Primary Cytomegalovirus Infection in Otherwise Healthy Adults with Fever of Unknown Origin: A 3-Year Prospective Survey

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Primary cytomegalovirus disease is probably still underestimated or missed in common clinical practice, and further prevalence studies should be performed, in particular in the setting of fever of under-determined origin (FUO) in adults. In a 3-year prospective survey of 123 consecutive adult patients referred for FUO often associated with a broad spectrum of constitutional signs and symptoms, 18 patients (14.6%) were found to have a primary cytomegalovirus infection, after a clinical, instrumental and laboratory workup. In the majority of cases, this syndrome was consistently associated with altered white blood cell count, abnormal T-lymphocyte subsets and ultrasonography-confirmed hepatosplenomegaly. On the other hand, altered white blood cell differential and serum hepatic enzymes, and constitutional signs and symptoms were absent in 11.1-27.8% of cases, and an initial laboratory cross-reaction with anti-Epstein-Barr IgM antibodies was detected in 44.4% of episodes. Non-specific signs and symptoms were the only features in 27.8% of patients with adult cytomegalovirus disease, thus, confirming that this disorder may be still clinically underestimated, until virologic assays are performed. A prolonged and varied spectrum of subjective disturbances (similar to those encountered in infectious mononucleosis), which often limited daily activities, involved nearly 30% of subjects, and lasted for 3-15 months after recovery of acute cytomegalovirus disease. In the clinical, laboratory, and instrumental workup for FUO, rapid recognition of a primary cytomegalovirus disease is useful to exclude alternative diagnoses, avoid non-necessary exposure to antibiotics, and reassure patients of their self-limiting, benign disorder.