Genital herpes



Introduction
Epidemiology
Aetiology
Pathophysiology
Clinical features
Investigations
Differential diagnosis
Management
Complications
Prognosis


Introduction

Genital herpes is a common viral infection caused by type 1 and 2 herpes simplex virus (HSV). HSV infection is lifelong and remains latent in sensory neurones after the initial infection, with the possibility of reactivation later. It is a sexually transmitted infection; transmission can occur even in the absence of symptoms, due to asymptomatic shedding of the virus by the host. The virus replicates inside epithelial cells at mucosal surfaces resulting in vesicles or ulceration of the genitals. Antiviral therapy has a limited role in management: it helps to reduce the severity and duration of symptoms and the risk of complications, but does not cure the patient.

Epidemiology

  • Incidence: 300.00 cases per 100,000 person-years
  • Peak incidence: 20-30 years
  • Sex ratio: 1:1
Condition Relative
incidence
Genital herpes1
Syphilis0.03
Behcet's syndrome0.003
Chancroid0.0002
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Genital herpes is caused by type 1 and 2 herpes simplex virus (HSV). These are both large, double-stranded DNA viruses. Both cause lifelong, incurable infections.
  • HSV-2:
    • HSV-2 is thought of as the 'classic' aetiology of genital herpes, however, HSV-1 is now increasingly recognised as a causative agent.
    • Around 15% of the population carry HSV-2.
    • Transmitted almost exclusively through genital-to-genital contact during sex.
    • Causes recurrence of anogenital symptoms more frequently and more severely than HSV-1.
  • HSV-1:
    • Main route of transmission is via oral-to-oral contact (causing oral herpes), but can also be via oral-genital contact (causing genital herpes).
    • Becoming increasingly more common in causing genital herpes due to increased rates of oral sex among younger generations.
    • Genital herpes due to HSV-1 usually has milder symptoms and a lower frequency of recurrence.
    • Around 65% of the population carry HSV-1, although this is mostly orally.

Pathophysiology

Acquisition of the virus
  • Type 1 and 2 herpes simplex virus (HSV) gain entry to the body through:
    • Breaks in the skin
    • Mucosal surfaces.
  • The virus replicates inside epithelial cells of the epidermis initially.
  • Next, the virus infections sensory or autonomic nerve endings and travels to the sensory ganglia.
    • It does this via retrograde axonal transport.
    • Once in the ganglia, the virus becomes latent, allowing avoidance of the immune system and hence enabling lifelong infection.
  • Patients are often asymptomatic when the virus is acquired.
    • The body usually launches an immune response against the virus, involving CD4+ and CD8+ T-cells in addition to antibody production.
  • If a patient shows symptoms of primary infection, this signifies the absence of an antibody response.

Reactivation
  • For this to occur, HSV travels back to the cutaneous or mucosal surface.
    • It does this via anterograde axonal transport.
  • The virus then undergoes lytic replication.
  • Whether symptomatic or asymptomatic reactivation, viral transmission can occur.
    • Symptoms can include tingling, burning or recurrence of ulcers.
  • Reactivation of latent HSV can be triggered by:
    • Local trauma (e.g. sexual intercourse)
    • Physical illness
    • Immunosuppression
    • Smoking
    • Stress
    • Alcohol intake
    • Ultraviolet light
    • Menstruation
    • Tight clothes and nylon underwear.

Clinical features

Symptoms vary for different people and between sexes. They are usually more severe during primary infection, with recurrences becomes less severe and less frequent with time.

Presentation in the first episode:
  • Genital lesions:
    • Grouped painful blisters which burst after 2-3 days, resulting in crusted erosions and ulcers on the external genitalia.
    • Lesions can also occur on the thigh, buttocks, cervix and rectum.
    • These can be extremely painful, making urinating and even sitting down painful (especially in women).
  • Other genital symptoms:
    • Tingling or burning pain around the genitals: often occur as a prodrome.
    • Dysuria (in women), which can lead to urinary retention.
    • Urethral or vaginal discharge.
  • Inguinal lymphadenopathy (30%):
    • Painful, bilateral enlargement.
  • Systemic illness:
    • Occur in around 50% of primary episodes.
    • Symptoms include: headache, fever, myalgia, malaise and constipation.
  • Duration:
    • Primary episodes can last up to 20 days.

Presentation in recurrent episodes (due to re-activation of latent HSV infection):
  • Prodrome:
    • Tingling and burning sensation in the genitals.
    • May precede the appearance of lesions by up to 48 hours.
  • Genital lesions:
    • Usually recur in the same area but lesions less severe than in the initial episode.
  • Duration:
    • Lesions crust and heal within 10 days.

Investigations

Confirmation of the presence of HSV infection and its type (HSV-1 or 2) are key for diagnosis, prognosis, management and counselling. Ideally genital herpes should be diagnosed in a specialised genitourinary medicine clinic to allow for type identification.
  • Polymerase chain reaction (PCR):
    • More sensitive than viral culture for detection of the virus, but not available in some locations.
    • Most effective if a scraped sample of an ulcer’s base can be taken.
    • Nucleic acid amplification tests (NAAT) are a type of PCR.
    • BASHH 2014 guidelines recommend NAAT as the first-line method of diagnosis in genital herpes.
  • Viral culture:
    • Most effective if a scraped sample of an ulcer’s base can be taken.
    • BASHH 2014 guidelines recommend viral culture to diagnose genital herpes if NAAT is not available.
  • Serology:
    • To test for HSV type-specific antibodies (IgG).
    • Presence of antibodies can be used to diagnose HSV infection.
    • BASHH 2014 guidelines state virus typing should be done via serology in all patients with a new diagnosis of genital herpes (in addition to NAAT or culture).

Consider testing for other sexually transmitted infections too if there is a history of unprotected sex.

Differential diagnosis

Genital ulceration can be of infectious or non-infection aetiology.

Infectious differentials for genital herpes (most common)
  • Primary syphilis
    • A sexually transmitted infection (STI) caused by Treponema pallidum, a spirochaetal bacterium.
    • Diagnosis involves clinical examination and serology.
    • Treatment is with penicillin.
    • Similarities: genital ulceration, sexual transmission.
    • Differences: singular, usually painless ulcer.
  • Chancroid
    • STI caused by the gram-negative Haemophilus ducreyi bacterium.
    • Rare in the UK; most common in resource-poor countries.
    • Treatment consists of antibiotic therapy.
    • Similarities: painful genital ulceration, sexual transmission.
    • Differences: single, deep ulcer.
  • Lymphogranuloma venereum
    • Caused by Chlamydia trachomatis infection.
    • Rare in the UK. Increasing in men who have sex with men.
    • First-line treatment is doxycycline.
    • Similarities: genital ulceration, lymphadenopathy.
    • Differences: lymphadenopathy is unilateral, lack of vesicles, single or few ulcers.
  • Candidiasis
    • A fungal infection.
    • Similarities: genital burning and irritation.
    • Differences: absence of ulcers and vesicles, presence of thick white discharge.

Non-infectious differentials for genital herpes (less common)
  • Behçet’s disease
    • A vasculitis resulting in mucocutaneous, vascular, ophthalmological, gastrointestinal, and CNS manifestations.
    • Similarities: genital ulceration.
    • Differences: absence of vesicles, coexistence of oral, eye, skin or neurological involvement.
  • Fixed drug eruption
    • Similarities: genital ulceration.
    • Differences: history of medicine use.
  • Genital trauma
    • Usually due to forced or excessively vigorous sexual intercourse.
    • Similarities: genital irritation and erythema.
    • Differences: abrasions rather than true ulcers.
  • Inflammatory bowel disease
    • Similarities: genital ulceration.
    • Differences: additional oral ulceration and gastrointestinal symptoms.

Management

Management of genital herpes depends on whether it is the patient’s first episode or a recurrence. All patients should be given verbal and written explanations about genital herpes, including cause, signs and symptoms, treatment, transmission, complications and prognosis.

Management of a first episode:
  • BASHH and NICE recommend that a first episode should ideally be diagnosed and treated at a specialist genitourinary medicine centre, especially if the patient is pregnant or immunocompromised.
  • Antiviral therapy
    • Indicated within 5 days of onset of symptoms or while new lesions are still forming.
    • Aims to reduce the duration and severity of the episode, but do not cure the patient.
    • Oral agents are more effective than topical agents.
    • Examples include acyclovir, valaciclovir and famciclovir.
  • Supportive care
    • Analgesia: paracetamol, ibuprofen, topical 5% lidocaine ointment
    • Saline bathing
    • Ice packs between the legs
    • Abstain from sexual intercourse until lesions have gone.

Management of recurrence:
  • Recurrences generally only cause mild symptoms and are self-limiting. Patients should be involved in treatment decisions.
  • Recurrences can be treated in general practice, but referral should be considered in pregnancy, immunocompromise and complications.
  • Supportive self-care only
    • Analgesia, saline bathing, ice packs.
    • Abstain from sexual intercourse until lesions have gone.
  • Episodic antiviral treatment
    • If attacks are infrequent, and self-care measures are not sufficiently controlling symptoms.
    • Reduces the duration and severity of the episode.
    • This could be self-initiated by patients, enabling early treatment induction and hence maximising effectiveness.
  • Suppressive antiviral therapy
    • BASHH and NICE recommend this for patients with at least 6 recurrences per year.
    • Duration of therapy is commonly 6 months to 1 year.

Management in pregnancy:
  • Specialist management is important during pregnancy to reduce the risk of transmission to the baby.
  • The Royal College of Obstetricians and Gynaecologists has published the advice below.
  • Antiviral therapy
    • If the first episode is before week 28 of the pregnancy, offer the mother antiviral therapy at that time, and then again from 36 weeks until the birth.
    • If the first episode is at or after week 28 of the pregnancy, advise the mother to take antiviral treatment from then until the birth.
  • Delivery method
    • If the first episode is within 6 weeks of the due date, offer an elective caesarean section to reduce the risk of neonatal herpes.
    • If the first episode is earlier in the pregnancy, normal vaginal birth is advised as the risk of transmission is very low.
    • Mothers should seek further advice from their midwife or doctor if they have any further concerns.

Advice for all patients:
  • Patients should disclose their herpes status to sexual partners.
  • Sexual intercourse should be avoided during symptomatic episodes (prodrome or genital lesions), as transmission is most likely at this time.
  • The virus can still spread to sexual partners even in the absence of symptoms, thus consistent condom use can lower the risk of spread.
  • Pregnant women should inform their healthcare provided of their herpes status so measures can be taken to reduce transmission to the baby.

Complications

Complications of genital herpes are uncommon, but can be serious.

Early complications:
  • Other sexually transmitted infections (STIs)
    • The presence of genital ulcers increases the patient’s risk of contracting other STIs, including HIV.
  • Psychosocial impact
    • Psychological distress and social stigma can impact on a patient’s quality of life and future sexual relationships.
    • Thus, it is important to provide verbal and written explanations about genital herpes to patients.
  • Superinfection of lesions
    • Bacterial (e.g. streptococcal) or fungal (Candida).
    • Usually occurs in the 1-2 weeks following the emergence of lesions.
  • Urinary retention
    • This could be due to dysuria and genital swelling.
  • Autoinoculation
    • To the fingers (herpetic whitlow) from scratching the itchy lesions.
    • To skin adjacent to the genitals (e.g. thighs).

Late complications:
  • Aseptic meningitis
    • Can occur during primary or recurrent episodes.
  • Sacral myeloradiculitis
    • Rare HSV-associated autonomic neuropathy.
    • Can cause urinary retention, perineal paraesthesia and erectile dysfunction.

Complications during pregnancy:
  • Neonatal HSV
    • Higher risk of transmission if the HSV is acquired by the mother during the 3rd trimester.
    • Can cause neonatal fever, seizures, sepsis or vesicular blisters.

Prognosis

  • Genital herpes is a chronic viral infection with a very variable course. Some patients will remain asymptomatic, while others will have frequent disease outbreaks of varying severity.
    • On average, following a symptomatic primary episode due to HSV-2, a patient will have 4 recurrences in the following year.
    • By contrast, the recurrence rate for HSV-1 is 4 times less frequent than HSV-2.
    • Over time, the frequency of recurrence usually reduces.