Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients
- Charles B Hicks, MD
Charles B Hicks, MD
- University of California, San Diego
- Meredith Clement, MD
Meredith Clement, MD
- Division of Infectious Diseases
- Duke University Medical Center
Syphilis is an infection caused by the bacterium Treponema pallidum. Most new cases of syphilis are sexually acquired. The clinical manifestations depend upon the stage of disease. Studies performed in the pre-antibiotic era permit a relatively complete understanding of the natural history of untreated syphilis. Information about the natural history of untreated syphilis in humans derives from data collected from several sources:
●In the late 19th century, a Norwegian physician described the evolution of infection in more than 1400 patients with primary and secondary syphilis. Because he believed that the available therapies at the time were highly toxic and of little benefit, patients received no treatment .
●Additional data were collected from a study of 382 adults with syphilis who underwent autopsies between 1917 and 1941 . This compilation provided pathologic confirmation of the late manifestations of syphilis.
●Finally, the infamous Tuskegee study conducted between 1932 and 1972 collected data on 431 black men whose syphilis was untreated .
The epidemiology, pathogenesis, and clinical manifestations of syphilis will be reviewed here. Discussions of the diagnosis and treatment of syphilis, as well as syphilis in special populations are found elsewhere:
- Clark EG, Danbolt N. The Oslo study of the natural course of untreated syphilis: An epidemiologic investigation based on a re-study of the Boeck-Bruusgaard material. Med Clin North Am 1964; 48:613.
- Rosahn PD. Autopsy studies in syphilis. 649 Information supplement #21, J Venereal Disease; U.S. Public Health Service Venereal Disease Division, Washington, DC 1947.
- ROCKWELL DH, YOBS AR, MOORE MB Jr. THE TUSKEGEE STUDY OF UNTREATED SYPHILIS; THE 30TH YEAR OF OBSERVATION. Arch Intern Med 1964; 114:792.
- Schaudinn FR, Hoffmann E. Vorlaufiger bericht uber das vorkommen von spirochaeten in syphilitischen krakheitsproducten und bei papillomen. Arbeiten aus dem K gesundheitsamte 1905; 22:527.
- Musher DM. Biology of Treponema pallidum. In: Sexually Transmitted Diseases, Holmes KK, Mardh PA, Sparling PF, et al (Eds), McGraw-Hill, New York 1990. p.205.
- Larsen SA. Syphilis. Clin Lab Med 1989; 9:545.
- Centers for Disease Control and Prevention. STD Surveillance case definitions. http://www.cdc.gov/std/stats/CaseDefinitions-2014.pdf (Accessed on March 21, 2014).
- Centers for Disease Control and Prevention (CDC). Primary and secondary syphilis--United States, 1998. MMWR Morb Mortal Wkly Rep 1999; 48:873.
- Mitka M. US effort to eliminate syphilis moving forward. JAMA 2000; 283:1555.
- Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2014. Atlanta: U.S. Department of Health and Human Services; 2015 http://www.cdc.gov/std/stats14/surv-2014-print.pdf (Accessed on November 23, 2015).
- Patton ME, Su JR, Nelson R, et al. Primary and secondary syphilis--United States, 2005-2013. MMWR Morb Mortal Wkly Rep 2014; 63:402.
- Wong W, Chaw JK, Kent CK, Klausner JD. Risk factors for early syphilis among gay and bisexual men seen in an STD clinic: San Francisco, 2002-2003. Sex Transm Dis 2005; 32:458.
- Landovitz RJ, Tseng CH, Weissman M, et al. Epidemiology, sexual risk behavior, and HIV prevention practices of men who have sex with men using GRINDR in Los Angeles, California. J Urban Health 2013; 90:729.
- Bowen V, Su J, Torrone E, et al. Increase in incidence of congenital syphilis - United States, 2012-2014. MMWR Morb Mortal Wkly Rep 2015; 64:1241.
- Global incidence and prevalence of selected curable sexually transmitted infections – 2008. Geneva:World Health Organization; 2012 http://www.who.int/reproductivehealth/publications/rtis/stisestimates/en/ (Accessed on November 23, 2015).
- World Health Organization. Report on global sexually transmitted infection surveillance 2013 http://apps.who.int/iris/bitstream/10665/112922/1/9789241507400_eng.pdf?ua=1 (Accessed on November 23, 2015).
- Gong XD, et al. Syphilis in China from 2000 to 2013: epidemiological trends and characterists. Chin J Dermatol 2014; 47:310.
- Hook EW 3rd, Marra CM. Acquired syphilis in adults. N Engl J Med 1992; 326:1060.
- Centers for Disease Control and Prevention (CDC). Transmission of primary and secondary syphilis by oral sex--Chicago, Illinois, 1998-2002. MMWR Morb Mortal Wkly Rep 2004; 53:966.
- Pathela P, Braunstein SL, Blank S, et al. The high risk of an HIV diagnosis following a diagnosis of syphilis: a population-level analysis of New York City men. Clin Infect Dis 2015; 61:281.
- MAGNUSON HJ, THOMAS EW, OLANSKY S, et al. Inoculation syphilis in human volunteers. Medicine (Baltimore) 1956; 35:33.
- French P. Syphilis. BMJ 2007; 334:143.
- Baker-Zander S, Sell S. A histopathologic and immunologic study of the course of syphilis in the experimentally infected rabbit. Demonstration of long-lasting cellular immunity. Am J Pathol 1980; 101:387.
- Salazar JC, Cruz AR, Pope CD, et al. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis 2007; 195:879.
- Wicher, K, et al. Immunopathology of syphilis. In: Pathogenesis and Immunology of Treponemal Infection, Schell, RF, et al (Eds), Marcel Dekker, New York, NY 1983. p.61.
- Sparling PF. Natural history of syphilis. In: Sexually Transmitted Diseases, Holmes KK, Mardh PA, Sparling PF, et al (Eds), McGraw-Hill, New York 1990. p.213.
- Musher D. Early syphilis. In: Sexually Transmitted Diseases, Holmes KK, Sparling PF, Mardh PA (Eds), McGraw-Hill, New York 1999. p.479.
- Chapel TA. The signs and symptoms of secondary syphilis. Sex Transm Dis 1980; 7:161.
- Pleimes M, Hartschuh W, Kutzner H, et al. Malignant syphilis with ocular involvement and organism-depleted lesions. Clin Infect Dis 2009; 48:83.
- D'Amico R, Zalusky R. A case of lues maligna in a patient with acquired immunodeficiency syndrome (AIDS). Scand J Infect Dis 2005; 37:697.
- Young MF, Sanowski RA, Manne RA. Syphilitic hepatitis. J Clin Gastroenterol 1992; 15:174.
- Reginato AJ. Syphilitic arthritis and osteitis. Rheum Dis Clin North Am 1993; 19:379.
- Hunte W, al-Ghraoui F, Cohen RJ. Secondary syphilis and the nephrotic syndrome. J Am Soc Nephrol 1993; 3:1351.
- Balba GP, Kumar PN, James AN, et al. Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. Am J Med 2006; 119:448.e21.
- Westeneng AC, Rothova A, de Boer JH, de Groot-Mijnes JD. Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. Am J Ophthalmol 2007; 144:781.
- Durnian JM, Naylor G, Saeed AM. Ocular syphilis: the return of an old acquaintance. Eye (Lond) 2004; 18:440.
- Kennedy JL, Barnard JJ, Prahlow JA. Syphilitic coronary artery ostial stenosis resulting in acute myocardial infarction and death. Cardiology 2006; 105:25.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 10-1998. A 46-year-old man with chest pain and coronary ostial stenosis. N Engl J Med 1998; 338:897.
- Early local infection
- Late infection
- STAGES OF DISEASE
- CLINICAL MANIFESTATIONS
- Early syphilis
- - Primary syphilis (chancre)
- - Secondary syphilis
- Generalized symptoms
- Dermatologic findings
- Gastrointestinal findings
- Musculoskeletal abnormalities
- Renal abnormalities
- - Neurologic/ocular findings
- Late syphilis
- - Tertiary syphilis
- Gummatous syphilis
- - Central nervous system
- LATENT SYPHILIS (ASYMPTOMATIC)
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS