Tóm tắt

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening hyperinflammatory syndrome characterized by excessive activation of the immune system, leading to symptoms such as fever, multilineage cytopenia, coagulopathy, and multi-organ failure, with a high risk of mortality. Its non-specific clinical presentation often poses a diagnostic challenge, especially when the line between primary and secondary HLH is blurred, as secondary triggers, such as infections, can unmask an underlying genetic condition. The incidence of HLH is elevated in patients with inborn errors of immunity (IEI).

Case report: We report the case of a 9-month-old male infant with classic HLH, including prolonged fever, hepatosplenomegaly, thrombocytopenia, elevated ferritin, and hemophagocytosis in the bone marrow aspirate. Notably, the patient also had an opportunistic Aspergillus infection, which is a hallmark of severe immunodeficiency. Genetic analysis revealed a rare co-occurrence of two pathogenic variants: a compound heterozygous c.859-3C>T mutation in UNC13D (causing familial hemophagocytic lymphohistiocytosis type 3) and a recessive c.158_161del mutation in CD40LG (causing hyper-IgM syndrome). The infant was diagnosed with HLH on the background of hyper-IgM syndrome based on HLH-2004 criteria and responded well to a combined treatment of chemotherapy and immunoglobulin replacement therapy.

Conclusions: This case highlights the crucial role of comprehensive IEI screening in patients with HLH, particularly those with a history of recurrent or opportunistic infections, to facilitate accurate diagnosis and optimize treatment strategies.