Hemophagocytic Lymphohistiocytosis in Pregnancy: A Systematic Review of Case Reports and Case Series

IF 9.9 1区医学 Q1 HEMATOLOGY

American Journal of Hematology Pub Date : 2025-07-22 DOI:10.1002/ajh.70013

Ali Abdelhay, Basant Eltaher, Mouna Reghis, Aditya Sanjeevi, Aniket-vijay Rao, Zachary Teibel, Daniel Grace, Peter Kouides

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引用次数: 0

Abstract

Aims

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome caused by excessive immune activation, leading to severe inflammation and multi-organ failure. While adult-onset HLH is well documented, pregnancy-related HLH remains under investigated, with limited data on its triggers, presentation, and management. We systematically review cases of pregnancy-related HLH in the literature, focusing on presentations, triggers, utilized treatments, and outcomes.

Methods

A systematic search of PubMed and Embase identified case reports and series describing HLH during pregnancy or postpartum. Data were extracted and analyzed using standardized methods, including frequency distributions for categorical variables and means with standard deviations for continuous variables. Quality was assessed using the Joanna Briggs Institute checklist. Statistical analysis was conducted using IBM SPSS version 26.

Results

The initial search identified 838 records, from which 66 case reports and 7 case series were included, covering 104 unique patients. The mean age of the patients was 29 years (SD 5.6 years). Presentations occurred between 7 weeks of gestation and up to 7 months after delivery; of these, 82.5% presented antepartum at an average gestational age of 24 weeks (SD 7.9 weeks), while 17.5% presented postpartum. Fever (100%), anemia (90.7%), and elevated ferritin levels (> 1000 ng/mL in 95.1%) were the most common findings. Infections were the most frequent triggers (42 patients, 40.4%), with Epstein–Barr virus (EBV) being the most frequently implicated pathogen (10 patients, 9.6%). Other triggers included systemic lupus erythematosus (10 patients, 9.6%), Adult-onset Still's Disease (7 patients, 6.7%), lymphoma (6 patients, 5.8%), and no identifiable trigger in 42 patients (40.4%). Regarding treatment, corticosteroids were used in 93.3% of cases, etoposide in 35.6%, cyclosporine in 17.3%, and intravenous immunoglobulins (IVIG) in 26%. Delivery stabilized or reversed the disease in 40.4% of cases. However, 45.6% of patients with prepartum onset experienced pregnancy loss. Nineteen patients (18.3%) died due to HLH.

Conclusion

This review highlights the distinct characteristics and challenges of HLH in pregnancy. Early diagnosis, a multidisciplinary approach, and individualized treatment strategies are crucial for improving maternal and fetal outcomes.

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妊娠期的噬血细胞性淋巴组织细胞增多症：病例报告和病例系列的系统回顾

噬细胞性淋巴组织细胞增多症（HLH）是一种罕见的、危及生命的综合征，由过度的免疫激活引起，可导致严重的炎症和多器官功能衰竭。虽然成人发病的HLH有很好的记录，但与妊娠相关的HLH仍在调查中，其触发、表现和管理方面的数据有限。我们系统地回顾了文献中与妊娠相关的HLH病例，重点关注表现、触发因素、使用的治疗方法和结果。方法系统检索PubMed和Embase，确定妊娠或产后描述HLH的病例报告和系列。使用标准化方法提取和分析数据，包括分类变量的频率分布和连续变量的标准差均值。使用乔安娜布里格斯研究所的检查表来评估质量。采用IBM SPSS version 26进行统计分析。结果初步检索到838份记录，其中包括66份病例报告和7个病例系列，涵盖104例独特患者。患者平均年龄29岁（SD 5.6岁）。出现在妊娠7周至分娩后7个月之间；其中，82.5%出现在平均胎龄24周（SD 7.9周）的产前，17.5%出现在产后。发烧（100%），贫血（90.7%），铁蛋白水平升高(>；1000 ng/mL（95.1%）是最常见的发现。感染是最常见的诱因（42例，40.4%），EBV是最常见的病原体（10例，9.6%）。其他触发因素包括系统性红斑狼疮（10例，9.6%）、成人发病斯蒂尔氏病（7例，6.7%）、淋巴瘤（6例，5.8%），42例（40.4%）患者无可识别的触发因素。在治疗方面，使用糖皮质激素的占93.3%，依托泊苷占35.6%，环孢素占17.3%，静脉注射免疫球蛋白（IVIG）占26%。40.4%的病例分娩后病情稳定或逆转。然而，45.6%的孕前发病患者出现妊娠丢失。19例（18.3%）患者死于HLH。结论本综述强调了妊娠期HLH的独特特点和挑战。早期诊断，多学科的方法，和个性化的治疗策略是改善母婴结局的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Hematology 医学-血液学

CiteScore

15.70

自引率

3.90%

发文量

363

审稿时长

3-6 weeks

期刊介绍： The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.