17.1 GENITAL HERPES
Herpes simplex virus (HSV) infection is by far the commonest cause of genital ulceration seen in general practice. Although HSV type 2 has traditionally been considered the commonest cause of genital herpes, studies have reported HSV type 1 infection in over 60% of cases, the virus being passed on by oro-genital contact.
Serological studies examining HSV-2 seroprevalence in various population groups have shown that up to 70% of infections are asymptomatic.
17.2 CLINICAL FEATURES
17.2.1 Primary attack (i.e. No previous exposure to HSV-1 or HSV-2)
Primary herpes is a miserable condition. Following an incubation period of 3-5 days (range 1-40 days), small blisters appear on the genitalia, often associated with a "flu-like" illness. The blisters soon break down to leave small tender ulcers that may eventually merge to produce quite extensive areas of painful ulceration (Figures 17.1 and 17.2). Lesions start to heal after about 12 days.
Herpes may cause a urethritis which presents as dysuria, often severe in nature.
Ninety percent of women have a cervicitis producing an excessive "vaginal" discharge.
Other clinical features include painful inguinal lym- phadenopathy, headache and photophobia (aseptic meningitis), urinary retention (sacral radiculopathy), pharyngitis, and extragenital lesions (on fingers, lips, buttocks).
17.2.2 First Attack: Non-primary
This is the first clinical episode of herpes in a patient who has had previous exposure to the virus (type 1 or type 2). Symptoms are usually much less severe than primary herpes owing to partial immunity.
Figure 17.1. Primary genital herpes affecting the penis
Figure 17.2. Primary genital herpes affecting the vulva
17.2.3 Recurrent Herpes
Approximately 90% of patients with type 2 genital herpes will suffer a recurrence within 1 year of their primary attack. This is in contrast to patients with HSV type 1 infection, in whom there is a 55% chance of recurrence. The frequency of recurrences also differs between the two viral types - on average 3-4 attacks per year with HSV-2 infection compared with twice a year with HSV-1.
Viral reactivation leading to symptomatic or asymptomatic viral shedding may be greatest during the first few months after a primary attack and should be discussed with patients diagnosed with primary infection. Symptoms of recurrent genital herpes are often mild. About 50% of patients will develop prodromal symptoms such as genital "pins and needles," shooting pains in the buttocks and legs, or inguinal discomfort associated with lymphadenopathy. Symptoms of sacral neuralgia are the most troublesome part of the recurrence for some patients.
The cervix is affected in only 10% of women with recurrent disease.
When lesions appear they tend to be few in number and heal within 1 week. A small number of patients, however, suffer more frequent and long-lasting attacks that can be particularly distressing (Figures 17.3 and 17.4).
Recent studies have suggested that symptoms of recurrent disease may be minimal and often ignored by the patient. This is an important issue that should be addressed when the diagnosis of herpes is first made. Taking note of minor genital symptoms and avoiding sexual contact at such times is important if the risk of transmission to partners is to be reduced.
Figure 17.3. Recurrent herpes of the penis
Figure 17.4. Recurrent herpes of the vulva
It is always wise to confirm the clinical diagnosis of herpes by positive viral culture or PCR. If initial swabs are negative patients should therefore be asked to re-attend immediately genital symptoms recur so that further swabs can be taken.
17.3 DIAGNOSIS OF GENITAL HERPES
Most laboratories are now able to perform herpes typing. This is of some prognostic significance regarding recurrence rate (see above) and can be helpful information when counseling patients.
The chances of obtaining a positive culture will depend very much on the stage of the lesion: ulcers shed more virus than crusting lesions. This needs to be explained to the patient who may not fully appreciate why they were diagnosed as having herpes at their initial consultation and then told a week or two later that their "herpes test" was negative. Some laboratories now perform PCR for diagnosing herpes infection. This is considered a much more sensitive method of diagnosis compared to viral culture.
Serological assays that distinguish between HSV type 1 and type 2 antibodies are now available but should be used selectively. Herpes serology is of no diagnostic value for primary herpes. Serology has a possible useful role in patients attending with recurrent genital ulceration and negative herpes culture. A negative result almost rules out herpes as a cause for the ulceration, although false negative results do occur, whereas a positive result for HSV type 2 antibody makes the diagnosis of genital herpes very likely.
Serology may also be helpful in couples where one partner has documented genital herpes and the other gives no history of infection. Positive HSV type 2 serology in the partner with no clinical history of herpes indicates previous infection and a degree of immunity, assuming that the infected partner has type 2 infection. This obviously reduces the anxiety associated with the possibility of herpes transmission during sexual intercourse. However, the converse must also be considered; a negative result may increase anxiety owing to concerns regarding the possibility of infecting the negative partner. Discussion with both partners is required and time given to consider the consequences.
Pregnant women with no history of genital herpes but with an infected partner may wish to avoid intercourse during the pregnancy if she proves HSV antibody negative (see section on "Pregnancy").
17.4.1 Primary Genital Herpes
Women tend to fare rather worse than men. The genital sores are often exquisitely tender, urination may be intolerable, and patients usually feel generally very unwell with myalgia, headaches, fever, etc. The following are the recommended:
- Take a swab for herpes virus culture or PCR.
- Advise taking aspirin or paracetamol (or stronger preparation) as required.
- Bathe the genital area twice daily with warm salty water and dry with the hair dryer on cool setting.
- Some women find it easier to pass urine while sitting in a warm bath.
- Prescribe aciclovir tablets 200 mg five times a day for 5 days, famciclovir 250 mg tds for 5 days, or valaciclovir 500 mg bd for 5 days.
- There is no place for topical aciclovir cream in treating primary herpes.
urinary retention secondary to sacral radiculopathy is uncommon and affects women and homosexual men more commonly than heterosexual men.
Approximately 10% of women suffer coincidental vaginal candidiasis. If there is generalized vulval erythema in addition to areas of ulceration or if symptoms persist after the ulcers have healed, consider treating for Candida with an oral agent such as fluconazole 150 mg stat dose or itraconazole 200 mg bd for 1 day. Most women are rather too sore to use pessaries or cream.
The diagnosis of herpes can be psychologically traumatic and a great deal of time is often required to provide adequate information about the disease. Some patients require further more intensive "counseling" to help them come to terms with the condition. Key issues which need to be addressed include the possibility of asymptomatic viral shedding, the effect this may have on current or future sexual relationships, and the use of condoms to provide some protection to sexual partners. The issue of herpes in pregnancy is discussed below.
17.4.2 Recurrent Herpes
Most patients cope extremely well with herpes. Attacks are usually infrequent and last only a few days and can be managed quite adequately by bathing the affected area with salty water and avoiding sexual contact while lesions are present.
A small number of patients suffer rather more painful and prolonged attacks and may benefit from a course of famciclovir (125 mg bd for 5 days), aciclovir tablets (200 mg five times a day for 3-5 days), valaciclovir 500 mg bd for 5 days or aciclovir cream (which must be used five times a day) taken or applied immediately when lesions appear. There has been some debate regarding the treatment of recurrent herpes with intermittent short courses of antiviral agents and concern raised about the possibility of generating resistant viral strains; however, this would appear to be more of an issue with immunosuppressed patients on longterm suppressive treatment. it is worth emphasizing that most patients with recurrent herpes do not require therapy.
For the small minority of patients who are plagued by very frequent and prolonged recurrences, it may be worth considering prophylactic therapy. This entails taking tablets on a daily basis for up to 1 year initially after which time the medication is stopped and the frequency of recurrences re-assessed. Current regimens include acyclovir 400 mg bd (a frequently used treatment), aciclovir 200 mg four times a day, famciclovir 250 mg bd, and valaciclovir 500 mg daily. Patients are usually reviewed at 3-monthly intervals. Viral shedding can occur whilst on suppressive treatment even in the absence of clinically obvious recurrences, a point worth mentioning to patients.
Neonatal herpes carries a significant mortality and morbidity but is fortunately a rare condition in the UK. The baby is at greatest risk if the mother develops primary herpes during the last trimester, particularly toward the time of labor. interestingly, recent studies have shown that most babies with neonatal herpes acquire their infection from mothers with asymptomatic primary herpes who are shedding virus during the birth.
There is minimal risk to the baby in women with recurrent disease. This is probably related to protective antibody passing across the placenta and to a much lower rate of viral shedding from the cervix in recurrent disease compared with primary infection. This is important to mention after diagnosing herpes as issues regarding future pregnancies are high on the list of worries. Women with a past history of genital herpes should be advised to present early in labor and undergo a careful examination for evidence of genital lesions. Although there is minimal risk to the baby, in view of the severity of neonatal herpes, most obstetricians would advise cesarean section rather than vaginal delivery if lesions are present. Daily aciclovir can be used in the last 4 weeks of pregnancy to reduce the risk of clinical recurrence and the need for cesarean section. Although aciclovir is not licensed for use in pregnancy, there is substantial evidence to support its safety.
The diagnosis and management of genital herpes can sometimes pose problems. Referral to GU medicine should therefore be considered even if it is just for discussion or to provide information.
17.5 OTHER CAUSES OF GENITAL ULCERATION
Vulval candidiasis may occasionally be mistaken for genital herpes particularly when there is severe vulval soreness with disruption of the vulva epithelium. Conversely, recurrent herpes may produce only minor vulval discomfort and be dismissed by the patient as simply an attack of "thrush." For this reason it is important to explain to patients with a history of herpes that minor genital symptoms may be a recurrence of their herpes and that necessary care should be taken during sexual intercourse.
Syphilis is now making a reappearance in the UK and should be considered in all patients presenting with genital ulceration. The primary chancre of primary syphilis is usually painless, although secondary infection may produce some tenderness (Figure 17.5). Patients should be referred to GU medicine if there is the slightest doubt regarding the clinical diagnosis of genital ulceration. Dark-ground microscopy for treponemes can be performed on site and optimal specimens will be obtained for herpes culture. Remember that syphilis serology may be negative in primary syphilis, although T. pallidum IgM antibody should be requested if a chancre is considered a possible diagnosis. IgM should become detectable toward the second week of infection with IgG becoming positive at about 4 weeks. However, it is still prudent to advise patients with genital ulceration of unknown cause to have repeat syphilis serology performed at 3 months after presentation.
The chancre of primary syphilis may pass unnoticed and the patient presents with the generalized rash of secondary syphilis often associated with lymphadenopathy and fever. Syphilis should be considered in the differential diagnosis of patients presenting with a glandular fever like illness and while your history taking moves toward sexual contacts please also consider HIV seroconversion illness.
Figure 17.5. Chancre of primary syphilis affecting the penis
17.5.3 Fixed Drug Eruption
More severe cases may lead to ulceration (see Chapter 16, page 93).
17.5.4 Chancroid and Lymphogranuloma Venereum
These are common tropical STIs but rare in the UK, although cases of LGV proctitis amongst men who have sex with men have recently been reported in Western Europe, including the UK. Remember to ask about sexual contact with partners from abroad.
17.5.5 Aphthous Ulceration and Behçet’s Disease
The genital ulcers in Behçet's disease are very tender and usually have a well-demarcated edge (Figure. 17.6). To make a diagnosis of Behçet's disease there should also be a history of oral ulceration together with eye, skin, or neurological complications.
In women, one more commonly sees simple aphthous ulceration affecting the mouth and labia, there being no other features to suggest Behçet's disease.
Traumatic lesions are usually the result of forced sexual intercourse or rather too vigorous oral sex. The lesions often appear as abrasions rather than true ulcers; however, a swab for herpes simplex virus culture should be performed as herpes may present in this fashion with the patient often under the misguided impression that the lesion was related to physical skin damage.
Figure 17.6. Genital ulcer of Behçet's syndrome (similar appearance with aphthous ulceration)
17.5.7 Ulcers of Lipschutz
In 1913, Lipschutz described cases of acute vulval ulceration associated with fever and lymphadenopathy. More recently, genital ulceration has been described as an uncommon complication of infectious mononucleosis and it is therefore possible that Lipschutz's original cases related to Epstein-Barr virus infection.
17.5.8 Bullous Skin Conditions
Pemphigus and cicatricial pemphigoid very occasionally present on the genitalia. The bullae may be short-lived leaving areas of eroded epithelium.
Any case of genital ulceration for which a definitive diagnosis cannot be made should ideally be referred to GU medicine for assessment and further investigation.