• Clinical science

Infectious mononucleosis (Kissing disease)


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: 5/1000 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

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



Clinical suspicion of IM is confirmed via antibody testing.

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

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.