Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as a complex cytokine storm. This hyperactive immune response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements in its treatment. The cytokine storm plays a crucial role in the treatment of HLH. Investigating the detailed mechanisms behind cytokine storms offers insights into targeted therapeutic approaches, potentially aiding in early intervention and improving the clinical outcome of HLH patients. To date, there is only one targeted therapy, emapalumab targeting interferon-γ, that has gained approval for primary HLH. This review aims to summarize the current treatment advances, emerging targeted therapeutics and underlying mechanisms of HLH, highlighting its newly discovered targets potentially involved in cytokine storms, which are expected to drive the development of novel treatments and offer fresh perspectives for future studies. Besides, multi-targeted combination therapy may be essential for disease control, but further trials are required to determine the optimal treatment mode for HLH.

中文翻译：

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噬血细胞性淋巴组织细胞增生症：目前的治疗进展、新兴的靶向治疗和潜在机制


噬血细胞性淋巴组织细胞增生症 （HLH） 是一种快速进展、危及生命的综合征，其特征是免疫激活过度，通常表现为复杂的细胞因子风暴。这种过度活跃的免疫反应会导致多器官衰竭和全身损伤，如果不及时治疗，会导致生存期极短。在过去的几十年里，尽管 HLH 越来越受到研究人员的关注，但其治疗几乎没有进展。细胞因子风暴在 HLH 的治疗中起着至关重要的作用。研究细胞因子风暴背后的详细机制可深入了解靶向治疗方法，可能有助于早期干预和改善 HLH 患者的临床结果。迄今为止，只有一种靶向治疗，即靶向干扰素-γ的 emapalumab，已获批用于治疗原发性 HLH。本文旨在总结目前的治疗进展、新兴的靶向治疗和 HLH 的潜在机制，重点介绍其新发现的可能参与细胞因子风暴的靶点，有望推动新疗法的开发，并为未来的研究提供新的视角。此外，多靶点联合治疗对于疾病控制可能是必不可少的，但需要进一步的试验来确定 HLH 的最佳治疗模式。