A 35-year-old pregnant woman at 20 weeks gestation is diagnosed with secondary syphilis (positive RPR and FTA-ABS). She reports a penicillin allergy (non-anaphylactic rash 10 years ago). What is the preferred treatment regimen?

## Treatment of Syphilis in Pregnancy **Key Point:** Penicillin is the ONLY reliably effective agent for preventing congenital syphilis. All pregnant women with syphilis, regardless of stage, must receive penicillin-based therapy. ### Why Penicillin is Non-Negotiable in Pregnancy **High-Yield:** Penicillin is the only antibiotic proven to: 1. Treat maternal syphilis effectively 2. Cross the placenta in adequate concentrations 3. Prevent congenital syphilis in the fetus 4. Achieve cure rates >95% when given before 16 weeks gestation No other antibiotic (doxycycline, cephalosporins, macrolides) has demonstrated efficacy in preventing fetal infection. ### Management of Penicillin Allergy in Pregnancy | Allergy Type | Management | |--------------|-------------| | Non-anaphylactic (rash) | Penicillin desensitization, then full treatment course | | Anaphylaxis/Stevens-Johnson | Penicillin desensitization (in hospital setting) | | Severe allergy | Desensitization is still preferred over alternatives | **Clinical Pearl:** Even severe penicillin allergy does not justify withholding penicillin in pregnancy with syphilis. Desensitization protocols exist and should be performed in a hospital setting with ICU backup. The risk of congenital syphilis (stillbirth, neonatal death, neurosyphilis) far outweighs the risk of allergic reaction during desensitization. ### Dosing for Secondary Syphilis in Pregnancy **Key Point:** Benzathine penicillin G 2.4 million units IM weekly × 3 doses (total 7.2 million units) is recommended for secondary and early latent syphilis in pregnancy. ### Why Other Options Fail - **Doxycycline:** Teratogenic (tooth discoloration, bone hypoplasia); contraindicated in pregnancy. Also does not reliably prevent congenital syphilis. - **Ceftriaxone:** Not proven to prevent congenital syphilis; inadequate placental penetration. - **Erythromycin:** Inadequate CSF and placental penetration; high failure rate for fetal treatment (up to 50%). **Warning:** Failure to treat maternal syphilis adequately results in congenital syphilis in 70–100% of cases if untreated in first trimester.