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Glandular fever ( Infectious mononucleosis )

Infectious mononucleosis- also known as glandular fever is a benign lymphoproliferative disorder – viral infection caused by Epstein- Barr virus 
( EBV ) in 90 % cases
 EBV is a lymphocrytovirus – member of the Y-herpesvirus family – infects atleast 90 % of the population worldwide
 ( majority have no recognizable illness ) by adulthood
 Rest of the cases are caused by
○ cytomegalovirus
○ human herpesvirus 6
○ toxoplasmosis
○ adenovirus
 Seroconversion –> commonest in younger children and usually asymptomatic

Disease of primarily teenagers and young adults occurring in approximately 7 % with sore throat

As most population is positive for EBV special precautions against transmission are not necessary in most cases

Pathophysiology EBV first infects the oropharyngeal epithelial cells via C3d receptors After initial replication in the nasopharynx the virus infects B cells Integrates into the lifecycle of healthy B lymphocytes and can remain as lifelong latent infection Humoral response -Directed against EBV structural proteins structural response-T-lymphocyte cellular response – critical in control and determining the clinical expression of EBV infection

Epidemiology-Teenagers or young adults ( 15-24 yrs ) 50 % of children have detectable EBV antibodies by 5 yrs of age and 90 % of people will have antibodies by 25 yrs Any age can be infected

Transmission-Intimate contact with body secretions- primarily oropharyngeal Kissing between an uninfected and an EBV-seropositive person who is shedding the virus symptomatically Blood products ( rare ) Potentially can be shed from uterine cervix – implicating genital transmission ( rare ) Incubation period-About 4-7 weeks

Fever , Lymphadenopathy- Symmetric and can involve any group of nodes Typically posterior or cervical Also be
♦ anterior cervical
♦ submandibular
♦ sub-occipital
♦ post-auricular
♦ epitrochlear
♦ axillary
♦ inguinal Sore throat-In up to 90 %
○ tonsillar enlargement
○ white creamy exudate on tonsills
Exudate rarely discolored and it does not involve pharyngeal mucosa

○ palatal petechiae Sore throat which fails to improve or becomes worse over several days Prodromal symptoms- malaise , fatigue , myalgia , chills , sweats , anorexia and retro orbital headache Splenomegaly (8 % ) Hepatomegaly ( 7 % ) Jaundice with deranged LFTs Non-specific rash – may be macular , petechial ,urticarial or erythema multiforme like or maculopapular rash following amoxicillin use Children < 3 yrs symptoms indistinguishable from other viral illnesses of childhood

Differential-Streptococcal pharyngitis Cytomegalovirus Human herpesvirus 6 ( Roseola ) Herpes simplex virus Type 1 Acute viral hepatitis Acute toxoplasmosis Primary HIV infection Rubella Adenovirus Leukemia 

Blood film
Large atypical lymphocytes ( not specific for EBV )
 Heterophile antibodies-heterogenous group of antibodies composed mostly of IgM class generated in presence of EBV infection

○ Paul-Bunnell test +ve 2nd week of illness in around 90 % cases 
○ Monospot test

Heterophile test may be falsely negative in up-to 25 % of adults in the 1st week of symptoms 
 PCR emerging as a sensitive method for detecting EBV infection ELISA- can detect IgM anti-EBV capsid antibodies ( at presentation – suggest acute infection )
○ AST and ALT may be elevated ( 2-3 times ULN )
○ AlkPo4 may rise during convalescence ( usually resolves itself )

Treatment- Self- limiting illness usually resolves by 3 weeks Rest , hydration , analgesia and antipyretics Symptomatic treatment and address any complication if present Exclusion from work or school not required Avoid kissing , sharing eating or drinking utensils Do not engage in contact sports or heavy lifting -1st month of illness ( if return to contact sports essential before 1 month- arrange an US to r/o splenomegaly ) Steroids- insufficient evidence to the efficacy of steroids for symptom control ( lack of research on SEs and long-term complications ) Antivirals- use not advocated yet Metronidazole- more evidence required

Referral-Airway compromise Suspected splenic rupture Dehydration or difficulty swallowing fluids Immunocompromised or post-transplant patients Patients with infectious mononucleosis but negative for EBV antibodies ( illness caused by others-see background )

Complications-Upper airway obstruction Splenic rupture ( rare < 1 % ) and usually in 1st 3 weeks of illness Neurological complications ( 1-5 % ) as
○ Encephalitis or aseptic meningitis
○ Facial nerve palsy
○ Transverse myelitis
○ Guillain- Barrè syndrome
○ Cranial nerve lesions Fatigue- lasting > 6 months ( CFS association questionable ) Immunocompromised people
○ Malignancy
○ HIV -oral hairy leukoplakia and diffuse interstitial pneumonitis Haematological
○ Thrombocytopenia
○ Neutropenia
○ Hemolytic anaemia Increased risk of Multiple sclerosis Myocarditis , pericarditis , pancreatitis , interstitial peuomonia , rhabdomyolysis and psychological problems Burkitts lymphoma in children and nasopharyngeal carcinoma



A section from Centers for Disease Control and Prevention which has information for clinicians and patients

NHS on glandular fever

Health Vic Victoria State Government on Glandular fever a concise page

Testing for EBV information for patients from Labtest Online Au


A review article from BMC Family Practice, a good read Epstein-Barr virus and its association with the disease – a review of relevance to general practice

Lab testing for EBV from CDC

Monospot test information from Gloucestershire Hospitals NHS Trust


  1. Rezk, Emtithal et al. “Steroids for symptom control in infectious mononucleosis.” The Cochrane database of systematic reviews vol. 2015,11 CD004402. 8 Nov. 2015, doi:10.1002/14651858.CD004402.pub3 (Abstract )
  2. Glandular fever ( infectious mononucleosis ) CKS NHS July 2015
  3. Infectious mononucleosis BMJ 2015 ;350:h1825
  4. Epstein-Barr Virus ( EBV ) infectious Mononucleosis  E Medicine
  5. Infectious Mononucleosis Merck Manual Professional Version
  6. Oxford Hanndbook of Clinical Pathology James Carton Oxford University Press
  7. What Elements Suggest Infectious Mononucleosis? Welch, Julie L. et al. Annals of Emergency Medicine, Volume 71, Issue 4, 521 – 522
  8. First Consult- Infectious Mononucleosis June 2013 Elsevier
  9. De Paor  M, O’Brien  K, Fahey  T, Smith  SM. Antiviral agents for infectious mononucleosis (glandular fever). Cochrane Database of Systematic Reviews 2016, Issue 12. Art. No.: CD011487. DOI: 10.1002/14651858.CD011487.pub2.
  10. Ónodi-Nagy, K., Kinyó, Á., Meszes, A. et al. Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization. All Asth Clin Immun 11, 1 (2015).
  11. Diagnosis and management of glandular fever in primary care
  12. Stat Pearls NCBI Bookshelf Mononucelosis





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