What is the recommended treatment for secondary syphilis?

Treatment of Secondary Syphilis

The recommended treatment for secondary syphilis is benzathine penicillin G 2.4 million units intramuscularly (IM) in a single dose. 1

First-line Treatment

• Benzathine penicillin G is the gold standard treatment for secondary syphilis
• Dosage: 2.4 million units IM as a single dose
• This recommendation comes from the Centers for Disease Control and Prevention (CDC) with a high strength of evidence 1
• The treatment is the same as for primary and early latent syphilis

Alternative Treatments for Penicillin-Allergic Patients

For patients with documented penicillin allergy, the following alternatives can be considered:

• Doxycycline 100 mg orally twice daily for 14 days 1
• Ceftriaxone 1 g IV/IM daily for 10 days 1
• Tetracycline 500 mg orally four times daily for 14 days 1

Monitoring and Follow-up

• Quantitative nontreponemal serologic tests (RPR or VDRL) should be repeated at 6,12, and 24 months 1
• Treatment success is indicated by a fourfold decline in titers within 12-24 months
• Approximately 15% of patients may not meet standard criteria for serological cure 12 months after adequate treatment 1
• Consider retreatment if:
  • Titers increase fourfold
  • An initially high titer fails to decline
  • Signs or symptoms attributable to syphilis develop

Partner Management

• All sexual partners should be evaluated clinically and serologically for syphilis 1
• 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
• If follow-up is uncertain, partners should be treated presumptively

Special Populations

Pregnant Women

• Penicillin is the only proven effective treatment for syphilis during pregnancy 1
• Desensitization is required if the patient is allergic to penicillin
• Missed doses are never acceptable in pregnancy; the full course must be repeated if any dose is missed

HIV-Infected Patients

• The same regimens as HIV-negative patients are recommended 1
• Closer follow-up is required for HIV-positive patients

Potential Challenges and Considerations

Penicillin Shortage

• Recent shortages of benzathine penicillin G have been reported 2
• In cases of unavailability, doxycycline may be used temporarily until benzathine penicillin G can be obtained

Jarisch-Herxheimer Reaction

• A self-limited reaction that can occur within 24 hours of treatment
• Characterized by fever, headache, myalgia, and worsening of cutaneous lesions
• Symptomatic treatment is usually sufficient

Serological Response

• Studies have shown that all patients with secondary syphilis treated with appropriate penicillin regimens achieve seronegativity within 24 months 3
• Doxycycline appears to have a slightly lower success rate compared to penicillin, particularly in late and undetermined syphilis infections 4

Precautions with Penicillin Administration

• Use with caution in individuals with histories of significant allergies and/or asthma 5
• Monitor for allergic reactions
• For patients with severe penicillin allergy, skin testing with major determinant and penicillin G can identify ~90-97% of allergic patients 1

Remember that early and appropriate treatment of secondary syphilis is crucial to prevent progression to later stages of the disease, which can cause irreversible damage to the central nervous system and cardiovascular system 2.