Infectious Disease

Infectious Mononucleosis (Glandular Fever)

Infectious mononucleosis is usually primary Epstein–Barr virus infection causing fever, exudative pharyngitis, lymphadenopathy and marked fatigue; the high-yield safety issues are avoiding unnecessary aminopenicillins, protecting an enlarged spleen and recognising airway, abdominal, hepatic, neurological and haematological complications.

In a nutshell

Infectious mononucleosis is usually EBV infection causing fever, exudative pharyngitis, posterior or generalised lymphadenopathy, marked fatigue and splenomegaly. Use a full blood count with a second-week heterophile test in immunocompetent adolescents and adults, use EBV-specific serology when the test is negative or unsuitable, offer HIV testing when acute HIV is a differential, avoid aminopenicillins, protect the spleen and escalate airway, abdominal, hepatic, haematological, neurological or cardiac complications.

Classic presentation

A young adult with prolonged fever, severe exudative sore throat, posterior cervical lymphadenopathy and profound fatigue, with atypical lymphocytes or a rash after amoxicillin.

Key points

EBV infects B cells and the reactive T-cell response produces atypical lymphocytes, lymphadenopathy, tonsillar enlargement and splenomegaly.
Heterophile antibodies can be negative early and are less reliable in young children and immunocompromised people.
If suspicion persists after a negative early test, repeat it or use EBV-specific serology; do not diagnose chronic infection from persistent EBV IgG.
Do not use amoxicillin, co-amoxiclav or ampicillin for uncomplicated glandular fever; treat a genuine bacterial co-infection through the current NICE pathway.
Avoid strenuous activity, heavy lifting and contact sport while acutely unwell and for at least the first month; return gradually and individually.
Offer HIV testing when acute HIV is part of the differential; no routine school exclusion is required once the person is well enough to attend.

First-line investigation

Full blood count and film plus a second-week heterophile antibody test in an immunocompetent adolescent or adult; use EBV-specific serology when early, negative, paediatric or immunocompromised, and check liver tests or alternative diagnoses according to the presentation.

Management

Recognise emergencies

Send urgently for stridor, drooling, inability to swallow saliva, severe breathing difficulty, severe dehydration or suspected deep-neck infection.^3,5,1
Treat sudden severe abdominal pain, collapse or peritonism as possible splenic rupture and arrange emergency resuscitation and surgical assessment.^3,1

Confirm the syndrome and exclude mimics

Use full blood count and film with a second-week heterophile test in immunocompetent adolescents and adults; repeat or use EBV-specific serology if the result is negative or unsuitable.^1,7,2
Check liver tests and offer HIV testing when acute HIV is part of the differential; consider CMV, toxoplasmosis, bacterial throat disease and haematological diagnoses according to context.^8,9,1,2

Support recovery

Give fluids, rest and age-appropriate analgesia; explain that the acute illness usually improves over 2–4 weeks but fatigue can last longer.^3,1,10
Avoid amoxicillin, co-amoxiclav and ampicillin unless a specialist has a compelling reason; treat confirmed bacterial co-infection through NICE NG84 and BNF.^4,5,11

Protect the spleen and manage complications

Avoid strenuous activity, heavy lifting and contact sport while acutely unwell and for at least the first month, then return gradually with individualised advice.^3,6,2
Use specialist-led corticosteroids only for selected severe complications such as impending airway obstruction; admit significant hepatic, haematological, neurological, renal or cardiac disease.^1,3,12

Safety-net and reduce transmission

Explain saliva transmission, avoid kissing and sharing cups or cutlery while unwell, and advise reassessment for worsening symptoms, persistent fever, progressive lymphadenopathy or disabling fatigue.^3,1
No routine school exclusion is required once the person is well enough to attend; return to work or study is symptom-led, while contact-sport return remains a separate spleen-safety decision.^13,3

Exam traps

A negative heterophile test in the first week does not exclude infectious mononucleosis.
A rash after amoxicillin in glandular fever is not automatically proof of a persistent penicillin allergy, but severe reactions still need assessment.
A positive throat culture can coexist with EBV and does not prove that streptococcus caused the whole syndrome.
Severe abdominal pain may be splenic rupture: treat it as an emergency.
Steroids are not routine treatment; reserve them for specialist-led severe complications such as impending airway obstruction.
Mononucleosis-like illness is an HIV indicator condition, so offer testing when acute HIV is in the differential.

Illustrations

Exudative tonsillitis in glandular feverA clinical photograph of markedly enlarged tonsils with exudate, resembling bacterial tonsillitis, in infectious mononucleosis.James Heilman, MD, Wikimedia Commons · CC-BY-SA-3.0

Atypical lymphocytes on the blood filmA blood film showing large reactive (atypical) lymphocytes, the hallmark of the immune response to Epstein–Barr virus.Ed Uthman, MD, Wikimedia Commons · CC-BY-2.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.