What are the recommended tests and treatment for tertiary syphilis?

Testing for Tertiary Syphilis

For tertiary syphilis, you must perform BOTH a nontreponemal test (VDRL or RPR) AND a treponemal test (FTA-ABS or TP-PA) together, because nontreponemal tests alone will miss approximately one-third to half of tertiary cases due to their markedly reduced sensitivity of only 47-64% in late-stage disease. 1

Critical Diagnostic Principle

• Never rely on a negative RPR or VDRL alone to exclude tertiary syphilis—approximately 36-53% of patients with true tertiary disease will have a negative nontreponemal test. 1
• Treponemal tests (FTA-ABS, TP-PA) remain highly sensitive and stay reactive for life in most patients, making them essential for detecting late-stage disease. 1

Recommended Testing Algorithm

Initial Serologic Testing

• Perform a nontreponemal test (VDRL or RPR) with quantitative reporting (e.g., 1:4,1:8,1:16). 2, 1
• Simultaneously perform a treponemal test (FTA-ABS or TP-PA). 1
• Both tests are required because using only one type is insufficient for diagnosis. 2

Test Interpretation

• Nontreponemal test titers should be reported quantitatively as they correlate with disease activity, though this correlation is weaker in tertiary disease than in early syphilis. 2, 1
• Do not use treponemal test titers to assess disease activity or treatment response—these remain positive regardless of cure and correlate poorly with disease activity. 2, 1
• A fourfold change in nontreponemal titer (two dilutions, e.g., 1:16 to 1:4) is necessary to demonstrate clinically significant change. 2

Clinical Manifestations to Assess

Cardiovascular Tertiary Syphilis

• Evaluate for aortitis, aortic aneurysm, and aortic regurgitation. 1

Neurosyphilis

• Assess for tabes dorsalis, general paresis, and meningovascular syphilis. 1
• Consider CSF examination, particularly in HIV-infected patients with suspected late-stage disease. 1, 3

Special Populations

HIV-Infected Patients

• HIV co-infection may cause atypical serologic results with unusually high, low, or fluctuating titers. 1
• CSF examination should be strongly considered for HIV-infected persons with suspected tertiary syphilis. 1, 3

Direct Detection Methods

• Darkfield examination and direct fluorescent antibody tests of lesion exudate or tissue are definitive methods for diagnosing early syphilis but are not applicable to tertiary disease where lesions are typically absent. 2

Follow-Up Testing Principles

• Sequential serologic tests must be performed using the same testing method (VDRL or VDRL, RPR or RPR), preferably by the same laboratory, to ensure comparable results. 2, 3
• Most patients with reactive treponemal tests will remain reactive for life regardless of treatment. 2
• Some patients may develop a "serofast reaction" where nontreponemal antibodies persist at low titers indefinitely despite adequate treatment. 2