Brik Simon Dafna, Yacobovich Joanne
Rina Zaizov Pediatric Hematology Oncology Division, Schneider Children's Medical Center of Israel, Petach Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israe.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, Hematology Unit, Rina Zaizov Pediatric Hematology Oncology Division, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Harefuah. 2023 Jan;162(1):31-36.
To characterize the clinical, demographic, laboratory, and molecular biologic findings in children with HLH diagnosed and treated in our center.
Hemophagocytic lymphohistiocytosis (HLH) is a rare immuno-hematologic disorder more common in children than adults. It is divided into two separate conditions which are not always easy to differentiate: familial/primary HLH (FHL) and acquired/secondary HLH associated with malignant, infectious, and other inflammatory conditions. FHL is a life-threatening disorder caused mainly by mutations in genes that code for proteins participating in perforin-dependent cell death.
We collected data from the records of all children who were diagnosed with HLH according to the accepted HLH criteria, and treated in the Schneider Children's Medical Center of Israel between the years 2004-2020. Demographic, clinical and laboratory data were summarized into a national database.
A total of 36 children (18 boys,18 girls) who were diagnosed as having HLH according to the diagnostic criteria and received treatment according to the Histiocyte Society '94 or 2004 international protocols, entered the study. Eleven of the patients were Arab (30%), while 25 were Jewish (70%). The most frequent clinical signs were fever (89%) and hepatosplenomegaly (61%). Laboratory tests showed bipenia in 100% and increased levels of Interleukin-2 receptor (IL-2R) in 97%. Mutations in 3 out of the 4 common HLH genes were found in 15 (42%) children. The most common mutant gene was MUNC 13-4 comprising 40% of mutant genes. Mutations were quite common among Arab patients (81%) compared to the Jewish HLH population (20%) (p<0.001). Patients bi-allelic MUNC 13-4 mutations had a particularly poor prognosis with 66% succumbing to the disease.
HLH is a severe, multisystem disorder. High clinical suspicion leading to timely diagnosis and treatment are crucial for preventing poor outcome and death. Genetic studies are of upmost importance in our population due to the high percentage of mutations, especially in the Arab population.
描述在我们中心诊断和治疗的噬血细胞性淋巴组织细胞增生症（HLH）患儿的临床、人口统计学、实验室及分子生物学特征。
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的免疫血液系统疾病，在儿童中比成人更常见。它分为两种不同的情况，并不总是容易区分：家族性/原发性HLH（FHL）和与恶性、感染及其他炎症性疾病相关的获得性/继发性HLH。FHL是一种危及生命的疾病，主要由编码参与穿孔素依赖性细胞死亡的蛋白质的基因突变引起。
我们从2004年至2020年间在以色列施耐德儿童医学中心根据公认的HLH标准诊断并接受治疗的所有患儿的病历中收集数据。人口统计学、临床和实验室数据被汇总到一个国家数据库中。
共有36名根据诊断标准被诊断为HLH并按照组织细胞协会1994年或2004年国际方案接受治疗的患儿进入研究。其中11名患者是阿拉伯人（30%），25名是犹太人（70%）。最常见的临床症状是发热（89%）和肝脾肿大（61%）。实验室检查显示100%有全血细胞减少，97%白细胞介素-2受体（IL-2R）水平升高。15名（42%）患儿中发现4种常见HLH基因中的3种存在突变。最常见的突变基因是MUNC 13-4，占突变基因的40%。与犹太HLH人群（20%）相比，突变在阿拉伯患者中相当常见（81%）（p<0.001）。双等位基因MUNC 13-4突变的患者预后特别差，66%死于该疾病。
HLH是一种严重的多系统疾病。高度的临床怀疑从而实现及时诊断和治疗对于预防不良结局和死亡至关重要。由于突变比例高，尤其是在阿拉伯人群中，基因研究在我们的人群中至关重要。
