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Syphilis — Clinical Guidelines

Overview

Syphilis is a sexually transmitted infection caused by Treponema pallidum, progressing through primary, secondary, latent, and tertiary stages. Untreated, it can lead to severe complications including congenital syphilis, neurosyphilis, and organ-specific manifestations. 1 2 21

Diagnosis

Clinical Presentation: Primary syphilis often presents with a painless chancre; secondary syphilis with rash, mucocutaneous lesions, and systemic symptoms. 1 2 14

Serological Tests: Non-treponemal tests (RPR, VDRL) for disease activity; treponemal tests (FTA-ABS, TPHA) for infection confirmation. 4 16 48

PCR and Histopathology: Useful in atypical presentations or when serology is inconclusive. 28 50

Management

Primary and Secondary Syphilis: Benzathine penicillin G 2.4 million units intramuscularly in a single dose. 1 16 20

Latent Syphilis: Same dose as primary/secondary, depending on duration; tertiary syphilis requires longer treatment courses, often with parenteral therapy. 1 20

Neurosyphilis: Intravenous aqueous crystalline penicillin G 18-24 million units daily for 10-14 days. 12 50

Alternative Antibiotics: For penicillin allergy, doxycycline or tetracycline (adults: 100 mg twice daily for 14-21 days; children: adjusted dose). 2 17

Special Populations

Pregnancy: Routine screening at booking and throughout pregnancy; early treatment crucial to prevent congenital syphilis. 1 8 24

Pediatrics: Similar treatment protocols as adults but with careful dose adjustment; congenital syphilis requires comprehensive pediatric care. 8 24

Elderly: No specific differences in management, but comorbidities must be considered in treatment selection. 17

Key Recommendations

Screening for Syphilis in Pregnant Women: Routine screening at booking and throughout pregnancy to prevent congenital syphilis. (Evidence: Strong 1 8 24)

Treatment of Primary and Secondary Syphilis: Use benzathine penicillin G 2.4 million units intramuscularly as first-line therapy. (Evidence: Strong 1 16 20)

Post-Exposure Prophylaxis (PEP) for Syphilis: Doxycycline 100 mg twice daily for 14 days for individuals exposed to syphilis. (Evidence: Moderate 2)

Neurosyphilis Management: Intravenous penicillin G for confirmed cases to prevent neurological complications. (Evidence: Strong 12 50)

References

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Contemporary Clinical Management of Otosyphilis for Practicing Otolaryngologists-A Scoping Review. The Laryngoscope 2025. link 6 Fuertes de Vega L, de la Torre García JM, Suarez Farfante JM, Ceballos Rodríguez MC. [Translated article] AEDV Expert Consensus for the Management of Syphilis. Actas dermo-sifiliograficas 2024. link 7 Zheng Y, Ye K, Ying M, He Y, Yu Q, Lan L et al.. Syphilis epidemic among men who have sex with men: A global systematic review and meta-analysis of prevalence, incidence, and associated factors. Journal of global health 2024. link 8 Laurentino ACN, Ramos BA, Lira CDS, Lessa IF, Taquette SR. Health care of sexual partners of adolescents with gestational syphilis and their children: an integrative review. Ciencia & saude coletiva 2024. link 9 Chen YC, Lin CP, Yang CH, Hwang YS, Cheng CK, Hwang DK et al.. Diagnosis and treatment of syphilitic uveitis: Taiwan experts consensus. 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Syphilis