Division of Pediatric Rheumatology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA.
Curr Opin Rheumatol. 2022 Sep 1;34(5):274-279. doi: 10.1097/BOR.0000000000000889. Epub 2022 Jul 5.
Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affecting children. MIS-C shares features with Kawasaki disease (KD) and cytokine storm syndrome (CSS) frequently requiring intensive care support. Although intravenous immunoglobulin (IVIg) and glucocorticoids (GCs) are effective therapeutics for most, refractory MIS-C is treated with various biologic disease-modifying antirheumatic drugs (bDMARDs). Understanding the clinical features, inflammatory cytokines, and genetic associations provides rationale for bDMARD in treating severe MIS-C.
Children with MIS-C have clinical KD features and often present in hypovolemic and cardiogenic shock requiring volume repletion (gastrointestinaI losses) and cardiac pressor support (epinephrine). Investigation of MIS-C serum reveals elevated pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18, interferon gamma (IFNγ), tumor necrosis factor (TNF)], but to a lesser extent than other established CSS. Gene sequencing of MIS-C children identifies heterozygous mutations in CSS associated genes. Treatment of refractory (IVIg and GC) MIS-C with bDMARDs to IL-1, IL-6, and TNF is efficacious for survival as well as resolving cardiac and coronary artery inflammation.
MIS-C is a postinfectious complication of SARS-CoV-2 resembling KD and CSS, both genetically and by pro-inflammatory cytokines. MIS-C that is refractory to IVIg and GC is routinely responsive to bDMARDs targeting IL-1, IL-6, and TNF.
儿童多系统炎症综合征（MIS-C）是严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的一种感染后并发症，主要影响儿童。MIS-C 与川崎病（KD）和细胞因子风暴综合征（CSS）有共同特征，经常需要重症监护支持。虽然静脉注射免疫球蛋白（IVIg）和糖皮质激素（GCs）对大多数患者有效，但难治性 MIS-C 则使用各种生物疾病修饰抗风湿药物（bDMARDs）治疗。了解临床特征、炎症细胞因子和遗传关联为治疗严重 MIS-C 使用 bDMARD 提供了依据。
MIS-C 患儿具有 KD 的临床特征，常表现为低血容量性和心源性休克，需要补充血容量（胃肠道丢失）和心脏加压支持（肾上腺素）。对 MIS-C 血清的研究表明，促炎细胞因子[白细胞介素（IL）-1、IL-6、IL-18、干扰素 γ（IFNγ）、肿瘤坏死因子（TNF）]水平升高，但程度低于其他已确立的 CSS。对 MIS-C 患儿进行基因测序，发现与 CSS 相关的基因存在杂合突变。对于难治性（IVIg 和 GC）MIS-C，使用 bDMARD 治疗 IL-1、IL-6 和 TNF 对生存和缓解心脏和冠状动脉炎症均有效。
MIS-C 是 SARS-CoV-2 的一种感染后并发症，与 KD 和 CSS 在遗传和促炎细胞因子方面具有相似性。对 IVIg 和 GC 治疗无效的 MIS-C 通常对靶向 IL-1、IL-6 和 TNF 的 bDMARD 有反应。
