Infectious Mononucleosis

Synonym: glandular fever

Usually a self-limiting infection caused by the Epstein-Barr virus, which is a human herpes virus (type 4 - HHV4).¹

• Clinical infection is particularly common in young adults.
• The incubation period is between 33-49 days.²

Most patients have few if any symptoms (most adults show serological evidence of previous EBV infection).

• Low grade fever, fatigue and prolonged malaise.
• Sore throat. Tonsillar enlargement is common and may be massive. Palatal petechiae, uvular oedema.
• Fine, macular non-pruritic rash, which rapidly disappears.
• Transient bilateral upper lid oedema.
• Lymphadenopathy, especially neck glands.
• Nausea and anorexia.
• Arthralgias and myalgias occur but are less common than in other viral infectious diseases and rarely severe.
• Other symptoms include cough, chest pain, and photophobia.
• Older adults and elderly patients often have few throat symptoms or signs and have little or no lymphadenopathy.
• Later signs include:
  • Mild hepatomegaly and splenomegaly (splenic enlargement returns to normal or near normal usually within three weeks after the clinical presentation) with tenderness over the spleen.
  • Jaundice (in less than 10% in young adults, but in as many as 30% of infected elderly patients).

• Exudative pharyngitis is commonly confused with group A streptococcal pharyngitis. 30% of patients with infectious mononucleosis have group A streptococcus in the oropharynx.
• Bilateral periorbital oedema without generalized oedema may also be due to Kawasaki disease, allergic reactions, or bilateral periorbital cellulitis.
• Prominent lymphadenopathy: leukaemia.
• Atypical lymphocytes must be differentiated from abnormal lymphocytes, which are associated with lympho-reticular malignancies.
• Other causes of abnormal liver function tests.
• Patients with a negative Paul Bunnell or Monospot reactions for 6 weeks and those with a negative EBV-specific test result, should be tested for the causes of heterophile-negative infectious mononucleosis. These include HIV, human herpes virus 6, toxoplasmosis, cytomegalovirus, rubella, viral hepatitis.

• Full blood count: leucocytosis; lymphocytosis; relative atypical lymphocyte count is greater than 20%. Elevated ESR.
• Mild elevation of the serum transaminases. Alkaline phosphatase and gamma-GT levels are not usually elevated.
• Heterophile antibody tests:
  • EB virus infection induces a variety of unrelated non-EB virus heterophile antibodies.
  • Sheep red blood cells agglutinate in the presence of heterophile antibodies and are the basis for the Paul-Bunnell test.
  • Agglutination of horse red cells on exposure to heterophile antibodies is the basis of the Monospot test.
  • Heterophile test antibodies are highly sensitive and specific, are present in peak levels 2-6 weeks after primary infection and they remain positive in low levels for up to a year. The heterophile antibody test results may be negative early in the course of infection.
• Specific tests for IgM antibodies to Epstein Barr virus.
• Abdominal ultrasound: for splenomegaly.

Epstein-Barr virus is also associated with:

• Burkitt's lymphoma.
• B-cell lymphomas in patients with immunosuppression.
• Undifferentiated carcinomas, e.g. of nasopharynx and salivary glands.
• Duncan's syndrome: rare, X-linked recessive; defective T cells fail to destroy EB virus infected cells; associated development of autoimmune disease and lymphoma.

• Advise patients to avoid contact sports for 6 weeks - because of risk of splenic rupture.³
• Avoid alcohol for duration of illness.³
• Advise paracetamol for analgesia and control of fever.
• No specific antiviral therapy is available.
• Short courses of corticosteroids are beneficial for haemolytic anaemia, central nervous system involvement or extreme tonsillar enlargement.
• Ampicillin and amoxicillin cause a maculopapular rash and should not be given in any patient who might have infectious mononucleosis.
• Patients may require hospital admission for intravenous fluids.
• Surgery is necessary for spontaneous splenic rupture, which is rare but may be the initial presentation of the condition.

• Extreme tonsillar enlargement may result in airway obstruction.
• Encephalitis and myocarditis are rare complications.
• Splenic rupture is rare, but potentially lethal.⁴ Splenectomy increases susceptibility to various infections.
• Haemolytic anaemia, thrombocytopenia.
• Neurological, including optic neuritis, transverse myelitis, aseptic meningitis, encephalitis, meningoencephalitis, cranial nerve palsies (especially facial palsy) or Guillain-Barre syndrome.
• Prolonged fatigue; depression.

• Usually asymptomatic or short duration and self-limiting.
• Some remain unwell for many weeks, months or even years.
• If splenic rupture is recognized and surgery performed quickly, the prognosis is good.