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


Following clinical suspicion of syphilis, laboratory confirmation can be obtained via direct detection of T. pallidum or via serology testing ( Table 1 ).[1,2,13,22,23,24,44,45,46,47,48,49,50]T. pallidum cannot be cultured. Serologic testing that includes nontreponemal tests and treponemal tests is considered the standard detection method in the US for primary, secondary, latent, and tertiary syphilis.[22] Nontreponemal tests are initially used to test or screen patients for syphilis and include the Venereal Disease Research Laboratory (VDRL) and the Rapid Plasma Reagin (RPR) tests.[22] Due to the rate of false-positive results from nontreponemal tests, all positive results should be confirmed with a treponemal-specific test such as the T. pallidum particle agglutination or the fluorescent treponemal antibody absorption test. In addition to the tests mentioned, the diagnosis of neurosyphilis is based on clinical symptoms and CSF analysis. The CDC recommends a lumbar puncture for patients with neurologic or ophthalmic disease, syphilis that has failed initial treatment, symptomatic tertiary syphilis, and HIV disease plus late latent syphilis or syphilis of unknown duration.[24] Some experts also recommend obtaining a lumbar puncture in all patients with latent syphilis whose nontreponemal titers are greater than or equal to 1:32 or in patients with HIV whose CD4+ cell count is less than 350 cells/mm3.[24] Abnormalities in CSF consistent with syphilis usually include an elevated leukocyte count with predominate lymphocytes and elevated protein.


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