What is the next step in management for a patient with a positive Rapid Plasma Reagin (RPR) test but a negative Venereal Disease Research Laboratory (VDRL) test?

Management of RPR Positive but VDRL Negative Results

When a patient has a positive Rapid Plasma Reagin (RPR) test but a negative Venereal Disease Research Laboratory (VDRL) test, the next step should be to perform a treponemal-specific test to confirm the diagnosis of syphilis. 1

Understanding Discordant Results

Discrepancies between nontreponemal tests (RPR and VDRL) can occur due to several factors:

1. Test Sensitivity Differences:

   • RPR is generally more sensitive than VDRL, detecting approximately 86.4% of cases compared to VDRL's lower sensitivity 2
   • Harrison et al. found that RPR was more sensitive than VDRL (174/200 vs 167/200) in syphilitic sera 3

2. Biological False Positives:

   • Biological false positive RPR reactions occur in 0.8-1.3% of the general population 1
   • Higher rates (4-10.7%) are seen in HIV-positive individuals 1
   • Common causes include autoimmune disorders, pregnancy, IV drug use, acute viral infections, advanced age, and hepatitis B or C infection 3

3. Early Primary Syphilis:

   • In early infection, RPR may become positive before VDRL 1
   • Approximately 80-85% of primary syphilis cases have positive RPR tests by the time chancres appear 1

Diagnostic Algorithm

1. Confirm with a Treponemal Test:

   • Perform a treponemal-specific test such as FTA-ABS, TP-PA, or EIA 3
   • These tests detect antibodies specific to T. pallidum and remain positive for life in most cases 1

2. If Treponemal Test is Positive:

   • This confirms current or past syphilis infection
   • Proceed with clinical staging to determine appropriate treatment 1
   • Consider the possibility of previously treated syphilis, as treponemal tests remain positive for life 3

3. If Treponemal Test is Negative:

   • The RPR result is likely a biological false positive
   • Consider causes of false positives and investigate accordingly 3
   • Repeat testing in 2-4 weeks may be warranted to rule out very early infection 3

Additional Considerations

• HIV Testing: The CDC recommends HIV testing for all patients with syphilis due to high co-infection rates 1
• Prozone Phenomenon: Consider the possibility of the prozone effect in VDRL testing, where extremely high antibody levels can cause false-negative results (occurs in approximately 0.83% of cases) 1
• Other STI Screening: Test for other sexually transmitted infections including gonorrhea and chlamydia 1

Treatment Approach

If syphilis is confirmed by treponemal testing, treatment should be based on disease staging:

• Early Syphilis (primary, secondary, early latent): Benzathine penicillin G 2.4 million units IM as a single dose 1
• Late Latent Syphilis or unknown duration: Benzathine penicillin G 2.4 million units IM weekly for 3 weeks 1
• For Penicillin-Allergic Patients: Doxycycline 100 mg orally twice daily for 2 weeks (early) or 4 weeks (late) 1

Follow-Up Testing

After treatment, monitor with quantitative nontreponemal tests:

• At 3,6,9, and 12 months post-treatment 1
• More frequent monitoring (every 3 months) for high-risk individuals, particularly those with HIV 1
• A four-fold decline in titer is expected within 3-6 months for primary/secondary syphilis 4

Pitfalls to Avoid

1. Relying solely on nontreponemal tests: Both RPR and VDRL have limitations in sensitivity and specificity 3
2. Ignoring the possibility of neurosyphilis: Consider CSF examination in patients with neurological symptoms, regardless of serology results 5
3. Assuming all positive RPRs with negative VDRLs are false positives: This pattern can occur in early infection 1
4. Overlooking HIV co-infection: HIV can alter the serological response to syphilis treatment 4

Remember that approximately 15-20% of patients may remain "serofast" with persistent low, unchanging titers after treatment, sometimes for life 1.