From the Research
A reactive RPR test with non-reactive treponemal antibody tests most likely represents a biological false positive RPR result rather than syphilis infection, and no treatment for syphilis is needed in this scenario unless there is strong clinical suspicion or known exposure. This interpretation is based on the understanding that RPR detects non-specific antibodies against cardiolipin rather than antibodies specifically against Treponema pallidum, leading to false positives in various conditions such as acute infections, autoimmune diseases, pregnancy, intravenous drug use, advanced age, or laboratory error 1.
The RPR titer in biological false positives is typically low (less than 1:8), though higher titers can occasionally occur in autoimmune conditions. If concerned about very early syphilis infection (before treponemal antibodies develop), repeat testing in 2-4 weeks may be warranted. For persistent unexplained reactive RPR results, evaluation for underlying autoimmune conditions might be appropriate, especially if other symptoms are present. It's also important to consider the prozone phenomenon, which can lead to a falsely nonreactive RPR assay result, especially in cases of high antibody titers, as noted in a study evaluating the frequency of this phenomenon in syphilis serology 2.
Key points to consider in the interpretation of these test results include:
- The sensitivity and specificity of the tests used, with treponemal tests generally being more specific but potentially less sensitive in very early infection 3.
- The clinical context, including symptoms and exposure history, which can guide the interpretation of serological results and the decision to treat or repeat testing.
- The potential for false-positive results with both nontreponemal and treponemal tests, and the need for confirmatory testing in many cases, as discussed in studies evaluating the performance of different testing algorithms 4, 5.
In practice, the approach to a reactive RPR with non-reactive treponemal tests should prioritize clinical assessment and consideration of the potential causes of false-positive results, rather than immediate treatment for syphilis, unless there are compelling clinical or epidemiological reasons to do so.