Objective Kawasaki disease (KD) is a systemic vasculitis with serious complications, especially the development of coronary artery lesions (CALs). The aim of this study was to identify the risk for the development of CALs with IVIG treatment of KD >10 days after illness onset in patients with different KD status, and explore potential moderators of the association between delayed treatment and CALs. Methods We performed a retrospective review of the medical records of KD patients. All patients were divided into two groups (conventional therapy group and delayed therapy group, IVIG treatment ≤10 days vs >10 days). We compared the demographic and clinical characteristics, laboratory data, and analyzed risk factors for CALs in patients who received IVIG treatment >10 days, and determined whether different status of KD modified the effects of delayed IVIG treatment on CALs. Results In the delayed IVIG treatment group, children were more likely to develop CALs and the proportion of incomplete KD was higher, compared with the conventional therapy group. The number of children younger than 12 months or older than 61 months was higher and children had higher BMI and were more likely to receive steroids before diagnosis in the delayed IVIG treatment group compared with the conventional therapy group. Delayed IVIG treatment was an independent risk factor for the development of CALs (adjusted OR = 2.90, 95%CI = 1.42, 5.91). Delayed therapy children with higher levels of C-reactive protein (>79 mg/L) and erythrocyte sedimentation rate (>34 mm/h) had the highest risk for developing CALs (OR = 5.68, 95%CI: 1.17, 27.59; OR = 4.11, 95%CI: 1.62, 10.46, respectively). Conclusion Delayed IVIG treatment was an independent risk factor for the development of CALs. Children in the delayed IVIG treatment group with higher levels of CRP and ESR (CRP >79 mg/L, ESR >34 mm/h) had the greatest likelihood of developing CALs.

Delayed Intravenous Immunoglobulin Treatment Increased the Risk of Coronary Artery Lesions in Children With Kawasaki Disease at Different Status

COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019–January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8–13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children’s health and help delineate long term follow-up management and prognosis.

/pdf/non-thyroidal-illness-syndrome-and-sars-cov-2-associated-58hfij6ruk.pdf

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Background We aimed to compare the ten different scores (by Kobayashi, Egami, Harada, Formosa, Sano, Piram et al., Wu et al., Yang et al., Tan et al., and Kanai et al.) to assess their performance in predicting IVIG resistance in Turkish children. Methods Complete and incomplete KD patients diagnosed with KD at Hacettepe University between June 2007 and September 2019 were evaluated retrospectively. Results A total of 129 patients, 79 boys (61.2%), with a median age 36 (IQR 19.5-57.0) months were evaluated. Sixteen patients (12.4%) had IVIG resistance. Sensitivity was low for all the ten scores. Tan, Sano, and Egami predictive models had the highest specificity (97.3, 89.4, 86.7%, respectively). Almost all scoring systems distinguished the group of patients with low risk for IVIG resistance but could not differentiate IVIG-resistant patients. Multivariate analysis for the laboratory features showed that platelet count Conclusions The current scoring systems had a low sensitivity for predicting the risk for IVIG resistance in Turkish children. On the other hand, increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance. Impact Intravenous immunoglobulin (IVIG) resistance may be observed in 10-20% of patients diagnosed with Kawasaki disease. Coronary artery involvement is more frequent in IVIG-resistant patients. It is important to predict the patients who might develop IVIG resistance to improve prognosis. The performance of the IVIG resistance predictive models in Kawasaki disease in our population is limited due to the low sensitivity.

Comparison of IVIG resistance predictive models in Kawasaki disease.

Background: In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD. Methods: We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019. Results: Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); P = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); P = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); P = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); P = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment. Conclusions: At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.

/pdf/effect-of-early-intravenous-immunoglobulin-therapy-in-3qjbqrkqnm.pdf

Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis.

Data on Kawasaki disease from tropical countries are scarce. Hence, this population-based study aims to determine the epidemiology, clinical characteristics, and outcome of Kawasaki disease in children enrolled in the Kawasaki disease registry between 2006 and 2019 in Southern Malaysia. Diagnosis of Kawasaki disease was made using standard criteria. Primary outcome measure was a coronary artery aneurysm. Multivariable logistic regression was used to analyze the associated risk factors for coronary artery aneurysm. There were 661 Kawasaki disease, with 27% incomplete and 11% atypical presentations. Male-to-female ratio was 2:1, and median age of diagnosis was 1.4 years (interquartile range 9 to 32 months). Incidence in children of less than 5 years was 14.8 (95% confidence interval [CI]: 13.6 to 16.0) per 100,000 population, higher in males (19/100,000) and Chinese (22/100,000), with a gradual increase from 5.7/100,000 in 2006 to 19.6/100,000 in 2019, p < 0.001. Incidence in children between 5 and 9 years old was 1.3 (95% CI: 0.9 to 1.6) per 100,000 population and remained stable over time. There was a seasonal pattern with peak incidence during the rainy season. Out of 625 intravenous immunoglobulins (IVIG)-treated Kawasaki disease, 7.4% were resistant, and 9% had coronary artery aneurysms. Atypical presentation, male sex, late diagnosis, and IVIG resistance were independent risk factors for coronary artery aneurysms.Conclusions: Despite the tropical climate, Kawasaki disease epidemiology is similar to non-tropic regions with seasonal patterns and a rising incidence. Atypical presentation, male sex, late diagnosis, and IVIG resistance were significantly associated with coronary artery aneurysms. What is Known: • Kawasaki disease predominantly occurs in males, children less than 5 years old, and the Asian population. • Male sex, late diagnosis, incomplete Kawasaki disease, and IVIG resistance were associated with coronary artery aneurysms. What is New: • In multi-ethnic Asian countries such as Malaysia, ethnic Chinese have a higher prevalence of Kawasaki disease compared to other ethnicities. • Kawasaki disease with atypical presentation can occur in both complete and incomplete Kawasaki disease and is significantly associated with a coronary artery aneurysm.

/pdf/epidemiology-clinical-characteristics-and-immediate-outcome-1zw5bcxhf9.pdf

Epidemiology, clinical characteristics, and immediate outcome of Kawasaki disease: a population-based study from a tropical country

While coronary artery abnormality (CAA) has been established as the most serious complication of Kawasaki disease (KD), there have been no detailed systematic reviews of the risk factors associated with this condition. We searched six databases and performed a systematic review and meta-analysis. Study-specific odds ratios (ORs) for each factor were pooled using a random effects model. We identified four risk factors for CAA children with KD: gender (OR, 1.75; 95% confidence interval [CI], 1.59-1.92), intravenous immunoglobulin (IVIG) resistance (OR, 3.43; 95% CI, 2.07-5.67), IVIG treatment beyond 10 days of onset of symptoms (OR, 3.65; 95% CI, 2.23-5.97), and increased C-reactive protein levels (OR, 1.02; 95% CI, 1.01-1.02). More number of the five typical symptoms of KD was identified as a protective factor against CAA (OR, 0.47; 95% CI, 0.33-0.66). Pediatric patients with IVIG resistant were more likely to develop CAA within 1 month of the onset of KD than the general population, even in patients with other risk factors for CAA. Thus, there is a potential risk of CAA misdiagnosis if echocardiography is not carried out frequently. In summary, we report four risk factors for CAA and a protective factor against CAA in children with KD. We recommend that pediatricians consider these factors much more closely. With accurate prediction and early preventive treatment in high-risk patients, we can expect a reduction in CAA rates. Further research is now required to investigate the associations between CAA and other factors including the interval between KD onset and IVIG administration, platelet count, and the duration of fever. We also need to confirm whether the frequency of echocardiography within a month of KD onset should be increased in IVIG-resistant patients.

/pdf/risk-factors-of-coronary-artery-abnormality-in-children-with-58yq54jqai.pdf

Risk Factors of Coronary Artery Abnormality in Children With Kawasaki Disease: A Systematic Review and Meta-Analysis.

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Risk Factors of Coronary Artery Abnormality in Children With Kawasaki Disease: A Systematic Review and Meta-Analysis.