A 28-year-old man presents with a painless ulcer on the glans penis for 3 weeks. On examination, the ulcer has a clean base with indurated edges and regional lymphadenopathy. Dark-field microscopy of exudate shows motile spirochetes. RPR is positive at 1:32 dilution. He is allergic to penicillin (anaphylaxis). What is the most appropriate next step in management?

Explanation

## Clinical Scenario Analysis This is a case of **primary syphilis** (chancre) with serological confirmation (positive RPR). The patient has a documented **penicillin anaphylaxis**, which is an absolute contraindication to penicillin and cephalosporins (cross-reactivity risk ~1–3% with third-generation cephalosporins, but anaphylaxis warrants avoidance). ## Management Algorithm for Penicillin-Allergic Syphilis ```mermaid flowchart TD A[Primary/Secondary Syphilis]:::outcome --> B{Penicillin allergy?}:::decision B -->|No allergy| C[Benzathine PCN G 2.4 MU IM]:::action B -->|Non-anaphylactic allergy| D[Ceftriaxone 1 g IM daily × 10 days]:::action B -->|Anaphylaxis/Severe allergy| E[Doxycycline 100 mg BD × 28 days]:::action E --> F[Verify serological response at 6-12 weeks]:::action C --> F D --> F ``` ## Antibiotic Choice in Penicillin Anaphylaxis | Antibiotic | Indication | Dosing | Duration | Notes | |---|---|---|---|---| | **Doxycycline** | Primary/secondary syphilis, PCN anaphylaxis | 100 mg BD PO | 28 days | **First-line alternative** in anaphylaxis; excellent CNS penetration | | Ceftriaxone | Primary/secondary syphilis, non-anaphylactic allergy | 1 g IM daily | 10 days | Avoid in anaphylaxis; cross-reactivity ~1–3% | | Azithromycin | Pregnancy (if PCN allergy) | 500 mg daily | 21 days | Lower cure rates (~90%); NOT recommended for non-pregnant adults | | Erythromycin | Congenital syphilis prophylaxis | 500 mg QID PO | 15 days | Inferior efficacy in adult syphilis; primarily for neonatal prophylaxis | ## Key Point **Key Point:** In penicillin-anaphylactic patients with primary or secondary syphilis, **doxycycline 100 mg BD for 28 days** is the gold-standard alternative. It achieves excellent tissue and CSF penetration and has cure rates ≥95% when used for the full 28-day course. ## Clinical Pearl **Clinical Pearl:** Doxycycline is contraindicated in pregnancy (teratogenic) and children <8 years; in these groups, desensitization to penicillin or azithromycin (with close follow-up) may be considered. However, in this adult male, doxycycline is ideal. ## High-Yield **High-Yield:** The duration matters: doxycycline must be given for **28 days** (not 10–14 days) to achieve adequate CNS penetration and prevent neurosyphilis relapse. Ceftriaxone (10 days) is only for non-anaphylactic allergy. ## Serological Follow-up After treatment, RPR/VDRL should decline 4-fold by 6–12 weeks (indicating cure). FTA-ABS/TP-PA will remain positive indefinitely (scar of infection).