• Clinical science

Infectious mononucleosis (EBV infection…)


Infectious mononucleosis (IM), also called "mono" or the "kissing disease", is an acute condition caused by the Epstein-Barr virus (EBV). The disease is highly contagious and spreads via bodily secretions, especially saliva. Infection frequently goes unnoticed in children; mainly adolescents and young adults exhibit symptoms. Symptomatic individuals typically first experience fever, malaise, and fatigue, which is later accompanied by acute pharyngitis, tonsillitis, lymphadenopathy, and/or splenomegaly lasting up to a month. IM is also sometimes associated with a measles-like exanthem, especially in individuals who are falsely diagnosed with bacterial tonsillitis and given ampicillin or amoxicillin. To avoid misdiagnosis, suspected cases are confirmed with a heterophile antibody test (monospot test), or in some cases, positive serology. Patients exhibit lymphocytosis, often with atypical T lymphocytes on a peripheral smear. IM is treated symptomatically, as it is usually self-limiting. Although complications are rare, IM is associated with atraumatic splenic rupture due to splenomegaly and multiple malignancies (e.g., Hodgkin's lymphoma, Burkitt lymphoma).


  • Approx. 90–95% of adults are EBV-seropositive worldwide.
  • Peak incidence: of symptomatic disease: 15–24 years
  • Incidence: 500/100,000 per year in the US


Epidemiological data refers to the US, unless otherwise specified.


  • Pathogen: Epstein-Barr virus (EBV), also called human herpes virus 4 (HHV-4)
  • Transmission: Infectious mononucleosis is highly contagious and spreads via bodily secretions, especially saliva; → "kissing disease"



EBV infects B lymphocytes in mucosal epithelium (e.g., oropharynx, cervix) via the CD21 receptor; → infected B lymphocytes induce a humoral (B-cell) as well as a cellular (T-cell) immune response → an increased concentration of “atypical” lymphocytes in the bloodstream, which are CD8+ cytotoxic T cells that fight infected B lymphocytes


Clinical features

  • Incubation period: 4–8 weeks
  • Clinical course
    • Symptoms typically occur in adolescents and young adults and last for 2–4 weeks.
    • Young children are often asymptomatic.
    • Symptoms in adults ≥ 40 years are less severe than in adolescents/young adults.
    • Chronic active disease is very rare (more frequent in Asia or South America).
  • Splenomegaly (50% of cases), fever, fatigue, malaise
  • Pharyngitis and/or tonsillitis (reddened, enlarged tonsils covered in pus); palatal petechiae
  • Bilateral cervical lymphadenopathy that may become generalized and can, in severe cases, lead to airway obstruction
  • Abdominal pain
  • Possibly hepatomegaly and jaundice
  • Maculopapular rash; (similar to measles): caused by the infection itself in about 5% of cases, but is generally associated with the administration of aminopenicillin (e.g., ampicillin or amoxicillin)

Splenomegaly can lead to a potentially life-threatening splenic rupture!



Clinical suspicion of IM is confirmed via antibody testing.

Serology Past infection Primary infection
anti-VCA IgM negative positive
anti-VCA IgG positive positive
Anti-EBNA-1 IgG positive negative

References: [3][5]


Histopathology of lymph nodes

  • Reactive follicular hyperplasia due to increased activation of B lymphocytes
  • Paracortical expansion through numerous, large immunoblasts (B and T cells), later expanding throughout the entire node
  • Atypical Reed-Sternberg-like cells may be observed, which is why the disease is sometimes mistaken for Hodgkin's disease.


Differential diagnoses


The differential diagnoses listed here are not exhaustive.


Symptomatic therapy

  • Avoid physical activity that may trigger splenic rupture (e.g., contact sports) for at least 3 weeks after the onset of symptoms.
  • Fluids (IV administration if necessary)
  • Analgesics/antipyretics (e.g., acetaminophen)
  • Steroids are not recommended for routine use but may be considered in complicated cases.

Tonsillitis is an important differential diagnosis that is often treated with aminopenicillins (e.g., ampicillin). However, if given to a patient with IM, the patient often develops a macular erythematous rash after 5–9 days!



Immunocompromised patients are more prone to complications.

Nervous system
Hematological system

Other organs

Associated malignancies


We list the most important complications. The selection is not exhaustive.