What does a negative RPR (Rapid Plasma Reagin) but positive Treponema pallidum (T. pallidum) and syphilis antibody test result indicate and how is it treated?

Diagnosis and Treatment of Latent Syphilis with Negative RPR but Positive Treponemal Tests

A negative RPR but positive T. pallidum and syphilis antibody tests indicates late latent syphilis or previously treated syphilis that requires treatment with benzathine penicillin G if not previously adequately treated.

Understanding Your Test Results

Your test results show a pattern known as "serodiscordance" or "reverse serology" where:

• RPR (Rapid Plasma Reagin) is negative
• T. pallidum antibody test is reactive
• Syphilis antibody test is reactive

This pattern typically indicates one of the following scenarios:

1. Late latent syphilis: The sensitivity of RPR for late latent syphilis ranges from 61-75% 1, meaning that up to 39% of people with late latent syphilis may have a negative RPR.

2. Previously treated syphilis: Treponemal tests (T. pallidum and syphilis antibody) typically remain positive for life after infection, even after successful treatment 1.

3. Very early primary syphilis: In rare cases, treponemal tests may become positive before the RPR, though this is uncommon 2.

Diagnostic Algorithm

1. Review medical history:

   • Previous syphilis diagnosis and treatment
   • Risk factors for syphilis exposure
   • Any symptoms consistent with syphilis (even if resolved)

2. Clinical evaluation:

   • If no documented history of adequately treated syphilis exists, you should be presumed to have late latent syphilis

3. Additional testing considerations:

   • If there's uncertainty, a repeat RPR test may be warranted
   • In some cases, PCR testing of any suspicious lesions can be helpful 2
   • IgM testing may help determine if the infection is active 3

Treatment Recommendations

For presumed late latent syphilis (or syphilis of unknown duration):

• Standard treatment: Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1, 4
• Penicillin allergy: Doxycycline 100 mg orally twice daily for 28 days (though penicillin is strongly preferred)

Special Considerations

HIV Status

• If you are HIV-positive, the same treatment regimen applies, but closer follow-up may be needed 1
• HIV infection can sometimes cause atypical serologic patterns 1

Follow-up Testing

• Repeat serologic testing (RPR) at 6,12, and 24 months is recommended
• Since your RPR is already negative, monitoring for a rise in titer would be important to detect reinfection

Common Pitfalls to Avoid

1. Misinterpreting as a false positive: When treponemal tests are positive but RPR is negative, this is often incorrectly dismissed as a false positive. This pattern actually represents either late latent syphilis or previously treated infection 1.

2. Relying solely on RPR: Using only nontreponemal tests like RPR for screening can miss up to 39% of late latent syphilis cases 1.

3. Assuming no treatment is needed: Without documented adequate prior treatment, a person with positive treponemal tests should receive full treatment for late latent syphilis 1.

4. Missing neurosyphilis: If you have any neurological symptoms, a lumbar puncture should be performed to rule out neurosyphilis 1.

The discordant pattern of negative RPR with positive treponemal tests is increasingly common with the reverse sequence screening algorithm used by many laboratories today 1. This pattern requires careful interpretation and, in the absence of documented adequate treatment, should prompt treatment for late latent syphilis to prevent potential progression to tertiary syphilis.