继发性噬血细胞性淋巴组织细胞增多症的诊断与治疗

doi:10.16150/j.1671-2870.2026.01.001

摘要/Abstract

摘要：

继发性噬血细胞性淋巴组织细胞增多症（secondary hemophagocytic lymphohistiocytosis，sHLH）是一种诱因和临床表现多样、病情凶险的过度炎症反应综合征，其早期识别与精准分类是有效治疗的前提。近年来，sHLH的诊疗取得了重要进展。笔者整合现有的指南、专家共识和临床研究证据，对sHLH的诊断和治疗进展进行系统性梳理。诊断方面，除了经典的HLH-2004标准，HScore评分系统及优化HLH炎症指数（inflammatory index, OHI）等新兴诊断工具提高了早期识别sHLH的准确率。sHLH可由多种内外源性因素触发，常见的病因分类包括感染相关HLH、恶性肿瘤相关HLH、巨噬细胞活化综合征、免疫治疗相关HLH以及移植相关HLH，其临床特征、实验室指标均存在差异，熟知这些特征差异将有助于分类鉴别和治疗指导。sHLH的治疗原则包括积极处理疑似诱发HLH的基础疾病，以及实施针对异常免疫激活与过度炎症反应的特异性治疗。若患者病情稳定且诱因明确，系统性治疗基础疾病并提供充分支持已足够；若患者出现病情恶化，应立即启动特异性治疗。特异性治疗方案中，除了经典的化疗方案，针对细胞因子等的靶向治疗也显示出良好疗效，成为改善sHLH患者预后的重要手段。

关键词: 继发性噬血细胞性淋巴组织细胞增多症, 过度炎症反应, 感染, 恶性肿瘤

Abstract:

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory syndrome characterized by diverse triggers and clinical manifestations. Early recognition and precise classification of sHLH are prerequisites for effective treatment. In recent years, significant progress has been made in the diagnosis and treatment of sHLH. This study systematically reviews the advances in the diagnosis and treatment of sHLH by integrating existing guidelines, expert consensus, and evidence from clinical research. In terms of diagnosis, in addition to the classic HLH-2004 criteria, emerging diagnostic tools such as the HScore scoring system and the optimized HLH inflammatory index (OHI) have improved the accuracy of early detection of sHLH. sHLH can be triggered by various endogenous and exogenous factors. Common etiological classifications include infection-associated HLH, malignant-tumor-associated HLH, macrophage activation syndrome, immunotherapy-associated HLH, and transplantation-associated HLH. Their clinical features and laboratory indicators differ, and understanding these characteristic differences is essential for classification, differential diagnosis, and treatment guidance. The treatment principles for sHLH include actively addressing the underlying condition suspected of inducing HLH, as well as implementing targeted treatment to control abnormal immune activation and excessive inflammatory responses. If the patient is stable and the trigger is clearly identified, systemic treatment of the underlying disease along with adequate support is sufficient. If the patient's condition deteriorates, specific treatment should be initiated immediately. In terms of specific treatment schemes, in addition to conventional chemotherapy, targeted therapies, particularly those against cytokines, have demonstrated favorable efficacy and have become crucial strategies for improving the prognosis of sHLH patients.

Key words: Secondary hemophagocytic lymphohistiocytosis, Excessive inflammatory response, Infection, Malignant tumor

中图分类号:

R446
R55

郭涛, 谢梦雨. 继发性噬血细胞性淋巴组织细胞增多症的诊断与治疗[J]. 诊断学理论与实践, 2026, 25(01): 1-8.

GUO Tao, XIE Mengyu. Diagnosis and treatment of secondary hemophagocytic lymphohistiocytosis[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(01): 1-8.

图/表 2

表1

表2

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评估参数	评分标准（得分）
已知潜在免疫抑制^a	否（0分）；是（18分）
体温（℃)	<38.4 ℃（0分）；38.4 ℃~39.4 ℃（33分）；>39.4℃（49分）
器官肿大	无（0分）；肝肿大或脾肿大（23分）；肝脾均肿大（38分）
血细胞减少系别数^b	1系（0分）；2系（24分）；3系（34分）
血清铁蛋白	<2 000 ng/mL（0分）；2 000~6 000 ng/mL（35分）；> 6 000 ng/mL（50分）
甘油三酯	<1.5 mmol/L（0分）；1.5~4.0 mmol/L（44分）；> 4.0 mmol/L（64分）
纤维蛋白原	>2.5 g/L（0分）；≤2.5 g/L（30分）
谷草转氨酶	<30 U/L（0分）；≥30 U/L（19分）
骨髓穿刺见噬血现象	否（0分）；是（35分）

sHLH分类类型	主要诱因/背景	特征性实验室/临床指标	诊断标准 / 工具
感染相关	病毒（以EBV最常见）最常见，其次为细菌、真菌、寄生虫等	CD8⁺ T细胞中CD38⁺/HLA-DR+ >7%，CD4^dimCD8⁺ T细胞高度活化	HLH-2004标准
恶性肿瘤相关	淋巴瘤最常见	OHI指数（sCD25>3 900 U/mL 且铁蛋白>1 000 ng/mL），sCD25/铁蛋白比值≥2.0	HLH-2004标准；HScore；OHI指数
巨噬细胞活化综合征	风湿免疫性疾病（全身型幼年特发性关节炎、SLE、成人斯蒂尔病等）	铁蛋白>10 000 ng/mL，血沉下降与CRP分离(假性正常化)，IL-18>2 438 pg/mL^[17]	HLH-2004标准；PRINTO标准；MAS初步指南
免疫治疗相关	CAR-T 治疗、免疫检查点抑制剂（ICI）	HGF、铁蛋白、CXCL9、IL-10、IL-18、IL-1RA等升高	HLH-2004标准
移植相关	造血干细胞移植后感染或使用ICI抗排异治疗	常伴严重感染，缺乏特异性指标	HLH-2004标准；HScore