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Infectious Mononucleosis

Infectious Mononucleosis is an acute viral illness most commonly caused by Epstein-Barr Virus (EBV), a member of the herpesvirus family. It occurs particularly often in adolescents and young adults and classically presents with fever, pharyngitis, cervical lymphadenopathy, and marked fatigue

Also called

Glandular fever

ICD-10

B27.9

Specialty

Infectious

Onset

Acute

Reviewed

August 2026
On This Page

Overview

–Infectious Mononucleosis is usually caused by primary EBV infection. The virus infects epithelial cells and B lymphocytes and then establishes lifelong latency.

 

The classic clinical picture is:

Fever + pharyngitis + posterior cervical lymphadenopathy + fatigue

 

Other common findings include splenomegaly, atypical lymphocytosis, and mild hepatitis.

Etiology & Risk Factors

-Etiology

–Infectious Mononucleosis is most commonly caused by Epstein-Barr Virus (EBV).

Transmission occurs mainly through:

  • Saliva
  • Kissing
  • Sharing drinks or utensils
  • Close oral contact

Less commonly, transmission can occur through blood or organ transplantation.

 

-Risk Factors for Infectious Mononucleosis

  • Adolescence or young adulthood
  • Close contact with infected individuals
  • Sharing drinks or utensils
  • Lack of previous EBV exposure

Pathophysiology

EBV exposure → infection of oropharyngeal epithelial cells → infection of B lymphocytes → immune activation → expansion of reactive CD8+ T lymphocytes → systemic symptoms → lymphadenopathy, pharyngitis, and atypical lymphocytosis

Clinical Presentation

-Symptoms:

Infectious Mononucleosis commonly causes:

  • Fever
  • Severe fatigue
  • Sore throat
  • Difficulty swallowing
  • Headache
  • Malaise
  • Loss of appetite

Other symptoms may include:

  • Abdominal discomfort
  • Nausea
  • Myalgia

Most acute symptoms improve within 1–2 weeks, although fatigue and malaise may last considerably longer

 

-Signs:

  • Posterior cervical lymphadenopathy
  • Tonsillar enlargement
  • Tonsillar exudates
  • Palatal petechiae
  • Splenomegaly
  • Mild hepatomegaly
  • Mild jaundice in some patients
Infectious Mononucleosis Overview
Infectious Mononucleosis Overview

History Taking

-Ask about:

  • Fever and duration
  • Sore throat
  • Fatigue
  • Difficulty swallowing
  • Neck swelling
  • Recent exposure to an infected person
  • Sharing drinks or utensils
  • Abdominal pain, particularly left upper quadrant pain
  • Previous EBV infection

Physical Examination

-General Examination

  • Temperature
  • General appearance
  • Hydration status
  • Severity of fatigue

 

-System-Specific Examination:

  • Inspect the throat and tonsils
  • Palpate cervical lymph nodes
  • Assess for splenomegaly
  • Assess for hepatomegaly
  • Examine for jaundice
  • Look for palatal petechiae
  • Assess the airway if there is severe tonsillar enlargement

Investigations

Infectious Mononucleosis · Investigations

Investigations — Exam Focus
InvestigationTypical findingExam significance
CBC with differentialLymphocytosis with atypical lymphocytes; neutropenia or thrombocytopenia may occur>10% atypical lymphocytes strongly supports the diagnosis
Peripheral blood smearLarge atypical/reactive lymphocytesClassic morphology of infectious mononucleosis
Heterophile antibody testUsually positive during acute illnessRapid screening test; may be false-negative early and in young children
EBV-specific serologyVCA IgM +, VCA IgG +, EBNA − → primary/recent infectionBest confirmatory pattern when heterophile test is negative or diagnosis is uncertain
Liver function testsElevated aminotransferases are commonSupports the diagnosis; helps assess hepatic involvement
High-Yield Exam Associations
What to order
• CBC + differential → lymphocytosis / atypical lymphocytes
• Heterophile antibody → rapid screening
• EBV serology → confirm recent infection when needed
• LFTs → often elevated
Interpretation
• VCA IgM + / EBNA − → acute primary EBV
• VCA IgG + / EBNA + → past infection
• Negative heterophile test early → does not exclude disease
• Heterophile testing is not recommended as the sole definitive EBV test
Most tested: >10% atypical lymphocytes + compatible clinical picture → strongly suggests infectious mononucleosis. Acute EBV → VCA IgM positive, EBNA negative.

Diagnosis

Infectious Mononucleosis is suspected clinically from:

Fever + pharyngitis + posterior cervical lymphadenopathy + fatigue → CBC showing lymphocytosis/atypical lymphocytes → heterophile antibody or EBV-specific serology when confirmation is needed

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Management

1. Definitive Treatment

Treatment for Infectious Mononucleosis is primarily supportive because uncomplicated EBV infection is usually self-limited.

 

2. Medical Treatment

  • Paracetamol or NSAIDs for pain and fever when appropriate

  • Adequate oral fluids

  • Corticosteroids only for specific severe complications

Corticosteroids may be considered for:

  • Impending upper airway obstruction

  • Severe tonsillar edema

  • Severe hemolytic anemia

  • Severe thrombocytopenia

 

Routine corticosteroid therapy is not recommended for uncomplicated Infectious Mononucleosis.

 

3. Supportive Management

  • Adequate hydration

  • Rest

  • Nutritional support

  • Avoid alcohol when liver inflammation is present

  • Avoid contact sports during the period of increased splenic rupture risk

Complications

  • Splenic rupture
  • Upper airway obstruction
  • Hepatitis
  • Hemolytic anemia
  • Thrombocytopenia
  • Meningoencephalitis
  • Guillain-Barré syndrome
  • Myocarditis
  • Prolonged fatigue

Prognosis

The prognosis of Infectious Mononucleosis is generally excellent, with most patients recovering completely without specific antiviral therapy. Fever and pharyngitis usually improve within a few weeks, while fatigue may persist longer. Serious complications are uncommon.

Key Points / Clinical Pearls

  • Infectious Mononucleosis is most commonly caused by EBV.
  • It primarily affects adolescents and young adults.
  • Transmission occurs mainly through saliva.
  • The classic presentation is fever, pharyngitis, and posterior cervical lymphadenopathy.
  • Marked fatigue is common.
  • Splenomegaly is an important finding.
  • CBC may show lymphocytosis and atypical lymphocytes.
  • Heterophile antibodies can support the diagnosis.
  • EBV-specific serology can confirm acute infection.
  • Heterophile tests may be negative early in disease.
  • Treatment is mainly supportive.
  • Routine antibiotics are not indicated because the infection is viral.
  • Amoxicillin or ampicillin can cause a characteristic rash in patients with EBV infection.