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

Natural History

Limited data are available regarding the natural course of untreated syphilis.[28,29,30,31,32,33] Two prospective and one retrospective study comprise the bulk of information on this subject, and the information provided by these studies is limited due to design flaws. The Oslo Study was a prospective natural history study that followed 1978 patients with primary or secondary syphilis from 1891 to 1951 and found a mortality rate of 17% for males and 8% for females.[28,29] Eventually, 28% of patients developed clinically evident complications of late disease including cardiovascular syphilis (10%), symptomatic neurosyphilis (6.5%), or late benign syphilis (16%), with both cardiovascular and neurosyphilis occurring more commonly in males. On autopsy, evidence of cardiovascular syphilis was found more frequently.

From 1932 to 1962, the Tuskegee study prospectively monitored 412 African American men with syphilis and compared them with 204 uninfected, matched controls.[31] Initial findings revealed that after 15 years of infection, approximately 75% of the men had clinically evident syphilitic complications of the cardiovascular system, central nervous system, and joints, which was fourfold greater than in age-matched, noninfected controls.[33] Mortality 20 years into the study was 40% in the syphilis group and 27% in the control group.[30] This study has been highly criticized for exploiting a vulnerable patient population. Available penicillin treatment was not offered to patients and written informed consent was not obtained.[2]

Lastly, Rosahn[32] conducted a review of 3907 autopsies performed at Yale between 1917 and 1941 and found that approximately 10% (n = 380) of these patients had clinical, serological, or autopsy evidence of syphilis. Of these patients, syphilis was the primary cause of death in 58%. Late complications of syphilis evident at autopsy included cardiovascular (83%), neurological (8%), and gummas (9%). Additionally, fewer patients with syphilis lived beyond the age of 70 years compared with those who were disease free.

In summary, approximately one-third of patients with untreated syphilis may develop late complications of the disease, with these occurring more frequently in men than in women.[1,2] Syphilitic lesions or pathophysiologic evidence of the disease may appear before clinical symptoms become apparent. Increased mortality and decreased longevity appear to accompany infection with syphilis.


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