Herpes Simplex, Genital

Ulcerated
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Diagnosis and reasoning

This patient has presented with genital ulcers. In the vast majority of cases, this is secondary to sexually transmitted infections (STI) such as genital herpes, syphilis and chancroid. Non infectious etiologies which may give rise to genital ulcers include Behcet's disease, Stevens-Johnson syndrome, Pemphigus, and fixed drug eruptions. Stevens-Johnson syndrome involves multiple mucocutaneous surfaces, while Pemphigus gives rise to generalized skin lesions, and Behcet's disease shows multisystemic manifestations such as uveitis and oral aphthous ulcers. Thus, the localized nature of her lesions argues against these diagnoses. The absence of drug therapy excludes fixed drug eruptions. Closer examination of the ulcers shows them to be multiple and shallow, with an erythematous base. This morphology is characteristic of herpes simplex (HSV) infection. Note that the ulcers of chancroid are deep and irregular with a purulent and necrotic base, while those of syphillis are usually single and painless. It is also useful to determine whether this is a primary HSV infection or a recurrence. In this patient, the onset of symptoms several days after sexual contact, presence of systemic features (such as fever and malaise), and absence of similar episodes in the past favor a primary infection. Note also that recurrences are typically preceded by prodromal symptoms such as tingling, itching, pain or paresthesia in the lumbosacral dermatomes. The next step should be an investigative workup including viral cultures and serology. In this patient, the positive cultures confirm the clinical diagnosis and additionally show the viral subtype to be HSV-2. In addition, the negative serology tests show this to be a primary infection (as seroconversion occurs approximately 8 to 12 weeks following the primary episode). Screening for HIV and Syphilis is also important as many of these patients are infected with multiple STIs. In addition, her husband should also be screened and his sexual contacts traced. Her management should include antiviral therapy with acyclovir, while an elective cesarean section should be offered to prevent neonatal herpes. Oral analgesics will provide pain relief. Intramuscular Penicillin would have been indicated if she was diagnosed with syphilis.


Discussion

HSV-2 is the commonest cause of genital ulcers worldwide. The prevalence among the general population of the United States alone is 16.2%. The causative agent is the DNA virus Herpes Simplex type 2. At the time of primary infection, the virus is taken up by the free sensory nerve endings of the dermis, following which it migrates along the spinal nerves to the sensory ganglia, where it remains for the lifetime of the patient. Following this, the virus undergoes cycles of dormancy followed by reactivation and shedding. These episodes of reactivation are termed "recurrences", and may be symptomatic or subclinical. In general, genital herpes is a self-limiting condition. However, infection in pregnancy adds an extra dimension of complexity, as this may result in the severe complication of neonatal herpes. Neonatal herpes results from vertical transmission at the time of delivery. It typically manifests as skin and eye disease, neurological disease (e.g. encephalitis), organ impairment and death. In primary infection, the risk of neonatal herpes may be as high as 30% to 50%, if delivery occurs before seroconversion. In a recurrence, the risk of neonatal herpes ranges from 2% to 5%, if active lesions are present. Otherwise, the risk is only 0.02% to 0.05%. Note that the risk is increased by pre-labor rupture of the membranes (PROM) and invasive obstetric procedures. The management of genital herpes in pregnancy involves treatment of the maternal infection and prevention of neonatal infection. Primary infections should be treated with antivirals (such as acyclovir), as this will reduce the duration and severity of symptoms. Recurrences typically do not require treatment unless severe. In addition, daily suppressive therapy may be considered in patients with a history of recurrences, in order to prevent reactivation close to the time of delivery. Note that acyclovir is considered to be safe in pregnancy, although caution is advocated in gestations < 20 weeks in duration. Given the high risk of vertical transmission, most guidelines recommend cesarean section if primary infection occurs in late pregnancy (e.g. within 6 weeks of the expected date of delivery - EDD). As the risk of transmission in a recurrence is significantly lower, the recommended management varies by country. The guidelines of the American College of Obstetricians and Gynecologists (ACOG) recommend cesarean section in patients with active genital lesions or prodromal symptoms. However, other guidelines (such as those of the Royal College of Obstetricians and Gynecologists - RCOG) are more conservative. Other important precautions include avoidance of invasive procedures such as fetal blood sampling, fetal scalp electrodes and forceps delivery in women with a history of recurrent HSV. Couples in whom the male partner is HSV-positive, and the woman is HSV-negative, may reduce the risk of primary infection during pregnancy by using barrier methods or abstaining from sexual intercourse (especially during the third trimester).


Take home messages

  1. Genital herpes is the commonest cause of genital ulcers worldwide.
  2. The presence of systemic symptoms suggests primary HSV infection.
  3. Primary infection in late pregnancy is an indication for elective cesarean section.
  4. Invasive procedures are best avoided in women with a history of recurrent HSV.

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  1. ACOG practice bulletin No 82: management of herpes in pregnancy(2006)
  2. Canadian Family Physician: Safety of antiviral medication for the treatment of herpes during pregnancy (2011)
  3. RCOG Green Top Guideline No. 30: Management of genital herpes in pregnancy (2007)
  4. SOGC Clinical practice guideline: Guidelines for the management of herpes simplex virus in pregnancy (2008)
  5. The Lancet: Genital Herpes (2008)