Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Curr Opin Allergy Clin Immunol. 2011 Dec;11(6):512-6. doi: 10.1097/ACI.0b013e32834c22f5.
Hemophagocytic lymphohistiocytosis (HLH) is more widely recognized by clinicians. No longer viewed as a disorder of young children, adult patients are now being identified and treated. In this review, I summarize clinical features of patients with recently identified genetic causes, discuss a new paradigm for understanding the clinical evolution of HLH, and update current results with hematopoietic cell transplantation.
The list of genetic defects underlying HLH continues to grow. Among the autosomal recessive defects underlying HLH, we add STX11 (Syntaxin 11) - a snare protein, and MUNC18-2 (also known as STXBP2 - Syntaxin-binding protein). These two proteins now join MUNC 13-4 as components of the degranulation machinery in cytotoxic lymphocytes, responsible for the delivery of Perforin and Granzyme B to selectively kill target cells. The mechanism of action in the newest X-linked disorder associated with HLH, XIAP deficiency (also termed XLP 2), is currently unknown. Treatment of HLH has also improved in recent years, at least in experienced centers where a significant number of patients are seen. Clinicians who are familiar with the dynamic evolution of the disease are learning how to modify treatment when initial or continuation therapy fails to achieve a stable clinical status, preferably clinical remission. Use of reduced intensity conditioning protocols pretransplant has resulted in superior short-term and long-term survival rates of greater than 85%.
Substantial progress continues to be made in exploring the complex cause and pathophysiology of HLH. Hand in hand, a greater recognition of the condition has led to improved treatments.
噬血细胞性淋巴组织细胞增生症（HLH）越来越受到临床医生的重视。HLH 不再被认为是一种儿童疾病，现在也有成年患者被诊断和治疗。在这篇综述中，我总结了最近发现的遗传原因导致的 HLH 患者的临床特征，讨论了理解 HLH 临床演变的新范例，并更新了造血细胞移植的最新结果。
导致 HLH 的遗传缺陷的清单继续增加。在导致 HLH 的常染色体隐性缺陷中，我们增加了 STX11（Syntaxin 11）-一种囊泡蛋白，和 MUNC18-2（也称为 STXBP2-Syntaxin 结合蛋白）。这两种蛋白现在与 MUNC13-4 一起成为细胞毒性淋巴细胞脱颗粒机制的组成部分，负责将穿孔素和颗粒酶 B 递送到靶细胞以选择性杀伤靶细胞。与 HLH 相关的最新 X 连锁疾病 XIAP 缺乏症（也称为 XLP2）的作用机制目前尚不清楚。近年来，HLH 的治疗也有所改善，至少在有大量患者就诊的经验丰富的中心是这样。熟悉疾病动态演变的临床医生正在学习如何在初始或维持治疗未能达到稳定的临床状态时，即临床缓解时，修改治疗方法。移植前使用强度降低的预处理方案可导致短期和长期生存率均超过 85%。
在探索 HLH 的复杂病因和病理生理学方面仍在继续取得重大进展。与此同时，对该疾病的认识提高导致了治疗方法的改进。
