What is the diagnosis and treatment for syphilis?

Diagnosis and Treatment of Syphilis

Syphilis should be treated with benzathine penicillin G as the first-line therapy, with specific dosing regimens based on disease stage to prevent progression to serious complications affecting mortality and quality of life. 1

Diagnosis

Diagnosis of syphilis involves a combination of clinical assessment and serological testing:

• Clinical presentation varies by stage:

  • Primary: Painless chancre (ulcer) at site of infection
  • Secondary: Widespread rash (often involving palms/soles), lymphadenopathy, fever, condyloma latum
  • Latent: Asymptomatic with positive serology
  • Tertiary: Gummas, cardiovascular disease, neurosyphilis 2, 3

• Laboratory testing:

  • Screening with nontreponemal tests (RPR or VDRL)
  • Confirmation with treponemal-specific tests
  • In cases with suspicious lesions but negative serology, consider dark-field microscopy, biopsy, or PCR 4

• Special considerations:

  • HIV-infected patients may have unusual serologic responses (higher titers, false negatives, or delayed reactivity)
  • When clinical findings suggest syphilis but serologic tests are nonreactive, alternative tests should be considered 4

Treatment

Primary, Secondary, and Early Latent Syphilis

• Benzathine penicillin G 2.4 million units IM in a single dose 1
• Alternative for penicillin-allergic non-pregnant patients:
  • Doxycycline 100 mg orally twice daily for 14 days 5
  • Tetracycline 500 mg orally four times daily for 14 days 1
  • Ceftriaxone 1-2 g daily either IM or IV for 10-14 days 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• 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 penicillin-allergic non-pregnant patients:
  • Doxycycline 100 mg orally twice daily for 28 days 5

Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
• Alternative for penicillin-allergic patients:
  • Ceftriaxone 2 g daily either IM or IV for 10-14 days 4

Special Populations

HIV-Infected Patients

• Same treatment regimens as HIV-negative patients but with closer follow-up
• HIV-infected patients should be evaluated clinically and serologically at 3,6,9,12, and 24 months after therapy 4
• Some specialists recommend CSF examination before treatment in HIV-infected persons with early syphilis, especially with CD4 count ≤350 cells/mL and/or RPR titer ≥1:32 4

Pregnant Women

• Only penicillin effectively treats both maternal infection and prevents congenital syphilis
• Pregnant women with penicillin allergy must undergo desensitization and receive penicillin 4, 1
• No alternative treatments are acceptable for pregnant women

Follow-Up

• Quantitative nontreponemal tests (RPR or VDRL) should be repeated at regular intervals:

  • For primary/secondary syphilis: Expect fourfold decline in titers within 6 months
  • For latent/late syphilis: Expect fourfold decline in titers within 12-24 months 1

• Treatment failure is indicated by:

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

• For neurosyphilis, CSF examination should be repeated every 6 months until the cell count normalizes 4

Partner Management

• All sexual partners should be evaluated clinically and serologically
• Partners exposed within 90 days of diagnosis should be treated presumptively even if seronegative
• Partners exposed >90 days before diagnosis should be treated based on clinical and serological evaluation 1

Common Pitfalls and Caveats

• Jarisch-Herxheimer reaction: Acute febrile reaction with headache, myalgia, and exacerbation of cutaneous lesions that may occur within 24 hours after treatment
• Penicillin allergy management: Skin testing with major determinant and penicillin G can identify ~90-97% of allergic patients; desensitization is required for pregnant women and patients with neurosyphilis 1
• Serological response: Approximately 15% of patients may not meet standard criteria for serological cure 12 months after adequate treatment 1
• Reinfection vs. treatment failure: Important to distinguish between the two when evaluating persistent or recurrent symptoms

Remember that untreated syphilis can lead to significant morbidity and mortality through progression to tertiary disease with cardiovascular, neurological, and other systemic complications. Early diagnosis and appropriate treatment are essential to prevent these outcomes.