Syphilis RPR May Fluctuate Before Treatment
By Carol A. Kemper, MD, FIDSA
Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation
SOURCE: Pandey K, Fairley CK, Chen MY, et al. Changes in the syphilis rapid plasma reagin titer between diagnosis and treatment. Clin Infect Dis 2023;76:795-799.
Rapid plasma reagin (RPR) titers may be more dynamic than previously recognized, which could affect interpretation of response to therapy. Based on retrospective data from a large Australian health service, which provides free STD and HIV testing and care, researchers analyzed RPR titers in persons age 16 years and older collected between 2011 and 2020. The authors conducted serologic testing for syphilis using an RPR test (Becton Dickinson), a Treponema pallidum particle agglutination assay, and either an enzyme-linked immunosorbent assay (Trepanostika EIA, bioMérieux — before January 2016) or a chemiluminescent immunoassay (LIAISON, DiaSorin) after January 2016.
A total of 96,158 patients underwent at least one syphilis test during this period. Of these, clinicians repeated a titer for 766 cases within 14 days of their initial presentation and before they were treated. Of these, 121 were diagnosed with primary syphilis, 100 with secondary syphilis, 339 with early latent infection, and 31 with late latent infection (175 were unclassified). The median RPR titer at the time of presentation was 1:32.
Of these 766 cases, 14.8% demonstrated a fourfold or higher change in their RPR titer within 14 days of presentation in the absence of treatment (83.2% of these showed higher titers and 16.8% showed lowered titers). These fluctuating titers were distributed evenly across syphilis stage, including 18% with primary infection, 19% of those with secondary infection, 15.6% of those with early latent disease, and 10.8% of those unclassified. Changes in RPR titer were more pronounced with a longer interval since initial testing: Within one to three days of the initial RPR testing, 5.8% recorded a change in RPR titers of fourfold or more. By comparison, 26.2% recorded a change in their RPR fourfold or more if repeat testing occurred 10-14 days later. Thus, of those 59 cases with repeat titers within two weeks, and who also underwent follow-up testing after treatment a median of 271 days later, five cases would have been classified as an insufficient response to therapy if the initial titer but not their subsequent titer was used.
Pandey et al observed fluctuations in syphilis RPR titers fourfold or more within two weeks of initial testing, in the absence of treatment, in 14.8% of persons. If treatment was delayed by 10-14 days, the potential for fourfold or more fluctuation in the RPR titer increased to 26%.
COMMENTARY
I have always thought of RPR titers as stable, especially in patients with longer-standing infection. But these data suggest patients with primary, secondary, and even early latent infection can exhibit what we would consider clinically significant changes in their titer in advance of treatment, which might affect the interpretation of their response to therapy. The more time between testing and treatment, the more likely the change in the titer. Since patients often are called back for treatment, these data suggest clinicians should obtain a repeat RPR at the time these patients return for treatment, effectively establishing a new baseline.
The more time between testing and treatment, the more likely the change in the titer. Since patients often are called back for treatment, these data suggest clinicians should obtain a repeat rapid plasma reagin at the time these patients return for treatment, effectively establishing a new baseline.
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