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Infectious mononucleosis (glandular fever)

SNOMED: 271558008747 words•Updated 03/03/2026
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Exam Tips

  • Classic triad: fever + severe pharyngitis + posterior cervical lymphadenopathy in a teenager/young adult.
  • Palatal petechiae, generalized lymphadenopathy, and splenomegaly increase diagnostic likelihood.
  • Do not prescribe amoxicillin/ampicillin when glandular fever is likely; a marked rash is common and can mislead as penicillin allergy.
  • Always counsel on splenic rupture risk and temporary avoidance of contact sports.
  • Think of mononucleosis-like illness if EBV tests are negative: CMV, HIV, toxoplasmosis, HHV-6, adenovirus.
  • Atypical older patient (>40 years) may present with jaundice/hepatomegaly rather than prominent sore throat or cervical nodes.

Definition

Infectious mononucleosis (glandular fever) is an acute systemic viral illness, usually caused by primary Epstein-Barr virus (EBV) infection, classically presenting with severe pharyngitis, fever, and lymphadenopathy. It is most common in adolescents and young adults, and although usually self-limiting, it can involve the liver and spleen and occasionally causes serious complications such as airway compromise or splenic rupture.

Pathophysiology

EBV (human herpesvirus 4) is transmitted mainly via saliva, infecting oropharyngeal epithelial cells and then B lymphocytes via CD21 receptors. The clinical syndrome is driven largely by a strong cytotoxic T-cell response against infected B cells, producing atypical lymphocytosis, fever, and lymph node enlargement. Viral replication in the oropharynx precedes symptoms, and EBV then establishes lifelong latency in memory B cells with intermittent asymptomatic shedding; splenic enlargement reflects reticuloendothelial/lymphoid hyperplasia and underlies rupture risk in early illness (see standard EBV life-cycle and lymphoid tissue diagrams in microbiology/immunology texts).

Risk Factors

  • Primary EBV infection in adolescence or young adulthood (especially 15-24 years)
  • Close-contact living environments (for example university halls, military barracks)
  • Intimate saliva exposure (kissing, sharing utensils/drinks)
  • Immunosuppression (higher risk of severe or complicated disease)
  • Lack of prior childhood EBV exposure (delayed primary infection)

Clinical Features

Symptoms

  • Severe sore throat
  • Low-grade fever
  • Marked fatigue and malaise
  • Headache, myalgia, anorexia
  • Neck lumps from cervical lymph node enlargement
  • Left upper quadrant discomfort (splenic enlargement)
  • Rash, especially after aminopenicillin exposure

Signs

  • Bilateral posterior cervical lymphadenopathy (may also involve anterior cervical, axillary, inguinal nodes)
  • Tonsillar enlargement with exudate ('whitewash') and pharyngeal erythema
  • Palatal petechiae
  • Splenomegaly (typically peaks in week 2)
  • Hepatomegaly or right upper quadrant tenderness
  • Occasional jaundice

Investigations

Full blood count with differential/blood film:Lymphocytosis with atypical lymphocytes; mild thrombocytopenia or neutropenia may occur
Liver function tests:Mild-to-moderate transaminitis (often raised ALT/AST), usually self-limiting; bilirubin may rise if jaundiced
Heterophile antibody test (Monospot/Paul-Bunnell type):Often positive in adolescents/adults after first week of symptoms; lower sensitivity early illness and in young children
EBV serology:Acute infection pattern: VCA-IgM positive (often with VCA-IgG), EBNA-IgG absent early
CRP/throat swab if bacterial co-infection suspected:Helps identify streptococcal tonsillitis when presentation is atypical or severe
Ultrasound abdomen (selective):Confirms splenomegaly or evaluates suspected splenic complication
Additional virology/serology (if EBV tests negative but mononucleosis-like illness persists):May identify CMV, HIV seroconversion, toxoplasmosis, HHV-6, or adenovirus

Management

Lifestyle Modifications

  • Rest, hydration, and graded return to activity based on symptoms
  • Avoid alcohol during acute illness and while liver enzymes are abnormal
  • Avoid contact sports/heavy lifting for at least 3 weeks from symptom onset; longer if splenomegaly or ongoing symptoms
  • Provide safety-net advice: urgent review for breathing difficulty, severe unilateral throat pain, dehydration, abdominal pain (especially LUQ), syncope, or jaundice

Pharmacological Treatment

Analgesic/antipyretic

  • Paracetamol 1 g orally every 4-6 hours when required (maximum 4 g/24 h in adults)

First-line for throat pain and fever; reduce maximum dose in low body weight, malnutrition, or hepatic impairment.

NSAID

  • Ibuprofen 400 mg orally up to three times daily with food (maximum 2.4 g/24 h prescribed adult dose)

Use if additional analgesia needed; avoid/caution in active peptic ulcer disease, significant renal impairment, NSAID-sensitive asthma, anticoagulation, or dehydration.

Antibiotics (only if proven/suspected bacterial co-infection)

  • Phenoxymethylpenicillin 500 mg orally four times daily for 10 days (adult streptococcal tonsillitis regimen)

Do not use antibiotics routinely for uncomplicated EBV. Avoid amoxicillin/ampicillin in suspected mononucleosis because a prominent rash is common.

Corticosteroid (specialist indication only)

  • Dexamethasone single dose (for example 10 mg oral/IV in adults) in severe tonsillar oedema/impending airway obstruction

Not routine treatment; reserve for airway compromise or other severe complications and involve ENT/acute care.

Surgical / Interventional

  • No routine surgery
  • Urgent ENT procedures for complications: peritonsillar abscess drainage, airway intervention if obstruction
  • Emergency operative/radiological management if splenic rupture occurs

Complications

  • Hepatitis (usually subclinical transaminitis), rarely fulminant hepatitis
  • Severe tonsillar hypertrophy, peritonsillar abscess, and rare upper airway obstruction
  • Splenic rupture (rare but life-threatening, usually within first 3 weeks)
  • Haematological complications: autoimmune haemolytic anaemia, thrombocytopenia, severe neutropenia
  • Neurological complications: meningoencephalitis, aseptic meningitis, Guillain-Barre syndrome, cranial neuropathies
  • Cardiac complications: myocarditis, pericarditis, conduction abnormalities
  • Prolonged post-viral fatigue
  • Very rare chronic active EBV with increased lymphoproliferative risk

Prognosis

Most patients recover with supportive care in 2-4 weeks, though sore throat can persist for around a month and fatigue may take months to fully resolve. Around 10% have prolonged fatigue, but most regain baseline function over time (often within 2 years). EBV then remains latent lifelong with intermittent asymptomatic shedding; immunocompromised patients have higher risk of symptomatic reactivation or severe disease.

Sources & References

✅NICE Guidelines(1)

📖Textbook References(20)

  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 322, 323)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1107)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 744, 745)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 637)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1477)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1107, 1108)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1147, 1148)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 743, 744)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 46, 47)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 54)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 58)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 380, 381)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 110)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 672)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 56)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 60)[context]
  • Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 47)[context]
  • [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1108)[context]
  • [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1433, 1434)[context]
  • [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 1434)[context]

Sources

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