How do I treat a patient with a negative Rapid Plasma Reagin (RPR) test but a positive Treponema test?

Management of Patients with Negative RPR but Positive Treponema Test

Patients with negative RPR but positive treponemal tests should be treated according to their most likely stage of syphilis, with benzathine penicillin G being the treatment of choice in most cases. 1

Understanding the Discordant Results

When a patient presents with a negative non-treponemal test (RPR) but a positive treponemal test, this pattern suggests one of the following scenarios:

• Very early primary syphilis (before RPR becomes positive)
• Previously treated syphilis
• Late-stage syphilis
• False-positive treponemal test (less common)

According to the CDC guidelines, this discordant pattern requires careful clinical interpretation 1.

Diagnostic Approach

1. Review patient history:

   • Previous syphilis treatment
   • Risk factors for syphilis
   • Clinical symptoms consistent with any stage of syphilis

2. Additional testing:

   • Consider repeat RPR testing to rule out prozone phenomenon (false-negative due to high antibody titers)
   • If clinical suspicion is high, additional diagnostic procedures may be necessary 1

Treatment Algorithm

Based on the most recent guidelines from the CDC 1:

1. If evidence suggests previously treated syphilis:

   • No treatment is necessary if adequate documentation of prior treatment exists
   • Monitor clinically

2. If untreated syphilis is suspected:

   • Early syphilis (primary, secondary, early latent): Benzathine penicillin G 2.4 million units IM as a single dose
   • Late latent or unknown duration syphilis: Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks
   • If neurosyphilis is suspected: Aqueous crystalline penicillin G 18-24 million units IV daily for 10-14 days

3. For penicillin-allergic patients:

   • Doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis)
   • For pregnant patients or those with neurosyphilis, desensitization to penicillin is recommended 1

Special Considerations

HIV Co-infection

• HIV-infected patients may have atypical serologic responses
• Treatment regimens are the same as for HIV-negative patients 2, 1
• More careful follow-up is essential for HIV-infected patients 2

Neurosyphilis Evaluation

• Consider CSF examination if:
  • Neurologic symptoms are present
  • CD4 count <350 cells/mm³ with high-titer VDRL (>1:32)
  • Treatment failure occurs 1

Follow-up Recommendations

• Clinical and serological evaluation at 3,6,9,12, and 24 months after therapy 1
• For patients with negative RPR but positive treponemal tests, follow-up should focus on:
  • Development of clinical symptoms
  • Conversion to RPR positivity (which would indicate active infection)
  • Response to treatment if administered

Common Pitfalls to Avoid

1. Misinterpreting the discordant results: A negative RPR with positive treponemal test does not rule out syphilis
2. Failing to consider the prozone phenomenon: High antibody levels can cause false-negative RPR results
3. Inadequate follow-up: Patients require careful monitoring, especially if treatment is initiated
4. Missing neurosyphilis: Consider CSF examination in high-risk patients or those with neurological symptoms

The management of discordant syphilis serology requires careful clinical judgment and appropriate staging to guide treatment decisions. When in doubt, treating according to the suspected stage of infection is the safest approach to prevent progression and complications.