Reexamining Syphilis: An Update on Epidemiology, Clinical Manifestations, and Management

Molly E Kent, PharmD; Frank Romanelli, PharmD MPH BCPS


The Annals of Pharmacotherapy. 2008;42(2):226-236. 

In This Article

Abstract and Introduction


Objective: To review the epidemiology, clinical features, diagnosis, and treatment of syphilis.
Data Sources: Studies and reviews were abstracted from MEDLINE (1950-April 2007) using the search term syphilis. All papers were cross-referenced to identify additional studies and reviews for inclusion.
Study Selection and Data Extraction: Pertinent original research articles, review articles, and book chapters were evaluated.
Data Synthesis: Syphilis is a spirochetal disease that has plagued mankind for centuries. Following a low incidence of syphilis in the US for the last 2 decades, rates are now increasing both in the US and other parts of the world. Once acquired, syphilis can pass through 4 distinct stages of disease: primary syphilis, secondary syphilis, latent syphilis, and tertiary syphilis, with each stage being characterized by different symptoms and levels of infectivity. Diagnosis is made primarily by serologic assays with nontreponemal tests such as the Venereal Disease Research Laboratory and the Rapid Plasma Reagin assay used for screening. Treponemal tests including the Treponema pallidum particle agglutination and the fluorescent treponemal antibody absorption test are then used for confirmation. Recommended treatment regimens are based largely on uncontrolled trials and clinical experience. Penicillin is the treatment of choice, with the preparation and treatment duration varying for different stages. Benzathine penicillin is the treatment of choice for all stages of syphilis except neurosyphilis, for which aqueous crystalline penicillin or procaine penicillin is used due to the central nervous system penetration of these formulations. Coinfection with both syphilis and HIV occurs frequently due to common risk factors. These 2 diseases interact with each other, making both diagnosis and treatment more complicated.
Conclusions: Clinicians should be aware of the signs and symptoms of syphilis as well as current guidelines for the management and treatment of this disease.


Syphilis, the "great imitator" of skin diseases, has been mankind's continuous companion for centuries. The exact origin of syphilis is unknown, but 2 main theories predominate.[1] The New World theory hypothesizes that syphilis was endemic to the Caribbean and brought to Europe by Columbus following his first voyage in 1492. The Old World theory suggests that syphilis was endemic to central Africa and arrived in Europe prior to the voyage of Columbus.[2] The discovery of penicillin in the mid-20th century brought with it the ability to cure syphilis. Since its introduction, penicillin has greatly aided in controlling the spread of syphilis, and the disease has remained relatively uncommon.[3] The Global Community, however, has been unable to eradicate this disease and it not only remains with mankind today, but its incidence is rapidly increasing in many parts of the world.[3,4,5,6,7]


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