Links To And Excerpts From The Cribsiders’ “#119: Epstein Barr Virus – A MONO-lithic Overview”

Posted on September 13, 2024 by Tom Wade MD

Today, I review, link to, and excerpt from The Cribsiders‘ #119: Epstein Barr Virus – A MONO-lithic Overview.*

*Engel S, Anosike I, Masur S, Chiu C, Berk J. “### Epstein Barr Virus – A MONO-lithic Overview”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ August 28, 2024.

All that follows is from the above resource.

Summary:

Join us and expert guest Dr. IJ Anosike (The Children’s Hospital at Montefiore) to dissect the complexities of diagnosing and managing Epstein-Barr virus!  From sneaky symptoms to tricky tests, Dr. Anosike provides insight on identifying and tackling this troublesome virus. Don’t miss this infectiously enlightening episode!

EBV Pearls

  1. EBV can be shed in saliva, even when patients are no longer symptomatic
  2. Use the “scratch test” to assess for splenomegaly – put stethoscope on the abdomen and then scratch finger along the abdomen’s surface – the quality of sound will become duller along the edge of the spleen/liver
  3. In most cases, antibody serologies to the viral capsid antigen is the test of choice for diagnosis. The presence of VCA IgM antibodies suggests acute infection while antibodies to EBV nuclear antigen suggest a past infection due to the timeframe in which these antibodies appear.
  4. Additional lab work to order includes a CBC and liver enzymes; lymphocytosis is common, prolonged illness may also be associated with anemia.
  5. Treatment with amoxicillin in patients with EBV can lead to a non-allergic morbilliform rash.

EBV Notes

Pathophysiology

  • EBV is a type of herpesvirus (type 4)
  • Acquired by close contact with a person who is actively shedding. The virus continues to shed in saliva even in asymptomatic individuals for several months.
  • The virus invades B lymphocytes which then spread the infection to the lymph nodes, spleen, liver, and throat.

Presentation

  • Classic triad: fever, exudative pharyngitis, cervical lymphadenopathy (usually posterior cervical chain)
  • Atypical presentations (more common in older patients):
    • Abdominal pain – this may be related to hepatitis or splenomegaly/splenic rupture.
    • Aseptic meningitis
    • Neurologic changes including (rarely) “Alice in Wonderland Syndrome” – distortion of perception
    • Tumor-associated manifestations including Burkett’s lymphoma

Physical Exam

Tip for assessing for splenomegaly:

  • Start in the inguinal area and work “up” (spleen grows inferiorly and medially)
  • Scratch test: scratch finger on abdomen while the stethoscope is on the abdomen – the quality of sound will become duller along the edge of the spleen/liver

Differential Diagnosis 

  • Strep pharyngitis: No hepatosplenomegaly, URI sx are rare
  • CMV: Uncommon in immunocompetent patients

Diagnosis

  • Serological testing: Directly tests for antibodies to the viral capsid antigen.
    • VCA IgM: + Suggests acute infection. Peaks quickly and typically drops after 2-4 weeks. If low positive, can repeat 2 weeks later to see if this is an emerging or resolving acute infection.
    • VCA IgG: + Suggests current or prior infection.
    • EBNA: + Suggests past infection. Shows up later in infection (6 weeks at the earliest, usually peaks around 6 months)
  • Heterophile antibody test (e.g., monospot). Latex agglutination test that indirectly identifies the antibodies that are fighting the virus. False negatives are common in the first 1-2 weeks and for patients <4 years old. Overall sensitivity can vary from ~50-90%.
  • PCR testing: Identifies residual virus circulating in the body – mostly used in immunocompromised patients.

Source: https://labpedia.net/epstein-barr-virus-ebv-infectious-mononucleosis/

Additional testing in patients diagnosed with EBV

  • CBC:
    • Often will have lymphocytosis (because the virus lives in lymphocytes), including the presence of atypical lymphocytes (10-30% of total lymphocyte count)
    • May develop thrombocytopenia: Concern for hemophagocytic lymphohistiocytosis (HLH),* which can be triggered by EBV – reduces counts of all blood cell lines
    • In more prolonged illness, the patient may have normocytic or microcytic anemia (anemia of chronic disease) – avoid iron in the setting of acute infection because it “fuels the infection.” Dr. Anosike suggests either rechecking once the patient is feeling better or checking iron studies, rather than presumptively starting iron supplementation.
  • Liver enzymes: May have elevated ALTs (typically in the hundreds)

*Resources on hemophagocytic lymphohistiocytosis:

Treatment

  • Rest where possible
  • No role for antibiotics. Note that amoxicillin in patients with EBV can lead to a non-allergic morbilliform rash – treatment is simply to stop the amoxicillin.
  • Antiviral therapy is not the standard of care – this is a self-resolving infection in most immunocompetent patients.

Anticipatory Guidance

  • Avoid contact sports for at least 4-6 weeks after symptom onset (allows spleen to return to baseline) – graduated return to play.
  • IgG provides lifelong protection in immunocompetent patients – however, impairing the immune system can reduce this. Burkitt lymphoma occurs due to a resurgence of EBV in lymphoid tissue.
  • Ongoing fatigue is not indicative of persistent virus circulating in the body.

Resources

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