Presence of coronary aneurysms during Kawasaki Disease (KD) correlates with lower levels of autoantibodies to both full form and spliced variant of immune regulator Del-1.

Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium. Del-1 has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against DEL-1 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not overall higher in children with KD. Elevation in Post-IVIG samples in comparison to pre-IVIG and convalescent samples supports the commonality of anti-Del-1 antibodies. Autoantibodies were notably lower in children with KD who had coronary Z score elevations in comparison to those who did not.

Immune and non-immune mechanisms that determine vasculitis and coronary artery aneurysm topography in Kawasaki disease and MIS-C.

The overlap between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) including coronary artery aneurysms (CAA) and broadly shared gastrointestinal and mucocutaneous disease is poorly defined. In this perspective, we highlight common age-related extravascular epicardial microanatomical and immunological factors that might culminate in CAA expression in both MIS-C and KD. Specifically, the coronary vasa vasorum originates outside the major coronary arteries. Widespread inflammation in the epicardial interstitial compartment in shared between KD and MIS-C. Age-related changes in the neonatal and immature coronary vasculature including the impact of coronary artery biomechanical factors including coronary vessel calibre, age-related vessel distensibility, flow, and vessel neurovascular innervation may explain the decreasing CAA frequency from neonates to older children and the virtual absence of CAA in young adults with the MIS-C phenotype. Other KD and MIS-C features including mucocutaneous disease with keratinocyte-related immunopathology corroborate that disease phenotypes are centrally influenced by inflammation originating outside vessel walls but a potential role for primary coronary artery vascular wall inflammation cannot be excluded. Hence, common extravascular originating tissue-specific responses to aetiologically diverse triggers including superantigens may lead to widespread interstitial tissue inflammation characteristically manifesting as CAA development, especially in younger subjects. Given that CAA is virtually absent in adults, further studies are needed to ascertain whether epicardial interstitial inflammation may impact on both coronary artery physiology and cardiac conduction tissue and contribute to cardiovascular disease- a hitherto unappreciated consideration.

Cyclosporine for the treatment of multisystem inflammatory syndrome in children with coronary artery aneurysms.

Multisystem inflammatory syndrome in children (MIS-C) is a newly described syndrome related to the COVID-19, resembling other known aetiologies, including Kawasaki disease. Cardiovascular involvement is common; left ventricle dysfunction and coronary artery aneurysm (CAA) are also observed. Many treatment guidelines recommend using intravenous immunoglobulin (IVIG) alone or with glucocorticoids as the first-line therapy. Biological agents, such as anakinra, are recommended for refractory cases, but the evidence is still accumulating. Moreover, the use of other treatment agents can be beneficial, especially when anakinra is unavailable. Here, we report the case of a 9-year-old girl who presented with MIS-C with CAAs. She received cyclosporine because two rounds of IVIG treatment were ineffective and the use of anakinra is not approved in Japan. Her cytokine profile showed that cyclosporine prevented exacerbation. The case highlights that cyclosporine therapy can be an option for the treatment of refractory MIS-C with CAA.

Coronary Artery Changes in Patients with Multisystem Inflammatory Syndrome in Children: Los Angeles Experience.

We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.

Understanding the Educational Support and Psychosocial Needs of Parents and Adolescents With Kawasaki's Disease and Coronary Artery Aneurysms.

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.

Anterior wall myocardial infarction in a 16-year-old man caused by coronary artery aneurysm during the outbreak of COVID-19.

BACKGROUND: Coronary artery aneurysm (CAA) is a potential cause of infarction. During the outbreak of coronavirus disease 2019 (COVID-19), home isolation and activity reduction can lead to hypercoagulability. Here, we report a case of sudden acute myocardial infarction caused by large CAA during the home isolation. CASE PRESENTATION: During the outbreak of coronavirus disease 2019 (COVID-19),a 16-year-old man with no cardiac history was admitted to CCU of Tang du hospital because of severe chest pain for 8 h. The patient reached the hospital its own, his electrocardiogram showed typical features of anterior wall infarction, echocardiography was performed and revealed local anterior wall dysfunction, but left ventricle ejection fraction was normal, initial high-sensitivity troponin level was 7.51 ng/mL (<1.0 ng/mL). The patient received loading dose of aspirin and clopidogrel bisulfate and a total occlusion of the LAD was observed in the emergency coronary angiography (CAG). After repeated aspiration of the thrombus, TIMI blood flow reached level 3. Coronary artery aneurysm was visualized in the last angiography. No stent was implanted. Intravascular ultrasound (IVUS) was performed and the diagnosis of coronary artery aneurysm was further confirmed. The patient was discharged with a better health condition. CONCLUSIONS: Coronary artery aneurysm is a potential reason of infarction, CAG and IVUS are valuable tools in diagnosis in such cases, during the outbreak of coronavirus disease 2019 (COVID-19), home isolation and activity reduction can lead to hypercoagulability, and activities at home should be increased in the high-risk patients.