Syphilis Testing: What to Order
Order both a nontreponemal test (RPR or VDRL) AND a treponemal test (FTA-ABS, TP-PA, or treponemal EIA/CLIA) for complete syphilis diagnosis, as a single test type is insufficient for accurate diagnosis. 1, 2, 3
Initial Screening Algorithm
Standard Two-Test Approach
- Begin with a nontreponemal test (RPR or VDRL) as the initial screening test, followed by treponemal confirmation if positive 1, 3
- Alternatively, some laboratories use the reverse sequence algorithm: start with a treponemal EIA/CLIA, then confirm with quantitative nontreponemal testing 1
- Both approaches are valid; the key is that both test types must ultimately be performed for complete diagnosis 2, 3
Quantitative Reporting is Essential
- Always request quantitative titers for nontreponemal tests (e.g., 1:4,1:16,1:64), not just "positive/negative" 1, 2
- Quantitative titers are critical for monitoring disease activity and treatment response 1, 4
Understanding What Each Test Tells You
Nontreponemal Tests (RPR/VDRL)
- Measure disease activity and correlate directly with active infection 1, 2, 4
- Become negative or low-titer after successful treatment in most patients 2, 4
- Use for monitoring treatment response - a fourfold decline in titer indicates successful treatment 1, 2, 4
- Sensitivity varies by stage: 62-78% in primary, 97-100% in secondary, 85-100% in early latent, 61-75% in late latent 4
Treponemal Tests (FTA-ABS, TP-PA, EIA/CLIA)
- Confirm true syphilis infection versus biological false-positive nontreponemal results 2, 3
- Remain positive for life in 75-85% of patients regardless of treatment 1, 2, 4
- Never use for monitoring treatment response - they correlate poorly with disease activity 1, 2, 4
- Sensitivity: FTA-ABS 82-91%, Treponemal EIA/CLIA 92-100% 2
Special Considerations for Your Patient Context
Liver Enzyme Elevations
- Syphilitic hepatitis occurs in 30-39% of patients with early syphilis and should be considered in the differential diagnosis 5, 6
- Liver involvement is associated with high RPR titers (≥1:64) 5
- Syphilitic hepatitis is defined by: elevated liver enzymes + positive syphilis serology + no alternative cause + improvement with antibiotic therapy 7
Anemia Considerations
- While anemia is not a classic manifestation of syphilis, secondary syphilis can present with systemic symptoms 2
- The combination of liver enzyme elevations and anemia warrants comprehensive evaluation including HIV testing 2, 5
Additional Testing Based on Clinical Scenario
HIV Testing is Mandatory
- Test all patients with syphilis for HIV infection 2, 4
- HIV-infected patients may have atypical serologic responses (unusually high, low, or fluctuating titers) 1, 2, 4
- HIV coinfection affects monitoring frequency and neurosyphilis risk 2, 4
When to Consider CSF Examination
- Neurologic symptoms (headache, vision changes, hearing loss, confusion) 2
- Ocular symptoms 2
- Late latent syphilis in HIV-infected patients 2
- Serum RPR titer >1:32 with CD4 count <350 cells/mm³ 2
Critical Pitfalls to Avoid
Testing Errors
- Never rely on a single test type - both nontreponemal and treponemal tests are required 2, 3
- Never use treponemal tests to monitor treatment - they remain positive regardless of cure 1, 2, 4
- Never compare titers between different test methods (VDRL vs RPR) - they are not directly interchangeable 1, 2
- Always use the same test method from the same laboratory for serial monitoring 1, 2
Interpretation Errors
- A positive RPR alone can be a false positive (0.6-1.3% of general population) - confirm with treponemal testing 2
- False positives occur with autoimmune diseases, pregnancy, HIV, hepatitis B/C, IV drug use, and advanced age 2
- In very early primary syphilis, both tests can be negative - consider darkfield microscopy if lesions present 3, 4