How do you stage syphilis based on laboratory (lab) tests?

Staging Syphilis Based on Laboratory Tests

Syphilis staging is primarily determined by a combination of clinical presentation and laboratory test results, with specific patterns of nontreponemal and treponemal antibody tests corresponding to different stages of infection. 1

Laboratory Tests for Syphilis Diagnosis

Types of Tests

• Nontreponemal tests: RPR, VDRL, TRUST

  • Detect antiphospholipid antibodies produced in response to infection
  • Used for screening and monitoring treatment response
  • Titers correlate with disease activity

• Treponemal tests: FTA-ABS, TP-PA, EIA, CIA

  • Detect antibodies specific to T. pallidum
  • Remain positive for life in most cases after infection
  • Used for confirmation

Laboratory Patterns by Stage

Primary Syphilis

• Nontreponemal tests:
  • Sensitivity: 50-92.7% 2, 1
  • May be negative in very early infection
  • Titers typically low (≤1:8)
• Treponemal tests:
  • Sensitivity: 95-100% 1
  • Become positive earlier than nontreponemal tests
• Direct detection: Dark-field microscopy or PCR from lesion may be positive

Secondary Syphilis

• Nontreponemal tests:
  • Sensitivity: 97-100% 2
  • Highest titers observed at this stage (often ≥1:32)
• Treponemal tests:
  • Sensitivity: nearly 100% 2, 1

Early Latent Syphilis

• Nontreponemal tests:
  • Sensitivity: 82-100% 2
  • Titers typically declining from secondary stage
• Treponemal tests:
  • Sensitivity: nearly 100% 1

Late Latent Syphilis

• Nontreponemal tests:
  • Sensitivity: 61-75% 2
  • Lower titers than early stages
  • May become nonreactive in 25-40% of untreated cases
• Treponemal tests:
  • Remain reactive in most cases

Tertiary Syphilis

• Nontreponemal tests:
  • Sensitivity: 47-64% 2
  • Often low titers or nonreactive
• Treponemal tests:
  • Usually remain reactive

Neurosyphilis

• Serum tests:
  • Similar to patterns in other stages
• CSF tests:
  • CSF-VDRL: Sensitivity 71-85% in symptomatic neurosyphilis, specificity 98-100% 2
  • CSF-RPR: Sensitivity 56-82% in symptomatic neurosyphilis 2
  • CSF treponemal tests: Higher sensitivity but lower specificity

Interpretation of Test Results

Nontreponemal Result	Treponemal Result	Interpretation
Positive	Positive	Confirmed syphilis (current or past)
Positive	Negative	Likely false-positive nontreponemal test
Negative	Positive	Possible very early infection, previously treated syphilis, or late-stage syphilis
Negative	Negative	No evidence of syphilis [1]

Special Considerations

Prozone Phenomenon

• False-negative nontreponemal tests due to antibody excess
• Most common in secondary syphilis
• If clinical suspicion is high but test is negative, request dilution of specimen

HIV Co-infection

• May have unusual serologic responses 1
• More likely to have false-negative results or delayed serologic response
• More intensive monitoring recommended

Serofast State

• Persistent low-titer positive nontreponemal tests despite adequate treatment
• Not indicative of treatment failure if titers have decreased appropriately

Practical Algorithm for Staging

1. Obtain both treponemal and nontreponemal tests
2. Assess nontreponemal titer:
   • High titers (≥1:32): Suggestive of early syphilis (primary, secondary, early latent)
   • Low titers (≤1:16): May indicate late latent or tertiary syphilis
3. Correlate with clinical presentation:
   • Primary: Chancre present, low titers
   • Secondary: Rash, condylomata lata, high titers
   • Latent: No symptoms, titers variable
   • Tertiary: End-organ damage, variable titers
4. Consider time course:
   • Early syphilis: Infection <1 year
   • Late syphilis: Infection >1 year or unknown duration

Remember that laboratory tests should always be interpreted in conjunction with clinical findings, as the sensitivity of nontreponemal tests varies significantly by stage, with highest sensitivity in secondary syphilis and lowest in late stages 2, 1.