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For further information, see CMDT Part 34-02: Syphilis

Key Features

Essentials of Diagnosis

  • The spirochete can infect almost any organ or tissue in the body and cause protean clinical manifestations

  • Transmission occurs most frequently during sexual contact

General Considerations

  • Caused by Treponema pallidum, a spirochete capable of infecting almost any organ or tissue in the body and of causing protean clinical manifestations (Table 34–1)

  • The risk of syphilis after unprotected sex with an individual with infectious syphilis is ~30–50%

  • Congenital syphilis: transplacental transmission occurs in infants of untreated or inadequately treated mothers

  • Two major clinical stages

    • Early (infectious) syphilis

    • Late syphilis

  • Stages are separated by a symptom-free latent period

  • During early latency (within the first year after infection) the infectious stage may recur

  • Early syphilis

    • Primary lesions (chancre and regional lymphadenopathy)

    • Secondary lesions (commonly involving skin and mucous membranes, occasionally bone, CNS, or liver)

    • Congenital lesions

  • Late syphilis consists of

    • So-called benign (gummatous) lesions involving skin, bones, and viscera

    • Cardiovascular disease (principally aortitis)

    • CNS and ocular syndromes

Table 34–1.Stages of syphilis and common clinical manifestations.


  • In 2018, the number of primary and secondary syphilis cases in the United States was 35,063, and the rate of 10.8 per 100,000 people represented an increase of 14% over 2017

  • Most cases of syphilis in the United States continue to occur in men who have sex with men (MSM)

  • However, despite the increase in primary and secondary syphilis in MSM, a concomitant increase in the incidence of HIV has not been observed

Clinical Findings

Symptoms and Signs


  • Painless ulcer (chancre) on genitalia, perianal area, rectum, pharynx, tongue, lip, or elsewhere 2–6 weeks after exposure

  • Nontender enlargement of regional lymph nodes


  • Generalized maculopapular skin rash

  • Mucous membrane lesions, which can be found on the lips, mouth, throat, ...

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