What is the workup for a patient with a positive Rapid Plasma Reagin (RPR) test?

Workup for Positive RPR Test

A positive Rapid Plasma Reagin (RPR) test requires confirmatory treponemal testing, clinical evaluation for disease staging, and appropriate treatment based on the stage of syphilis. 1

Initial Diagnostic Steps

1. Confirmatory treponemal testing:

   • Perform a treponemal-specific test such as FTA-ABS (Fluorescent Treponemal Antibody Absorption) or TP-PA (T. pallidum Particle Agglutination) 2, 1
   • These tests detect antibodies specific to T. pallidum and remain positive for life in most cases

2. Clinical evaluation:

   • Complete physical examination focusing on:
     • Skin and mucous membranes (for chancres, rash)
     • Lymph nodes
     • Neurological assessment
     • Ocular examination
   • Detailed sexual history to determine potential exposure time

3. RPR titer quantification:

   • Higher titers (≥1:16) more likely represent active infection 1
   • Lower titers may indicate early infection, previously treated infection, or biological false positive 1

Interpretation of Results

Positive RPR + Positive Treponemal Test:

• Indicates current or past syphilis infection
• Disease staging is required to determine treatment:
  • Primary: Genital, anal, or oral ulcer (chancre)
  • Secondary: Rash, mucocutaneous lesions, lymphadenopathy
  • Early latent: Asymptomatic, infection <1 year
  • Late latent: Asymptomatic, infection >1 year or unknown duration
  • Tertiary: Gummas, cardiovascular or late neurologic manifestations

Positive RPR + Negative Treponemal Test:

• Biological false positive (BFP) reaction 2
• BFP rates: 0.8-1.3% in general population, higher (4-10.7%) in HIV-positive individuals 2, 1
• Common causes of BFP:
  • Autoimmune disorders (SLE, rheumatoid arthritis)
  • Pregnancy
  • IV drug use
  • Acute viral infections
  • Advanced age
  • Hepatitis B or C infection

Additional Testing

1. HIV testing:

   • Essential due to high co-infection rates 1
   • HIV affects syphilis presentation, progression, and follow-up requirements

2. Lumbar puncture (indicated in):

   • Neurological or ophthalmologic symptoms
   • Treatment failure
   • Late latent syphilis or unknown duration
   • HIV co-infection with CD4 <350 or RPR ≥1:32
   • Tertiary syphilis

3. Other STI screening:

   • Gonorrhea and chlamydia testing
   • Hepatitis B and C testing

Special Considerations

Pregnancy

• All pregnant women should be screened at first prenatal visit
• High-risk women should be retested in third trimester and at delivery 1

HIV Co-infection

• Same treatment regimens apply but closer follow-up required 1
• Higher rates of neurologic complications
• Consider CSF examination more liberally

Common Pitfalls to Avoid

1. Misinterpreting RPR titers:

   • Prozone phenomenon: False-negative results in high-titer samples 1
   • Serofast state: Persistent low, unchanging titers after treatment (15-20% of patients) 1

2. Inadequate follow-up:

   • Switching between different nontreponemal tests (RPR vs. VDRL)
   • Relying on treponemal tests to monitor treatment response
   • Failing to distinguish between treatment failure and reinfection 1

3. Overlooking neurosyphilis:

   • CSF examination is critical in altered patients 1
   • No single laboratory test is perfectly sensitive/specific for neurosyphilis

Remember that while treponemal tests typically remain reactive for life regardless of treatment, nontreponemal tests like RPR are useful for monitoring treatment response, with a fourfold decrease in titer indicating treatment success 1, 3.