A 32-year-old woman at 8 weeks of gestation is found to have a positive rapid plasma reagin (RPR) test during routine antenatal screening. She denies any symptoms. Which investigation is most appropriate to confirm active syphilis and guide treatment decisions in pregnancy?

## Diagnosis of Syphilis in Pregnancy ### Clinical Context Syphilis in pregnancy poses significant risk of congenital transmission, stillbirth, and neonatal disease. Accurate diagnosis is critical to initiate timely penicillin therapy, which is safe and effective in pregnancy. ### Investigation of Choice **Key Point:** Repeat RPR with titer quantification combined with FTA-ABS (or TP-PA) is the gold standard for confirming active syphilis and assessing treatment response. ### Diagnostic Algorithm ```mermaid flowchart TD A[Positive RPR on screening]:::outcome --> B[Repeat RPR with titer]:::action B --> C{Titer ≥1:8 or rising?}:::decision C -->|Yes| D[Perform FTA-ABS or TP-PA]:::action C -->|No| E[Likely false positive or old infection]:::outcome D --> F{FTA-ABS positive?}:::decision F -->|Yes| G[Active syphilis - treat with penicillin]:::action F -->|No| H[False positive RPR - observe]:::outcome ``` ### Why This Combination? | Test | Interpretation | Clinical Use | |---|---|---| | **RPR (non-treponemal)** | Quantitative; titers correlate with disease activity | Screening and monitoring treatment response | | **FTA-ABS (treponemal)** | Qualitative; remains positive for life | Confirms treponemal infection; distinguishes true from false positive | | **Combination** | RPR + FTA-ABS = gold standard | Confirms diagnosis AND assesses activity | **High-Yield:** RPR alone can be false positive (autoimmune disease, pregnancy, malignancy); FTA-ABS confirms true infection. Rising RPR titer in pregnancy = active disease requiring immediate penicillin G treatment. **Clinical Pearl:** Penicillin G (aqueous crystalline or procaine) is the only reliably effective drug for preventing congenital syphilis and is safe throughout pregnancy. Erythromycin does NOT reliably prevent fetal infection. **Mnemonic:** **VDRL/RPR + FTA = Confirm Syphilis** - VDRL/RPR: Non-treponemal (screening, activity) - FTA-ABS: Treponemal (confirms true infection) [cite:Park 26e Ch 3; Harrison 21e Ch 297]