Revision as of 19:39, 22 December 2014 by Raimyp (talk | contribs) (Differential Diagnosis)


  • Syphilis is caused by the spirochete Treponema pallidum.
  • Usually sexually transmitted
  • Causes a wide range of systemic manifestations that are characterized by episodes of active disease interrupted by periods of latency
  • Approximately 30% of asymptomatic contacts examined within 30 days of exposure have infection


  • Spirochetes penetrate intact mucous membranes or microscopic dermal abrasions.
  • Transmission through sexual contact with infectious lesions, infection in utero, blood transfusion, and organ transplantation
  • Blood from a patient with incubating or early syphilis is infectious.
  • Characterized by multiple stages separated by periods of latency: primary, secondary, latent and tertiary

Clinical Features

Primary Syphilis

  • Primary lesion appears after an incubation of 2-6 weeks
    • Single painless papule that becomes eroded and indurated, cartilaginous consistency on palpation
    • Minority of patients can have multiple lesions or atypical appearance
    • Occurs at point of contact: penis, rectum, mouth, external genitalia, cervix, or labia
    • Heals in 4-6 weeks
  • Regional lymphadenopathy that is painless and firm

Secondary Syphilis

  • Characterized by generalized mucocutaneous lesions and lymphadenopathy but can also be found in other tissues[1]
  • Skin lesions are usually maculopapular, pale red or pink, non-pruritic, discrete, and distributed on the trunk and proximal extremities. They may be subtle.
  • They progress to more wide spread papular lesions that frequently involve the palms and soles.
    • Appears 6-8 weeks after the chancre heals and subsides within 2-6 weeks
    • Healing chancre may still be present in ~15% of cases. The stages may overlap more frequently in HIV patients. [2]
    • In intertriginous areas, papules can enlarge to produce broad, moist, pink or gray-white infectious lesions called condylomata lata
  • CSF abnormalities are detected in as many as 40% during this stage. CNS involvement can be symptomatic or asymptomatic.
  • Constitutional symptoms may accompany or precede secondary syphilis. Can include: sore throat, fever, weight loss, malaise, anorexia, headache, and meningismus
  • Less common complications include: hepatitis, nephropathy, gastritis, proctitis, rectosigmoid mass arthritis, periositis, optic neuritis, iritis, uveitis, pupillary abnormalities

Differential Diagnosis


There are nontreponemal and treponemal tests. The major difference is that the treponemal test measures the antibody directed against the treponemal antigens and are more specific however often more expensive and less available. Definitive diagnosis is darkfield microscopy.

Nontreponemal Tests:

  • Venereal Disease Research Laboratory (VDRL)*
  • Rapid Plamsa Reagin (RPR)*
  • Toludine Red Unheated Serum Test (TRUST)

Most commonly in the ED, the VDRL and RPR will be the ordered screening test

Treponemal Test:

  • Fluorescent treponemal antibody absorption (FTA-ABS)
  • Microhemagglutination test for antibodies to Treponema pallidum (MHA-TP)
  • Treponemal pallidum particle agglutination assay (TP-PA)
  • Treponema pallidum enzyme immunoassay (TP-EIA)


Treatment is primary with penicillin with dosing and type of penicillin determined by the stage of disease[3] Treatment requires antimicrobial therapy. Advanced stages require a prolonged course due to the slow growth time of T. pallidum.

Early Stage

This is classified as primary, secondary, and early latent syphilis less than one year.

Treatment Options:

  • Penicillin G Benzathine 2.4 million units IM x 1
    • Repeat dose after 7 days for pregnant patients and HIV infection
  • Doxycycline 100mg oral twice daily for 14 days as alternative

Late Stage

Late stage is greater than one year duration, presence of gummas, or cardiovascular disease

Treatment Options:


There are 3 Major options with none showing greater efficacy than others:

  • Penicillin G 3-4 million units IV every 4 hours x 10-14 days
  • Penicillin G 24 million units continuous IV infusion x 10-14 days
  • Penicillin G Procaine2.4 million units IM daily + probenecid 500mg oral every 6 hours for 10-14 days.
  • Alternative:
  • Desensitization to the penicillin allergy is still the preferred method of treatment for patients with early and late stage disease (especially during pregnancy)


  • Primary and late stage syphilis can be discharge however close followup should be provided for each
  • Neurosyphilis should be admitted

See Also


  1. Chapel TA. The signs and symptoms of secondary syphilis. Sex Transm Dis. 1980;7(4):161–164.1.
  2. Chesson HW, Heffelfinger JD, Voigt RF, Collins D. Estimates of primary and secondary syphilis rates in persons with HIV in the United States, 2002. Sex Transm Dis 2005; 32:265.
  3. Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1–207