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Syphilis

What's new

The U.S. Preventive Services Task Force (USPSTF) has reaffirmed its recommendation to perform early universal screening for syphilis in pregnancy, or at the earliest available opportunity if initial screening was not conducted early in pregnancy. .

Background

Overview

Definition
Syphilis is a STI caused by the bacterium Treponema pallidum subspecies pallidum.
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Pathophysiology
The pathophysiology of syphilis involves the entry of Treponema pallidum through mucous membranes or broken skin during sexual contact. Within days to weeks, Treponema pallidum disseminates via blood and lymphatic vessels and accumulates in perivascular spaces of different organs, leading to various clinical manifestations.
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Epidemiology
The incidence of primary and secondary syphilis in the US is estimated at 17.7 per 100,000 person-years. The incidence of late syphilis or syphilis of unknown duration in the US is estimated at 26.3 per 100,000 person-years.
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Risk factors
Risk factors for syphilis include unprotected sex, having multiple sexual partners, homelessness, history of HIV, history of other STIs, tobacco use, and illicit drug use.
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Disease course
The clinical course of syphilis is divided into stages. Primary syphilis is characterized by a chancre, typically a single, painless, indurated ulcer with a clean base discharging clear serum. Secondary syphilis involves multisystem manifestations such as a non-itching skin rash, fever, and generalized lymphadenopathy. The latent stage is asymptomatic, and tertiary syphilis can involve neurological, cardiovascular, or gummatous complications.
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Prognosis and risk of recurrence
The prognosis of syphilis is generally good if detected and treated early, with penicillin being the mainstay of treatment.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of syphilis are prepared by our editorial team based on guidelines from the British Association for Sexual Health and HIV (BASHH 2025,2024), the U.S. Department of Health and Human Services (DHHS 2025), the U.S. Preventive Services Task Force (USPSTF 2025,2016), the American College of Obstetricians and Gynecologists (ACOG 2024), the Center ...
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Screening and diagnosis

Indications for screening, patients at risk: as per BASHH 2024 guidelines, obtain routine serological screening for syphilis every 6 months in patients with HIV.
B
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  • Indications for screening (pregnancy)

  • Indications for screening (choice of test)

Diagnostic investigations

Confirmatory testing: as per BASHH 2024 guidelines, obtain dark ground microscopy on possible chancres where appropriate expertise and equipment are available.
B
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Diagnostic procedures

CSF analysis
As per BASHH 2024 guidelines:
Do not perform routine CSF assessment in patients without symptomatic disease, regardless of HIV status.
D
Perform CSF examination if there is clinical evidence of neurological involvement, except in cases of ophthalmic or otological syphilis where it is rarely useful, irrespective of disease stage.
B
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Medical management

Antibiotic therapy, general principles: as per BASHH 2024 guidelines, initiate parenteral treatment with the appropriate penicillin antibiotic as the treatment of choice.
B
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  • Antibiotic therapy, early syphilis (HIV-negative)

  • Antibiotic therapy, early syphilis (HIV-positive)

  • Antibiotic therapy, latent syphilis (HIV-negative)

  • Antibiotic therapy, latent syphilis (HIV-positive)

  • Antibiotic therapy, tertiary syphilis (HIV-negative)

  • Antibiotic therapy, tertiary syphilis (HIV-positive)

  • Antibiotic therapy, neurosyphilis, ocular and auricular syphilis (HIV-negative)

  • Antibiotic therapy, neurosyphilis, ocular and auricular syphilis (HIV-positive)

  • Corticosteroids

  • Management of sexual contacts

Specific circumstances

Pediatric patients: as per CDC 2021 guidelines, administer benzathine penicillin G 50,000 units/kg body weight IM, up to the adult dose of 2, 400,000 units, in a single dose in infants and pediatric patients with syphilis.
E
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  • Pregnant patients (HIV-negative, early syphilis)

  • Pregnant patients (HIV-negative, late syphilis)

  • Pregnant patients (HIV-positive)

  • Patients with congenital syphilis

  • Patients with solid organ transplants

Patient education

General counseling
As per BASHH 2024 guidelines:
Provide patients with a clear explanation of their diagnosis of syphilis and its implications, reinforced with written information.
B
Advise patients with early, infectious syphilis to abstain from sexual contact until all lesions (if any) have resolved or until 2 weeks after treatment completion.
B
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Preventative measures

Post-exposure prophylaxis: as per BASHH 2025 guidelines, offer doxycycline post-exposure prophylaxis in cisgender gay, bisexual, and other MSM and transgender women at elevated risk of acquiring syphilis.
A
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Follow-up and surveillance

Laboratory follow-up, serology
As per BASHH 2024 guidelines:
Obtain follow-up with syphilis serology every 3 months for 6 months, then at 12 months, and if indicated (such as HIV co-infection), every 6 months or until serofast.
B
Recognize that serological response in patients with HIV may be slower than in patients without HIV.
B
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  • Laboratory follow-up (CSF analysis)

  • Management of treatment failure or reinfection