Herpes genitalis

Published on 18/03/2015 by admin

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Herpes genitalis

Rachel A. Gordon, Rana Majd Mays and Stephen K. Tyring

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Herpes genitalis, or genital herpes, is a recurrent vesicular eruption of the skin and mucosa in the region between the navel and the buttocks, usually preceded by prodromal symptoms including itching, burning, and tingling. It is a common sexually transmitted disease caused predominantly by herpes simplex virus type 2 (HSV-2), but can also be caused by HSV-1. Primary infection may have associated influenza-like systemic signs, including fever, headache, malaise, and myalgia, which occur two to 20 days post exposure. Tender lymphadenopathy may also develop in the second and third weeks. Recurrences generally lack systemic symptoms and are less severe than the primary outbreak. Lesions of recurrences occur in the same area but are fewer in number and heal more quickly. Typical lesions of recurrent outbreaks manifest as grouped papules on an erythematous base which progress to thin-walled vesicles, ulcers, and then soft crusts. Dry crusts form in 3 to 4 days, allowing for healing. Residual hypopigmentation, hyperpigmentation, and scarring may occur with healing.

Management strategy

As no cure exists for herpes genitalis, treatment is aimed at reducing the number of recurrences using suppressive therapy and at promoting rapid healing when a recurrence is present. In addition, treatment aims to reduce infectivity by reducing viral shedding, and to reduce complications such as urinary retention and aseptic meningitis. In the past, acyclovir, both topical and oral, was used as a first-line treatment for recurrences. Given acyclovir’s low bioavailability, it requires frequent dosing. The standard dosing of oral acyclovir for a recurrence is 200 mg five times daily for 5 days. Alternative regimens have also been shown to be effective, including 400 mg three times daily for 5 days, 800 mg three times daily for 2 days, and 800 mg twice daily for 5 days. The frequent dosing of acyclovir led to the development of valacyclovir and famciclovir (the prodrugs of acyclovir and penciclovir, respectively) as alternative therapies with improved bioavailability. The use of topical acyclovir should be discouraged as it is less effective than oral acyclovir. Valacyclovir has been shown to be effective when dosed 500 mg twice daily for 3 days or 1000 mg once daily for 5 days. A dosing regimen of oral valacyclovir, given 2000 mg twice daily for 1 day, has been studied and shown to be more convenient; however, further comparative studies are needed. Famciclovir is effective when prescribed as 1000 mg twice daily for 1 day. It may also be taken as 125 mg twice daily for 5 days. Acyclovir, valacyclovir, and famciclovir may all be used for suppressive therapy.

Immunocompromised individuals have more frequent recurrences and can develop more severe lesions, thus requiring longer treatment periods with higher doses than those used in the immunocompetent. Severe cases may require intravenous therapy. Suppressive dosage regimens have been used in this population. Long-term therapy may lead to the selection of resistant strains of virus. In acyclovir-resistant cases, intravenous therapy with foscarnet may be required.

Another important aspect of genital herpes management is psychosocial. The recurrent nature of genital HSV infection can have severe emotional and psychological impact on patients. Counseling serves to help them cope with the infection and to prevent sexual and perinatal transmission. A physician can empower patients, allowing them to better manage the disease by educating them about the disease process.

Specific investigations

Diagnosis may be made clinically when the history and presentation are consistent with HSV infection. When possible, laboratory confirmatory testing should be used. Severe or refractory cases may be due to underlying immunosuppression, which should be investigated further.

First-line therapies

imageValacyclovir (Valtrex) A
imageAcyclovir (Zovirax) A
imageFamciclovir (Famvir) A

Acute reactivation episodes

Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials.

Johnston C, Saracino M, Kuntz S, Magaret A, Selke S, Huang ML, et al. Lancet 2012; 379(9816): 641–7. Erratum in: 2012. Lancet. 379(9816): 616.

Three separate, complementary open-label cross-over studies compared no medication with acyclovir 400 mg twice daily (standard dose), valacyclovir 500 mg daily (standard dose) with acyclovir 800 mg three times daily (high dose), and standard-dose valacyclovir with valacyclovir 1 g three times daily (high dose). Participants were HIV negative, HSV-2 seropositive and collected genital swabs four times daily. Treatment lasted between four and seven weeks; the primary end-point was shedding rate. High-dose acyclovir was associated with less viral shedding than standard-dose valacyclovir, but there was no significant difference in time to lesion healing between the groups. High-dose valacyclovir had less viral shedding and shorter lesion healing time when compared to its standard dose. Viral shedding persisted even in high-dose regimens, and more potent therapy is needed to prevent HSV transmission.

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