A fatal case of concurrent EBV-induced meningitis, ARDS, and HLH in an immunocompetent adult: a case report

Rationale Epstein-Barr virus (EBV) typically causes self-limited infections in immunocompetent adults. Life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH), meningitis, and acute respiratory distress syndrome (ARDS) are exceptionally rare and have not been previously reported to occur concurrently in a single patient. This case highlights the catastrophic potential of EBV and underscores a critical therapeutic dilemma: balancing the need for aggressive immunosuppressive therapy to control life‑threatening HLH against the risk of exacerbating uncontrolled EBV viremia and severe infections in a critically ill patient. Patient concerns A 34-year-old immunocompetent woman presented with a 10-day history of high-grade fever (39.9 °C) and persistent headache. Diagnoses The diagnosis of Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) was confirmed by meeting 5 of 8 HLH-2004 criteria in the setting of extreme EBV viremia (1.48 × 10⁸copies/mL), with high EBV DNA load additionally detected by metagenomic next-generation sequencing (mNGS) in cerebrospinal fluid (239 EBV reads) and lower respiratory tract samples (145,386 EBV reads). Concurrently, EBV meningitis was confirmed by CSF findings (lymphocytic pleocytosis, elevated protein, and hypoglycorrhachia) alongside positive mNGS. She also met the Berlin criteria for ARDS, with bilateral pulmonary infiltrates on imaging and a PaO₂/FiO₂ ratio of 200 prior to ICU admission (on low-flow oxygen, consistent with moderate ARDS). Shortly after ICU admission, her oxygenation deteriorated to a PaO₂/FiO₂ ratio of 81 on mechanical ventilation with PEEP of 10 cmH₂O, meeting criteria for severe ARDS. Interventions Management was restricted to organ support (mechanical ventilation, continuous renal replacement therapy), ganciclovir antiviral therapy, and broad-spectrum antibiotics. Crucially, guideline-directed immunomodulatory therapy for HLH (e.g., corticosteroids/etoposide per HLH-2004) was not administered due to delayed diagnosis, lack of institutional expertise, and socioeconomic constraints. Outcomes The patient’s condition deteriorated rapidly, with progression to fatal multi-organ failure and death on hospital day 5 (illness day 15). Lessons This case demonstrates that EBV can trigger a fulminant, lethal triad of HLH, meningitis, and ARDS even in immunocompetent hosts, which has not been previously reported in a single patient. It underscores that high-risk EBV-HLH mandates immediate immunomodulation, as antiviral and supportive care alone are catastrophically insufficient. Early recognition and overcoming barriers to administering complex, urgent therapies are essential to improving outcomes.