What is the difference between RPR (Rapid Plasma Reagin) and IgG (Immunoglobulin G) tests for syphilis diagnosis?

RPR vs IgG for Syphilis Diagnosis

Fundamental Distinction

RPR (Rapid Plasma Reagin) and IgG tests serve completely different diagnostic purposes in syphilis: RPR is a nontreponemal test that measures disease activity and guides treatment decisions, while treponemal IgG tests (like TP-PA, FTA-ABS, TPHA) detect antibodies that remain positive for life regardless of treatment status. 1, 2

RPR (Nontreponemal Test)

What It Measures

• RPR detects antibodies against cardiolipin-cholesterol-lecithin antigens released during cellular damage from active infection 3
• Titers correlate directly with disease activity and should always be reported quantitatively 2
• RPR becomes negative or low-titer after successful treatment in most patients 1

Sensitivity by Disease Stage

• Primary syphilis: 62-78% sensitive (misses 22-38% of early cases) 3, 4
• Secondary syphilis: 97-100% sensitive 3, 4
• Early latent syphilis: 85-100% sensitive 1, 4
• Late latent syphilis: 61-75% sensitive (negative in 25-39% of cases) 1, 4

Clinical Uses

• Primary role: Monitoring treatment response—a fourfold decline in titer indicates successful treatment 1, 2
• Distinguishing active infection from past treated disease 1
• Detecting reinfection (fourfold increase from baseline) 1
• Specificity is 87-100%, with false positives rare at titers ≥1:8 3, 1

Treponemal IgG Tests

What They Measure

• Detect specific antibodies against Treponema pallidum antigens 2, 5
• Include TP-PA, FTA-ABS, TPHA, and automated CLIA/CLEIA assays 6, 5
• Remain positive for life in most patients (85-100%) regardless of treatment 1, 2

Sensitivity by Disease Stage

• Primary syphilis: 82-91% for traditional tests (FTA-ABS, HA, PA); 92-100% for newer CLIA/CLEIA/IC assays 6
• Secondary syphilis: Approaches 100% 5
• All stages: Generally more sensitive than RPR, especially in late disease 6, 7

Clinical Uses

• Primary role: Confirming syphilis exposure (current or past) 2
• Initial screening in reverse algorithm approaches 5
• Cannot be used to monitor treatment response or detect reinfection 1, 2

Critical Diagnostic Algorithm

Both Tests Are Required for Complete Diagnosis

The CDC explicitly states that a positive treponemal test alone is insufficient for diagnosis—nontreponemal tests must also be performed to distinguish active infection from past treated disease. 1, 2

Interpretation Patterns

Pattern 1: RPR+ / Treponemal IgG+

• Indicates active syphilis requiring treatment 2
• Stage determined by clinical findings and RPR titer 1

Pattern 2: RPR- / Treponemal IgG+

• Most commonly represents past treated syphilis 1, 2
• Can also represent late latent/tertiary syphilis with waning nontreponemal antibodies (occurs in 25-39% of late cases) 1, 4
• Requires treatment as late latent syphilis if no documented adequate prior treatment 2

Pattern 3: RPR+ / Treponemal IgG-

• Likely false-positive RPR (autoimmune disease, pregnancy, infection) 7
• Repeat testing recommended 5

Pattern 4: RPR- / Treponemal IgG-

• Rules out syphilis (current or past) 1

Treatment Monitoring: RPR Only

Never use treponemal IgG tests to assess treatment response—they remain positive regardless of cure and correlate poorly with disease activity. 1, 2

Expected RPR Response After Treatment

• Early syphilis: Fourfold decline within 6-12 months indicates success 1
• Late latent syphilis: Fourfold decline within 12-24 months 1
• 15-25% of patients treated during primary syphilis achieve complete RPR seroreversion (negative) after 2-3 years 1
• Many remain "serofast" with persistent low titers (typically <1:8) indefinitely 1

Common Pitfalls to Avoid

Critical Error #1: Switching Between RPR and VDRL

• RPR and VDRL titers are NOT interchangeable and cannot be compared directly 2, 4
• Sequential monitoring must use the same test type, preferably by the same laboratory 1, 2, 4
• If a patient was diagnosed with VDRL, continue using VDRL; if RPR, continue with RPR 4

Critical Error #2: Using Treponemal Tests for Treatment Monitoring

• Treponemal IgG remains positive for life in 75-85% of treated patients 1, 2
• Cannot distinguish treatment success from failure 1
• Cannot detect reinfection 1

Critical Error #3: Misinterpreting RPR-/Treponemal+ Pattern

• This pattern does NOT automatically mean "old treated infection" 1, 2
• In late latent/tertiary syphilis, RPR is negative in 25-39% of active cases 1, 4
• Without documented adequate prior treatment, this pattern requires treatment as late latent syphilis 2

Special Considerations

HIV-Infected Patients

• Standard serologic tests remain accurate for most HIV patients 1, 2
• Some may have atypical responses with unusually low, high, or fluctuating titers 1, 4
• Require more frequent monitoring (every 3 months instead of 6 months) 1
• False-negative serologic tests rarely reported; if clinical suspicion high with negative serology, pursue darkfield examination or biopsy 1

Very Early Primary Syphilis

• Both RPR and treponemal tests can be negative in the first 1-4 weeks after infection 1, 4
• Darkfield microscopy or direct fluorescent antibody testing of lesion exudate is definitive during this window 2