Syphilis is a vertically or sexually transmitted infection caused by Treponema pallidum subspecies pallidum.
In the primary stage of acquired syphilis, there is an appearance of a painless ulcer (chancre). Then in the secondary stage, there are skin rashes and sores on mucous membranes.
In the latent stage, it is asymptomatic and not communicable. It is in the tertiary or late stage that it is symptomatic but not communicable; it usually appears 10-20 years after 1st infection.

Syphilis%20-%20primary Diagnosis


Stages of Acquired Syphilis
  • Primary: Appearance of painless ulcer (chancre) that heals spontaneously
  • Secondary: Skin rashes and sores on mucous membranes
  • Latent: Asymptomatic and not communicable
    • May be early (infection occurred <2 years) or late (infection occurred >2 years ago)
  • Tertiary or late: Symptomatic but not communicable, appears 10-20 years after 1st infection
  • May affect internal organs (eg brain, nerves, eyes, heart)


  • The typical finding is a single chancre in the anogenital area, usually with regional lymphadenopathy
    • Any anogenital ulcer is considered syphilitic unless proven otherwise
    • Atypical presentations include multiple, painful, purulent and destructive ulcers
  • The presence of vesicles alone on physical exam is most consistent with herpes simplex virus-2 (HSV-2)
  • Unless ruled out, treat the patient for other etiologies of genital ulcers (eg genital herpes, chancroid, lymphogranuloma venereum, granuloma inguinale, Behcet's syndrome, or trauma) based on local prevalence patterns
    • Please see Chlamydia - Uncomplicated Anogenital Infection Disease Management Chart for details

 Alternative Diagnosis

  • Consider ruling out conditions that can imitate early syphilis such as eczema, atopic dermatitis, contact dermatitis, erythema multiforme, pityriasis rosea, Hodgkin's lymphoma, viral exanthem, or systemic allergy


  • Details of previous treatment, blood donation, other treponemal infections

Physical Examination

  • Perform general assessment and look for signs of sexually transmitted infections (STI)
    • Inspect mucocutaneous regions, including the mouth and pharynx
    • Inspect external genitalia for cutaneous lesions, inflammation, urethral discharge and anatomic irregularities
    • Palpate inguinal lymph nodes
    • Perform perianal inspection
    • Do illuminated speculum exam to visualize cervix, vaginal walls and to evaluate endocervical and vaginal discharges
    • If vaginal discharge is present, obtain specimens for Chlamydia test, gonorrhea culture, Gram stain, and Trichomonas slide if tests are available
  • Search for systemic signs of syphilis
    • Generalized, non-itchy, polymorphic rash on the palms and soles, mucocutaneous lesions, nodules/plaques or ulcers
    • Condylomata lata, patchy alopecia, anterior uveitis
    • Generalized lymphadenopathy
    • Meningitis, cranial nerve palsies, general paresis, tabes dorsalis
    • Signs of aortic regurgitation, aortic aneurysm

Laboratory Tests

Direct Demonstration of Organism

  • May use specimens from lesions or infected lymph nodes to make a definitive diagnosis of early syphilis using one of the following tests:
    • Darkfield microscopy - with few false-negative but no false-positive results
      • If test is initially negative, repeat test on 3 consecutive days
    • Direct fluorescent antibody (DFA) test
    • Polymerase chain reaction (PCR)

Serologic Tests

  • Used to make a presumptive diagnosis of syphilis
    • Use >1 type of serologic test to make a diagnosis of syphilis because false-positive nontreponemal test (NTT) results may occur secondary to various medical conditions
    • May be negative in primary syphilis

Nontreponemal Tests (NTT)

  • Also called cardiolipin antigen or Reagin test
  • Screening tests which usually correlate with disease activity, help in staging the infection and monitoring treatment response and assessing reinfection
  • Positive in approximately 85% of patients with primary syphilis within 1 week of chancre development
  • A 4-fold change in titer, equivalent to a change of 2 dilutions, is necessary to demonstrate a clinically significant difference between 2 NTTs that were obtained using the same serologic test
  • Sequential serologic tests in patients should be done using the same testing method, preferably in the same lab
  • Biologic false-positive reaginic tests may be seen in pregnancy, post immunization, recent myocardial infarction (MI) and in many febrile infective illnesses
  • Eg Venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) tests

Treponemal Tests (TT)

  • For confirmatory purposes, help validate results and decrease false positives
  • Correlate poorly with disease activity and should not be used to assess treatment response
  • Positive in 90% of patients with primary syphilis
  • If test is positive, should be followed by NTT with titer to help direct patient management
  • If NTT is negative, a different treponemal test should be done to validate results of the 1st test
  • A reactive TT usually remains reactive for the rest of a person’s life regardless of treatment
  • Eg Fluorescent treponemal antibody absorption test (FTA-ABS), T pallidum particle agglutination test (TP-PA), T pallidum hemagglutination assay (TPHA), Treponemal enzyme immunoassay (EIA)/Immunoglobulin G (IgG), IgG immunoblot test for T pallidum
    • EIA is positive in previously treated, incompletely treated, or untreated patients; therefore, NTT should be requested for a person with a positive EIA

Specific Anti-T pallidum Immunoglobulin M (IgM) Antibody Tests

  • Recommended when TP-PA or EIA is positive and NTT is negative in patients with clinical signs suggestive of syphilis
  • Help in monitoring the serological response to treatment in NTT-negative primary syphilis
  • Eg 19S-immunoglobulin M-fluorescent treponemal antibody absorption (19S-IgM-FTA-ABS) test, IgM immunoblot for T pallidum, Anti-T pallidum IgM-antibody test using EIA

Other Diagnostic Approaches

  • CSF analysis for a neurosyphilis diagnosis shows elevated WBC count (predominantly lymphocytes) and protein (can be observed in the absence of a reactive CSF VDRL test) 
  • Used as a cerebrospinal fluid (CSF) marker, the B cell chemoattractant chemokine (CXCL 13) may help determine neurosyphilis cases
  • Immunochromatographic strip testing may be used as a rapid point-of-care screening tool for high-risk patients in low-income countries
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