A Kobayashi- és a Kawanet-pontrendszer prediktív értéke Kawasaki-kóros betegeink immunglobulin-rezisztenciája és kardiológiai szövődményei szempontjából.

Összefoglaló. Bevezetés: A Kawasaki-szindróma immunvasculitis, amely kezeletlenül kardiológiai szövődményekhez vezethet. A korai intravénás immunglobulin-terápia mérsékli a szövődményeket, de az esetek 10–20%-a rezisztens a kezelésre. Ennek előrejelzésére világszerte számos rizikóbecslő pontrendszert használnak. Célkitűzés: A Kobayashi- és a Kawanet-pontrendszer prediktív értékének vizsgálata betegeink intravénás immunglobulin-rezisztenciája és kardiológiai szövődményei vonatkozásában. Tudomásunk szerint ez az első magyarországi vizsgálat, amely Kawasaki-szindróma esetében pontrendszerek prediktív értékét méri fel. Módszer: Retrospektív pilotvizsgálatunkban kigyűjtöttük a 2005. január és 2020. április között Kawasaki-szindróma miatt ápolt betegeink adatait. Mindegyiküknél Kobayashi-, illetve Kawanet-pontot számoltunk, valamint megvizsgáltuk azok specificitását, szenzitivitását az intravénás immunglobulin-rezisztencia, illetve a kardiológiai szövődmények előrejelzése szempontjából. A Kobayashi-pontrendszerben 4, a Kawanet-pontrendszerben pedig 2 pont vagy annál magasabb érték jelez rizikót. Eredmények: Kawasaki-szindrómát 28 gyereknél véleményeztünk, 13 esetben észleltünk mérsékelt, 4 esetben súlyos szövődményt. 4 betegünk bizonyult intravénás immunglobulinra rezisztensnek. A rezisztencia szempontjából a Kobayashi-pontrendszer alacsony szenzitivitást (25%), illetve magas specificitást (91,6%), míg a Kawanet-pontrendszer mérsékelt szenzitivitást (50%) és specificitást (50%) mutatott. A szövődmények szempontjából hasonló eredményeket kaptunk, Kobayashi-pontrendszer: szenzitivitás: 17%; specificitás: 100%, illetve Kawanet-pontrendszer: szenzitivitás: 47%; specificitás: 45%. Következtetés: A legtöbb, nem ázsiai országban készült tanulmányhoz hasonlóan az intravénás immunglobulin-rezisztencia előrejelzésében a Kobayashi-pontrendszer vizsgálatunkban sem bizonyult hatékonynak. Ezzel szemben, magasabb szenzitivitása miatt, a Kawanet-pontrendszer intravénás immunglobulin-rezisztenciát előre jelző hatékonyságát érdemes lenne nagyobb esetszámban vizsgálni a hazai populációban is. A kardiológiai szövődmények előrejelzésére egyik pontrendszer sem bizonyult alkalmasnak. Orv Hetil. 2021; 162(47): 1885–1890. Summary. Introduction: Kawasaki disease is an immunovasculitis, which, without treatment, leads to cardiac complications. Early intravenous immunoglobulin therapy moderates complications, however, 10–20% of patients are resistant to the therapy. Numerous risk score systems are used worldwide to predict this. Objective: To assess the predictive value of the Kobayashi and Kawanet score systems regarding intravenous immunoglobulin resistance and cardiac complications in our department’s patient cohort. To our best knowledge, this is the first study in Hungary, which examines the predictive value of score systems in the case of Kawasaki disease. Method: In our study, we identified the patients treated for Kawasaki disease between January 2005 and April 2020. In each case, we calculated both the Kobayashi and the Kawanet score, and we examined their specificity and sensitivity regarding the prediction of intravenous immunoglobulin resistance and cardiac complications. In the Kobayashi score system, values above 4, in the Kawanet score system, values above 2 signal risk. Results: We identified 28 patients with Kawasaki disease. We observed moderate complications in 13, severe complications in 4 cases. 4 of our patients were resistant to intravenous immunoglobulin therapy. Regarding intravenous immunoglobulin resistance in our patient cohort, we detected low sensitivity (25%) and high specificity (91.6%) in the case of Kobayashi score, and moderate sensitivity (50%) and specificity (50%) in the case of Kawanet score. Regarding complications, we found similar results in the case of Kobayashi (sensitivity: 17%; specificity: 100%) and the Kawanet (sensitivity: 47%; specificity: 45%) score system. Conclusion: Similarly to the majority of non-Asian studies, we found the Kobayashi score system ineffective in predicting intravenous immunoglobulin resistance. However, due to its higher sensitivity, the predictive value of the Kawanet score system regarding intravenous immunoglobulin resistance is worth examining in a larger patient population in Hungary. Regarding the prediction of cardiac complications, both score systems were found to be ineffective. Orv Hetil. 2021; 162(47): 1885–1890.

Prediction of repeated intravenous immunoglobulin resistance in children with Kawasaki disease

Background Repeated intravenous immunoglobulin (IVIG) resistance prediction is one of the pivotal topics in Kawasaki disease (KD). Those non-responders of repeated IVIG treatment might be improved by an early-intensified therapy to reduce coronary artery lesion and medical costs. This study investigated predictors of resistance to repeated IVIG treatment in KD. Methods A total of 94 children with IVIG-resistant KD treated at our hospital between January 2016 and August 2020 were retrospectively analyzed. According to the therapeutic effect of a second dose IVIG treatment, the children were divided into repeated IVIG-responsive group and repeated IVIG-resistant group, and the clinical and laboratory data were compared. Predictors of repeated IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Results The Pre-IVIG laboratory data showed the percentage of neutrophils (N%) and levels of serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly higher in repeated IVIG-resistant group compared with repeated IVIG-responsive group, while levels of serum sodium and albumin (ALB) were significantly lower (P < 0.05). The post-IVIG laboratory values of N% and C-reactive protein (CRP) were significantly higher in the repeated IVIG-resistant group compared with repeated IVIG-responsive group, while hemoglobin and ALB were lower (P < 0.05). Pre-IVIG PCT and post-IVIG CRP exhibited AUC of 0.751 and 0.778 respectively in predicting repeated IVIG resistance in KD. Pre-IVIG PCT > 1.81ng/ml (OR 4.1, 95 % CI 1.4 ~ 12.0, P < 0.05) and post-IVIG CRP > 45 mg/L (OR 4.6, 95 % CI 1.3 ~ 16.2, P < 0.05) were independent predictors of repeated IVIG resistance in KD. Conclusions Our study illustrates the serum PCT level before initial IVIG treatment and CRP after initial IVIG could be used to predict repeated IVIG resistance in KD.

Treatment of Kawasaki Disease: A Network Meta-Analysis of Four Dosage Regimens of Aspirin Combined With Recommended Intravenous Immunoglobulin

Aspirin was once believed to reduce the mortality of Kawasaki disease (KD) due to its effect on the thrombotic occlusion of coronary arteries. However, conflicting evidence has been found regarding aspirin treatment and its benefit in patients with acute KD. We compared the efficacy of different aspirin doses in acute KD. A literature search of PubMed, EMBASE, and Cochrane databases was conducted to identify studies comparing different doses of aspirin for acute KD. The primary outcome of interest was coronary artery lesions (CAL). We used random-effects network meta-analysis. Six retrospective studies, including 1944 patients receiving aspirin in doses of 0, 3–5, 30–50, or 80–100 mg/kg/day, were selected. The risks of CAL were not significantly different for the various doses of aspirin compared to the placebo: odds ratio (OR) was 1.10 [95% confidence interval (CI): 0.70–1.71] for patients with aspirin 3–5 mg/kg/day; OR = 1.23 (95% CI: 0.67–2.26) for aspirin 30–50 mg/kg/day, and OR = 1.59 (95% CI: 0.74, 3.421) for 80–100 mg/kg/day. The P-score ranged from 0.76 for placebo to 0.19 for aspirin 80–100 mg/kg/day. The different doses of aspirin exhibited no significant difference with regard to the efficacy of CAL or with the secondary outcomes of intravenous immunoglobulin resistance or hospital stays for acute KD. Therefore, we found that treatment without any aspirin is not inferior to other doses of aspirin and can also slightly reduce the risk of CAL.

Association Between Serum miR-221-3p and Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease

ObjectivesIntravenous immunoglobulin (IVIG) resistance was a major cause of coronary artery lesions in children with Kawasaki disease (KD). However, the cause of IVIG resistance in KD remains unknown. miR-221-3p has been confirmed involved in cardiovascular diseases and rheumatoid arthritis. The purpose of this study was to investigate the association between miR-221-3p and IVIG resistance in children with KD.Methods55 KD patients and 29 healthy controls (HCs) were enrolled in this study. KD patients were divided into group of sensitive to IVIG (IVIG-response, n=42) and group of resistant to IVIG (IVIG-resistance, n=13). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the levels of miR-221-3p.ResultsCompared with the HCs group, miR-221-3p were significantly increased in the KD group (p < 0.05), and the IVIG-resistance group had higher levels of miR-221-3p than those in the IVIG-response group (p < 0.05). CRP (C-reactive protein), PCT (procalcitonin), NLR (neutrophil-lymphocyte ratio) were positively correlated with miR-221-3p in KD patients. In addition, the group of IVIG resistance had a higher level of Kobayashi Score (p <0.001). The receiver operating characteristic (ROC) curve showed that miR-221-3p had a better value for diagnosis IVIG resistance in children with KD than Kobayashi Score and the combination of both with the AUC of 0.811 (95% CI, 0.672-0.951), 0.793 (95% CI, 0.618-0.968) and 0.797 (95% CI, 0.619-0.974), respectively.ConclusionsmiR-221-3p might be involved in the pathogenesis of KD and IVIG resistance and miR-221-3p can be used as a new potential biomarker to predict of IVIG resistance in children with KD.

Prediction of Repeated Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease

Background: Repeated intravenous immunoglobulin (IVIG) resistance prediction is one of the pivotal topics in Kawasaki disease (KD). Those non-responders of repeated IVIG treatment might be improved by an early-intensified therapy to reduce coronary artery lesion and medical costs. This study investigated predictors of resistance to repeated IVIG treatment in KD.Methods: A total of 94 children with IVIG-resistant KD treated at our hospital between January 2016 and August 2020 were retrospectively analyzed. According to the therapeutic effect of a second dose IVIG treatment, the children were divided into repeated IVIG-responsive group and repeated IVIG-resistant group, and the clinical and laboratory data were compared. Predictors of repeated IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis.Results: The laboratory data of the percentage of neutrophils (N%) and levels of serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission were significantly higher in repeated IVIG-resistant group compared with repeated IVIG-responsive group, while levels of serum sodium (Na+) and albumin (ALB) were significantly lower (P<0.05). The clinic data showed no significant differences between the two groups. PCT exhibited the largest AUC (0.751) in predicting repeated IVIG resistance in KD compared with N%, Na+, ALB, and NT-proBNP. PCT>1.81ng/ml was an independent predictor of repeated IVIG resistance in KD (OR 4.161, 95% CI 1.441~12.017, P=0.008). Conclusions: Our study illustrates the serum PCT level before initial IVIG treatment could be used to predict repeated IVIG resistance in KD.

Predictive value of serum lipid for intravenous immunoglobulin resistance and coronary artery lesion in Kawasaki disease

Context Intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) prediction are pivotal topic of interests in Kawasaki disease (KD). However, data on the predictive value of lipid profile for both IVIG resistance and CALs are limited. Purpose To investigate the predictive validity of lipid profile for IVIG resistance and CALs in KD. Design Prospective cohort study. Setting West China Second University Hospital. Patients 363 KD patients were divided into the initial IVIG-resistant group and initial IVIG-responsive group; repeated IVIG-resistant group and repeated IVIG-responsive group; CAL+ group and CAL- group. Main Outcome Measures Validity of lipid profile in predicting IVIG resistance and CALs. Results TG was significantly higher whereas TC, HDL-C, LDL-C as well as Apo A were significantly lower in initial IVIG-resistant subjects, with cut-off values of 1.625 mmol/L, 3.255 mmol/L, 0.475 mmol/L, and 1.965 mmol/L and 0.665 g/L, yielding sensitivities of 52%, 70%, 52%, 61%, 50%, and specificities of 68%, 53%, 78%, 71%, 81%, respectively. TC, LDL-C, and Apo A levels were significantly lower in repeated IVIG-resistant subjects, with cut-off values of 3.20 mmol/L, 1.78 mmol/L, 0.605 g/L, producing sensitivities of 91%, 70%, 57% and specificities of 55%, 67%, 70%, respectively. Apo-A level was significantly lower in the CAL group, with cut-off value of 0.805g/L, yielding sensitivity of 66% and specificity of 54%. Conclusions Lipid profiles were significantly dysregulated in KD patients suffering IVIG resistance and CALs. Some of them, such as LDL-c and Apo-A, could serve as complementary laboratory markers for predicting both IVIG resistance and CALs.

Homozygous of MRP4 Gene rs1751034 C Allele Is Related to Increased Risk of Intravenous Immunoglobulin Resistance in Kawasaki Disease

Background: Kawasaki disease (KD) is a systemic vasculitis in childhood, which mainly causes damage to coronary arteries, and intravenous immunoglobulin (IVIG) is the initial therapy. IVIG resistance increased risk of coronary complication in KD. And genetic background is involved in the occurrence of IVIG resistance. Our previous study indicated the susceptibility of Multi-drug resistance protein 4 (MRP4) SNPs to KD. This study was to clarify the relationship between MRP4 polymorphisms and IVIG resistance.Methods: We genotyped the six polymorphisms of MRP4 gene in 760 cases of KD using Taqman methods.Results: Among the six polymorphisms, only the rs1751034 polymorphism was significantly associated with IVIG resistance in KD [CC vs. TT: adjusted odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.21–5.34; CC vs. TT/TC: adjusted OR = 2.33, 95% CI = 1.12–4.83, p = 0.023]. Combined analysis of three polymorphisms indicated that patients with 3–6 risk genotypes exhibited significantly elevated risk of IVIG resistance, when compared with those with 0–2 risk genotypes (adjusted OR = 1.52, 95% CI = 1.04–2.22, p = 0.0295). Stratified analysis revealed that in term of age and gender, rs1751034 CC carriers were associated with increased risk of IVIG resistance in those aged ≤ 60 months (adjusted OR = 2.65, 95% CI = 1.23–5.71, p = 0.0133). The presence of three or more risk genotypes was significantly associated with risk of IVIG resistance in children younger than 5 years of age and males.Conclusion: Our results suggest that MRP4 rs1751034 CC is associated with increased risk of IVIG resistance in KD.