Diseases Characterized by Genital, Anal, or Perianal Ulcers

In the United States, the majority of young, sexually active patients who have genital, anal, or perianal ulcers have either genital herpes or syphilis. The frequency of each condition differs by geographic area and population; however, genital herpes is the most prevalent of these diseases. More than one etiologic agent (e.g., herpes and syphilis) can be present in any genital, anal, or perianal ulcer. Less common infectious causes of genital, anal, or perianal ulcers include chancroid, LGV, and donovanosis. GUDs (e.g., syphilis, herpes, and LGV ) might also present as oral ulcers. Genital herpes, syphilis, chlamydia, gonorrhea, and chancroid have been associated with an increased risk for HIV acquisition and transmission. Genital, anal, or perianal lesions can also be associated with infectious and  noninfectious conditions that are not sexually transmitted (e.g., yeast, trauma, carcinoma, aphthae or Behcet’s disease, fixed drug eruption, or psoriasis).

A diagnosis based only on medical history and physical examination frequently can be inaccurate. Therefore, all persons who have genital, anal, or perianal ulcers should be evaluated. Specific evaluation of genital, anal, or perianal ulcers includes 1) syphilis serology tests and darkfield examination from lesion exudate or tissue, or NAAT if available; 2) NAAT or culture for genital herpes type 1 or 2; and 3) serologic testing for type specific HSV antibody. In settings where chancroid is prevalent, NAAT or culture for Hemophilus ducreyi should be performed.

No FDA-cleared NAAT for diagnosing syphilis is available in the United States, but multiple FDA-cleared NAATs are available for diagnosing HSV-1 and HSV-2 in genital specimens. Certain clinical laboratories have developed their own syphilis and HSV NAATs and have conducted Clinical Laboratory Improvement Amendment (CLIA) verification studies with genital specimens. Type-specific serology for HSV-2 might aid in identifying persons with genital herpes (see Genital Herpes, Type-Specific Serologic Tests). Additionally,  biopsy of ulcers with immunohistochemistry can help identify the cause of ulcers that are unusual or that do not respond to initial therapy. HIV testing should be performed on all persons not known to have HIV infection who present with genital, anal, or perianal ulcers. (see Diagnostic Considerations, under the Syphilis, Chancroid, LGV, Genital Herpes Simplex Virus,  or HIV sections). NAAT testing at non-genital sites should be considered for cases in which GUDs are suspected (e.g., oral manifestations of syphilis, herpes, or LGV). Commercially available NAATs have not been cleared by FDA for these indications but can be used by laboratories that have met regulatory requirements for an off-label procedure.

Because early syphilis treatment decreases transmission possibility, public health standards require health-care providers to presumptively treat any patient with a suspected case of infectious syphilis at the initial visit, even before test results are available. Presumptive treatment of a patient with a suspected first episode of genital herpes also is recommended, because HSV treatment benefits depends on prompt therapy initiation. The clinician should choose the presumptive treatment on the basis of the clinical presentation (i.e., HSV lesions begin as vesicles and primary syphilis as a papule) and epidemiologic circumstances (e.g., high incidence of disease among populations and communities and travel history). For example, syphilis is so common among MSM that any man who has sex with men presenting with a genital ulcer should be presumptively treated for syphilis at the initial visit after syphilis and HSV tests are performed. After a complete diagnostic evaluation > 25% of patients who have genital ulcers might not have a laboratory-confirmed diagnosis [425].