• Clinical science



Syphilis is a predominantly sexually transmitted bacterial infection with the spirochete Treponema pallidum. The disease presents with four distinct, successive clinical stages if left untreated. Primary syphilis manifests with a painless chancre (primary lesion), typically on the genitals. Secondary syphilis is characterized by a polymorphic, maculopapular rash that also appears on the palms and soles. The first two stages are followed by an asymptomatic phase (latent syphilis), in which the disease may resolve entirely or progress to tertiary syphilis. During the tertiary stage, characteristic granulomas (gumma) may appear, which can cause irreversible organ damage, particularly in the cardiovascular system (syphilitic aortic aneurysm) and the CNS (neurosyphilis). Diagnosis requires serologic analyses, including nontreponemal tests for screening purposes and treponemal tests for confirmation. Further tests may directly detect T. pallidum (dark field microscopy, PCR) if a specimen of infected tissue or blood can be obtained. The first-line treatment for syphilis is penicillin, which should be administered after an infection has been confirmed. Congenital syphilis, a complication seen in children of women who have syphilis during pregnancy, is discussed in another learning card.


  • Sex: > (6:1)
  • Incidence: 10.8/100,000 per year in the US
  • Peak incidence: 20–29 years


Epidemiological data refers to the US, unless otherwise specified.


  • Pathogen
  • Transmission
    • Sexual contact (via small mucocutaneous lesions)
    • Vertical

Treponema bacteria (particularly during stages I/II) are highly contagious! Sexual contact with a partner who suffers from active syphilis will lead to infection in 30% of cases!



  • Spirochetes invade the body → disseminate systemically within hours → bind to endothelial cells → inflammatory reaction → endarteritis and perivascular inflammatory infiltrate


Clinical features

Incubation period

  • 10–90 days; on average 21 days

Primary syphilis

  • Primary lesion (chancre)
    • Typically starts out as a solitary, raised papule (usually on the genitals)
    • Evolves into painless, firm ulcer with indurated borders and smooth base
    • Resolves spontaneously within 3–6 weeks, typically without scarring
  • Regional (usually inguinal) nontender lymphadenopathy

Secondary syphilis

  • Begins approx. 8–12 weeks after primary infection; typically lasts 2–6 weeks
  • Constitutional symptoms
  • Specific features
    • Polymorphic rash
      • Typically nonpruritic macular or papular rash
      • Disseminated; involves trunk and extremities, also the palms and soles
      • Reddish-brown or copper-colored
      • Heals within 6 months; , but may recur
    • Condylomata lata
      • Broad-based, wart-like papular erosions
      • Located in the anogenital region, intertriginous folds, and on oral mucosa
    • Additional lesions

Latent syphilis

  • No clinical symptoms, despite seropositivity
  • May last months, years, or even for the entire life of the patient
  • Disease may resolve, reactivate, or progress to tertiary syphilis

Tertiary syphilis

During pregnancy: see congenital syphilis

Syphilis (also known as “the great imitator”) may have a very broad clinical presentation that mimics many other diseases!


Serological testing

Two separate serological tests are required to establish a diagnosis of syphilis: Nontreponemal tests are used for screening purposes, while treponemal tests confirm the diagnosis. In early primary syphilis, both types of test may be nonreactive. Therefore, direct detection of the treponemes is usually preferred during this stage.

1. Nontreponemal tests

2. Treponemal tests

Direct detection of the pathogen

In vitro cultivation of Treponema pallidum is not possible!

Patients diagnosed with syphilis should also be screened for other sexually transmitted diseases (HIV, gonorrhea, chlamydia)!



Penicillin is the drug of choice for treatment of syphilis!



We list the most important complications. The selection is not exhaustive.



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last updated 06/16/2020
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