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# Infectious mononucleosis

Mononucleosis is usually caused by the Epstein-Barr virus. It brings fever, sore throat, swollen neck glands, tiredness and an enlarged spleen.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Palatine tonsils](https://durgical.com/en/anatomy/palatine-tonsil/)
- [Neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/)
- [Spleen](https://durgical.com/en/anatomy/spleen/)
- [Pharynx](https://durgical.com/en/anatomy/pharynx/)
- [Liver](https://durgical.com/en/anatomy/liver/)

## In biochemistry

- [Lactate dehydrogenase (LDH) as a lab marker](https://durgical.com/en/biochemistry/topics/lactate-dehydrogenase-as-a-lab-marker/)

## Microorganisms that cause it

- [Epstein–Barr virus](https://durgical.com/en/microbiology/epstein-barr-virus/)

## In the clinical exam

- [Lymph node examination](https://durgical.com/en/clinical-exam/lymph-node-examination/)
- [Mouth and pharynx examination](https://durgical.com/en/clinical-exam/mouth-and-pharynx-examination/)

## Why it happens

- [Oncogenic viruses and H. pylori: the table to know](https://durgical.com/en/general-pathology/oncogenic-viruses-and-h-pylori-the-table-to-know/)
- [Innate and adaptive immunity: overview](https://durgical.com/en/physiology/innate-and-adaptive-immunity-overview/)
- [Blood cells on a smear: erythrocytes, leukocytes, platelets](https://durgical.com/en/histology/blood-cells-on-a-smear-erythrocytes-leukocytes-platelets/)
- [Lymph node and spleen under the microscope](https://durgical.com/en/histology/lymph-node-and-spleen-under-the-microscope/)

## What it is

A clinical syndrome of fever, pharyngitis and lymphadenopathy with atypical lymphocytes, usually caused by primary Epstein-Barr virus (EBV) infection in adolescents and young adults.

## Who gets it

EBV infects most people worldwide. In Latin America and other settings with crowding, infection usually happens in early childhood and is mild or silent; the classic syndrome appears when the first infection occurs in adolescence or early adulthood, which is more common in higher-income groups.

## Causes

- Epstein-Barr virus (human herpesvirus 4) in about 90% of cases
- Less often cytomegalovirus, acute HIV, Toxoplasma or human herpesvirus 6 (mononucleosis-like syndrome)
- Spread mainly through saliva («kissing disease»), also shared utensils; rarely transfusion or transplant

## Risk factors

- Age 15 to 24 years with no previous infection
- Close contact with saliva: kissing, sharing cups or utensils
- Living in dormitories or crowded settings

## Pathophysiology

EBV infects oropharyngeal epithelium and then B lymphocytes through the CD21 receptor, causing their proliferation. Cytotoxic CD8 T cells expand to control infected B cells; these reactive T cells are the atypical lymphocytes seen on the smear and cause the swelling of tonsils, lymph nodes, [liver](https://durgical.com/en/anatomy/liver/) and spleen. The virus then remains latent in memory B cells for life and is linked to some lymphomas and nasopharyngeal carcinoma.

## Symptoms and signs

- Triad: fever, exudative pharyngitis and lymphadenopathy, especially posterior cervical nodes
- Marked fatigue that may last weeks
- Splenomegaly (about half of cases) and sometimes hepatomegaly with mild hepatitis
- Palatal petechiae and eyelid oedema
- Maculopapular rash, very frequent after amoxicillin or ampicillin

## Red flags

- Sudden left upper abdominal or left shoulder pain, dizziness or hypotension (splenic rupture)
- Stridor, drooling or difficulty breathing from massive tonsil swelling
- Jaundice or bleeding
- Pallor, dark urine or marked weakness (haemolytic anaemia)
- Neurological signs such as confusion, seizures or weakness

## Diagnosis

**Clinical**
Fever, pharyngitis and posterior cervical lymphadenopathy in an adolescent or young adult, with palpable [spleen](https://durgical.com/en/anatomy/spleen/) or palatal petechiae.

**Tests**
Lymphocytosis with more than 10% atypical lymphocytes; mildly raised transaminases. Heterophile antibody test (Monospot), which can be negative early and in young children. EBV-specific antibodies: VCA IgM indicates acute infection; EBNA antibodies appear later.

**Imaging**
Not routine. Abdominal ultrasound to measure the spleen or when splenic rupture is suspected; CT in an unstable patient after trauma.

## Differential diagnosis

- Streptococcal pharyngitis
- Cytomegalovirus infection
- Acute HIV infection
- Toxoplasmosis
- Acute leukaemia or lymphoma

## Goal of treatment

Relieve symptoms while the infection resolves on its own, and prevent and detect complications, especially splenic rupture and airway obstruction.

## Treatment

**Conservative**
Rest according to tolerance, hydration, analgesics and antipyretics such as paracetamol or NSAIDs, and saltwater gargles.

**Lifestyle**
Contact sports and heavy lifting are avoided for at least about 3 to 4 weeks, or until the spleen is no longer enlarged.

**Medical**
Corticosteroids only for complications such as threatened airway obstruction, severe haemolytic anaemia or thrombocytopenia; antivirals offer little benefit and antibiotics are not indicated.

**Surgical**
Emergency splenectomy or splenic preservation surgery when there is splenic rupture with haemodynamic instability.

## Complications

- Splenic rupture, rare but potentially fatal, mostly in the first weeks
- Upper airway obstruction from tonsillar hypertrophy
- Autoimmune haemolytic anaemia and thrombocytopenia
- Hepatitis, encephalitis, Guillain-Barré syndrome and myocarditis
- Long-term EBV associations: Burkitt and Hodgkin lymphoma, nasopharyngeal carcinoma, post-transplant lymphoproliferative disorder

## Prognosis

Excellent in most cases: fever and sore throat settle in about two weeks, although fatigue may last months. Serious complications are uncommon.

## Prevention

- No vaccine is available
- Not sharing cups, utensils or kisses with someone who is ill

## Test yourself

Think of the answer, then tap the question to see it.

## Through which receptor does EBV infect B lymphocytes?

CD21, the receptor for complement fragment C3d.

## What are the atypical lymphocytes in mononucleosis?

Reactive cytotoxic CD8 T cells responding to EBV-infected B cells.

## What happens if a patient with mononucleosis is given amoxicillin?

A diffuse maculopapular rash appears in a high proportion of patients; it is not a true penicillin allergy.

## What is the most feared acute complication and how is it prevented?

Splenic rupture; patients avoid contact sports and heavy exertion until the spleen returns to normal size.

## Which test detects heterophile antibodies?

The Monospot test (Paul-Bunnell heterophile antibody test).

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## Related conditions

- [Streptococcal pharyngitis](https://durgical.com/en/conditions/streptococcal-pharyngitis/)
- [Splenic injury](https://durgical.com/en/conditions/splenic-injury/)
- [Cytomegalovirus infection](https://durgical.com/en/conditions/cytomegalovirus-infection/)
- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- [Toxoplasmosis](https://durgical.com/en/conditions/toxoplasmosis/)
- [Hodgkin lymphoma](https://durgical.com/en/conditions/hodgkin-lymphoma/)
- [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/)
- [Nasopharyngeal carcinoma](https://durgical.com/en/conditions/nasopharyngeal-carcinoma/)
- [Autoimmune haemolytic anaemia](https://durgical.com/en/conditions/autoimmune-haemolytic-anaemia/)
- [Guillain-Barré syndrome](https://durgical.com/en/conditions/guillain-barre-syndrome/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Mononucleosis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000591.htm) (MedlinePlus (U.S. National Library of Medicine), 2024).

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Source: https://durgical.com/en/conditions/infectious-mononucleosis/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/infectious-mononucleosis/