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Herpes Genitalis: Symptoms, Diagnosis and Treatment

References: (CDC Guidelines, 2006) (Kimberlin and Rouse, 2004) (Whitley and Roizman, 2001).

Definition of genital herpes

Genital herpes is an infection of the external genitals with herpes simplex virus (HSV-1 or -2), resulting in clusters of inflamed papules and vesicles.

Epidemiology

There is an age-related increase in HSV-2 prevalence from 7% (15–19 years) to 28% (40–44 years). Same with HSV-1, there exists an age-related increase in prevalence, with far greater manifestation: 20% (<5 years), 40–60% (20–40 years). Most infected individuals are asymptomatic. Risk groups for the HSV-2 infection are: sexually active young people with multiple partners, sex workers, lack of condom use, MSM, and living in an urban area.

Etiology of Genital Herpes

Pathogen:

Herpes simplex virus 1 (oral type) or 2 (genital type). HSV-2 causes genital recurrences more often.

Morphology of herpes simplex virus:

The family of herpes viruses is of icosahedral shape; they contain double-stranded DNA (84 proteins). The capsid (a protein cage) encases the DNA, wrapped by an envelope (lipid bilayer).

Mechanisms of genital herpes infection:

The virus binds to cell membrane receptors, and endocytosis and dissolution of the viral shell (envelope) follow. The capsid gets via axoplasmic transport to the nucleus of the sensory neuron. Viral proteins are generated in three cycles (immediate early, early, and late proteins). After the outbreak and healing of herpes genitalis, HSV-DNA remains in the neuron's nucleus without viral replication (latency). After a highly variable time, various factors (see below) may trigger a further clinical manifestation of herpes genitalis (recurrence). Viral shedding may remain asymptomatic.

Immune response:

HSV inhibits the presentation of immunologically important protein fragments on the MHC class 1 proteins. Furthermore, HSV inhibits DNA transcription, destroys mRNA, and inhibits the apoptosis of the host cell in response to the viral infection.

Transmission of genital herpes:

HSV is transmitted through oral-genital or genital contact.

Signs and Symptoms of Genital Herpes

Genital sores:

Grouped papels or vesicles on an erythematous base are pathognomonic for genital herpes. After rupturing, they form an ulcer and heal within 1–4 weeks.

First Manifestation of Herpes Genitalis:

Balanitis, urethritis or herpetic vulvovaginitis, sometimes without typical genital sores. The symptoms of the first infection are more pronounced. If there already has been an oral HSV-1 infection, the symptoms of primary genital herpes are attenuated.

Complications of Genital Herpes:

1% of the patients with primary genital herpes develop an autonomic dysfunction with urinary retention, erectile dysfunction, constipation, and sensory losses. Sometimes, (intermittent) catheterization for several weeks is necessary.

Mild meningitis is relatively common with primary herpes (13–20%). Herpes encephalitis is less common and has a mortality rate of around 70%.

Neonatal herpes simplex may develop after vaginal birth and presents either with a local infection (skin, eye or mouth), disseminated manifestation (internal organs) or encephalitis.

Recurrent Genital Herpes:

HSV-2 often causes recurrent genital herpes with typical genital sores (see above). The lesions are painful; there may be inguinal lymphadenopathy. Frequently, patients feel genital paresthesias before a manifestation of recurrent herpes genitalis becomes visible. A third of the patients develop frequent recurrences (>6 per year), while a third rarely develop recurrences (<1 relapse per year).

Trigger of recurrent genital herpes:

The following factors may trigger recurrent genital herpes: physical or emotional stress, fever (cold sores), UV light, injury, and local infections.

Herpes vegetans:

Insufficient healing of the genital sores in patients with immunodeficiency results in exophytic or ulcerative lesions with hyperkeratosis.

Diagnosis of Genital Herpes

Signs and symptoms are usually sufficient for diagnosis (see above). Virus typing is possible by PCR from swabs from ruptured vesicles. Furthermore, serological tests can reveal a HSV infection in the past, but disease activity cannot be measured. A detailed history and examination of any sexual partner are necessary.

Treatment of Genital Herpes

Therapy of First Manifestation:

Administration of a virostatic agent as soon as possible (after clinical diagnosis) for five days: Aciclovir 200 mg 1-1-1-1-1 p.o., Aciclovir 400 mg 1-1-1 p.o., Famciclovir 250 mg 1-1-1 p.o. oder Valaciclovir 500 mg 1-0-1 p.o. Intravenous administration is necessary only in severe cases, e.g., with encephalitis. The antiviral medication relieves symptoms and accelerates the healing of the lesions but cannot affect the likelihood of disease recurrence. Very early initiation of therapy is critical for efficiency.

Therapy of recurrent genital herpes:

Prescribe on-demand medication for five days, dosage see above. The start of therapy with begin of prodromal symptoms can prevent the outbreak of the disease relapse.

Local Therapy:

Local antiviral therapy has only little clinical effect and is not recommended.

Prophylaxis of genital herpes:

Condom use; sexual abstinence, especially concerning partners with genital lesions.

Experimental Therapy:

Vaccinations show promising results in animal experiments; several clinical trials have started.

References

Center for Disease Control and Prevention.: Sexually transmitted diseases treatment guidelines 2006.
in: MMWR
2006; 55 (No. RR-11): 1–93.

Kimberlin und Rouse 2004 KIMBERLIN, D. W. ; ROUSE, D. J.: Clinical practice. Genital herpes.
In: N Engl J Med
350 (2004), Nr. 19, S. 1970–7

Liu and Li (NEJM 2023): Case Report: Herpes vegetans. https://www.nejm.org/doi/full/10.1056/NEJMicm2215873

Whitley und Roizman 2001 WHITLEY, R. J. ; ROIZMAN, B.: Herpes simplex virus infections.
In: Lancet
357 (2001), S. 1513–18

  Deutsche Version: Herpes genitalis