What stage of syphilis is an asymptomatic patient in with reactive Syphilis Treponemal Antibody (STAb) (Syphilis Treponemal Ab) and Treponema pallidum Hemagglutination Assay (TPHA) tests, but a non-reactive Rapid Plasma Reagin (RPR) test?

Syphilis Staging in Asymptomatic Patient with Reactive Treponemal Tests and Non-Reactive RPR

This patient most likely has latent syphilis—either late latent syphilis (if infection occurred >1 year ago or duration unknown) or early latent syphilis (if infection occurred within the past year), or represents successfully treated syphilis from the past. 1

Understanding the Serologic Pattern

Your patient presents with a classic serologic pattern that requires careful interpretation:

• Reactive treponemal tests (CMIA and TPHA) with non-reactive RPR indicates one of three possibilities: primary syphilis (very early infection), successfully treated syphilis, or latent syphilis 1
• Treponemal tests remain positive for life in most patients regardless of treatment or disease activity, making them unsuitable for distinguishing active from past infection 1
• The non-reactive RPR is the critical finding that helps narrow the differential diagnosis 1

Staging Algorithm

Step 1: Rule Out Primary Syphilis

• Primary syphilis is unlikely but must be excluded because nontreponemal tests can be non-reactive in very early infection 1
• Perform a thorough physical examination specifically looking for:
  • Chancre or ulcer at potential infection sites (genitals, oral cavity, rectum) 1
  • If any suspicious lesions are present, obtain darkfield microscopy or direct fluorescent antibody testing 1
• If no chancre is present and the patient is truly asymptomatic, primary syphilis is effectively ruled out 1

Step 2: Determine if Previously Treated

• Review medical records meticulously for any documentation of:

  • Previous positive syphilis tests 1
  • Prior treatment with appropriate penicillin regimens 1
  • Previous RPR titers and their trajectory over time 1

• If adequately treated in the past:

  • This pattern represents successfully treated syphilis with persistent treponemal antibodies (which is expected) 1
  • No further treatment is needed 1
  • The non-reactive RPR indicates successful serologic response 1

Step 3: Stage as Latent Syphilis if Untreated

If no treatment history exists or treatment was inadequate, this is latent syphilis 1:

• Early latent syphilis = infection acquired within the past 12 months 2

  • Requires detailed sexual history to establish timing 1
  • RPR sensitivity is 85-100% in early latent disease 2
  • However, 8-18% of early latent cases can have non-reactive RPR 2

• Late latent syphilis = infection >12 months ago or unknown duration 1

  • This is the most likely diagnosis when timing cannot be established 1
  • RPR sensitivity drops to 61-75% in late latent disease 2
  • Non-reactive RPR occurs in 25-39% of late latent cases 2

Critical Clinical Actions

Immediate Evaluation Required:

• Obtain detailed sexual and medical history focusing on:

  • Timing of potential exposure (to distinguish early vs. late latent) 1
  • Previous syphilis testing and treatment 1
  • Symptoms of secondary syphilis in the past year (rash, mucocutaneous lesions, adenopathy) 1

• Perform HIV testing on all patients with syphilis 1

  • HIV-infected patients may have atypical serologic responses 1
  • They require more frequent monitoring and CSF examination for late latent disease 1

• Assess for neurosyphilis, ocular, or otic involvement by asking about:

  • Neurologic symptoms 1
  • Visual changes 1
  • Hearing loss 1
  • These require CSF examination and IV penicillin therapy 1

Treatment Recommendations:

If no prior adequate treatment documented:

• For early latent syphilis (infection <1 year): Benzathine penicillin G 2.4 million units IM as a single dose 1

• For late latent syphilis or unknown duration (most likely scenario): Benzathine penicillin G 2.4 million units IM once weekly for 3 consecutive weeks 1

• When duration cannot be established, treat as late latent syphilis to ensure adequate therapy 1

Important Caveats and Pitfalls

• Do not assume the non-reactive RPR rules out active infection 3

  • Age >35 years is independently associated with non-reactive RPR in both primary and late latent syphilis 3
  • Middle-aged and elderly patients are particularly prone to this pattern 3

• The prozone phenomenon can cause false-negative RPR 4

  • Occurs in 0.5% of reactive samples, particularly in secondary syphilis with very high antibody titers 4
  • If secondary syphilis is suspected clinically, request RPR testing at dilutions 4

• Never use treponemal test titers to monitor treatment response 1

  • They remain positive for life and do not correlate with disease activity 1

• Sequential testing must use the same method (RPR vs. VDRL) and preferably the same laboratory 1

Follow-Up Monitoring

• After treatment, monitor with quantitative RPR at 6,12, and 24 months 1
• A fourfold decline in RPR titer indicates successful treatment 1
• Some patients remain "serofast" with persistent low-level positive RPR titers despite adequate treatment, which does not indicate failure 1
• In this case, since baseline RPR is non-reactive, expect it to remain non-reactive after treatment 1