What is the next step after a patient tests positive for Rapid Plasma Reagin (RPR) and what treatment is recommended for syphilis?

Confirmatory Treponemal Testing After Positive RPR

After a positive RPR test, you must perform confirmatory treponemal testing (such as TP-PA, FTA-ABS, or treponemal EIA/CIA) to establish the diagnosis of syphilis, as both nontreponemal and treponemal tests must be reactive for definitive diagnosis. 1, 2

Diagnostic Algorithm Following Positive RPR

Immediate Next Step

• Order a treponemal-specific test (TP-PA, FTA-ABS, or treponemal EIA/CIA) to confirm the diagnosis 1, 3
• The traditional algorithm starts with the nontreponemal test (RPR) and confirms reactive results with a more specific treponemal test 2

Interpretation of Results

If treponemal test is POSITIVE (RPR+/Treponemal+):

• This confirms active syphilis infection or past treated infection 1, 3
• Determine the stage of syphilis based on clinical presentation, history, and RPR titer 1
• Initiate stage-appropriate penicillin therapy 1

If treponemal test is NEGATIVE (RPR+/Treponemal-):

• This represents a biological false positive RPR 2
• No treatment for syphilis is indicated 2
• Consider investigating underlying conditions causing false positive: autoimmune disorders, viral infections (HIV, hepatitis), pregnancy, advanced age, malaria, or injection drug use 2
• Biological false positive RPR results typically occur at low titers (≤1:8) 2

Treatment Recommendations Based on Stage

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

• Benzathine penicillin G 2.4 million units IM as a single dose 1
• For pregnant women in the third trimester or those with secondary syphilis, some experts recommend a second dose of benzathine penicillin G 2.4 million units IM one week after the initial dose 1

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

• Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1, 3

Neurosyphilis, Ocular Syphilis, or Otic Syphilis

• Aqueous crystalline penicillin G 18-24 million units per day (administered as 3-4 million units IV every 4 hours or continuous infusion) for 10-14 days 1
• CSF examination should be performed when neurosyphilis is suspected 1

Special Populations

HIV-Infected Patients

• Standard serologic tests remain accurate and reliable for most HIV-infected patients 1, 3
• Some HIV-infected patients may have atypical serologic responses or slower serologic improvement after treatment 4
• Consider more intensive follow-up for HIV-infected patients, as they are less likely to achieve a fourfold decline in RPR titers after treatment 4
• Recent evidence suggests that single-dose benzathine penicillin G plus 7-day doxycycline achieves higher serologic response rates (79.5% vs 70.3%) compared to benzathine penicillin G alone in HIV-infected patients with early syphilis 5

Pregnant Women

• All pregnant women must be screened for syphilis early in pregnancy 1
• Penicillin is the only therapy with documented efficacy for preventing maternal transmission and treating fetal infection 1
• Pregnant women with penicillin allergy should be desensitized and treated with penicillin 1
• Women treated during the second half of pregnancy are at risk for Jarisch-Herxheimer reaction, which may precipitate premature labor or fetal distress 1

Monitoring Treatment Response

Follow-up Serologic Testing

• Use quantitative nontreponemal tests (RPR or VDRL) to monitor treatment response 3
• Sequential tests should use the same testing method, preferably by the same laboratory 3
• A fourfold decline in titer (two dilutions) represents a clinically significant treatment response 1, 3

Expected Serologic Response Timeline

• For primary and secondary syphilis: expect a 2-3 tube decline by 6-12 months 1, 6
• By 36 months, 72% of patients with primary syphilis and 56% with secondary syphilis achieve RPR seroreversion 6
• Patients with higher baseline RPR titers and earlier stage disease are more likely to achieve serologic cure 1, 6

Critical Pitfalls to Avoid

• Never treat based solely on a positive RPR without treponemal confirmation, as biological false positives are common 2, 3
• Do not use treponemal tests to monitor treatment response, as they remain positive for life in most patients regardless of treatment 3
• Do not compare titers between different test types (VDRL vs RPR), as they are not directly comparable 2, 3
• Do not substitute erythromycin or other non-penicillin regimens in pregnant women, as they do not reliably cure fetal infection 1
• Patients who fail to achieve a fourfold decline in nontreponemal titers within 6-12 months (for early syphilis) should be evaluated for treatment failure, reinfection, or neurosyphilis 1