EBV

Question 1

EBV usually presents in young adults such as college students/ military

What is incubation period?

Answer 1

4 to 8 weeks

Question 2

What are symptoms of acute EBV infection?

Answer 2

low grade fever

fatigue

sore throat

lymphadenopathy

arthralgia

bilateral periorbital oedema - without generalised oedema can be mistaken for allergic reaction or Kawasaki disease

hepatomegaly/ splenomegaly - returns to normal within 3 weeks of of initial illness

Question 3

Previous testing used to involve testing for heterophile antibodies. Heterophile antibodies are induced by external antigens. Heterophile means it reacts with proteins across species lines (sheep/ horse)

What are the the names of these tests?

Answer 3

Paul-Bunnell test: sheep red blood cells agglutinate in the presence of heterophile antibodies.

Monospot® test: horse red blood cells agglutinate on exposure to heterophile antibodies.

Positivity increases over first six weeks.
Titre does not correlate with disease
Remain in blood for 4-8 weeks, but can persist for 1 year

Question 4

What diseases can cause false positive Monospot test?

Answer 4

Infection - eg, toxoplasmosis, rubella, CMV, HIV, herpes simplex virus, malaria, viral hepatitis.

Malignancy - eg, lymphomas (particularly Burkitt’s lymphoma), leukaemias, cancer of the pancreas.

Connective tissue diseases - eg, rheumatoid arthritis, systemic lupus erythematosus.

Question 5

Patients who remain heterophile-negative after six weeks with a mononucleosis illness are considered to be heterophile-negative IM and should be tested for EBV-specific antibodies

Which antibody tests are performed?

What do they represent?

Answer 5

anti-VCA IgG - rises later than IgM. Remains positive for life

anti-VCA IgM. Produced early.Peaks at 4-8 weeks, then usually disappears. Can help establish whether infection is recent or not. Remains positive for 1 year

EBNA IgG- EBV nuclear antigen. Produced at 6-8 weeks. Can help establish whether infection is recent or not

EBV viral load by PCR - if immunosuppressed may not have antibody resposne

Beware false negative results early in infection, or children <2

Question 6

Which conditions is EBV associated with?

Answer 6

Burkitt’s lymphoma.

B-cell lymphomas in patients with immunosuppression.

Undifferentiated carcinomas - eg, cancer of the nasopharynx and cancer of the salivary glands.

Multiple sclerosis.

Question 7

What is management of infectious mononucleosis?

Do children need to stay off school?

Answer 7

Avoid contact sports 3 weeks due to risk of splenic rupture

No treatment required

May require admission for fluids

Avoid amoxicillin as causes itchy maculopapular rash

Do not need to stay off school as most people have been infected

Question 8

What are complications of EBV infection?

Answer 8

Extreme tonsillar enlargement may result in upper airway obstruction.

Myocarditis

Splenic rupture

Haemolytic anaemia, thrombocytopenia.

Acute interstitial nephritis, glomerulonephritis.

Neurological, including optic neuritis, transverse myelitis, aseptic meningitis, encephalitis and meningoencephalitis, cranial nerve palsies (especially facial palsy) or Guillain-Barré syndrome.

Prolonged fatigue; depression.

Burkitt’s lymphoma

B-cell lymphoma

Salivary gland carcinoma

MS

Question 9

EBV serology

What results expect:

• early primary infection

Answer 9

VCA IgM - pos

VCA IgG - neg

EBNA IgG - neg

Re-check serology in 2 weeks, or use another platform

Patient is considered susceptibile to EBV infection if they do not have VCA IgG or EBNA IgG

Question 10

EBV serology

What results expect:

• acute primary infection

Answer 10

VCA IgM - pos

VCA IgG - pos

EBNA IgG - neg

high or rising level of anti-VCA IgG strongly suggests acute infection. Resolution of the illness may occur before the diagnostic antibody levels appear

Question 11

EBV serology

What results expect:

• past infection

Answer 11

VCA IgM - neg

VCA IgG - pos

EBNA IgG - pos

rare cases anti-EBNA antibodies may not be detected in past infection

Question 12

EBV serology

What results expect:

• late primary infection or reactivation

Answer 12

VCA IgM - pos

VCA IgG - pos

EBNA IgG - pos

Question 13

What is significance of isolated EBNA IgG?

Answer 13

Unusual, but likely represents past infection

Question 14

What is significance of isolated anti-VCA IgG

Answer 14

Few possibilities -

prior infection, who have lost/ never shown EBNA IgG

Acute infection - either IgM has disappeared, or will appear late

Question 15

EBV can cause post-transplant lymphoproliferative disorders.

What are treatment approaches?

Answer 15

Reducing immunosuppression by 20%

Rituximab CD20 monoclonal antibody once a week for four weeks

Chemotherapy - CNS lymphoma protocol e.g methotrexate/ cytarabine

Question 16

What is probable and proven EBV related disease in haematology patient?

Answer 16

Probable
lymphadenopathy
low viral load e.g <500 copies/ml

Proven
EBV detected from organ by biopsy
usually higher viral load

Question 17

Haematology patient

What are indications for treatment?

Answer 17

EBV virus detectable in blood

Organ damage - lymphadenopathy or other organ involved

Question 18

Haematology patient

EBV viral load 10000 copies/ml

Widespread lymphadenopathy

How would you manage?

Answer 18

CT CAP - assess disease
Bone marrow aspirate
Lymph node aspirate

Reduce immunosuppression if possible

EBV viral load is >500, with evidence of disease, then requires treatment with rituximab

If no reduction in viral load or disease improvement, consider repeat rituximab infusion 14 days later

EBV viral load weekly until at least 3 months after last positive result

Repeat CT CAP 2 months after therapy, to ensure good response