Syphilis: Risk factors and clinical manifestation

This guide is about management of primary, secondary, latent and tertiary syphilis. Some information about neurosyphilis and congenital syphilis is included, however their treatment is outside the scope of this document. Individuals with these conditions should be managed by or in consultation with an infectious disease specialist or an experienced colleague.

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Risk factors

Common risk factors for syphilis:

Other activities that may increase potential exposure to STBBIs include anonymous sexual partnering, street involvement and substance use.

Transmission

Syphilis is transmitted by direct contact with an infectious lesion or through vertical transmission during pregnancy. Primary, secondary and early latent stages are considered infectious, with an estimated risk of transmission per partner of 51% to 64%Footnote 3. Early latent syphilis is considered infectious because of the 25% chance of relapse to the secondary stageFootnote 4.

The primary mode of syphilis transmission is by vaginal, anal and oral sexual contactFootnote 1. Other routes of transmission (e.g. kissing and needle-sharing) are rareFootnote 5.

Transplacental transmission can occur as early as nine (9) weeks gestationFootnote 6 and throughout pregnancy. Most infants with congenital syphilis are infected in utero, but they can also be infected by contact with an active genital lesion at the time of delivery. The risk of transmission is related to both stage of syphilis as well as gestational age at time of diagnosis and treatment, with the greatest risk of transmission in pregnant people acquiring syphilis near termFootnote 7. The risk of transmission to the fetus is 70% to 100% in untreated pregnant people with primary or secondary syphilis and 40% with early latent syphilisFootnote 8,Footnote 9.

In a recent systematic review, adverse pregnancy outcomes occurred in 76.8% of untreated pregnancies compared to 13.7% of uninfected pregnanciesFootnote 10. Even after treatment, there remains a significantly higher risk of adverse pregnancy outcomes compared to uninfected pregnanciesFootnote 11.

Clinical manifestations

The clinical manifestations of syphilis are usually described according to stage of disease: primary, secondary, latent, congenital, neurosyphilis and tertiary syphilis.

Note: Neurosyphilis may occur at any stage.

Health care practitioners should consider syphilis in people presenting with rashes or genital ulcerative disease and/or proctitis.

Primary syphilis

Usually occurs three (3) weeks after infection but can range from three (3) to 90 days. The primary manifestation is a painless lesion (chancre). In persons practicing receptive sex, the lesion(s) may be intra-anal, oral or on the internal genital tract and may go unnoticed. Regional lymphadenopathy may occur.

Secondary syphilis

This stage typically starts with the development of a rash. The characteristic rash of secondary syphilis may appear as rough, red, or reddish brown spots on the palms of the hands and the bottoms of the feet. Rashes with a different appearance may occur on other parts of the body and may be so faint that they are not noticed.

Signs and symptoms usually occur between two (2) to 12 weeks, but can occur up to six (6) months after infection and may include:

Secondary syphilis can also manifest with signs and symptoms of meningitis (e.g. headaches), uveitis/retinitis (e.g. blurred vision, eye redness, flashes or floaters) or otic symptoms (e.g. hearing loss, tinnitus).

Latent syphilis

Early latent syphilis

Asymptomatic infection of less than one (1) year duration.

Late latent syphilis

Asymptomatic infection of more than one (1) year duration.

Congenital syphilis

Early congenital syphilis

If present, symptoms typically occur before the second year of life. Two-thirds of infections may be asymptomatic. Clinical manifestations may include:

Late congenital syphilis

Clinical manifestations are usually identified two (2) years after birth and can include:

Neurosyphilis

Treponema pallidum can infect the central nervous system and cause neurosyphilis during any stage of syphilis. It can occur in cases of untreated primary infection, up to 20 years or more after infection.

Neurosyphilis may be asymptomatic or present with:

HIV alters the natural course of syphilis and sometimes results in a more rapid progression to neurosyphilis and more aggressive and atypical signs of infectionFootnote 12,Footnote 13.

Early neurosyphilis

Early neurosyphilis occurs within the first year of infection. Approximately 5% of those affected will experience manifestations such as meningitis, cranial neuritis, ocular involvement and meningovascular diseaseFootnote 14.

Late neurosyphilis

Late neurosyphilis occurs more than one (1) year after infection with 2% to 5% experiencing general paresis and 2% to 9% experiencing tabes dorsalisFootnote 14.

Tertiary syphilis

Untreated primary infection may progress to neurosyphilis, cardiovascular syphilis or gumma.

Cardiovascular syphilis

Occurs from 10 to 20 years after exposure and may present with:

Syphilitic gumma

Occurs from one (1) to 46 years after exposure but most cases will develop within 15 years.

Gummatous lesions cause tissue destruction and can occur on any organ. Clinical manifestation will depend on the site involved.

References

Footnote 1

Singh AE, Romanowski B. Syphilis: Review with emphasis on clinical, epidemiologic, and some biologic features. Clin Microbiol Rev. 1999;12(2):187-209.

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Footnote 2

Choudhri Y, Miller J, Sandhu J, Leon A, Aho J. Infectious and congenital syphilis in canada, 2010-2015. Can Commun Dis Rep. 2018;44(2):43-48.

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Footnote 3

Stoltey JE, Cohen SE. Syphilis transmission: A review of the current evidence. Sexual health. 2015;12(2):103-109.

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Footnote 4

Gjestland T. The oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the boeck-bruusgaard material. Acta Derm Venereol Suppl (Stockh). 1955;35(Suppl 34):3-368; Annex I-LVI.

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Footnote 5

Edwards S, Carne C. Oral sex and transmission of non-viral STIs. Sex Transm Infect. 1998;74(2):95-100.

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Footnote 6

Harter CA, Benirschke K. Fetal syphilis in the first trimester. American Journal of Obstetrics & Gynecology. 1976;124(7):705-711.

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Footnote 7

De Santis M, De Luca C, Mappa I, et al. Syphilis infection during pregnancy: Fetal risks and clinical management. Infect Dis Obstet Gynecol. 2012;2012.

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Footnote 8

Sanchez PJ, Wendel GD,Jr, Grimprel E, et al. Evaluation of molecular methodologies and rabbit infectivity testing for the diagnosis of congenital syphilis and neonatal central nervous system invasion by treponema pallidum. J Infect Dis. 1993;167(1):148-157.

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Footnote 9

Finelli L, Berman SM, Koumans EH, Levine WC. Congenital syphilis. Bull World Health Organ. 1998;76 Suppl 2:126-128.

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Footnote 10

Qin J, Yang T, Xiao S, Tan H, Feng T, Fu H. Reported estimates of adverse pregnancy outcomes among women with and without syphilis: A systematic review and meta-analysis. PLoS One. 2014;9(7):e102203.

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Footnote 11

Lumbiganon P, Piaggio G, Villar J, et al. The epidemiology of syphilis in pregnancy. Int J STD AIDS. 2002;13(7):486-494.

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Footnote 12

Karp G, Schlaeffer F, Jotkowitz A, Riesenberg K. Syphilis and HIV co-infection. Eur J Intern Med. 2009;20(1):9-13.

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Footnote 13

Zetola NM, Klausner JD. Syphilis and HIV infection: An update. Clinical Infectious Diseases. 2007;44(9):1222-1228.

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Footnote 14

Golden MR, Marra CM, Holmes KK. Update on syphilis: Resurgence of an old problem. JAMA. 2003;290(11):1510-1514. doi: 10.1001/jama.290.11.1510 [doi].

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