What is the next step if a serum Venereal Disease Research Laboratory (VDRL) test is positive?

What to Do if Serum VDRL is Positive

If your serum VDRL is positive, you must immediately confirm the result with a treponemal test (FTA-ABS, TP-PA, or EIA) to distinguish between true syphilis infection and a false-positive result, then proceed with staging and treatment based on the combined serologic pattern. 1, 2

Immediate Confirmatory Testing

• Perform a treponemal test (FTA-ABS, TP-PA, TPPA, or EIA/chemiluminescence assay) on the same serum sample to confirm true syphilis infection versus biological false-positive VDRL 1, 2
• Obtain a quantitative VDRL titer (not just positive/negative) as this baseline value is essential for monitoring treatment response and detecting reinfection 2, 3
• Test for HIV infection in all patients with reactive syphilis serology, as HIV coinfection significantly affects management, monitoring frequency, and risk of neurosyphilis 1, 2, 4

Interpretation of Results

If VDRL Positive + Treponemal Test Positive:

• This confirms active or past syphilis infection requiring further evaluation 2, 3
• VDRL titers ≥1:8 are highly specific for true infection with essentially no false positives at this threshold 2
• Proceed to clinical staging and treatment algorithm below 2, 4

If VDRL Positive + Treponemal Test Negative:

• This represents a biological false-positive VDRL result 5, 6
• Common causes include pregnancy, autoimmune diseases, recent vaccination, or injection drug use 1
• False-positive VDRL results are typically low titer (<1:8) 1
• Repeat testing in 10 weeks is recommended, as 95% of biological false-positive results revert to non-reactive by this timeframe 7
• No treatment is needed unless treponemal test becomes positive 7

Clinical Staging and Evaluation

Assess for Primary Syphilis:

• Look for painless chancre or ulcer at the site of inoculation (genitals, oral, rectal) 2, 4
• Perform darkfield microscopy or direct fluorescent antibody testing of any lesion exudate if available, as this is the definitive diagnostic method 3, 4
• If primary syphilis is confirmed: Treat with benzathine penicillin G 2.4 million units IM as a single dose 2, 4

Assess for Secondary Syphilis:

• Examine for diffuse maculopapular rash (especially involving palms and soles), mucocutaneous lesions, condyloma lata, or generalized lymphadenopathy 2
• VDRL titers are typically highest in secondary syphilis (often ≥1:32) 8
• If secondary syphilis is confirmed: Treat with benzathine penicillin G 2.4 million units IM as a single dose 2

Assess for Latent Syphilis:

• Early latent syphilis is defined as infection acquired within the past 12 months with no clinical manifestations 2
• Late latent syphilis is infection >12 months ago or unknown duration with no clinical manifestations 2
• Treatment for early latent: Benzathine penicillin G 2.4 million units IM as a single dose 2
• Treatment for late latent or unknown duration: Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks 2, 3

Screen for Neurosyphilis or Ocular Syphilis:

• Perform lumbar puncture with CSF examination if any of the following are present: 1, 2
  • Neurologic symptoms (headache, confusion, vision changes, hearing loss, cranial nerve palsies)
  • Ocular symptoms (uveitis, vision changes, eye pain)
  • Late latent syphilis (>1 year duration) in HIV-infected patients
  • Serum VDRL titer >1:32 with CD4 count <350 cells/mm³ (expert opinion varies)
  • Treatment failure (persistent symptoms or fourfold titer increase after treatment)
• CSF VDRL is 49-87% sensitive and 74-100% specific for neurosyphilis, but can be completely normal in up to 40% of ocular syphilis cases 1
• If neurosyphilis is confirmed: Treat with aqueous crystalline penicillin G 18-24 million units per day IV (3-4 million units every 4 hours or continuous infusion) for 10-14 days 2, 4

Treatment Considerations

Penicillin Allergy:

• For non-pregnant patients with early syphilis: Doxycycline 100 mg orally twice daily for 14 days is an acceptable alternative 2, 4, 9
• For late latent syphilis, neurosyphilis, or pregnancy: Penicillin desensitization is required, as penicillin is the only proven effective treatment 2, 4

Special Populations:

• HIV-infected patients require more frequent monitoring at 3-month intervals (instead of 6-month intervals) and have higher risk of neurosyphilis 1, 2
• Pregnant women must be treated with penicillin regimens appropriate for the stage of syphilis to prevent congenital syphilis 1
• All pregnant women should have serologic status documented at least once during pregnancy, and in high-risk populations, also at 28 weeks and delivery 1

Follow-Up Monitoring Protocol

For Early Syphilis (Primary, Secondary, Early Latent):

• Repeat quantitative VDRL at 6 and 12 months after treatment using the same test method, preferably by the same laboratory 2, 3
• Treatment success is defined as a fourfold decline in VDRL titer (e.g., from 1:32 to 1:8) within 6-12 months 2
• For HIV-infected patients: Monitor at 3,6,9, and 12 months 2

For Late Latent Syphilis:

• Repeat quantitative VDRL at 6,12,18, and 24 months after treatment 2
• Treatment success is defined as a fourfold decline in titer within 12-24 months 2
• For HIV-infected patients: Monitor at 3,6,9,12,18, and 24 months 2

Treatment Failure Indicators:

• Clinical signs or symptoms persist or recur (new chancre, rash, neurologic symptoms, ocular symptoms) 2
• Sustained fourfold increase in VDRL titer compared to post-treatment baseline 2
• Failure of VDRL titer to decline fourfold within the expected timeframe 2
• If treatment failure is suspected: Re-test for HIV, perform CSF examination, and re-treat with three additional weekly doses of benzathine penicillin G 2.4 million units IM unless neurosyphilis is confirmed 2

Common Pitfalls to Avoid

• Never use treponemal test titers (FTA-ABS, TP-PA) to monitor treatment response, as these remain positive for life in most patients regardless of cure 2, 3, 4
• Never compare VDRL and RPR titers directly or switch between test methods during follow-up, as they are not directly comparable 2, 3
• Do not assume persistent low titers indicate treatment failure, as some patients remain "serofast" with stable low titers (typically <1:8) despite adequate treatment 2
• Do not delay treatment while waiting for darkfield microscopy results if clinical suspicion is high and diagnostic capabilities are limited 4
• Do not forget to evaluate and presumptively treat all sexual contacts within the past 90 days for primary syphilis, 6 months for secondary syphilis, and 1 year for early latent syphilis 4

Partner Notification and Prevention

• Evaluate and treat all sexual contacts within the appropriate timeframe based on the stage of syphilis 4
• Sexual transmission occurs primarily when mucocutaneous lesions are present, which is uncommon after the first year of infection 4
• Warn patients about possible Jarisch-Herxheimer reaction (acute febrile reaction with fever, headache, myalgia) within 24 hours of treatment, which is common in early syphilis and does not indicate treatment failure 4