What is the treatment difference between relapse and reinfection of secondary syphilis?

Treatment Differences Between Relapse and Reinfection of Secondary Syphilis

The treatment for secondary syphilis relapse requires three weekly injections of benzathine penicillin G 2.4 million units IM, while reinfection is treated with a single dose of benzathine penicillin G 2.4 million units IM. 1

Distinguishing Relapse from Reinfection

• Relapse is characterized by persistent or recurrent signs/symptoms after appropriate treatment without new exposure, while reinfection occurs after new sexual exposure to an infected partner 1
• Both conditions present with similar clinical manifestations, including recurrence of symptoms or a sustained fourfold increase in nontreponemal test titers 1
• Distinguishing between relapse and reinfection is often difficult clinically, requiring detailed sexual history to determine possibility of reexposure 2

Diagnostic Approach

• For both conditions, perform a thorough clinical evaluation and serologic testing with nontreponemal tests (RPR or VDRL) 3
• Treatment failure (relapse) should be suspected if there is no fourfold decrease in titer within 6 months after therapy for secondary syphilis 1, 3
• CSF examination is recommended in cases of suspected treatment failure/relapse to rule out neurosyphilis, unless reinfection is clearly established 1
• HIV testing should be performed in all patients with suspected treatment failure or reinfection 1

Treatment Protocol for Relapse (Treatment Failure)

• Administer benzathine penicillin G 2.4 million units IM once weekly for 3 weeks 1
• CSF examination should be performed before re-treatment unless reinfection is certain 1, 2
• If CSF examination indicates neurosyphilis, treat according to neurosyphilis protocols (aqueous crystalline penicillin G 18-24 million units per day for 10-14 days) 3, 2
• For penicillin-allergic patients, doxycycline 100 mg orally twice daily for 14 days can be used, though penicillin desensitization is preferred 4

Treatment Protocol for Reinfection

• Administer a single dose of benzathine penicillin G 2.4 million units IM, the same as for initial infection 1
• For penicillin-allergic patients, doxycycline 100 mg orally twice daily for 14 days is recommended 1, 4
• HIV-infected patients with reinfection may benefit from enhanced therapy (three weekly doses of benzathine penicillin G), though this is not universally recommended 1

Follow-Up Recommendations

• For relapse cases: Clinical and serologic follow-up at 3-month intervals is recommended 1, 2
• For reinfection cases: Follow-up at 6 and 12 months after treatment 1
• HIV-infected patients should be evaluated more frequently (every 3 months) regardless of whether they experienced relapse or reinfection 1, 3
• A fourfold decline in nontreponemal test titers within 6-12 months indicates adequate treatment response 3

Special Considerations

• Some patients may remain serofast (persistent low-level positive titers) despite adequate treatment, which does not necessarily indicate treatment failure 3
• HIV-infected patients may have atypical serologic responses and slower serologic clearance after treatment 1, 3
• The increasing prevalence of syphilis, particularly among high-risk populations, necessitates vigilant screening and prompt treatment 5, 6
• Recent benzathine penicillin G shortages have complicated treatment, but it remains the first-line therapy for all stages of syphilis 7, 6

Common Pitfalls to Avoid

• Do not compare titers between different test types (e.g., VDRL vs. RPR) as they are not directly comparable 3
• Do not assume that persistent low-titer reactivity necessarily indicates treatment failure or reinfection 3
• Avoid using macrolide antibiotics empirically due to widespread resistance in T. pallidum 6
• Never skip CSF examination in cases of suspected treatment failure unless reinfection is clearly established 1, 2