From the Guidelines
A positive syphilis screen with negative confirmatory testing likely represents a false positive result, and no treatment is needed in this scenario unless there is high clinical suspicion for early syphilis. This pattern typically occurs with treponemal screening tests (like EIA or CIA) followed by negative non-treponemal tests (RPR or VDRL) 1. The discrepancy may be due to previous treated syphilis, very early infection, or cross-reactivity from other conditions like autoimmune diseases, pregnancy, or other spirochetal infections.
Key Considerations
- If early syphilis is suspected based on symptoms or recent exposure, repeat testing in 2-4 weeks is recommended.
- For high-risk patients with concerning exposures, some clinicians may consider empiric treatment with Benzathine penicillin G 2.4 million units IM once while awaiting repeat testing.
- Always obtain a thorough sexual history and consider HIV testing, as co-infection is common, especially in patients with neurosyphilis, where diagnosis depends on various combinations of reactive serologic test results, abnormalities of cerebrospinal fluid (CSF) cell count or protein, or a reactive VDRL-CSF with or without clinical manifestations 1.
Documentation and Follow-up
- Document the false positive result in the patient's chart to avoid unnecessary future treatment, but ensure appropriate follow-up if the patient has risk factors for syphilis.
- Consider CSF examination before treatment of HIV-infected persons with early syphilis, with follow-up CSF examination following treatment in persons with initial abnormalities, as some specialists recommend intensified therapy when CNS syphilis is suspected in these persons 1.
From the Research
Positive Syphilis Screen with Negative Results
- A positive syphilis screen with negative results for other tests can occur due to various reasons, including the type of testing algorithm used 2.
- The reverse algorithm, which involves screening with a treponemal assay first, can increase disease detection but may also lead to an increase in false-positive test results 2.
- In some cases, a positive treponemal test may not be confirmed by a nontreponemal test, resulting in a negative result 3.
- The positive predictive value for syphilis associated with an isolated unconfirmed reactive treponemal chemiluminescence assay or enzyme immunoassay is low if the epidemiological risk and clinical probability for syphilis are low 3.
Interpretation of Test Results
- The interpretation of test results depends on various factors, including the type of test used, the stage of the disease, and the patient's clinical presentation 4, 5.
- A single dose of benzathine penicillin G is the recommended treatment for early syphilis, and treatment response is typically assessed based on serology 4, 5.
- In some cases, patients may remain seropositive after treatment, a condition known as the "serofast state" 5.
Clinical Implications
- A positive syphilis screen with negative results for other tests may require further evaluation and testing to confirm the diagnosis 2, 3.
- Clinicians should consider the patient's clinical presentation, epidemiological risk, and laboratory results when interpreting test results and making treatment decisions 4, 5, 3.
- The management of syphilis requires a comprehensive approach, including diagnosis, treatment, and follow-up care 6, 4, 5, 3.