Key Facts

Infectious mononucleosis (glandular fever) is the clinical syndrome caused by primary EBV infection, predominantly affecting adolescents and young adults. Most infections are self-limiting but complications can be serious.

Epidemiology

• 95% of adults worldwide are EBV seropositive
• Primary infection in early childhood: usually subclinical
• Adolescent/young adult primary infection: symptomatic mononucleosis in ~50%
• Peak incidence: 15–24 years
• Known as the 'kissing disease' — spread via saliva

Aetiology

• EBV (HHV-4): double-stranded DNA virus, Herpesviridae family (Gammaherpesvirinae)
• Transmission: saliva (kissing, shared utensils); rare: blood transfusion, transplant
• Incubation: 4–6 weeks (adolescents/adults)
• After primary infection, EBV establishes lifelong latency in B-lymphocytes

Pathophysiology

• EBV infects oropharyngeal epithelial cells → B-lymphocyte infection via CD21 receptor
• Infected B-cells proliferate → polyclonal B-cell activation → atypical lymphocytes (reactive CD8+ T-cells)
• Heterophile antibodies: cross-reactive IgM antibodies (basis of Monospot test)
• Splenomegaly: reactive lymphoid hyperplasia
• Oncogenic potential: EBV latent genes (LMP1, EBNA) promote B-cell immortalisation → lymphoma risk in immunocompromised

Typical Presentation

• Prodrome: malaise, fatigue, headache (1–2 weeks)
• Sore throat: severe pharyngitis with tonsillar enlargement and grey-white exudate (can mimic streptococcal pharyngitis)
• Fever: high, lasting 1–2 weeks
• Lymphadenopathy: cervical (especially posterior triangle), generalised in some
• Splenomegaly: ~50% (usually mild)
• Hepatomegaly: ~10%
• Fatigue: prominent, may persist for weeks to months

Other Features

• Periorbital oedema (Hoagland sign)
• Petechiae at junction of hard and soft palate
• Jaundice (hepatitis in ~5%)
• Rash: spontaneous in ~5%; ~90% if given amoxicillin

Complications

• Airway obstruction: massive tonsillar enlargement
• Splenic rupture: rare, 0.1–0.5%; usually weeks 2–3; avoid contact sports ≥4 weeks
• Haemolytic anaemia: cold agglutinins (anti-i)
• Thrombocytopenia: immune-mediated
• Hepatitis: raised transaminases in ~80% (usually mild)
• Neurological: Guillain-Barré, cranial nerve palsies, meningoencephalitis (rare)

Red Flags

• Stridor or drooling (airway compromise)
• Left upper quadrant pain (splenic rupture)
• Severe jaundice
• Prolonged or worsening symptoms >4 weeks
• Immunocompromised patient (risk of lymphoproliferative disease)

Bedside

• Throat examination: tonsillar enlargement, exudate, palatal petechiae
• Abdominal palpation: splenomegaly (gentle — risk of rupture)

Bloods

• FBC and blood film: lymphocytosis with >10% atypical lymphocytes (large, reactive T-cells)
• Monospot test (Paul-Bunnell/heterophile antibody): positive in ~85% by week 2; may be negative early or in children <4 years
• EBV serology: VCA IgM (acute infection), VCA IgG (past/current), EBNA IgG (past infection — negative in acute)
• LFTs: elevated transaminases in ~80%; raised bilirubin in ~5%
• CRP: mildly elevated
• Throat swab: exclude concurrent Group A Strep (~5% co-infection rate)

Imaging

• USS abdomen: if splenomegaly suspected or abdominal pain (assess splenic size)
• CT neck: if airway compromise or parapharyngeal abscess suspected

Special Tests

• EBV PCR: for immunocompromised patients or diagnostic uncertainty
• Direct antiglobulin test (DAT/Coombs): if haemolysis suspected

Non-pharmacological

• Rest: avoid strenuous activity and contact sports for ≥4 weeks from symptom onset (splenic rupture risk)
• Adequate hydration and nutrition
• Avoid alcohol: during hepatitis phase
• Return to sport: guided by symptoms; ultrasound to assess splenic size if uncertain

Pharmacological

• Symptomatic: paracetamol and/or ibuprofen for fever and pain
• Avoid amoxicillin/ampicillin: causes widespread maculopapular rash in EBV infection
• Short course corticosteroids: only for specific complications:
  • Airway obstruction (impending): dexamethasone 0.15mg/kg or prednisolone 1mg/kg for 3–5 days
  • Severe thrombocytopenia
  • Autoimmune haemolytic anaemia
• Aciclovir: NOT routinely recommended (does not alter clinical course despite reducing viral shedding)
• Antibiotics: only if confirmed secondary bacterial infection (NOT empirical)

Surgical/Interventional

• Tonsillectomy: rarely needed for recurrent obstruction
• Splenectomy: for splenic rupture (emergency)
• Emergency airway management: if severe tonsillar swelling

Referral Criteria

• ENT: airway compromise, peritonsillar abscess
• Haematology: severe cytopenias, suspected lymphoproliferative disease
• Emergency surgery: suspected splenic rupture
• GP follow-up: most cases managed in primary care with safety-netting

• Self-limiting in most cases; acute illness resolves in 2–4 weeks
• Fatigue may persist for 3–6 months (occasionally longer)
• Splenic rupture: ~0.1–0.5%; mortality <5% with prompt surgery
• Full recovery expected in >95% of immunocompetent patients
• EBV-associated malignancy: lifetime risk increased but absolute risk low in immunocompetent
• PTLD: major risk in transplant recipients on immunosuppression
• Chronic active EBV infection: extremely rare; poor prognosis

EBV Serology Interpretation

EBV-Associated Conditions