Infectious mononucleosis is an acute self-limiting disease caused by an orally transmitted herpesvirus, Epstein–Barr virus. The disease typically involves fever, enlarged lymph glands and malaise, with elevated blood lymphocyte counts that reflect an exaggerated cellular immune response to the infection. Epstein–Barr virus is widespread in all human populations and is most often acquired asymptomatically in infancy. However, in affluent societies, primary infection can be delayed until the second or third decade, when 25–50% of those involved may develop symptoms. Hence infectious mononucleosis is typically a disease affecting adolescents or young adults in the Western world. Almost all patients recover completely within a few weeks but rare cases with persistent, even fatal, symptoms do occur and involve those with a pre-existing immune defect or rare individuals where the virus infection spreads into atypical cell types. There is no obvious association between this virus and so-called chronic fatigue syndrome.

Key concepts:

• Infectious mononucleosis is caused by Epstein–Barr virus, an orally transmitted human herpesvirus that is common in all human populations.
  
• Most individuals acquire Epstein–Barr virus asymptomatically early in life, then carry the virus for life without undue effect.
  
• Only when primary infection has been delayed until adolescence or young adulthood is there a substantial risk of mononucleosis developing; hence, the disease is largely confined to affluent societies where delayed infection is more common.
  
• Infectious mononucleosis is self-limiting and ‘immunopathological’ in nature: that is, the symptoms (fever and malaise) are caused not by the virus infection per se, but by the patient mounting an exaggerated cellular immune response to that infection.
  
• Most (but not all) cases with the relevant clinical symptoms and large numbers of atypical mononuclear cells in the blood will be Epstein–Barr virus-related; however, definite diagnosis requires serological testing for IgM antibodies to Epstein–Barr virus.
  
• Cases where severe disease symptoms persist are extremely rare and involve either patients with a pre-existing immune defect or individuals where the virus infection has spread into atypical cell types.
  
• A history of proven infectious mononucleosis brings with it an increased risk of subsequently developing another Epstein–Barr virus -associated disease, Hodgkin lymphoma.