Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Pediatrics, Akita University Graduate School of Medicine, Akita, Japan.
Pediatr Int. 2023 Jan-Dec;65(1):e15516. doi: 10.1111/ped.15516.
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory disorder characterized by hypercytokinemia caused by excessive activation of cytotoxic T cells and macrophages. HLH is caused by a variety of factors and is classified into primary and secondary HLH. Familial HLH (FHL) types 1-5, X-linked lymphoproliferative syndrome types 1 and 2, and FHL syndrome with hypopigmentation are all examples of primary HLH. Secondary HLH, on the other hand, is linked to infections, malignant tumors, autoimmune diseases, and other diseases. The causes of HLH vary, and finding the underlying disease is critical for diagnosis and treatment. The majority of HLH is caused by the aforementioned conditions; however, approximately 10% of cases are caused by rare diseases such as inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Novel IEI, such as RhoG, MAP kinase activating death domain, TIM3, and ZNFX1 deficiencies, have recently been identified as causes of HLH. IEM patients are rarely associated with HLH. Surprisingly, children with lysinuric protein intolerance and lysosomal acid lipase deficiency (Wolman disease) frequently develop HLH. This review focuses on the most recent knowledge of HLH caused by rare diseases such as IEI and IEM.
噬血细胞性淋巴组织细胞增生症（HLH）是一种潜在致命的过度炎症性疾病，其特征是细胞毒性 T 细胞和巨噬细胞过度激活导致细胞因子过度产生。HLH 由多种因素引起，可分为原发性和继发性 HLH。家族性 HLH（FHL）1-5 型、X 连锁淋巴组织增生综合征 1 型和 2 型以及伴有色素减退的 FHL 综合征均属于原发性 HLH。另一方面，继发性 HLH 与感染、恶性肿瘤、自身免疫性疾病等疾病有关。HLH 的病因各不相同，找到潜在疾病对诊断和治疗至关重要。大多数 HLH 是由上述情况引起的；然而，约 10%的病例是由罕见疾病引起的，如先天性免疫缺陷（IEI）和先天性代谢缺陷（IEM）。最近发现 RhoG、MAP 激酶激活死亡域、TIM3 和 ZNFX1 缺乏等新型 IEI 是 HLH 的病因。IEM 患者很少与 HLH 相关。令人惊讶的是，患有赖氨酸尿蛋白不耐受和溶酶体酸性脂肪酶缺乏症（Wolman 病）的儿童常发生 HLH。本综述重点介绍了由 IEI 和 IEM 等罕见疾病引起的 HLH 的最新知识。
