Infectious Mononucleosis

Synonym: glandular fever, kissing disease

Infectious mononucleosis is usually a self-limiting infection caused by Epstein-Barr virus (EBV) (which is a human herpes virus) that is particularly common in adolescents and children.¹

• Clinical infection is particularly common in young adults. The infection is therefore most common in populations with many young adults, such as active-duty military personnel and college students.²
• The incidence of infectious mononucleosis shows no consistent seasonal peak.²
• The incubation period is between 33-49 days.³

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 and 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 generalised 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.

See separate article Infectious Mononucleosis Tests.

• 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:
  • EBV infection induces a variety of unrelated non-EBV 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 EBV
• Abdominal ultrasound: for splenomegaly

EBV 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 EBV infected cells; associated development of autoimmune disease and lymphoma

• Advise patients to avoid contact sports for 6 weeks - because of risk of splenic rupture.⁴
• Avoid alcohol for duration of illness.⁴
• Advise paracetamol for analgesia and control of fever.
• No specific antiviral therapy is available.
• There is insufficient evidence to recommend steroid treatment for symptom control in glandular fever.⁵
• 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 upper airway obstruction.
• Myocarditis and cardiac conduction abnormalities are rare complications.
• Splenic rupture is rare, but potentially lethal.⁶ Splenectomy increases susceptibility to various infections.
• Haemolytic anaemia, thrombocytopenia.
• Acute interstitial nephritis.
• 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.
• Fatigue and myalgia may persist for several or even many months after the acute infection has resolved.²
• If splenic rupture is recognised and surgery performed quickly, the prognosis is good.