Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Coronary artery assessment in Kawasaki disease with dual-source CT angiography to uncover vascular pathology.

BACKGROUND: Kawasaki disease (KD) is a vasculitis with formation of coronary artery aneurysms (CAAs) that can lead to myocardial ischemia. Echocardiography is the primary imaging modality for the coronary arteries despite limited visualization. Coronary angiography (CAG) is the gold standard yet invasive with high-radiation exposure. To date however, state-of-the-art CT scanners enable high-quality low-dose coronary computed tomographic angiography (cCTA) imaging. The aim of our study in KD is to report (i) the diagnostic yield of cCTA compared to echocardiography, and (ii) the radiation dose. METHODS AND RESULTS: We collected data of KD patients who underwent cCTA. cCTA findings were compared with echocardiography results. In 70 KD patients (median age 15.1 years [0.5-59.5 years]; 78% male; 38% giant CAA), the cCTA identified 61 CAAs, of which 34 (56%, with a Z score > 3, in 22 patients) were not detected by echocardiography. In addition, the left circumflex (aneurysmatic in 6 patients) was always visible upon cCTA and not detected upon echocardiography. Calcifications, plaques, and/or thrombi were visualized by cCTA in 25 coronary arteries (15 patients). Calcifications were seen as early as 2.7 years after onset of disease. In 5 patients, the cCTA findings resulted in an immediate change of treatment. The median effective dose (ED) in millisievert differed significantly (p < 0.01) between third-generation dual-source and other CT scanners (1.5 [0.3-9.4] (n = 56) vs 3.8 [1.7-20.0] (n = 14)). CONCLUSIONS: The diagnostic yield of third-generation dual-source cCTA combined with reduced radiation exposure makes cCTA a favorable diagnostic modality to complete the diagnosis and long-term treatment indications for KD. KEY POINTS: • cCTA is a favorable diagnostic modality to complete the diagnosis and long-term treatment indications for Kawasaki disease. • Kawasaki disease patients with proven coronary artery involvement on echocardiography require additional imaging.

Dissecting Kawasaki disease: a state-of-the-art review.

Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. The diagnosis is based on the presence of persistent fever and clinical features including exanthema, lymphadenopathy, conjunctival injection, and changes to the mucosae and extremities. Although the etiology remains unknown, the current consensus is that it is likely caused by an (infectious) trigger initiating an abnormal immune response in genetically predisposed children. Treatment consists of high dose intravenous immunoglobulin (IVIG) and is directed at preventing the development of CAA. Unfortunately, 10-20% of all patients fail to respond to IVIG and these children need additional anti-inflammatory treatment. Coronary artery lesions are diagnosed by echocardiography in the acute and subacute phases. Both absolute arterial diameters and z-scores, adjusted for height and weight, are used as criteria for CAA. Close monitoring of CAA is important as ischemic symptoms or myocardial infarction due to thrombosis or stenosis can occur. These complications are most likely to arise in the largest, so-called giant CAA. Apart from the presence of CAA, it is unclear whether KD causes an increased cardiovascular risk due to the vasculitis itself. CONCLUSION: Many aspects of KD remain unknown, although there is growing knowledge on the etiology, treatment, and development and classification of CAA. Since children with previous KD are entering adulthood, long-term follow-up is increasingly important. What is known: • Kawasaki disease (KD) is a pediatric vasculitis with coronary artery damage as its main complication. • Although KD approaches its 50th birthday since its first description, many aspects of the disease remain poorly understood. What is new: • In recent years, multiple genetic candidate pathways involved in KD have been identified, with recently promising information about the ITPKC pathway. • As increasing numbers of KD patients are reaching adulthood, increasing information is available about the long-term consequences of coronary artery damage and broader cardiovascular risk.