Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is an underdiagnosed, life-threatening syndrome caused by impaired downregulation of immune activation. The primary (Mendelian) form typically manifests in children, whereas acquired HLH is more common in adults, often triggered by infections, malignancy, or autoimmune disease. We report an adult presenting with nonspecific constitutional symptoms ultimately diagnosed with HLH precipitated by Epstein-Barr virus (EBV) infection. Case Description A 37-year-old man with recent left facial herpes zoster presented with progressive facial numbness and 2 months of fever, anorexia, weight loss, and fatigue. On admission, he was febrile, hypotensive, and tachycardic. Examination revealed incoherent speech, seborrheic dermatitis, and axillary macular hyperpigmented lesions. Laboratory testing demonstrated pancytopenia (WBC 0.7 × 10³/µL, Hgb 9.2 g/dL, Plt 14 × 10³/µL) compared to normal counts 2 months prior. Additional pertinent abnormalities included hypertriglyceridemia 443 mg/dL, hypofibrinogenemia 86 mg/dL, hyperferritinemia 75,000 ng/mL, elevated LDH 1058 U/L, and AST 129 U/L. Soluble IL-2R was 27,572 U/mL. Peripheral smear showed leukopenia with absent monocytes, severe thrombocytopenia, and occasional acanthocytes. Bone marrow biopsy demonstrated 95% cellularity with increased histiocytes, hemophagocytosis, and EBV positivity; flow cytometry excluded malignancy. Extensive infectious workup was negative for HIV, viral hepatitis, histoplasma, coccidioides, or cryptococcus. Blood cultures were negative for bacterial, fungal, or mycobacterial pathogens. Parvovirus, CMV, HSV, and EBV IgG were positive, but only EBV PCR was markedly elevated at 1,040,000 copies/mL. Brain CT and MRI were non-revealing. CT chest/abdomen/pelvis showed bilateral pulmonary consolidation, hepatosplenomegaly, and no lymphadenopathy. Bronchoscopy with BAL was negative for infection. The calculated H Score of 253 indicated 99% probability of HLH. Given the high viral load and exclusion of other etiologies, EBV-associated HLH was diagnosed. He required short-term vasopressor support. Broad-spectrum antibiotics and liposomal amphotericin B were initiated during evaluation. HLH Therapy included intravenous dexamethasone taper, etoposide, rituximab, and intrathecal methotrexate with hydrocortisone for neurologic involvement. Discussion Hemophagocytic lymphohistiocytosis represents a cytokine release syndrome driven by dysregulated immune activation, frequently progressing to multiorgan failure and death. In a pooled analysis, mortality among critically ill adults has been reported at approximately 58% and infections constitute the most common precipitating factor. Secondary HLH frequently manifests as a sepsis-like critical illness unresponsive to sepsis-directed therapies, making timely recognition difficult due to overlapping clinical features. Our case highlights the diagnostic challenge of HLH, the importance of identifying precipitating triggers in acquired HLH, and emphasizes that prompt recognition and timely initiation of therapy are crucial for survival. This abstract is funded by: None
Wu et al. (Fri,) studied this question.
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