Syphilis: CDC Diagnosis and Treatment Guidelines

WHAT IS IT?

Syphilis is a sexually transmitted infection caused by Treponema pallidum.  Symptoms, diagnostic tests and treatment vary depending on stage of the disease. The syphilis rates in the US have continued to rise over the past decade. Without treatment, syphilis can damage the brain, nerves, eyes, and cardiovascular system.

Screening for Syphilis

Who to Screen

• The USPSTF task force recommends screening for the following populations (Grade A recommendation: “Offer or provide this service”)
  • Asymptomatic, nonpregnant adolescents and adults who are at increased risk for syphilis infection
  • All pregnant women early in pregnancy
  • Factors associated with increased risk for syphilis include
    • Higher prevalence of infection in particular communities
    • Sociodemographic and behavioral factors (e.g., multiple sex partners, prevalence of syphilis is higher in males, men who have sex with men, drug use, persons living with HIV, young adults, and persons with a history of incarceration, sex work, or military service)

How to Screen

• Traditional screening: Initial “nontreponemal” antibody test (i.e., Venereal Disease Research Laboratory [VDRL] test or rapid plasma reagin [RPR] test) to detect biomarkers released from damage caused by syphilis infection, followed by a confirmatory “treponemal” antibody detection test (i.e., fluorescent treponemal antibody absorption [FTA-ABS] or T pallidum particle agglutination test [TP-PA])
• Reverse sequence screening algorithm: Automated treponemal test (such as an enzyme-linked [EIA], chemiluminescence [CIA], or multiplex flow immunoassay [immunoblot]) performed first, followed by a nontreponemal test
  • If the test results of the reverse sequence algorithm are discordant, a second treponemal test (preferably using a different treponemal antibody) is performed

Primary Syphilis

Early disease, characterized by an ulcer or chancre at the infection site approximately 3 weeks after infection

• Diagnosis
  • Darkfield examination and molecular tests of fluid/tissue for T. pallidum are definitive methods or
  • Presumptive diagnosis requires both a (1) nontreponemal test (VDRL or RPR) and (2) a treponemal test (FTA-ABS, EIA, CIAs and immunoblots, rapid treponemal tests or TP-PA)
• Treatment
  • Benzathine penicillin G 2.4 million units IM in a single dose

Secondary Syphilis

Symptoms can be diffuse and variable  

• Symptoms
  • Skin rash (classically with involvement of palms and soles) | Mucocutaneous lesions | Lymphadenopathyn | Fever | Alopecia | Ocular symptoms | Headache | Hepatitis
  •  Typically develops several weeks to months after primary infection
•  Diagnosis
  • Same as for primary syphilis
• Treatment
  • Same as for primary syphilis

Latent Syphilis

No symptoms and no current evidence of primary, secondary, or tertiary disease

• Diagnosis of early latent syphilis
  • Documented seroconversion or sustained ( >2 weeks) fourfold or greater increase in nontreponemal test or unequivocal symptoms of primary/secondary syphilis or a sex partner with documented primary/secondary syphilis all within the past year
• Treatment
  • Early latent (acquired within 1 yr): Benzathine penicillin G 2.4 million units IM single dose
  • Late latent (acquired > 1 yr): Benzathine penicillin G 7.2 million units total given IM in 3 weekly doses of 2.4 million units each

Tertiary Syphilis

Gummas, cardiovascular syphilis (CNS involvement (for neurosyphilis treatment, see below) 

• Diagnosis
  • Appearance of soft skin lesions and ulcers
  • CXR shows linear calcifications of aorta
  • Perform LP to rule out neurosyphilis
• Treatment
  • Benzathine penicillin G 7.2 million units administered as 3 weekly doses of 2.4 million units

Neurosyphilis

Note: Can occur at any stage | Includes cranial nerve dysfunction, meningitis, stroke, altered mental status, auditory/ophthalmic abnormalities | Tabes dorsalis and paresis are late manifestations and can occur 10 to 30 years after infection 

• Diagnosis
  • Lumbar puncture: Test CSF for white blood cell count, protein and VDRL
• Treatment
  • Aqueous crystalline penicillin G, 3 to 4 million units IV every 4 hours for 10 to 14 days or penicillin G procaine, 2.4 million units IM daily plus probenicid 500 mg orally 4 times daily, for 10 to 14 days

Note: The durations of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for latent syphilis | Therefore, benzathine penicillin, 2.4 million units IM once per week for 1 to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy

KEY CLINICAL POINTS:

• Penicillin Allergy
  • Patients with penicillin allergy should be desensitized and treated with penicillin whenever possible
  • Doxycycline 100 mg BID x 14 days or tetracycline 500 mg 4 times daily for 14 days can be used for nonpregnant penicillin-allergic patients with primary or secondary syphilis
• Counsel patients regarding Jarisch-Herxheimer reaction
  • Acute febrile reaction frequently accompanied by headache, myalgia, and fever
  • Occurs within initial 24 hours after initiation of any syphilis therapy
  • Reaction to treatment and not an allergic reaction to penicillin
  • Occurs most frequently among persons who have early syphilis (likely due to heavier bacterial loads at this stage)
  • Manage with antipyretics
• Nontreponemal titers decline after treatment and eventually become negative
• Treponemal tests remain positive for life
• Follow-up at
  • 6, 12, 18 and 24 months after therapy and should include serology
• If symptoms persist or recur, or there is a >4 fold increase in nontreponemal test titer persisting more than 2 weeks
  • consider reinfection or treatment failure
  • retreat and check HIV status
• Sexual transmission occurs only when mucocutaneous lesions are present and is uncommon after the first year
• Persons exposed sexually to those with primary, secondary or early latent syphilis should be evaluated clinically and serologically

Learn More – Primary Sources:

USPSTF: Screening for Syphilis Infection in Pregnant Women

USPSTF: Screening for Syphilis Infection in Nonpregnant Adolescents and Adults

CDC Sexually Transmitted Diseases: Syphilis

CDC: Syphilis During Pregnancy Treatment Guidelines

BMJ Clinical Updates: Syphilis

CDC (MMWR): Missed Opportunities for Preventing Congenital Syphilis — United States, 2022

Related ObG Topics:

Gonorrhea: CDC Diagnosis and Treatment Guidelines

Chlamydia: CDC Recommendations for Diagnosis and Treatment

Ulcerative Genital Conditions in the HIV-Positive Woman

STI Screening in Pregnancy: CDC Recommendations

Screening for Sexually Transmitted Infections – Who, When and How Often?

Medical Evaluation of the Rape Victim