What is the next step in management for a 32‑year‑old man with reactive syphilis serology, positive Treponema pallidum antibody, past herpes simplex virus type 1 infection, and negative HIV?

Management of Reactive Syphilis Serology in a 32-Year-Old HIV-Negative Man

The next step is to obtain a quantitative nontreponemal test (RPR or VDRL titer) to determine disease activity and stage the infection, followed by appropriate penicillin-based treatment once staging is complete. 1

Immediate Diagnostic Steps

Confirm Active Infection vs. Past Treated Disease

• A positive treponemal antibody test alone cannot distinguish between active infection and previously treated syphilis, as treponemal tests remain positive for life in 75-85% of patients regardless of treatment status. 1
• You must obtain a quantitative nontreponemal test (RPR or VDRL with titer) to assess current disease activity—this is the critical missing piece of information. 1
• If the nontreponemal test is reactive with any titer, this indicates active infection requiring treatment. 2, 1
• If the nontreponemal test is non-reactive, this suggests either very early primary syphilis (before antibody development), late latent/tertiary disease (where 25-39% have non-reactive RPR), or successfully treated past infection. 1

Clinical Staging Assessment

Perform a focused physical examination looking for stage-specific manifestations: 1

• Primary syphilis: painless genital, anal, or oral chancre/ulcer 1, 3
• Secondary syphilis: diffuse rash (especially palms/soles), mucocutaneous lesions, condyloma latum, lymphadenopathy, fever 1, 3, 4
• Tertiary syphilis: cardiovascular signs (aortic regurgitation, aneurysm), gummatous lesions, neurologic symptoms 1, 4
• Neurosyphilis (any stage): headache, vision changes, hearing loss, cranial nerve palsies, confusion, stroke-like symptoms 1, 3

Treatment Based on Stage

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

• Benzathine penicillin G 2.4 million units IM as a single dose is the definitive treatment. 5, 1, 3
• Early latent syphilis is defined as asymptomatic infection acquired within the past 12 months. 1

Late Latent Syphilis (>1 Year or Unknown Duration)

• Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks (total 7.2 million units). 1, 3
• This applies when you cannot definitively establish that infection occurred within the past year. 1

If Neurosyphilis is Suspected or Confirmed

• Lumbar puncture with CSF examination is mandatory if any neurologic or ocular symptoms are present. 5, 1
• Aqueous crystalline penicillin G 18-24 million units per day IV (administered as 3-4 million units every 4 hours or continuous infusion) for 10-14 days. 1
• Some experts recommend following IV therapy with benzathine penicillin G 2.4 million units IM weekly for 3 weeks. 1

Critical Additional Management Steps

HIV Testing Confirmation

• Although this patient tested negative for HIV, document when that test was performed—if it was done during the window period of a recent syphilis exposure, repeat HIV testing at 3 months is warranted. 5, 1
• Syphilis as a genital ulcer disease facilitates HIV transmission, making concurrent testing essential. 6

Partner Notification and Evaluation

• Sexual contacts must be identified and evaluated based on the stage of syphilis: 1
  • Primary syphilis: contacts from 3 months plus duration of symptoms
  • Secondary syphilis: contacts from 6 months plus duration of symptoms
  • Early latent: contacts from 1 year prior
• All identified contacts should be treated presumptively. 1

Follow-Up Monitoring Schedule

• For early syphilis: clinical and serologic evaluation at 6 and 12 months after treatment. 1, 7
• For late latent syphilis: evaluation at 6,12, and 24 months after treatment. 1, 7
• Treatment success is defined as a fourfold decline in nontreponemal titer within 6-12 months for early syphilis or 12-24 months for late latent disease. 1, 7
• Use the same nontreponemal test method (RPR vs. VDRL) at the same laboratory for all follow-up testing, as titers are not interchangeable between methods. 1, 7

Common Pitfalls to Avoid

• Do not treat based solely on a positive treponemal test without obtaining a quantitative nontreponemal titer—you cannot stage the infection or monitor treatment response without this baseline value. 1
• Do not assume the herpes simplex virus type 1 infection is relevant to syphilis management—it is a separate issue and does not alter syphilis treatment. 5
• Do not use alternative antibiotics (doxycycline, ceftriaxone, azithromycin) as first-line therapy—penicillin remains the only proven effective treatment with decades of clinical experience. 5, 1, 3
• Do not skip CSF examination if any neurologic or ocular symptoms are present, even subtle ones like mild headache or blurred vision. 1
• Approximately 15-25% of patients remain "serofast" with persistent low-level positive titers (<1:8) after successful treatment—this does not indicate treatment failure and does not require re-treatment. 1, 7