What is the appropriate management for a patient with a Rapid Plasma Reagin (RPR) titer of 1:2 but a negative Treponema Pallidum Assay (TPA)?

Management of a Patient with RPR Titer 1:2 and Negative TPA

A low-titer RPR (1:2) with a negative treponemal test (TPA) represents a biological false positive result and does not indicate syphilis infection; no treatment for syphilis is required. 1, 2

Understanding Syphilis Diagnostic Testing

• Syphilis diagnosis requires both nontreponemal (RPR/VDRL) and treponemal (TPA/FTA-ABS) tests to be reactive, as recommended by the Centers for Disease Control and Prevention 1, 3
• Nontreponemal tests like RPR can yield biological false positive results in many medical conditions unrelated to syphilis 1
• When a nontreponemal test is positive but a treponemal test is negative, this is considered a biological false positive result, not syphilis 2, 3
• The traditional testing algorithm begins with an inexpensive nontreponemal test (RPR), then confirms reactive specimens with a more specific treponemal test 1

Biological False Positive RPR Results

• Biological false positive RPR results typically occur at low titers (≤1:8) 1
• Multiple conditions can cause biological false positive RPR results, including:
  • Autoimmune disorders (particularly SLE) 1
  • Viral infections (HIV, HCV, HBV) 1
  • Pregnancy 1
  • Advanced age (>60 years) 1
  • Malaria 1
  • Injection drug use 1

Clinical Approach

• No treatment for syphilis is indicated when the treponemal test is negative 2, 3
• Consider investigating for underlying conditions that may cause biological false positive RPR results 1
• Testing for autoimmune disorders, viral infections (HIV, HCV, HBV), and other inflammatory conditions may be warranted 1
• The specificity of RPR testing varies across studies but generally ranges from 95-98%, meaning false positives do occur 1

Follow-up Recommendations

• If clinical suspicion for syphilis remains high despite the negative treponemal test:
  • Consider repeat testing in 2-4 weeks to rule out very early primary syphilis (when treponemal tests may not yet be reactive) 2, 3
  • Consider alternative treponemal test methods if the initial test was an EIA or CIA 3
• If clinical suspicion is low, no further syphilis testing is needed 2

Pitfalls to Avoid

• Do not treat for syphilis based solely on a reactive nontreponemal test without treponemal confirmation 1, 2
• Do not confuse a low-titer biological false positive with the prozone phenomenon, which can cause false negative RPR results in high-titer samples 4
• Avoid comparing titers between different test types (e.g., VDRL vs. RPR) as they are not directly comparable 3
• Remember that some rapid point-of-care tests have poor sensitivity for low RPR titers (1:2 or lower), detecting only 7.6%-56.5% of such cases 5