Herpes simplex (HSV) or Herpes hominis

Epidemiology

• viral shedding occurs during active infection
• viral shedding may also occur in asymptomatic individuals
  • most common source of HSV transmission to sexual partners
• asymptomatic shedding is more prevalent in HIV-infected patients
• infection is spread via respiratory droplets & direct contact
  • secretions, including saliva are infective
• Herpes gladiatorum is acquired & passed through contact sports
• Herpetic whitlow (an infection of the fingers) common among dentists, dental hygienists & pulmonary nurses prior to adherence to universal precautions
• eczema herpiticum, a widespread viral infection in patients with pre-existing cutaneous disorders, i.e. atopic dermatitis
• neonatal infection
  • may be life-threatening
  • linked to mothers with primary infection during pregnancy
• humans are only known reservoir
• seroprevalence of HSV1 is 54% & HSV2 is 16%
  • lower among teens 30% & 1.2%
  • higher among adults 40-49 years of age 64% & 26%

Pathology

• ballooning degeneration of epidermal cells
• intra-epidermal vesicle
• histology indistinguishable from Herpes zoster
• putative receptor is heparan sulfate proteoglycan
• following primary infection, the virus enters nerve endings & ascends to the dorsal root ganglia where it remains in a latent stage until reactivated
• TNFSF14 (CD258) acts as a receptor

Genetics

• TNFRSF14 mediates HSV entry into activated human T-cells

Clinical manifestations

• primary infections
  • tend to occur in children & young adults 3-7 after exposure
  • asymptomatic primary infections also occur
  • constitutional symptoms of include:
    • low-grade fever, headache, myalgias, malaise
  • primary infection typically involves orofacial or genital skin
    • also see genital Herpes
  • regional lymphadenopathy may occur
  • vesicular lesions (grouped)
    • erythematous base, surrounding erythema
    • transition to pustules with ulceration or crusting within 48 hours is common
    • lesions generally last 2-6 weeks & heal without scarring
    • may rapidly evolve into superficial mucocutaneous ulcers or fissures in immunocompromised hosts
    • persistent, painful, non-healing ulcers suggests chronic mucocutaneous Herpes simplex in an immunocompromised host
    • in later stages of HIV infection, ulcers may coalesce to form large denuded areas in the anogenital region
  • lesions may be painful, or burning
• recurrent or reactivation infection
  • generally result from changes in the immune system
  • fatigue, stress, menses, local skin trauma, exposure to sunlight may contribute
  • prodrome of fatigue, paresthesias to the affected area, lasting 12-24 hours
  • may involve orofacial or genital skin
  • grouped vesicular lesions with surrounding erythema
    • begin to evolve within 24 hours
    • vesicles coalesce & rupture within 4 days leaving crusted lesions
    • crusted lesions shed in 7-10 days leaving pink surface
  • recurent HSV has been linked to recurrent erythema multiforme

* images

Laboratory

• Herpes simplex virus DNA (most sensitive & specific)
  • obtain swab from ulcer base
• Herpes simplex virus identified by culture: 10-14 days
  • characteristic ballooning of cultured cells
• Herpes simplex virus Ag in tissue
  • direct fluorescence antigen testing
    • unroof vesicle
    • scrape lesion with wooden spatula
• Herpes simplex serology
  • Latex antibody, types 1 & 2
  • > 4-fold rise in acute & convalescent antibody titers
  • of limited value: most adults are seropositive
• acyclovir-resistance (if indicated)
• Tzanck smear (older test, neither sensitive nor specific)
• see ARUP consult

Complications

• ocular Herpes (keratitis)
• acute retinal necrosis may occur in patients with AIDS
• Herpes encephalitis or meningitis in immunocompromised patients
  • see Herpes simplex encephalitis
• secondary infection may occur
  • complication of atopic dermatitis (eczema herpeticum)

Differential diagnosis

• impetigo
• Behcet's syndrome
• Coxsackie virus
• syphilis
• Stevens-Johnson syndrome
• herpangina
• aphthous stomatitis
• varicella (Herpes zoster, shingles)
• see Herpes simplex type 2 for differential diagnosis of genital lesions

Management

• reconfirmation of HSV diagnosis not needed prior to treatment unless clinical picture suggests another diagnosis
• acyclovir, famciclovir or valacyclovir
  • most effective if started at presentation
  • diminish symptoms of HSV-1 & HSV-2
  • reduce subsequent outbreaks & viral shedding
  • even high-dose antivirals do not eliminate HSV-2 viral shedding
• acyclovir
  • begin therapy as soon as possible
  • empiric therapy with IV acyclovir while workup in progress for clinically severe Herpes infection
  • 200 mg PO 5 times/day or 400 mg PO TID for 7-10 days
  • the dose is doubled for immunocompromised hosts
  • suppressive dose: 400 mg PO BID
  • topical acylovir available;
    • marginal effectiveness
    • not recommended; not cost-effective
  • neonatal herpes simplex treated for 6 months with acyclovir (300 mg/m2 body surface area TID) improves neurologic outcomes
  • topical acyclovir not effective for genital herpes
• valacyclovir 500-1000 mg PO BID for 7-10 days
  • chronic daily valacyclovir 500-1000 mg PO QD may reduce risk of sexual transmission of HSV-2
• famciclovir 500 mg every 8 hours for 7-10 days
  • suppressive dose: 250 mg PO BID
• acyclovir-resistant HSV infections
  • foscarnet 40-60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours, or
  • cidofovir (dosing not clear)
  • plus trifluorothymidine (ophthalmic) applied topically
  • duration of therapy: at least 10 days
• prognosis:
  • most patients recover from primary & recurrent infections without complications
  • patient with HIV or other immunological disorders are at higher risk of complications
• prevention
  • vaccine development has been unsuccessful
  • condoms useful for HSV2 prevention
  • antiviral prophylaxis
    • indications:
      • immunosuppressed patients
      • > 6 episodes/year
    • self-initiated vs long-term suppression
    • chronic daily valacyclovir 500-1000 mg PO QD may reduce risk of sexual transmission of HSV-2
    • topical acyclovir not effective for genital herpes
  • HIV1 patients should optimize antiretroviral therapy

More general terms

• herpesviridae

More specific terms

• Herpes simplex encephalitis
• Herpes simplex type 1 (HSV-1, HHV-1); human herpesvirus 1
• Herpes simplex type 2 (HSV-2); human herpesvirus 2

Additional terms

• acyclovir (ACV, Zovirax, Sitavig)
• foscarnet (Foscavir)
• herpes simplex virus DNA
• Herpes virus infection
• ocular Herpes simplex
• valacyclovir (Valtrex)

Patient information

Herpes simplex patient information