Objectives The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome. Data sources The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods. Data synthesis Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay. Conclusions This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.

Multisystem Inflammatory Syndrome in Children Associated With Coronavirus Disease 2019 in a Children's Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up.

Kawasaki disease (KD) is a common medium vessel systemic vasculitis that usually occurs in small children It has a predilection for the coronary arteries, but other medium sized arteries can also be involved The etiology of this disorder remains a mystery Though typical presentation of KD is quite characteristic, it may also present as incomplete or atypical disease in which case the diagnosis can be very challenging As both incomplete and atypical forms of KD can be associated with serious coronary artery complications, the pediatrician can ill afford to miss these diagnoses The American Heart Association has enunciated consensus guidelines to facilitate the clinical diagnosis and treatment of this condition However, there are still several issues that remain controversial Intravenous immunoglobulin remains the cornerstone of management but several other treatment modalities, especially glucocorticoids, are increasingly finding favour We review here some of the contemporary issues, and the controversies thereon, pertaining to management of KD

Controversies in diagnosis and management of Kawasaki disease

A healthy 25-year-old woman developed COVID-19 disease with clinical characteristics resembling Multisystem Inflammatory Syndrome in Children (MIS-C), a rare form of COVID-19 described primarily in children under 21 years of age. The patient presented with 1 week of weakness, dyspnea, and low-grade fevers, followed by mild cough, sore throat, vomiting, diarrhea, and lymph node swelling. She was otherwise healthy, with no prior medical history. Her hospital course was notable for profound acute kidney injury, leukocytosis, hypotension, and cardiac dysfunction requiring ICU admission and vasopressor support. MIS-C-like illness secondary to COVID-19 was suspected due to physical exam findings of conjunctivitis, mucositis, and shock. She improved following IVIG, aspirin, and supportive care, and was discharged on hospital day 5. MIS-C-like illness should be considered in adults presenting with atypical clinical findings and concern for COVID-19. Further research is needed to support the role of IVIG and aspirin in this patient population.

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A young adult with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)-like illness: a case report.

Background Kawasaki disease (KD) is now the leading cause of acquired heart disease in children in developed countries. Intravenous immunoglobulin (IVIG) and aspirin were considered as the standard initial treatment of KD for decades. However, the optimal dose of aspirin has remained controversial. In recent years, many studies compared the efficacy of low-dose with high-dose aspirin in the acute phase of KD, but the results have not always been consistent. Therefore, we performed this meta-analysis to evaluate the efficacy of low-dose aspirin compared with high-dose for the initial treatment of KD. Methods Studies related to aspirin therapy for KD were selected from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Google scholar through Mar 25th, 2019. Data were analyzed using STATA Version 15.1. Additionally, publication bias and sensitivity analysis were also performed by STATA version 15.1. Results Six studies were included in our analysis of the rate of coronary artery lesion (CAL), five reports for IVIG-resistant KD (rKD), and four for the duration of fever and hospitalization. However, no significant differences were found between low-dose and high-dose aspirin groups in the incidence of CAL (risk ratio (RR), 0.85; 95%CI (0.63, 1.14); P = 0.28), the risk of rKD (RR, 1.39; 95%CI (1.00, 1.93); P = 0.05), and duration of fever and hospitalization (the mean standard deviation (SMD), 0.03; 95%CI (-0.16, 0.22); P = 0.78). Conclusion Low-dose aspirin (3-5 mg·kg-1·d-1) may be as effective as the use of high-dose aspirin (≥30 mg·kg-1·d-1) for the initial treatment of KD. Further well-designed randomized clinical trials are needed to evaluate the efficacy of low-dose aspirin for the initial treatment of KD.

/pdf/efficacy-between-low-and-high-dose-aspirin-for-the-initial-2ebmjr5wzb.pdf

Efficacy between low and high dose aspirin for the initial treatment of Kawasaki disease: Current evidence based on a meta-analysis.

Kawasaki disease (KD) has become the most common form of pediatric systemic vasculitis. Although patients with KD received intravenous immunoglobulin (IVIG) therapy, coronary arterial lesions (CALs) still occurred in 5%-10% of these patients during the acute stage. CALs may persist and even progress to stenosis or obstruction. Therefore, CALs following KD are currently the leading cause of acquired heart diseases in children. The etiology of CALs remains unknown despite more than four decades of research. Two unsolved problems are IVIG unresponsiveness and the diagnosis of incomplete KD. The two subgroups of KD patients with these problems have a high risk of CAL. In April 2017, the American Heart Association (AHA) updated the guidelines for the diagnosis, treatment, and long-term management of KD. Compared with the previous KD guidelines published in 2004, the new guidelines provide solutions to the aforementioned two problems and emphasize risk stratification by using coronary artery Z score systems, as well as coronary severity-based management and long-term follow-up. Therefore, in this study, we merged the AHA Scientific Statement in 2017 with recent findings for Taiwanese KD patients to provide potential future care directions for Taiwanese patients with KD.

State-of-the-art acute phase management of Kawasaki disease after 2017 scientific statement from the American Heart Association.

BACKGROUND: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA to be used. We aimed to evaluate the noninferiority of ASA at an antiplatelet dose in acute KD in preventing coronary artery (CA) abnormalities. METHODS: This is a multicenter, retrospective, nonrandomized cohort study including children 0 to 10 years of age with acute KD between 2004 and 2015 from 5 institutions, of which 2 routinely use low-dose ASA (3–5 mg/kg per day) and 3 use high-dose ASA (80 mg/kg per day). Outcomes were CA abnormalities defined as a CA diameter with a z score ≥2.5. We assessed the risk difference of CA abnormalities according to ASA dose. All subjects received ASA and intravenous immunoglobulin within 10 days of fever onset. RESULTS: There were 1213 subjects included, 848 in the high-dose and 365 in the low-dose ASA group. There was no difference in the risk of CA abnormalities in the low-dose compared with the high-dose ASA group (22.2% vs 20.5%). The risk difference adjusted for potential confounders was 0.3% (95% confidence interval [CI]: −4.5% to 5.0%). The adjusted risk difference for CA abnormalities persisting at the 6-week follow-up was −1.9% (95% CI: −5.3% to 1.5%). The 95% CI of the risk difference of CA abnormalities adjusted for confounders was within the prespecified 5% margin considered to be noninferior. CONCLUSIONS: In conjunction with intravenous immunoglobulin, low-dose ASA in acute KD is not inferior to high-dose ASA for reducing the risk of CA abnormalities.

https://pediatrics.aappublications.org/content/pediatrics/139/6/e20170098.full.pdf

Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease

Cardiac inflammatory myofibroblastic tumor (IMT) is a rare entity affecting predominantly infants, children, and young adults. Although most tumors have a benign clinical course after complete surgical resection, some have significant clinical effects. We report the case of a 9-year-old girl who had sudden cardiac death as a result of occlusion of the left circumflex coronary artery. A review of 57 cases of cardiac IMTs reported in the literature in terms of epidemiology, clinical presentation, histologic and immunohistologic features, and outcome is presented. Recognition of this rare abnormality is important in order to initiate prompt surgical intervention.

Inflammatory myofibroblastic tumor of the aortic valves causing sudden cardiac death: a case report and review of the literature.

Postnatal Recurrence and Transesophageal Inducibility of Prenatally Treated Fetal Supraventricular Tachycardia.

The biventricular contribution to chronic pulmonary hypertension of the extremely premature infant

BackgroundCoarctation of the aorta (CoA) is challenging to diagnose in early postnatal life. We aimed to describe the resource utilization and predictors for the need of intervention in an antenatal suspicion of CoA.MethodsA retrospective study of infants with an antenatal suspicion of CoA born at ≥37 weeks was performed. Those not requiring intervention (normal) were compared with those who required cardiac surgery (CoA). Strain was measured using speckle-tracking echocardiography.ResultsA total of 51 newborns were included; 40 (78%) were considered normal and 11 (22%) underwent intervention. Echocardiography occurred within the first day of life for both groups. Right ventricular (RV) predominance was present in the CoA group, as demonstrated by the left ventricular (LV) end-systolic eccentricity index (1.60 [0.28] vs 2.16 [0.45]; P < 0.001) and by a larger RV end-diastolic area (EDA) in apical 4-chamber (A4C) relative to LV-EDA—with a ratio of 1.56 [0.23] vs 1.02 [0.2]; P < 0.001. An RV/LV EDA ratio in A4C ≥1.3 had a high probability for CoA (area under the curve = 0.97). Newborns with CoA had a lower RV deformation (peak systolic strain rate: −0.98 [0.17] vs −0.83 [0.2]; P = 0.02). Intraclass correlation coefficient for the EDA ratio revealed a good inter-rater agreement (0.76; 95% confidence interval: 0.55-0.87). Analysis with rater #2 revealed that the EDA ratio ≥1.3 predicted 100% of CoA.ConclusionsThe majority of those with an antenatal suspicion of CoA did not require intervention but were high consumers of resources. Within the first day of life, the ventricular EDA ratio in A4C may help predicting those with true CoA requiring intervention. 

Claudia Renaud

Papers

Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease

Inflammatory myofibroblastic tumor of the aortic valves causing sudden cardiac death: a case report and review of the literature.

Postnatal Recurrence and Transesophageal Inducibility of Prenatally Treated Fetal Supraventricular Tachycardia.

The biventricular contribution to chronic pulmonary hypertension of the extremely premature infant

Early echocardiography predicts intervention need in antenatal suspicion of coarctation of the aorta