Synonym

• Nontreponemal test for syphilis
• RPR
• Syphilis screening test

Tubes

• Red, tiger top, or gel separator tube
• Lavender top tube acceptable at some laboratories
• 5-7 mL of venous or cord blood

Additional information

• Avoid collection of sample immediately after a meal
• Alcohol consumption is to be avoided for 24 hrs before test
• Handle the specimen gently to prevent hemolysis
• Reject lipemic or hemolyzed samples
• If delayed separate serum and store sample at 4^°-8^°C up to 72 hrs or at –20^°C up to 1 week

Info

• The rapid plasma regain (RPR) test is a screening test, from blood, for syphilis (Treponema pallidum) infection
• The RPR test is a rapid flocculation test performed by using a cardiolipin-lecithin-cholesterol carbon containing antigen (modified VDRL antigen) reagent mixed with the patient's serum, to give reproducible qualitative and quantitative results
• Syphilis is a venereal disease caused by Treponema pallidum, a spirochete usually spread during sexual contact, across the placenta infecting the unborn child, and also by exposure to infected blood

Clinical

• The clinical utility of the RPR test includes:
• Screening for primary and secondary syphilis
• To monitor the therapeutic response in syphilis and to detect reinfection
• To detect neurosyphilis [Central nervous system (CNS) infection from syphilis]
• Aids in the diagnosis of congenital syphilis
• For evaluation of sexual partners of patients with syphilis
• After treatment in patients with early-stage syphilis, to monitor declining reactivity (at 3-mo intervals for 1 yr)
• Pregnant women should be tested at their first prenatal visit, third trimester (28 weeks), and again at delivery
• Untreated syphilis progresses through 4 stages namely primary, secondary, latent, and tertiary stages. The RPR test becomes reactive in early primary phase and the titers peak at secondary phase, and decrease in the late phase of syphilis
• Primary Syphilis:
• The primary lesion (a chancre) appears 10-90 days (average 21 days) after exposure to syphilis and heals within 3-6 weeks
• Clinically, this is seen as a small sore or ulcer that is painless (the chancre) with regional lymphadenopathy
• Diagnostic sensitivity varies by technique (for primary stage):
• RPR test: 30% within one week and 90% after three weeks
• Dark-field microscopy of skin lesion: 80%
• Treponemal-specific tests: 76-84%
• Secondary syphilis:
• Begins 2 to 8 weeks following the onset of chancre
• The clinical manifestation include:
• Skin and mucous membranes:
• Condyloma latum
• Diffuse rash
• Renal system:
• Glomerulonephritis
• Nephrotic syndrome
• Liver: Hepatitis
• Central nervous system:
• Headache
• Meningismus
• Cranial neuropathy
• Iritis
• Uveitis
• Constitutional symptoms:
• Fever
• Malaise
• Generalized lymphadenopathy
• Arthralgias
• Weight loss
• Diagnostic sensitivity varies by technique (for secondary stage):
• RPR test: 100%
• Dark-field microscopy of skin lesion: 80%
• Treponemal-specific tests: 100%
• Latent syphilis:
• Usually occurs in the first year of infection and does not manifest clinically, but is infectious in pregnancy and by transfusion
• RPR test is non-reactive during this stage
• Tertiary or late syphilis:
• This is a slowly progressive condition which may affect any organ, and usually occurs 1-10 years after the initial infection
• The clinical spectrum of this stage includes:
• Cutaneous gummatous lesion
• Cardiovascular syphilis usually begins 5-10 years after initial infection and may result in aortic aneurysm, incompetence of the aortic valve, and narrowing of the coronary ostia
• Neurosyphilis which occurs in 10% of untreated syphilis patients, and is seen clinically as:
• Seizures
• Ataxia
• Aphasia
• Paresis
• Hyperreflexia
• Cognitive/Personality changes
• Visual changes (Argyll Robertson pupil)
• Hearing loss
• Neuropathy
• Loss of bowel or bladder function
• Tabes dorsalis
• Diagnostic sensitivity varies by technique (for tertiary stage):
• RPR test: 90%
• VDRL test on CSF (for Neurosyphilis): 75%
• Treponemal-specific tests: 94-96%
• Congenital syphilis:
• This occurs when a child is born to a mother with secondary or tertiary syphilis. RPR test on cord blood should be correlated with the maternal test
• Clinical evidence of early congenital syphilis includes manifestations such as:
• Generalized lymphadenopathy
• Glomerulonephritis
• Hemorrhagic rhinitis
• Hepatosplenomegaly
• Hydrops
• Neurologic symptoms
• Perioral fissures
• Periostitis
• Pseudoparalysis, due to pain secondary to osteochondritis
• Thrombocytopenia
• Vesicular or bullous macular rash
• Clinical manifestations of late congenital syphilis include:
• Prominent frontal bones, depression of nasal bridge (saddle nose), abnormal maxilla development, anterior tibial bowing
• Clutton joints
• Interstitial keratitis and vision loss
• Hutchinson's teeth
• Mulberry molars
• Decreased hearing or deafness
• Paroxysmal cold hemoglobinuria
• Gummatous involvement
• Saber shins
• Rhagades scars
• Infants born to infected mothers may have positive RPR results due to passive maternal antibody transfer or early infection, which should be confirmed by treponemal specific tests

Additional information

• Epidemiologic risk factors for having syphilis include:
• Unprotected or promiscuous sex
• Intravenous (IV) drug use
• Health care workers
• People aged 20-29 years
• Blacks are at higher risk than Whites
• Syphilis is more common in men than women
• The RPR test is a better first line screening test than the VDRL test because:
• It is a rapid technique
• It has higher diagnostic sensitivity and specificity
• It has lower false positive rate
• It offers better follow-up of treatment response
• A positive RPR test is not conclusive of syphilis and should be confirmed by treponemal specific tests that include:
• Fluorescent treponemal antibody-absorption test (FTA-ABS)
• Microhemagglutination - Treponema pallidum (MHA-TP)
• Treponema pallidum immobilization (TPI)
• Line Immunoassay (LIA)
• A negative RPR test does not rule out syphilis, as it may be falsely negative due to:
• Recent infection (14-21 days) with no detectable immunologic changes. Repeat tests should be performed at 1-wk, 1-mo, and 3-mo intervals to establish the presence or absence of disease
• During latent and tertiary phase of syphilis
• Impaired immune system (e.g. AIDS)
• Prozone reaction in secondary phase of syphilis
• If the patient is treated at the seronegative primary stage, the RPR remains nonreactive
• A person treated during seropositive primary stage usually becomes nonreactive within 6 months of treatment
• Factors interfering with test results include:
• Lipemic or hemolyzed sample
• Alcohol decreases reaction intensity during test
• Immunosuppression
• The newer immunochromatographic strip test (ICS) has a better sensitivitythan the RPR test and can be done in a non-laboratory setting
• Related laboratory tests include:
• CSF analysis
• Dark field microscopy
• Gram stain
• Hepatitis B
• Hepatitis C
• HIV testing
• Immunochromatographic strip test (ICS)
• Treponemal specific tests (MHA-TP, TPI, FTA-ABS, and LIA)
• Venereal diagnosis research laboratory (VDRL) test

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

Normal results (negative RPR) may be reported as:

• Nonreactive
• Negative
• No flocculation
• Titer: <1:2

Indeterminate results may be reported as:

• Weakly reactive
• Slight flocculation

Abnormal results (positive RPR) may be reported as:

• Reactive
• Definite flocculation
• Titer: >1:8

High Result

A high result is a positive RPR, which may be reported as:

• Reactive
• Definite flocculation
• Titer: >1:8

A positive RPR may represent true infection with syphilis, or may be due to a false positive result.

Conditions associated with false positive RPR results include:

• Active immunization in children
• Age (Elderly)
• Blood loss (repeated)
• Brucellosis
• Chancroid
• Chickenpox
• Common cold
• Filariasis
• Hepatitis (Infectious)
• Hyperproteinemia
• Infectious mononucleosis
• Leishmaniasis
• Leprosy
• Leptospirosis (Weil's disease)
• Lupus erythematosus
• Lyme disease
• Lymphogranuloma venereum
• Malaria
• Measles
• Periarteritis nodosa
• Pneumonia (atypical or pneumococcal)
• Pregnancy
• Rat-bite fever
• Relapsing fever
• Rheumatic fever
• Rheumatoid arthritis
• Scarlet fever
• Subacute bacterial endocarditis
• Trypanosomiasis
• Tuberculosis (advanced pulmonary)
• Typhus fever
• Vaccinia
• Yaws (Treponema pertenue infection)

References

• Angue Y et al. Syphilis serology testing: a comparative study of Abbot Determine, Rapid Plasma Reagin (RPR) card test and Venereal Disease Research Laboratory (VDRL) methods. P N G Med J. 2005 Sep-Dec;48(3-4):168-73.
• ARUP Laboratories®. Treponema pallidum (Rapid Plasma Reagin) with Reflex to Titer. [Homepage on the internet]©2007. Last updated in September 2006. Last accessed on February 5, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0050471.jsp
• Brown DL et al. Diagnosis and Management of Syphilis. Am Fam Physician. 2003 Jul 15;68(2):283-90. Available at URL: http://www.aafp.org/afp/20030715/283.html
• Centers for Disease Control: Congenital Syphilis --- United States, 2002. MMWR.August 13, 2004 / 53(31);716-719. [Homepage on the Internet]. Last reviewed on August 12, 2004. Last accessed on January 27, 2007. Available at URL: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5331a4.htm
• Centers for Disease Control: Primary and Secondary Syphilis --- United States, 2003--2004.MMWR.March 17, 2006 / 55(10);269-273. [Homepage on the Internet]. Last reviewed 0n March 16, 2006. Last accessed on January 27, 2007. Available at URL: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5510a1.htm?s_cid=mm5510a1_e
• eMedicine from WebMD®. Syphilis. [Homepage on the Internet] ©1996-2006. Last updated on August 1, 2006. Last accessed on January 27, 2007. Available at URL: http://www.emedicine.com/med/topic2224.htm
• Laboratory Corporation of America. Rapid Plasma Reagin (RPR), Quantitation. [Homepage on the internet]©2003. Last updated on September 26, 2006. Last accessed on January 27, 2007. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/se024400.htm
• Libois A et al. HIV and Syphilis: When to Perform a Lumbar Puncture. Sex Transm Dis. 2006 Jul 19; [Epub ahead of print].
• Montoya PJ et al. Comparison of the diagnostic accuracy of a rapid immunochromatographic test and the rapid plasma reagin test for antenatal syphilis screening in Mozambique. Bull World Health Organ, Feb. 2006, vol.84, no.2, p.97-104. ISSN 0042-9686.
• Peeling RW et al. Diagnostic tools for preventing and managing maternal and congenital syphilis: an overview. Bull World Health Organ. 2004 Jun;82(6):439-46.
• U.S. Preventive Services Task Force. Screening for Syphilis: Brief Update. July 2004. Agency for Healthcare Research and Quality, Rockville, MD. Last reviewed in July 2004. Last accessed on January 27, 2007. Available at URL: http://www.ahrq.gov/clinic/3rduspstf/syphilis/syphilup.htm
• UTMB Laboratory Survival Guide®. RAPID PLASMA REAGIN. [Homepage on the Internet]© 2006. Last reviewed on September 6, 2006. Last accessed on January 27, 2007. Available at URL: http://www.utmb.edu/lsg/LabSurvivalGuide/micro/RAPID%20PLASMA%20REAGIN.html