What is the treatment for a patient with a positive Rapid Plasma Reagin (RPR) test and a negative Fluorescent Treponemal Antibody Absorption (FTA-ABS) test?

Management of FTA-ABS Negative, RPR Positive Results

A positive RPR with a negative FTA-ABS test most likely represents a biological false positive reaction and does not require treatment for syphilis in most cases. 1

Understanding the Discordant Results

When faced with a positive nontreponemal test (RPR) and a negative treponemal test (FTA-ABS), it's important to understand the significance of this pattern:

• Nontreponemal tests (RPR/VDRL): Measure antibodies to cardiolipin, which can be elevated in syphilis but also in many other conditions
• Treponemal tests (FTA-ABS): More specific for syphilis as they detect antibodies against T. pallidum components

Interpretation Algorithm:

1. Confirm the results:

   • Repeat both tests to rule out laboratory error
   • Use the same testing method (especially for RPR) and preferably the same laboratory 1

2. Consider biological false positive (BFP) causes:

   • Acute causes: Recent vaccination, viral infections
   • Chronic causes: Autoimmune diseases, chronic infections, advanced age, pregnancy
   • BFPs typically have low titers (≤1:8), but can occasionally be higher

3. Evaluate RPR titer level:

   • Low titers (≤1:8): More likely to be BFP
   • High titers (≥1:16): Consider the possibility of early syphilis with delayed treponemal antibody development or false-negative treponemal test

4. Consider rare scenarios:

   • Early primary syphilis (before treponemal antibodies develop)
   • HIV co-infection (can cause atypical serologic patterns) 1, 2
   • FTA-negative syphilis (rare but documented) 2

Management Approach

For typical cases (low-titer RPR, negative FTA-ABS):

1. Do not treat for syphilis
2. Investigate for underlying conditions causing BFP
3. Consider repeat testing in 2-4 weeks if early syphilis is suspected

For high-titer RPR (≥1:16) with negative FTA-ABS:

1. Consider additional treponemal testing (TP-PA or other treponemal test)
2. If clinical suspicion for syphilis is high, consider:
   • Testing for HIV (may affect serologic patterns) 1
   • Performing direct detection methods if lesions are present
   • Immunoblot testing for T. pallidum-specific antigens may be helpful 2

For patients with neurological/otological symptoms:

Even with this serologic pattern, be cautious about attributing symptoms to syphilis. The predictive value of a positive FTA-ABS in otologic practice is only 22%, and the predictive value would be even lower with a negative FTA-ABS 3.

Important Caveats

• False-negative treponemal tests: While rare, they have been documented, especially in HIV-infected individuals 2
• Prozone phenomenon: Very high antibody titers can cause false-negative results; diluting the specimen may reveal reactivity
• Technical factors: Improper test performance or interpretation can affect results

Follow-up Recommendations

• If clinical suspicion for syphilis remains low and no treatment is given, consider repeating both tests in 2-4 weeks
• If underlying conditions causing BFP are identified, manage those appropriately
• Document the serologic pattern in the patient's record to avoid unnecessary future treatments

The guidelines emphasize that serologic tests must be interpreted in the clinical context, and that no single test can be used alone to diagnose or exclude syphilis 1.