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Herpes Genitalis: Symptoms, Diagnosis and Treatment
Definition of genital herpes
Genital herpes is a sexual transmitted infection 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, 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 a genital 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
NAAT swab:
Virus detection and typing is possible using a NAAT swat from genital lesions. Blind genital swabs in asymptomatic patients do not rule out the presence of an HSV infection.
Serology:
The detection of the (past) HSV infection and typing is possible via antibodies. No statement can be made about the disease activity.
Further examinations:
If necessary, further tests for sexually transmitted diseases. Diagnosis and counseling of sexual partners.
Treatment of Genital Herpes
Therapy of First Manifestation:
Administration of a virostatic agent as soon as possible (after clinical diagnosis) for five days, up to ten days in the event of delayed recovery or complications: 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:
The patient should have on-demand medication ready and start treatment by himself. Starting therapy at the time of prodromal symptoms can sometimes prevent the relapse or alleviates the intensity of the recurrence. On-demand medication has higher doses for a shorter time period: aciclovir 800 mg 1-0-1 p.o. for two days, famciclovir 1 g 1-0-1 p.o. for one day or valaciclovir 500 mg 1-0-1 p.o. for three days.
Suppressive therapy for frequent relapses:
Frequent recurrences and asymptomatic viral shedding can be treated with long-term suppressive therapy. Despite long-term therapy, however, individual recurrences of the disease are possible and the risk of disease transmission in a stable partnership is only halved. The safety of long-term therapy is best documented for aciclovir (up to 18 years); there is no evidence of cumulative toxicity. Dosage for long-term therapy: aciclovir 400 mg 1-0-1 p.o., famciclovir 250 mg 1-0-1 p.o. or valaciclovir 250 mg 1-0-1 p.o. The dosage can be increased if the response is insufficient: aciclovir 400 mg 1-1-1 p.o. or valaciclovir 500 mg 1-0-1 p.o.
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 clinical trials.
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References
Center for Disease Control and Prevention: “Sexually Transmitted Infections (STI) Treatment Guidelines,” 2021. [Online]. Available: https://www.cdc.gov/std/treatment-guidelines/STI-Guidelines-2021.pdf
IUSTI, “European guidelines for the management of genital herpes,” 2017. [Online]. Available: https://iusti.org/wp-content/uploads/2019/12/Herpes.pdf.
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
Whitley und Roizman 2001 WHITLEY, R. J. ;
ROIZMAN, B.:
Herpes simplex virus infections.
In: Lancet
357 (2001), S. 1513–18
Deutsche Version: Herpes genitalis