How is secondary syphilis diagnosed?

As with primary syphilis, the most specific test is dark-field microscopy. Special stains on skin biopsies are diagnostic as well. More often, screening tests for syphilis such as nontreponemal serologic tests are utilized, usually a rapid plasma reagin (RPR) or a Venereal Disease Research Laboratory (VDRL) test is ordered. Nontreponemal serologic tests for syphilis detect antibodies to reagin, a cholesterol-lecithin-cardiolipin antigen that cross-reacts with antibodies present in the sera of patients with syphilis. These antibodies are not specific for syphilis and should always be confirmed by a specific test for syphilis, usually a fluorescent treponemal antibody–absorption (FTA-ABS) or the microhemagglutination–T. pallidum (MHA-TP) test. Nontreponemal serologic tests for syphilis are positive in almost all cases of secondary syphilis. Adequate treatment causes the titer to decline to low titers or nonreactivity.

Domantay-Apostol GP, Handog EB, Gabriel MT: Syphilis: the international challenge of the great imitator, Dermatol Clin 26:191– 202, 2008.