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Skin-nontumor / Clinical Dermatology

Infectious disorders

Epstein-Barr virus (EBV)

Reviewer: Ha Kirsten Do, M.D., IUPUI (see Reviewers page)
Revised: 21 July 2011, last major update June 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.


● 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

Diagnosis / laboratory

● 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


● 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

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)

Clinical images


Micro description

● Oropharyngeal epithelium has intense lymphoproliferative response

Cytology description

● Characteristic atypical lymphocytes

Cytology images

Atypical lymphocytes have indented and slightly larger cytoplasm with nucleoli

Differential diagnosis

● Toxoplasmosis
● Viral hepatitis

End of Skin-nontumor / Clinical Dermatology > Infectious disorders > Epstein-Barr virus

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