Syphilis Diagnosis and Monitoring using Rapid Plasma Reagin

Introduction to RPR Testing

The Centers for Disease Control and Prevention recommends RPR as a nontreponemal antibody test used in the diagnosis and monitoring of syphilis infection, which detects nonspecific or nontreponemal antibodies that develop during syphilis infection 1, 2
RPR is one of the primary antiphospholipid antibody tests used to detect host antibodies made in response to phosphatidylcholine taken up from mammalian tissue by Treponema pallidum, the bacterium that causes syphilis 1

RPR shows varying sensitivity depending on the stage of syphilis, with sensitivity ranging from 88.5% in primary syphilis to 100% in secondary syphilis, and 95.7% in latent untreated syphilis 3
The American College of Physicians recommends that RPR test results be reported quantitatively as titers, which usually correlate with disease activity, with a fourfold change in titer considered clinically significant when monitoring treatment response 2

The Centers for Disease Control and Prevention states that RPR and VDRL are equally valid assays, but quantitative results cannot be compared directly as RPR titers often are slightly higher than VDRL titers, with several high-quality studies reporting similar or higher sensitivity of RPR compared to VDRL 2, 4
RPR has been shown to have higher specificity compared to VDRL in multiple studies, with a specificity of 94.3% compared to treponemal tests 4

The Infectious Diseases Society of America recommends that sequential serologic tests in individual patients be performed using the same testing method, preferably by the same laboratory, with RPR titers used to monitor treatment responses, and a fourfold decrease in titer indicating successful treatment 2
A positive RPR test should always be confirmed with a treponemal-specific test to establish a definitive diagnosis of syphilis, according to the American College of Physicians 5

False-positive RPR results can occur in various conditions, including HIV infection, hepatitis B, hepatitis C, autoimmune diseases, and pregnancy, with a biological false positive rate of 10.7% in HIV+ patients and 8.3% in HBV+ patients 3, 6
Nontreponemal tests like RPR usually become nonreactive with time after treatment; however, in some patients, nontreponemal antibodies can persist at a low titer for a long period, sometimes for life, known as the "serofast reaction" 2

The Centers for Disease Control and Prevention recommends that a combination of a non-reactive RPR with a reactive treponemal antibody test is the expected serologic "scar" following successful treatment of syphilis 7
Treponemal antibodies remain reactive for life in most patients regardless of treatment or disease activity, with only 15-25% of patients treated during primary stage reverting to non-reactive after 2-3 years 7

The Centers for Disease Control and Prevention suggests that active syphilis is unlikely if all of the following are absent: no clinical signs or symptoms, no fourfold or greater increase in RPR titer, no new sexual exposure to a partner with confirmed syphilis, and no documented seroconversion or new reactive treponemal test within the past 12 months 7, 8
In patients with previous treated syphilis, nontreponemal tests have poor sensitivity for detecting past infection, with RPR showing only 30.7% sensitivity in "previous syphilis" cases compared to 100% in active "infective syphilis" 9

A fourfold increase in RPR titer indicates new infection or treatment failure, according to the Centers for Disease Control and Prevention 7
The Centers for Disease Control and Prevention recommends considering HIV status, as HIV-infected patients can have atypical serologic responses with unusually low, high, or fluctuating titers 7