Confirmatory Testing After a Positive RPR
After a positive Rapid Plasma Reagin (RPR) test, a treponemal test such as TP-PA (Treponema pallidum particle agglutination), FTA-ABS (fluorescent treponemal antibody-absorbed), or another treponemal immunoassay should be performed to confirm the diagnosis of syphilis. 1
Diagnostic Algorithm for Syphilis
Initial screening with RPR (non-treponemal test)
Confirmatory testing options (treponemal tests):
Important Considerations
- Treponemal tests detect antibodies specific to T. pallidum and remain positive for life in most patients, even after successful treatment 1
- Non-treponemal tests like RPR measure antibodies to cardiolipin and can be used to monitor treatment response 1
- False-positive RPR results are more common in:
- Women (0.27% vs 0.20% in men)
- Patients over 60 years (0.34% vs 0.25% in younger patients) 1
Alternative Testing Approach
Some laboratories use a reverse sequence algorithm:
- Start with a treponemal test
- If positive, follow with a non-treponemal test (RPR)
- If discordant results (treponemal reactive/non-treponemal nonreactive), perform a second treponemal test to rule out false positives 1
Special Situations
- Neurosyphilis evaluation: If late latent syphilis, CD4 count <350 cells/mm³ with high-titer VDRL (>1:32), or treatment failure is present, consider lumbar puncture with CSF-VDRL testing 1
- CSF testing: For suspected neurosyphilis, both VDRL and treponemal tests (TP-PA or FTA-ABS) may be performed on CSF 2, 3
- CSF-VDRL has high specificity but limited sensitivity for neurosyphilis 1
Follow-up Testing
After treatment, quantitative non-treponemal tests (RPR or VDRL) should be used to monitor response:
- Expected fourfold decline in titers within 6 months for primary/secondary syphilis
- Follow-up testing recommended at 3,6,9, and 12 months after treatment 1
Pitfalls to Avoid
- Do not rely solely on non-treponemal tests for diagnosis due to their limited sensitivity, especially in primary syphilis
- Treponemal tests can remain positive for life, so they cannot distinguish between current and past treated infections
- FTA-ABS, while highly sensitive, can occasionally give equivocal or false-negative results 4
- Failure to confirm a positive RPR with a treponemal test may lead to misdiagnosis and inappropriate treatment
Remember that proper diagnosis of syphilis requires correlation of laboratory findings with clinical presentation and history of exposure.