Department of Health Sciences, University of Florence, Florence, Italy.
Immunology Division, Section of Pediatrics, Meyer Childrens Hospital IRCCS, Florence, Italy.
Front Immunol. 2024 Feb 13;15:1282804. doi: 10.3389/fimmu.2024.1282804. eCollection 2024.
Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied.
This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management.
A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria.
A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups.
A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.
噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见且危及生命的疾病，其特征是严重的免疫稳态失调。虽然家族性 HLH（FHL）是已知的病因，但其他先天性免疫缺陷（IEI）在儿科 HLH 中的作用仍研究不足。
本系统综述旨在评估除 FHL（IEInotFHL）以外的 IEI 所致儿科 HLH 患者的临床特征、诱因、实验室数据、治疗和结局，强调准确识别和管理的重要性。
在 PubMed、EMBASE、MEDLINE 和 Cochrane Central 中进行了符合纳入标准的研究的系统检索。通过 JBI 标准进行质量评估。
全面检索共获得符合纳入标准的 108 项研究，涉及 178 例患者。根据 2022 年 IUIS 分类，我们确定了 46 种不同的 IEI。联合免疫缺陷、免疫调节紊乱和吞噬细胞缺陷是与 HLH 最常相关的 IEI。在 75%的病例中，HLH 先于 IEI 诊断，且常伴有未被识别的严重感染史。诱因反映了 IEI 组内特定的感染易感性。肝脏和中枢神经系统受累较 FHL 病例少见。治疗方法和结局各异，且缺乏长期随访数据，限制了对各 IEI 组治疗效果的评估。
在儿科 HLH 中，全面评估免疫、感染和遗传方面至关重要。仅依赖 FHL 或 EBV 易感性疾病的检测是不够的，因为其他多种 IEI 也可能导致 HLH。早期识别 HLH 作为潜在的警告信号，有助于及时进行诊断性检查，并为改善结局提供个体化的治疗干预。
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425，PROSPERO，CRD42022371425。
