Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Infectious mononucleosis
Infectious diseases, microbiology and sexual health · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Time-critical presentation
Escalate stridor, drooling, respiratory distress, severe dysphagia with dehydration, confusion, focal neurology, jaundice with coagulopathy or left upper-quadrant pain and shock. Suspected splenic rupture requires immediate resuscitation and surgical assessment.
Overview
Recognise Epstein–Barr virus infectious mononucleosis, protect the airway and spleen, distinguish alternative causes of glandular-fever illness and avoid unnecessary antibiotics and unsafe activity.
Epstein–Barr virus spreads mainly through saliva and infects oropharyngeal epithelium and B lymphocytes. Adolescents and young adults commonly develop the recognisable mononucleosis syndrome, whereas children may have mild disease. Fatigue can persist for weeks even after fever and throat symptoms resolve.
Diagnosis is clinical plus selective testing. Full blood count may show lymphocytosis and atypical lymphocytes; liver enzymes are often raised. Heterophile antibody testing is convenient but imperfect early in illness. EBV viral-capsid and nuclear-antigen patterns can establish acute versus previous infection when uncertainty changes counselling or investigation.
Management protects airway, hydration and spleen while avoiding iatrogenic harm. Antibiotics are used only for proven bacterial coinfection. Severe tonsillar obstruction, haemolysis, thrombocytopenia or neurological disease may require hospital and specialist management. Persistent nodes, cytopenia or systemic decline deserve reassessment rather than indefinite attribution to EBV.
Key points
The typical syndrome combines fever, pharyngitis, posterior cervical lymphadenopathy and fatigue, but age and immune status alter presentation.
Aetiology
01
Epstein-Barr virus exposure
Salivary transmission introduces EBV to the oropharynx, with close contact increasing exposure during adolescence and young adulthood.
02
Age-related expression
Primary infection is often mild in childhood but more commonly produces mononucleosis when first acquired during adolescence or adulthood.
03
Immune status
Altered cellular immunity changes clinical expression and increases the risk of persistent replication or EBV-associated lymphoproliferative disease.
Pathophysiology
1
Oropharyngeal infection
EBV replicates in oropharyngeal tissue and infects B lymphocytes through specific surface receptors before spreading through lymphoid tissue.
2
B-cell expansion
Infected B cells circulate and activate, while viral latency allows lifelong persistence after the acute illness resolves.
3
Cytotoxic immune response
Reactive T lymphocytes expand to control infected B cells, producing atypical lymphocytosis, lymph-node enlargement and systemic symptoms.
4
Reticuloendothelial enlargement
Immune-cell proliferation in liver and spleen causes hepatitis and splenomegaly, creating a temporary risk of splenic injury.
Clinical features and red flags
Typical glandular-fever syndrome
Fever, marked fatigue, exudative pharyngitis and posterior cervical or generalised lymphadenopathy with lymphocytosis support infectious mononucleosis.
Threatened airwayRed flag
Progressive tonsillar swelling, muffled voice, drooling, stridor, inability to swallow or respiratory effort requires urgent airway-capable assessment.
Splenic complicationRed flag
Left upper-quadrant or shoulder-tip pain, dizziness, hypotension or collapse during acute illness suggests splenic injury or rupture.
Atypical or prolonged course
Prominent genital ulceration, cytopenias, progressive focal nodes, substantial jaundice or symptoms beyond the expected trajectory prompts a broader differential.
Investigations
01Full blood count and blood filmFirst step
Why
Identify lymphocytosis, atypical lymphocytes, cytopenia and an alternative haematological pattern.
Interpretation and limitations
Atypical lymphocytes support but do not prove EBV. Severe anaemia, thrombocytopenia, blasts or persistent abnormalities require urgent review.
02Heterophile antibody test
Why
Provide rapid support for infectious mononucleosis in an appropriate age and illness window.
Interpretation and limitations
Early false negatives occur and sensitivity is lower in children. A positive result is interpreted with the syndrome rather than used as a population screen.
03EBV-specific serology
Why
Resolve acute, past or absent infection when heterophile testing is negative or diagnostic certainty matters.
Interpretation and limitations
Viral capsid IgM supports recent infection, while EBV nuclear antigen usually indicates later or past infection; laboratory pattern and immune status require interpretation.
04Liver tests and coagulation when indicated
Why
Assess common hepatitis and identify rare severe hepatic dysfunction.
Interpretation and limitations
Mild transaminase elevation is frequent. Marked jaundice, rising INR or encephalopathy is not routine and requires urgent specialist investigation.
Differential diagnosis
01
Streptococcal tonsillitis
Prominent sore throat and exudate overlap; validated clinical assessment and bacterial testing identify patients who may benefit from antibiotics.
02
Acute HIV infection
Fever, rash, pharyngitis and lymphadenopathy with relevant exposure require the correct antigen-antibody and nucleic-acid pathway, consent and reliable result follow-up.
03
Cytomegalovirus or toxoplasmosis
Mononucleosis-like fever and atypical lymphocytes with negative EBV testing suggest alternative infections according to immune and exposure context.
04
Haematological malignancy
Persistent focal nodes, cytopenia, weight loss or blasts require haematology assessment and sometimes tissue rather than repeated viral attribution.
Management
01Uncomplicated syndromeSupport recovery and protect the spleenFirst stepThe patient is stable, drinking and has no airway, hepatic, haematological or abdominal emergency.+
1Confirm the clinical pattern, use selective FBC and EBV testing when helpful and avoid antibiotics unless bacterial infection is established.
2Provide fluids, appropriate analgesia, rest and written advice about fatigue, alcohol while liver tests are abnormal and transmission through saliva.
3Advise no collision sport, heavy lifting or other trauma-risk activity for at least the first month after symptom onset and until clinically recovered, with individual review before high-risk return.
02Airway or severe complicationEscalate beyond routine supportive careEscalationThere is stridor, inability to swallow, severe cytopenia, neurological disease, hepatic failure or suspected splenic rupture.+
Complications
01
Upper-airway obstruction
Marked tonsillar and pharyngeal inflammation can impair swallowing and ventilation and may require airway-capable specialist management.
02
Splenic rupture
Enlarged friable spleen can bleed spontaneously or after trauma, causing abdominal or shoulder pain, shock and emergency surgery.
03
Haematological or neurological disease
Haemolytic anaemia, thrombocytopenia, encephalitis, meningitis and neuropathy are uncommon immune-mediated complications that may require admission and specialist treatment.
04
Prolonged functional impairment
Fatigue and reduced exercise capacity can continue for weeks, disrupting study and work even after acute inflammation settles.
Monitoring and follow-up
Reassess airway, swallowing and hydration promptly if throat swelling progresses or oral intake falls.
Provide emergency advice for left upper-quadrant or shoulder-tip pain, dizziness and collapse; document the first-month restriction on contact sport, heavy lifting and trauma-risk work and the criteria for individual return.
Repeat FBC or liver tests only when initial abnormalities are clinically important, worsening or needed to guide return to activity and treatment.
Review persistent fever, focal lymphadenopathy, weight loss, cytopenia or deteriorating function for alternative infection or malignancy.
Explain that fatigue may outlast infectivity and throat symptoms, while graded return to activity should avoid both premature trauma risk and unnecessary prolonged bed rest.
Special situations
The rash is not simple penicillin proof
An aminopenicillin-associated rash during EBV does not automatically establish persistent IgE-mediated allergy; record the phenotype and arrange later assessment when relevant.
Early screening can be negative
A negative heterophile test in the first illness days should prompt timing-aware serology or reassessment rather than immediate exclusion.
The spleen may be silent
Palpation is insensitive for enlargement, so absence of a palpable spleen cannot alone authorise early collision sport.
Fatigue needs a second look when atypical
Persistent tiredness is common, but progressive nodes, anaemia, weight loss or organ dysfunction should not be labelled post-viral without reassessment.
Common pitfalls
01
Prescribing amoxicillin for exudative pharyngitis without assessing EBV.
02
Excluding infectious mononucleosis after one early negative heterophile test.
03
Using routine corticosteroids for uncomplicated sore throat or fatigue.
04
Clearing collision sport solely because the spleen is not palpable.
05
Attributing persistent focal lymphadenopathy and cytopenia indefinitely to previous EBV.
Practice
Two practice questions
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Question 1 of 2
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Infectious diseases, microbiology and sexual healthOriginal SBA
Negative early heterophile test
A university student has five days of fever, posterior cervical lymphadenopathy, exudative pharyngitis and lymphocytosis, but the heterophile test is negative. What is the best interpretation?
Sources and review status3 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Examine the airway, hydration, liver and spleen and ask about abdominal pain; tonsillar appearance alone cannot determine severity.
A heterophile antibody test may be negative early or in younger people. EBV-specific serology clarifies timing when the diagnosis matters and the initial test is non-diagnostic.
Avoid amoxicillin or ampicillin for uncomplicated suspected EBV because they do not treat the virus and commonly provoke a widespread rash.
Treatment is usually rest, fluids and appropriate analgesia. Corticosteroids are not routine and are reserved for selected severe complications with specialist input.
Advise no contact or collision sport, heavy lifting or other trauma-risk activity for at least the first month after symptom onset and until clinically recovered; use individual specialist review for ongoing splenomegaly or high-risk return.
Consider acute HIV, cytomegalovirus, streptococcal tonsillitis, toxoplasmosis, haematological malignancy and diphtheria where epidemiology or features do not fit.
05Targeted alternative-infection testing
Why
Investigate streptococcus, acute HIV, CMV, toxoplasma or diphtheria according to exposure and phenotype.
Interpretation and limitations
Avoid indiscriminate panels. Acute HIV requires the correct antigen-antibody or nucleic-acid pathway and appropriate consent and follow-up.
1
Perform ABCDE, involve ENT, anaesthetic, surgical, haematology or liver teams according to the complication and obtain urgent blood tests and imaging without destabilising the airway.
2Use corticosteroids only for a selected severe indication through specialist care; treat bacterial coinfection or haemodynamic compromise on its own evidence.
3Monitor closely until airway, hydration, blood counts, liver function or abdominal findings have demonstrably stabilised.
03Diagnosis remains uncertainTest the competing syndromeHeterophile testing is negative early, exposure is atypical or symptoms and results do not fit EBV.+
1Review timing, sexual and travel exposure, medicines, vaccination and exact lymph-node distribution and inspect for rash, hepatosplenomegaly and mucosal disease.
2Use EBV-specific serology and targeted HIV, CMV, streptococcal, toxoplasma or haematological investigations rather than repeating one screening test indefinitely.
3Reassess persistent focal lymphadenopathy, cytopenia or systemic decline for malignancy or another chronic infection and arrange tissue when indicated.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Relieves fever and throat pain to support hydration during uncomplicated illness.
Paracetamol
For most adults give 500 mg to 1 g by mouth at intervals of at least four hours, no more than 4 g daily.
Reduce maximum exposure in low weight, liver dysfunction, malnutrition or heavy alcohol use, and check combination remedies to avoid overdose.
Reduces critical inflammatory swelling or immune-mediated harm when supportive care is insufficient.
Corticosteroid for selected severe complication
Use a short specialist-directed systemic regimen only for threatened airway or another accepted severe immune complication.
Not routine for fatigue or uncomplicated pharyngitis; exclude bacterial deep-neck infection, monitor glucose and secondary infection, and document the precise indication and stop plan.