What is the priority blood work for a patient suspected of having syphilis?

Priority Blood Work for Suspected Syphilis

For patients suspected of having syphilis, the priority blood work should include both nontreponemal (RPR or VDRL) and treponemal tests, with the nontreponemal test typically performed first in the traditional algorithm. 1

Diagnostic Algorithm

Initial Testing

1. Nontreponemal test (first-line screening):

   • Rapid Plasma Reagin (RPR) or
   • Venereal Disease Research Laboratory (VDRL) test

2. Treponemal-specific test (confirmation if nontreponemal test is positive):

   • Fluorescent Treponemal Antibody Absorption (FTA-ABS)
   • T. pallidum Particle Agglutination (TP-PA)

Alternative Approach (Reverse Sequence)

Some laboratories use the reverse sequence algorithm:

1. Treponemal test first (screening)
2. Nontreponemal test (if treponemal test is positive)
3. Second treponemal test (if discordant results)

Test Performance by Stage of Disease

Primary Syphilis

• Nontreponemal tests have variable sensitivity:
  • RPR: 71-92.7% sensitivity 2
  • VDRL: 50-78.4% sensitivity 2
• False negatives are common in early primary syphilis

Secondary Syphilis

• Both tests have excellent sensitivity:
  • RPR: 91-100% sensitivity 2
  • VDRL: 100% sensitivity 2

Latent Syphilis

• Early latent: VDRL sensitivity 82.1-100% 2
• Late latent: RPR/VDRL sensitivity 61-75% 2

Special Considerations

HIV Co-infection Testing

• HIV testing should be performed in all patients with suspected syphilis due to:
  • High co-infection rates
  • Altered presentation in HIV-positive patients
  • Potential impact on treatment and follow-up 1

Additional Testing Based on Clinical Presentation

• For suspected neurosyphilis: Lumbar puncture for CSF analysis

  • CSF-VDRL (specificity 99%) 3
  • CSF-RPR (specificity 99.3%) 3
  • CSF cell count and protein

• For pregnant patients: More frequent serologic testing and closer follow-up 1

Common Pitfalls and Caveats

1. Prozone phenomenon: False-negative results in high-titer specimens

   • Solution: Request dilution testing if clinical suspicion is high

2. Biological false positives: Can occur in 0.8-1.3% of the general population due to:

   • Autoimmune disorders
   • Pregnancy
   • IV drug use
   • Viral infections (HCV, HIV) 1

3. Test selection issues:

   • RPR and VDRL titers are not directly comparable
   • Switching between test types during follow-up should be avoided

4. Seronegative window period:

   • Early primary syphilis may have negative serologic tests
   • Consider direct detection methods (dark-field microscopy or PCR) for genital lesions

Follow-up Testing

After treatment, quantitative nontreponemal tests should be performed at:

• 3 months
• 6 months
• 9 months
• 12 months

A four-fold decline in titer (e.g., 1:32 to 1:8) indicates adequate treatment response 1, 4.

Conclusion

The combination of nontreponemal and treponemal tests is essential for accurate diagnosis of syphilis, with test selection guided by clinical presentation and stage of disease. High-titer RPR (≥1:32) is associated with increased risk of neurosyphilis, particularly in HIV-infected patients with CD4+ counts ≤350 cells/μL 5.