Diagnosis and treatment of secondary hemophagocytic lymphohistiocytosis

doi:10.16150/j.1671-2870.2026.01.001

Abstract

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

CLC Number:

R446
R55

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

Figures/Tables 2

Table 1

Table 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