Infectious Mononucleosis

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Infectious mononucleosis (IM)\: caused by Epstein-Barr virus (EBV), characterised by fever, pharyngitis, and cervical
lymphadenopathy.
Incidence\: a
Transmission\: primarily via salivary secretions (kissing, sharing utensils); incubation period of 30-50 days.
Pathophysiology\: EBV infects B lymphocytes, causing lymphocytosis (primarily CD8+ T cells); triggers heterophile antibody
production detectable in blood tests.
Symptoms\: fever, tonsillar pharyngitis, bilateral cervical lymphadenopathy, fatigue, headache, myalgia, splenomegaly
(50%), and hepatomegaly (10-30%).
Diagnosis\: positive monospot test, atypical lymphocytosis (>10%), or elevated liver function tests (transaminitis); EBV-
speci
Management\: supportive care (rest, hydration, analgesia); avoid strenuous activities to prevent splenic rupture.
Complications\: splenic rupture (rare), airway obstruction, pericarditis, encephalitis, Guillain-Barré syndrome,
thrombocytopaenia, and chronic fatigue.
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Introduction

Infectious mononucleosis (IM), otherwise known as glandular fever, is characterised by the triad of fever, pharyngitis and
cervical lymphadenopathy.
1
IM most commonly a
cases are self-limiting and will resolve within 2-4 weeks; however, fatigue and malaise can persist signi
2-3
In a very small number of cases, life-threatening complications such as airway obstruction or splenic rupture can occur.
4

Aetiology

Approximately 90% of cases of IM are caused by Epstein-Barr virus (EBV).
1-4
EBV (also known as human herpes virus 4) is a double-stranded DNA virus from the herpes family. It is extremely
widespread and has infected approximately 95% of adults worldwide. In the UK, 85% of under 25s and 93% of people aged
22-24 are EBV positive, respectively.
5-6
IM is the most common manifestation of EBV, which predominantly a
children is usually asymptomatic, and IM in over 30s is uncommon.
3
EBV is also associated with other disorders, including\:
6-7Lymphoma (B cell, T cell, Hodgkin’s, Burkitt’s)
Nasopharyngeal carcinomaGastric carcinoma
Oral hairy leukoplakia
Acalculous cholecystitis
Neurological manifestations (e.g. multiple sclerosis, Guillain-Barré syndrome, encephalitis, transverse myelitis)
Haematological manifestations (e.g. lymphoproliferative disorders, thrombocytopaenia, haemolytic anaemia)
Transmission
EBV is primarily transmitted through salivary secretions. Infection most commonly results from kissing or sharing of food
utensils, hence IM is frequently referred to as “kissing disease”
4
.
Oral shedding persists for several months, although EBV is not particularly contagious, so onward infection is relatively
ine
3-4
exposure.
Less commonly, EBV can be transmitted via breastfeeding and sexual contact.
4
Pathophysiology
Following contact with EBV-positive oropharyngeal secretions, EBV infects the oropharyngeal epithelium and lymphoid
tissues. Through infecting oropharyngeal B lymphocytes, EBV induces a lytic infection cycle, enabling viral replication,
which is then disseminated via the lymphoreticular system.
3-4
Infected B lymphocytes also induce the release of heterophile antibodies, which can be detected in blood tests to
support a diagnosis of EBV infection.
1
Disseminated EBV infection produces a T-cell-mediated immune response, which aims to suppress primary EBV infection.
The e
atypical lymphocytosis (primarily CD8+ T cells and CD16+ natural killer cells), which is commonly associated with IM.
3-4
Once primary infection is suppressed, EBV persists as a lifelong latent infection prone to periodic reactivation and viral
shedding.
4
EBV-negative mononucleosis
Other causes of mononucleosis include\:
4
HIV
Cytomegalovirus (CMV)
Other human herpes viruses
T o x o p l a s m a g o n d i i
S t r e p t o c o c c u s p y o g e n e s
Mononucleosis syndrome
Infectious mononucleosis is primarily used to describe cases caused by EBV
infection. Mononucleosis syndrome should be used when the illness is due to a non-EBV aetiology.
3

Risk factors

Risk factors for EBV infection and IM include\:
3-4
Kissing
Sharing food or food utensils
Breastfeeding
Sexual contactClinical features
History
Most patients with acute IM will present with the classic triad of fever, tonsillar pharyngitis and bilateral cervical
lymphadenopathy. This is often preceded by several days of malaise.
3-4
Other notable symptoms include\:
Headache
Lethargy
Myalgia
Rash
Hoarseness
Cervicalgia
Nausea
Anorexia
Clinical examination
Most patients will have palpable and tender cervical lymphadenopathy in addition to pharyngitis. Pharyngitis may be
exudative and, in some cases, is accompanied by petechiae of the palate.
3-4
Other examination
3-4, 8
Splenomegaly\: present in 50-60% of cases and typically resolves within 3-4 weeks
Hepatomegaly\: present in 10-30% of cases
Jaundice
Periorbital oedema\: present in 10-35% of cases

Di

Important di
2-3, 8
Group A streptococcal pharyngitis\: may be clinically indistinguishable if tonsillar exudate is present
Non-EBV mononucleosis
Bacterial tonsillitis
Peritonsillar abscess
In

Investigations

Most cases of IM are self-limiting and can be safely investigated and managed in primary care.
Bedside investigations
All patients should have basic observations to assess for fever and evidence of systemic illness.
Laboratory investigations
Relevant blood tests that may be requested include\:
2,3,8
Full blood count\: raised white cells with lymphocytosis and prominent atypical lymphocytes (reactive CD8+ T cells)
Liver function tests\: hepatic involvement is present in approximately 90% of cases, typically as a mild self-limiting
transaminitis (ALT and AST >2-3 times upper normal limit)
Monospot test\: for all patientsMonospot test
Primary EBV infection of B lymphocytes results in the release of heterophile antibodies, which react with animal
antigens including horses.
The monospot test exposes a patient’s blood sample to a solution rich in equine erythrocytes. A positive
agglutination reaction con
9
The test should be obtained in the second week of illness as tests within the
negative rate.
3
EBV-speci
are highly sensitive and speci
test.
3,8
Imaging
For mild cases of IM, imaging is not usually required.
Where hepatosplenomegaly is present, abdominal ultrasound may be helpful to monitor for resolution, particularly in
athletes.
3

Diagnosis

IM should be suspected in all adolescents or young adults who present with typical symptoms.
2
In addition to a typical clinical presentation, IM is likely if investigations demonstrate\:
2-3
Positive monospot test, OR
>50% lymphocytosis and >10% atypical lymphocytes (reactive CD8+ T cells), OR
>20% reactive lymphocytes
If EBV-speci
suggests latent infection.
4

Management

Most cases of IM result in mild symptoms that are self-limiting within 2-4 weeks. Patients should be advised to rest and
maintain hydration until symptoms subside. Simple analgesics and antipyretics should be encouraged for symptom
management. 2-3
Isolation is not required and patients should aim to return to normal daily activities at the earliest
opportunity.
Patients should avoid strenuous exercise or contact sports within the
rupture.
2
Admission to hospital is only required if severe symptoms are present or signi
thrombocytopaenia, splenic rupture) are suspected.
2
Penicillin-induced rash
Patients with suspected or conpenicillins due to the risk
of developing a maculopapular rash. The mechanism of this rash is not fully understood but is suspected to
represent an EBV-induced hypersensitivity reaction. It is associated with amoxicillin, ampicillin and other beta-
lactams.
10Figure 1. Maculopapular exanthem
following amoxicillin treatment in a
patient with infectious mononucleosis

Complications

Acute complications
Acute complications of IM are rare but should be recognised. Notable complications include\:
2-4
Airway obstruction\: due to tonsillar oedema or peritonsillar abscess (quinsy)
Cardiac\: pericarditis, myocarditis and arrhythmias
Neurological\: encephalitis (in around 1%), aseptic meningitis, Guillain-Barré syndrome and optic neuritis
Haematological\: thrombocytopenia (in 25-50%) and autoimmune haemolytic anaemia
Splenic rupture\: occurs in less than 1%, but 50% of cases of splenic rupture are spontaneous
Acalculous cholecystitis
Deep neck space infections
Long-term complications
There are also some potential long-term complications associated with IM\:
2,3
Chronic fatigue\: fatigue may persist for several months after initial infection in around 10% of cases; the majority of these
recover within 2 years
Lymphoproliferative cancers\: particularly Hodgkin's lymphoma and Burkitt lymphoma
Chronic active EBV infection
Multiple sclerosis

References

Mohseni M, Boniface MP, Graham C. M o n o n u c l e o s i s . StatPearls. 2023. Available from\: [LINK].
NICE CKS. G l a n d u l a r f e v e r ( i n f e c t i o u s m o n o n u c l e o s i s ) . 2021. Available from\: [LINK].
BMJ Best Practice. Infectious mononucleosis. 2021. Available from\: [LINK].
UpToDate. I n f e c t i o u s m o n o n u c l e o s i s . 2024. Available from\: [LINK].
UpToDate. V i r o l o g y o f E p s t e i n-B a r r V i r u s . 2023. Available from\: [LINK].
Hoover K, Higginbotham K. E p s t e i n-B a r r V i r u s . StatPearls. 2023. Available from\: [LINK].
UpToDate. C l i n i c a l m a n i f e s t a t i o n s a n d t r e a t m e n t o f E p s t e i n-B a r r i n f e c t i o n . 2024. Omori MS. I n f e c t i o u s M o n o n u c l e o s i s ( I M ) i n E m e r ge n c y M e d i c i n e . Medscape. 2022. Available Available from [LINK].
from\: [LINK].
StuempLINK].
Ónodi-Nagy K, Kinyó Á, Meszes A, et al. A m o x i c i l l i n r a s h i n p a t i e n t s w i t h i n f e c t i o u s m o n o n u c l e o s i s \: e v i d e n c e o f t r u e d r u g
s e n s i t i z a t i o n . Allergy, Asthma & Clinical Immunology. 2015 Jan 9;11(1).
Image references
Figure 1. Ónodi-Nagy K, et al. A m o x i c i l l i n r a s h i n p a t i e n t s w i t h i n f e c t i o u s m o n o n u c l e o s i s \: e v i d e n c e o f t r u e d r u g s e n s i t i z a t i o n .
Allergy, Asthma & Clinical Immunology. License\: [CC BY 4.0]. Available from\: [LINK].Reviewer
Mrs Amy Campbell
Otorhinolaryngology Registrar

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Contents

Introduction
Aetiology
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