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

Abstract

Background:

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 underdetermined origin (FUO) in adults.

Patients and Methods:

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.

Results:

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.

Conclusion:

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.