Herpesviruses 1 & 2, Nonoral & Nongenital

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-2 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 HSV 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

• Clinical risk factors for invasive HSV in infants include younger age, prematurity, seizure at home, ill appearance, fever, vesicular rash, thrombocytopenia, and CSF

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 in 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 ...