Last updated: July 28, 2022

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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 (darkfield 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 article.


Epidemiological data refers to the US, unless otherwise specified.

Treponema bacteria (particularly during stages I and II) are highly contagious.

  • Spirochetes invade the body → disseminate systemically within hours → bind to endothelial cells → inflammatory reaction → endarteritis and perivascular inflammatory infiltrates [2]

Incubation period [4]

  • 10–90 days
  • On average 21 days

Primary syphilis

Secondary syphilis

Remember that Secondary Syphilis causes Systemic Symptoms.

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


  • Chronic, destructive granulomatous lesions with a necrotic center that tend to ulcerate
  • May affect any organ, e.g., skin, internal organs, bones

Cardiovascular syphilis


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

Syphilis during pregnancy

Approach [6]

Serological testing [7][8]

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 tests may be nonreactive. Therefore, direct detection of the treponemes is usually preferred during this stage.

Nontreponemal tests

False-Positive results on VDRL with Pregnancy, Viral infection (e.g., EBV, hepatitis), Drugs (e.g., chlorpromazine, procainamide), Rheumatic fever (rare), Lupus, and leprosy.

Treponemal tests

Direct detection of the pathogen [7][8]


Treponema pallidum cannot be cultivated in vitro.

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.

  1. Syphilis. Updated: January 1, 2018. Accessed: April 20, 2020.
  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. Georgiev VS. Infectious Diseases in Immunocompromised Hosts. CRC Press ; 1997
  4. Syphilis - CDC Fact Sheet (Detailed). Updated: January 30, 2017. Accessed: December 3, 2020.
  5. O'Byrne P, MacPherson P. Syphilis.. BMJ. 2019; 365 : p.l4159. doi: 10.1136/bmj.l4159 . | Open in Read by QxMD
  6. The Diagnosis, Management and Prevention of Syphilis: An Update and Review. Updated: March 1, 2019. Accessed: June 16, 2020.
  7. 2015 Sexually Transmitted Diseases Treatment Guidelines: Syphilis. Updated: July 27, 2016. Accessed: March 27, 2017.
  8. Morbidity and Mortality Weekly Report (MMWR) - Sexually Transmitted Diseases Treatment Guidelines, 2015. Updated: June 5, 2015. Accessed: October 18, 2017.
  9. Syphilis Laboratory Case Definition (LCD). Updated: March 14, 2017. Accessed: December 3, 2020.
  10. Nayak S, Acharjya B. VDRL test and its interpretation.. Indian J Dermatol. 2012; 57 (1): p.3-8. doi: 10.4103/0019-5154.92666 . | Open in Read by QxMD
  11. Karaca Y, Cöplü N, Gözalan A, Oncül O, Akin L, Esen B. [Establishment of an algorithm for serological testing of syphilis identification].. Mikrobiyol Bul. 2010; 44 (1): p.35-45.
  12. 2017 Nationally Notifiable Conditions. Updated: January 1, 2017. Accessed: March 22, 2017.
  13. Butler T. The Jarisch–Herxheimer reaction after antibiotic treatment of spirochetal infections: A review of recent cases and our understanding of pathogenesis. Am J Trop Med Hyg. 2016; 96 (1): p.46-52. doi: 10.4269/ajtmh.16-0434 . | Open in Read by QxMD
  14. Yang C, Lee N, Lin Y, et al. Jarisch‐Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the HIV infection epidemic: Incidence and risk factors. Clin Infect Dis. 2010; 51 (8): p.976-979. doi: 10.1086/656419 . | Open in Read by QxMD
  15. Chen J, Lee L. Posterior placoid chorioretinitis: An unusual ocular manifestation of syphilis.. Clinical ophthalmology (Auckland, N.Z.). 2008; 2 (3): p.669-73. doi: 10.2147/opth.s2743 . | Open in Read by QxMD

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