What is the treatment for tertiary syphilis?

Treatment for Tertiary Syphilis

For tertiary syphilis without neurosyphilis, the recommended treatment is benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals. 1

Understanding Tertiary Syphilis

Tertiary syphilis specifically refers to:

• Gummatous syphilis (granulomatous lesions)
• Cardiovascular syphilis
• But does NOT include all forms of neurosyphilis 1

Treatment Algorithm

Step 1: Evaluate for Neurosyphilis

• Mandatory: Perform CSF examination before initiating therapy for all patients with symptomatic late syphilis 1
• Look for: cognitive dysfunction, motor/sensory deficits, ophthalmic/auditory symptoms, cranial nerve palsies, meningitis signs 1

Step 2: Treatment Based on Evaluation

If NO evidence of neurosyphilis:

• First-line: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1

If evidence of neurosyphilis is present:

• First-line: Aqueous crystalline penicillin G 18–24 million units per day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10–14 days 1
• Alternative: Procaine penicillin 2.4 million units IM once daily PLUS Probenecid 500 mg orally four times a day, both for 10–14 days 1
• Consider supplementing with benzathine penicillin G 2.4 million units IM once per week for up to 3 weeks after completion of neurosyphilis treatment 1

Step 3: Management for Penicillin-Allergic Patients

For tertiary syphilis without neurosyphilis:

• Consultation with infectious disease specialist is mandatory 1
• Alternative options:
  • Doxycycline 100 mg orally twice daily for 28 days 1, 2
  • Tetracycline 500 mg orally four times daily for 28 days 1

For neurosyphilis in penicillin-allergic patients:

• Preferred approach: Penicillin desensitization followed by standard penicillin treatment 1
• Alternative if desensitization impossible: Ceftriaxone 2 g daily IV for 10-14 days (limited data) 1

Special Considerations

Cardiovascular Syphilis

• Some providers treat all patients with cardiovascular syphilis using the neurosyphilis regimen 1
• Management should involve consultation with an infectious disease specialist 1

HIV Co-infection

• HIV-infected persons with clinical evidence of tertiary syphilis should have CSF examination before therapy 1
• Treatment regimens are the same as for HIV-negative patients 1
• Close clinical and serologic monitoring is essential 1

Follow-up

• Limited information is available concerning clinical response and follow-up of patients with tertiary syphilis 1
• Close serologic monitoring is essential to ensure treatment success

Common Pitfalls to Avoid

1. Failing to perform CSF examination before initiating therapy in symptomatic late syphilis
2. Misdiagnosing neurosyphilis - can occur during any stage of infection and requires specific treatment
3. Inadequate follow-up after treatment
4. Using alternative regimens without specialist consultation in penicillin-allergic patients
5. Treating cardiovascular syphilis without infectious disease specialist involvement

The management of tertiary syphilis is complex and often requires a multidisciplinary approach with infectious disease specialists, particularly for patients with penicillin allergies or cardiovascular involvement.