Laboratory testing for infectious mononucleosis. Cautions to observe in interpreting results

In the vast majority of cases, diagnosis of infectious mononucleosis is relatively simple and the illness is not serious. Performing tests for specific Epstein-Barr virus (EBV) antibodies in these cases is not necessary. However, when the clinical manifestations are atypical or unusually severe, especially when the heterophil antibody test is negative, specific EBV antibody tests may be needed. The EBV antibodies used in diagnosis are IgG antibodies to viral capsid antigen (VCA), IgM antibodies to VCA, and antibodies to early antigen (anti-D) and Epstein-Barr nuclear antigen (EBNA). The diagnosis of infectious mononucleosis may be made when IgG-VCA, IGM-VCA, and anti-D antibodies are present and EBNA antibodies are absent. EBNA antibodies appear later and, together with IgG-VCA antibodies, persist indefinitely. Still, infectious mononucleosis often cannot be diagnosed with certainty because of the difficulties in interpreting laboratory findings. The diagnosis must be made with caution and possible sources of error considered when test results are interpreted.