Diagnostic Testing for Tertiary Syphilis
For tertiary syphilis diagnosis, use both nontreponemal tests (VDRL or RPR) and treponemal tests (FTA-ABS or TP-PA) together, recognizing that nontreponemal tests have significantly reduced sensitivity (47-64%) in tertiary disease, making them unreliable when used alone. 1, 2
Understanding the Diagnostic Challenge in Tertiary Syphilis
Tertiary syphilis presents unique diagnostic challenges because the standard serologic approach becomes less reliable:
Nontreponemal tests (VDRL/RPR) have markedly reduced sensitivity in tertiary syphilis at only 47-64%, meaning approximately one-third to half of patients with true tertiary syphilis will have a negative RPR or VDRL 1, 2
Treponemal tests (FTA-ABS, TP-PA) remain highly sensitive and stay reactive for life in most patients, making them more reliable for detecting late-stage disease 3, 1
Using only one type of serologic test is insufficient for diagnosis because false-positive nontreponemal results can occur with various medical conditions, and the combination is required for accurate interpretation 3, 1
Recommended Diagnostic Algorithm
Initial Serologic Testing
Perform both a nontreponemal test (VDRL or RPR) AND a treponemal test (FTA-ABS or TP-PA) on all patients with suspected tertiary syphilis 3, 1
Report nontreponemal test results quantitatively (e.g., 1:4,1:8,1:16) as titers correlate with disease activity, though this correlation is weaker in tertiary disease 3
Direct Detection Methods
Darkfield examination and direct fluorescent antibody tests of lesion exudate or tissue are definitive methods for diagnosing syphilis when lesions are present, though these are more applicable to early syphilis 3, 1
For gummatous lesions in tertiary syphilis, consider biopsy with direct microscopy as an adjunct to serologic testing 3, 2
Clinical Manifestations to Assess
Tertiary syphilis can present with:
Cardiovascular abnormalities (aortitis, aortic aneurysm, aortic regurgitation) 3
Neurologic manifestations (tabes dorsalis, general paresis, meningovascular syphilis) 3
Ophthalmic and auditory abnormalities 3
Gummatous lesions (destructive granulomatous lesions in skin, bone, or viscera) 3
Critical Pitfalls to Avoid
Never rely on a negative nontreponemal test alone to exclude tertiary syphilis, as 36-53% of tertiary cases will be RPR/VDRL negative 1, 2
Do not use treponemal test titers to assess disease activity or treatment response, as these remain positive regardless of cure and correlate poorly with disease activity 3, 1
Do not compare titers between different nontreponemal test types (VDRL vs RPR), as RPR titers are often slightly higher than VDRL titers and cannot be directly compared 3, 1
Always use the same testing method from the same laboratory for sequential testing to accurately monitor any changes 3, 1
Special Considerations for HIV-Infected Patients
HIV-infected patients may have atypical serologic results with unusually high, low, or fluctuating titers 3, 2
Standard serologic tests remain accurate and reliable for most HIV patients, but consider additional testing methods (biopsy, direct microscopy) if results are discordant with clinical presentation 3, 2
CSF examination should be considered for HIV-infected persons with suspected late-stage syphilis 2
Interpretation of Common Serologic Patterns
Treponemal positive/Nontreponemal negative pattern commonly represents late latent or tertiary syphilis with waning nontreponemal antibodies, and warrants treatment as late latent syphilis 1, 2
Both tests positive with low nontreponemal titers (typically <1:8) suggests adequately treated past infection or late-stage disease requiring clinical correlation 1, 2