Adult-onset primary hemophagocytic syndrome with concurrent Epstein–Barr virus infection: a case report with literature review

Objective: To investigate the clinical and laboratory features, phenotypic characteristics, associated genes, and treatment strategies for adult primary hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical characteristics and underlying causes of an adult primary HLH patient were analyzed according to the HLH-2004 diagnostic criteria. Gene sequences of HLH-related genes (UNC13D, PRF1, STX11, STXBP2, RAB27A, etc.) in the patient and his family were amplified using polymerase chain reaction (PCR) and subsequently analyzed. Results: The confirmed case involved a 42-year-old male patient presenting with recurrent fever, pancytopenia, hepatosplenomegaly, lymphadenopathy, elevated serum ferritin (600 ng/mL), significantly decreased NK cell activity (3.57%), and elevated soluble CD25 (2777 U/mL), all of which led to a diagnosis of HLH according to the HLH-2004 diagnostic criteria. The patient's serum EBV-DNA was elevated and was associated with cryptococcal infection of the central nervous system. After antiviral and antifungal treatments, EBV-DNA levels normalized, cerebrospinal fluid examination returned to normal, and primary HLH with an UNC13D gene mutation was confirmed by gene sequencing. Conclusions: While primary HLH is more prevalent in infants and young children, it can also occur in adolescents and adults, often being misdiagnosed as secondary HLH due to concurrent EBV infection. Molecular genetic alterations are crucial for distinguishing primary from secondary HLH, and HLH-related gene screening remains essential in adult patients.