Sexually Transmissible Infections in Clinical Practice

16. A Young Woman with Genital Ulceration

Alexander McMillan1, 2  

(1)

Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk

(2)

University of Edinburgh, Edinburgh, Uk

Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer

Email: a.amcmm@btinternet.com

Abstract

Carol, a 23-year-old woman, attends you, her General Practitioner, with a 3 day history of pain and swelling of the vulva, slightly increased vaginal discharge, and pain on passing urine. When she examined herself using a mirror she noticed that there were many “cuts” all over the genital area. She has difficulty walking on account of the pain. Carol has been generally unwell for a few days and has felt feverish. She has not noticed a skin rash. Previously her general health has been good with no serious illnesses. She is not receiving any medication, and she has not applied ointments or lotions to her genitals. Her most recent menstrual period was 7 days previously and was normal. She has no previous history of genital ulceration. She has been in a regular relationship with Mark for 2 years, and she has had no other sexual contacts in that time. Mark, a 35-year-old man, attends with Carol. He has no symptoms and has no past history of sexually transmitted infections. Both he and Carol had had a sexual health screen shortly after they began their relationship. Neither was identified as having a sexually transmitted infection, although serological testing for previous exposure to herpes simplex virus was not undertaken (seeCase 1 ). He tells you that his only sexual partner within the preceding 2 years has been Carol, but previously he has had several heterosexual relationships. They had vaginal and oral sex about 1 week previously. Condoms are used as contraception, but they have used the same brand for several months; they do not use lubricant.

Carol, a 23-year-old woman, attends you, her General Practitioner, with a 3 day history of pain and swelling of the vulva, slightly increased vaginal discharge, and pain on passing urine. When she examined herself using a mirror she noticed that there were many “cuts” all over the genital area. She has difficulty walking on account of the pain. Carol has been generally unwell for a few days and has felt feverish. She has not noticed a skin rash. Previously her general health has been good with no serious illnesses. She is not receiving any medication, and she has not applied ointments or lotions to her genitals. Her most recent menstrual period was 7 days previously and was normal. She has no previous history of genital ulceration. She has been in a regular relationship with Mark for 2 years, and she has had no other sexual contacts in that time. Mark, a 35-year-old man, attends with Carol. He has no symptoms and has no past history of sexually transmitted infections. Both he and Carol had had a sexual health screen shortly after they began their relationship. Neither was identified as having a sexually transmitted infection, although serological testing for previous exposure to herpes simplex virus was not undertaken (seeCase 1 ). He tells you that his only sexual partner within the preceding 2 years has been Carol, but previously he has had several heterosexual relationships. They had vaginal and oral sex about 1 week previously. Condoms are used as contraception, but they have used the same brand for several months; they do not use lubricant.

16.1 What Is the Most Likely Diagnosis?

The most likely diagnosis is primary genital herpes (see Table 16.1 for a classification of herpes simplex virus infection) – there is genital ulceration and systemic features (infrequent in non-primary or recurrent episodes).

Table 16.1.

Classification of herpes simplex virus infection.

1. Primary infection. This is an infection which may be asymptomatic, remain localized, or become generalized in an individual who has not been previously infected with either type of HSV as shown by a lack of antibodies to any herpes simplex virus

2. Initial infection. This denotes the first infection by one HSV type. It may be a primary infection in those without serological evidence of a previous herpetic infection (seronegative by a sensitive assay) or a non-primary in those with evidence of previous infection (seropositive). Clinically primary and non-primary initial infections may be indistinguishable on physical examination

3. Latency. There is apparent recovery but some virus remains dormant in nervous tissue, particularly in certain sensory ganglion cells; this is latency (latent means hidden)

4. Recurrence. The reactivated virus may on occasion initiate a peripheral lesion in the dermatome relating to the sensory ganglion. The lesion is referred to as a recurrent lesion and the phenomenon is recurrence

 

Carol appears distressed and has difficulty sitting. The temperature is 37.6°C. The oral cavity and the pharynx appear normal. Multiple vesicles and ulcerated areas are found at the introitus, on the inner aspects of the labia minora, and on the labia majora (Fig16.1 ). The inguinal lymph nodes are enlarged and tender.

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Figure 16.1.

Vesicles and ulcers on vulva.

16.2 Do These Findings Confirm the Diagnosis of Primary Genital Herpes?

The clinical findings are consistent with a diagnosis of primary genital herpes. Table 16.2 shows other causes of anogenital ulceration. As the psychological impact of genital herpes is often considerable, however, it is good practice to confirm the diagnosis by laboratory testing. This is done by obtaining fluid from a vesicle or material from the base of an ulcer using a cotton wool-tipped applicator stick and sending it in viral transport medium to the laboratory for the detection of specific HSV DNA using a nucleic acid amplification assay. The use of type-specific primers allows identification of the infecting HSV type. Alternatively, if a NAAT is unavailable, the specimen can be cultured in tissue culture; this, however, is a less sensitive diagnostic test.

Table 16.2.

Causes of anogenital ulceration.

Infective causes

Dermatological conditions

Systemic diseases

Varicella zoster virus infection

Treponema pallidum

Chlamydia trachomatis a

Haemophilus ducreyi

Klebsiella granulomatis

Pyogenic ulceration

Trichomonas vaginalis

Candida spp.

Sarcoptes scabiei

Mycobacterium tuberculosis b

Entamoeba histolytica b

Trauma

Chemical burns

Lichen sclerosus et atrophicus

Lichen simplex

Erosive lichen planus

Pemphigus vulgaris

Pemphigoid

Fixed drug eruption

Other drug reactions (e.g., to Foscarnet)

Squamous intraepithelial lesions of the vulva or penis

Squamous cell carcinoma

Erythema multiforme

Pyoderma gangrenosum

Behcet’s syndrome

Crohn’s disease

aLymphogranuloma venereum genotypes.

bRare

In the case of herpes zoster, the lesions are confined to the dermatome, and not, as in Carol’s case, widely distributed. Vulvovaginal candidiasis can produce vulval swelling and discomfort, but pruritus is more likely than the severe pain reported in this case. The ulceration of primary syphilis is usually solitary and painless, but that of secondary syphilis may be multiple, although the lesions may cause some discomfort they are unlikely to produce severe pain. Chancroid (caused by Haemophilus ducreyi) is associated with multiple painful ulcers, but in Western Europe, it is usually diagnosed in individuals returning from geographical areas where the condition is prevalent, such as sub-Saharan Africa. The ulcer of lymphogranuloma venereum is usually solitary and symptomless, but multiple painful lesions may occur. As in the case of chancroid, most infections are recognized in individuals returning from tropical regions. The slow-growing, granulomatous ulceration of donovanosis, caused by Klebsiella granulomatis, is an unlikely diagnosis, most cases being identified in individuals from a few developing countries such as Papua New Guinea. Trichomoniasis can produce superficial vulval ulceration, but this is an unlikely cause of the painful lesions reported here. Scabies is associated with papular, often excoriated lesions on the genitalia; itch is the predominant symptom, and lesions would be found elsewhere on the body. Trauma or chemical burns can be discounted as causes of the genital ulceration in this case, and the lack of a history of drug ingestion rules out drug reactions. Lichen sclerosus et atrophicus can be associated with small eroded areas that may be sore. As Carol has an acute onset illness with systemic features, this is an unlikely diagnosis. Lichen simplex results from rubbing in response to itch and is often associated with fissuring. Carol’s history is not compatible with this diagnosis. Lichen planus may also be associated with erosions at the introitus and inner aspects of the labia minora, but, again an acute onset with fever would be unusual. Pemphigus vulgaris can affect the vagina and vulva, and although associated with bullae, the blisters are easily ruptured producing erosions that are often painful. The history is not that of malignant disease, and the absence of associated features makes systemic diseases unlikely as a cause of Carol’s genital ulceration.

16.3 What Is Your Immediate Management of Your Patient?

Antiviral drugs should not be withheld pending the results of the laboratory tests. The use of such agents within 5 days of the development of the clinical features of the infection has been shown to reduce the duration of the acute episode. The duration of new lesion formation, and the healing time are also shortened. Delay in initiating antiviral therapy beyond 5 days confers no benefit over placebo. Table 16.3shows the antiviral drugs currently used in the management of primary or initial episode genital herpes.

Table 16.3.

Drugs used for the treatment of primary or initial episode genital herpes.

Aciclovir 200 mg five times daily by mouth for 5 days

OR

Aciclovir 400 mg three times daily by mouth for 7–10 days

OR

Valaciclovir 500 mg twice daily by mouth for 5 days

OR

Famciclovir 250 mg three times daily by mouth for 5 days

 

Analgesia should be provided, and she should be advised to have frequent baths. When there is extensive ulceration of the inner aspects of the labia minora, the woman should be instructed to separate these during bathing to prevent the subsequent formation of fibrous adhesions.

When primary genital herpes arises during the course of a relationship, individuals consider that their partner has been unfaithful. It is therefore helpful at this stage to discuss a little of the nature of herpes simplex virus infection and to provide written information. In particular, it is important to point out that the majority of individuals (about 80%) infected with HSV, either type 1 (HSV-1) or type 2 (HSV-2), acquire the infection and never show features characteristic of either genital or orolabial herpes. Intermittent re-activation of virus in either the trigeminal or the sacral ganglia can result in centrifugal axonal transport1of infectious virions to skin or mucous membranes with the possibility of transmission to a partner. Exposure of a susceptible individual at this time through vaginal or anal intercourse, or oral–genital sex, can result in infection of that person with or without clinical features. As most episodes (about 90%) of sub-clinical shedding of virus last for only 2 days, it is quite by chance whether or not sexual contact occurs at the time of viral excretion. Mark has had previous sexual partners and it is possible that he acquired HSV through contact with one of these women. Alternatively, he could have acquired oral–labial HSV-1 when he was a child and transmitted reactivated virus during oral–genital sex.

As individuals are often distressed at the first consultation, they are often not receptive to much information. For this reason it is useful to invite both Carol and Mark to re-attend about 1 week later for further counseling.

When you see Carol and Mark you have the results of the virological tests. Herpes simplex virus type 2 DNA has been detected in the material taken from the genital vesicles/ulcer. Her symptoms have improved markedly, but after accessing some internet sites, some of which she found alarming, she has a number of questions.

·               a) Is there a cure for genital herpes?

No. Although the current antiviral drugs are useful in the treatment of primary or initial genital herpes, they do not prevent the development of latency in the dorsal root ganglia.

·               b) What are the chances of the herpes recurring?

After the primary or initial infection there may be no further clinical manifestations throughout life. In the year following symptomatic primary genital herpes associated with HSV-2, however, symptomaticrecurrence is common. It has been shown that up to 90% of individuals have recurrences, with a recurrence rate of about four to five episodes per year. (Significantly fewer recurrences are found in those who have had symptomatic primary HSV-1 genital infection: about one episode per year). In people who have had a prolonged initial illness (>35 days), the interval between primary infection and recurrence tends to be shorter and the recurrence rate to be twice as frequent as those with a less prolonged episode. Men tend to have more recurrences than women. In those patients who have had either HSV-1 or HSV-2 primary infections, the recurrence rates in the second year after the initial infection are significantly less than during the first year, although there is much variation in recurrence rates between individuals during that year. In many patients there is a reduction in recurrence rate in subsequent years, suggesting that the pool of reactivatable virus in the ganglia diminishes with time; the rate of decrease in recurrences, however, tends to become smaller with the passage of time. It should be noted, however, that about one-quarter of individuals have at least one more recurrence in year 5 than in year 1.

In recurrent genital herpes recurrences may be heralded by a prodromal sensation of tingling, occurring 30 min to 48 h before the appearance of lesions. In some patients, stabbing pains in the distribution of the sciatic nerve that last for several days may herald the recurrence. Several small vesicular lesions then appear and may coalesce. Lesions tend to increase in size over the first 3 days of the episode, remain static for about a week and resolve rapidly thereafter. The symptoms are substantially milder than those of the initial episode and constitutional symptoms are infrequent. Symptoms, however, tend to be more severe in women than in men.

The rate of symptomless shedding of HSV after recovery from an initial episode of genital herpes depends on the type of HSV. About 10% of women who have had primary HSV-1 infection and about 20% who have had primary or non-primary HSV-2 infection have symptomless excretion of virus at some time during the first year after the initial episode. Virus is more commonly excreted during the first 3 months than during subsequent months. About one-third of episodes of symptomless virus shedding occur in the 7 days preceding a symptomatic recurrence, and about one-fifth in the 7 days after such a recurrence. As has been noted with symptomatic recurrence (see above), sub-clinical shedding of virus is more likely to occur within 12 months of the initial episode of genital herpes than in subsequent years. Women who have frequent symptomatic recurrences (>12 per year) are also more likely to have sub-clinical shedding of HSV. There is no doubt that symptomless viral shedding is an important source of infection to sexual partners.

·               c) Am I at increased risk of cervical cancer?

No. Some years ago it was thought that HSV was associated with cervical caner. This has now been shown to be untrue.

For a discussion on the management of genital herpes in pregnancy, see Case 29 .

Footnotes

1

Axonal transport. The whole phenomenon requires translation of the virus from the periphery to the sensory ganglion and back again by way of, it is believed, the cytoplasm within the axon. The rate of translocation from the skin to the ganglion lies within the range of 2–10 mm per hour.