Review of Management Options for Genital Herpes Infections

Meredith Davidson, MSc, BSc, BPHE¹ and Melinda Gooderham, MD, FRCPC²

^1. Queen’s University, Kingston, ON, Canada
^2. Skin Centre for Dermatology and Skin Laser Clinic, Peterborough, ON, Canada

Introduction

Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus (HSV). HSV type 2 (HSV-2) causes approximately 60% of the primary genital HSV infections in Canada.¹ However, the type 1 strain (HSV-1), traditionally associated with oral herpes, is capable of causing a similar clinical picture. It is estimated that 20% to 40% of Canadians are HSV-2 seropositive, while studies have consistently shown that the great majority are unaware of their disease status.¹ Although treatment exists, there is currently no cure for genital herpes and infection is, therefore, lifelong. Consequently, patients should be informed about clinical signs and symptoms of genital herpes, as this may help them to recognize symptomatic infection and seek early treatment, thereby contributing to improved management and therapeutic efficacy.

Brief Overview of the Disease

• Transmission of genital herpes occurs when there is direct contact with secretions or skin of a person who is actively shedding virus.
• The clinical course of genital herpes varies greatly from patient to patient; up to 75% of infected individuals are asymptomatic.¹
• Polymerase chain reaction (PCR) testing has demonstrated that viral shedding occurs on up to 40% of asymptomatic days.²
• Asymptomatic viral shedding leads to a precarious situation in which individuals can unwittingly transmit the disease to sexual contacts.
• Symptomatic genital HSV infection is manifested 7-10 days after exposure by a prodrome of tingling and pain that precedes the lesions by up to a day.
• The initial or primary outbreak is generally more severe and may have multiple genital or anorectal ulcerations. Recurrent episodes are usually less intense and of shorter duration.
• Clinical presentation includes developed clusters of papules on an erythematous base, which then become vesicles, pustules, and later erosions. During initial infection, these lesions crust over by day 7-14 and generally heal by the fourth week without scarring.
• An initial episode is often accompanied by dysuria, urinary retention, tender inguinal and femoral lymphadenopathy, as well as systemic symptoms that can include fever, malaise, and headache.
• After the initial infection, the virus remains latent in the sacral dorsal root ganglion and, at variable intervals, travels back down the nerve root and causes asymptomatic shedding or mucocutaneous outbreaks that are usually less intense than the initial episode.³
• Recurrent episodes can be triggered by stress, infection, trauma, or menstruation, and have a prodrome of burning and tenderness for 2 hours to 2 days, followed by papules and vesicles lasting 4-15 days until re-epithelialization.²
• In the first year after infection, an untreated patient will experience an average of four further episodes.
• Complications associated with genital HSV infection include:^3,4
  • disseminated HSV
  • aseptic meningitis
  • autonomic dysfunction with urinary retention
  • vertical transmission from an infected mother to her newborn
  • increased risk of HIV transmission.

Diagnosis

• Diagnosis is usually made clinically, but laboratory tests should be used to confirm the diagnosis. This can be done with viral culture, HSV detection, or serology.³
• To obtain a sample from an active clinical lesion for laboratory analysis:
  • choose the most recent of the vesicles and gently lift the roof of the vesicle with a needle tip or scalpel blade to expose the underlying material
  • instill collected swab in viral culture media and send to the lab as per usual practice (takes 5 days to culture)
  • alternatively, transfer swab to a glass slide and send for immediate direct immunofluorescence testing (rapid detection).
• Type specific serology can be done, however, this can only be used to determine past infection or asymptomatic HSV infection; this test is helpful for determining between HSV-1 and HSV-2.⁴
• A Tzanck smear showing multinucleated giant cells has been used historically, but may not always be practical in a clinic setting.
• Consider testing for other bacterial causes of ulcerative lesions, such as Treponema pallidum and Haemophilus ducreyi, depending on the demographics of the population.³

Treatment Rationale

• Treatment is aimed at reducing patient discomfort, transmission of the virus, duration of the outbreak, and risk of complications.
• Treatment should be initiated as soon as possible without waiting for laboratory results (ideally within 72 hours of symptom onset in order to minimize duration and severity of illness).
• Conservative measures include analgesics and sitz baths to alleviate the pain.
• Intermittent urinary catheterization may be necessary if urinary retention results from autonomic dysfunction.

Available Treatments

Topical Therapy

• Although oral agents are the standard of practice in the treatment of genital herpes, topical administration of 5% acyclovir is an option for those patients who do not wish to receive oral therapy, who are on multiple oral medications (e.g. elderly, multiple comorbidities), or if cost is an issue. It allows prompt and convenient treatment to be initiated by the patient when symptoms first develop.
• Topical therapy with 5% acyclovir can be used for initial outbreaks; treatment must be started during the prodromal stage (Table 1).
• Randomized double-blind, placebo controlled studies have shown that topical acyclovir 5% in an ointment or cream base reduces viral shedding, time to healing, duration of pain, and new lesion formation for initial episode of genital herpes.^5-7
• Many other topical agents are currently being investigated, including immune response modifiers, other antivirals, microbicides, and oligodeoxynucleotides with variable results reported.²

Oral Therapy

• There are three oral anitviral agents available: acyclovir, valacyclovir, and famciclovir (Tables 1, 2 and 3).
• Efficacy for all three agents is comparable with respect to duration and severity of the lesions, as well as reduction in the incidence of complications, such as meningitis.
• Decisions about which agent to use is dependent upon dosing and price, with acyclovir being the least expensive and valacyclovir requiring less frequent dosing.
• Suggested duration for treatment is 7-10 days, however, this should be extended if lesions are not healed or new lesions are developing.
• Recurrent episodes will require therapy and can be treated according to the severity and frequency of outbreaks.
• Episodic therapy (Table 2) is suitable for patients with mild or infrequent outbreaks.
• Suppressive therapy (Table 3) is required for patients with either severe or frequent episodes (> 6 episodes per year).

Intravenous (IV) Therapy

• Only acyclovir is available for IV administration and should be reserved for use in severe cases, immunocompromised patients, or in patients with complications requiring hospitalization.
• The dose is 5-10 mg per kg body weight every 8 hours.²

Conclusion

Genital herpes is a chronic sexually transmitted infection that has the potential to cause both physical and psychological distress. The disease is spread by direct contact and manifests either asymptomatically or with pain and lesions that begin as clusters of papules and develop into vesicles or ulcerations. Diagnosis is usually clinical, but is best confirmed with swab sample testing. Treatment should be initiated as soon as possible after symptom onset and aims to reduce the severity and duration of symptoms, as well as the risk of complications. Oral antivirals are the mainstay of treatment, but in patients who are unable or unwilling to use these agents, topical 5% acyclovir may be a therapeutic option, particularly for managing initial symptoms of HSV outbreaks. Adjunctive therapies include analgesics and sitz baths. IV acyclovir is reserved for the most severe cases requiring hospitalization and/or in immunocompromised patients.

References

1. Steben M, et al. Can J Hum Sex 6(2):127-34 (1997).
2. Viera MH, et al. Int J Dermatol 49(7):733-49 (2010 Jul).
3. Gupta R, et al. Lancet 370(9605):2127-37 (2007 Dec 22).
4. Sen P, et al. BMJ 334(7602):1048-52 (2007 May 19).
5. Corey L, et al. N Engl J Med 306(22):1313-9 (1982 Jun 3).
6. Kinghorn GR, et al. Antiviral Res 3(5-6):291-301 (1983 Dec).
7. Thin RN, et al. Br J Vener Dis 59(2):116-9 (1983 Apr).