From the Research
A negative RPR test does not completely rule out syphilis, and additional testing with treponemal-specific tests such as FTA-ABS, TP-PA, or EIA/CIA should be performed if clinical suspicion remains. The RPR test has limitations in sensitivity, particularly in early primary syphilis, late latent syphilis, or treated syphilis, with false-negative results possible during the "window period" or in patients with very early infection or advanced disease 1. According to a study published in 2019, treponemal immunoassays demonstrated excellent sensitivity for secondary, early latent, and seropositive primary syphilis, but the sensitivity of FTA-ABS in primary syphilis was poor 2. Another study from 2013 found that the concordance rate between VDRL and AutoRPR was 67.5%, with 164 discrepant cases being VDRL reactive but AutoRPR negative, highlighting the potential for false-negative results with RPR testing 3. Therefore, if clinical suspicion for syphilis remains despite a negative RPR, additional testing should be performed to confirm or rule out the diagnosis.
Some key points to consider include:
- False-negative RPR results can occur during the "window period" or in patients with very early infection or advanced disease
- Treponemal-specific tests such as FTA-ABS, TP-PA, or EIA/CIA may detect infection when non-treponemal tests like RPR are negative
- Direct examination of lesion exudate by darkfield microscopy or PCR testing may be necessary for diagnosis in cases of suspected primary syphilis with negative serologic tests
- The prozone phenomenon can cause false-negative results in patients with high antibody titers
- Additional testing should be performed if clinical suspicion for syphilis remains despite a negative RPR, as the RPR test has limitations in sensitivity.
It is essential to consider the clinical presentation and medical history of the patient when interpreting the results of syphilis testing, as a negative RPR test does not completely rule out the diagnosis of syphilis 1, 2.