 44 children with initial complete KD and 51 matched healthy controls. Methylation at five CpG sites within the NLRC4 promoter region was evaluated. RESULTS: Compared to controls, NLRC4 methylation significantly decreased in KD patients (CpG1: p = 2.93E-06; CpG2: p = 2.35E-05; CpG3: p = 6.46E-06; CpG4: p = 2.47E-06; CpG5: p = 1.26E-05; average methylation: p = 5.42E-06). These changes were significantly reversed after intravenous immunoglobulin (IVIG) treatment. ROC curve analysis demonstrated remarkable diagnostic capability of mean NLRC4 gene methylation for KD (areas under ROC curve = 0.844, sensitivity = 0.75, p = 9.61E-06, 95% confidence intervals were 0.762-0.926 for mean NLRC4 methylation). In addition, NLRC4 promoter methylation was shown to be significantly negatively correlated with the levels of central granulocyte percentage, age, mean haemoglobin quantity and mean erythrocyte volume. Besides, NLRC4 promoter methylation was positively correlated with lymphocyte percentage, lymphocyte absolute value. CONCLUSIONS: Our work revealed the role of peripheral NLRC4 hypomethylation in KD pathogenesis and IVIG treatment response, could potentially serve as a treatment monitoring biomarker, although its precise functions remain to be elucidated.

Prediction of coronary artery lesions in children with Kawasaki syndrome based on machine learning.

OBJECTIVE: Kawasaki syndrome (KS) is an acute vasculitis that affects children < 5 years of age and leads to coronary artery lesions (CAL) in about 20-25% of untreated cases. Machine learning (ML) is a branch of artificial intelligence (AI) that integrates complex data sets on a large scale and uses huge data to predict future events. The purpose of the present study was to use ML to present the model for early risk assessment of CAL in children with KS by different algorithms. METHODS: A total of 158 children were enrolled from Women and Children's Hospital, Qingdao University, and divided into 70-30% as the training sets and the test sets for modeling and validation studies. There are several classifiers are constructed for models including the random forest (RF), the logistic regression (LR), and the eXtreme Gradient Boosting (XGBoost). Data preprocessing is analyzed before applying the classifiers to modeling. To avoid the problem of overfitting, the 5-fold cross validation method was used throughout all the data. RESULTS: The area under the curve (AUC) of the RF model was 0.925 according to the validation of the test set. The average accuracy was 0.930 (95% CI, 0.905 to 0.956). The AUC of the LG model was 0.888 and the average accuracy was 0.893 (95% CI, 0,837 to 0.950). The AUC of the XGBoost model was 0.879 and the average accuracy was 0.935 (95% CI, 0.891 to 0.980). CONCLUSION: The RF algorithm was used in the present study to construct a prediction model for CAL effectively, with an accuracy of 0.930 and AUC of 0.925. The novel model established by ML may help guide clinicians in the initial decision to make a more aggressive initial anti-inflammatory therapy. Due to the limitations of external validation and regional population characteristics, additional research is required to initiate a further application in the clinic.

The impact of glucocorticoids therapy on cutaneous wounds in Kawasaki disease: A meta-analysis of randomized controlled trials.

Kawasaki disease (KD) is one of the most challenging diseases that is defined as an acute vasculitis that affects the coronary arteries primarily in children. It causes complications if left untreated at early stages, ultimately leading to death. Corticosteroids have been recognized to treat and cause great impact on the patients with KD. Glucocorticoid is one of the main corticosteroids that are being used to treat KD and cutaneous wounds. However, ineffectiveness of a few glucocorticoids can limit the efficacy of this treatment. This study particularly aimed to elucidate the impact of glucocorticoids on cutaneous wounds in KD. To perform the meta-analysis, a comprehensive literature survey was conducted to unveil the studies and research conducted on Kawasaki patients that revealed different glucocorticoids in the form of specific interventions influencing KD. The literature was searched using numerous keywords, screened and data was extracted to perform the meta-analysis and then it was conducted using the metabin function of R package meta. A total of 2000 patients from both intervention and control groups were employed to carry out the meta-analysis to analyse and evaluate the impact of glucocorticoids on curing KD and cutaneous wounds in patients. The results disclosed that glucocorticoids along with other steroids, mainly IVIG (intravenous immunoglobulin), was an effective intervention to patients suffering from Kawasaki. The results depicted significant outcomes with the values (risk ratio [RR]: 1.08, 95% confidence interval [CI]: 0.58-2.00, p < 0.01) and enlightened the fact that adopting different glucocorticoids may significantly improve the efficacy of skin lesions along with KD. Hence, interventions of glucocorticoids must be utilized in the clinical practice to reduce the incidence of skin wounds and adverse effects caused due to KD.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. METHODS: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. RESULTS: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. CONCLUSION: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Risk factors and an early predictive model for Kawasaki disease shock syndrome in Chinese children.

BACKGROUND: Kawasaki disease shock syndrome (KDSS), though rare, has increased risk for cardiovascular complications. Early diagnosis is crucial to improve the prognosis of KDSS patients. Our study aimed to identify risk factors and construct a predictive model for KDSS. METHODS: This case-control study was conducted from June, 2015 to July, 2023 in two children's hospitals in China. Children initially diagnosed with KDSS and children with Kawasaki disease (KD) without shock were matched at a ratio of 1:4 by using the propensity score method. Laboratory results obtained prior to shock syndrome and treatment with intravenous immunoglobulin were recorded to predict the onset of KDSS. Univariable logistic regression and forward stepwise logistic regression were used to select significant and independent risk factors associated with KDSS. RESULTS: After matching by age and gender, 73 KDSS and 292 KD patients without shock formed the development dataset; 40 KDSS and 160 KD patients without shock formed the validation dataset. Interleukin-10 (IL-10) > reference value, platelet counts (PLT) < 260 × 109/L, C-reactive protein (CRP) > 80 mg/ml, procalcitonin (PCT) > 1ng/ml, and albumin (Alb) < 35 g/L were independent risk factors for KDSS. The nomogram model including the above five indicators had area under the curves (AUCs) of 0.91(95% CI: 0.87-0.94) and 0.90 (95% CI: 0.71-0.86) in the development and validation datasets, with a specificity and sensitivity of 80% and 86%, 66% and 77%, respectively. Calibration curves showed good predictive accuracy of the nomogram. Decision curve analyses revealed the predictive model has application value. CONCLUSIONS: This study identified IL-10, PLT, CRP, PCT and Alb as risk factors for KDSS. The nomogram model can effectively predict the occurrence of KDSS in Chinese children. It will facilitate pediatricians in early diagnosis, which is essential to the prevention of cardiovascular complications.