Case Report: Hemophagocytic lymphohistiocytosis in an infant associated with cytomegalovirus infection and X-linked primary immunodeficiency

Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disorder often driven by primary immunodeficiencies like X-linked lymphoproliferative syndrome (XLP) in infants. Case description We report a 2-month-old male with primary immunodeficiency who developed HLH triggered by cytomegalovirus (CMV), confirmed via bone marrow PCR and hemophagocytosis findings. Initial immunophenotyping during acute hyperinflammation showed marked secondary disruptions across lymphocyte subpopulations, including severe lymphopenia in CD4+ T cells and pre-germinal center B cells. Genetic sequencing identified a pathogenic hemizygous variant in the XIAP/BIRC4 gene, confirming X-linked lymphoproliferative syndrome type 2 (XLP-2). The patient was managed with the HLH-2004 protocol, valganciclovir, immunoglobulins, and transfusions, complicated by severe pancytopenia. Conclusion This case demonstrates an atypical XLP-2 presentation where CMV, rather than Epstein-Barr virus, triggered HLH. Following stabilization and viral clearance, the patient successfully underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched family donor. On day +30 post-HSCT, molecular chimerism confirmed 97.87% donor engraftment. On day +39 post-HSCT, the infant is clinically stable, actively recovering at last assessment from grade II cutaneous graft-versus-host disease (GvHD) under immunosuppression, with low-level CMV viral reactivation (951 copies/mL) managed under close surveillance. At the comprehensive 9-month follow-up from initial presentation, the patient maintained overall systemic stability without evidence of disease relapse or secondary organ dysfunction, highlighting the necessity of long-term monitoring in post-transplant cGvHD management, and proving the life-saving role of early genetic diagnosis and timely HSCT.