Pathogenesis, clinical manifestations, and treatment of early syphilis
- Charles B Hicks, MD
Charles B Hicks, MD
- University of California, San Diego
- Duke University Medical Center
- P Frederick Sparling, MD
P Frederick Sparling, MD
- Professor of Medicine and Microbiology and Immunology
- University of North Carolina at Chapel Hill
Syphilis is a chronic infection caused by the bacterium Treponema pallidum. The manifestations of disease are notoriously protean, occurring in any one individual in different stages over time .
The epidemiology, pathogenesis, clinical manifestations, diagnosis, and therapy of early syphilis will be reviewed here. Late syphilis and the pathophysiology, natural history, and serologic diagnosis of syphilis are discussed separately. Syphilis in the HIV-infected patient is discussed elsewhere. (See "Pathogenesis, clinical manifestations, and treatment of late syphilis" and "Pathophysiology, transmission, and natural history of syphilis" and "Diagnostic testing for syphilis" and "Epidemiology, clinical presentation, and diagnosis of syphilis in the HIV-infected patient".)
Early syphilis — Early syphilis is defined as the stages of syphilis that typically occur within the first year after acquisition of the infection. These include primary, secondary, and early latent syphilis (see "Pathophysiology, transmission, and natural history of syphilis"). Central nervous system associated diseases (ie, neurosyphilis) can also occur within the first year after infection. (See "Neurosyphilis".)
Latent syphilis — Latent syphilis is characterized by asymptomatic infection with a normal physical examination in association with a positive serology. Latent syphilis is categorized as "early" or "late" depending upon the established date of infection. Early latent syphilis infers infection within one year. All other cases are referred to as late latent syphilis . (See "Pathophysiology, transmission, and natural history of syphilis", section on 'Latent syphilis'.)
The importance of correct classification is related to the risk of transmission and duration of treatment:
- Hook EW 3rd, Marra CM. Acquired syphilis in adults. N Engl J Med 1992; 326:1060.
- Centers for Disease Control and Prevention. STD Surveillance case definitions. http://www.cdc.gov/std/stats/CaseDefinitions-2014.pdf (Accessed on March 21, 2014).
- http://www.cdc.gov/std/treatment/2010/default.htm (Accessed on October 16, 2014).
- Peterman TA, Kahn RH, Ciesielski CA, et al. Misclassification of the stages of syphilis: implications for surveillance. Sex Transm Dis 2005; 32:144.
- Schachter J. Classification of latent syphilis: is it time to change the case definition? Sex Transm Dis 2005; 32:143.
- Hart G. Syphilis tests in diagnostic and therapeutic decision making. Ann Intern Med 1986; 104:368.
- 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.
- Patton ME, Su JR, Nelson R, et al. Primary and secondary syphilis--United States, 2005-2013. MMWR Morb Mortal Wkly Rep 2014; 63:402.
- Hook EW 3rd, Peeling RW. Syphilis control--a continuing challenge. N Engl J Med 2004; 351:122.
- Gong XD, et al. Syphilis in China from 2000 to 2013: epidemiological trends and characterists. Chin J Dermatol 2014; 47:310.
- Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009; 58:1.
- Centers for Disease Control and Prevention (CDC). Sexually transmitted disease surveillance - 2011. http://www.cdc.gov/std/stats11/Surv2011.pdf (Accessed on April 10, 2013).
- 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.
- Centers for Disease Control and Prevention (CDC). Congenital syphilis--United States, 2002. MMWR Morb Mortal Wkly Rep 2004; 53:716.
- 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.
- French P. Syphilis. BMJ 2007; 334:143.
- Musher D. Early syphilis. In: Sexually Transmitted Diseases, Holmes KK, Sparling PF, Mardh PA (Eds), McGraw-Hill, New York 1999. p.479.
- 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.
- Pleimes M, Hartschuh W, Kutzner H, et al. Malignant syphilis with ocular involvement and organism-depleted lesions. Clin Infect Dis 2009; 48:83.
- Chapel TA. The signs and symptoms of secondary syphilis. Sex Transm Dis 1980; 7:161.
- 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.
- 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.
- DiCarlo RP, Martin DH. The clinical diagnosis of genital ulcer disease in men. Clin Infect Dis 1997; 25:292.
- Mahoney JF, Arnold RC, Harris A. Penicillin Treatment of Early Syphilis-A Preliminary Report. Am J Public Health Nations Health 1943; 33:1387.
- Douglas JM Jr. Penicillin treatment of syphilis: clearing away the shadow on the land. JAMA 2009; 301:769.
- MAGNUSON HJ, THOMAS EW, OLANSKY S, et al. Inoculation syphilis in human volunteers. Medicine (Baltimore) 1956; 35:33.
- Drugs for sexually transmitted infections. Treat Guidel Med Lett 2004; 2:67.
- The Pink Sheet" F-D-C Reports, Chevy Chase, MD, December 6, 2004, p. 17.
- Centers for Disease Control and Prevention (CDC). Inadvertent use of Bicillin C-R to treat syphilis infection--Los Angeles, California, 1999-2004. MMWR Morb Mortal Wkly Rep 2005; 54:217.
- Gruber F, Kastelan M, Cabrijan L, et al. Treatment of early syphilis with azithromycin. J Chemother 2000; 12:240.
- 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.
- Hook EW 3rd, Behets F, Van Damme K, et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010; 201:1729.
- Bai ZG, Wang B, Yang K, Tian JH, Ma B, Liu Y, Jiang L, Gai QY, He X, LiY. Azithromycin versus penicillin G benzathine for early syphilis. Cochrane Database of Systematic Reviews 2012, Issue 6. Art No.: CD007270.
- Centers for Disease Control and Prevention (CDC). Azithromycin treatment failures in syphilis infections--San Francisco, California, 2002-2003. MMWR Morb Mortal Wkly Rep 2004; 53:197.
- Lukehart SA, Godornes C, Molini BJ, et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. N Engl J Med 2004; 351:154.
- Ballard RC, Berman SM, Fenton KA. Azithromycin versus penicillin for early syphilis. N Engl J Med 2006; 354:203.
- Martin IE, Gu W, Yang Y, Tsang RS. Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai, China. Clin Infect Dis 2009; 49:515.
- Van Damme K, Behets F, Ravelomanana N, et al. Evaluation of azithromycin resistance in Treponema pallidum specimens from Madagascar. Sex Transm Dis 2009; 36:775.
- Holmes KK. Azithromycin versus penicillin G benzathine for early syphilis. N Engl J Med 2005; 353:1291.
- Marra CM, Colina AP, Godornes C, et al. Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum. J Infect Dis 2006; 194:1771.
- Johnson RC, Bey RF, Wolgamot SJ. Comparison of the activities of ceftriaxone and penicillin G against experimentally induced syphilis in rabbits. Antimicrob Agents Chemother 1982; 21:984.
- Centers for Disease Control and Prevention (CDC). Outbreak of syphilis among men who have sex with men--Southern California, 2000. MMWR Morb Mortal Wkly Rep 2001; 50:117.
- 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; 337:307.
- Calonge N, U.S. Preventive Services Task Force. Screening for syphilis infection: recommendation statement. Ann Fam Med 2004; 2:362.
- Rekart ML, Patrick DM, Chakraborty B, et al. Targeted mass treatment for syphilis with oral azithromycin. Lancet 2003; 361:313.
- Early syphilis
- Latent syphilis
- Men who have sex with men
- HIV-infected patients
- Women and minority groups
- CLINICAL MANIFESTATIONS
- Incubating syphilis
- Primary syphilis
- Secondary syphilis
- - Rash
- - Systemic symptoms
- - Lymphadenopathy
- - Alopecia
- - Hepatitis
- - Gastrointestinal abnormalities
- - Musculoskeletal abnormalities
- - Renal abnormalities
- - Neurologic abnormalities
- - Ocular abnormalities
- DIFFERENTIAL DIAGNOSIS
- Benzathine penicillin G
- - Early syphilis
- - Early versus late latent syphilis
- - Jarisch-Herxheimer reaction
- Penicillin allergic patients
- - Tetracyclines
- - Macrolides
- - Ceftriaxone
- PATIENT MONITORING
- SCREENING AND PREVENTION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS