Correll Colleen K, Binstadt Bryce A
Division of Rheumatology, Department of Pediatrics, University of Minnesota Amplatz Children's Hospital, Minneapolis, Minnesota.
Pediatr Res. 2014 Jan;75(1-2):176-83. doi: 10.1038/pr.2013.187. Epub 2013 Nov 8.
Systemic juvenile idiopathic arthritis (s-JIA) is clinically distinct from other types of JIA. It is typified by extraarticular features such as quotidian fevers, rash, splenomegaly, lymphadenopathy, laboratory abnormalities (including leukocytosis, thrombocytosis, anemia, hyperferritinemia, and elevated inflammatory markers), and a close association with the macrophage activation syndrome. Recent investigations have highlighted dysregulation of the innate immune system as the critical pathogenic driver of s-JIA. Key innate immune mediators of s-JIA are the macrophage-derived cytokines interleukin-1 (IL-1) and IL-6. Increased understanding of the roles of IL-1 and IL-6 in the pathogenesis of s-JIA has led to major changes in therapeutic options. Until recently, the most commonly used medications included corticosteroids, methotrexate, and tumor necrosis factor (TNF) inhibitors, which are incompletely effective in most cases. Newer biologic agents targeting IL-1 and IL-6 have proven very effective in treating s-JIA and in minimizing corticosteroid exposure. Here we review recent advances in the understanding of the pathogenesis of s-JIA and the recent clinical trials that have revolutionized the care of children with s-JIA.
全身型幼年特发性关节炎（s-JIA）在临床上与其他类型的幼年特发性关节炎不同。其典型表现为关节外特征，如每日发热、皮疹、脾肿大、淋巴结病、实验室检查异常（包括白细胞增多、血小板增多、贫血、高铁蛋白血症和炎症标志物升高），以及与巨噬细胞活化综合征密切相关。最近的研究强调先天性免疫系统失调是s-JIA的关键致病驱动因素。s-JIA的关键先天性免疫介质是巨噬细胞衍生的细胞因子白细胞介素-1（IL-1）和白细胞介素-6。对IL-1和IL-6在s-JIA发病机制中作用的进一步了解导致了治疗选择的重大变化。直到最近，最常用的药物包括皮质类固醇、甲氨蝶呤和肿瘤坏死因子（TNF）抑制剂，这些药物在大多数情况下效果并不完全理想。针对IL-1和IL-6的新型生物制剂已被证明在治疗s-JIA和尽量减少皮质类固醇暴露方面非常有效。在此，我们综述了对s-JIA发病机制的最新认识进展以及最近彻底改变s-JIA患儿治疗的临床试验。
