What is the best way to diagnose secondary syphilis?

The diagnosis of secondary syphilis requires a health care provider with a strong index of suspicion. The cutaneous manifestations of secondary syphilis may mimic other skin diseases, including pityriasis rosea, psoriasis, erythema multiforme, pityriasis lichenoides et varioliformis acuta, and some drug reactions. It is a good rule of thumb to consider secondary syphilis in any patient having a generalized dermatitis with associated lymphadenopathy.

As with primary syphilis, the most specific tests are the demonstration of the spirochete either in a skin biopsy or on darkfield examination, which can be performed on either the secondary skin lesions or on aspirates from lymph nodes. In contrast to primary syphilis, serologic tests are almost invariably positive. The only exception is when there is a false-negative reaction due to a prozone phenomenon, which occurs in 1% to 2% of patients with secondary syphilis. The prozone phenomenon occurs when the titers are very high and can be eliminated by diluting the serum.

Hoang MP, High WA, Molberg KH: Secondary syphilis: a histologic and immunohistochemical evaluation, J Cutan Pathol 31:595–599, 2004.