Cytomegalovirus viremia as a cause of fever of unknown origin in an immunocompetent adult

Background: Cytomegalovirus (CMV) infection in immunocompetent adults is usually mild; severe hyperinflammatory phenotypes occur rarely. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterised by uncontrolled immune activation; cytomegalovirus is a recognised but uncommon trigger. Overlapping features with other inflammatory disorders complicate timely diagnosis and management. Case description: We report a 28-year-old previously healthy male with several days of gastrointestinal and upper respiratory symptoms followed by persistent fevers and a transient petechial, later salmon-pink, macular rash. Vital signs showed tachycardia and tachypnoea as well as SpO2 of 93%. Initial broad infectious work-up was negative. Laboratory tests revealed leucocytosis with lymphocytic predominance, transaminitis (ALT 138 U/l, AST 103 U/l), elevated ferritin, C-reactive protein 20 mg/l, triglycerides 166 mg/dl and splenomegaly. Cerebrospinal fluid showed mild lymphocytic pleocytosis. H-score suggested moderate probability for HLH; bone marrow biopsy demonstrated rare haemphagocytosis without malignancy. The differential included adult-onset Still’s disease given the Yamaguchi criteria. Indomethacin improved fevers, but leucocytosis persisted. Serum cytomegalovirus polymerase chain reaction returned positive on day 5 and was corroborated by plasma cell-free DNA testing; the Epstein-Barr virus polymerase chain reaction became negative. Valganciclovir was initiated, with prompt clinical and laboratory improvement. Conclusion: Cytomegalovirus can precipitate a hyperinflammatory state mimicking adult-onset Still’s disease and secondary hemophagocytic lymphohistiocytosis in immunocompetent hosts. Early consideration of cytomegalovirus with timely molecular testing in fever of unknown origin, paired with parallel evaluation for hemophagocytic lymphohistiocytosis, may expedite therapy and improve outcomes.