Johns Hopkins Division of Infectious Diseases
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Author: Anne Marie Rompalo Last modified: December 19, 2001


  • Syphilis is a sexually acquired infection caused by Treponema pallidum, which remains chronic without treatment.
  • The disease is characterized by episodes of active disease interrupted by periods of latent infection.
  • Incubation period is estimated to be between 10 and 90 days.
  • Primary (1°) and secondary (2°) stages are considered to be new or incident infections; other stages are latent syphilis and late syphilis are these are considered as prevalent infections.
  • Early clinical manifestations (1° and 2° stages) primarily involve the skin and mucosal surfaces; latent disease has no clinical signs or symptoms; late manifestations may affect virtually any organ s
  • Neurosyphilis can occur at any stage of syphilis
  • Major routes of transmission are sexual and vertical (in utero from infected pregnant woman via blood spread to her fetus).
  • Risk of infection after sexual exposure is about 30%.
  • An infected individual is most contagious to sexual partners during the primary and secondary stages of his infection when lesions or rash are present.
  • Currently, syphilis rates are low. Outbreaks, however, are still occurring.


  • Currently in the U.S., rates of syphilis are high:
  • in some urban areas throughout the U.S.
  • in rural areas in the South;
  • among members of minority groups who suffer from poverty, lack of access to health care, and breakdown of stable community and personal relationships.
  • Recent outbreaks have been associated in men who have sex with men (MSM). Many of these cases are co-infected with HIV and some have partners identified through bathhouses and the Internet.


  • Primary syphilis:
  • Chancre: local lesion at the site of sexual contact
  • It can appear as an ulcer which is painless, and has a firm
  • If the ulcer is on the penis, lymph nodes in the groin area can be swollen on both sides of the groin but not necessarily painful to touch.
  • Secondary syphilis:
  • Rash: may be flat or raised to the touch and sometimes scaley; usually does not itch; may involve palms and soles in 60%.
  • Lymph nodes can be generally swollenFever, chills, aching muscles and joints
  • Mucous patches (5-30%): flat patches involving oral cavity, pharynx, larynx, and genitals.
  • Condylomata lata (5-25%): moist, heaped, wart-like, papules that occur in warm areas of the body where skin touches skin (most commonly, gluteal folds, perineum, perianal)
  • Hair loss in patches: may involve the eyebrows
  • Latent syphilis:
  • No clinical manifestations. Only evidence is positive serologic test for syphilis.
  • Tertiary syphilis:
  • Late benign syphilis: gummas, which are destructive lesions that can mimic cancer, may occur in skeletal, spinal, and mucosal areas, eyes, and viscera (lung, stomach, liver, genitals, breast, eyes, b
  • Cardiovascular syphilis: ascending aortic aneurysm, aortic insufficiency; coronary ostial stenosis; average appearance at about 20-30 years after infection.
  • Neurosyphilis:
  • Asymptomatic neurosyphilis can occur at any stage.
  • Early forms of neurosyphilis:
  • Acute syphilitic meningitis, a basilar meningitis that typically involves cranial nerves VI, VII and VIII
  • Meningovascular syphilis, presents as a stuttering stroke-like syndrome and seizures.
  • Late forms of neurosyphilis:
  • Usually occur decades after infection and are rarely seen
  • Parenchymatous syphilis
  • General paresis (dementia)
  • Tabes dorsalis
  • Ocular involvement can also be early or late. Uveitis may be the most common early presentation.


  • Primary syphilis:
  • Genital herpes simplex virus infection
  • Chancroid
  • Cancer
  • Secondary Syphilis:
  • Pity


  • Definitive diagnosis:
  • Identification of Treponema pallidum in lesions and tissue:
  • Darkfield microscopy, or
  • Direct fluorescent antibody - T. pallidum (DFA-TP)
  • Presumptive diagnosis:
  • Serological tests: Need a positive nontreponemal test AND a positive treponemal test
  • Nontreponemal tests: VDRL(Venereal Disease Research Laboratory), or RPR (Rapid Plasma Reagin); both are reported in titers;
  • Treponemal test: TP-PA (Treponema pallidum Particle Agglutination, FTA-ABS (Fluorescent Treponemal Antibody-Absorbed).
  • Benzathine penicillin G 2.4 million units IM.
  • Penicillin allergic: doxycycline 100 mg po twice daily for 2 weeks (OR) tetracycline 500 mg po 4 times daily for 2 weeks.
  • Azithromycin is currently being studied as an alternate treatment.
  • Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks.
  • Penicillin allergic: doxycycline 100 mg po twice daily for 4 weeks (OR) tetracycline 500 mg po 4 times daily for 4 weeks.
  • Aqueous crystalline penicillin G 18-24 million units IV daily for 10-14 days (OR)
  • Procaine penicillin G 2.4 million units IM daily plus probenecid 500 mg po 4 times daily, both for 10-14 days.
  • Penicillin allergic: Patients who are skin-test-reactive should be hospitalized, desensitized, and treated with penicillin.
  • Daily ceftriaxone therapy has been used by some experts, though dosage has not been standardized and efficacy has not been established in clinical trials.
  • When treating neurosyphilis in late latent or unknown duration
  • Follow-up titers should be compared to the nontrepemal titer obtained on day of treatment.
  • Primary, secondary and early latent syphilis: Quantitative VDRL or RPR at 6 and 12 months
  • Latent: quantitative VDRL or RPR at 6, 12, 18, and 24 months.
  • Neurosyphilis: serological testing as above, with repeat CSF examination if CSF pleocytosis present initially, at 6-month intervals until normal.
  • HIV-infected patients: 3, 6, 9, and 12 months for primary and secondary syphilis and early latent; 6, 12, 18, and 24 months for latent syphilis.
  • Recommend HIV test for all patients with syphilis and consider retesting in 3-6 months if initially negative.
  • Treatment failure: perform CSF examination if any of the following occur:
  • Clinical signs or symptoms persist or recur.
  • There is a sustained 4-fold increase in titer.
  • An initially high-titer nontreponemal test fails to show a 4-fold decrease within 6-12 months for primary or secondary syphilis, or 12-24 months for latent syphilis.
  • NOTE: If CSF normal, retreat with 3 IM injections of benzathine penicillin
  • If CSF abnormal treat for neurosyphilis.
  • Refer all sexual contacts for therapy
  • Prevention: Abstinence, monogamy, reduction in number of sexual contacts.
  • Barriers such as condoms do not protect against all body secretions and skin lesions. Nevertheless, they should be employed as part of an overall educational program stressing sex with uninfected part
  • If there is a question of exposure, rapid evaluation by the health department and medical staff is indicated.
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