Treponema pallidum, a spirochete, causes the three stages of syphilis infections: primary, secondary, and tertiary stages. Primary syphilis is characterized by a chancre (Fig. 87-1), a single painless ulcer with indurated borders that develops on the penis, vulva, or other areas of sexual contact. The primary chancre heals and disappears after 3 to 6 weeks, and the secondary stage occurs after several additional weeks. Rash and lymphadenopathy are the most common symptoms of secondary syphilis. The rash consists of nonpruritic dull red or pink papules that begin on the trunk and flexor surfaces of the extremities and subsequently spread to the palms and soles. Constitutional symptoms such as fever, malaise, headache, and sore throat are common before spontaneous resolution of this second stage. Tertiary or latent syphilis develops in about one-third of patients and can begin 3 to 20 years after the initial infection. Involvement of the nervous system (meningitis, dementia, tabes dorsalis), cardiovascular system (thoracic aneurysm), and widespread granulomatous lesions (gummata) are characteristic of tertiary syphilis.
Treponema pallidum cannot be cultured in the laboratory and testing is a challenge because there is no single optimal diagnostic test. The sensitivity and specificity of tests for syphilis depend on the stage of the disease and type of test. Nontreponemal tests such as Venereal Disease Research Laboratory (VDRL) and rapid plasma regain (RPR) detect nonspecific antibodies that are indicative of infection but do not become detectable until 1 to 4 weeks after a chancre appears. Positive results for these screening tests must subsequently be confirmed with an immunoassay specific for T. pallidum antibodies. A presumptive diagnosis of syphilis is made if a positive result on a nontreponemal antibody test is supported by a positive confirmatory result on a treponemal antibody test. Direct visualization of organisms using darkfield microscopy is diagnostic for primary, secondary, or early congenital syphilis.