Recurrent Herpes Simplex Virus Infection

Recurrent herpes infection of the mouth (recurrent herpes labialis [RHL]; recurrent intraoral herpes simplex infection [RIH]) occurs in patients who have experienced a previous herpes simplex infection and who have serum-antibody protection against another exogenous primary infection. In otherwise healthy individuals, the recurrent infection is confined to a localized portion of the skin or mucous membranes. Recurrent herpes is not a re-infection but a reactivation of virus that remains latent in nerve tissue between episodes in a
nonreplicating state.Herpes simplex has been cultured from the trigeminal ganglion of human cadavers, and recurrent herpes lesions commonly appear after surgery involving the ganglion.Recurrent herpes may also be activated by trauma to the lips, fever, sunburn, immunosuppression, and menstruation.The virus travels down the nerve trunk to infect epithelial cells, spreading from cell to cell to cause a lesion.
The published evidence demonstrating that RAS is not caused by herpesvirus induced many to believe that recurrent herpes infection of the oral region occurred only on the lips and not on the oral mucosa; this has been shown to be false. RAS and herpes lesions can both exist intraorally and are two separate and distinct disease processes.All patients who experience primary herpes infection do not experience recurrent herpes. The number of patients with a history of primary genital infection with HSV1 who subsequently experience recurrent HSV infections is approximately 15%.The recurrence rate for oral HSV1 infections is estimated to be between 20 and 40%.
Studies have suggested several mechanisms for reactivation of latent HSV, including low serum IgA,decreased cellmediated immunity, decreased salivary antiherpes activity,
and depression of ADCC (antibody-dependent cell-mediated cytotoxicity)and interleukin-2 caused by prostaglandin release in the skin.
Individuals with T-lymphocyte deficiencies owing to AIDS or transplant or cancer chemotherapy may develop large chronic lesions(see “Herpes Simplex Virus Infection in Immunosuppressed Patients,” below) or, rarely, disseminated HSV infection.
CLINICAL MANIFESTATIONS
RHL, the common cold sore or fever blister, may be precipitated by fever, menstruation, ultraviolet light, and perhaps emotional stress. The lesions are preceded by a prodromal period of tingling or burning. This is accompanied by edema at the site of the lesion, followed by formation of a cluster of small vesicles (Figure 4-25). Each vesicle is 1 to 3 mm in diameter, with the size of the cluster ranging from 1 to 2 cm. Occasionally, the lesions may be several centimeters in diameter, causing discomfort and disfigurement. These larger lesions are more common in immunosuppressed individuals. The frequency of recurrences varies.
RIH lesions in otherwise normal patients are similar in appearance to RHL lesions, but the vesicles break rapidly to form ulcers. The lesions are typically a cluster of small vesicles or ulcers, 1 to 2 mm in diameter, clustered on a small portion of the heavily keratinized mucosa of the gingiva, palate, and alveolar ridges, although RIH lesions can occasionally involve other mucosal surfaces
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(Figure 4-26). In contrast, lesions of RAS tend to be larger, to spread over a larger area of mucosa, and to have a predilection for the less heavily keratinized buccal mucosa, labial mucosa, or floor of the mouth.
DIAGNOSIS
If laboratory tests are desired, RIH can be distinguished from RAS by cytology smears taken from the base of a fresh lesion. Smears from herpetic lesions show cells with ballooning degeneration and multinucleated giant cells; those from RAS lesions do not. For more accurate results, cytology smears may also be tested for HSV using fluorescein-labeled HSV antigen. Viral cultures also are used to distinguish herpes simplex from other viral lesions, particularly varicella-zoster infections.
TREATMENT
Recurrent herpes infections of the lips and mouth are seldom more than a temporary annoyance in otherwise normal individuals and should be treated symptomatically. Patients who experience frequent, large, painful, or disfiguring lesions may request professional consultation. The clinician should first attempt to minimize obvious triggers. Some recurrences can be eliminated by the wearing of sunblock during intense sun exposure.
Recurrent Herpes Simplex Virus Infection

 Drugs are available that suppress the formation and shorten the healing time of new recurrent lesions. Acyclovir, the original antiherpes drug, has been shown to be both safe and effective. The newer antiviral drugs such as valacyclovir, a prodrug of acyclovir, and famciclovir, a prodrug of penciclovir, have greater bioavailability than does acyclovir, but they do not eliminate established latent HSV. However, in the mouse model, famciclovir appeared to decrease the rate of HSV latency.The clinical importance of this finding in human HSV infection is not known. The effectiveness of these antiherpes drugs to prevent recurrences of genital HSV has been studied extensively. Acyclovir 400 mg twice daily, valacyclovir 250 mg twice daily, and famciclovir 250 mg were each highly effective in preventing genital recurrences.

Recurrent Herpes Simplex Virus Infection

The use of antiherpes nucleoside analogues to prevent and treat RHL in otherwise normal individuals is controversial. Systemic therapy should not be used to treat occasional or trivial RHL in otherwise healthy individuals, but episodic use to prevent lesions in susceptible patients before highrisk activities such as skiing at high altitudes or before undergoing procedures such as dermabrasion or surgery involving the trigeminal nerve is justifiable. Some clinicians advocate the use of suppressive antiherpes therapy for the small percentage of RHL patients who experience frequent deforming episodes of RHL. Acyclovir 400 mg twice daily has been shown to reduce the frequency and severity of RHL in this group of patients.Both acyclovir and penciclovir are available in topical formulations, but use of these preparations shortens the healing time of RHL by less than 2 days.