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SEXUALLY TRANSMITTED DISEASES: SYPHILIS

Syphilis is caused by infection with the spirochete T. pallidum. The organism is transmitted through the skin or mucous membranes and causes systemic infection if left untreated.

Clinical Findings

Primary syphilis occurs 2 to 4 weeks after sexual exposure, manifesting as a painless genital sore or chancre. Chancres can occur anywhere on the genitals as well as the mouth and lips. Once the chancre heals, syphilis enters a latent stage. Latent infection is divided into early (contracted within 1 year) and late latent infection. This is an important distinction, since late infection may require a longer duration of therapy.

Weeks to months later, 25% of untreated patients will develop secondary syphilis. The classic sign of secondary syphilis is a rash of 5 to 20 mm red or red-brown papules that affects the entire body. Involvement of the palms and soles is characteristic. Other symptoms of secondary syphilis include lymphadenopathy, fever, sore throat, headache, malaise, weight loss, and a patchy alopecia. Secondary syphilis resolves spontaneously, but without treatment, patients may suffer recurrent episodes for years. Tertiary syphilis is characterized by visceral and cardiac involvement. Occasionally gummas, erosions or granulomatous lesions, may appear on the skin or in visceral organs.

In neurosyphilis, T. pallidum infects the central nervous system. Neurologic involvement can manifest as meningitis, general paresis, meningovascular strokes, tabes dorsalis, and a host of other neurologic symptoms.

Diagnosis

All patients with syphilis should be tested for HIV infection. The variety of presentations can make syphilis a difficult diagnosis to make. Laboratory testing is imperative. In primary syphilis, the presence of a chancre allows for easier diagnosis and laboratory testing. The definitive tests for early syphilis are dark-field examination and direct fluorescent antibody tests of lesion exudates or tissue.

If there are no skin lesions, serology must be used. Because many diseases can cause positive syphilis tests, two types of serologic tests, treponemal and nontreponemal, should be used to diagnose syphilis:

Treponemal serologic tests

Fluorescent treponemal antibody absorbed (FTA-ABS)

T. pallidum particle agglutination

Nontreponemal serologic tests

Veneral Disease Research Laboratory (VDRL)

Rapid plasma reagin (RPR)

Nontreponemal tests change with disease activity and should be reported numerically. A fourfold change in titer (e.g., two dilutions) is necessary to demonstrate a clinically significant difference. The RPR and VDRL tests cannot be compared directly because RPR titers tend to run higher. Although these test results usually become negative after treatment, occasionally they will remain positive for life (serofast reaction). Treponemal serologies tend to remain positive for life, regardless of treatment. These treponemal tests do not correlate with disease activity.

Neurosyphilis is a challenging diagnosis. VDRL can be performed on cerebrospinal fluid. The test is highly specific but insensitive. A positive VDRL result on cerebrospinal fluid is diagnostic of neurosyphilis. If the VDRL is negative, FTA-ABS can be performed on the sample. The FTA-ABS is less specific but is highly sensitive. Some experts believe that a negative FTA-ABS finding on cerebrospinal fluid excludes neurosyphilis. Patients with uveitis should be considered to have neurosyphilis and have cerebrospinal fluid examination.

Treatment

Although there are different antibiotic regimens for each stage of syphilis, penicillin is the mainstay of treatment for each. Patients should be followed for resolution or absence of symptoms. Nontreponemal serologies should be rechecked at 6 and 12 months following therapy. If symptoms or titers remain unchanged, a cerebrospinal fluid analysis should be performed. Treatment of partners to prevent re-infection is also very important in resistant cases. In patients with neurosyphilis, reevaluation of cerebrospinal fluid should also be performed.