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Syphilis

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Updated 2024 NIH/HIVMA/CDC/IDSA guidelines for the diagnosis and management of syphilis.

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 American College of Obstetricians and Gynecologists (ACOG 2024), the Center for Disease Control (CDC 2024,2021), the Infectious Diseases Society of America (IDSA/CDC/NIH/HIVMA 2024), the International Union Against Sexually Transmitted Infections (IUSTI 2021), the U.S. Preventive Services Task Force ...
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Screening and diagnosis

Indications for screening, patients at risk: as per IUSTI 2021 guidelines, evaluate and treat for syphilis as a precautionary measure in individuals with STIs, unless previous adequate treatment for syphilis is documented.
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  • Indications for screening (pregnancy)

Diagnostic investigations

Confirmatory testing: as per IUSTI 2021 guidelines, obtain a reflex quantitative non-treponemal test (reaching at least 1:8-1:16 dilution) on the same serum in patients tested positive on a treponemal test used alone for primary screening.
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Diagnostic procedures

CSF analysis: as per IUSTI 2021 guidelines, do not perform CSF assessment in patients with early syphilis (whether HIV-positive or HIV-negative), unless there are neurological, ocular, or auricular symptoms.
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Medical management

Antibiotic therapy, early syphilis, HIV-negative: as per CDC 2021 guidelines, administer benzathine penicillin G 2, 400,000 units IM in a single dose in adult patients with primary or secondary syphilis.
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  • 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.
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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

Preventative measures

Post-exposure prophylaxis: as per CDC 2024 guidelines, counsel MSM and transgender women who have had a bacterial STI (specifically syphilis, Chlamydia, or gonorrhea) in the past 12 months that doxycycline can be used as post-exposure prophylaxis to prevent these infections. Offer persons in this group a prescription for doxycycline post-exposure prophylaxis (200 mg, not to exceed 200 mg every 24 hours) after shared decision-making, to be self-administered within 72 hours after having oral, vaginal, or anal sex.
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Follow-up and surveillance

Laboratory follow-up: as per IUSTI 2021 guidelines, obtain a quantitative titer measurement on the first day of treatment to provide a baseline for measuring subsequent changes in antibody titers.
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  • Management of treatment failure or reinfection