Ep 228 – Infectious mononucleosis

In this episode, Dr Roger Henderson discusses infectious mononucleosis, a common viral illness that can present a surprisingly complex diagnostic and clinical challenge. Most often associated with Epstein–Barr virus (EBV), infectious mononucleosis is particularly familiar in adolescents and young adults, where fever, pharyngitis, lymphadenopathy and fatigue can create a classic clinical picture. But recognising the syndrome is only the beginning. Similar presentations can occur with other infections, including acute HIV and cytomegalovirus, while complications such as airway obstruction and splenic rupture, although uncommon, require careful attention. Here, he explores how EBV infection presents, how to approach diagnosis and differential diagnosis, what evidence-based supportive management involves, and the key advice GPs should give patients about activity, recovery and potential complications.

Key take-home points

• Infectious mononucleosis is most commonly caused by EBV, one of the most widespread human infections worldwide.
• EBV infection is usually asymptomatic when acquired during childhood, whereas symptomatic infectious mononucleosis is more common during adolescence and early adulthood.
• Transmission occurs mainly through close personal contact and exposure to saliva, with an incubation period of approximately 4 to 8 weeks.
• The classic clinical picture is fever, pharyngitis and lymphadenopathy, often accompanied by significant fatigue.
• Cervical lymphadenopathy is common, while splenomegaly occurs in approximately half of affected patients.
• A mononucleosis-like presentation is not specific to EBV. Consider group A streptococcus, cytomegalovirus, acute HIV, toxoplasmosis and other viral infections, as well as non-infectious causes such as drug reactions and lymphoma.
• A complete blood count commonly shows leucocytosis, lymphocytosis and atypical lymphocytes, while liver function tests may demonstrate mild transaminase elevation.
• EBV-specific antibody testing provides stronger diagnostic performance than heterophile antibody testing, although a Monospot test may be useful because it is faster and less expensive.
• A negative heterophile antibody test does not necessarily exclude EBV infection; confirmatory EBV-specific antibody testing should be considered when clinical suspicion remains high.
• Acute HIV infection can closely resemble infectious mononucleosis. If clinical suspicion remains high despite negative initial testing, HIV RNA testing should be considered.
• Imaging is not routinely required for uncomplicated infectious mononucleosis and is generally reserved for suspected complications such as airway obstruction, splenic rupture or haemophagocytic lymphohistiocytosis.
• Management is primarily supportive, focusing on hydration, rest, nutrition and symptom control. Routine antiviral therapy and corticosteroids are not recommended for uncomplicated disease.
• Splenic rupture is rare but potentially life-threatening, so patients should receive clear advice about avoiding strenuous activity during the early stages of illness and delaying contact sports.
• Most patients recover completely, but fatigue can persist for several months and, in some cases, 6 months or longer. Clear counselling about gradual recovery is therefore an important part of management.

Key references

1. Ebell MH, et al. JAMA. 2016;315(14):1502-1509. doi: 10.1001/jama.2016.2111.
2. Vouloumanou EK, et al. Curr Opin Hematol. 2012;19(1):14-20. doi: 10.1097/MOH.0b013e32834daa08.
3. De Paor M, et al. Cochrane Database Syst Rev. 2016;12:CD011487. doi: 10.1002/14651858.CD011487.pub2.
4. Putukian M, et al. Clin J Sport Med. 2023;33(4):359-367. doi: 10.1097/JSM.0000000000001161.
5. Gomes K, Goldman RD. Can Fam Physician. 2023;69(2):101-102. doi: 10.46747/cfp.6902101.
6. Shi T, et al. J Med Virol. 2020;93(6):3824-3834. doi: 10.1002/jmv.26558.