Acute EBV-Associated Systemic Inflammatory Syndrome Presenting as PUO With FDG-Avid Generalized Lymphadenopathy,...

Pyrexia of unknown origin (PUO) remains a diagnostic challenge, particularly when associated with lymphadenopathy, multisystem involvement and positive autoimmune serology. Distinguishing between infectious, inflammatory and malignant causes is often difficult, especially when advanced imaging demonstrates findings suggestive of lymphoma. A previously healthy man in his late 40s presented with a 10-day history of intermittent fever, myalgia, joint stiffness and pleuritic chest pain. During admission, he developed photophobia, mild neck stiffness, progressive upper and lower limb pain and weakness resulting in impaired mobility. Investigations demonstrated marked systemic inflammation with a C-reactive protein (CRP) of 235 mg/L and an erythrocyte sedimentation rate (ESR) of 105 mm/hr despite a normal white cell count (WCC). Extensive microbiological investigations including blood cultures, cerebrospinal fluid analysis, bacterial and fungal molecular testing, tuberculosis screening and viral polymerase chain reaction (PCR) testing were negative apart from detectable Epstein-Barr virus (EBV) DNA and positive EBV IgM serology. Autoimmune screening revealed positive ANA, anti-Ro52, anti-Ro60 and anti-La antibodies with low complement C4. Cardiac magnetic resonance imaging (MRI) confirmed acute myopericarditis. Positron emission tomography-computed tomography (PET-CT) demonstrated fluorodeoxyglucose (FDG)-avid supra- and infradiaphragmatic lymphadenopathy with splenic involvement highly suspicious for lymphoma. However, excisional cervical lymph node biopsy demonstrated reactive lymphoid hyperplasia without evidence of malignancy. Clinical improvement began approximately during the second week after admission and occurred without immunosuppressive therapy.