• Results in most cases from infection with the Epstein–Barr virus (EBV) (a herpesvirus):
    • Non-EBV causes of infectious mononucleosis (IM):
      • Cytomegalovirus (CMV)
      • Adenovirus
      • Hepatitis A
      • Herpesvirus 6
      • HIV
      • Rubella
      • Toxoplasma gondii
      • Group A β-hemolytic streptococci
  • >90% of adults on serologic testing demonstrate prior infection with EBV:
    • Most do not recollect specific IM symptoms
  • Mode of transmission is close or intimate contact particularly with saliva from “shedders” who may or may not be symptomatic:
    • Nickname “kissing disease”
    • Viral shedding in saliva can persist intermittently for life
    • May occur after transfusions/transplants
  • Incubation period: 4–6 wk
  • Immunologic response:
    • T-cells response:
      • T-cell response is responsible for an elevated absolute lymphocyte count and the associated clinical symptoms and complications
      • Subtype of the T-cell lineage, cytotoxic CD8 cells (Downey cells), contain eccentrically placed and lobulated nuclei with vacuolated cytoplasm: The “atypical lymphocytes” seen on differential
    • B-cell response:
      • EBV infects and replicates in B-cells
      • B-cells are then transformed into plasmacytoid cells that secrete immunoglobulins
      • IgM antibody secreted: The heterophile antibody which is reactive against red cell antigens
  • Mortality from IM is rare, but may occur due to the following complications:
    • Airway edema
    • Neurologic complications
    • Secondary bacterial infection
    • Splenic rupture
    • Hepatic failure
    • Myocarditis
  • EBV infection has also been strongly linked to African Burkitt lymphoma and nasopharyngeal carcinoma

Pediatric Considerations
  • In children <4 yr, infection with EBV is often asymptomatic
  • In children who do become symptomatic, there is propensity toward atypical presentations:
    • Neutropenia, pneumonia, and varied rashes
    • Mesenteric lymphadenopathy and splenomegaly can cause the illness to present with abdominal pain and be confused with appendicitis
    • Infants and toddlers can present with only irritability and failure to thrive so must be considered when no other source can be identified

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