From the Guidelines
A positive syphilis screen with negative RPR suggests a possible false positive screening test, past treated syphilis, very early infection, or late/latent syphilis. The recommended approach is to confirm with a treponemal test like TP-PA or FTA-ABS if not already done 1. If confirmation testing is positive, treat for late latent syphilis with benzathine penicillin G 2.4 million units IM weekly for 3 weeks. If confirmation is negative, no treatment is needed as this represents a false positive screen. For patients with HIV or neurological symptoms, consider CSF examination to rule out neurosyphilis 2. This pattern occurs because screening tests detect antibodies that remain positive for life after infection, while RPR measures active disease and can become negative after successful treatment. Follow-up testing with repeat RPR in 2-4 weeks may be helpful in early infection cases where the RPR hasn't yet become positive. Document all test results and treatment in the patient's record, as the screening test will likely remain positive for life even after appropriate treatment.
Some key points to consider:
- False-positive results can occur, especially in patients with certain medical conditions or who are taking certain medications 3.
- The sensitivity and specificity of screening tests can vary, and confirmatory testing is essential to rule out false positives 4.
- Patients with HIV or neurological symptoms require special consideration, as they may be at higher risk for neurosyphilis 5.
- Treatment guidelines recommend benzathine penicillin G for late latent syphilis, and alternative antibiotics may be considered in patients with penicillin allergies 6.
- Screening intervals and follow-up testing are crucial to ensure that patients receive appropriate treatment and to monitor for potential complications 7.
From the Research
Positive Syphilis Screen with Negative RPR
- A positive syphilis screen with a negative RPR (Rapid Plasma Reagin) test result can occur in some cases, and the treatment approach may vary depending on the stage of the disease and other factors 8, 9, 10, 11, 12.
- Studies have compared the effectiveness of doxycycline versus benzathine penicillin in treating early syphilis, with some showing similar serological response rates between the two treatments 9, 10, 11.
- However, one study found that patients with latent or indeterminate syphilis treated with doxycycline had a higher rate of serofast (a condition where the RPR test remains positive despite treatment) compared to those treated with penicillin 8.
- Another study found that a combination of single-dose benzathine penicillin G plus doxycycline resulted in higher serologic responses compared to single-dose benzathine penicillin G alone in people with HIV 12.
- The treatment approach for a positive syphilis screen with a negative RPR test result should be individualized, taking into account the patient's medical history, stage of the disease, and other factors, and may involve consultation with a healthcare professional 8, 9, 10, 11, 12.
Treatment Options
- Doxycycline is a recommended second-line treatment for syphilis, especially in cases where penicillin is not feasible 8, 9, 10, 11.
- Benzathine penicillin G is the preferred treatment for early syphilis, but doxycycline may be used as an alternative in certain cases 9, 10, 11.
- The combination of single-dose benzathine penicillin G plus doxycycline may be considered in certain cases, such as in people with HIV 12.