Next Step After Positive RPR: Confirmatory Treponemal Testing
A positive RPR test must be confirmed with a specific treponemal test (FTA-ABS, TP-PA, or treponemal EIA/CLIA) to establish a definitive diagnosis of syphilis and distinguish true infection from biological false-positive results. 1
Immediate Confirmatory Testing
- Order a treponemal-specific test (FTA-ABS, TP-PA, MHA-TP, or treponemal EIA/CLIA) to confirm the diagnosis, as the RPR alone is insufficient for diagnosis 1, 2
- The treponemal test has 82-100% sensitivity and 95-98% specificity for confirming true syphilis infection 1, 2
- A positive RPR with a negative treponemal test indicates a biological false-positive RPR, which occurs in 0.6-5% of cases and can be caused by autoimmune diseases, pregnancy, HIV infection, hepatitis B/C, injection drug use, or advanced age 1, 2
Concurrent Essential Actions
- Test for HIV immediately in all patients with confirmed syphilis, as HIV status critically affects monitoring frequency, risk of neurosyphilis, and treatment response 1, 2
- Document the quantitative RPR titer (e.g., 1:8,1:32), as titers correlate with disease activity and guide treatment monitoring 1
- Perform a thorough clinical examination looking specifically for:
- Primary syphilis: painless chancre or ulcer at infection site 1
- Secondary syphilis: diffuse rash (especially palms/soles), mucocutaneous lesions, lymphadenopathy 1
- Tertiary syphilis: cardiovascular, neurologic, or gummatous manifestations 1
- Neurosyphilis symptoms: headache, vision changes, hearing loss, confusion 2
Staging the Infection
Once treponemal testing confirms syphilis, determine the stage to guide treatment:
- Primary syphilis: Chancre present, treat with single dose benzathine penicillin G 2.4 million units IM 1
- Secondary syphilis: Rash and systemic symptoms, treat with single dose benzathine penicillin G 2.4 million units IM 1
- Early latent syphilis (acquired within past 12 months): No symptoms, treat with single dose benzathine penicillin G 2.4 million units IM 1
- Late latent or unknown duration: No symptoms but acquired >12 months ago or unknown timing, treat with benzathine penicillin G 2.4 million units IM weekly for 3 weeks 1
Special Considerations Requiring CSF Examination
- Neurologic or ocular symptoms of any kind mandate lumbar puncture before treatment 1, 2
- HIV-infected patients with late latent syphilis should undergo CSF examination to exclude neurosyphilis 1, 2
- Consider CSF examination if RPR titer >1:32 with CD4 count <350 cells/mm³ in HIV-infected patients 2
- If neurosyphilis is confirmed, treat with aqueous crystalline penicillin G 18-24 million units per day IV for 10-14 days 1
Critical Pitfalls to Avoid
- Never use treponemal test titers to monitor treatment response—they remain positive for life regardless of cure 2
- Do not compare RPR and VDRL titers directly—they are not interchangeable and sequential testing should use the same method, preferably the same laboratory 1, 2
- False-positive RPR results are rare at titers ≥1:8, so high titers strongly indicate true infection 2
- Do not delay treatment in high-risk patients (pregnant women, symptomatic secondary syphilis, known recent exposure) while awaiting confirmatory testing—treat empirically 2
Pregnancy-Specific Management
- Pregnant women with confirmed syphilis must be treated with penicillin regardless of stage, as it is the only therapy proven to prevent congenital syphilis 1, 2
- Penicillin-allergic pregnant women require desensitization—alternative antibiotics are not acceptable 1, 2
- Some experts recommend an additional dose of benzathine penicillin G 2.4 million units IM one week after initial treatment for pregnant women with primary, secondary, or early latent syphilis 1
- Treatment must occur >4 weeks before delivery for optimal outcomes 1