2.5.10 Genital herpes simplex

Genital herpes is considered as one of the most frequent sexually transmitted infections in Europe. In epidemiological studies, the seroprevalence has been up to 15-20%, but there is a substantial variation between countries and populations. The incidence of HSV infection as a measure of the primary infection is difficult to quantify, partly due to unrecognized or asymptomatic infections. It is estimated that the incidence of genital herpes simplex in European countries ranges from 5 to 24 per 100 persons per year.

Genital herpes simplex is the primary infection or a recurrence of the genital mucosa or adjacent skin by human herpes simplex virus (HSV) type 1 or 2.

The causative pathogens are human herpes viruses (HSV) type 1 and 2, which both belong to the most common human viral infections worldwide. Thus, genital herpes is one of the most common causes of genital ulcers in Europe. HSV-1 mainly associates with facial skin and mucosal infections and HSV-2 is more prevalent in genital infections. Clinical symptoms can be caused by primary infection or recurrences. After the primary infection, HSV remains latent in regional neuronal ganglia from where the virus spreads to the mucous membrane or skin epithelial cells via sensory neurons. HSV infection can recur spontaneously or as a consequence of different stimuli. The recurrent lesions typically appear at same or closely adjacent skin or mucosa sites.

Primary infection

Both HSV-1 and HSV-2 are possible, the first being increasingly prevalent.

In males, the most common clinical features are grouped vesicles and erosions on the penis. The erosions are painful and, if untreated, can last up to 2-3 weeks. The inguinal lymph nodes can be tender and patients can have flu-like symptoms with fever and myalgia.

In females, the lesions tend to be more erosive and ulcerative. Typical sites are the vulvar area and the mucosae of the vagina and cervix. Many patients experience dysuria and pelvic pain. Flu-like symptoms with fever may occur and the disease course may be more severe in females.

Succeeding the primary infection, immunity develops but is of short duration and does not always protect from recurrences.

Recurrence

Recurrent genital herpes is mostly due to HSV-2.

During recurrences the symptoms are usually milder and of shorter duration than in the primary infection and have a tendency to reappear in the genital area, but not always at the identical site. HSV recurrence can occur spontaneously or be triggered individual provoking factors: minor trauma (e.g. after sexual intercourse), genital infections (e.g. Candida-vaginitis), ultraviolet radiation (sun exposure), menstrual cycle (especially before the menstrual bleeding) and emotional stress.

The primary infection usually lasts 2-3 weeks, but recurrences are shorter, 7-10 days. A prolonged course and spread to larger areas are possible in immunocompromised patients.

In males, erosions are typically seen on the glans penis or shaft. In females, the vulvar area and the mucosae of the vagina and cervix are most often affected. In the genital area, intact blisters are rarely seen but rather painful ulcerations.

HSV-1 and HSV-2 can be detected from the skin and mucosal lesions of the skin by viral culture, HSV antigen test (direct immunofluorescence) or preferably nucleic acid amplification tests. Serological tests are usually not helpful in genital herpes simplex, because they only confirm the carrier status of the patient and seroprevalence is very high in the general population.

A biopsy is usually necessary only in prolonged ulcers (exclusion of malignancy). Histologic changes of HSV-infection are distinctive: intraepidermal blister, keratinocytes show nuclear changes, multinucleation and viral inclusions. There is also a mixed inflammatory infiltrate.

Most important differential diagnoses are trauma-induced ulcers (e.g. during sexual intercourse), genital aphthae, herpes zoster (shingles), syphilis (primary chancre), ulcerative candida- infections and weeping irritant and allergic contact dermatitis. In travel-related cases, chancroid (ulcus molle) and granuloma inguinale must also be considered. Typical clinical features are easy to recognize, but challenging are patients with untypical presentations, such as intermittent genital itching, fissures and transient painful erythema.