Division of Rheumatology, Seattle Children's Hospital, Seattle, WA, USA.
Division of Rheumatology, Seattle Children's Hospital, Seattle, WA, USA.
Best Pract Res Clin Rheumatol. 2020 Aug;34(4):101515. doi: 10.1016/j.berh.2020.101515. Epub 2020 May 7.
Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening state of immune hyperactivation that arises in the setting of genetic mutations and infectious, inflammatory, or neoplastic triggers. Sustained, aberrant activation of cytotoxic CD8 T cells and resultant inflammatory cytokine release are core pathogenic mechanisms. Key clinical features include high persistent fever, hepatosplenomegaly, blood cytopenia, elevated aminotransferase and ferritin levels, and coagulopathy. HLH is likely under-recognized, and mortality remains high, especially in adults; thus, prompt diagnosis and treatment are essential. Familial forms of HLH are currently treated with chemotherapy as a bridge to hematopoietic stem cell transplantation. HLH occurring in rheumatic disease (macrophage activation syndrome) is treated with glucocorticoids, IL-1 blockade, or cyclosporine A. In other forms of HLH, addressing the underlying trigger is essential. There remains a pressing need for more sensitive, context-specific diagnostic tools. Safer, more effective therapies will arise with improved understanding of the cellular and molecular mechanisms of HLH.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的、危及生命的免疫过度激活状态，可由遗传突变以及感染、炎症或肿瘤触发。细胞毒性 CD8 T 细胞的持续异常激活和由此产生的炎症细胞因子释放是核心发病机制。主要临床特征包括持续性高热、肝脾肿大、血细胞减少、转氨酶和铁蛋白水平升高以及凝血功能障碍。HLH 可能认识不足，死亡率仍然很高，尤其是在成年人中；因此，及时诊断和治疗至关重要。家族性 HLH 目前采用化疗作为造血干细胞移植的桥梁治疗。风湿性疾病（巨噬细胞活化综合征）引起的 HLH 采用糖皮质激素、IL-1 阻断或环孢素 A 治疗。其他类型的 HLH 则需要针对潜在触发因素进行治疗。迫切需要更敏感、更具针对性的诊断工具。随着对 HLH 的细胞和分子机制的深入了解，将出现更安全、更有效的治疗方法。
