About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Caused by EBV (HHV-4) — transmitted by saliva ("kissing disease"). Peak incidence in 15-25 year olds. Incubation 4-6 weeks
- Classic triad: fever, pharyngitis (often severe, exudative tonsillitis), and generalised lymphadenopathy (especially posterior cervical). Also: fatigue, hepatosplenomegaly, petechial rash on palate
- Diagnosis: Monospot/Paul-Bunnell test (heterophile antibodies — positive in ~85% by week 2). Atypical lymphocytes on blood film (activated T-cells). EBV-specific serology (IgM VCA) for confirmation
- Treatment: supportive — rest, fluids, paracetamol. AVOID amoxicillin/ampicillin (causes characteristic maculopapular rash in ~90%). Avoid contact sports for 6-8 weeks (splenic rupture risk)
- Complications: splenic rupture (rare but life-threatening), airway obstruction (tonsillar enlargement), hepatitis, Guillain-Barré, chronic fatigue. EBV is associated with Burkitt lymphoma, nasopharyngeal carcinoma, post-transplant lymphoproliferative disease
Overview
Infectious mononucleosis (glandular fever) is an acute infection caused by Epstein-Barr virus (EBV/HHV-4), a gamma-herpesvirus. It is spread through saliva and primarily infects B-lymphocytes and oropharyngeal epithelium. EBV establishes lifelong latency in B-cells. In young children, primary EBV infection is usually subclinical; in adolescents and young adults, it presents as glandular fever. The illness typically lasts 2-4 weeks but fatigue can persist for months.
Epidemiology
EBV infects >95% of the world population by adulthood. In developed countries, primary infection is often delayed to adolescence/early adulthood, which is when symptomatic glandular fever occurs. In the UK, it is one of the most common causes of prolonged sore throat and fever in 15-25 year olds, frequently affecting university students.
Clinical Features
Symptoms
Severe sore throat — often the most prominent symptom, may resemble streptococcal tonsillitis
Fever (often high and prolonged, 1-2 weeks)
Profound fatigue and malaise (may persist for weeks-months)
Headache and myalgia
Abdominal pain (splenomegaly)
Signs
Tonsillar enlargement with white/grey exudate (may be bilateral, severe, almost meeting in midline)
Generalised lymphadenopathy — posterior cervical chain is particularly characteristic
Splenomegaly (~50%) and hepatomegaly (~10%)
Periorbital oedema (early sign, ~30%)
Palatal petechiae
Maculopapular rash (particularly if given amoxicillin/ampicillin — ~90%)
Jaundice (if hepatitis present — uncommon)
Investigations
First-line
Monospot / Paul-Bunnell testDetects heterophile antibodies — rapid test. Sensitivity ~85% by week 2 of illness. May be FALSE NEGATIVE in first week and in children <12 years. False positives rare
FBC and blood filmRaised lymphocyte count with ATYPICAL LYMPHOCYTES (>10% — large activated T-cells with abundant cytoplasm and irregular nucleus). Mild thrombocytopenia common
Second-line
EBV-specific serologyIgM to viral capsid antigen (VCA) = acute infection. IgG VCA + EBNA antibodies = past infection. Used when Monospot is negative but clinical suspicion remains
LFTsMildly deranged in ~80% (transaminitis — usually 2-3× normal). Rarely clinically significant hepatitis
Specialist
Throat swabTo exclude concurrent Group A Strep pharyngitis (co-infection occurs in ~5%)
HIV testIf Monospot negative and clinical picture consistent — HIV seroconversion mimics glandular fever closely
Management
NICE CKS — Glandular Fever1
Supportive treatment
- Rest, adequate fluids, paracetamol and ibuprofen for fever and throat pain
- Most cases resolve within 2-4 weeks; fatigue may persist for several months
- No specific antiviral treatment — aciclovir does NOT improve outcomes in EBV
2
Key avoidances
- Do NOT prescribe amoxicillin or ampicillin — causes a characteristic maculopapular rash in ~90% of EBV patients (not a true allergy but should be avoided)
- Avoid contact sports for 6-8 WEEKS — risk of splenic rupture (spleen is enlarged and vulnerable)
- Avoid alcohol during active illness (hepatitis risk)
3
When to consider admission
- Airway compromise from severe tonsillar enlargement — may need short course steroids (dexamethasone) or ENT review
- Dehydration from inability to swallow
- Suspected splenic rupture: acute left upper quadrant pain → emergency USS/CT → surgical emergency
Complications
- Splenic rupture: Rare but life-threatening — avoid contact sports for 6-8 weeks
- Airway obstruction: Massive tonsillar enlargement — may need steroids or very rarely tonsillectomy
- Hepatitis: Mild transaminitis common; rarely clinical jaundice
- Autoimmune haemolytic anaemia: Cold agglutinins (IgM) — Coombs positive
- Guillain-Barré syndrome: Rare post-infectious complication
- Chronic fatigue: Post-viral fatigue can persist for months — reassure and support
- EBV-associated malignancies: Burkitt lymphoma (endemic African type), nasopharyngeal carcinoma, Hodgkin lymphoma, PTLD (post-transplant)
UKMLA Exam Tips
- 1Sore throat + posterior cervical lymphadenopathy + splenomegaly + atypical lymphocytes = glandular fever
- 2Amoxicillin rash in EBV: maculopapular, NOT a penicillin allergy — do not label as penicillin-allergic
- 3Monospot negative + glandular fever picture = consider: (1) early EBV (repeat in 1 week), (2) HIV seroconversion, (3) CMV, (4) toxoplasmosis
- 4Avoid contact sports for 6-8 weeks — splenic rupture risk. This is the most commonly tested complication
- 5Atypical lymphocytes = activated T-cells (NOT the infected B-cells — the T-cells are responding to infected B-cells)
- 6EBV is associated with Burkitt lymphoma (c-MYC translocation t(8;14)), nasopharyngeal carcinoma, and PTLD
practicetest your knowledge on infectious mononucleosisApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — infectious diseases and beyond.
open q-bank