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For further information, see CMDT Part 32-01: Human Herpesviruses

Key Features

Essentials of Diagnosis

  • Spectrum of illness from stomatitis and urogenital lesions (see Herpesviruses 1 & 2, Oral & Genital) to facial nerve paralysis (Bell palsy) and encephalitis

  • Variable intervals between exposure and clinical disease, since herpes simplex virus (HSV) causes both primary (often subclinical) and reactivation disease

General Considerations

  • Risk factors for HSV transmission include

    • Black race

    • Female sex

    • History of sexually transmitted infections

    • An increased number of partners

    • Contact with commercial sex workers

    • Lower socioeconomic status

    • Young age at onset of sexual activity

    • Total duration of sexual activity

  • Asymptomatic shedding of either virus is common and may be responsible for transmission

  • Asymptomatic HSV-2–infected individuals shed the virus less frequently than those with symptomatic infection

  • HSV-2 seropositivity

    • Increases the risk of HIV acquisition (it is threefold higher among persons who are HSV-seropositive than among those who are HSV-2 seronegative)

    • Reactivates more frequently in advanced HIV infection

Clinical Findings

Symptoms and Signs

Ocular disease

  • Uveitis

  • Keratitis

    • Usually unilateral and associated with impaired visual acuity

    • Lesions limited to the epithelium usually heal without affecting vision

    • Stromal involvement can cause uveitis, scarring, and eventually blindness

    • Recurrences are frequent

  • Blepharitis and keratoconjunctivitis

  • Acute retinal necrosis

Neonatal and congenital infection

  • Both types 1 and 2 rarely infect the fetus and induce congenital malformations (organomegaly, bleeding, and central nervous system [CNS] abnormalities)

  • Maternal infection during the third trimester is associated with the highest risk of neonatal transmission

CNS disease

  • Herpes simplex encephalitis

    • Presents with nonspecific symptoms: a flu-like prodrome, followed by headache, fever, behavioral and speech disturbances, and focal or generalized seizures

    • Temporal lobe is often involved

  • HSV-1 infection may enhance the development of Alzheimer disease by promoting tau phosphorylation or via cofilin-1 dysregulation

  • Both HSV-1 and HSV-2 are increasingly recognized as a cause of mild, nonspecific neurologic symptoms and are also associated with benign recurrent lymphocytic (Mollaret) meningitis

  • Primary HSV-2 infection in women often presents as aseptic meningitis

  • Recurrent meningitis from HSV-2 occurs in both younger and older individuals

Disseminated infection

  • Occurs in the setting of immunosuppression, or rarely with pregnancy

  • Skin lesions are not always present but are a particular complication in patients with atopic eczema (eczema herpeticum) and burns

  • Pneumonia can occur in both immunocompetent and immunosuppressed persons

Bell palsy

  • HSV-1 infection is a cause of Bell palsy

Esophagitis, urethritis, and proctitis

  • HSV-1 can cause

    • Esophagitis in immunocompromised patients

  • HSV esophagitis rarely is accompanied by significant upper gastrointestinal hemorrhage

  • Proctitis often occurs mainly in men who have sex with ...

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