A Case With Typical Clinical Manifestations of Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Temporally Associated With SARS-CoV-2 Infection.

Whether Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2 infection are two distinct syndromes or part of the same spectrum is not fully understood. In this report, we present the case of a five-year-old boy who fully satisfied the diagnostic criteria for both KD and MIS-C associated with SARS-CoV-2 infection. He tested positive for SARS-CoV-2 on an oropharyngeal swab antigen test approximately four weeks before the onset of symptoms. He had severe abdominal pain. Abdominal ultrasound showed ascites. He improved with initial (2 g/kg) and additional (1 g/kg) intravenous immunoglobulin (IVIG) therapy and intravenous methylprednisolone (initial dose, 2 mg/kg/day). Our case may lead to clarification of the pathogenesis of both diseases. Additionally, the recent history of SARS-CoV-2 infection for children with prolonged fever and no clear focus of infection should be checked, and, if present, clinicians should consider MIS-C temporally associated with SARS-CoV-2 infection. IVIG therapy is important for children with MIS-C who meet the diagnostic criteria for KD, even if diagnosed with MIS-C.

Prediction Models for Intravenous Immunoglobulin Resistance in Kawasaki Disease: A Meta-analysis.

CONTEXT: Approximately 10% to 20% of patients with Kawasaki disease (KD) are refractory to initial intravenous immunoglobulin (IVIG) therapy. KD is mainly associated with coronary artery abnormalities. OBJECTIVES: To identify and evaluate all developed prediction models for IVIG resistance in patients with KD and synthesize evidence from external validation studies that evaluated their predictive performances. DATA SOURCES: PubMed Medline, Dialog Embase, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from inception until October 5, 2021. STUDY SELECTION: All cohort studies that reported patients diagnosed with KD who underwent an initial IVIG of 2 g/kg were selected. DATA EXTRACTION: Study and patient characteristics and model performance measures. Two authors independently extracted data from the studies. RESULTS: The Kobayashi, Egami, Sano, Formosa, and Harada scores were the only prediction models with 3 or more external validation of the161 model analyses in 48 studies. The summary C-statistics were 0.65 (95% confidence interval [CI]: 0.57-0.73), 0.63 (95% CI: 0.55-0.71), 0.58 (95% CI: 0.55-0.60), 0.50 (95% CI: 0.36-0.63), and 0.63 (95% CI: 0.44-0.78) for the Kobayashi, Egami, Sano, Formosa, and Harada models, respectively. All 5 models showed low positive predictive values (0.14-0.39) and high negative predictive values (0.85-0.92). LIMITATIONS: Potential differences in the characteristics of the target population among studies and lack of assessment of calibrations. CONCLUSIONS: None of the 5 prediction models with external validation accurately distinguished between patients with and without IVIG resistance.

Beta-lactam allergy and drug challenge test in children: a systematic review and meta-analysis.

BACKGROUND: Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test. METHODS: We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021. RESULTS: The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I2 = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I2 = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I2 = 38%) from 18 studies. CONCLUSIONS: The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare. IMPACT: Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.

A Case Report of Respiratory Syncytial Virus-Infected 8p Inverted Duplication Deletion Syndrome with Low Natural Killer Cell Activity.

The 8p inverted duplication deletion [inv dup del(8p)] is a complex structural rearrangement in chromosome 8. Patients with this chromosomal abnormality exhibit developmental delay, facial dysmorphism, central nervous abnormalities, hypotonia, orthopedic abnormalities, and congenital heart defects. However, cellular immune function in inv dup del(8p) syndrome has never been reported. We present the case of a 1-month-old boy with inv dup del(8p) syndrome who had severe respiratory syncytial (RS) virus bronchiolitis. Natural killer (NK) cells are recruited to airway epithelium in the early phase of RS viral infection. A cluster of defensin genes (DEFs), which are deleted in inv dup del(8p), are located in 8p23.1. Human defensins are involved in antiviral activity through the NK cell-mediated cytotoxic pathway and envelope disruption in the normal immune response. This patient showed lower NK cell activity and α-defensin level compared with healthy controls. These results suggest that decreased NK cell activity can result from DEF haploinsufficiency. In addition to a skeletal deformity with chromosomal abnormality, NK cell-mediated immune deficiency may account for the exacerbation of RS virus bronchiolitis.

Regional variation in the development of neonatal hyperbilirubinemia and relation with sunshine duration in Japan: an ecological study.

BACKGROUND: Few studies have investigated the regional variations in the development of neonatal hyperbilirubinemia. This study aimed to investigate regional variations in medical costs for neonatal hyperbilirubinemia and the correlations between sunshine duration and medical care costs for neonatal hyperbilirubinemia in an ecological study, using the National Database of Japan. METHODS: We obtained data on the annual medical costs for neonatal hyperbilirubinemia, annual live births, and annual sunshine duration in each prefecture from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data, Vital Statistics in Japan, and System of Social and Demographic Statistics Prefectural Data Basic Data from 2014 to 2017. We created choropleth maps showing the regional variations (quartiles) in the annual medical costs for neonatal hyperbilirubinemia per 10 live births and the annual sunshine duration in each prefecture. We used Pearson's correlation coefficients to evaluate the associations between the annual sunshine duration and annual medical care costs for neonatal hyperbilirubinemia per 10 live births in each prefecture. RESULTS: The Tohoku region (on the Sea of Japan side) and the Hokuriku region were likely to have higher medical care costs for neonatal hyperbilirubinemia and shorter sunshine duration than the rest of the country. There were weak and negative correlations between the annual sunshine duration and the annual medical care costs for neonatal hyperbilirubinemia. The correlation coefficients ranged from -0.086 to -0.33. CONCLUSION: There could be regional variations in the medical care costs for neonatal hyperbilirubinemia in Japan. Short sunshine duration could be a prognostic factor for the development of neonatal hyperbilirubinemia.

Routine varicella vaccination program and hospitalization for herpes zoster in Japan.

Whether reducing exposure to varicella by the implementation of the routine varicella vaccination program for children leads to increased incidence of herpes zoster (HZ) remains controversial. The aim of the present study was to identify the trend in the hospitalization associated with HZ before and after the introduction of routine varicella vaccination by using nationally representative data from an inpatient database in Japan. Data were obtained on the number of inpatients hospitalized for HZ from the "Survey on the effect of the introduction of Diagnosis Procedure Combination (DPC) database" and the total population in Japan from the Population Estimates created by the former Statistics Bureau between fiscal years 2013 and 2018. The data from the DPC hospitals only and all hospitals in the survey were analyzed separately. The trends in the annual incidence of HZ hospitalization were identified. The trends in the annual hospitalization for HZ per 100,000 persons were then analyzed by age group (0-20, 21-40, 41-60, 61-79, and ≥80 years of age). The annual number of hospitalizations for HZ was approximately 20,000 in the DPC hospitals and 25,000 in all hospitals, showing no upward trend. The age-specific annual hospitalization rate for HZ did not increase in all the age groups. As age increased, the hospitalization rate also increased. This study presents no upward trend in the hospitalizations for HZ after the implementation of the routine varicella vaccination program in Japan.

Comparison of Machine Learning Models for Prediction of Initial Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease.

We constructed an optimal machine learning (ML) method for predicting intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD) using commonly available clinical and laboratory variables. We retrospectively collected 98 clinical records of hospitalized children with KD (2-109 months of age). We found that 20 (20%) children were resistant to initial IVIG therapy. We trained three ML techniques, including logistic regression, linear support vector machine, and eXtreme gradient boosting with 10 variables against IVIG resistance. Moreover, we estimated the predictive performance based on nested 5-fold cross-validation (CV). We also selected variables using the recursive feature elimination method and performed the nested 5-fold CV with selected variables in a similar manner. We compared ML models with the existing system regardless of their predictive performance. Results of the area under the receiver operator characteristic curve were in the range of 0.58-0.60 in the all-variable model and 0.60-0.75 in the select model. The specificities were more than 0.90 and higher than those in existing scoring systems, but the sensitivities were lower. Three ML models based on demographics and routine laboratory variables did not provide reliable performance. This is possibly the first study that has attempted to establish a better predictive model. Additional biomarkers are probably needed to generate an effective prediction model.