Wagner Yuval, Adam Dganit, Pomeranz Engelberg Galit, Pomeranz Avishalom, Messinger Yoav H
Pediatric Department, Meir Medical Center, Kfar Saba, Israel.
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Pediatric Health Med Ther. 2024 Mar 7;15:111-120. doi: 10.2147/PHMT.S446681. eCollection 2024.
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory cytokine storm. It can be secondary to infections, malignancies, autoimmune diseases, or the manifestation of genetic disorders, including primary immune deficiency. HLH requires a high index of suspicion and is challenging for community hospitals.
Medical records of children with HLH admitted to the Meir Medical Center in Israel between 2014 and 2017 were reviewed.
Nine children met ≥5/8 HLH-2004 criteria. The median age was 1.1 year, and 78% of the patients were aged <2 years. All patients had prolonged fever, cytopenia, and elevated soluble interleukin-2 receptor, and 89% had elevated ferritin levels. Of three children who underwent gene panel evaluation, one had heterozygote genetic variants of and of unclear significance, whereas the other two had no variants. Infection was identified in 8 of 9 patients: adenovirus, HHV6, EBV, and Streptococcus Group A. Only 2 patients received HLH-2004 therapy (dexamethasone, etoposide, cyclosporin-A) and the others received dexamethasone and/or intravenous gamma globulins (IVIG), with rapid resolution of fever (median 2 days). One patient (11%) died of Pseudomonas septicemia and multiorgan failure. At a median follow-up of 7 years (range 2.6-8.1 years), all others (8/9) are long-term survivors with no recurrent HLH, but 2 patients developed adenovirus-related bronchiolitis obliterans.
Children presenting with prolonged fever and abnormal blood counts should be evaluated with ferritin, triglycerides, and fibrinogen levels which indicate possible HLH. Early intervention with corticosteroids and/or IVIG may prevent deterioration, spare them from chemotherapy and provide time for more elaborate testing to identify true HLH. Unfortunately, mortality remains a significant risk for these children.
噬血细胞性淋巴组织细胞增生症（HLH）是一种潜在致命的高炎症性细胞因子风暴。它可能继发于感染、恶性肿瘤、自身免疫性疾病或遗传性疾病的表现，包括原发性免疫缺陷。HLH需要高度怀疑，对社区医院来说具有挑战性。
回顾了2014年至2017年期间入住以色列梅尔医学中心的HLH患儿的病历。
9名儿童符合≥5/8的HLH-2004标准。中位年龄为1.1岁，78%的患者年龄<2岁。所有患者均有长期发热、血细胞减少和可溶性白细胞介素-2受体升高，89%的患者铁蛋白水平升高。在接受基因检测的3名儿童中，1名有意义不明的 和 的杂合子基因变异，而另外两名没有变异。9名患者中有8名确诊感染：腺病毒、HHV6、EBV和A组链球菌。只有2名患者接受了HLH-2004治疗（地塞米松、依托泊苷、环孢素A），其他患者接受了地塞米松和/或静脉注射丙种球蛋白（IVIG），发热迅速消退（中位时间2天）。1名患者（11%）死于铜绿假单胞菌败血症和多器官功能衰竭。中位随访7年（范围2.6 - 8.1年），其他所有患者（8/9）均为长期存活者，无HLH复发，但2名患者发生了腺病毒相关的闭塞性细支气管炎。
出现长期发热和血常规异常的儿童应检测铁蛋白、甘油三酯和纤维蛋白原水平，以评估是否可能患有HLH。早期使用皮质类固醇和/或IVIG进行干预可能预防病情恶化，使他们无需接受化疗，并为更详细的检测留出时间以确诊真正的HLH。不幸的是，这些儿童的死亡率仍然很高。
