Late onset of familial haemophagocytic lymphohistiocytosis 2 associated with heterozygous PRF1 mutation: challenges in diagnosis and treatment

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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition caused by immune overactivation. Familial HLH (f-HLH), such as f-HLH 2, is associated with mutations in the PRF1 gene, essential for ruling out secondary HLH. Aim - to describe a clinical case of late onset f-HLH 2 associated with a heterozygous mutation in the PRF1 gene in a 13-year-old boy. Case report. A 13-year-old boy presented with fever, nausea, vomiting, abdominal pain, and jaundice. Examination revealed hepatosplenomegaly, elevated liver enzymes, hyperbilirubinemia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, and reduced NK-cells and T-lymphocytes. Cytomegalovirus (CMV) was detected by polymerase chain reaction. Pancytopenia soon developed. Bone marrow biopsy confirmed hemophagocytosis, leading to a diagnosis of secondary HLH associated with CMV. Treatment included intravenous immunoglobulin, HLH 2004 protocol (without etoposide), and ganciclovir, with initial improvement. However, cytopenia recurred after dexamethasone was stopped. Ruxolitinib was introduced alongside cyclosporine (CsA), leading to normalisation of liver function, spleen size, lymphocyte subpopulations, and haemogram. Cytopenia returned after ruxolitinib cessation. Whole-exome sequencing revealed a heterozygous PRF1 gene mutation, confirming the diagnosis of f-HLH 2. Conclusions. Timely laboratory diagnostics, bone marrow biopsy, genetic testing, and appropriate treatment are critical in preventing complications and improving outcomes in HLH. Early intervention with specific therapies, such as immunosuppressants and genetic evaluation, is essential in managing f-HLH 2. The study was conducted in accordance with the principles of the Declaration of Helsinki. The informed consent of the child's parents was obtained for the study. The authors declare no conflict of interest.