Syphilis infection - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Syphilis is a common sexually transmitted infection. An estimated 6 million new infections occurred worldwide in 2016. Incidence of congenital, primary, and secondary syphilis is increasing.
Caused by the spirochetal bacterium Treponema pallidum, subspecies pallidum.
Clinical presentation is often asymptomatic, but can manifest in a number of ways.
A painless ulcer (chancre) in the anogenital region is a hallmark of primary infection.
Diagnosis is usually straightforward after clinical exam and serologic tests.

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History & Exam
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Definition

Epidemiology

Etiology

Pathophysiology

Images

Electron micrograph of Treponema pallidum on cultures of cotton-tail rabbit epithelium cells
A primary vulvar syphilitic chancre due to Treponema pallidum bacteria
A penile chancre located on the proximal penile shaft: primary syphilitic infection
Gummatous lesions on the dorsal surface of the left hand
Secondary syphilitic papulosquamous rash on the torso and upper body
Secondary syphilitic lesions on the face
Secondary syphilis presenting pigmented macules and papules on the skin
Secondary syphilitic lesions of vagina
This was a case of congenital syphilis resulting in the death of this newborn infant
This newborn presented with symptoms of congenital syphilis that included lesions on the soles of both feet
Interstitial keratitis
Peg-shaped, notched central incisors (Hutchinson teeth)
Osteoperiostitis of the tibia ("saber shins")
Clutton joints

Citations

Key Articles

Stoltey JE, Cohen SE. Syphilis transmission: a review of the current evidence. Sex Health. 2015 Apr;12(2):103-9.[Abstract][Full Text]
British Association for Sexual Health and HIV (BASHH). UK national guidelines on the management of syphilis. December 2015 [internet publication].[Full Text]
World Health Organization. Guidelines for the treatment of Treponema pallidum (syphilis). 2016 [internet publication].[Full Text]
Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.[Abstract][Full Text]
Stoltey JE, Cohen SE. Syphilis transmission: a review of the current evidence. Sex Health. 2015 Apr;12(2):103-9.[Abstract][Full Text]
World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women. 2017 [internet publication]. [Full Text]
World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women. 2017 [internet publication]. [Full Text]
World Health Organization. Guidelines for the treatment of Treponema pallidum (syphilis). 2016 [internet publication].[Full Text]
World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women. 2017 [internet publication]. [Full Text]

Referenced Articles

1. Stoltey JE, Cohen SE. Syphilis transmission: a review of the current evidence. Sex Health. 2015 Apr;12(2):103-9.[Abstract][Full Text]
2. Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005 Jan;18(1):205-16.[Abstract][Full Text]
3. Newman L, Kamb M, Hawkes S, et al. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data. PLoS Med. 2013;10(2):e1001396.[Abstract][Full Text]
4. British Association for Sexual Health and HIV (BASHH). UK national guidelines on the management of syphilis. December 2015 [internet publication].[Full Text]
5. Goh BT. Syphilis in adults. Sex Transm Infect. 2005 Dec;81(6):448-52.[Abstract][Full Text]
6. O'Byrne P, MacPherson P. Syphilis. BMJ. 2019 Jun 28;365:l4159. [Erratum in: Syphilis. BMJ. 2019 Jul 19;366:l4746.] [Abstract][Full Text]
7. World Health Organization. Guidelines for the treatment of Treponema pallidum (syphilis). 2016 [internet publication].[Full Text]
8. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.[Abstract][Full Text]
9. Ghanem KG, Ram S, Rice PA. The modern epidemic of syphilis. N Engl J Med. 2020 Feb 27;382(9):845-54.[Abstract]
10. British Association for Sexual Health and HIV (BASHH). UK national guidelines on the management of syphilis. December 2015 [internet publication].[Full Text]
11. World Health Organization. Report on global sexually transmitted infection surveillance, 2018. 2018 [internet publication].[Full Text]
12. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance, 2021. Apr 2023 [internet publication].[Abstract][Full Text]
13. Edmondson DG, Hu B, Norris SJ. Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. mBio. 2018 Jun 26;9(3).[Abstract][Full Text]
14. Lee V, Kinghorn G. Syphilis: an update. Clin Med (Lond). 2008 Jun;8(3):330-3.[Abstract][Full Text]
15. Stoltey JE, Cohen SE. Syphilis transmission: a review of the current evidence. Sex Health. 2015 Apr;12(2):103-9.[Abstract][Full Text]
16. Centers for Disease Control and Prevention. Transmission of primary and secondary syphilis by oral sex - Chicago, Illinois, 1998-2002. MMWR Morb Mortal Wkly Rep. 2004 Oct 22;53(41):966-8.[Abstract][Full Text]
17. French P. Syphilis. BMJ. 2007 Jan 20;334(7585):143-7.[Abstract]
18. Ropper AH. Neurosyphilis. N Engl J Med. 2019 Oct 3;381(14):1358-63.[Abstract]
19. Clark EG, Danbolt N. The Oslo study of the natural course of untreated syphilis. Med Clin North Am. 1964;48:613-21.
20. Chaudhary PM, Roninson IB. Activation of MDR1 (P-glycoprotein) gene expression in human cells by protein kinase C agonists. Oncol Res. 1992;4(7):281-90.[Abstract]
21. Peterman TA, Heffelfinger JD, Swint EB, et al. The changing epidemiology of syphilis. Sex Transm Dis. 2005 Oct;32(10 suppl):S4-10.[Abstract]
22. Centers for Disease Control and Prevention. Outbreak of syphilis among men who have sex with men - Southern California, 2000. MMWR Morb Mortal Wkly Rep. 2001 Feb 23;50(7):117-20.[Abstract]
23. Janier M, Unemo M, Dupin N, et al. 2020 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol. 2021 Mar;35(3):574-88.[Abstract]
24. Keuning MW, Kamp GA, Schonenberg-Meinema D, et al. Congenital syphilis, the great imitator-case report and review. Lancet Infect Dis. 2020 Jul;20(7):e173-9.[Abstract]
25. Saloojee H, Velaphi S, Goga Y, et al. The prevention and management of congenital syphilis: an overview and recommendations. Bull World Health Organ. 2004 Jun;82(6):424-30.[Abstract][Full Text]
26. National Institute for Health and Care Excellence. Recommendations on reducing sexually transmitted infections. Jun 2022 [internet publication].[Full Text]
27. Holmes KK, Levine R, Weaver M. Effectiveness of condoms in preventing sexually transmitted infections. Bull World Health Organ. 2004 Jun;82(6):454-61.[Abstract]
28. Tobian AA, Serwadda D, Quinn TC, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009 Mar 26;360(13):1298-309.[Abstract][Full Text]
29. US Preventive Services Task Force. Syphilis infection in pregnant women: screening. Sept 2018 [internet publication].[Full Text]
30. Molina JM, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018 Mar;18(3):308-17.[Abstract][Full Text]
31. Brown DL, Frank JE. Diagnosis and management of syphilis. Am Fam Physician. 2003 Jul 15;68(2):283-90.[Abstract]
32. Rompalo AM, Lawlor J, Seaman P, et al. Modification of syphilitic genital ulcer manifestations by coexistent HIV infection. Sex Transm Dis. 2001 Aug;28(8):448-54.[Abstract][Full Text]
33. Lafond RE, Lukehart SA. Biological basis for syphilis. Clin Microbiol Rev. 2006 Jan;19(1):29-49.[Abstract][Full Text]
34. Tucker JD, Li JZ, Robbins GK, et al. Ocular syphilis among HIV-infected patients: a systematic analysis of the literature. Sex Trans Infect. 2011 Feb;87(1):4-8.[Abstract]
35. Rottingen JA, Cameron DW, Garnett GP. A systematic review of the epidemiologic interactions between classic sexually transmitted diseases and HIV: how much is really known? Sex Transm Dis. 2001 Oct;28(10):579-97.[Abstract]
36. Centers for Disease Control and Prevention. Sexually transmitted disease (STDs): syphilis & MSM fact sheet. 22 July 2021 [internet publication].[Full Text]
37. Fojaco RM, Hensley GT, Moskowitz L. Congenital syphilis and necrotizing funisitis. JAMA. 1989 Mar 24-31;261(12):1788-90.[Abstract]
38. Hammerschlag MR, Guillén CD. Medical and legal implications of testing for sexually transmitted infections in children. Clin Microbiol Rev. 2010 Jul;23(3):493-506.[Abstract][Full Text]
39. Wheeler HL, Agarwal S, Goh BT. Dark ground microscopy and treponemal serological tests in the diagnosis of early syphilis. Sex Transm Infect. 2004 Oct;80(5):411-4.[Abstract]
40. Centers for Disease Control and Prevention. Sexually transmitted diseases: syphilis. CDC fact sheet (detailed). 10 August 2021 [internet publication].[Full Text]
41. Centers for Disease Control and Prevention (CDC). Discordant results from reverse sequence syphilis screening - five laboratories, United States, 2006-2010. MMWR Morb Mortal Wkly Rep. 2011 Feb 11;60(5):133-7.[Abstract][Full Text]
42. Park IU, Fakile YF, Chow JM, et al. Performance of treponemal tests for the diagnosis of syphilis. Clin Infect Dis. 2019 Mar 5;68(6):913-18.[Abstract][Full Text]
43. Pope V. Use of treponemal tests to screen for syphilis. Infect Med. 2004;21:399-402.
44. Seña AC, Wolff M, Behets F, et al. Rate of decline in nontreponemal antibody titers and seroreversion after treatment of early syphilis. Sex Transm Dis. 2017 Jan;44(1):6-10.[Abstract][Full Text]
45. US Food and Drug Administration. Possible false RPR reactivity with BioPlex 2200 Syphilis Total & RPR test kit following a COVID-19 vaccine - letter to clinical laboratory staff and health care providers. Dec 2021 [internet publication].[Full Text]
46. Smith G, Holman RP. The prozone phenomenon with syphilis and HIV-1 co-infection. South Med J. 2004 Apr;97(4):379-82.[Abstract]
47. Kingston AA, Vujevich J, Shapiro M, et al. Seronegative secondary syphilis in 2 patients coinfected with human immunodeficiency virus. Arch Dermatol. 2005 Apr;141(4):431-3.[Abstract]
48. British Association for Sexual Health and HIV (BASHH). BASHH national guideline on the management of sexually transmitted infections and related conditions in children and young people 2021. 2021 [internet publication].[Full Text]
49. Lam TK, Lau HY, Lee YP, et al. Comparative evaluation of the INNO-LIA syphilis score and the MarDx Treponema pallidum immunoglobulin G Marblot test assays for the serological diagnosis of syphilis. Int J STD AIDS. 2010 Feb;21(2):110-3.[Abstract]
50. Hagedorn HJ, Kraminer-Hagedorn A, de Bosschere K, et al. Evaluation of INNO-LIA syphilis assay as a confirmatory test for syphilis. J Clin Microbiol. 2002 Mar;40(3):973-8.[Abstract][Full Text]
51. Gayet-Ageron A, Lautenschlager S, Ninet B, et al. Sensitivity, specificity and likelihood ratios of PCR in the diagnosis of syphilis: a systematic review and meta-analysis. Sex Transm Infect. 2013 May;89(3):251-6.[Abstract]
52. Gayet-Ageron A, Sednaoui P, Lautenschlager S, et al. Use of Treponema pallidum PCR in testing of ulcers for diagnosis of primary syphilis. Emerg Infect Dis. 2015 Jan;21(1):127-9.[Abstract][Full Text]
53. Shahrook S, Mori R, Ochirbat T, et al. Strategies of testing for syphilis during pregnancy. Cochrane Database Syst Rev. 2014 Oct 29;(10):CD010385.[Abstract][Full Text]
54. Pan American Health Organization (PAHO). Guidance on syphilis testing in Latin America and the Caribbean: improving uptake, interpretation, and quality of testing in different clinical settings. 2015. 2015 [internet publication].[Full Text]
55. Luger AF, Schmidt BL, Kaulich M. Significance of laboratory findings for the diagnosis of neurosyphilis. Int J STD AIDS. 2000 Apr;11(4):224-34.[Abstract]
56. Lavi R, Yarnitsky D, Rowe JM, et al. Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial. Neurology. 2006 Oct 24;67(8):1492-4.[Abstract]
57. Arendt K, Demaerschalk BM, Wingerchuk DM, et al. Atraumatic lumbar puncture needles: after all these years, are we still missing the point? Neurologist. 2009 Jan;15(1):17-20.[Abstract]
58. Nath S, Koziarz A, Badhiwala JH, et al. Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet. 2018 Mar 24;391(10126):1197-204.[Abstract]
59. Rochwerg B, Almenawer SA, Siemieniuk RAC, et al. Atraumatic (pencil-point) versus conventional needles for lumbar puncture: a clinical practice guideline. BMJ. 2018 May 22;361:k1920.[Abstract][Full Text]
60. Ahmed SV, Jayawarna C, Jude E. Post lumbar puncture headache: diagnosis and management. Postgrad Med J. 2006 Nov;82(973):713-6.[Abstract][Full Text]
61. Arevalo-Rodriguez I, Ciapponi A, Roqué i Figuls M, et al. Posture and fluids for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2016 Mar 7;(3):CD009199.[Abstract][Full Text]
62. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 752: prenatal and perinatal human immunodeficiency virus testing. Obstet Gynecol. 2018 Sep;132(3):e138-42.[Abstract][Full Text]
63. National Institute for Health and Care Excellence (UK). Antenatal care. 19 August 2021 [internet publication].[Full Text]
64. Simundic AM, Bölenius K, Cadamuro J, et al. Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Clin Chem Lab Med. 2018;56(12):2015-38.[Abstract]
65. Hollier LM, Harstad TW, Sanchez PJ, et al. Fetal syphilis: clinical and laboratory characteristics. Obstet Gynecol. 2001 Jun;97(6):947-53.[Abstract]
66. Ropper AH. Neurosyphilis. N Engl J Med. 2019 Oct 3;381(14):1358-63.[Abstract]
67. Arnesen L, Serruya S, Duran P. Gestational syphilis and stillbirth in the Americas: a systematic review and meta-analysis. Rev Panam Salud Publica. 2015 Jun;37(6):422-9.[Abstract][Full Text]
68. Cole M, Perry K. MHRA 04109: ten syphilis EIAs. UK: HSMO; 2004.
69. Creegan L, Bauer HM, Samuel MC, et al. An evaluation of the relative sensitivities of the venereal disease research laboratory test and the Treponema Pallidum particle agglutination test among patients diagnosed with primary syphilis. Sex Transm Dis. 2007 Dec;34(12):1016-18.[Abstract]
70. Manavi K, Young H, McMillan A. The sensitivity of syphilis assays in detecting different stages of early syphilis. Int J STD AIDS. 2006 Nov;17(11):768-71.[Abstract]
71. Cantor A, Nelson HD, Daeges M, et al. Screening for syphilis in nonpregnant adolescents and adults: systematic review to update the 2004 US Preventive Services Task Force recommendation [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Jun. Report No: 14-05213-EF-1.[Abstract][Full Text]
72. Lewis DA. Chancroid: clinical manifestations, diagnosis, and management. Sex Transm Infect. 2003 Feb;79(1):68-71.[Abstract][Full Text]
73. Patterson K, Olsen B, Thomas C, et al. Development of a rapid immunodiagnostic test for Haemophilus ducreyi. J Clin Microbiol. 2002 Oct;40(10):3694-702.[Abstract][Full Text]
74. US Preventive Services Task Force. Syphilis infection in nonpregnant adults and adolescents: screening. Sep 2022 [internet publication][Full Text]
75. World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women. 2017 [internet publication]. [Full Text]
76. World Health Organization. Screening donated blood for transfusion-transmissible infections: recommendations. 2009 [internet publication].[Abstract][Full Text]
77. Tucker JD, Bu J, Brown LB, et al. Accelerating worldwide syphilis screening through rapid testing: a systematic review. Lancet Infect Dis. 2010 Jun;10(6):381-6.[Abstract]
78. World Health Organization. The use of rapid syphilis tests. 2006 [internet publication].[Full Text]
79. Young H. Guidelines for serological testing for syphilis. Sex Transm Infect. 2000 Oct;76(5):403-5.[Abstract]
80. Centers for Disease Control and Prevention. Recommendations for partner services programs for HIV infection, syphilis, gonorrhea, and chlamydial infection. MMWR Recomm Rep. 2008 Nov 7;57(RR-9):1-83;quiz CE1-4.[Abstract][Full Text]
81. World Health Organization. WHO guideline on self-care interventions for health and well-being, 2022 revision. Jun 2022 [internet publication].[Full Text]
82. Lin JS, Eder ML, Bean SI. Screening for syphilis infection in pregnant women: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018 Sep 4;320(9):918-25. [Abstract][Full Text]
83. World Health Organization, Department of Reproductive Health and Research. The global elimination of congenital syphilis: rationale and strategy for action. 2007 [internet publication].[Full Text]
84. Menezes EV, Yakoob MY, Soomro T, et al. Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy. BMC Pregnancy Childbirth. 2009 May 7;9(suppl 1):S4.[Abstract][Full Text]
85. Hawkes SJ, Gomez GB, Broutet N. Early antenatal care: does it make a difference to outcomes of pregnancy associated with syphilis? A systematic review and meta-analysis. PLoS One. 2013;8(2):e56713.[Abstract][Full Text]
86. Blencowe H, Cousens S, Kamb M, et al. Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality. BMC Public Health. 2011 Apr 13;11(suppl 3):S9.[Abstract][Full Text]
87. Chen XS, Peeling RW, Yin YP, Mabey D. Improving antenatal care to prevent adverse pregnancy outcomes caused by syphilis. Future Microbiol. 2011 Oct;6(10):1131-4.[Abstract]
88. Hawkes S, Matin N, Broutet N, et al. Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis. Lancet Infect Dis. 2011 Sep;11(9):684-91.[Abstract]
89. Munkhuu B, Liabsuetrakul T, Chongsuvivatwong V, et al. One-stop service for antenatal syphilis screening and prevention of congenital syphilis in Ulaanbaatar, Mongolia: a cluster randomized trial. Sex Transm Dis. 2009 Nov;36(11):714-20.[Abstract]
90. World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women. 2017 [internet publication]. [Full Text]
91. Stoner BP. Current controversies in the management of adult syphilis. Clin Infect Dis. 2007 Apr 1;44(suppl 3):S130-46.[Abstract][Full Text]
92. Parkes R, Renton A, Meheus A, et al. Review of current evidence and comparison for effective syphilis treatment in Europe. Int J STD AIDS. 2004 Feb;15(2):73-88.[Abstract]
93. Hook EW 3rd, Martin DH, Stephens J, et al. A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis. 2002 Aug;29(8):486-90.[Abstract]
94. Riedner G, Rusizoka M, Todd J, et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med. 2005 Sep 22;353(12):1236-44.[Abstract][Full Text]
95. Lukehart SA, Godornes C, Molini BJ, et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med. 2004 Jul 8;351(2):154-8.[Abstract][Full Text]
96. World Health Organization. Guidelines for the treatment of Treponema pallidum (syphilis). 2016 [internet publication].[Full Text]
97. Ansotegui IJ, Melioli G, Canonica GW, et al. IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper. World Allergy Organ J. 2020 Feb;13(2):100080.[Abstract][Full Text]
98. Chastain DB, Hutzley VJ, Parekh J, et al. Antimicrobial desensitization: a review of published protocols. Pharmacy (Basel). 2019 Aug 9;7(3):112.[Abstract][Full Text]
99. World Health Organization. WHO guideline on syphilis screening and treatment for pregnant women. 2017 [internet publication]. [Full Text]
100. Walker GJ, Walker D, Molano Franco D, et al. Antibiotic treatment for newborns with congenital syphilis. Cochrane Database Syst Rev. 2019 Feb 15;(2):CD012071.[Abstract][Full Text]
101. Liang Z, Chen YP, Yang CS, et al. Meta-analysis of ceftriaxone compared with penicillin for the treatment of syphilis. Int J Antimicrob Agents. 2016 Jan;47(1):6-11.[Abstract]
102. Liu HY, Han Y, Chen XS, et al. Comparison of efficacy of treatments for early syphilis: A systematic review and network meta-analysis of randomized controlled trials and observational studies. PLoS One. 2017 Jun 28;12(6):e0180001.[Abstract][Full Text]
103. Faculty of Sexual and Reproductive Healthcare. Barrier methods for contraception and STI prevention. August 2015 [internet publication].[Full Text]
104. Ng BE, Butler LM, Horvath T, et al. Population-based biomedical sexually transmitted infection control interventions for reducing HIV infection. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD001220.[Abstract][Full Text]
105. de Walque D, Dow WH, Nathan R, et al. Incentivising safe sex: a randomised trial of conditional cash transfers for HIV and sexually transmitted infection prevention in rural Tanzania. BMJ Open. 2012 Feb 8;2(1):e000747.[Abstract][Full Text]
106. British Association for Sexual Health and HIV (BASHH). BASHH National Guideline on the Management of Sexually Transmitted Infections and Related Conditions in Children and Young People 2021. 2021 [internet publication].[Full Text]