What are the next steps for a 35-year-old asymptomatic patient with a reactive syphilis antibody screen and a Rapid Plasma Reagin (RPR) quantitation of 1:8?

Management of Asymptomatic Syphilis with RPR 1:8

This patient requires immediate treatment with benzathine penicillin G 2.4 million units IM, determination of syphilis stage through clinical history and examination, HIV testing, and consideration of CSF examination if any high-risk features are present. 1

Immediate Diagnostic Steps

Confirm the Diagnosis and Stage

• The reactive treponemal antibody screen confirms syphilis infection, and the RPR titer of 1:8 indicates active disease requiring treatment. 1
• Obtain a detailed sexual history to determine timing of infection: documented seroconversion, fourfold titer increase, symptoms of primary/secondary syphilis in the past year, or partner with known early syphilis all indicate early latent syphilis. 1
• Without these criteria, classify as late latent syphilis or syphilis of unknown duration. 1
• Perform a thorough physical examination of all mucosal surfaces including oral cavity, perianal area, perineum, and genitals (under foreskin if uncircumcised) to exclude primary or secondary lesions. 1

Essential Concurrent Testing

• All patients with syphilis must be tested for HIV infection. 1, 2
• HIV status significantly impacts monitoring requirements and may reveal atypical serologic responses. 1

Indications for CSF Examination

Perform lumbar puncture if any of the following are present: 1

• Neurologic signs or symptoms (cranial nerve dysfunction, meningitis, stroke, altered mental status, loss of vibration sense)
• Ophthalmic symptoms (iritis, uveitis)
• Auditory symptoms
• Evidence of tertiary syphilis
• Treatment failure (persistent symptoms or fourfold titer increase after appropriate therapy)
• HIV infection with CD4 count ≤350 cells/mL or RPR titer ≥1:32 1

Important caveat: Even asymptomatic patients with appropriate serologic responses can develop neurosyphilis, particularly if RPR remains ≥1:8 after treatment. 3 Consider CSF examination for any patient with persistent titers or clinical concerns, regardless of initial treatment response. 3

Treatment Regimen

If Early Latent Syphilis (acquired within past year)

• Benzathine penicillin G 2.4 million units IM as a single dose 1, 4

If Late Latent or Unknown Duration

• Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1, 4
• This longer regimen accounts for slower organism division in late-stage disease. 1

If Neurosyphilis Confirmed

• Aqueous crystalline penicillin G 18-24 million units per day IV (3-4 million units every 4 hours) for 10-14 days 1, 4
• Some experts recommend following with 3 weekly doses of benzathine penicillin G 2.4 million units IM. 1

Penicillin Allergy

• For non-pregnant patients: Doxycycline 100 mg orally twice daily for 14 days (early latent) or 28 days (late latent/unknown duration) 1
• For pregnant patients or those with neurosyphilis: Penicillin desensitization is mandatory, as no alternative is proven effective. 1, 5
• Avoid azithromycin due to documented resistance and treatment failures. 1

Follow-Up Monitoring

Serologic Monitoring Schedule

• For early latent syphilis: Repeat quantitative RPR at 6 and 12 months after treatment 1, 4, 2
• For late latent or unknown duration: Repeat quantitative RPR at 6,12,18, and 24 months after treatment 1, 4
• Treatment success is defined as a fourfold (2 dilution) decrease in RPR titer (e.g., from 1:8 to 1:2 or nonreactive). 1, 4

Important Monitoring Considerations

• RPR titers can change significantly even within days of initial testing, so repeat the RPR on the day of treatment if it differs from the diagnostic date. 6
• Use the same testing method (RPR vs VDRL) and preferably the same laboratory for serial monitoring, as results are not directly comparable between methods. 1
• Some patients (15-25%) remain "serofast" with persistent low titers (typically <1:8) after successful treatment; this does not indicate treatment failure. 1, 4

Treatment Failure Criteria

Retreat if any of the following occur: 1, 4

• Failure to achieve fourfold titer decrease within 6-12 months (early syphilis) or 12-24 months (late syphilis)
• Fourfold titer increase after initial decline
• New or persistent clinical signs or symptoms

For treatment failure, perform CSF examination before retreatment to exclude neurosyphilis. 1, 4

Critical Pitfalls to Avoid

• Never rely on a single serologic test type—both nontreponemal (RPR) and treponemal tests are required for diagnosis, as false-positive nontreponemal results occur with various medical conditions. 1
• Do not assume asymptomatic disease excludes neurosyphilis—13 of 17 patients (76%) in one study who progressed to neurosyphilis despite appropriate treatment and serologic response were asymptomatic. 3
• HIV-infected patients may have slower or incomplete serologic responses (56% vs 38% without fourfold decrease at 6 months), requiring more intensive follow-up. 7
• Patients with initial RPR <1:32 and HIV co-infection show significantly slower titer decline and warrant closer monitoring. 7
• Always examine sexual partners exposed within 90 days before diagnosis and treat presumptively. 8