What is the diagnostic and treatment approach for a patient suspected of having syphilis?

Syphilis Confirmation Diagnosis

Definitive Diagnostic Approach

The diagnosis of syphilis requires both a nontreponemal test (VDRL or RPR) AND a treponemal test (FTA-ABS, TP-PA, or MHA-TP) performed together, as using only one type of serologic test is insufficient for diagnosis. 1, 2, 3

Direct Detection Methods (When Lesions Present)

• Darkfield microscopy of lesion exudate or tissue is the gold standard for diagnosing primary syphilis when lesions are present. 3, 4
• Direct fluorescent antibody staining (DFA-TP) of lesion material serves as an alternative to darkfield examination when available. 3
• These direct methods provide definitive diagnosis without waiting for serologic conversion. 3

Standard Serologic Testing Algorithm

Two-Test Approach Required

• Screen with nontreponemal tests (VDRL or RPR) and confirm ALL reactive nontreponemal tests with treponemal tests (FTA-ABS, TP-PA, or MHA-TP). 1, 2, 3
• Report nontreponemal test results quantitatively (e.g., 1:4,1:8,1:16) as titers correlate with disease activity. 1, 2, 3
• A fourfold change in titer (equivalent to two dilutions, such as 1:16 to 1:4) is necessary to demonstrate clinically significant difference. 1, 2

Understanding Test Characteristics

Nontreponemal tests (RPR/VDRL):

• Sensitivity varies by stage: 88.5% in primary, 100% in secondary, 85-100% in early latent, 61-75% in late latent, and only 47-64% in tertiary syphilis. 2, 5
• False-positive results occur in 0.6-1.3% of the general population, with higher rates in autoimmune diseases, pregnancy, HIV infection, hepatitis B/C, IV drug use, and advanced age. 2
• These tests eventually become nonreactive after successful treatment in most patients. 1, 2

Treponemal tests (FTA-ABS, TP-PA, MHA-TP):

• Remain reactive for life in most patients (85-100%) regardless of treatment or disease activity. 1, 2
• Should NEVER be used to assess treatment response or monitor disease activity. 2, 5
• 15-25% of patients treated during primary syphilis may revert to serologically nonreactive after 2-3 years. 1, 2

Interpretation of Combined Results

• Positive nontreponemal + Positive treponemal = Confirmed syphilis (active or past infection; use clinical context and titers to determine). 2, 3
• Positive nontreponemal + Negative treponemal = Biological false-positive RPR requiring investigation for autoimmune disease, pregnancy, or viral hepatitis. 2
• Negative nontreponemal + Negative treponemal = Syphilis effectively ruled out (no current or past infection). 2
• Negative nontreponemal + Positive treponemal = Either treated past infection OR late-stage disease (remember: 25-39% of late latent and 36-53% of tertiary cases have negative RPR/VDRL). 2, 5

Special Diagnostic Considerations

HIV-Infected Patients

• Standard serologic tests remain accurate for most HIV-infected patients, though atypical responses can occur. 1, 3
• Unusual serologic responses include titers that are higher or lower than expected, or delayed appearance of seroreactivity. 1, 2
• False-negative serologic tests have been reported; if clinical suspicion is high with negative serology, pursue biopsy or darkfield examination. 2
• More frequent monitoring (every 3 months instead of 6 months) is required. 2

Neurosyphilis Diagnosis

• CSF examination showing reactive CSF-VDRL plus CSF WBC >10 cells/µL confirms neurosyphilis. 3
• CSF-VDRL is highly specific but insensitive—a reactive test confirms neurosyphilis, but a nonreactive test does NOT exclude it. 3
• CSF white blood cell count is typically elevated at 10-200 cells/µL with mononuclear predominance. 3
• Avoid blood contamination during lumbar puncture as it can cause false-positive CSF-VDRL results. 3

Pregnancy Screening

• Screen all pregnant women at first prenatal visit, at 28 weeks in high-risk populations, and at delivery. 2, 3
• Evaluate all infants born to seropositive mothers with quantitative nontreponemal test on infant serum (NOT cord blood). 3

Critical Pitfalls to Avoid

• Never rely on a single test type for diagnosis—both nontreponemal and treponemal tests are required. 1, 2, 3
• Never use treponemal test titers to monitor treatment response—they remain positive regardless of cure. 2, 5
• Ensure sequential testing uses the same methodology (RPR vs VDRL), preferably by the same laboratory, as titers are not interchangeable. 1, 2
• Be aware of the prozone phenomenon: false-negative nontreponemal tests can occur with very high antibody titers; dilute serum if clinical suspicion is high. 3
• In late-stage disease (late latent or tertiary), never exclude syphilis based on negative RPR/VDRL alone—up to 39% of late latent and 53% of tertiary cases will be negative. 2, 5

Staging for Treatment Decisions

• Early latent syphilis: Documented infection <1 year, serologic evidence without clinical manifestations. 3
• Late latent syphilis: Documented infection >1 year or unknown duration. 3
• Proper staging is essential as it determines treatment duration (single dose vs. three weekly doses of benzathine penicillin G). 4, 6