Genital Ulcers (Case 49)

Pφ

HSV is a dsDNA virus; there are two different HSV subtypes, HSV-1 and HSV-2. Although HSV-1 has typically been associated with herpes labialis (cold sores) and HSV-2 with genital ulcers, an increasing proportion of cases of genital HSV have been documented to be due to HSV-1. HSV viral replication occurs first in epidermal and dermal cells at mucosal surfaces or abraded skin. Virus then enters nerve endings and is transported intra-axonally to nerve cell bodies, most commonly in the sacral root ganglia. Viral replication occurs in the ganglia and surrounding tissues, followed by centrifugal spread back to mucosal surfaces via the peripheral sensory nerves. After the primary infection has resolved, HSV DNA can be found in a small proportion of ganglion cells. When reactivation occurs, peripheral sensory nerves transport virus back to the mucosal surface, and recurrent genital lesions appear. Many individuals with evidence of HSV-2 infection, based on positive serology, may never have clinically recognizable genital ulcer disease, yet these individuals may still intermittently shed virus and transmit the infection to their partners. It is important to emphasize to patients that viral shedding (and therefore transmission to partners) occurs even in the absence of visible lesions.

TP

Patients with symptomatic primary genital infection present with multiple bilateral genital lesions characteristically in various stages of evolution from vesicles to pustules to shallow ulcerations; lesions have an erythematous base. The cervix and the urethra may be involved, and patients may complain of dysuria and vaginal discharge. Tender inguinal lymphadenopathy is common, and patients may have significant systemic symptoms including fever, headache, myalgias, and generalized malaise. Recurrent disease is much milder, with fewer lesions that are usually unilateral without systemic symptoms. Recurrence occurs in 90% of those with symptomatic primary infection.

Dx

A presumptive diagnosis of genital HSV can be made based on history and physical examination; however, the clinician should attempt to confirm the diagnosis with a viral culture or antigen detection test. It is currently believed that up to 50% of primary genital HSV infections are due to HSV-1; in HSV-1 genital infection, recurrences and subclinical viral shedding are much less common than with HSV-2 infections. This information is important when counseling patients regarding risk of recurrent disease and transmission. The type-specific serologic tests (those that reliably distinguish between HSV-1 and HSV-2) may be useful in some clinical settings, including patients who have recurrent ulcers with a negative culture or those with a past clinical diagnosis of genital HSV that was never virologically confirmed.

Pφ

T. pallidum, a spirochete, is the causative organism of syphilis and can penetrate intact mucosal surfaces or gain entry into the tissues through abraded skin. The organism disseminates via the lymphatics and the bloodstream; virtually every organ can be affected. Disease is classified into the following stages: incubating syphilis, primary, secondary, latent, and tertiary. An ulcer at the site of inoculation (chancre) is the major manifestation of primary disease. On histopathology, chancres demonstrate infiltration by plasma cells with proliferation of endothelial cells and fibroblasts of small blood vessels, leading to the classic histopathologic finding of obliterative endarteritis.

TP

Chancres are usually single ulcers, but several lesions may occur; the lesion is typically painless and therefore may not be noticed by the patient. Chancres are round lesions with raised regular borders that have firm induration on palpation. The ulcer base does not have an exudate. Nontender inguinal adenopathy is frequently found. Genital lesions may also occur in secondary syphilis, where the generalized rash appears as raised, moist papular lesions.

Dx

A definitive diagnosis of syphilis may be established by dark field examination or direct fluorescent antibody testing of exudate from the ulcer base. This testing is not available in many settings; therefore, serologic testing can allow a presumptive diagnosis in a patient with a compatible clinical presentation. A two-step serologic testing strategy is as follows: Nontreponemal (nonspecific) tests are the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests; these tests are reported qualitatively as a titer. If this test is positive, it is confirmed with a treponemal (specific) test such as the fluorescent treponemal antibody absorbed (FTA-ABS) or the T. pallidum particle agglutination (TP-PA) test.

Pφ

Worldwide, chancroid is thought to be one of the most common causes of genital ulcer disease; however, this infection is much more common in the developing countries of Asia, Africa, and Latin America than in the United States. In the United States the disease has generally occurred in outbreaks in urban areas, often in association with the trading of sex for drugs, particularly crack cocaine.

The causative organism, H. ducreyi, gains entry through breaks in the epithelial surface during sexual contact with an individual with active infection. The ability of the organism to evade phagocytosis is thought to be important in pathogenesis. On histopathology, the ulcers have been shown to contain numerous CD4-positive T lymphocytes.

TP

Typical lesions begin as a tender erythematous papule, which then becomes pustular; the pustule then ruptures to form an ulcerative lesion. There may be single or multiple lesions, and the lesions are painful. The ulcer base is described as granulomatous, frequently with a purulent exudate; the ulcer border is ragged but not indurated. Approximately half of the patients will have tender, enlarged inguinal lymph nodes, frequently unilateral, which may suppurate and drain (buboes).

Dx

H. ducreyi is a fastidious organism that requires specialized media for growth and is therefore difficult to isolate in culture. DNA amplification techniques have been developed to aid in diagnosis but are not yet widely available. The CDC recommend that a clinical diagnosis of chancroid is appropriate in patients who have all of the following: (1) single or multiple painful genital ulcers; (2) no evidence of infection with T. pallidum by either dark field examination of exudate from the ulcer or serologic tests for syphilis performed at least 7 days after the appearance of the ulcer; (3) a typical clinical presentation and appearance of the ulcer; and (4) a negative test for the presence of HSV from the ulcer exudate.