Skin nontumor

Infectious disorders

Epstein-Barr virus (EBV)

Author: Ha Kirsten Do

Last author update: 1 June 2011
Last staff update: 1 December 2020

Copyright: 2002-2023,, Inc.

PubMed Search: Epstein-Barr virus [title] AND EBV [title]

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Cite this page: Do HK. Epstein-Barr virus (EBV). website. Accessed March 22nd, 2023.
Definition / general
  • Ubiquitous virus in humans; also known as human herpes virus type 4 (Wikipedia)
  • EBV infectious mononucleosis causes viral pharyngitis in all age groups, but particularly in young adults
  • Infection usually occurs by age 15 - 25
  • In US, nearly 50% seroconvert by age 5; 12% of college aged adults convert each year, and half develop acute infectious mononucleosis (US Centers for Disease Control)
  • EBV is transmitted via saliva, and initially infects B cells of oropharyngeal epithelium
  • The circulating infected B cells spread to entire reticuloendothelial system in liver, spleen and peripheral lymph nodes
Clinical features
  • Incubation period ranges from 1 - 2 months
  • Primary EBV infections are either asymptomatic or cause infectious mononucleosis, also known as glandular fever
  • Infectious mononucleosis has symptoms of fever, lympahedenopathy and sore throat; also petechia of posterior pharynx (can also be seen in group A streptococcal pharyngitis), not present in other pharyngitis
  • May affect other organs
  • Skin involvement in 10%; described as maculopapular exanthema with faint, diffuse, non-itchy rash, initially of trunk and upper arms, lasting for one week; rash is less intense than the transient, morbilliform, hypersensitivity reaction type rash of extensor surfaces appearing 7-10 days after treatment with beta-lactam antibiotics (ampicillin, amoxicillin and cephalosporin)
  • Complications include spontaneous splenic rupture, which requires surgical intervention
  • Can cause oral hairy leukoplakia or non-Hodgkin lymphoma in patients with severe immunosuppression, including HIV
  • In areas within Africa, prediposes children to Burkitt lymphoma
  • Japanese or other Asians may develop chronic infections

  • Chronic active EBV infection: chronic recurrent infectious mononucleosis-like symptoms, high mortality due to virus-associated hemophagocytic syndrome, NK/T cell lymphoma, EBV related cardiovascular disease and large vessel arteritis; also hypersensitivity to mosquito bites in 1 / 3 (may be initial symptom), causing necrotic skin ulceration and scarring
  • Nonspecific tests are CBC with differential, elevated ESR, liver function tests
  • Specific tests are heterophile antibody tests, monospot test (sensitivity of 85%, specificity of 100%); if original monospot test is negative, repeat in 6 weeks if high suspicion
  • Also antibodies to EBV capsid and nuclear antigen (for surgical specimens); PCR assay for EBV DNA
Case reports
  • 11 year old Japanese-Filipino girl with chronic active EBV infection and mosquito bite hypersensitivity, leading to EBV+, NK/T cell lymphoma (Hum Pathol 2005;36:212)
  • Usually bed rest and analgesia during febrile stage
  • Acyclovir and ganciclovir sometimes prescribed to reduce EBV shedding, but effectiveness is questionable
  • Short course of corticosteroids are indicated if hemolytic anemia, thrombocytopenia, CNS involvement or severe tonsillar enlargement
  • May have prolonged malaise for several months
Microscopic (histologic) description
  • Oropharyngeal epithelium has intense lymphoproliferative response
Cytology description
  • Characteristic atypical lymphocytes
Cytology images

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Atypical lymphocytes have indented and slightly larger cytoplasm with nucleoli

Differential diagnosis
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