Infectious Mononucleosis
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Direct answer
Infectious mononucleosis is a clinical syndrome of fever, pharyngitis, lymphadenopathy and splenomegaly, most often caused by Epstein-Barr virus, a herpesvirus that infects B lymphocytes. Atypical lymphocytes on the peripheral smear and a positive heterophile antibody test support the diagnosis. Management is supportive, and the enlarged spleen must be protected because it is at risk of rupture.
What you must remember
- Causative agent: Epstein-Barr virus, human herpesvirus 4, enters B cells through the CD21 receptor and then establishes lifelong latency.
- Atypical lymphocytes: Reactive, activated T cells; more than about 10 per cent of leucocytes is a classic threshold for the diagnosis.
- Paul-Bunnell test: Heterophile antibodies agglutinate sheep red cells, and the test is less sensitive in young children, who may need EBV-specific serology.
- Ampicillin rash: A maculopapular rash after ampicillin or amoxicillin during mononucleosis is not a true penicillin allergy and should not lead to allergy labelling.
- Splenic rupture: Contact sports and heavy lifting are avoided until the spleen returns to normal size, usually for several weeks.
- Complications: Haemolytic anaemia, thrombocytopenia, hepatitis, airway obstruction and Guillain-Barré syndrome; corticosteroids are reserved for airway compromise or severe haemolysis or thrombocytopenia.
A worked example: a student with sore throat and fever
Consider a 19-year-old student with ten days of fever, exudative tonsillitis, tender posterior cervical nodes and an enlarged spleen. The white count is 14 x 10^9 per litre with about 40 per cent atypical lymphocytes, and the heterophile test is positive. Her doctor first suspects streptococcal pharyngitis and prescribes amoxicillin, and a maculopapular rash appears on day five. This is the classic ampicillin rash of mononucleosis, so the drug is reviewed and she is not labelled as penicillin-allergic. Supportive care with fluids and analgesia continues, and liver enzymes and platelet counts are checked. She is advised to avoid contact sports for several weeks and to return at once for left upper abdominal or shoulder tip pain, which can signal splenic rupture. If the picture is atypical or the test is negative, EBV-specific serology settles the diagnosis. Discharge advice repeats the warning about the spleen and explains that fatigue can last several weeks, so the student can plan study and sport accordingly. Follow-up blood counts and liver tests are repeated if the initial abnormalities were marked, and a repeat count is useful if new bleeding, jaundice or a persistent sore throat develops.
Where the exam tries to catch you
Mononucleosis is a favourite for confusing differentials. Streptococcal pharyngitis can look similar, but mononucleosis has lymphadenopathy beyond the neck, splenomegaly and atypical lymphocytes. The Paul-Bunnell test is often negative in the first week and in young children, so a negative result does not exclude EBV, and cytomegalovirus infection frequently gives a heterophile-negative picture. The ampicillin rash is a dependable trap: examiners ask whether a rash after amoxicillin is an allergy, and in mononucleosis the answer is no. Acute HIV, toxoplasmosis and drug reactions can also mimic the illness, which is why a viral picture with a negative heterophile test prompts further serology.
Frequently asked questions
Which test confirms infectious mononucleosis when the heterophile test is negative?
EBV-specific serology, including VCA IgM and the pattern of EBNA antibodies, or EBV PCR, confirms infection when the Paul-Bunnell or Monospot test is negative. This matters most in young children and in the first week of illness.
Why does ampicillin cause a rash in infectious mononucleosis?
Patients with EBV infection develop a maculopapular rash after aminopenicillins, and the mechanism is not classic IgE-mediated allergy. The rash therefore does not establish true penicillin allergy and should not automatically lead to lifelong labelling.
Is corticosteroid treatment routine in infectious mononucleosis?
No. Corticosteroids are reserved for airway obstruction, severe haemolytic anaemia, severe thrombocytopenia or neurological complications. Supportive care is the mainstay for most patients with uncomplicated infectious mononucleosis.
Which malignancies are linked with Epstein-Barr virus?
Epstein-Barr virus is linked with Burkitt lymphoma, nasopharyngeal carcinoma, some Hodgkin lymphomas and post-transplant lymphoproliferative disorder, and with oral hairy leukoplakia in HIV. These associations are high-yield in NEET-PG pathology and microbiology.