• Clinical science

Syphilis

Abstract

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.

Epidemiology

  • Sex: > (10:1)
  • Incidence: 6.3/100,000 per year in the US
  • Peak incidence: 20–29 years

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

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!

References:[3][4]

Pathophysiology

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

References:[3]

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

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!
References:[3][5][6][7][8][9][10]

Diagnostics

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

  • Indication: definite tests to detect primary and secondary syphilis when a specimen can be obtained (e.g., exudative chancre, condyloma)
  • Interpretation: confirmation of diagnosis, but negative results do not rule out syphilis
  • Available tests

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)!

References:[3][11][6][12][13][14]

Treatment

Penicillin is the drug of choice for treatment of syphilis!
References:[3][13][15]

Complications

References:[13][16][17]

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

Prevention

  • Condoms prevent transmission of syphilis and other STDs.
  • Syphilis is a nationally notifiable disease.

References:[18]

  • 1. Centers for Disease Control and Prevention. 2014 Sexually Transmitted Diseases Surveillance: National Profile: Syphilis. https://www.cdc.gov/std/stats14/syphilis.htm. Updated November 17, 2015. Accessed March 27, 2017.
  • 2. Patton ME, Su JR, Nelson R, Weinstock H. Primary and secondary syphilis: United States, 2005-2013. MMWR Morb Mortal Wkly Rep. 2014; 63(18): pp. 402–406. pmid: 24807239.
  • 3. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
  • 4. Georgiev VS. Infectious Diseases in Immunocompromised Hosts. CRC Press; 1997.
  • 5. James WD, Berger T, Elston D. Andrews' Diseases of the Skin: Clinical Dermatology. Philadelphia, PA: Elsevier Health Sciences; 2015.
  • 6. Haran P. Syphilis. In: Stuart Bronze M. Syphilis. New York, NY: WebMD. http://emedicine.medscape.com/article/229461. Updated October 7, 2016. Accessed March 25, 2017.
  • 7. Evans AS, Brachman PhS. Bacterial Infections of Humans: Epidemiology and Control. Springer; 1998.
  • 8. Hicks CB, Clement M. Syphilis: Epidemiology, Pathophysiology, and Clinical Manifestations in HIV-Uninfected Patients. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/syphilis-epidemiology-pathophysiology-and-clinical-manifestations-in-hiv-uninfected-patients. Last updated November 21, 2016. Accessed March 27, 2017.
  • 9. National Institute of Allergy and Infectious Diseases. Syphilis. https://www.niaid.nih.gov/diseases-conditions/syphilis. Updated March 27, 2017. Accessed March 27, 2017.
  • 10. Knudsen RP. Neurosyphilis. In: Singh NN. Neurosyphilis. New York, NY: WebMD. http://emedicine.medscape.com/article/1169231. Updated June 15, 2016. Accessed March 27, 2017.
  • 11. Hicks CB, Clement M. Syphilis: Screening and Diagnostic Testing. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/syphilis-screening-and-diagnostic-testing. Last updated October 22, 2016. Accessed March 22, 2017.
  • 12. Birnbaum NR, Goldschmidt RH, Buffett WO. Resolving the common clinical dilemmas of syphilis. Am Fam Physician. 1999; 59(8): pp. 2233–2240. url: http://www.aafp.org/afp/1999/0415/p2233.html.
  • 13. Centers for Disease Control and Prevention. 2015 Sexually Transmitted Diseases Treatment Guidelines: Syphilis. https://www.cdc.gov/std/tg2015/syphilis.htm. Updated July 27, 2016. Accessed March 27, 2017.
  • 14. Workowski KA, Bolan GA. Morbidity and Mortality Weekly Report (MMWR) - Sexually Transmitted Diseases Treatment Guidelines, 2015. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm. Updated June 5, 2015. Accessed October 18, 2017.
  • 15. Hicks CB, Clement M. Syphilis: Treatment and monitoring. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/syphilis-treatment-and-monitoring. Last updated September 7, 2016. Accessed March 27, 2017.
  • 16. 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): pp. 46–52. doi: 10.4269/ajtmh.16-0434.
  • 17. 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): pp. 976–979. doi: 10.1086/656419.
  • 18. Centers for Disease Control and Prevention. 2017 Nationally Notifiable Conditions. https://wwwn.cdc.gov/nndss/conditions/notifiable/2017/. Updated January 1, 2017. Accessed March 22, 2017.
last updated 11/19/2018
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