21 Anogenital herpes

‘Herpes’ is named from ancient Greek ‘to creep or crawl’ with the typical spreading skin lesions described by Hippocrates.

Herpes simplex virus (HSV) types 1 and 2 is a neurotropic virus, about 200nm in diameter, with a central DNA core covered by an icosahedral capsid and enveloped in a lipid membrane derived from the host cell. There are two viral types: HSV-1 (usually transmitted by contact with infected orolabial mucosa) and HSV-2 (usually transmitted by contact with infected genital mucosa sexually or at delivery). HSV is readily inactivated at room temperature and by drying; therefore fomite and aerosol spread are unusual. Previous oral HSV-1 infection protects against genital HSV-1 but not HSV-2 disease, although it reduces severity of first-episode genital herpes and makes asymptomatic seroconversion more likely.

HSV-1 antibodies (usually indicating oral infection) ↑ with age up to ~80%, (more common in low socio-economic groups). ↑ prevalence rate at adolescence suggests transmission by sexual contact. HSV-2 antibodies (usually indicating anogenital infection) appear at puberty and correlate with sexual activity, with a lifetime seroprevalence rate of 10–80%, greater in ♀. Only 5–20% of those with HSV-2 antibodies recollect previous symptoms. Over the past 20 years there has been a disproportionate ↑ in HSV-1 as a cause of initial AGH especially in young ♀, now with up to 80% affected, but lower rates are found (35–45%) in ♂. HSV-2 sexual transmission rate between discordant couples is about 15–20% per year (↑ from ♀ to ♂). Transmission follows direct skin contact rather than from genital fluids. In ♀ hormonal contraceptive use, bacterial vaginosis and high-density vaginal group B streptococcal infection have been reported as risk factors for genital HSV-2 shedding. Male circumcision may provide a weak protective effect against HSV-2 infection.

~70% of new infections acquired from asymptomatic viral shedders. 25% of those presenting with a first clinical HSV-2 episode have HSV-2 antibodies, indicating previous asymptomatic acquisition (pre-existing genital herpes). Over 60% of newly acquired HSV-2 infections are asymptomatic (↑ in ♂). In those with symptoms, 13% have atypical clinical features.

Incubation period is variable but typically 3–14 days. Clinical features and course of HSV-1, HSV-2, and AGH are similar, although severity of symptoms (systemic and local) and complications ↑ in ♀.

Constitutional symptoms occur within firstst week in over 50% (fever, headache, malaise, and myalgia). Non-1° infections are less likely to have constitutional or severe symptoms.

Local symptoms include pain, irritation, regional tender lymphadenopathy, and discharge—vaginal and urethral (~33% of ♂ with 1° HSV-2). Typically, vesicles appear over a local area of erythema and may become pustular before breaking down to form multiple tender ulcers with local oedema being common (Plate 12). Persist for 4–15 days before being followed by crusting (if keratinized skin) and re-epithelialization. New lesions (crops) during episode occur in 75%, usually within first 10 days. Mean resolution time without treatment 17–20 days (but may take up to 6 weeks) and viral shedding time about 12 days.

Problems with micturition, including urine retention, more common in ♀ than in ♂. Cervicitis occurs in 70–90% (with HSV-2). ♂ may develop 2° phimosis.

Anal infection, usually related to anal sexual contact, if symptomatic presents with pain, irritation, discharge, tenesmus, and sacral autonomic dysfunction. External peri-anal lesions only seen in ~50%.

Extra-anogenital lesions occur around groin, buttocks, lips, fingers (whitlow), and eyes (keratoconjunctivitis), and by infecting eczematous skin (eczema herpeticum).

Following initial AGH:

Signs and symptoms are confined to affected anogenital site. Prodrome (local skin tingling, sciatic nerve pain) occurs up to 48 hours before appearance of lesions in ~50%. Although symptomatic recurrences are more common in ♂, severity ↑ in ♀. Lesions similar to initial infection but area of skin involvement one-tenth and re-epithelialization occurs in 6–10 days with viral shedding about 4 days. Cervical infection only found in 15–30% of ♀.

Main complication is psychological, especially if recurrences are frequent, and include: shame, frustration, depression, and withdrawal from social and sexual interaction.

Rarely erythema multiforme.

Recurrent rectal/peri-rectal herpes in men more likely to be HSV-1.

Very common, especially when recurrent. May present as non-specific erythema, erosions, fissures, and even frenal tear.

For many patients diagnosis of AGH infection and implications of recurrence can provoke severe emotions often fuelled by misinformation. Although chronic psychological morbidity may have an adverse effect, acute anxiety situations and everyday stresses do not ↑ recurrences. Time spent discussing AGH and its implications is important in its management. Points to consider include accurate information on natural course of infection, recurrences (prodromes and their recognition); management and implications of current episode and possible future recurrences, the avoidance of sexual contact until a week after the lesions disappear, and in future recurrences from the onset of the prodrome (to cover the period of highest risk of viral shedding), relevance of infection to current and potential future relationships, balanced consideration of potential to transmit infection both with and without symptoms (understood by the patient and clearly documented), safe sex issues and condom information, and issues relating to pregnancy.

Information received initially may not be retained, so an information leaflet containing key points should be supplied. Useful website: Herpes Viruses Association (  www.herpes.org.uk).

Typically mild and self-limiting. Unless unusually severe, antiviral treatment is of limited benefit in reducing duration and viral shedding. General advice and support are often adequate.

May be considered for infrequent but regular recurrences. Should be commenced as early as possible, ideally at prodrome to reduce duration by a median of 1–2 days. Therefore patient-initiated treatment should be arranged by providing medication in anticipation of next episode to commence before signs appear. This approach may have a placebo effect as it gives reassurance that medication is available. Treatment regimens are same as for initial herpes except that famciclovir is reduced to 125mg twice daily. Short treatments have also shown to be effective, i.e. aciclovir 800mg 3 times daily for 2 days, famciclovir 1g twice daily for 1 day, valaciclovir 500mg twice daily for 3 days.

Usually considered for >6 recurrences a year. Provide continuous treatment for 6–12 months and then discontinue for reassessment. If recurrences resume at a high level, further suppressive treatment may be required. >90% have a significant reduction in recurrences (mean recurrence rates of 12.8/year pretreatment falling to 1.8 during treatment). ~20% experience a reduction in frequency of recurrences after completion. Daily suppressive treatment with valaciclovir has been shown to reduce HSV-2 transmission among HSV-2 discordant couples by 75% for clinical disease and reduced acquisition (measured by serology) by 48%.

Rarely found in immunocompetent patients but reported in ~6% of those with immunosuppression, including HIV infection. Resistant strains can be treated with foscarnet and cidofovir.

Extract from the plant Echinacea purpura has been advocated in treatment of genital herpes, but a double-blind trial in recurrent AGH showed no significant benefit when compared with placebo.

Overall mortality has substantially ↓ in past 20 years but still ~20% of survivors have long-term neurological sequelae.

Consult local guidelines (which may vary) .

Avoid intercourse during partner’s recurrences. Advise about risk of acquiring HSV-1 through cunnilingus. Routine HSV screening of pregnant ♀ and routine antepartum HSV swabs in those with a history of AGH are not recommended. Consider type-specific serology if:

Aciclovir is well tolerated and has been shown to be safe in pregnancy (from Pregnancy Registry data up to 1999), but its use is not currently licensed. Therefore, although it is widely prescribed, this must be discussed with the patient and documented. Oral aciclovir should be prescribed as indicated for initial episodes and IV aciclovir for severe genital or disseminated infection with case reports demonstrating significantly improved survival. It is rarely indicated for the treatment of recurrences during pregnancy.

A systematic review of suppressive aciclovir prescribed in pregnancy (after 36 weeks of gestation) demonstrated a 75% ↓ in recurrences at delivery and a 40% ↓ in Caesarean section rate for recurrent AGH. Viral detection at delivery was reduced by 90% (although shedding was not completely eliminated), and there were no cases of neonatal infection. For ♀ with recurrent AGH, USA guidelines recommend offering suppressive treatment at or beyond 36 weeks and UK guidelines recommend discussing this with ♀ who opt for a Caesarean section if active lesions at delivery (although careful consideration is required with concomitant HIV infection). In addition, suppressive treatment may be considered for those with first-episode genital herpes in 1st and 2nd trimester (to ↓ risk of clinical recurrence at term), for those with HIV infection, and to male partners if pregnant ♀ is serodiscordant.

There are no documented adverse fetal effects because of medication exposure. There are insufficient data for the use of valaciclovir and famciclovir in pregnancy.

Routinely advised for all ♀ with initial genital herpes at term and for those acquiring initial infection after 34 weeks gestation but not indicated for 1st and 2nd trimester acquisition. If vaginal delivery is unavoidable, the mother and baby should be treated with aciclovir. The use of Caesarean section for a recurrence at term is contentious, with UK guidelines recommending that the mode of delivery should be discussed with the ♀ and individualized based on the clinical circumstances and her preferences. However, in a large study of ♀ with recurrence at delivery neonatal herpes occurred in 1.2% infants delivered by Caesarean section compared with 7.7% delivered vaginally. Therefore US guidance recommends Caesarean section for those with prodromal symptoms or active lesions at delivery.

Caesarean section not advised for ♀ with history of AGH but no active genital lesions at delivery.

IV aciclovir 10mg/kg body weight 8 hourly for 10 days.