What is the recommended workup and treatment for syphilis?

Syphilis Workup and Treatment

The recommended workup for syphilis involves serologic testing with nontreponemal and treponemal tests, followed by treatment with benzathine penicillin G as the first-line therapy for all stages of syphilis. 1

Diagnostic Workup

Serologic Testing

1. Initial screening:

   • Traditional algorithm: Nontreponemal test (RPR or VDRL) followed by treponemal test confirmation
   • Reverse sequence algorithm (increasingly used): Treponemal EIA/CIA followed by nontreponemal test

2. Confirmatory testing:

   • For positive nontreponemal tests: Confirm with treponemal-specific tests (TP-PA or FTA-ABS)
   • For discordant results (positive treponemal, negative nontreponemal): Additional treponemal testing may be needed

3. Special considerations:

   • Primary syphilis: Dark-field microscopy of lesion exudate is definitive when available
   • Neurosyphilis: Lumbar puncture with CSF examination when neurological symptoms are present

Treatment Recommendations by Stage

Primary, Secondary, and Early Latent Syphilis

• First-line treatment: Benzathine penicillin G 2.4 million units IM in a single dose 1
• Alternative for non-pregnant, penicillin-allergic patients:
  • Doxycycline 100 mg orally twice daily for 14 days (primary/secondary) or 28 days (early latent) 1, 2
  • Tetracycline 500 mg orally four times daily for 14 days (primary/secondary) or 28 days (early latent) 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• First-line treatment: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
• Alternative for non-pregnant, penicillin-allergic patients:
  • Doxycycline 100 mg orally twice daily for 28 days 1, 2
  • Tetracycline 500 mg orally four times daily for 28 days 1

Neurosyphilis

• First-line treatment: Penicillin G aqueous 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
• For penicillin-allergic patients, desensitization is required before treatment

Special Populations

Pregnant Women

• Only recommended treatment: Penicillin G at stage-appropriate dosing 1
• Penicillin-allergic pregnant women must undergo desensitization followed by penicillin treatment
• Alternative antibiotics are not recommended during pregnancy

HIV-Infected Patients

• Same treatment regimens as non-HIV infected patients
• Closer follow-up required
• Consider lumbar puncture to rule out neurosyphilis, especially with late latent syphilis 1

Sexual Partners

• Partners exposed within 90 days of diagnosis of primary, secondary, or early latent syphilis should be treated presumptively, even if seronegative 1
• Long-term partners of patients with late latent syphilis should be evaluated clinically and serologically 1

Follow-up and Monitoring

1. Serologic follow-up:

   • Quantitative nontreponemal tests (RPR, VDRL) at 6,12, and 24 months after treatment 1
   • For HIV-infected patients: More frequent monitoring at 3,6,9,12, and 24 months 1

2. Treatment success criteria:

   • Four-fold decline in nontreponemal test titers within 6 months for primary/secondary syphilis
   • Four-fold decline within 12-24 months for latent/late syphilis 1, 3

3. Treatment failure indicators:

   • Failure of nontreponemal test titer to decrease fourfold within appropriate timeframe
   • Persistence or recurrence of signs/symptoms
   • Sustained fourfold increase in nontreponemal test titer 1

Common Pitfalls and Caveats

• Jarisch-Herxheimer reaction: Patients should be warned about this potential reaction (fever, headache, myalgia) that can occur within 24 hours of treatment
• Prozone phenomenon: False-negative nontreponemal tests can occur with high antibody titers; dilution of serum may be necessary
• Serofast state: Some patients maintain low-positive nontreponemal titers despite adequate treatment
• HIV testing: All patients with syphilis should be tested for HIV due to high co-infection rates 1
• Penicillin allergy: For patients with neurosyphilis or pregnancy, penicillin remains the only effective treatment option; desensitization is required for allergic patients 1, 3

Prevention

• Counsel patients on safer sex practices, including consistent and correct condom use
• Screen high-risk populations regularly
• Test and treat sexual partners appropriately 1