The spirochete Treponema pallidum causes syphilis. Transmission occurs primarily through sexual contact during the primary, secondary, and early latent stages of infection. Prenatal transmission is also possible.

Aortic regurgitation or aneurysm, meningitis, and widespread central nervous system damage can result from advanced syphilis.

The typical patient history points to unprotected sexual contact with an infected person or with multiple or anonymous sexual partners. A patient with primary syphilis may present with one or more chancres (small, fluid-filled lesions) on the genitalia, anus, fingers, lips, tongue, nipples, tonsils, or eyelids. In female patients, chancres may develop on the cervix or vaginal wall. These usually painless lesions start as papules and then erode. They have indurated, raised edges and clear bases and typically heal after 3 to 6 weeks, even when untreated. In the primary stage, palpation may reveal enlarged unilateral or bilateral regional lymph nodes (adenopathy).

In secondary syphilis (beginning within a few days or up to 8 weeks after the initial chancres appear), the patient may complain of headache, nausea, vomiting, malaise, anorexia, weight loss, sore throat, and a slight fever.

Inspection may reveal symmetrical mucocutaneous lesions. The rash of secondary syphilis may appear macular, papular, pustular, or nodular. Lesions are uniform, well defined, and generalized. Macules typically erupt between rolls of fat on the trunk and proximally on the arms, palms, soles, face, and scalp. In warm, moist body areas the lesions enlarge and erode, producing highly contagious, pink or grayish white lesions (condylomata lata).