Clinical Guide > Comorbidities and Complications > HSV

Herpes Simplex, Mucocutaneous

January 2011

Chapter Contents


Herpes simplex virus (HSV) types 1 and 2 cause both primary and recurrent oral and genital disease. HSV usually appears as a vesicular eruption of the mucous membranes of the oral or perioral area, vulva, perianal skin, rectum, and occasionally the inguinal or buttock areas. The eruption develops into tender or painful ulcerated lesions that frequently are covered with a clear yellow crust. In some patients, however, the typical painful vesicular or ulcerative lesions may be absent. Persons with HIV disease and low CD4 cell counts have more frequent recurrences of HSV and more extensive ulcerations than do HIV-uninfected people. Persistent HSV eruption (lasting >1 month) is an AIDS-indicator diagnosis.

S: Subjective

The patient may complain of eruption of red, painful vesicles or ulcers ("fever blisters") with or without an exudate in the mouth, on the lips (and occasionally in nares), on the genitals, or in the perianal area. The patient may complain of burning, tingling, or itching before eruption of the lesions.

The vesicles will rupture and ulcerate, generally crusting over and healing in approximately 7-14 days. The lesions may be pruritic and are often painful. As immunosuppression progresses, the lesions may recur more frequently, grow larger or coalesce, and become chronic and nonhealing.

Perform a history, asking the patient about the symptoms described above, duration, associated symptoms, and history of HSV or similar infection.

O: Objective

Look for grouped vesicular or ulcerative lesions on an erythematous base on the mouth, anus, or external genitals, or ones that are visible on speculum or anoscopic examination. When immunosuppression is severe, lesions may coalesce into large, painful, and nonhealing ulcerations that spread to the skin of the thighs, lips, face, or perirectal region. These chronic erosive lesions may be confused with a chronic bacterial infection or decubitus ulcer, and should prompt consideration of acyclovir-resistant HSV infection. Recurrent lesions may start atypically, first appearing as a fissure, pustule, or abrasion.

A: Assessment

A partial differential diagnosis includes the following:

P: Plan

Diagnostic Evaluation

A clinical diagnosis of HSV often can be made on the basis of the patient's symptoms and clinical appearance, but symptoms and signs may be variable. Also, HSV-1 (rather than HSV-2) is increasingly the cause of initial episodes of anogenital herpes. For these reasons, current guidelines recommend laboratory testing to establish the diagnosis of HSV and to determine its type.

For cell culture or polymerase chain reaction (PCR), obtain a specimen from a freshly opened vesicle or the base of an ulcer for culture confirmation. Note that lesions that are >72 hours old or are beginning to resolve may not show HSV in culture.

PCR is more sensitive for detection of herpes DNA in ulcerative lesions, but is more expensive to perform and is less widely available than viral culture. If virologic test results are positive, typing should be performed to determine the type of HSV. Negative results do not rule out the possibility of HSV infection.

If cultures are negative and there is a high suspicion of HSV infection, skin may be taken from the edge of an ulcer for biopsy. Biopsy material also may be cultured. Tzanck smears are not sensitive or specific.

Type-specific serologic tests may be useful in the evaluation of patients in whom a diagnosis of genital HSV is not clear. Current guidelines also recommend that serologic testing be considered for HIV-infected individuals, for MSM, and for those who present for STI evaluation. Glycoprotein G (gG)-based serologic assays are recommended, as older assays do not reliably differentiate HSV-1 antibody from HSV-2 antibody.

Strongly consider checking for syphilis with a rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test in any patient who presents with genital, anal, or oral ulceration.


Empiric treatment for suspicious lesions often is initiated in the absence of laboratory confirmation. In some instances, treatment can be started empirically and, if no response is seen within 7-10 days, laboratory studies can be undertaken.

Episodic outbreak

Note: Dosage must be adjusted for patients with renal impairment.

Duration of treatment: 5-10 days. Short-course therapy (1-3 days) usually is not recommended for persons with HIV infection.

Symptomatic treatment helps the healing of lesions but does not prevent recurrences. Large, extensive ulcers may need to be treated for a longer period of time.

Severe disease

Treat initially with acyclovir 5 mg/kg IV Q8H (10 mg/kg for encephalitis).

Acyclovir-resistant HSV

The diagnosis of acyclovir-resistant HSV should be suspected if lesions fail to respond to 7-10 days of standard therapy and should be confirmed with culture and sensitivities. Cross-resistance to valacyclovir and ganciclovir will be present, and cross-resistance to famciclovir is likely. The usual alternative treatment is foscarnet (40 mg/kg IV Q8H); other possibilities include IV cidofovir, topical imiquimod, and topical cidofovir. An HIV specialist should be consulted.

Chronic suppresive therapy

Consider suppressive therapy with acyclovir (400 mg PO BID), famciclovir (500 mg PO BID), or valacyclovir (500 mg PO BID) for patients with frequent or severe recurrences and those with HSV-2. Acyclovir dosage may need to be increased to 800 mg BID or TID for individuals whose HSV episodes are not adequately suppressed by 400 mg BID. Treatment may be continued indefinitely. Note that suppressive therapy also reduces the risk of transmission of HSV. Effective antiretroviral therapy (ART) also may reduce the frequency of HSV outbreaks.

HSV During Pregnancy

Acyclovir appears to be safe and effective for use by pregnant women and remains the drug of choice. Few data are available on the use of valacyclovir and famciclovir during pregnancy.

It is important to avoid peripartum transmission of HSV. For women with recurrent or new genital HSV late in pregnancy, obstetric or infectious disease specialists should be consulted. All women should be evaluated carefully for symptoms and signs of genital HSV.

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