Infectious Mononucleosis

 

• Background

  Aka glandular fever, mono.

  Cause

  • Infection by Epstein-Barr virus (EBV, human herpesvirus 4), a double-stranded DNA virus.
  • A number of other pathogens can cause mononucleosis syndromes: CMV, syphilis, HIV seroconversion, toxoplasma, brucella.

• Signs and symptoms

  • Generalised or cervical lymphadenopathy.
  • Systemic symptoms: low-grade fever, fatigue/malaise, anorexia.
  • Pharyngitis. Like Group A Strep, there may be tonsillar enlargement, exudate, and palatal petechiae, but unlike Group A Strep there is also rhinorrhea, congestion and cough.
  • Splenomegaly (50%). Hepatomegaly and jaundice, suggesting EBV hepatitis, is less common (10%).
  • Bilateral upper eyelid oedema.
  • If patients are mistakenly given a β-lactam antibiotic, this may result in a diffuse maculopapular rash, although this association has been questioned.

• Investigations

  Bloods:

  • FBC: ↑lymphocytes, ↓platelets.
  • ↑ESR, differentiating from Group A Strep.
  • Mild ↑ALT/AST.

  Diagnosis:

  • Heterophile antibody tests, either Monospot or Paul-Bunnell. Tests not for an EBV Ab, but the non-specific 'heterophilic' IgM released by EBV-stimulated B-cells. 70% sensitive initially, but reaches 90% by 3 weeks.
  • EBV antibodies if heterophile -ve. >95% sensitive. Viral capsid antigen (VCA) IgM and Ab to early antigen (EA) are +ve in the acute phase, while VCA-IgG and EBV nuclear antigen (EBNA) IgG become +ve within weeks.
  • EBV PCR is an alternative.

  Others:

  • Blood film: atypical lymphocytes.
  • Throat swab: should be -ve for Group A Strep, though some are asymptomatic carriers.
  • Consider abdo US for splenomegaly and LP if there is meningism.

• Management

  • Usually self-resolves.
  • Paracetamol for fever and pain.
  • Prednisolone PO can be used if there is airway obstruction or haemolytic anaemia.
  • To prevent splenic rupture, avoid contact sport for 8 weeks and avoid alcohol during illness, though evidence for the latter is weak.

• Complications

  Short-term:

  • Post-viral fatigue may persist for months.
  • Splenic rupture.
  • Autoimmune haemolytic anaemia or thrombocytopenia.
  • Myocarditis
  • Glomerulonephritis
  • CNS: meningoencephalitis, Guillain-Barré, optic neuritis, transverse myelitis.

  Long-term:

  • 2-fold multiple sclerosis risk in those who have had infectious mononucleosis (though the absolute risk is still <1%).

• Epstein-Barr virus (EBV)

  Aka human herpesvirus 4 (HHV-4).

  Epidemiology and transmission

  • Spread through saliva or droplets. Kissing is a common transmission method.
  • 90% of people are exposed at some point in their lives.
  • In developing countries, infection often occurs in early childhood and is asymptomatic.
  • In the developed world, around 50% are infected by age 12. Among those infected later, 50% develop some symptoms, with 30% developing infectious mononucleosis.

  Pathophysiology and life cycle

  • Double-stranded, DNA virus.
  • In the oropharynx, infects epithelial cells and B cells in lymphoid tissue. Subsequently spreads through the lymphatic system.
  • 4-6 weeks incubation time.
  • EBV mimics innate B cell activation signals, causing proliferation and differentiation to antibody-secreting plasma cells.
  • Provokes massive cytotoxic T cell response against viral antigens. The T and B cells produce the characteristic lymphadenopathy of infectious mononucleosis.
  • Some latent infected cells remain after the acute illness.

  Long-term complications

  • Cancer: Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma.
  • Hairy leukoplakia: non-malignant warty lesion on lateral tongue in the immunosuppressed. Can be scraped off.
  • MS. Near 100% EBV exposure in MS patients, vs. 90% in general population.