What to do with a patient with syphilis who was treated a year ago with initial titers (Rapid Plasma Reagin (RPR)) 1:64 and now has a titer of 1:132?

Management of Syphilis with Rising Titers After Treatment

A patient with syphilis treated one year ago with initial RPR titers of 1:64 and current titers of 1:132 should undergo cerebrospinal fluid (CSF) examination and be retreated for latent syphilis, even if the CSF examination is negative. 1

Assessment of Treatment Failure

• This represents a greater than fourfold increase in titers (from 1:64 to 1:132), which meets the criteria for serological treatment failure according to CDC guidelines 1
• A fourfold increase in titers after treatment suggests either reinfection or treatment failure, both requiring intervention 1
• When titers increase fourfold after initial therapy, a CSF examination is mandatory to rule out neurosyphilis 1

Recommended Management Algorithm

1. Perform CSF examination immediately to evaluate for neurosyphilis 1

   • Look for CSF abnormalities such as elevated protein, pleocytosis, or positive VDRL test 1

2. Clinical evaluation for signs/symptoms of:

   • Neurologic involvement (auditory disease, cranial nerve dysfunction, meningitis, stroke, altered mental status) 1
   • Ophthalmic manifestations (iritis, uveitis) 1
   • Evidence of tertiary syphilis (aortitis, gumma) 1

3. Retreatment regardless of CSF results:

   • Even if CSF examination is negative, retreatment for latent syphilis should be initiated 1
   • For patients without neurosyphilis: Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at 1-week intervals 1
   • For patients with neurosyphilis: Follow neurosyphilis treatment protocol (typically aqueous crystalline penicillin G) 1

4. For penicillin-allergic patients:

   • If no evidence of neurosyphilis: Doxycycline 100 mg orally twice daily for 28 days 1, 2
   • If neurosyphilis is present: Penicillin desensitization is required as there are no proven alternatives 1

Follow-Up After Retreatment

• Repeat quantitative nontreponemal serologic tests at 6,12, and 24 months after retreatment 1
• Expect at least a fourfold decline in titers within 12-24 months after retreatment 1
• If titers fail to decline appropriately after retreatment, consider additional CSF examination 1

Important Considerations

• The significant rise in titer (from 1:64 to 1:132) is concerning and requires immediate intervention, as it exceeds the fourfold increase threshold that defines treatment failure 1
• HIV testing should be performed if not already done, as HIV status can affect syphilis treatment response 1, 3
• Low CD4 counts (<350 cells/ml) are associated with higher rates of serological failure after treatment 3
• Even with appropriate treatment, complete seroreversion is uncommon - only about 17% of patients achieve this by 12 months 4

Common Pitfalls to Avoid

• Don't wait and observe: A fourfold increase in titers requires immediate action, not watchful waiting 1
• Don't skip CSF examination: This is essential when titers increase fourfold after treatment 1
• Don't assume reinfection without investigation: While reinfection is possible, treatment failure must be ruled out through proper evaluation 5
• Don't expect rapid seroreversion: Even with successful retreatment, titers may decline slowly and complete seroreversion is uncommon 4