Editorial

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Open AccessEditorial

Kawasaki Disease, MIS-C and COVID-19

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Ying-Hsien Huang

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Ho-Chang Kuo

Children 2023, 10(10), 1587; https://doi.org/10.3390/children10101587 - 22 Sep 2023

Viewed by 369

Abstract

Kawasaki disease (KD) is a form of systemic vasculitis characterized by inflammation of blood vessels throughout the body, and its exact cause remains unknown [...] Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

Research

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Open AccessArticle

Basophils Predict Mite Sensitization in Patients with Kawasaki Disease

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Children 2023, 10(7), 1209; https://doi.org/10.3390/children10071209 - 12 Jul 2023

Viewed by 453

Abstract

Background: Patients with Kawasaki disease (KD) are at a significantly increased risk of allergic diseases. Immunoglobulin E (IgE) is an immunoglobulin that mediates allergic sensitization to various allergens and is related to various allergic diseases. However, few studies have analyzed specific IgE [...] Read more.

Background: Patients with Kawasaki disease (KD) are at a significantly increased risk of allergic diseases. Immunoglobulin E (IgE) is an immunoglobulin that mediates allergic sensitization to various allergens and is related to various allergic diseases. However, few studies have analyzed specific IgE on allergy biomarkers after KD is diagnosed. Objective: This study aimed to investigate the pattern of specific IgE levels against food and inhalant allergens. Methods: This retrospective study was conducted in Taiwan to identify patients admitted with KD. A subset of 453 admitted KD children younger than or equal to five years of age with intravenous immunoglobulin (IVIG) was followed up at our clinic with available specific IgE data. Results: The most common allergens were Dermatophagoides farina or pteronyssinus, house-dust, and cockroach mix. Positive specific IgE for Dermatophagoides farina or pteronyssinus was less common in children diagnosed with KD who were two years old or younger (p = 0.028). KD patients with higher basophils before IVIG (p = 0.010 and 0.018 for two different mites) and higher C-reactive protein (CRP, p = 0.030 and 0.028) after IVIG were at higher risk of mite sensitization. Integrated mite sensitization demonstrated higher basophils before IVIG, age at KD diagnosis, and the male sex to be clinically meaningful after logistic regression models. Conclusions: This study is the first to suggest that specific IgE in KD patients may be correlated with age at KD diagnosis, as well as basophils. Further longitudinal prospective studies are warranted to clarify the unique profile of specific IgE in KD patients. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessArticle

Reappraisal of VEGF in the Pathogenesis of Kawasaki Disease

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Children 2022, 9(9), 1343; https://doi.org/10.3390/children9091343 - 01 Sep 2022

Cited by 2 | Viewed by 1106

Abstract

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In [...] Read more.

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In a prospective study of 42 Taiwanese KD patients (18.9 ± 12.2 months, M/F 22/20) treated with intravenous immunoglobulin (IVIG), a series of VEGF levels was measured from the acute to convalescent phases. KD patients were classified into two subgroups with (n =20) and without (n = 22) acute coronary artery lesions (CALs). Control samples were obtained from 30 febrile controls (19.1 ± 13.7 months, M/F 13/17). In KD patients, VEGF levels in the pre-IVIG acute phase were significantly higher than those in the subacute and convalescent phases (both p < 0.001). In KD patients with CALs, VEGF levels significantly increased immediately in the post-IVIG phase (p = 0.039), and then significantly decreased in the subacute phase (p = 0.002). KD patients with acute CALs had higher median VEGF levels than those without acute CALs from acute to convalescent phases. In the subacute phase, KD patients with acute CALs had significantly higher VEGF levels (p = 0.022) than those without acute CALs. Our data show that VEGF did not decrease after IVIG treatment, and increased significantly after IVIG treatment in KD patients with acute CALs in acute phase. VEGF might be related to the complications of CALs in KD patients. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessArticle

Combination of Hemoglobin-for-Age Z-Score and Plasma Hepcidin Identified as a Novel Predictor for Kawasaki Disease

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Children 2022, 9(6), 913; https://doi.org/10.3390/children9060913 - 18 Jun 2022

Cited by 5 | Viewed by 1391

Abstract

Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we [...] Read more.

Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we developed a novel predictor using the hemoglobin-for-age z-score (HbZ) and plasma hepcidin to differentiate Kawasaki disease (KD) from febrile children (FC). There were 104 FC and 115 KD subjects (89 typical KD; 26 incomplete KD) for this study, and data were collected on the biological parameters of hemoglobin and plasma hepcidin levels. A receiver operating characteristic curve (auROC), multiple logistics regression, and support vector machine analysis were all adopted to develop our prediction condition. We obtained both predictors, HbZ and plasma hepcidin, for distinguishing KD and FC. The auROC of the multivariate logistic regression of both parameters for FC and KD was 0.959 (95% confidence interval = 0.937–0.981), and the sensitivity and specificity were 85.2% and 95.9%, respectively. Furthermore, the auROC for FC and incomplete KD was 0.981, and the sensitivity and specificity were 92.3% and 95.2%, respectively. We further developed a model of support vector machine (SVM) classification with 83.3% sensitivity and 88.0% specificity in the training set, and the blind cohort performed well (78.4% sensitivity and 100% specificity). All data showed that sensitivity and specificity were 81.7% and 91.3%, respectively, by SVM. Overall, our findings demonstrate a novel predictor using a combination of HbZ and plasma hepcidin with a better discriminatory ability for differentiating from WBC and CRP between children with KD and other FC. Using this predictor can assist front-line physicians to recognize and then provide early treatment for KD. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessArticle

Cardiovascular Manifestations in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19 According to Age

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Children 2022, 9(5), 583; https://doi.org/10.3390/children9050583 - 20 Apr 2022

Cited by 2 | Viewed by 1755

Abstract

Cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus-19 disease is often observed with a high risk of heart failure. The aim is to describe cardiovascular involvement, management and early outcome in MIS-C by comparing cardiovascular manifestations in children younger [...] Read more.

Cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus-19 disease is often observed with a high risk of heart failure. The aim is to describe cardiovascular involvement, management and early outcome in MIS-C by comparing cardiovascular manifestations in children younger and older than 6 years old. This retrospective observational study included 25 children with MIS-C, admitted to a single pediatric center between March 2020 and September 2021. The median age was 5 years (13 patients under 6 years and 12 over 6 years); coronary artery abnormalities were observed in 77% of preschoolers, with small and medium aneurysms in half of the cases and two cases of mild ventricular dysfunction. School-age children presented myopericardial involvement with mild to moderate ventricular dysfunction in 67% of cases, and two cases of transient coronary dilatation. There was a significant NT-pro-BNP and inflammatory markers increase in 25 of the patients, and mild elevation of troponin I in 9. All patients were treated with intravenous immunoglobulin and corticosteroids, and 8 with anakinra. None of the patients needed inotropes or intensive care unit admission. Our study shows the frequent cardiovascular involvement in MIS-C with a peculiar distribution, according to different age group: coronary artery anomalies were more frequent in the younger group, and myopericardial disease in the older one. A prompt multitarget, anti-inflammatory therapy could probably contribute to a favorable outcome. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessArticle

Complement 3 and the Prognostic Nutritional Index Distinguish Kawasaki Disease from Other Fever Illness with a Nomogram

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Children 2021, 8(9), 825; https://doi.org/10.3390/children8090825 - 20 Sep 2021

Cited by 2 | Viewed by 1753

Abstract

Objective: This study aimed to establish a model to distinguish Kawasaki disease (KD) from other fever illness using the prognostic nutritional index (PNI) and immunological factors. Method: We enrolled a total of 692 patients (including 198 with KD and 494 children with febrile [...] Read more.

Objective: This study aimed to establish a model to distinguish Kawasaki disease (KD) from other fever illness using the prognostic nutritional index (PNI) and immunological factors. Method: We enrolled a total of 692 patients (including 198 with KD and 494 children with febrile diseases). Of those, 415 patients were selected to be the training group and 277 patients to be the validation group. Laboratory data, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), and immunological factors, were retrospectively collected for an analysis after admission. We used univariate and multivariate logistic regressions and nomograms for the analysis. Result: Patients with KD showed significantly higher C3 and a lower PNI. After a multivariate logistic regression, the total leukocyte count, PNI, C3, and NLR showed a significance (p < 0.05) and then performed well with the nomogram model. The areas under the ROC in the training group and the validation group were 0.858 and 0.825, respectively. The calibration curves of the two groups for the probability of KD showed a near agreement to the actual probability. Conclusions: Compared with children with febrile diseases, patients with KD showed increased C3 and a decreased nutritional index of the PNI. The nomogram established with these factors could effectively identify KD from febrile illness in children. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessCase Report

Incomplete Kawasaki Disease with Peripheral Facial Nerve Palsy and Lung Nodules: A Case Report and Literature Review

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Giovanni Maria Di Marco

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Monica Gelzo

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Giuseppe Castaldo

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Celeste Tucci

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Raffaella Margherita Iodice

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Maria Concetta Lonardo

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Vincenzo Tipo

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Antonietta Giannattasio

Children 2023, 10(4), 679; https://doi.org/10.3390/children10040679 - 03 Apr 2023

Viewed by 1018

Abstract

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher [...] Read more.

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher incidence of coronary arteries lesions and may be an indicator of a more severe disease. Here, we describe a case of lower motor neuron facial nerve palsy complicating KD and perform an extensive literature review to better characterize clinical features and treatment of patients with KD-associated facial nerve palsy. The patient was diagnosed at the sixth day of disease and presented extensive coronary artery lesions. A prompt treatment with intravenous immunoglobulins, aspirin and steroids obtained a good clinical and laboratory response, with resolution of facial nerve palsy and improvement of coronary lesions. The incidence of facial nerve palsy is 0.9–1.3%; it is often unilateral, transient, more frequent on the left and seemingly associated with coronary impairment. Our literature review showed coronary artery involvement in the majority of reported cases (27/35, 77%) of KD with facial nerve palsy. Unexplained facial nerve palsy in young children with a prolonged febrile illness should prompt consideration of echocardiography to exclude KD and start the appropriate treatment. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessCase Report

Can Breastfeeding Protect from Multi-System Inflammatory Syndrome in Children (MIS-C)? A Preliminary Study

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Xavier Rodríguez-Fanjul

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Sergio Verd

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Sonia Brio

Children 2022, 9(8), 1160; https://doi.org/10.3390/children9081160 - 02 Aug 2022

Cited by 1 | Viewed by 1072

Abstract

Background: Breastfeeding prevents Kawasaki disease (KD), as well as several autoimmune disorders. Since there is an overlap between the Multi-System Inflammatory Syndrome in children following SARS-CoV-2 infection (MIS-C) and KD, this case series aims to analyze the association between breastfeeding and MIS-C. Methods: [...] Read more.

Background: Breastfeeding prevents Kawasaki disease (KD), as well as several autoimmune disorders. Since there is an overlap between the Multi-System Inflammatory Syndrome in children following SARS-CoV-2 infection (MIS-C) and KD, this case series aims to analyze the association between breastfeeding and MIS-C. Methods: A series of 16 cases of children with MIS-C admitted to three pediatric facilities between January 2021 and May 2022 were conducted. Breastfeeding rate was estimated through the Brief Breastfeeding and Milk Expression Recall Survey. Results: Out of 16 children, 9 (56%) had been breastfed at birth. Discussion: Our breastfeeding rate is below the median Spanish rate for initial breastfeeding. These findings do not clearly support the hypothesis that breastfeeding might prevent MIS-C. Conclusion: Contrary to the role of breastfeeding in KD prevention, our case series cannot answer with certainty the question about whether or not breastfeeding does protect children against MIS-C. These findings require confirmation in larger studies. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

Open AccessCase Report

Efficacy of Anakinra on Multiple Coronary Arteries Aneurysms in an Infant with Recurrent Kawasaki Disease, Complicated by Macrophage Activation Syndrome

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Grazia Bossi

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Alessia Claudia Codazzi

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Children 2022, 9(5), 672; https://doi.org/10.3390/children9050672 - 05 May 2022

Cited by 2 | Viewed by 1486

Abstract

Kawasaki disease (KD) is rare in infants less than 3 months of age, and its recurrence is exceptional. Infants with KD are at higher risk of severe clinical presentation, therapy failure, complications and coronary aneurysms (CAAs), and this is the reason they deserve [...] Read more.

Kawasaki disease (KD) is rare in infants less than 3 months of age, and its recurrence is exceptional. Infants with KD are at higher risk of severe clinical presentation, therapy failure, complications and coronary aneurysms (CAAs), and this is the reason they deserve more aggressive therapy and a strict clinical follow-up. We report a 2-month-old male with KD, complicated by Macrophage Activation Syndrome (MAS). Despite timely and aggressive therapy with immunoglobulins, steroids and aspirin, multiple CAAs developed. Two-month therapy with anakinra completely reverted all the aneurysms. After six months, the infant experienced KD relapse and was successfully re-treated with immunoglobulins, steroids and aspirin. A strict echocardiographic follow-up did not show recurrence of aneurysms. Two years later, the child is healthy, without cardiac sequelae. In our experience, anakinra was effective in reverting multiple aneurysms and its effect proved to be long-lasting, even in front of KD recurrence. Based on this evidence, it seems reasonable to hypothesize not to limit the use of anakinra as rescue therapy for complicated or refractory KD, but to consider the possibility of adding it to first-line therapies for some subgroups of very-high-risk patients, in order to strengthen the prevention of CAAs. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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Open AccessCase Report

Appendicitis as a Leading Manifestation of Kawasaki Disease in Older Children

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Children 2022, 9(2), 193; https://doi.org/10.3390/children9020193 - 02 Feb 2022

Cited by 4 | Viewed by 1495

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Kawasaki disease (KD) is a systematic inflammatory disease with multiple organ involvement. Timely diagnosis and prompt management are essential for successful treatment. KD, with an atypical presentation, remains a diagnostic challenge for physicians. We report a five-year-old boy who presented with appendicitis. An [...] Read more.

Kawasaki disease (KD) is a systematic inflammatory disease with multiple organ involvement. Timely diagnosis and prompt management are essential for successful treatment. KD, with an atypical presentation, remains a diagnostic challenge for physicians. We report a five-year-old boy who presented with appendicitis. An appendectomy was performed; however, his fever persisted. The boy was diagnosed with KD and intravenous immunoglobulin was administered. His symptoms resolved, and he had an uneventful recovery. Furthermore, we performed a literature review with 13 cases identified in the literature. Most cases were male, and the average age was older than typical for KD. In conclusion, KD may present with abdominal complaints and appendicitis may be a rare initial presentation of KD. Multidisciplinary cooperation and high awareness are warranted for timely diagnosis, especially in older children experiencing persistent fever after an appendectomy. Full article

(This article belongs to the Special Issue Kawasaki Disease, MIS-C and COVID-19)

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