When to recheck Rapid Plasma Reagin (RPR) after treating for Syphilis?

From the Guidelines

After treating syphilis, RPR titers should be rechecked at 6,12, and 24 months following treatment for primary and secondary syphilis, and at 6,12,24, and 36 months for latent or tertiary syphilis, as recommended by the most recent guidelines 1. The first follow-up should occur at 3 months for all patients. Treatment is considered successful when there is a fourfold decrease in titer (e.g., from 1:32 to 1:8) within 6 months for primary/secondary syphilis or within 12-24 months for later stages. If titers fail to decline appropriately or if symptoms persist, treatment failure or reinfection should be suspected, warranting additional evaluation and possibly retreatment. For HIV-positive patients, more frequent monitoring may be necessary, with some guidelines suggesting evaluation at 3-month intervals instead of 6-month intervals 1. The standard treatment for primary, secondary, or early latent syphilis is a single dose of benzathine penicillin G 2.4 million units IM, while late latent or tertiary syphilis requires three weekly doses of the same medication. RPR titers may remain positive at low levels (serofast state) even after successful treatment, especially in patients who have had syphilis for longer periods before treatment. Key considerations for follow-up include:

• Re-treatment should be considered for those who have a sustained fourfold increase in serum nontreponemal titers after an initial reduction after treatment, or have persistent or recurring clinical signs or symptoms of disease 1.
• Certain specialists recommend retreating persons with early syphilis who do not experience at least a fourfold decrease in serum nontreponemal titers 6--12 months after therapy 1.
• If CSF examination does not confirm the diagnosis of neurosyphilis, such persons should receive 2.4 million units IM benzathine penicillin G administered at 1-week intervals for 3 weeks 1.

From the Research

Rechecking RPR after Treating Syphilis

• The timing of rechecking RPR (Rapid Plasma Reagin) after treating syphilis is crucial for assessing treatment response and detecting potential treatment failure or repeat infection 2, 3, 4, 5.
• According to a study published in 2002, serological response to therapy was evaluated at 3,6,9, and 12 months following therapy, and participants whose RPR test became nonreactive or whose RPR titer decreased ≥2 dilutions were classified as responding to therapy 2.
• Another study published in 2017 found that although the decline in RPR titers was ≥4-fold among 88.0% of participants at 3 months and ≥8-fold among 77.8% at 6 months, only 9.6% achieved complete RPR seroreversion at 6 months and 17.1% at 12 months after therapy 3.
• A 2012 study evaluated RPR titer variation during the 14 days after therapy and found that 20% of patients showed a titer increase of at least 1 dilution in the 14 days after therapy, but these changes rarely influenced assessment of therapeutic outcome 4.
• The management of adult syphilis guidelines suggest that CSF examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms, and in those persons with early syphilis who do not achieve a ≥4-fold serologic decline in their RPR titers 6-12 months after adequate therapy 5.

Factors Influencing RPR Rechecking

• Male sex and baseline RPR titers ≤1:32 were associated with higher odds of seroreversion compared with females and titers >1:32 3.
• HIV status and CD4 cell counts may also influence the interpretation of RPR results, with HIV-infected persons with syphilis of any stages whose RPR titers are ≥1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis 5.

Recommendations for RPR Rechecking

• RPR testing should be performed at 3,6,9, and 12 months after therapy to assess treatment response 2, 3.
• CSF examination should be considered in persons with early syphilis who do not achieve a ≥4-fold serologic decline in their RPR titers 6-12 months after adequate therapy, and in those with late latent infection who do not achieve a similar decline within 12-24 months 5.
• Paired RPR testing (simultaneous testing of acute and convalescent samples) may enable a more accurate determination of delta RPR compared with individual testing, but individual testing performed equally well in one study 6.