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Syphilis is a sexually transmitted disease caused by the bacterium Treponema pallidum. It is often called “the great imitator” because many of its signs and symptoms are indistinguishable from those of other diseases. In the United States, syphilis occurs mainly in women 20 to 24 years of age and in men 35 to 39 years of age. In the first decade of the 21st century, reported syphilis cases have increased 2% to 5% annually. More than half of the reported cases occur in men who have sex with men.

The primary syphilitic lesion, a chancre, appears at the primary site of inoculation without other symptoms after an incubation period of 6 to 90 days (mean 21 days). In most cases, it occurs as a single lesion on the penis, but more than one chancre may be present. The chancre begins as a papule that later erodes. A grayish yellow and sometimes slightly hemorrhagic crust may be present on the surface of the erosion. The smooth base is usually moist, clean, and red. A serous exudate can be easily expressed. The classic chancre, uncomplicated by secondary infection, has a smooth, regular border that is neither rolled nor ragged. It represents an erosion of the skin surface rather than a deeper ulceration, and consequently the lesion heals without scar formation. The palpable induration is a result of vascular alterations and lymphocyte infiltration.

Chancres pursue a slow, indolent course that is characteristically pain free and accompanied in more than two thirds of cases by inguinal lymphadenopathy. As spirochetes migrate into the body, the chancre heals gradually (and without treatment) over 3 to 6 weeks.
When syphilis occurs concurrently with other sexually transmitted diseases or infections, the chancre may lack characteristic features. In such cases, the primary penile lesion may be erroneously diagnosed as chancroid, superficial abscess, or simple abrasion. Chancres can also occur ventrally on the frenulum and appear as small, atypical erosions. A presentation with phimosis with rubbery induration of the foreskin or as other atypical lesions should be investigated for syphilis. Intraurethral chancres, often manifesting as edema at the urethral meatus, can be misdiagnosed as mild non-specific urethritis.
The definitive diagnosis rests on the dark-field demonstration of the spirochete Treponema pallidum in the serum exudate from the primary lesion or from aspirated fluid from an indurated lymph node. Serologic tests (rapid plasma reagin [RPR], Venereal Disease Research Laboratory [VDRL], fluorescent treponemal antibody-absorption test [FTA-ABS]) become positive only when antibodies are produced and become detectable several days or weeks from the appearance of the chancre. Worthy of its title as the “great imitator,” syphilis may begin after direct inoculation into the vascular or lymphatic circulation without development of a primary skin lesion.
Syphilis is easily cured in the primary stage, but it is imperative to recognize and to properly treat syphilis early rather than to allow it to further evolve into its more refractory secondary and tertiary stages. Skin rash and mucous membrane lesions characterize the secondary stage of syphilis. The rash appears anywhere on the body and usually does not cause itching. Characteristically, it is rough, red, or reddish brown and occurs on the palms of the hands and the bottoms of the feet. Sometimes the rash is faint and barely noticeable. Additional symptoms may include fever, lymphadenopathy, sore throat, patchy hair loss, headaches, weight loss, muscle aches, and fatigue. Secondary syphilis will also resolve without treatment. Tertiary or latent syphilis can last for years. The late stages of syphilis can appear 10 to 20 years after the infection was first acquired. In late syphilis, damage to internal organs, including the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints is possible. Signs and symptoms include difficulty coordinating muscle movements, foot drop, paralysis, numbness, gradual blindness, dementia, and death.