American Journal of Clinical Dermatology

, Volume 7, Issue 5, pp 291–304 | Cite as

Cutaneous Manifestations of Syphilis

Recognition and Management
  • Stephan Lautenschlager
Therapy in Practice


After a marked decline in the number of syphilis cases in the context of AIDS prevention campaigns, a significant increase has been observed in states of the former Soviet Union since 1994. In recent years, outbreaks have also been reported in the US, Canada, and several European countries. The current epidemic in the US and in different parts of Europe has largely involved men who have sex with men, many of whom are infected with HIV. Since a misdiagnosis of syphilis can have serious consequences for the patient and also for pregnancies and newborns, clinicians should be aware of the many manifestations of syphilis and difficulties in the diagnosis and management of the disease. Younger clinicians in particular are no longer familiar with the diverse clinical symptoms and the complex diagnostics of syphilis. Patients co-infected with HIV may present with atypical clinical manifestations and laboratory test results. Furthermore, through its association with an increased risk of HIV infection, syphilis has acquired a new potential for morbidity and mortality, and the diagnosis of syphilis should be routinely considered in patients with uveitis, sudden deafness, aortic thoracic aneurysm, or pregnancy.

Only a minority of syphilis infections are detected in the primary stage. This may be because of atypical locations and, occasionally, atypical morphology of the lesions; however, it may also be because of the difficulty of detecting the pathogen. In the secondary stage, which is clinically extremely diverse, the diagnosis is confirmed serologically. There is a need for increased awareness of the symptoms and signs of acute infections, together with a willingness to consider the diagnosis of syphilis in patients with vague symptoms. An increasing number of diagnostic tests (both specific and nonspecific) are now available. However, in the absence of clinical symptoms or in cases with a low titer or inconsistent test results, diagnosis of syphilis can be difficult or even impossible. Treatment and follow-up should follow current guidelines designed for the involved area.

In this article, the cutaneous manifestations of syphilis and their diagnostic and therapeutic management are described in detail.


Syphilis Congenital Syphilis Venereal Disease Research Laboratory Sudden Deafness Secondary Syphilis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author has received grants to conduct epidemiologic studies of sexually transmitted infection in Switzerland but has no conflicts of interest that are directly relevant to the contents of this article.


  1. 1.
    Golden MR, Marra CM, Holmes KK. Update on syphilis: resurgence of an old problem. JAMA. 2003; 290: 1510–4PubMedCrossRefGoogle Scholar
  2. 2.
    Hook III EW, Marra CM. Acquired syphilis in adults. N Engl J Med. 1992; 326: 1060–9PubMedCrossRefGoogle Scholar
  3. 3.
    Garnett GP, Aral SO, Hoyle DV, et al. The natural history of syphilis: implications for the transmission dynamics and control of infection. Sex Transm Dis. 1997; 24: 185–200PubMedCrossRefGoogle Scholar
  4. 4.
    Sanchez MR. Syphilis. In: Freedberg IM, Eisen AZ, Wolff K, et al., editors. Fitzpatrick’s dermatology in general medicine. New York: McGraw-Hill, 2003: 2163–88Google Scholar
  5. 5.
    van Duynhoven YT. The epidemiology of Neisseria gonorrhoeae in Europe. Microbes Infect. 1999; 1: 455–64PubMedCrossRefGoogle Scholar
  6. 6.
    US Centers for Disease Control and Prevention. Summary of notifiable diseases: United States, 2003. MMWR Moth Mortal Wkly Rep. 2005; 52: 1–85Google Scholar
  7. 7.
    Chesson HW, Dee TS, Aral SO. AIDS mortality may have contributed to the decline in syphilis rates in the United States in the 1990s. Sex Transm Dis. 2003; 30: 419–24PubMedCrossRefGoogle Scholar
  8. 8.
    Tichonova L, Borisenko K, Ward H, et al. Epidemics of syphilis in the Russian Federation: trends, origins, and priorities for control. Lancet. 1997; 350: 210–3PubMedCrossRefGoogle Scholar
  9. 9.
    US Centers for Disease Control and Prevention. Outbreak of syphilis among men who have sex with men: Southern California, 2000. MMWR Moth Mortal Wkly Rep. 2001; 50: 117–20Google Scholar
  10. 10.
    Nicoll A, Hamers FF. Are trends in HIV, gonorrhoea, and syphilis worsening in western Europe?. BMJ. 2002; 324: 1324–7PubMedCrossRefGoogle Scholar
  11. 11.
    Peterman TA, Heffelfinger JD, Swint EB, et al. The changing epidemiology of syphilis. Sex Transm Dis. 2005; 32: S4–10PubMedCrossRefGoogle Scholar
  12. 12.
    Fenton KA, Lowndes CM. Recent trends in the epidemiology of sexually transmitted infections in the European Union. Sex Transm Infect. 2004; 80: 255–63PubMedCrossRefGoogle Scholar
  13. 13.
    Tikhonova L, Salakhov E, Southwick K, et al. Congenital syphilis in the Russian Federation: magnitude, determinants, and consequences. Sex Transm Infect. 2003; 79: 106–10PubMedCrossRefGoogle Scholar
  14. 14.
    Masher DM. Early syphilis. In: Holmes KK, Sparling PF, Mardh P, et al., editors. Sexually transmitted diseases. New York: McGraw-Hill, 1999: 479–85Google Scholar
  15. 15.
    DiCarlo RP, Martin DH. The clinical diagnosis of genital ulcer disease in men. Clin Infect Dis. 1997; 25: 292–8PubMedCrossRefGoogle Scholar
  16. 16.
    Lynn WA, Lightman S. Syphilis and HIV: a dangerous combination. Lancet Infect Dis. 2004; 4: 456–66PubMedCrossRefGoogle Scholar
  17. 17.
    Lautenschlager S. Sexually transmitted infections in Switzerland: return of the classics. Dermatology. 2005; 210: 134–42PubMedCrossRefGoogle Scholar
  18. 18.
    Lacey HB, Higgins SP, Graham D. An outbreak of early syphilis: cases from North Manchester General Hospital. Sex Transm Infect. 2001; 77: 311–3PubMedCrossRefGoogle Scholar
  19. 19.
    Dourmishev LA, Dourmishev AL. Syphilis: uncommon presentations in adults. Clin Dermatol. 2005; 23: 555–64PubMedCrossRefGoogle Scholar
  20. 20.
    Hutchinson CM, Hook III EW, Shepherd M, et al. Altered clinical presentation of early syphilis in patients with human immunodeficiency virus infection. Ann Intern Med. 1994; 121: 94–100PubMedGoogle Scholar
  21. 21.
    Chapel TA, Prasad P, Chapel J, et al. Extragenital syphilitic chancres. J Am Acad Dermatol. 1985; 13: 582–4PubMedCrossRefGoogle Scholar
  22. 22.
    Schöfer H. Syphilis, Klinik der Treponema-pallidum-Infektion. Hautarzt. 2004; 55: 112–9PubMedCrossRefGoogle Scholar
  23. 23.
    Haustein UF, Pfeil B, Zschiesche A. Analyse der von 1983-1991 an der Universitäts-Hautklinik Leipzig beobachteten Syphilisfdlle. Hautarzt. 1993; 44: 23–9PubMedGoogle Scholar
  24. 24.
    Alam F, Argiriadou AS, Hodgson TA, et al. Primary syphilis remains a cause of oral ulceration. Br Dent J. 2000; 189: 352–4PubMedGoogle Scholar
  25. 25.
    Ashton M, Sopwith W, Clark P, et al. An outbreak no longer: factors contributing to the return of syphilis in Greater Manchester. Sex Transm Infect. 2003; 79: 291–3PubMedCrossRefGoogle Scholar
  26. 26.
    Arunkumar S, Prasad S, Loganathan B, et al. Extragenital chancre of the tongue. Int J STD AIDS. 1997; 8: 655–6PubMedCrossRefGoogle Scholar
  27. 27.
    Hourihan M, Wheeler H, Houghton R, et al. Lessons from the syphilis outbreak in homosexual men in east London. Sex Transm Infect. 2004; 80: 509–11PubMedCrossRefGoogle Scholar
  28. 28.
    Edwards S, Carne C. Oral sex and transmission of non-viral STIs. Sex Transm Infect. 1998; 74: 95–100PubMedCrossRefGoogle Scholar
  29. 29.
    Edwards S, Carne C. Oral sex and the transmission of viral STIs. Sex Transm Infect. 1998; 74: 6–10PubMedCrossRefGoogle Scholar
  30. 30.
    Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect. 1999; 75: 3–17PubMedCrossRefGoogle Scholar
  31. 31.
    Doherty L, Fenton KA, Jones J, et al. Syphilis: old problem, new strategy. BMJ. 2002; 325: 153–6PubMedCrossRefGoogle Scholar
  32. 32.
    US Centers for Disease Control and Prevention. Transmission of primary and secondary syphilis by oral sex: Chicago, Illinois, 1998-2002. MMWR Moth Mortal Wkly Rep. 2004; 53: 966–8Google Scholar
  33. 33.
    Bonci A, Di Lemia V, Lo Scocco G, et al. A patient with primary syphilis of the finger. Acta Derm Venereol. 2001; 81: 382–3PubMedCrossRefGoogle Scholar
  34. 34.
    de Koning GA, Blog FB, Stolz E. A patient with primary syphilis of the hand. Br J Vener Dis. 1977; 53: 386–8PubMedGoogle Scholar
  35. 35.
    Weber B. Fin Fall von syphilitischem Primäraffekt am Lid. Klin Monatsbl Augenheilkd. 1982; 180: 565–6PubMedCrossRefGoogle Scholar
  36. 36.
    Donofrio P. Unusual location of syphilitic chancre: case report. Genitourin Med. 1986; 62: 59–60PubMedGoogle Scholar
  37. 37.
    Lautenschlager S, Schwarzkopf S, Borelli S. Presternal indurated ulceration: primary syphilis. Dermatology. 2006; 212: 200–2PubMedCrossRefGoogle Scholar
  38. 38.
    Allison SD. Extragenital syphilitic chancres. J Am Acad Dermatol. 1986; 14: 1094–5PubMedCrossRefGoogle Scholar
  39. 39.
    Fournier A. Treatment and prophylaxis of syphilis. London: Rebman Limited, 1906Google Scholar
  40. 40.
    Hutchinson CM, Hook III EW. Syphilis in adults. Med Clin North Am. 1990; 74: 1389–416PubMedGoogle Scholar
  41. 41.
    Rompalo AM, Joesoef MR, O’Donnell JA, et al. Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study. Sex Transm Dis. 2001; 28: 158–65PubMedCrossRefGoogle Scholar
  42. 42.
    Martin DH, Mroczkowski TF. Dermatologic manifestations of sexually transmitted diseases other than HIV. Infect Dis Clin North Am. 1994; 8: 533–82PubMedGoogle Scholar
  43. 43.
    Friedli A, Chavaz P, Harms M. Alopecia syphilitica: report of two cases in Geneva. Dermatology. 2001; 202: 376–7PubMedCrossRefGoogle Scholar
  44. 44.
    Wenhai L, Jianzhong Z, Cao Y. Detection of Treponema pallidum in skin lesions of secondary syphilis and characterization of the inflammatory infiltrate. Dermatology. 2004; 208: 94–7PubMedCrossRefGoogle Scholar
  45. 45.
    Division of STD Prevention, US National Center for HIV, STD, and TB Prevention. Recommendations for public health surveillance of syphilis in the United States [online]. Atlanta (GA): Centers for Disease Control and Prevention, 2003. Available from URL: [Accessed 2006 Sep 13]Google Scholar
  46. 46.
    World Health Organization. Guidelines for the management of sexually transmitted infections [online]. Geneva: WHO, 2003. Available from URL: [Accessed 2006 Aug 10]Google Scholar
  47. 47.
    Zeltser R, Kurban AK. Syphilis. Clin Dermatol. 2004; 22: 461–8PubMedCrossRefGoogle Scholar
  48. 48.
    Sale RR, Deshpande SG, Dharmadhikari NJ, et al. Late cutaneous syphilis. Cutis. 1997; 59: 135–7Google Scholar
  49. 49.
    Löwhagen GB. Syphilis: test procedures and therapeutic strategies. Semin Dermalot. 1990; 9: 152–9Google Scholar
  50. 50.
    Cummings MC, Lukehart SA, Marra C, et al. Comparison of methods for the detection of Treponema pallidum in lesions of early syphilis. Sex Transm Dis. 1996; 23: 366–9PubMedCrossRefGoogle Scholar
  51. 51.
    Palmer HM, Higgins SP, Herring AJ, et al. Use of PCR in the diagnosis of early syphilis in the United Kingdom. Sex Transm Infect. 2003; 79: 479–83PubMedCrossRefGoogle Scholar
  52. 52.
    Wheeler HL, Agarwal S, Gob BT. Dark ground microscopy and treponemal serological tests in the diagnosis of early syphilis. Sex Transm Infect. 2004; 80: 411–4PubMedCrossRefGoogle Scholar
  53. 53.
    Rogstad KE, Simms I, Fenton KA, et al. Screening, diagnosis and management of early syphilis in genitourinary medicine clinics in the UK. Int J STD AIDS. 2005; 16: 348–52PubMedCrossRefGoogle Scholar
  54. 54.
    Liu H, Rodes B, Chen CY, et al. New tests for syphilis: rational design of a PCR method for detection of Treponema pallidum in clinical specimens using unique regions of the DNA polymerase I gene. J Clin Microbiol. 2001; 39: 1941–6PubMedCrossRefGoogle Scholar
  55. 55.
    Young H. Syphilis: serology. Dermatol Clin. 1998; 16: 691–8PubMedCrossRefGoogle Scholar
  56. 56.
    Gob BT, Voorst Vader PC. European guideline for the management of syphilis. Int J STD AIDS. 2001; 12 Suppl. 3: 14–26Google Scholar
  57. 57.
    Schöfer H, Brockmeyer NH, Hagedorn HJ, et al. Syphilis: Leitfnie der DSTDG zur Diagnostik and Therapie. Hautarzt. 2005; 56: 1084–100CrossRefGoogle Scholar
  58. 58.
    Rolfs RT, Joesoef MR, Hendershot EF, et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N Engl J Med. 1997 Jul 31; 337 (5): 307–14PubMedCrossRefGoogle Scholar
  59. 59.
    Young H. Guidelines for serological testing for syphilis. Sex Transm Infect. 2000; 76: 403–5PubMedCrossRefGoogle Scholar
  60. 60.
    US Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Morb Mortal Wkly Rep. 2006; 55 (No. RR-11): 1–100Google Scholar
  61. 61.
    Nandwani R, Evans DT. Are you sure it’s syphilis? A review of false positive serology. Int J STD AIDS. 1995; 6: 241–8PubMedGoogle Scholar
  62. 62.
    Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev. 1995; 8: 1–21PubMedGoogle Scholar
  63. 63.
    Kuznetsov AV, Burgdorf WH, Prinz JC. Latent syphilis confirmed by polymerase chain reaction in 2 HIV-positive patients with inconclusive serologic test results. Arch Dermatol. 2005; 141: 1169–70PubMedCrossRefGoogle Scholar
  64. 64.
    Smith G, Holman RP. The prozone phenomenon with syphilis and HIV-1 co-infection. South Med. 2004; 97: 379–82CrossRefGoogle Scholar
  65. 65.
    Taniguchi S, Osato K, Hamada T. The prozone phenomenon in secondary syphilis. Acta Derm Venereol. 1995; 75: 153–4PubMedGoogle Scholar
  66. 66.
    Egglestone SI, Turner AJ. Serological diagnosis of syphilis. PHLS Syphilis Serology Working Group. Commun Dis Public Health. 2000; 3: 158–62PubMedGoogle Scholar
  67. 67.
    Koff AB, Rosen T. Nonvenereal treponematoses: yaws, endemic syphilis, and pinta. J Am Acad Dermatol. 1993; 29: 519–35PubMedCrossRefGoogle Scholar
  68. 68.
    Marangoni A, Sambri V, Cavrini F, et al. Treponema denticola infection is not a cause of false positive Treponema pallidum serology. New Microbiol. 2005; 28: 215–21PubMedGoogle Scholar
  69. 69.
    Erbelding EJ, Vlahov D, Nelson KE, et al. Syphilis serology in human immunodeficiency virus infection: evidence for false-negative fluorescent treponemal testing. J Infect Dis. 1997; 176: 1397–400PubMedCrossRefGoogle Scholar
  70. 70.
    Schmidt BL. Evaluation of a new particle gel immunoassay for determination of antibodies against Treponema pallidum. J Clin Microbiol. 2004; 42: 2833–5PubMedCrossRefGoogle Scholar
  71. 71.
    Schmidt BL, Edjlalipour M, Luger A. Comparative evaluation of nine different enzyme-linked immunosorbent assays for determination of antibodies against Treponema pallidum in patients with primary syphilis. J Clin Microbiol. 2000 Mar; 38 (3): 1279–82PubMedGoogle Scholar
  72. 72.
    Schöfer H. Diagnostik and Behandlung der Syphilis: Leitlinien der DSTDG. MedReport. 2004; 28: 12Google Scholar
  73. 73.
    Backhouse JL, Nesteroff SI. Treponema pallidum western blot: comparison with the FTA-ABS test as a confirmatory test for syphilis. Diagn Microbiol Inf Dis. 2001 Jan; 39 (1): 9–14CrossRefGoogle Scholar
  74. 74.
    Goldmeier D, Hay P. A review and update on adult syphilis, with particular reference to its treatment. Int J STD AIDS. 1993; 4: 70–82PubMedGoogle Scholar
  75. 75.
    Hicks CB, Benson PM, Lupton GP, et al. Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus (HIV) with Kaposi sarcoma: a diagnostic dilemma. Ann Intern Med. 1987; 107: 492–5PubMedGoogle Scholar
  76. 76.
    Augenbraun M, Rolfs R, Johnson R, et al. Treponemal specific tests for the serodiagnosis of syphilis. Syphilis and HIV Study Group. Sex Transm Dis. 1998; 25: 549–52PubMedCrossRefGoogle Scholar
  77. 77.
    Haslett P, Laverty M. The prozone phenomenon in syphilis associated with HIV infection. Arch Intern Med. 1994; 154: 1643–4PubMedCrossRefGoogle Scholar
  78. 78.
    Malone JL, Wallace MR, Hendrick BB, et al. Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy. Am J Med. 1995; 99: 55–63PubMedCrossRefGoogle Scholar
  79. 79.
    Javier M, Chastang C, Spindler E, et al. A prospective study of the influence of HIV status on the seroreversion of serological tests for syphilis. Dermatology. 1999; 198: 362–9CrossRefGoogle Scholar
  80. 80.
    Rompalo AM, Cannon RO, Quinn TC, et al. Association of biologic false-positive reactions for syphilis with human immunodeficiency virus infection. J Infect Dis. 1992; 165: 1124–6PubMedCrossRefGoogle Scholar
  81. 81.
    National guideline for the management of early syphilis. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect. 1999 Aug; 75 Suppl. 1: S29–33Google Scholar
  82. 82.
    National guideline for the management of late syphilis. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect. 1999 Aug; 75 Suppl. 1: S34–7Google Scholar
  83. 83.
    Parkes R, Renton A, Meheus A, et al. Review of current evidence and comparison of guidelines for effective syphilis treatment in Europe. Int J STD AIDS. 2004; 15: 73–88PubMedCrossRefGoogle Scholar
  84. 84.
    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; 353: 1236–44PubMedCrossRefGoogle Scholar
  85. 85.
    Lukehart SA, Godomes C, Molini BJ, et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med. 2004; 351: 154–8PubMedCrossRefGoogle Scholar
  86. 86.
    Mitchell SJ, Engelman J, Kent CK, et al. Azithromycin-resistant syphilis infection: San Francisco (CA), 2000-2004. Clin Infect Dis. 2006; 42: 337–45PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Outpatient Clinic of DermatologyTriemli HospitalZurichSwitzerland

Personalised recommendations