What is the recommended treatment for a patient with a reactive syphilis test (Syphilis Ab/IgG/IgM)?

Management of Reactive Syphilis Serology (Treponemal Test Positive)

A reactive treponemal test (Syphilis Ab/IgG/IgM) requires immediate confirmation with a quantitative nontreponemal test (RPR or VDRL) to determine if this represents active infection requiring treatment versus prior treated or untreated infection. 1, 2

Immediate Diagnostic Steps

Obtain a quantitative nontreponemal test (RPR or VDRL) immediately - this is essential to distinguish active infection from past exposure, as treponemal tests remain positive for life regardless of treatment status. 1, 3

Clinical Assessment Required

• Screen for neurologic symptoms: headache, vision changes, hearing loss, cranial nerve deficits 1, 4
• Screen for ocular symptoms: uveitis, optic neuritis 1, 4
• Obtain sexual history: timing of last exposure, number of partners, condom use 5
• HIV testing is mandatory for all patients with reactive syphilis serology, as HIV co-infection alters management and monitoring 1, 4

If any neurologic or ocular symptoms are present, lumbar puncture is mandatory before initiating treatment. 1, 4

Treatment Algorithm Based on Clinical Stage

If RPR/VDRL is Reactive (Active or Latent Infection)

The stage of syphilis determines treatment duration:

Early Syphilis (Primary, Secondary, or Early Latent <1 year)

• Benzathine penicillin G 2.4 million units IM as a single dose 2, 5, 6
• This achieves 90-100% treatment success rates 6

Late Latent Syphilis (>1 year duration or unknown duration)

• Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks (total 3 doses) 1, 2, 6

Neurosyphilis (Any Stage with CNS Involvement)

• Aqueous crystalline penicillin G 18-24 million units IV daily (administered as 3-4 million units every 4 hours) for 10-14 days 4, 3

Penicillin Allergy Management

For non-pregnant patients with documented penicillin allergy:

• Early syphilis: Doxycycline 100 mg orally twice daily for 14 days 2, 7, 3
• Late latent syphilis: Doxycycline 100 mg orally twice daily for 28 days 2, 7, 3
• Neurosyphilis or pregnancy: Penicillin desensitization is mandatory - no alternatives are acceptable 2, 4, 8

Critical caveat: Ceftriaxone 1 g IV/IM daily for 10 days is an alternative with comparable efficacy to benzathine penicillin for early syphilis, but should not be used in neurosyphilis. 2

Post-Treatment Monitoring

Obtain quantitative nontreponemal tests (RPR or VDRL) using the same test method at the same laboratory:

• Early syphilis: At 3,6,12, and 24 months 1, 2, 3
• Late latent syphilis: At 6,12, and 24 months 1, 3
• HIV co-infected patients: Every 3 months instead of 6-month intervals 1

Expected serologic response:

• Fourfold decline in titer within 6 months for primary/secondary syphilis 2, 3, 6
• Fourfold decline within 12-24 months for latent syphilis 1, 3, 6
• 15-25% of patients become seronegative within 2-3 years after treatment of primary syphilis 1

Serofast State

Approximately 44-56% of patients with late latent syphilis remain seropositive despite adequate treatment - this "serofast state" does not indicate treatment failure if titers remain stable and low (RPR ≤1:4). 1, 6, 9

Critical Pitfalls to Avoid

• Never use treponemal tests to monitor treatment response - they remain positive for life and cannot distinguish active from treated infection 10, 3
• Do not use amoxicillin-based regimens - enhanced penicillin therapy (benzathine penicillin plus amoxicillin/probenecid) did not improve outcomes and is not recommended 2
• HIV-infected patients may have atypical serologic responses with unusually low, high, or fluctuating titers - consider CSF examination for late-latent syphilis in this population 1, 4
• Jarisch-Herxheimer reaction may occur within 24 hours of treatment initiation, particularly in early syphilis 4