Syphilis%20-%20primary Diagnosis

• 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

• 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

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