How to treat a patient with a reactive Fluorescent Treponemal Antibody Absorption (FTA-ABS) test and a non-reactive Rapid Plasma Reagin (RPR) test?

Management of Reactive FTA-ABS with Non-Reactive RPR

Treat this patient with benzathine penicillin G 2.4 million units IM once weekly for 3 weeks (total 7.2 million units) for presumed late latent syphilis, unless you can document adequate prior treatment. 1

Understanding This Serologic Pattern

This combination of reactive treponemal test (FTA-ABS) with non-reactive nontreponemal test (RPR) most commonly represents one of three scenarios:

• Late latent or tertiary syphilis where nontreponemal antibodies have waned over time, which is the most clinically important possibility 1
• Previously treated syphilis where the treponemal test remains positive for life but the RPR has appropriately declined 2
• False-positive treponemal test, though this is less likely with FTA-ABS compared to other treponemal tests 1

The key diagnostic challenge is that nontreponemal tests like RPR have significantly reduced sensitivity in late-stage disease, with sensitivity dropping to only 30.7-56.9% in previously treated syphilis and 47-76% in late latent/tertiary syphilis 3, 2. This means a negative RPR does NOT rule out active late syphilis. 2

Treatment Algorithm

Step 1: Review Treatment History

If documented adequate prior treatment exists:

• Review records to confirm appropriate penicillin regimen was given for the stage of syphilis diagnosed 2
• Verify that a fourfold decline in RPR titers occurred within 6-12 months after treatment 2
• If both conditions met, no additional treatment is needed 1

If treatment history is uncertain, inadequate, or absent:

• Proceed immediately to treatment for late latent syphilis 2
• Administer benzathine penicillin G 2.4 million units IM once weekly for 3 weeks 1

Step 2: Assess for Active Disease

Before or concurrent with treatment, evaluate for clinical signs that would change management:

Red flags requiring immediate reassessment:

• Neurologic symptoms (confusion, vision changes, hearing loss, cranial nerve palsies) 2
• Ocular symptoms (uveitis, optic neuritis) 2
• New chancre or mucocutaneous lesions 2
• Cardiovascular symptoms (aortic regurgitation, chest pain) 2

If any red flags present:

• Perform lumbar puncture for CSF examination to rule out neurosyphilis 2, 1
• CSF VDRL is diagnostic when reactive, though sensitivity is only 49-87% 4
• CSF leukocyte count >5 WBCs/mm³ is a sensitive indicator for neurosyphilis 1
• If neurosyphilis confirmed, switch to aqueous crystalline penicillin G 18-24 million units per day IV for 10-14 days 2

Step 3: HIV Testing

All patients with syphilis must be tested for HIV 2

• HIV-infected patients may have atypical serologic patterns 2, 1
• HIV-infected patients require more frequent monitoring (every 3 months instead of 6 months) 2
• Consider CSF examination for all HIV-infected persons with late-latent syphilis or syphilis of unknown duration 2

Follow-Up Recommendations

For newly diagnosed and treated late latent syphilis:

• Clinical follow-up is recommended, though serologic response may be minimal 1
• Many patients will remain "serofast" with persistent low-level RPR titers (<1:8) for life 2
• The serofast state does not represent treatment failure 2

Do not perform routine serologic follow-up if:

• Patient has documented prior adequate treatment 1
• No clinical signs or symptoms of active disease 2

Critical Pitfalls to Avoid

• Never rely on RPR alone to exclude late syphilis - the sensitivity is too low in late-stage disease 3, 2
• Never assume a reactive treponemal test alone means active infection - treponemal tests remain positive for life in most patients regardless of treatment 2
• Never compare titers between different test types (VDRL vs RPR) as they are not directly comparable 2, 1
• Never use treponemal tests to monitor treatment response - only nontreponemal tests (RPR/VDRL) should be used for this purpose 1
• Do not assume persistent low-titer RPR reactivity indicates treatment failure - this serofast state is common and expected 2

Special Considerations for Penicillin Allergy

If the patient has documented penicillin allergy:

• Penicillin desensitization is strongly preferred for late latent syphilis 2
• Doxycycline 100 mg orally twice daily for 14 days can be used for early syphilis only, but is not optimal for late latent disease 2