Herpes simplex and other anogenital ulcers

• Herpes simplex infection is by far the commonest cause of genital ulceration presenting to clinics in the UK.
• Painful, multiple ulcers are highly likely to be HSV but syphilis can present with multiple painful ulcers.
• Ulcers caused by multiple infections (eg syphilis, HSV and chancroid) are occasionally seen.
• Always perform syphilis serology in patients presenting with genital ulcers
• Always request a syphilis PCR (same sample as HSV PCR) in MSM and any patient with an atypical ulcer
• Always ask for a senior opinion if ulcers are atypical
• See ‘Other causes of anogenital ulceration’ for more detail.

Genital herpes is caused by infection with the herpes simplex viruses (HSV) of which there are two types (HSV-1 and HSV-2). Patients may present with an initial episode (which may be a primary infection) or with recurrent episodes.

Definitions

Initial episode: First episode with either HSV-1 or HSV-2. Dependent on whether the individual has had prior exposure to the other type, this is further subdivided into:

• Primary infection: first infection with either HSV-1 or HSV-2 in an individual with no pre-existing antibodies to either type.
• Non-primary infection: first infection with either HSV-1 or HSV-2 in an individual with pre-existing antibodies to the other type.

Recurrent episode: recurrence of clinical symptoms due to reactivation of pre-existent HSV-1 or HSV-2 infection after a period of latency.

First episode genital herpes: Clinical presentation

• Only about 1/3 of individuals develop symptoms around the time of infection acquisition. In these individuals, symptoms usually develop within 2-weeks of sexual contact.
• Prior infection with one type of HSV usually makes symptoms less severe during first infection with the other type of HSV.
• Commonest presentation is blisters or painful ulceration of external genitalia, sometimes affecting the cervix and/or rectum (HSV causes anal lesions and occasionally proctitis is MSM)
• Erosions or fissures may be present in the absence of true ulcers or blisters
• Systemic flu-like symptoms (e.g. malaise, fever and myalgia) more common with first episodes of primary infection, than non-primary
• Inguinal or femoral tender lymph node enlargement (commonly bilateral in first episode genital HSV but unilateral in recurrences)
• Severe dysuria, particularly in women
• Vaginal or urethral discharge (less common) – due to presence of vaginal and urethral ulceration and inflammation.

Complications

• Bacterial superinfection of skin lesions
• Labial adhesions, phimosis, paraphimosis
• Urinary retention (result of severe pain or autonomic neuropathy)
• Autoinoculation to fingers and other skin (e.g. thighs, whitlow, keratitis)
• Neurological complications - aseptic meningitis, encephalitis, etc
• Eczema herpeticum
• Disseminated HSV disease (in immunosuppression, pregnancy, etc)
• Increases both HIV transmission and acquisition risks (in untreated HIV infection)
• Vertical transmission

A clinical diagnosis is sufficient for the initiation of treatment and counselling. If in doubt, ask the GUM senior clinician for a second opinion. The presence of multiple lesions at evolving stages (e.g. erythema, blister, ulcer and crusting/ resolution stage of development) is strong supportive evidence for an HSV diagnosis. Always take samples for microbiological confirmation and include syphilis PCR in MSM and any atypical ulcer in viral transport medium. Sample several sites if possible. Syphilis serology should always be performed in patients presenting with genital ulceration.

From the NaSH test order set STI test: Ulcers select HSV 1/2 PCR and the appropriate site. If MSM or atypical ulcers select HSV/Syph PCR and request syphilis PCR in addition. Ensure that the sample site is written on the virology serology request form. If requesting syphilis PCR you should request ‘early suspected’ syphilis blood serology.

Investigations

• HSV (and, if appropriate syphilis) PCR from the ulcer, as noted above
• NAAT tests (lower vaginal swab in women, urine in men) at first visit if tolerated – can be deferred if the patient is in pain or distressed.
• Blood for syphilis and HIV serology in all cases: if a patient with genital ulceration declines blood for syphilis serology this should be documented.
• MC+S if suspicion of pyogenic ulceration or bacterial superinfection
• Prescribe specific antiviral therapy if lesions have been present for more than five days, new lesions are appearing or systemic symptoms are persisting.

• In very severe cases, consider giving 10 days of therapy, or review at 5 days and continue therapy for a further 5 days, if lesions have not resolved.
• Saline bathing to discourage the formation of labial adhesions.
• Instillagel or lidocaine ointment for local anaesthesia if lesions are causing significant pain, tenderness and dysuria.
• Prescribe or advise oral analgesia
• Advise to take time off work if systemically unwell
• Admit to hospital if there is signs of urinary retention, intractable pain, meningitis or a female patient in the second or third trimester of pregnancy.

Pregnancy

Refer to protocol for management of STIs in pregnant women and discuss case with senior.

• Acknowledge this can be distressing but with time it will get better.
• Use patient information leaflet to support counselling process and guide patients towards online advisory group (herpes.org.uk).
• The first episode is usually the most severe.
• Stress that although infection is life-long, symptomatic recurrences are usually mild and only require treatment if they are frequent or severe.
• Infection is common: 50% of people have HSV-1 and 10-15% have HSV-2 by the age of 30 years.
• The risk of recurrence with HSV-1 infection is significantly less than that with HSV-2 (HSV-1 – 40-50% chance of recurrence; HSV 2 - 89% chance of recurrence in the first year after a symptomatic primary infection).
• Recurrences tend to reduce in frequency over time (most people with HSV 1 get one or two recurrences in the first year, then less often: Draw parallels with cold sores in childhood. Patients with symptomatic HSV2 infection will get around 4 recurrences per year, on average, early on after infection).
• Asymptomatic carriage of the virus is common. No indication of infidelity in long term partner.
• No effect on fertility. Not a problem in pregnancy unless the primary infection occurs during late pregnancy. See pregnancy section of the protocol.
• Herpes infection can both increase HIV transmission and acquisition risks.
• Transmission rates are lower from female to male, compared to vice versa. E.g. The transmission rate for HSV-2 overall is 10% per year.
  Transmission from a male to a female partner is up to 17%, and female to male is 3%.
• Subclinical shedding plays a major role in the transmission of infection. It is usually commonest in the first year after acquisition and in patients with frequent symptomatic episodes. Subclinical virus shedding tends to reduce in frequency over time.
• 50% of supposedly asymptomatic HSV-2 seropositive women can be taught to recognise genital herpes recurrences after counselling. Thus, there is at least the potential for prevention of transmission by educating patients to recognise symptomatic recurrences.
• Patients should be advised to refrain from sexual intercourse during symptomatic episodes or their prodrome, as viral shedding is highest during these periods.
• Consistent and correct use of condoms, even when asymptomatic, can reduce transmission of virus though not prevent it.
• There was a successful prosecution in England in 2014 for the transmission of HSV. Clients should be advised that they should inform all partners of their HSV status. Discussions with patients around transmission and disclosure should be documented.

 Follow up

Not always required.
In the case of a severe primary episode, review at 5 days to confirm that no new lesions appearing. If new lesions are appearing or severe constitutional symptoms persist, give a further five days course of acyclovir. Otherwise consider review at 2 weeks when virological results are available. Patients should be offered NAAT tests at review, if deferred at first visit.

Clinical Presentation

Recurrences are usually mild and self-limiting. Symptoms include:

• Recurrent ulceration, erosions or fissures.
• Occasionally other recurrent symptoms suggestive of HSV – recurrent
  urethritis, unexplained culture negative dysuria, leg or buttock pain.

If the patient gives a history suggestive of previous attacks but there is no previous virological evidence, attempt viral detection with PCR if vesicles or ulcers are present. If the patient has recurrent symptoms suggestive of genital herpes, but the diagnosis has not been confirmed by the detection of viral DNA in lesions, AND no lesions are present at review the patient should reattend for an Urgent Care appointment when lesions recur or can take away a viral swab, that they can use to self sample at the start of the next episode. Alternatively, the use of type specific HSV serology can be considered (only after discussion with GUM consultant).

If recurrences are very frequent, or increase in frequency after a period of infrequent episodes, consider triggers and underlying causes. Any irritant to the skin (candida, contact dermatitis, other dermatoses) can trigger more frequent episodes, as can exposure to UV light. Other causes of immunosuppression including HIV infection and steroid treatment should also be considered.

Treatment

Strategies include:

• Supportive therapy
• Patient initiated episodic antiviral therapy
• Suppressive antiviral therapy

Management will depend on the severity of symptoms, frequency of recurrences and the relationship status of the individual. The majority of patients with recurrent herpes will require only supportive measures.
Episodic and suppressive therapy is rarely required in patients with genital HSV 1 but episodic therapy may be considered in HSV 2.

Patient initiated episodic antiviral therapy

Treatment with aciclovir, if initiated within 6-12 hours of symptoms starting, may abort 20-30% episodes with lesions (i.e. episodes do not progress to ulceration) and will reduce the duration of an episode by a median of 1-2 days. Despite the relatively marginal clinical benefit of PIT, it may be preferable to some patients to the idea of suppressive therapy.

Suppressive therapy

Patients with virologically confirmed genital herpes and a recurrence rate of more than six episodes of genital herpes in the last 12 months, or where recurrences are less frequent but are severe or have significant psychological impact, can be offered suppressive therapy. Suppressive therapy can also reduce virus transmission to negative partners, though not absolutely prevent it. Transmission reduction has only been demonstrated in clinical trials for HSV2 infection and Valaclovir suppressive therapy.

Suppressive herpes therapy has not been demonstrated to affect HIV transmission or acquisition risks in HSV seropositive individuals.

Give a 3 month supply, writing to the GP using the standard letters on NaSH).
Alternatively, the patient can be reviewed after 3 months to confirm that suppressive therapy has worked before writing to the GP.

At 12 months the patient can either:

• Discontinue therapy without further review and assess frequency of recurrence (warn that there may be a ‘rebound’ episode on discontinuing treatment, therefore the minimum period of assessment should include two recurrences).
• Re-attend for review and discuss whether to continue or discontinue therapy, taking into account prior frequency and severity of episodes, virus type, relationship status, psychological impact etc.

Dosage reductions are clinically inappropriate, but it is acceptable for patients to switch between using medication for episodic therapy and periods of suppression (eg during holidays, or when with a new sexual partner).

Although herpes simplex virus is the commonest cause, always consider the multiple other causes of genital ulceration:

In the clinical history, consider:

• Duration of the ulceration
• Detailed sexual history with dates (Remember that the prepatent period of syphilis can vary between 10 and 90 days.)
• Travel history
• Are the lesions painful and tender? The sores of herpes and chancroid are usually painful and tender.
• Are there any associated features? For example, painful and tender inguinal lymph node enlargement may be found in primary genital herpes
• Is there a past history of genital ulceration? Recurrent ulceration is a feature of genital herpes, particularly with herpes simplex virus type 2 infection.
• Is there a history of travel to geographical areas where conditions such as chancroid, lymphogranuloma inguinale and donovanosis are more prevalent than in Western Europe? Ulcers may be due to more than one infection (e.g. chancroid and HSV).
• Is there a history of dermatological conditions?
• Is there a history, such as a generalised skin rash, joint symptoms, bowel symptoms or oral ulceration, suggestive of systemic disease?
• Is there a recent history of application of topical agents, such as disinfectants, to the affected area?
• Is there a history of trauma?
• Has the patient used any drugs, whether prescribed or otherwise, in the weeks before the appearance of the ulceration? In the case of fixed drug eruption, there may be a previous history of genital bulla formation or ulceration following the use of that particular drug.
• Review genital washing history.

On physical examination:

• Are the lesions single or multiple? Genital herpes and chancroid usually cause multiple lesions, but primary syphilis (chancre) is often a single ulcer.
• Are the lesions tender, as in genital herpes and chancroid? Or are they less painful than they appear – suggesting syphilis.
• Is the lesion indurated, as is the case in typical primary syphilis? (Often not the case in extragenital chancres, such as in the anal canal).
• Does the lesion bleed easily? Chancroid is associated with multiple ulcers that bleed easily, whereas the primary lesion of syphilis and genital HSV tends not to bleed.
• Are there local associated features, such as uni- or bilateral inguinal lymph node enlargement or bubo formation? Lymphogranuloma venereum and chancroid are associated with tender and, usually, unilateral inguinal lymph gland enlargement and abscess formation.

• HSV /SyphilisPCR and full sexual health screen.
• Request syphilis serology (lab form– tick ‘supsect early syphilis’)
• Consider bacteriological culture of ulcer if suspicious of pyogenic ulceration of secondary bacterial superinfection of ulcer.

Further investigations

• Discuss with GUM consultant
• Discuss with the laboratory before taking/sending any of the samples below.

Herpes – counselling points

• There are 2 types of herpes virus – herpes 1 and 2. Type 1 is now the commonest type we see associated with symptomatic genital herpes. It is the type traditionally associated with cold sores. About 50-70% population carry at least one herpes virus in their system/body so it is normal to have antibodies to herpes. Most of these people have the virus in their mouth (cold sore virus – HSV 1).
• Of those 50-70%, only about half (ie 1/3 population) can ever recollect any symptoms suggestive of herpes, so don’t know that they are carriers.
• Most of the time the virus is asleep but occasionally wakes up for a few hours, sometimes longer – if sex happens at that time, then a partner can get infected.
• When the virus wakes up it may produce symptoms but often it doesn’t, so a person, even if they know they are a carrier, doesn’t necessarily know when they are infectious and when they are not.

Putting all of above together,

It is common for a person to get a first attack of herpes within a long term stable relationship and does not imply that the partner has been unfaithful. Also as the majority of people carry herpes in their mouth, oral sex is a common way of getting genital herpes. As the partner may not have any symptoms they may not therefore be aware that they have HSV that they can pass on.

Then about the episode:

The first attack is generally the worst. There is usually a systemic immune response during this time to the HSV infection so a person can feel a bit ‘fluey’ as well as sore from the herpes ulcers. Therefore it’s normal to feel pretty crap for a few days, so take plenty of rest, paracetamol or neurofen (and if relevant) let mum/partner run around after you a bit.

There is no cure for the virus – it is something that remains in the system for life, but most of the time it is asleep and not causing any problems. The tablets given for a first attack put the virus to sleep within about 48 hours and so in 48 hours, people normally start to feel a bit better. The tablets do not heal up the sores that have already developed, but they stop the virus making new sores and therefore allow the body to start the healing process. Most people have healed up within 7-10 days.

During that time, take regular baths so that the sores don’t get infected. If it’s very sore to pee, do it in the bath. (think about Lignocaine gel to help) Avoid soap/bath gel etc – just plain tepid water for washing – caution re labial adhesions.

Future recurrences

Type 2 virus tends to recur more often than type 1 but everybody’s response to the virus is unpredictable and the majority of people don’t have any further problems. Only time will tell. The first year is the worst so don't worry if you seem to have a few episodes in the first year - the frequency will reduce over time.

If a recurrence occurs, the virus is usually only awake for a much shorter period of time and is very localized and so the symptoms are much milder and clear up much more quickly. Hence there is no need for further tablets as generally the virus has already gone back to sleep by the time someone realizes what is happening and gets the tablets, so they have little added benefit. It is essentially like having a cold sore on the genitals and usually people do not find it too uncomfortable. If you do decide to take treatment for symptomatic episodes, then treatment needs started preferably within 6-12 hours to see any benefit.

Occasionally some people have troublesome attacks in which case they should come back to the clinic to discuss treatment options. But to start with they should just wait and see what happens. For occasional individuals, depending on severity, psychological distress etc, consider giving episodic treatment to keep at home for future recurrences.

Also, not every tingling/itching/discomfort is the start of an attack although it is very easy once someone knows they have herpes to attribute everything to that – but everyone gets intermittent tingling/itching etc and so again they should be encouraged to wait and see rather than immediately seeking medical advice.

Pregnancy (if relevant)

Brief reassurance that now they have the virus, pregnancy should be fine as any developing baby will have mum’s antibodies to protect it but if there was a recurrence with ulcers at the time of delivery, some obstetricians may decide to opt for a section as extra safety precaution. Women with herpes should be encouraged to inform their midwife about a previous diagnosis soon after becoming pregnant.

Males should be advised to inform their partners, especially if considering pregnancy, as precautions may be required to prevent their partner picking up infection during pregnancy.

Partners:

Current partner is likely to already be infected (may have been the source of infection) if they have been together a while, in which case they are a carrier and therefore there is no problem.

Potential to pass to future partners is low but unpredictable which is the problem about herpes – condoms will give some protection but not 100% as they only cover the bits that they cover and the virus can be in the surrounding areas of skin.

Not having sex during symptomatic episodes and using condoms consistently can help reduce passing on the virus to casual partners. Remember also however, that good chance that future partners may already carry the virus silently.

We recommend that patients inform current and future partners regarding their diagnosis.

The order of above will change according to patient/questions asked, etc, but I think is probably the general gist of what I try to get across, in the terminology I usually use.