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Infectious Mononucleosis (Glandular Fever)

NICE CKS Infectious mononucleosis (glandular fever). Last revised: Nov 2024.

Infectious Mononucleosis (Glandular Fever)

Infectious mononucleosis, also known as glandular fever, is an acute viral upper respiratory tract infection most commonly caused by Epstein-Barr virus (EBV). It classically presents with fever, sore throat, and cervical lymphadenopathy.

This updated UKMLA guide to infectious mononucleosis is based on NICE CKS, which covers causes, symptoms, complications, diagnosis and management.

Cause

Infectious mononucleosis is an acute viral upper respiratory tract infection, most commonly caused by Epstein-Barr virus (EBV) or HHV-4.

The term ‘mononucleosis-like illness‘ is often used if symptoms are caused by a non-EBV aetiology, such as CMV, HHV-6, toxoplasmosis, HIV, or adenovirus

Transmission

EBV is primarily transmitted through close contact with the saliva of an infected person

  • Such as kissing, sharing utensils
  • Therefore, infectious mononucleosis is also known as the “kissing disease”

Epidemiology

Acute infectious mononucleosis is most common in 15-24 y/o

>95% of adults worldwide have been infected with EBV, but most of these adults have asymptomatic or subclinical infections

Clinical Features

Classic triad of infectious mononucleosis (and mononucleosis-like illness):

  • Fever (often low-grade)
  • Cervical lymphadenopathy
    • Classically bilateral posterior cervical lymphadenopathy (→ bull neck appearance)
    • But may also affect other lymph nodes (e.g. anterior cervical chain, submandibular, suboccipital, postauricular)
  • Sore throat (usually severe)
    • Transient palatal petechiae and pharyngeal inflammation are common
    • Tonsillar enlargement and tonsillar exudates

Other clinical features:

  • Prodromal symptoms (e.g. general malaise, fatigue, myalgia, chills, sweats, anorexia, headache)
  • Hepatomegaly, splenomegaly
  • Abdominal pain
  • Fine, diffuse maculopapular rash

A stereotypical infectious mononucleosis presentation is a patient who is treated with amoxicillin for presumed streptococcal tonsillitis/pharyngitis, then develops a widespread maculopapular rash.

Complications

Acute complications:

  • Splenic rupture (from splenomegaly)
    • Rare (<1%) but potentially life-threatening
    • Tends to occur spontaneously rather than traumatically
  • Hepatitis
  • Quinsy (which may cause upper airway obstruction)
  • Pericarditis, myocarditis
  • Meningoencephalitis
  • Acute kidney injury

EBV infection is also a well-established risk factor for:

  • Multiple sclerosis
  • Lymphoproliferative cancers
    • Hodgkin’s lymphoma
    • Burkitt lymphoma (aggressive non-Hodgkin B-cell lymphoma)
    • Nasopharyngeal carcinoma

Investigation and Diagnosis

Key investigations to diagnose infectious mononucleosis:

Test / purpose Description
Confirmatory test Monospot test (heterophile antibody test)

  • 1st line for most patients
  • To be performed in the 2nd week of illness

EBV serology

  • 1st line for those <4 y/o and immunocompromised
  • To be performed at least 1 week after the illness
Supportive laboratory findings FBC:

  • Lymphocytosis
  • Mild neutropaenia
  • Autoimmune haemolytic anaemia
  • Mild thrombocytopaenia

LFT:

  • ↑ AST and ALT during the acute phase of infection

If the Monospot test and EBV serology are negative, but clinical suspicion of infectious mononucleosis remains, consider:

  • Repeat testing (as early tests may be falsely -ve)
  • Alternative causes of a mononucleosis-like illness:
    • CMV
    • Toxoplasmosis
    • HIV (seroconversion illness)

Management

Infectious mononucleosis is managed conservatively

  • Explain that most symptoms usually last for 2-4 weeks
  • Paracetamol and/or ibuprofen for pain and fever
  • Advise to rest as needed and maintain adequate hydration
  • Limit the spread of infection
    • Good hand and respiratory hygiene practices
    • Avoid kissing, sharing food and utensils
    • Routine exclusion from work, school or nursery is NOT necessary
  • To reduce the risk of splenic rupture
    • Avoid heavy lifting and contact or collision sports (e.g. rugby) for 3 weeks after symptom onset
    • After 3 weeks, activities can be resumed if the patient is asymptomatic and has no signs of acute infection
  • Avoid excessive alcohol intake during the acute illness

Arrange emergency hospital admission if the person has ANY of the following:

  • Signs of upper airway obstruction, such as stridor and respiratory distress
  • Signs of severe dehydration that cannot be managed in primary care
  • A suspected serious or life-threatening complication, such as quinsy, splenic rupture, or sepsis

References

Related Articles

Pharyngitis / Tonsillitis

Quinsy (Peritonsillar Abscess)

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