What is the recommended method for confirming syphilis diagnosis?

How to Confirm Syphilis Diagnosis

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

Definitive Diagnostic Methods for Early Syphilis

Darkfield microscopy and direct fluorescent antibody (DFA) testing of lesion exudate or tissue are the definitive methods for diagnosing early syphilis when lesions are present. 1, 3

• These direct detection methods provide immediate confirmation of Treponema pallidum infection without waiting for antibody development 1
• Darkfield examination should be performed on suspicious lesions or body fluids (such as nasal discharge in congenital syphilis) 1
• Direct fluorescent antibody staining can be used on lesion material when darkfield microscopy is unavailable 1

Serologic Testing Algorithm

Two-Test Approach Required

• Nontreponemal tests (VDRL or RPR) must be performed quantitatively and reported with titers 1, 3
• Treponemal tests (FTA-ABS or TP-PA) are used for confirmation 1, 3
• False-positive nontreponemal results can occur with various medical conditions, making confirmation with treponemal testing essential 1

Nontreponemal Test Characteristics

• Antibody titers correlate with disease activity and are used to monitor treatment response 1, 3
• A fourfold change in titer (equivalent to two dilutions, such as 1:16 to 1:4) represents a clinically significant difference 1, 2
• Sequential tests must use the same method (VDRL or RPR) and preferably the same laboratory, as RPR titers are often slightly higher than VDRL titers and cannot be directly compared 1, 3

Treponemal Test Characteristics

• Remain reactive for life in most patients (85%) regardless of treatment or disease activity 1, 2
• 15-25% of patients treated during primary syphilis may revert to serologically nonreactive after 2-3 years 1, 2
• Should NOT be used to monitor treatment response or assess disease activity 2, 3

Stage-Specific Diagnostic Considerations

Primary Syphilis

• Characterized by painless chancre at infection site 2, 4
• Darkfield microscopy or DFA testing of the chancre provides immediate diagnosis 1, 3
• Serologic tests may be negative early in infection (seronegative window period) 5

Secondary Syphilis

• Clinical manifestations include rash, mucocutaneous lesions, and lymphadenopathy 1, 2
• Both nontreponemal and treponemal tests are highly sensitive (97-100%) at this stage 3

Latent Syphilis

• Defined by serologic evidence without clinical manifestations 1
• Early latent: documented infection within the past 12 months 2
• Late latent: infection >12 months or unknown duration 2
• Nontreponemal test sensitivity decreases in late latent disease (61-75%) 2, 3

Neurosyphilis

• CSF examination is required for diagnosis 1
• CSF-VDRL is highly specific but not sensitive—a reactive test confirms neurosyphilis, but a nonreactive test does not exclude it 1
• CSF abnormalities include mononuclear pleocytosis (10-200 cells/µL), elevated protein, and reactive CSF-VDRL 1
• A reactive CSF-VDRL plus CSF WBC >10 cells/µL supports the diagnosis 1

Special Populations

HIV-Infected Patients

• Standard serologic tests remain accurate for most HIV-infected patients 1, 3
• May have atypical responses with unusually high, low, or delayed titers 1, 2
• False-positive nontreponemal tests not confirmed by treponemal tests may be more common 1
• CSF examination is recommended for all HIV-infected persons with late-latent syphilis or syphilis of unknown duration 1, 2
• Some specialists recommend CSF examination for all HIV-infected persons with syphilis if serum RPR ≥1:32 or CD4+ count <350 cells/µL 1

Pregnant Women

• Maternal serum testing is preferred over umbilical cord blood, which can be contaminated 1
• No mother should leave the hospital without documented serologic status at least once during pregnancy and preferably at delivery 1
• All pregnant women with syphilis should be tested for HIV 1

Congenital Syphilis

• Quantitative nontreponemal test (RPR or VDRL) must be performed on infant serum, not cord blood 1
• Treponemal testing on newborn serum is not necessary due to transplacental transfer of maternal IgG antibodies 1
• Infant serum titer fourfold greater than mother's titer indicates probable congenital infection 1
• Pathologic examination of placenta with fluorescent antitreponemal antibody staining is recommended 1

Common Pitfalls to Avoid

• Never use only one type of serologic test for diagnosis 1, 3
• Never compare titers between different test types (VDRL vs. RPR) 2, 3
• Never use treponemal test titers to assess treatment response or disease activity 2, 3
• Do not assume persistent low-titer nontreponemal reactivity indicates treatment failure—this "serofast" state is common and does not necessarily represent active infection 1, 2
• If serologic tests do not confirm suspected syphilis, pursue alternative diagnostic procedures including repeat serology in 1-2 weeks, exclusion of prozone phenomenon, biopsy, or darkfield examination 1