Clinical update in sexually transmitted disease –2014

GENITAL ULCERATIVE DISEASE: HERPES, SYPHILIS, OTHERS

The risk of acquiring HIV is two to five times higher if one is exposed to it when a genital ulcerative disease is present.^20,21

In the United States, most cases of genital, anal, or perianal ulcers in sexually active persons are due to genital herpes or syphilis.⁸ Other causes include chancroid, granuloma inguinale, lymphogranuloma venereum, and noninfectious causes.

Although the frequency of these conditions varies by geographic area and demographic profile, herpes is the most prevalent of them.⁸ HSV-2 infection is one of the most prevalent STDs in the United States, with approximately 17% of all adolescents and adults infected,^1,22 and a much higher prevalence in persons who use drugs.²³

A thorough medical history and physical examination should be conducted. In addition, an accurate diagnosis requires specific tests: syphilis serology, dark field microscopy (if available), and culture or polymerase chain reaction (PCR) testing for herpes.⁸ A positive serologic test for HSV-1 or HSV-2 is enough to make the diagnosis in a patient whose symptoms suggest herpes, even if PCR and culture are negative.

GENITAL HERPES: MOSTLY ASYMPTOMATIC

Genital herpes is caused by HSV-1 or HSV-2. Of these, HSV-1 is on the rise, causing an increasing proportion of first episodes of genital herpes in some populations. It may now account for most new genital herpes infections in young women and in men who have sex with men.^8,24

Most people infected with HSV-1 or HSV-2 have no symptoms or have subclinical disease. When symptoms do occur, one or more vesicles may appear on or around the genitals, rectum, or mouth. The average incubation period after exposure is 4 days (range 2–12).²⁵ The first episode of genital herpes is often associated with systemic symptoms (eg, fever, headache, myalgia, and malaise) and local symptoms (eg, dysuria, vaginal or urethral discharge, and inguinal adenopathy).^26,27

Genital herpes often recurs, especially during the first year. Recurrences are less frequent with HSV-1 than with HSV-2.

Diagnosing genital herpes requires laboratory testing

Diagnosing genital herpes by clinical signs and symptoms is both insensitive and nonspecific. Therefore, laboratory testing should be performed for patients who present with genital ulcerative disease.

Virologic tests. Viral culture and nucleic acid amplification methods, including PCR assays, are the preferred virologic tests for herpes.⁸ Although viral culture is widely available, its sensitivity depends on the stage of the lesion and rapidly declines as lesions begin to heal. PCR assays are more sensitive than viral culture, can be done in automated systems, and are increasingly being used in clinical settings.²⁶ However, if the patient has no active lesions at the time of testing, failure to detect herpes by culture or PCR does not guarantee that the patient is not infected, as viral shedding is intermittent.

Serologic tests. Type-specific antibodies to HSV develop during the first several weeks following infection and persist indefinitely. Providers should specifically request serologic type-specific immunoglobulin G (IgG) assays. IgM testing for HSV should not be used, as IgM testing is not type-specific. Moreover, although some clinicians believe IgM is a good test for early infection because levels rise early and then decline, IgM may be positive during recurrent episodes.⁸

Both laboratory-based assays and point-of-care tests for HSV-2 are available. They are performed on capillary blood or serum and have sensitivities that range from 80% to 100% and specificities greater than 96%, compared with HSV-2 immunoblot and Western blot testing as the standard.^28,29

False-negative results may be more frequent in the early stages of infection. HSV-2 antibody indicates anogenital infection, while HSV-1 antibody might also be due to orolabial infection, which is something to keep in mind in a patient without genital symptoms.⁸

Treatment can control herpes but not eradicate it

Several herpes vaccines have undergone clinical trials, but an effective one remains elusive.^30,31

Antiviral therapy is used to control signs and symptoms of clinical disease but does not eradicate latent virus. For initial clinical episodes of genital herpes, the CDC recommends acyclovir, valacyclovir, or famciclovir for 7 to 10 days.⁸ In patients with established genital herpes, daily suppressive antiviral therapy can reduce recurrences, subclinical shedding, and the likelihood of transmission to partners; famciclovir is somewhat less efficacious for suppressing viral shedding.⁸

A diagnosis of herpes can carry considerable stigma, which can substantially interfere with a patient’s current and future relationships.^25,32,33 Sex partners of patients with genital herpes may benefit from evaluation and counseling. Clinicians should appreciate the psychological impact of a genital herpes diagnosis and address these concerns by providing education, counseling, and support while encouraging patients to recognize that herpes is a manageable condition.³⁴

SYPHILIS IS INCREASING IN MEN WHO HAVE SEX WITH MEN

Since 2001, rates of syphilis, a systemic disease caused by Treponema pallidum, have been increasing in men who have sex with men.^3,35 As of 2011, this group accounts for approximately 72% of all cases of primary and secondary syphilis in the United States.³

Primary syphilis is characterized by a firm, painless chancre at the site of inoculation. The chancre lasts 3 to 6 weeks and heals regardless of treatment. However, if the infected person does not receive adequate treatment, the infection progresses to the secondary stage.²⁶

Secondary syphilis typically starts with a nonpruritic rash, usually macular or papular, on the trunk and extremities, classically including the palms and soles. Other symptoms may include alopecia, lymphadenopathy, condylomata, and systemic symptoms.

Without treatment, the infection can progress to latent syphilis, which is further categorized as early (acquired during the preceding year), late latent, or of unknown duration.²⁶

Practical diagnosis of syphilis relies on serologic testing

Definitive diagnosis of early syphilis requires dark field microscopy or PCR to detect T pallidum in lesion exudate or tissue.⁸ However, because there are no commercially available tests for T pallidum, serologic testing is the mainstay.

Two types of serologic tests must be performed to diagnose syphilis: a nontreponemal test and a treponemal test.⁸

Nontreponemal tests:

• The Venereal Disease Research Laboratory (VDRL) test
• The rapid plasma reagin (RPR) test.

Treponemal tests:

• T pallidum passive particle agglutination (TP-PA) assay
• Fluorescent treponemal antibody absorbed (FTA-ABS) test
• Enzyme immunoassay (EIA)
• Chemiluminescence immunoassay (CIA).

Using only one type of serologic test is in-sufficient for diagnosis because each type has limitations, including the possibility of false-positive results.

Nontreponemal test results may correlate with disease activity, and results should be reported quantitatively; a fourfold change in titer, equivalent to a change of two dilutions, is needed to demonstrate a clinically significant difference between two nontreponemal test results using the same serologic test.⁸