EBV / glandular fever / infectious mononucleosis

see also:

• viruses
• tonsillitis
• NSW: patient information sheet (pdf)

• Epstein-Barr Virus (EBV) is the virus that causes glandular fever (infectious mononucleosis or IM)
• a frequent infection, particularly in young adults, mainly due to spread via saliva such as kissing or sharing drinks
• EBV is transmitted via intimate contact with body secretions, primarily oropharyngeal secretions.
• EBV infects the B cells in the oropharyngeal epithelium.
• The organism may also be shed from the uterine cervix, implicating the role of genital transmission in some cases.
• On rare occasion, EBV is spread via blood transfusion.
• A rapid and efficient T-cell response results in control of the primary EBV infection and lifelong suppression of EBV.
• Ineffective T-cell response (such as in those on immunosuppressants for Mx of transplants) may result in excessive and uncontrolled B-cell proliferation, resulting in B-lymphocyte malignancies

• incubation period 1-2 months
• most patients are asymptomatic (50% of 5yr olds and 90% of adults show serologic evidence of past infection)
• when infection occurs during adolescence, it causes infectious mononucleosis pharyngitis picture in ~50%
• when infection occurs in the elderly, it mainly causes a viral hepatitis picture

• fever
• malaise
• fatigue may be profound initially, but usually settles after a variable period but often takes 3 months, but may be longer in some resulting in Chronic fatigue syndrome
  • reporting of prominent fatigue: 41% during acute illness; 71% at 1 month; 43% at 2 months; 9% at 6 months;
• pharyngitis - often pustular with bilateral large inflamed “kissing” tonsils which may compromise airway, and later, palatial petechiae (these also can occur in Strept tonsillitis)
• generalised lymphadenopathy - in particular, the finding of posterior cervical LN's helps differentiate it from bacterial tonsillitis which generally only causes anterior cervical lymphadenitis, but adenitis is uncommon in the elderly who mainly present with an anicteric viral hepatitis.
• splenomegaly may be present but usually returns to normal by 3 weeks
  • rarely may result in splenic rupture (1-2% of symptomatic cases) - thus contact sports should be avoided if splenomegaly is present
• abnormal LFTs are common but jaundice occurs in < 10% of young adults and in ~30% of the elderly with acute EBV
• early, transient, faint macular rash is common but easily missed
• early and transient bilateral upper-lid edema
• widespread macular rash may occur, but particularly likely if the patient has received amoxycillin
• leukocytosis, rather than leukopenia, often with atypical lymphocytes > 20% +/- thrombocytopenia
• Monospot IM screen may be negative in the first week or two and overall has a sensitivity of 85% (in children over age 2yrs) and specificity of 100%
  • those with negative Monospot but suggestive clinical picture may need weekly Monospot tests for up to 6 weeks.
• ESR is usually raised (but is not so in Strep tonsillitis!)
• rarely may cause:
  • pancreatitis
  • acalculous cholecystitis
  • myocarditis
  • mesenteric adenitis
  • myositis
  • glomerulonephritis
  • optic neuritis
  • EBV infections of the CNS:
    • EBV may account for ~5% of children admitted with encephalitis¹⁾²⁾
    • EBV has a tropism for the deep nuclei, neuroimaging can show characteristic multiple foci of T2-weighted or FLAIR hyper intensity in the hemispheric cortex, brain stem, bilateral thalami, and basal ganglia³⁾, although one study suggests MRI is only abnormal in 71% of paediatric patients with EBV encephalitis ⁴⁾
    • compared to other herpes virus-associated encephalitis, EBV encephalitis is characterized by a higher degree of meningeal involvement, elevated CSF protein levels, lower glucose levels, and a reduced T-lymphocyte count in peripheral blood⁵⁾
    • transverse myelitis
    • acute cerebellar ataxia
    • aseptic meningitis
    • encephalitis
    • meningoencephalitis
    • cranial nerve (CN) palsies (particularly CN VII)
    • very rarely, may cause a ultra-rapidly progressing severe leukoencephalopathy (ADEM)
  • Guillain-Barré syndrome
  • selective immunodeficiency to EBV, which occurs in persons with X-linked lymphoproliferative syndrome, may result in severe, prolonged, or even fatal infectious mononucleosis
  • fatal hepatic necrosis is a rare complication, and is more likely in males

• FBE, IM screen +/- LFTs are generally performed
• if significant dysphagia or potential airway risk, admit for iv fluids and iv dexamethasone
• patients with splenomegaly should be warned to avoid contact sports
• if clearly EBV and not Strept tonsillitis, avoid antibiotics, and particularly amoxycillin as likely to develop a florid rash
• encouraged to rest as much as possible and to refrain from active physical activity for 3 weeks
• seek specialist advice if immunocompromised or rare complication

• neoplasia risk:
  • endemic Burkitt lymphoma in children in malarial countries such as Africa
  • Hodgkin's lymphoma - 3x risk; 40% of HL cases in Western countries are EBV genome-positive
  • Non-Hodgkin's lymphoma
  • hairy leukoplakia
  • leiomyomas and leiomyosarcomas in immunocompromised children
  • nasopharyngeal carcinoma appears to be always caused by EBV, high prevalence in southern China and other parts SE Asia
  • Most instances of post-transplant lymphoproliferative disorder (PTLD) are associated with EBV.
  • B-cell lymphomas (post-transplant lymphoma PTL) risk if on immunosuppressants for Mx of transplants
• multiple sclerosis (MS) risk 20 fold in those with high titres of EBV antibodies and a specific HLA-DR15 or HLA-A genotype⁶⁾
• there is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome