Essentials of Diagnosis
  •  History of sexual contact (often unreliable).
  •  Painless ulcer on genitalia, perianal area, rectum, pharynx, tongue, lip, or elsewhere 2-6 weeks after exposure.
  •  Nontender enlargement of regional lymph nodes.
  •  Fluid expressed from lesion contains T pallidum by immunofluorescence or darkfield microscopy.
  •  Serologic test for syphilis often positive.

General Considerations
This is the stage of invasion and may pass unrecognized. The typical lesion is the chancre at the site or sites of inoculation, most frequently located on the penis, labia, cervix, or anorectal region. Anorectal lesions are especially common among men who have sex with men. The primary lesion occurs occasionally in the oropharynx (lip, tongue, or tonsil) and rarely on the breast or finger. The chancre starts as a small erosion 10-90 days (average, 3-4 weeks) after inoculation that rapidly develops into a painless superficial ulcer with a clean base and firm, indurated margins, associated with enlargement of regional lymph nodes, which are rubbery, discrete, and nontender. Bacterial infection of the chancre may occur and may lead to pain. Healing occurs without treatment, but a scar may form, especially with secondary bacterial infection. Although the “classic” ulcer of syphilis has been described as nontender, nonpurulent, and indurated, only 31% of patients have this triad.

Laboratory Findings
The serologic test for syphilis is usually positive 1-2 weeks after the primary lesion is noted; rising titers are especially significant when there is a history of previous infection. Immunofluorescence or darkfield microscopy shows treponemes in at least 95% of chancres. Cerebrospinal fluid pleocytosis has been reported in 10-20% of patients with primary syphilis.

Differential Diagnosis
The syphilitic chancre may be confused with chancroid (usually painful), lymphogranuloma venereum (uncommon in the United States), genital herpes, or neoplasm. Any lesion on the genitalia should be considered a possible primary syphilitic lesion.

Treatment
Benzathine penicillin G, 2.4 million units intramuscularly in the gluteal area, is given once. For the nonpregnant penicillin-allergic patient, doxycycline, 100 mg orally twice daily for 2 weeks, or tetracycline, 500 mg orally four times a day for 2 weeks, can be used. There is more clinical experience with tetracycline, but compliance is probably better with doxycycline. As noted above, ceftriaxone and azithromycin can be used in the penicillin-allergic patient.