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La enfermedad de Kawasaki supone la segunda vasculitis más frecuente en la infancia. La implantación del tratamiento con inmunoglobulina intravenosa ha permitido reducir la historia natural de la enfermedad, así como disminuir la tasa de complicaciones cardiovasculares. Sin embargo, el aneurisma coronario y el infarto miocárdico siguen suponiendo sus principales complicaciones. La medición del diámetro coronario mediante ecocardiografía es la base del tratamiento del paciente con lesiones coronarias, ya que este tamaño es la principal variable que se emplea para decidir el plan de actuación. No obstante, se dispone de otras pruebas útiles para su valoración. Además del aneurisma, existen otras complicaciones cardiovasculares menos relevantes, como la miocarditis, el síndrome de shock, valvulopatías, etc. La creciente cohorte de pacientes con secuelas cardiovasculares que necesitan seguimiento obliga al aumento del interés de los facultativos en esta enfermedad. Kawasaki disease means the second most frequent vasculitis in the pediatric age. The introduction of immunoglobulin therapy has achieved to reduce its natural history and the cardiovascular complications. Nevertheless, the main complication of Kawasaki disease are the coronary aneurysm and the following vessel obstruction. The coronary diameter measurement made from echocardiography is the basis in these patients’ clinical management since this size is considered the main determining factor to choose the most suitable therapy. Nonetheless, we have other useful tests that can be also used. Besides aneurysms, we can find less relevant cardiovascular complications such as myocarditis, shock syndrome, heart valve diseases, etc. The growing cohort of patients diagnosed in early childhood of cardiovascular complications needed of follow-up forces us to increase the interest of physician about this disease.

Background: Multi-system inflammatory syndrome in children and Kawasaki disease have overlapping clinical features but comparative echocardiographic studies are lacking. Methods: We reviewed echocardiography findings of all multi-system inflammatory syndrome cases between 1st April and 31st July, 2020 and typical Kawasaki disease patients with coronary arteries abnormalities consecutively followed between 1st October, 2016 and June 30th, 2019. Results: We included 40 multi-system inflammatory syndrome children (25 males, 62.5%) and 45 Kawasaki disease patients (31 males, 68.9%) at a mean age of 6.4 years old and 8 years old, respectively. Four out of 40 multi-system inflammatory syndrome children had coronary arteries abnormalities. Left ventricle ejection fraction was normal in both groups. Global longitudinal strain was normal although Kawasaki disease group had significantly lower values (–20.0 versus –21.7%; p = 0.02). Basal segments were the most affected in Kawasaki disease patients with significant differences in the basal anterior, anterolateral, and anteroseptal strain: –18.2 versus –23.0% (p = 0.002), –16.7 versus –22.0% (p < 0.001), –16.7 versus –19.5% (p = 0.034), respectively. The basal anterolateral and anteroseptal segments in Kawasaki disease patients were the only ones with an absolute reduction of longitudinal strain (–16.7% both) consistent with the greater left main coronary involvement in this cohort. Conclusions: Our findings are consistent with the transient cardiac involvement in multi-system inflammatory syndrome, as opposed to the subtle and chronic myocardial involvement in Kawasaki disease children with coronary arteries abnormalities. We speculate that the mechanism of cardiac impairment in the few multi-system inflammatory syndrome children with reduced global longitudinal strain is not related to coronary arteries abnormalities.

During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host’s immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study’s findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.

Background: Previous epidemiological investigations examining the association between Kawasaki disease (KD) and cerebrovascular disease have had conflicting results. We analyzed the association between KD and cerebrovascular disease by conducting a population-based retrospective cohort study designed to investigate the hypothesis that KD could be a risk factor for subsequent cerebrovascular disease. Methods: From the National Health Insurance Research Database of Taiwan, the data of children (aged 0–18 years old) with KD (n=8467) were collected. Starting with the first year of study observation (referred to as the baseline year), data was collected for each child with KD, and 4 non-KD patients matched for sex, urbanization level of residence, and parental occupation were randomly selected to form the non-KD cohort (n=33 868) for our analysis. For the period from January 1, 2000, to December 31, 2012, we calculated the follow-up person-years for each patient, which is the time from the index date to the diagnosis of cerebrovascular disease, death, or the end of 2012. Furthermore, we compared the incidence, the incidence rate ratio, and the 95% CI of cerebrovascular disease between the KD and non-KD cohorts. Results: The overall cerebrovascular disease incidence rate was found to be 3.19-fold higher, which is significantly higher, in the KD cohort than in the non-KD cohort (14.73 versus 4.62 per 100 000 person-years), and the overall risk of cerebrovascular disease remained higher in the KD cohort (adjusted hazard ratio, 3.16 [95% CI, 1.46–6.85]). Furthermore, children aged Conclusions: This nationwide retrospective cohort study shows that KD may increase the risk of subsequent cerebrovascular disease, especially in those with KD aged

Purpose: Few studies have compared the effects of low-concentration (5%) and high-concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low- and high-concentration IVIG preparations in children with KD, using a national inpatient database in Japan.Method: We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identified those receiving high- and low-concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results.Result: We identified 48,046 patients with KD and created 4:1 propensity score-matched pairs between the low- and high-concentration IVIG groups. There was a significant difference in the percentage with IVIG resistance between the two groups (20.6% vs 24.1%; risk difference, 3.5% [95% confidence interval, 2.3-4.7]; p < 0.001). However, there was no significant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% confidence interval, −0.34 to 0.37]; p = 0.953). The instrumental variable analyses showed similar results.Conclusions: The proportion of CAAs did not differ significantly between those receiving low- and high-concentration IVIG. To confirm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed.

Background: We examined the characteristics of Kawasaki disease (KD) patients who presented with limited and faint principal clinical features. Methods: We retrospectively reviewed the clinical records of 62 KD patients who presented with limited and faint clinical features at admission. A clinical feature that was recognizable by even junior doctors was defined as a definite feature (d-Feature), and a feature that was faint and recognizable by only experienced doctors was defined as a faint feature (f-Feature). Results: At admission, 82% of patients presented with fever and ≤1 d-Feature. Two days later, the d-Features increased in number and diagnoses of KD were established in 32 patients with fever and ≥4 d-Features. In 30 patients with ≤3 d-Features, experienced doctors recognized f-Features and diagnosed KD in 22 patients because of fever and ≥4 features. Among eight patients with ≤3 features, experienced doctors diagnosed six patients as incomplete KD considering their faint abnormal echocardiographic findings. For the remaining two patients, experienced doctors decided to commence KD treatments considering the patients’ clinical course. Conclusions: Sufficient clinical experience is essential during the diagnosis of KD in patients presenting with limited and f-Features. Educational programs for junior doctors on how to recognize f-Features and evaluate faint abnormal coronary artery findings are necessary.

The case of a 14-year-old girl with acute myocardial infarction due to coronary artery aneurysms (CAAs) of unknown origin, which resembled coronary artery lesions caused by Kawasaki disease, is reported. She was transferred to our hospital due to chest pain with ST-T elevation. She had no history of Kawasaki disease. On the first admission, she was misdiagnosed with acute myocarditis. Then, 54 days later, she experienced chest pain with exertional dyspnea. Her electrocardiogram showed negative T waves in the chest leads. A CAA of the left coronary artery was suspected on two-dimensional echocardiography. Coronary angiograms showed 90% stenosis and multiple CAAs of the left anterior descending artery and the bifurcation of the left coronary artery. Both the right coronary artery and left circumflex artery were occluded. A left ventriculogram showed dyskinesis and an aneurysm at the apex. She underwent triple-vessel coronary artery bypass grafting, and her symptoms improved. In addition, an intracranial aneurysm was also found on cerebral angiography. There were no specific laboratory findings other than SS-A antibodies. It was suspected that the weakness of the vessels was related to the disease. It may have been a different disease that was never previously detected, but her CAAs were Kawasaki-like CAAs. Learning objective A timely precise diagnosis of acute myocardial infarction is unlikely to be made in children because they are rare. The present patient was initially misdiagnosed as having acute myocarditis, because the coronary arteries could not be detected by two-dimensional echocardiography. Either computed tomographic angiography or magnetic resonance angiography is recommended in patients with ST-T abnormalities on the electrocardiogram if it is difficult to identify the coronary arteries. In this case, the patient had a rare coronary artery disease in which the cause of the coronary artery aneurysms was unknown.

Objective We aimed to develop a nomogram to predict risk of resistance to intravenous immunoglobulin (IVIG) in children with Kawasaki disease in eastern China. Methods We retrospectively analysed the data of children with Kawasaki disease who received IVIG during hospitalisation at Soochow University Affiliated Children’s Hospital. IVIG resistance was defined as recrudescent or persistent fever ≥36 h after the end of the IVIG infusion. Baseline variables were analysed using least absolute shrinkage and selection operator (LASSO) to identify the predictors of IVIG resistance, which were then used to construct a predictive nomogram. Calibration curve and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the model. The predictive nomogram was validated on test sets of external data and prospective data. Results Between January 2015 and December 2020, 1293 Kawasaki disease patients were hospitalized in Soochow University Affiliated Children’s Hospital. Among them, 72 (5.57%) showed IVIG resistance. LASSO identified haemoglobin, percentage of neutrophils, C-reactive protein level, platelet count, serum albumin, serum sodium, serum alkaline phosphatase, coronary artery damage, and complete Kawasaki disease as risk factors for IVIG resistance. The nomogram constructed using these factors showed satisfactory discriminatory power (AUC, 0.75), and sensitivity (0.74) and specificity (0.64). In the external data and prospective data, the AUC was 0.66 and 0.83, respectively, the sensitivity was 0.86 and 1, respectively, and the specificity was 0.49 and 0.60, respectively. Conclusions The predictive nomogram constructed using nine factors associated with IVIG resistance in children with Kawasaki disease could be a useful tool for identifying patients likely to show IVIG resistance. This nomogram may help reduce the risk of coronary artery lesions.Key MessagesNone of the IVIG resistance scoring systems has shown consistently good performance in previous studies. Tools to predict the risk of IVIG resistance in eastern China are lacking.In our series, haemoglobin level, percentage of neutrophils, platelet count, coronary artery damage, incomplete Kawasaki disease, and CRP, serum albumin, serum sodium, and serum alkaline phosphatase levels were risk factors of IVIG resistance in hospitalized children in the eastern China cities of Suzhou and Fuzhou.We propose an easy-to-use nomogram to predict the risk factors of IVIG resistance in hospitalized children.

Background Multisystem inflammatory syndrome in children (MIS-C) is a newly recognized condition affecting children with recent infection or exposure to coronavirus disease 2019 (COVID-19). MIS-C has symptoms that affect multiple organs systems, with some clinical features resembling Kawasaki disease (KD) and toxic shock syndrome (TSS). Objective of the Review Our goal was to review the current literature and describe the evaluation and treatment algorithms for children suspected of having MIS-C who present to the emergency department. Discussion MIS-C has a wide clinical spectrum and diagnosis is based on a combination of both clinical and laboratory findings. The exact mechanism of immune dysregulation of MIS-C is not well understood. Physical findings may evolve and do not necessarily appear at the same time. Gastrointestinal, cardiac, inflammatory, and coagulopathy manifestations and dysfunction are seen frequently in MIS-C. Conclusions The diagnosis of MIS-C is based on clinical presentation and specific laboratory findings. In the emergency setting, a high level of suspicion for MIS-C is required in patients exposed to COVID-19. Early diagnosis and prompt initiation of therapy offer the best chance for optimal outcomes.

BACKGROUND: American Heart Association (AHA) guidelines for management of Kawasaki disease (KD) rely on coronary artery (CA) z-scores from echocardiograms. Compared with echocardiography, cardiac CT (CCT) offers better visualization of distal segments and evaluation for thrombosis and stenosis. Despite increasing use of CCT in KD, CA z-scores for CCT are not available and measurement concordance between imaging modalities is a critical knowledge gap. METHODS: We retrospectively reviewed KD patients with CA aneurysms who had concurrent echocardiography and CCT between 2016-2020. Patients were included if they had history of CA z-scores of ≥ 3 on echocardiography during their clinical course. Agreement between CCT and echocardiography was assessed using Bland-Altman analysis. RESULTS: Paired CCT and echocardiography studies were available in 18 patients (21 studies). The largest CA aneurysms were large/giant (z-score ≥10) in 14 studies, medium (z-score ≥5

Aim: To study the association between non-SARS, non-MERS human coronavirus (HCoV) infections and Kawasaki disease (KD). Methods: Meta-analysis of observational studies published until 1 May 2021. Results: Out of 571 papers retrieved through database search, 10 provided data of 17,732 children. Age ranged from 0.2–14.9 years with 66% being male and 71% being complete KD. Compared with controls, there was an increased risk of developing KD in those detected to have HCoV infection (OR: 2.3 [95% CI: 1.06–4.99]; p = 0.03). The GRADE evidence for all outcomes was of ‘low certainty’. Conclusion: A ‘low certainty’ of evidence suggests an increased risk of KD in children infected with HCoV. We need multi-center, prospective studies to support or refute this finding. PROSPERO protocol registration: CRD42021251582.

Recently, few reports have described a serious condition linked to SARS-CoV-2 that mimics Kawasaki disease called multisystem inflammatory syndrome, especially in children (MIS-C) and young adults. In this work, we report on a severe form of MIS in a young female adult previously infected by SARS-CoV-2. She was treated by plasmapheresis with albumin and steroids, however outcome was fatal. We discuss the pathogenesis of this rare and life threatening entity and suggest some therapeutic regimen. This syndrome should not be misdiagnosed with an infectious or a drug induced cutaneous rash in the current context of COVID-19 pandemic.

Objective: This study aimed to describe the clinical characteristics and the different phenotypes of children with multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19 and to evaluate the risk conditions that favored a greater severity of the disease during a 12-month period at a pediatric reference hospital in Colombia. Methods: A 12-month retrospective observational study of children under the age of 18 years who met criteria for MIS-C. Results: A total of 28 children presented MIS-C criteria. The median age was 7 years. Other than fever (100%) (onset 4 days prior to admission), the most frequent clinical features were gastrointestinal (86%) and mucocutaneous (61%). Notably, 14 (50%) children had Kawasaki-like symptoms. The most frequent echocardiographic abnormalities were pericardial effusion (64%), valvular involvement (68%), ventricular dysfunction (39%), and coronary artery abnormalities (29%). In addition, 75% had lymphopenia. All had at least one abnormal coagulation test. Most received intravenous immunoglobulin (89%), glucocorticoids (82%), vasopressors (54%), and antibiotics (64%). Notably, 61% had a more severe form of the disease and were admitted to an intensive care unit (median 4 days, mean 6 days); the severity predictors were patients with the inflammatory/MIS-C phenotype (OR 26.5; 95%CI 1.40–503.7; p=0.029) and rash (OR 14.7; 95%CI 1.2–178.7; p=0.034). Two patients had macrophage activation syndrome. Conclusions: Coronary artery abnormalities, ventricular dysfunction, and intensive care unit admission were frequent, which needs to highlight the importance of early clinical suspicion.

Kawasaki disease is an acute vasculitis affecting children, which can lead to coronary artery (CA) aneurysms. Optical coherence tomography (OCT) has identified CA wall damage in KD patients, but it is unclear if these findings correlate with any distensibility changes in the CA and how these changes evolve over time. This paper seeks to establish the link between OCT findings and vessel distensibility with a novel deep learning coronary artery segmentation system and use the segmentation framework to automatically analyze the temporal evolution of coronary stiffness over many years. 27 KD patients underwent catheterization with coronary angiography of the left coronary artery (LCA), followed by OCT of proximal and distal segments of the LCA. Changes in the CA caliber over the cardiac cycle were measured automatically and compared against OCT findings suggestive of KD-related vascular damage. In addition, 34 KD patients with regressed or persistent CA aneurysms were followed with serial CA angiography over an average of 14.5 years. Distensibility changes were calculated using a deep learning coronary artery segmentation framework and evaluated longitudinally. Distensibility in the coronary arteries after KD negatively correlated with increasing severity of OCT findings of KD-related vessel damage. KD patients have a significant increase in CA wall stiffness at 1 year after diagnosis, which then plateaus subsequently, compared to controls. Also, patients with persistent CA aneurysms have a statistically significant increase in wall stiffness over time in comparison to those with regressed CA aneurysms. Distensibility changes in the CA of KD patients calculated using our automated deep learning approach correlates with the severity of OCT findings of KD-related CA damage. This decreased distensibility peaks at 1 year in KD patients when following longitudinally and is more severe in those with persistent CA aneurysms.

Hyponatremia is one of the common electrolyte disorders that can accompany many diseases. Kawasaki disease is also one of these situations. Kawasaki disease is the most common vasculitis in children under the age of five years and can occur with very different clinical pictures. Since Kawasaki shock syndrome has been described more recently, its unknown features are high. In this case report, we presented a patient who presented to the emergency department with the clinical findings of hyponatremia and was diagnosed with Kawasaki shock syndrome.

Kawasaki disease (KD) is an acute self-limited syndrome that predominantly affects children. Coronary sequelae have been identified to be responsible for a small, but significant percentage of young adults who present with myocardial ischemia. In this study, we present a case of an elderly patient with possible coronary sequelae of KD. A 76-year-old man was referred to our outpatient department for silent myocardial ischemia. Axial images of coronary computed tomography showed multiple lumens in the proximal left anterior descending (LAD) artery. Coronary angiography demonstrated braid-like appearance in the proximal and distal segment of the LAD. Coronary intervention was successfully performed for the proximal LAD lesion using directional atherectomy (DCA) catheter. Microscopic examination of the DCA specimens showed the following histological features: tissues in densely hyalinized fibrosis with occasional microcalcification, or those containing a number of smooth muscle cells (SMCs) with myxoid extracellular matrix. There was paucity of cholesterin crystals and aggregation of foamy cells. In addition, scarcely any inflammatory cell filtration was identified. In the section of SMC-containing samples, formation of multiple re-canalized vessels embracing endothelial cells was confirmed. These histopathologic findings indicated that the present coronary artery lesion has a high possibility of very late cardiovascular sequelae caused by arteritis due to KD, rather than arteriosclerosis. This is the oldest adult case with coronary artery disease possibly resulting from KD sequelae. This case highlights that KD sequelae must be considered as a cause of coronary artery lesion even in older patients.

Introduction: The etiology of Kawasaki disease (KD), an inflammatory and cardiovascular disorder, remains largely unexplained after more than 50 years of intensive research. In recent years, the association between KD and atopic diseases had been explored by some observational studies. We systematically reviewed and summarized the literature on the relationship between KD and atopic diseases. Methods: MEDLINE and EMBASE were searched to identify observational studies on the association between KD and atopic diseases from inception to May 2021. Odds ratio (OR) was pooled using random-effects models. Heterogeneity was assessed using the I2 and Cochran Q statistics. Primary outcomes were to compare the prevalence of KD among individuals with atopic diseases to nonatopic disease controls and the prevalence of atopic diseases among individuals with KD to non-KD controls. Results: Thirteen studies, including 12,651 cases and 170,708 controls, were included in this meta-analysis. In cross-sectional studies, KD was associated with allergic rhinitis (n = 6; OR, 1.69; 95% CI, 1.52–1.87), asthma (n = 3; OR, 1.72; 95% CI, 1.38–2.14), allergic conjunctivitis (n = 2; OR, 1.95; 95% CI, 1.68–2.27), and atopic dermatitis (n = 3; OR, 1.35; 95% CI, 1.22–1.49). In case-control and cohort studies, KD was associated with allergic rhinitis (n = 3; OR, 1.35; 95% CI, 1.28–1.43), asthma (n = 8; OR, 1.40; 95% CI, 1.19–1.65), allergic conjunctivitis (n = 1; OR, 1.74; 95% CI, 1.45–2.09), and atopic dermatitis (n = 3; OR, 1.39; 95% CI, 1.26–1.53). Conclusion: KD diagnosed was associated with four common atopic diseases. Among the four allergic diseases, allergic conjunctivitis and asthma have the highest correlation with KD, which may provide a direction for exploring the etiology of KD.

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.

The aim of this study was to explore the associations between the aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT) and coronary artery lesions (CALs) among patients with Kawasaki disease (KD). Medical records of KD patients presenting to a single center between January 2019 and December 2020 were retrospectively collected and analyzed. Univariate, multivariable-adjusted analyses, subgroup analyses, restricted cubic spline test, and fitted curves were used to evaluate the associations between AST/ALT and CALs. A total of 831 patients were enrolled, of which 201 (24.2%) had CALs on admission and 21 (2.5%) developed CALs de novo after intravenous immunoglobulin (IVIG). Multivariable-adjusted analyses models revealed that a lower AST/ALT was associated with an increased risk of CALs on admission when AST/ALT was a continuous variable (P = 0.007) and when it was a categorical variable (P for trend = 0.004). Each unit increase in AST/ALT was associated with a 22% lower risk of CALs on admission (odds ratio = 0.78, 95% confidence interval 0.65–0.94). A negative linear relationship was noted between AST/ALT and the risk of CALs on admission in both observed and fitted models. However, such associations were not observed in AST/ALT and CALs de novo after IVIG. None of the variables significantly modified the association between AST/ALT and CALs on admission and CALs de novo after IVIG (P > 0.05). Our findings suggested that AST/ALT was a risk factor of CALs, but was not associated with progressive CALs.

Aims Multisystemic inflammatory syndrome in children (MIS‐C) is a condition noted in some children asymptomatic but positive to Sars‐cov‐2 antibody and it presents clinical and laboratory changes similar to Kawasaki disease (KD). Oral changes have also been observed. This systematic review evaluated oral manifestations detected in children with MIS‐C and KD associated to COVID‐19. Methods and Results This work was registered at PROSPERO (#CRD42020225909), following PRISMA guidelines. A comprehensive research was conducted in MEDLINE, Web of Science, EMBASE, LILACS, Scopus, and Grey Literature through August 2021, based on original research evaluating children diagnosed with MIS‐C or KD related to COVID‐19. Two authors independently screened all retrieved references. Twenty five selected studies evaluated 624 children, mean age 8.78 years. The assessment of the risk of bias (ROB) showed that most of them presented low ROB. Oral manifestations were erythematous mucous membrane, oral ulcers lesions, dry, swollen and cracked lips, and strawberry tongue. Conclusion MIS‐C and KD share the same oral manifestations and their identification may lead to an early diagnosis.

ObjectivesDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still’s disease with atypical lung disease. We sought to characterise features of patients with Still’s disease with DRESS compared with drug-tolerant Still’s controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.MethodsIn a case/control study, we collected a multicentre series of patients with Still’s disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still’s controls (n=65). We retrospectively analysed clinical data from all Still’s subjects and typed 94/131 for HLA. European Still’s-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still’s cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still’s-DRESS cases (n=64) compared with drug-tolerant Still’s controls (n=30). KD subjects (n=19) were similarly studied.ResultsStill’s-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still’s-DRESS (64%) versus drug-tolerant Still’s (3%; p=1.2×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.ConclusionsDRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

Whether the acute inflammation caused by Kawasaki disease will have an effect on the endothelial function of coronary arteries in the future is unknown.Methods:The coronary flow velocity reserve of the left anterior descending artery was examined by transthoracic Doppler echocardiography in 189 patients (male 125, female 64) with a history of Kawasaki disease and 10 volunteers (control). Their ages ranged from 6 to 40 years (median 22 years). The patients were divided into nine groups based on the left anterior descending artery lesions. The coronary flow velocity reserve was measured by intravenous administration of adenosine triphosphate (0.15 mg/kg/minute) while fasting. The coronary flow velocity reserve was calculated as the ratio of hyperaemic to basal mean diastolic flow velocities. The respective groups were as follows: control, no coronary artery lesions (n = 39), no coronary artery lesions in the right coronary artery (n = 29), regression (n = 11), aneurysm at the bifurcation of the left coronary artery (n = 26), aneurysm of the left anterior descending artery (n = 15), localised stenosis Results:The coronary flow velocity reserve was significantly lower in the localised stenosis ≥75%, segmental stenosis and coronary artery grafting groups than in the other groups (p < 0.05).Conclusions:The endothelial function in the epicoronary artery was preserved in patients with a history of Kawasaki disease and dilated coronary artery lesions.

Background Post‐COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C‐reactive protein (CRP), interleukin 6 (IL6) as well as N‐terminal probrain natriuretic peptide (NT‐proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. Methodology This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017‐June 2018), with 71 MISC patients over a period of 6 months (July 2020‐December 2020). The non‐parametric Mann‐Whitney U test was used to test for similarity in distributions of the samples of CRP, NT‐proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. Results Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT‐proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P 935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.

The impact of the COVID-19 pandemic, and implemented restrictions on the frequency of pediatric rheumatic diseases remain unknown, while they have probably prevented common infections in children. We present the effects of the COVID-19 on our pediatric rheumatology practice in a main referral center. We retrospectively reviewed the medical records of patients presenting to pediatric rheumatology department in 4 years before March 2020 and compared it to the pandemic year (March 2020–March 2021). Since there was an overall decrease in patient numbers, we calculated the percentage according to the total number of that year. A total of 32,333 patients were evaluated. The mean annual number of patients decreased by 42% during the COVID-19 pandemic. When follow-up visits (25,156) were excluded, there were 2818 new diagnoses of rheumatic diseases. In the pre-pandemic period, familial Mediterranean fever (FMF) (n = 695, 28.1%) was the most frequent, whereas in the pandemic period multisystem inflammatory syndrome in children (MIS-C) (n = 68, 19.2%) was the most common diagnosis. There were no significant differences in the percentages of juvenile idiopathic arthritis, autoimmune diseases, rare autoinflammatory diseases, and other vasculitides. However, there was a significant decrease in patients diagnosed with FMF, IgA vasculitis (IgAV), acute rheumatic fever (ARF), classic Kawasaki disease (KD), and macrophage activation syndrome (MAS) (all p

Noncerebral vasculitis is a wide-range noninfectious inflammatory disorder affecting the vessels. Vasculitides have been categorized based on the vessel size, such as large-vessel vasculitis, medium-vessel vasculitis, and small-vessel vasculitis. In this document, we cover large-vessel vasculitis and medium-vessel vasculitis. Due to the challenges of vessel biopsy, imaging plays a crucial role in diagnosing this entity. While CTA and MRA can both provide anatomical details of the vessel wall, including wall thickness and enhancement in large-vessel vasculitis, FDG-PET/CT can show functional assessment based on the glycolytic activity of inflammatory cells in the inflamed vessels. Given the size of the vessel in medium-vessel vasculitis, invasive arteriography is still a choice for imaging. However, high-resolution CTA images can depict small-caliber aneurysms, and thus can be utilized in the diagnosis of medium-vessel vasculitis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Kawasaki disease is the leading cause of acquired heart disease in children and most frequently affects infants and young children. This disease is a systemic vasculitis that invades medium-sized arteries, including the coronary arteries. Coronary arteritis can begin as early as day 6 of fever and lead to permanent damage. Thus, early recognition and treatment significantly reduces the risk for developing coronary artery aneurysms. The overlapping clinical features of multisystem inflammatory syndrome in children secondary to COVID-19 could potentially contribute to a delay in the identification of Kawasaki disease. The clinical similarities and differences are discussed, along with recent guidelines.

Introduction Kawasaki disease (KD) with coronary artery aneurysms (complex KD) presents relentless challenges for families. Psychosocial experiences and needs were explored. Method A descriptive, exploratory study of adolescents and parents using a needs survey and psychosocial instruments (anxiety, depression, and functional impairment). Results Fifty-one parents and 38 adolescents participated. Predominant interests were for information sheets, newsletters, Web sites, and phone applications. Gaps in disease-specific knowledge and awareness of coronary artery aneurysms between parents and adolescents were identified. Psychosocial concerns for adolescents included symptoms of anxiety (22%), depression (13%), and functional impairment (22%). Multivariable analyses indicated higher depression scores associated with longer travel distance from specialists (p = .04). Parent-reported social concerns for their adolescent were associated with higher anxiety (p = .005) and functional impairment (p = .005). Written commentary complemented the findings. Discussion Care protocols require psychosocial assessment/referral and the use of virtual platforms. The groundwork was laid for developing patient and family-centered strategies.

Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly asymptomatic or have mild symptoms compared with the more severe coronavirus disease 2019 (COVID-19) described in adults. However, SARS-CoV-2 is also associated with a widely reported but poorly understood paediatric systemic vasculitis. This multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. Epidemiological, clinical and immunological differences classify MIS-C as being distinct from Kawasaki disease. Differences include the age range, and the geographical and ethnic distribution of patients. MIS-C is associated with prominent gastrointestinal and cardiovascular system involvement, admission to intensive care unit, neutrophilia, lymphopenia, high levels of IFNγ and low counts of naive CD4+ T cells, with a high proportion of activated memory T cells. Further investigation of MIS-C will continue to enhance our understanding of similar conditions associated with a cytokine storm., In this timely Review, the authors compare and contrast two forms of childhood inflammatory vasculitis: Kawasaki disease and the coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children, highlighting epidemiological, clinical and immunological differences that suggest they should be classified as distinct syndromes., Key points Multisystem inflammatory syndrome in children (MIS-C) is characterized by exaggerated innate and adaptive immune responses following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in predisposed children.Clinical presentation of MIS-C involves multiple organ systems, with prominent involvement of the gastrointestinal and cardiovascular systems.The factors that trigger the development of MIS-C in children exposed to or infected with SARS-CoV-2 are not yet known.Results from epidemiological, clinical and immunological investigations have revealed that although MIS-C has phenotypic similarities to Kawasaki disease, they are different syndromes.The approach to treatment of MIS-C aims to mute the augmented inflammatory response.

The COVID-19 pandemic has caused significant disease across the globe but children seem to be much less affected than adults. Coincidentally with the first wave of the pandemic, a cluster of children with fever, hyperinflammation and shock were identified, and this was first described as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) by the Royal College of Paediatrics and Child Health. Patients with this novel condition were transferred to tertiary centres for management, increasing the pressure in these hospitals that were already extremely busy. There are multiple challenges related to the identification of patients presenting with PIMS-TS given that they mimic multiple other well-known paediatric conditions, like Kawasaki disease and toxic shock syndrome. Investigations and admission criteria to a district general hospital (DGH) need to be well established, and clear guidance should be available for easy decision making in a busy paediatric emergency department. Furthermore, these children can deteriorate suddenly and rapidly; close monitoring is vital, and any deterioration must be taken seriously and addressed immediately. All children who present severely ill, with shock and multiorgan failure, should be retrieved to a paediatric intensive care unit. As our knowledge of the condition has developed, more patients are now managed in a DGH, with virtual multidisciplinary team involvement. This paper outlines a structured approach to management of children presenting with suspected PIMS-TS in a DGH.

PURPOSE OF REVIEW: The main purpose of this review is to present newly reported cutaneous manifestations of systemic vasculitis, updates in investigations to verify systemic involvement in cases with cutaneous vasculitis and new therapeutic guidelines. The spectrum of COVID-19-related vasculitis is also covered. RECENT FINDINGS: Only a few reports highlighted new cutaneous presentations or associations with some systemic vasculitic entities. For example, the association of inflammatory disorders with Takayasu arteritis, the importance of considering Kawasaki disease in febrile children with erythema nodosum, the development of necrotic ulcers on fingers and toes in Behcet's disease and the possible presence of polyarteritis nodosa-like pathological features in vulvar ulcers of Behcet's disease. New attempts to classify cutaneous manifestations of giant cell arteritis (GCA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the diagnostic investigations for cutaneous vasculitis cases to verify systemic involvement are discussed. Treatment of systemic vasculitis with cutaneous vasculitis should be tailored according to disease status. A plethora of reports in the past 2 years focused on the broad spectrum of COVID-19 vasculitic manifestations. SUMMARY: Although newly reported cutaneous manifestations of systemic vasculitis are relatively uncommon, the plethora of reports in the past 2 years on COVID-19 vasculitis necessitates the expansion of the classification of vasculitis associated with probable cause to include severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) vasculitis.

Purpose of Review We highlight the new clinical entity multisystem inflammatory syndrome in children (MIS-C), the progress in understanding its immunopathogenesis, and compare and contrast the clinical and immunologic features of MIS-C with Kawasaki disease (KD). Recent Findings Studies show immune dysregulation in MIS-C including T lymphocyte depletion and activation, T cell receptor Vbeta skewing, elevated plasmablast frequencies, increased markers of vascular pathology, and decreased numbers and functional profiles of antigen-presenting cells. Summary MIS-C is a late manifestation of infection with SARS-CoV-2 associated with marked immune activation and many potential mechanisms of immunopathogenesis. MIS-C and KD have clinical similarities but are distinct. Myocardial dysfunction with or without mild coronary artery dilation can occur in MIS-C but generally corrects within weeks. In contrast, the coronary arteries are the primary target in KD, and coronary artery sequelae can be lifelong. Supportive care and anti-inflammatory therapy appear to hasten improvement in children with MIS-C, and there is hope that vaccines will prevent its development.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a new hyperinflammatory variant that evolved during the coronavirus disease 2019 (COVID-19) pandemic. Although the precise pathophysiology of MIS-C is uncertain, it is thought to be due to immune dysregulation occurring after recovery from acute infection. Purpose: Our study aimed to analyze the clinical spectrum, laboratory parameters, imaging characteristics, treatment strategies, and short-term outcomes of children with a diagnosis of MIS-C. Methods: This retrospective and prospective observational study included children less than 16 years of age who were admitted to the pediatric unit of a tertiary care teaching hospital in south India between August 2020 to January 2021 with a diagnosis of MIS-C according to World Health Organization (WHO) criteria. Results: Twenty-one children were included in the analysis; all had fever with variable combinations of other symptoms. The mean age was 6.9 years; 71.4% were male. Gastrointestinal (80.9%) and cardiovascular (80.9%) systems were the most commonly affected. The majority of children had elevated inflammatory markers, and 16 (76.2%) had echocardiographic abnormalities mimicking Kawasaki disease. Eleven (52.4%) children required intensive care admission, three (14.3%) required supplemental oxygen, and four (19%) required inotropes. Nine (42.9%)were treated with intravenous immunoglobulin alone, six (28.6%) with steroids alone, and three(14.3%) with steroids and immunoglobulin. The median hospital stay was 6 days; there were no fatalities. Overweight/obesity, elevated ferritin, and mucocutaneous involvement were significantly associated with a prolonged hospital stay (≥7 days). Sixteen (76.2%) children were followed up till now and all of them had no clinical concerns. Conclusion: MIS-C is an emerging disease with variable presentation. A high index of suspicion is necessary for its early identification and appropriate management. Further research is essential for developing optimal treatment strategies.

Coronavirus infection poses a particular danger in relation to decompensation of existing chronic diseases and specific damage to the cardiovascular system (CVS) both during an acute infection and during convalescence. Objective of the study: to summarize current knowledge about the potential involvement of CVS in the development and progression of acute COVID-19 infection and multisystem inflammatory syndrome (MIS) in children and to form an sense of the predictive value, diagnostic tactics and treatment of cardiac anomalies during the coronavirus pandemic. A search was performed in MEDLINE, PubMed, e-library using the search terms «cardiovascular disease in COVID-19/MIS in children», «congenital heart disease/pulmonary hypertension/prolonged QT interval and COVID-19 in children» to identify articles published from April 1, 2020 to May 1, 2021. A literature review indicates that cardiac disorders associated with the new coronavirus infection in children, in the vast majority of cases, developed during MIS, which manifests itself in the form of febrile fever, external signs of Kawasaki disease, hyperinflammatory state and multi-organ damage with an emphasis on CVS. Cardiovascular symptoms occur in the vast majority of children with MIS, and in more than half of the patients – by the type of myocardial dysfunction and/or shock, somewhat less often – in the form of ECG changes, pericardial effusion, сoronary artery ectasia. Against the background of treatment with steroids, intravenous human immunoglobulin (IVIG) and biologic drugs in combination with inotropic support in almost all children, the morphofunctional characteristics of CVS are restored to normal or subnormal levels in a few days. The need for extracorporeal membrane oxygenation and lethal cases are rare. The possibility of developing myocarditis (including fatal), pulmonary hypertension and cardiac arrhythmias associated with COVID-19 in pediatric patients with discussion of possible pathophysiological mechanisms was also described. Long-term observation of this category of persons is necessary due to the uncertain prognosis and the risk of progression of cardiac manifestations. An early comprehensive diagnosis of cardiac disorders and monitoring of the identified changes in children with MIS and acute coronavirus infection are needed. (English) [ABSTRACT FROM AUTHOR][ABSTRACT FROM AUTHOR] Copyright of Pediatriya named after G. N. Speransky is the property of Pediatria, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To explore the diagnostic value of deep learning algorithm in coronary arteries in children with Kawasaki disease, convolutional neural network (CNN) was applied in the segmentation of dual-source computed tomography (CT) (DSCT) image information of coronary artery lesions in children with Kawasaki disease. A CNN algorithm was improved, and the range image U-net (RIU-Net) was adopted to segment the CT image for convolution feature extraction. The improved model was fused with squeeze and excitation module and pyramid pooling to fabricate a new network (RISEU-Net), in which the ability of image features extraction was enhanced. Ninety children with coronary artery lesion of Kawasaki disease were selected and rolled into a control group (n = 45) and observation group (n = 45). The constructed model was used to segment the CT images of the two groups of patients, and the accuracy, sensitivity, and Dice of image segmentation were compared. The results showed that the utilization of key image features was improved after the SE module and pyramid pooling were integrated on the RIU-Net network. The lowest LOSS value of the RISEU-Net network was stable at about 0.02, and the effect was very fast during the training process. The sensitivity and accuracy of the constructed model to image detection were 95.6% and 96.7%, respectively. The negative predictive rate was 97.3%, and the positive predictive rate of 92.7%, which were all higher than those in the control group. The Dice values of RISEU-Net-N, RISEU-Net, and RIU-Net were 0.7765, 0.8562, and 0.8356, respectively. In summary, the RIU-Net network model proposed showed reliable feasibility and effectiveness for DSCT image segmentation, which effectively improved the clinical information evaluation of CT images of coronary artery lesions in children with Kawasaki disease, showing crucial reference for the development of intelligent medical equipment.

Background Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormalities in children. Although clinical trials of monoclonal antibodies and anti-cytokine biologics that block cytokine cascades have been conducted, the studies have revealed contradictory results. To examine the effectiveness of treatment with monoclonal antibodies and anti-cytokine biologics for KD patients, we conducted this systematic review and meta-analysis. Methods Relevant randomized controlled trials (RCTs) and observational studies (e.g., cohort studies, case-control studies, case-series, and case-reports) were included to summarize available evidence, both qualitatively and quantitatively. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI were used for systematic research. Meta-analysis of the included studies was conducted using fixed-effect or random-effects models, depending on the degree of between-study heterogeneity. We assessed coronary artery and treatment outcomes of the interventions. The certainty of evidence and risk of bias were assessed using the GRADE and Cochrane risk of bias tool. The protocol of this review is registered with PROSPERO (CRD42016033079). Results Results: Of all searched studies, 183 studies were qualitatively analyzed. We finally included four randomized controlled trials with 456 patients in quantitative syntheses. Monoclonal antibodies and anti-cytokine biologics did not reduce the frequency of CAA (risk ratio [RR], 0.93; 95% confidence interval [95%CI], 0.65 to 1.32, low certainty of evidence), compared with the conventional treatment with IVIG. However, the frequency of treatment resistance (RR, 0.60; 95%CI, 0.38 to 0.95, moderate certainty of evidence) was reduced by the antibodies. We found no statistical differences in either “any adverse event” (RR, 0.92; 95%CI, 0.80 to 1.06, low certainty of evidence) or “adverse events attributable to the administration of the medication” (RR, 1.10; 95%CI, 0.72 to 1.69, low certainty of evidence) between the two groups. Conclusion Conclusions: Although monoclonal antibodies and anti-cytokine biologics were not effective in reducing the frequency of CAA in KD patients, the frequency of treatment resistance might be reduced by those agents compared with conventional IVIG therapy alone.

Intravenous immunoglobulin (IVIG) is used in the treatment of immunological, inflammatory and neurological conditions. We aimed to describe the trends in IVIG utilization in Taiwan. We identified patients receiving IVIG through the national health insurance (NHI) database. We described the distribution of IVIG use according to main indications. During 2008–2017, IVIG distribution grew 10% per year on average. The population IVIG dose was 8.0 g per thousand capita. Among the total distribution, approximately 60% were NHI-reimbursed. Pediatrics (52.3%), rheumatology (14.0%) and hematology/oncology (11.4%) accounted for the top three services in terms of IVIG consumption. Primary and secondary immune deficiency (29.8%), Kawasaki disease (20.5%) and thrombocytopenia (16.8%) were the top three indications. Neurological conditions only accounted for 3%. In brief, unlike countries with high population use, the proportion of reimbursed IVIG used for neurological conditions was low. Further studies on self-paid IVIG use is needed to completely understand utilization in Taiwan.

Background and Objectives: Kawasaki Disease (KD) incidence has been on the rise globally throughout the years, particularly in the Asia Pacific region. KD can be diagnosed based on several clinical criteria. Due to its systemic inflammatory nature, multi-organ involvement has been observed, making the diagnosis of KD more challenging. Notably, several studies have reported KD patients presenting with hepatobiliary abnormalities. Nonetheless, comprehensive data regarding the hepatobiliary manifestations of KD are limited in Malaysia, justifying a more in-depth study of the disease in this country. Thus, in this article, we aim to discuss KD patients in Malaysia with hepatobiliary manifestations. Materials and Methods: A total of six KD patients with hepatobiliary findings who presented at Hospital Canselor Tuanku Muhriz (HCTM) from 2004 to 2021 were selected and included. Variables including the initial presenting signs and symptoms, clinical progress, laboratory investigations such as liver function test (LFT), and ultrasound findings of hepatobiliary system were reviewed and analyzed. Results: Out of these six KD patients, there were two patients complicated with hepatitis and one patient with gallbladder hydrops. Different clinical features including jaundice (n = 3) and hepatomegaly (n = 4) were also observed. All patients received both aspirin and intravenous immunoglobulin (IVIG) as their first-line treatment and all of them responded well to IVIG. The majority of them (n = 5) had a complete recovery and did not have any cardiovascular and hepatobiliary sequelae. Conclusions: Despite KD mostly being diagnosed with the classical clinical criteria, patients with atypical presentations should always alert physicians of KD as one of the possible differential diagnoses. This study discovered that hepatobiliary manifestations in KD patients were not uncommon. More awareness on the epidemiology, diagnosis, and management of KD patients with hepatobiliary manifestations are required to allow for the initiation of prompt treatment, thus preventing further complications.

Introduction: While the clinical course of SARS-CoV-2 infection seems to be milder or asymptomatic within the pediatric population, growing attention has been laid to the rare complication elicited by virus, multisystem inflammatory syndrome in children temporarily associated with COVID-19 (MIS-C). Published definition and criteria of MIS-C include persistent fever, multisystem involvement, and elevated markers of inflammation, without obvious microbial inflammation or other plausible diagnosis. However, the aim of this case report is to emphasize the diversity of symptoms of MIS-C, beyond the defined criteria. Case Presentation: We present a 10-year-old boy with 8p23.1 microdeletion syndrome and multiple comorbidities who initially came to our attention due to hematuria, persistent fever, rash, and elevated markers of inflammation. Within the next 2 days, his condition worsened despite the broad-spectrum antibiotic therapy. Assuming his past history of SARS-CoV-2 exposure, MIS-C was suspected. A high level of clinical suspicion was further supported by significant clinical features (vomiting, abdominal pain, conjunctivitis, arrhythmia, and mild left ventricular systolic dysfunction with pleural effusion) along with laboratory findings (elevated ESR, CRP, proBNP, D-dimers and fibrinogen, positive IgG SARS-CoV-2 antibodies, and negative microbiological cultures). The patient was given intravenous immunoglobulin (IVIG) and began to show instantaneous clinical and laboratory improvement. Conclusion: Despite numerous reports of MIS-C cases in children, there are still many uncertainties regarding the clinical presentation and laboratory findings, as well as mechanisms beyond this intriguing disorder. In our case, for the first time hematuria is reported as an early symptom of MIS-C. We strongly believe that reporting various manifestations and outcomes in MIS-C patients will lead to improved diagnosis, treatment, and overall understanding of this novel inflammatory condition.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and serious complication of Sars-Cov-2 infection. Dermatologic manifestations are present in the majority of patients. Skin lesions found in children with MIS-C are classified into four categories: morbilliform, reticulated, scarlatiniform, and urticarial lesions. Clinicopathologic characterization within these categories is limited. Thus, we present a clear example of an urticarial lesion in the context of MIS-C with well-documented clinicopathologic phenomena. A previously healthy 16 year old female presented with three weeks of an itchy, burning rash initially presenting on her right forearm (and lasting greater than 24 hours without migration) before spreading diffusely. She also reported fever, cough, myalgias, nausea, and vomiting of four weeks' duration. Physical examination revealed an edematous, maculopapular, non-blanching, erythematous rash covering the patient's upper extremities, abdomen, back, anterior thighs, and face. The patient tested positive for COVID-19. A low-grade leukocytoclastic vasculitis was noted along with intraluminal fibrin and rare microthrombi in vessels of the mid to deep dermis. The patient was diagnosed with MIS-C and urticarial vasculitis. She was treated with steroids and naproxen for subsequent MIS-C flares. Dapsone treatment was started for the urticarial vasculitis. This article is protected by copyright. All rights reserved.

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers, and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and erythrocyte sedimentation rate (ESR). In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of N-terminal pro-brain natriuretic peptide, troponin and aspartate aminotransferase were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and alanine aminotransferase and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.

Coronary artery aneurysm (CAA) is a clinical entity defined by a focal enlargement of the coronary artery exceeding the 1.5-fold diameter of the adjacent normal segment. Atherosclerosis is the main cause in adults and Kawasaki disease in children. CAA is a silent progressive disorder incidentally detected by coronary angiography, but it may end with fatal complications such as rupture, compression of adjacent cardiopulmonary structures, thrombus formation and distal embolization. The pathophysiological mechanisms are not well understood. Atherosclerosis, proteolytic imbalance and inflammatory reaction are involved in aneurysmal formation. Data from previously published studies are scarce and controversial, thereby the management of CAA is individualized depending on clinical presentation, CAA characteristics, patient profile and physician experience. Multiple therapeutic approaches including medical treatment, covered stent angioplasty, coil insertion and surgery were described. Herein, we provide an up-to-date systematic review on the pathophysiology, complications and management of CAA.

Kawasaki disease (KD) in adolescence and adulthood is often underrecognized, because KD predominantly affects infants and young children below the age of 5 years. We report four cases of KD in patients 16-32 years of age. The first department that the patients visited was the Department of Otolaryngology, Obstetrics, or General Internal Medicine. Since KD almost always develops as cutaneous and mucosal manifestations, dermatologists have a particularly significant role in diagnosing KD in adolescents and adults. KD should be kept in mind for febrile patients of any age group presenting with exanthem.

In this case report, we describe a Kawasaki-like multisystem inflammatory syndrome (MIS-A) in a 33-year old man that occurred 19 days after a SARS-CoV-2 infection. The main features at presentation were profound myocarditis, bilateral non-purulent conjunctivitis, mediastinal lymphadenopathy, and acute kidney failure and laboratory evidence of hyperinflammation. He received ACE-inhibition and beta-blockers for his heart failure and made a fairly rapid spontaneous recovery over the subsequent 8 days.

Background. A large number of clinical masks and also insufficient vigilance of doctors regarding Kawasaki syndrome in a child with long-term fever impede timely diagnosis of Kawasaki syndrome. The purpose of the study was to increase the diagnostic efficiency of Kawasaki disease based on a retrospective analysis of its clinical course and outcomes in children under our supervision. Materials and methods. Case histories were analyzed in 7 children aged from 7 months to 6 years, who were treated in the cardiopulmonary department of Children’s Clinical Hospital 2 in Dnipro. The diagnosis of Kawasaki disease was verified based on diagnostic criteria in accordance with the current clinical protocol. Routine research methods and echocardiography were performed for all patients. Results. The study revealed late diagnosis of Kawasaki disease, already at the stage of formation of coronary artery aneurysms, in 43 % of cases. The complexity of diagnosing Kawasaki syndrome was due to the lack of a full range of typical symptoms. The incomplete presentation was noted mainly in children of the first three years of life and included symptoms such as conjunctivitis, maculopapular rash, and oral lesions in various combinations. Echocardiography revealed coronary artery aneurysms in 57 % of cases, mostly in infants with incomplete presentation of Kawasaki disease. Against the background of therapy (intravenous immunoglobulin and aspirin), we observed a significant regression of coronary artery aneurysms in all patients. Conclusions. Infants most often have incomplete presentation of Kawasaki syndrome, which complicates its diagnosis. In this regard, prolonged fever in combination even with 2–3 typical signs should be an absolute indication for echocardiography with mandatory visualization of the coronary arteries., Актуальность. Своевременной диагностике синдрома Кавасаки препятствует большое количество клинических масок болезни, а также недостаточная настороженность врачей в отношении этого заболевания у длительно лихорадящего ребенка. Цель: повысить эффективность диагностики болезни Кавасаки на основании ретроспективного анализа клинического течения и исходов заболевания у детей, находившихся под нашим наблюдением. Материалы и методы. Проведен анализ историй болезни 7 детей в возрасте от 7 месяцев до 6 лет с болезнью Кавасаки, находившихся на лечении в кардиопульмонологическом отделении ДГКБ № 2 г. Днепр. Диагноз болезни Кавасаки был верифицирован на основе диагностических критериев в соответствии с действующим клиническим протоколом. Всем больным были проведены рутинные методы исследования, ЭхоКГ (Д). Результаты. В ходе исследования отмечена поздняя диагностика болезни Кавасаки (на этапе формирования аневризм коронарных артерий) в 43 % наблюдаемых случаев. Сложность диагностики синдрома Кавасаки была обусловлена отсутствием полного комплекса типичных клинических признаков. Неполный вариант отмечался преимущественно у детей первых трех лет жизни и включал такие симптомы, как конъюнктивит, пятнисто-папулезная сыпь и поражение ротовой полости в различных комбинациях. ЭхоКГ-исследование выявило наличие аневризм коронарных артерий в 57 % случаев, преимущественно у детей раннего возраста с неполным вариантом болезни Кавасаки. На фоне проводимой терапии (внутривенный иммуноглобулин и аспирин) мы наблюдали значительный регресс аневризм коронарных артерий у всех пациентов. Выводы. У детей раннего возраста наиболее часто встречается неполный вариант синдрома Кавасаки, что затрудняет его диагностику. В связи с этим длительная лихорадка в сочетании даже с 2–3 типичными признаками должна быть абсолютным показанием к проведению ЭхоКГ с обязательной визуализацией коронарных артерий., Актуальність. Своєчасній діагностиці синдрому Кавасакі перешкоджає велика кількість клінічних масок хвороби, а також недостатня настороженість лікарів щодо цього захворювання у дітей із тривалою лихоманкою. Мета: підвищити ефективність діагностики хвороби Кавасакі на підставі ретроспективного аналізу клінічного перебігу та результатів захворювання у дітей, які перебували під нашим спостереженням. Матеріали та методи. Проведено аналіз історій хвороби 7 дітей віком від 7 місяців до 6 років із хворобою Кавасакі, які перебували на лікуванні в кардіопульмонологічному відділенні МДКЛ № 2 м. Дніпра. Діагноз хвороби Кавасакі був верифікований на підставі діагностичних критеріїв згідно з чинним клінічним протоколом. До всіх хворих були застосовані рутинні методи дослідження, ЕхоКГ (Д). Результати. Під час дослідження відзначено пізню діагностику хвороби Кавасакі (на етапі формування аневризм коронарних артерій) в 43 % спостережуваних випадків. Складність діагностики синдрому Кавасакі була обумовлена відсутністю повного комплексу типових ознак. Неповний варіант відзначався переважно в дітей перших трьох років життя і включав такі симптоми, як кон’юнктивіт, плямисто-папульозне висипання й ураження ротової порожнини в різноманітних комбінаціях. ЕхоКГ-дослідження виявило аневризми коронарних артерій у 57 % випадків, переважно у дітей раннього віку з неповним варіантом хвороби Кавасакі. На тлі проведеної терапії (внутрішньовенний імуноглобулін та аспірин) ми спостерігали значний регрес аневризм коронарних артерій у всіх пацієнтів. Виснов­ки. У дітей раннього віку найбільш часто спостерігається неповний варіант синдрому Кавасакі, що ускладнює його діагностику. У зв’язку з цим тривала лихоманка в поєднанні навіть з 2–3 типовими ознаками повинна бути абсолютним показанням до проведення ЕхоКГ з обов’язковою візуалізацією коронарних артерій.

Background:Coronary artery aneurysms are well-described in Kawasaki disease and the Multisystem Inflammatory Syndrome in Children and are graded using Z scores. Three Z score systems (Boston, Montreal, and DC) are widely used in North America. The recent Pediatric Heart Network Z score system is derived from the largest diverse sample to-date. The impact of Z score system on the rate of coronary dilation and management was assessed in a large real-world dataset.Methods:Using a combined dataset of patients with acute Kawasaki disease from the Children’s Hospital at Montefiore and the National Heart, Lung, and Blood Institute Kawasaki Disease Study, coronary Z scores and the rate of coronary lesions (Z ≥ 2.0) and aneurysms (Z ≥ 2.5) were determined using four Z score systems. Agreement among Z scores and the effect on Kawasaki management were assessed.Results:Of 333 patients analysed, 136 were from Montefiore and 197 from the Kawasaki Disease Study. Age, sex, body surface area, and rate of coronary lesions did not differ between the samples. Among the four Z score systems, the rate of acute coronary lesions varied from 24 to 55%. The mean left anterior descending Z scores from Pediatric Heart Network and Boston had a large uniform discrepancy of 1.3. Differences in Z scores among the four systems may change anticoagulation management in up to 22% of a Kawasaki population.Conclusions:Choice of Z score system alone may impact Kawasaki disease diagnosis and management. Further research is necessary to determine the ideal coronary Z score system.

Kai Guo,1 Lijuan Qiu,1 Yufen Xu,2 Xiaoqiong Gu,2 Linyuan Zhang,3 Kun Lin,3 Xiaohuan Wang,1 Shanshan Song,1 Yu Liu,1 Zijian Niu,1 Shuxuan Ma1 1Department of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Clinical Lab, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shuxuan MaDepartment of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health No. 56 Nan Lishi Road, Xi Cheng District, Beijing, 100045, People’s Republic of ChinaTel +86 10 59616422Email masxfwyy@sina.comBackground: Kawasaki disease (KD) is a multisystem vasculitis in infants and young children and involved in the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation. Genetic factors may increase the risk of KD. To assess the association between rs7248320 in long noncoding RNA (lncRNA) AC008392.1 located in the upstream region of CARD8 and the risk of KD, a case–control study was conducted in the Han Chinese population.Methods: This study genotyped the polymorphism rs7248320 in the lncRNA AC008392.1 gene using the TaqMan real-time polymerase chain reaction assay. The genetic contribution of rs7248320 was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. The association between rs7248320 and KD susceptibility was analyzed by performing a hospital-based case–control study including 559 KD patients and 1055 non-KD controls.Results: In this study, a significant relationship between rs7248320 and KD risk was observed in the genotype/allele frequency distribution. The rs7248320 polymorphism was associated with a significantly decreased risk of KD after adjustment for age and sex (AG vs AA: adjusted OR = 0.80, 95% CI: 0.64– 0.99, P = 0.0421; GG vs AA: adjusted OR = 0.71, 95% CI: 0.51– 1.00, P = 0.0492; AG/GG vs AA: adjusted OR = 0.78, 95% CI: 0.63– 0.96, P = 0.0186). Moreover, the rs7248320 G allele also exhibited a decreased risk for KD (adjusted OR = 0.83, 95% CI: 0.72– 0.97, P = 0.0193) compared with the A allele. In the stratification analysis, compared to the rs7248320 AA genotype, AG/GG genotypes were more protective for males (OR = 0.71, 95% CI: 0.55– 0.93, P = 0.0122).Conclusion: This study suggests for the first time that the lncRNA AC008392.1 rs7248320 polymorphism may be involved in KD susceptibility in the Han Chinese population.Keywords: Kawasaki disease, rs7248320, AC008392.1, CARD8, lncRNA, single-nucleotide polymorphism

Background Multiinflammatory syndrome in children (MIS-C) is a novel and rare inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2 infection in school-age children. Reports in the past year have suggested a multisystem pathophysiology characterized by hyperinflammation, gastrointestinal distress, and cardiovascular complications. Clinical laboratory investigations, including routine blood testing for inflammatory (e.g., C-reactive protein, ferritin) and cardiac (e.g., troponin, brain natriuretic peptides) markers have provided insight into potential drivers of disease pathogenesis, highlighting the role of the laboratory in the differential diagnosis of patients presenting with similar conditions (e.g., Kawasaki disease, macrophage activating syndrome). Content While few studies have applied high-dimensional immune profiling to further characterize underlying MIS-C pathophysiology, much remains unknown regarding predisposing risk factors, etiology, and long-term impact of disease onset. The extent of autoimmune involvement is also unclear. In the current review, we summarize and critically evaluate available literature on potential pathogenic mechanisms underlying MIS-C onset and discuss the current and anticipated value of various laboratory testing paradigms in MIS-C diagnosis and monitoring. Summary From initial reports, it is clear that MIS-C has unique inflammatory signatures involving both adaptive and innate systems. Certain cytokines, inflammatory markers, and cardiac markers assist in the differentiation of MIS-C from other hyperinflammatory conditions. However, there are still major gaps in our understanding of MIS-C pathogenesis, including T cell, B cell, and innate response. It is essential that researchers not only continue to decipher initial pathogenesis but also monitor long-term health outcomes, particularly given observed presence of circulating autoantibodies with unknown impact.

Background Kawasaki disease (KD), which was first described by Tomisaku Kawasaki in 1967, is a syndrome that results in acute systemic vasculitis, affecting mainly infants and children, and is a major cause of acquired heart disease in developed countries. KD is diagnosed based on certain characteristic symptoms and echocardiogram results. It has been reported that neck and abdominal ultrasound is also reliable diagnostic method. Nevertheless, abdominal ultrasound is not a routine procedure in KD. Moreover, dilatation of the common bile duct (CBD) has been rarely reported in previous cases. Case presentation: A 4-year-old boy presented with fever and markedly high transaminase level (AST, 5,323 U/L, ALT, 1,554 U/L). The patient was diagnosed as having KD based on characteristic symptoms and echocardiogram findings. Neck and abdominal ultrasound revealed dilatation of the CBD as well as cervical lymphadenopathy resembling a cluster of grapes, thickening of the gallbladder wall, and increased periportal echogenicity throughout the liver parenchyma. The patient received initial treatment with intravenous immunoglobulin (IVIG) at day 4 of fever, following which, transaminase level decreased. The patient received second-line treatment with IVIG and prednisolone because of recurrent fever on day 6. Dilatation of the CBD was improved from 6.6 mm on day 4 to 3.1 mm on day 8. Although re-dilatation was observed, it gradually diminished and normalized (4.3 mm on day 28, 4.0 mm on day 63, 3.3 mm on day 105, and 2.8 mm on day 182). Conclusion This case highlights the usefulness of abdominal ultrasound and the importance of considering dilatation of the CBD as one of the complications of KD. Because abdominal ultrasound is not a routine procedure in KD, it is possible that dilatation of the CBD in KD is quite latent if not investigated thoroughly. Further prospective studies to support these findings are warranted.