RPR and the Serologic Diagnosis of Syphilis

Clinical Review & Education JAMA Diagnostic Test Interpretation RPR and the Serologic Diagnosis of Syphilis Meredith E. Clement, MD; Charles B. Hicks, MD A 45-year-old man presents in clinic for follow-up after a recent emergency department evaluation for dysuria. He was diagnosed with gonococcal urethritis and treated with in- tramuscular ceftriaxone and oral azithromycin. His dysuria resolved and he now feels well. He was divorced 10 years previously and has since had multiple sexual partners. He re- ports sex only with women. His examination is normal, including the genitalia and skin. He has no neurologic deficits. Screening for other sexually transmitted infections reveals hepa- titis B virus serologies consistent with previous immunization, a negative human immuno- deficiency virus (HIV) enzyme immunoassay (EIA), and reactive syphilis test results (Table 1). The patient does not recall prior syphilis diagnosis or treatment. The local health de- partment has no record of syphilis testing for him. Table 1. Patient Test Results Laboratory Test Value Reference Range RPR Nonreactive TP-EIA Reactive Nonreactive Abbreviations: RPR, rapid plasma reagin; TP-EIA, Treponema pallidum enzyme immunoassay. HOW DO YOU INTERPRET THESE RESULTS? A. The patient has latent syphilis and requires 2.4 million U intramuscularly of benzathine penicillin G weekly for 3 doses (total 7.2 million U penicillin). B. The patient has low titers representing the serofast state and does not require treatment. C. The patient has falsely elevated titers and should undergo repeat testing. D. The patient needs a lumbar puncture to assess for asymptomatic neurosyphilis. Answer A. The patient has latent syphilis and requires 2.4 million U intra- muscularly of benzathine penicillin G weekly for 3 doses (total 7.2 million U penicillin). Test Characteristics A clear understanding of the diagnosis of syphilis is of particular pub- lic health importance because the incidence of syphilis in the United States is increasing. Currently, an estimated 55 000 new cases are diagnosed each year. 1 Treponema pallidum, the spirochete that causes syphilis, cannot be cultured. Thus, diagnosis requires indi- rect techniques such as serologic testing, relying on the detection of both treponemal and nontreponemal antibodies. Treponemal tests detect antibodies to specific antigenic components of T pall- idum, while nontreponemal tests detect antibodies to a nonspe- cific cardiolipin-cholesterol-lecithin reagin antigen produced by the host in response to syphilis infection. 2 The rapid plasma reagin (RPR), a nontreponemal test, has tra- ditionally been used as an initial screening test for syphilis because it is widely available, relatively easy to perform, and inexpensive (Medicare midpoint reimbursement, RPR with reflex titer, $8.11). 3 Additionally, RPR is a quantitative test and antibody titers can be monitored to assess treatment response. 4 However, the RPR re- quires a visual assessment for the presence of flocculation (aggre- gation of particles), a process that requires laboratory technologist time and is not suitable for automation. Furthermore, false- positive results may occur in the setting of autoimmune disease, pregnancy, tuberculosis, or other inflammatory conditions; thus, RPR testing requires confirmation with treponemal serologic tests such as the T pallidum enzyme immunoassay (TP-EIA). 5 Although false- positive results also occur with TP-EIA, it is unlikely that a patient will have both false-positive reagin and false-positive treponemal se- rologies. Therefore, the presence of a reactive nontreponemal test and a reactive treponemal test is diagnostic of syphilis (Table 2). 4,6,7 Application to This Patient This patient has late latent syphilis and should receive 3 weekly in- jections of benzathine penicillin G. Because the patient is asymptomatic with reactive serologies, he has latent syphilis. Latent syphilis can be divided into early- latent syphilis, diagnosed within 1 year of infection, and late-latent syphilis, diagnosed 1 year or more after infection. When the date of original infection is unknown, the patient is considered to have late- latent syphilis. 8,9 Early-latent syphilis is treated with a single intramuscular dose of benzathine penicillin G, while late-latent syphilis requires 3 weekly doses of benzathine penicillin G. 6 Following successful treatment, the RPR declines over time and may become nonreactive. However, the RPR may remain reactive at a low titer (generally <1:8), a condition referred to as the serofast state. The serofast state does not apply to this patient because he has no previous syphilis history. He does not have falsely elevated titers; his treponemal and nontreponemal tests were both reactive, making the diagnosis of syphilis and obviating the need for repeat testing. Because T pallidum can invade the central ner- JAMA November 12, 2014 Volume 312, Number 18 Copyright 2014 American Medical Association. All rights reserved. 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