Interpretation of Reactive RPR with Negative Treponema Pallidum Test
A reactive Rapid Plasma Reagin (RPR) test with a negative Treponema pallidum test most likely indicates a false-positive RPR result and does not represent true syphilis infection. 1
Understanding Syphilis Testing Algorithms
The diagnosis of syphilis typically involves a two-step approach:
Non-treponemal tests (RPR or VDRL):
- Detect antibodies to cardiolipin (not specific to T. pallidum)
- Used for screening and monitoring treatment response
- Can yield false-positive results in many conditions unrelated to syphilis 2
Treponemal tests (TP-PA, FTA-ABS, EIA, chemiluminescent immunoassay):
- Detect antibodies specific to T. pallidum
- More specific than non-treponemal tests
- Remain positive for life in most treated patients 1
Interpretation of Discordant Results
According to the CDC and Infectious Diseases Society of America guidelines, when a non-treponemal test (RPR) is positive but the treponemal test is negative, this pattern strongly suggests a false-positive RPR result 1.
The interpretation table from current guidelines clearly states:
| Non-Treponemal Result | Treponemal Result | Interpretation |
|---|---|---|
| Positive | Negative | Likely false-positive non-treponemal test |
Common Causes of False-Positive RPR Results
False-positive RPR results can occur in numerous medical conditions, including:
- Autoimmune disorders (systemic lupus erythematosus, antiphospholipid syndrome)
- Acute viral infections
- Chronic inflammatory conditions
- Pregnancy
- Advanced age
- Malignancies
- Intravenous drug use
- Laboratory error 1
Important Considerations
Prozone Phenomenon: In rare cases (0.06% of all samples, 0.5% of reactive samples), extremely high antibody titers can cause a false-negative RPR result due to the prozone effect 3. This is unlikely in your scenario since the RPR is already reactive.
Early Infection: Very early syphilis might occasionally present with a reactive RPR and negative treponemal test if tested during the seroconversion window. However, this is extremely rare, as treponemal tests typically become positive earlier than non-treponemal tests 1.
Test Sensitivity: The sensitivity of RPR varies by disease stage (50-92.7%), while treponemal tests have higher sensitivity (95-100%) 1. This further supports that a positive RPR with negative treponemal test is most likely a false positive.
Recommended Follow-up
For patients with this pattern of results:
- Clinical correlation is essential - assess for risk factors and clinical signs of syphilis
- Consider repeat testing in 2-4 weeks if clinical suspicion remains high
- Evaluate for other conditions that might cause false-positive RPR results
- No treatment for syphilis is indicated based on this pattern alone unless there are compelling clinical reasons 1
Pitfalls to Avoid
- Don't assume syphilis infection based solely on a reactive RPR without treponemal confirmation
- Don't initiate treatment for syphilis without confirmation when the treponemal test is negative
- Don't forget to investigate other causes of the patient's symptoms and the false-positive RPR
Remember that the specificity of treponemal tests is extremely high (95-100%), making a negative result a strong indicator against true syphilis infection when combined with clinical assessment 1.