General
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• Sexually transmitted disease, usually caused by herpes simplex virus 2 (HSV2) and HSV1, which are DNA viruses
• References: eMedicine

Terminology
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• The Herpesviridae family has at least 8 viruses known to infect man: HSV1, HSV2, Epstein Barr virus (EBV), Cytomegalovirus (CMV), Varicella Zoster Virus (VZV), Human herpes virus 6 (exanthum subitum or roseola infantum), Human herpes virus 7 and Human herpes virus 8 (Kaposi's sarcoma-associated herpes virus)

Epidemiology
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• Sexually transmitted; spreads by direct contact with lesions
• Also spreads by asymptomatic shedding when no lesion is apparent

Sites
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• Genital region, mouth; also other areas

Etiology
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• Although historically caused mainly by HSV2, now 5-30% of primary outbreaks of genital herpes are caused by HSV1
• Blisters contain large number of viral particles and are very contagious

Clinical features
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• HSV infection is the most common cause of genital ulceration (BJU Int 2002;90:498)
• Multiple (6-10) small (1-2 mm) papules and macules, followed by vesicles that rupture and cause painful ulcers, usually at tip of penis or on shaft
• Atypical presentations include fissures, furuncles, linear excoriations and ulcerations
• In immunocompromised patients, especially those HIV-positive, ulcerations can be deep and persistent
• Blisters occur around anus in men who have sex with men
• Usually diagnosed clinically, with confirmation by culture, direct fluorescent antibody, skin biopsy and PCR for viral DNA
• Primary outbreak: occurs 3-14 days after exposure; patients usually asymptomatic but rarely have systemic symptoms of fever, headache, muscle ache, fatigue, swollen and tender lymph nodes
• After infection, viral genome remains in latent state in nuclei of sensory neurons for life
• Recurrences: may not occur at all, or up to 40 years after primary outbreak and usually milder than initial outbreak

Treatment
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• Antiviral drugs reduce frequency, duration and severity of outbreaks, and asymptomatic shedding
• Antiviral medications include aciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir) and penciclovir (Wikipedia)

Clinical images
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Multiple vesicles and ulcerations on surface

Vesicles on same red base

Lesions in later stage of healing

Atypical lesions resembling erosions

Crusting lesion resembling scabies

Micro description
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• Multinucleated giant cells with ground glass nuclei due to intranuclear virus
• More common at interface between ulcerated and non-ulcerated areas
• Intraepithelial vesicles contain rounded acantholytic keratinocytes
• Keratinocytes show viral cytopathic changes of ground-glass nuclei, nuclear molding and multinucleated giant epithelial cells
• Well-defined acidophilic inclusions can also be seen

Micro images
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Multinucleated giant cells with inclusions (right-vulva)

HSV2 antibody highlights
virus in cells at interface

Focal ulceration

Multinucleated giant
cells at edge of ulcer

Cytology images
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HSV cellular changes

Positive stains
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• HSV1 or HSV2

Electron microscopy images
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Drawing (fig 2a)

Negative stain (fig 2c)

Enveloped, linear, double-stranded DNA

"Fried-egg" appearance (fig 2g)

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