Syphilis presents as an indurated, painless genital ulcer about 3 weeks after exposure, followed by painless regional adenopathy. The ulcer heals in 4-6 weeks, followed by a generalized rash. Chancres in the cervix or rectum cause regional iliac nodes, which are not palpable.

100,000 (US); 12,000,000 (Global)
Treponema pallidum infection;
3 weeks (10-90 days); [ABX Guide] Chancre (lasts 4-6 weeks and incubation rarely exceeds 6 weeks); Secondary syphilis (lasts 2-6 weeks and appears 6-8 weeks after chancre heals); [Harrison ID, p. 659-60]
Indurated, painless genital ulcer about 3 weeks after exposure, followed by painless regional adenopathy; Ulcer heals in 4-6 weeks, followed by a generalized rash; [CCDM]
The ulcer of primary syphilis has indurated, raised borders and a clean base (like man's oxford shirt collar buttonhole). [ABX Guide] The chancres usually appear on the external genitalia and also can be seen at other sites: mouth, cervix, and anus. Regional lymphadenopathy accompanies the chancre. [PPID, p. 2874-5] Chancres in the cervix or rectum cause regional iliac nodes, which are not palpable. [Cecil, p. 1984]

Condyloma lata are highly infectious, warty growths that may be seen in primary syphilis or in later stages. A papular rash on the trunk and extremities, including palms and soles, marks the beginning of secondary syphilis about 4-10 weeks after the appearance of the chancre. Complications during secondary syphilis may include meningitis, arthritis, glomerulonephritis, periostitis, and subclinical hepatitis. [ID, p. 899] Also associated with secondary syphilis are mucous patches, generalized lymphadenopathy, conjunctivitis, and uveitis. [Guerrant, p. 290, 1000] Myocarditis is a feature of secondary syphilis. [Cohen, p. 562] About 50% of patients with secondary syphilis have generalized lymphadenopathy often associated with hepatosplenomegaly. [Merck Manual, p. 1708] Multifocal lymphadenitis is a common feature of secondary syphilis. {Merck Manual, p. 998] The rash begins macular and is often pink, coppery, or dusky red; it may become papulosquamous resembling pityriasis rosea. In some cases, the rash appears as ringed or annular lesions, especially on the face. [Cecil, p. 1984-5] The rash of secondary syphilis is maculopapular or pustular. Lesions of the skin and mucous membranes occur in greater than 95% of cases. Temporary loss of hair may occur in patches on the scalp and in the beard and eyebrows. Constitutional symptoms are common and include fever, malaise, pharyngitis, anorexia, lymphadenopathy, and arthralgias. Condylomata lata appear as plaques in moist intertriginous areas. [PPID, p. 2875-6] Meningeal syphilis is one of the three forms of neurosyphilis that presents within the first year as headache, vomiting, neck stiffness, cranial neuropathy, seizures, and mental status changes. [Harrisons, p. 428]

Latent syphilis is divided into early latent (first year) and late latent. In the first year, patients are considered infectious and about 25% of patients have relapses of secondary syphilis. In late latent syphilis, patients are asymptomatic and not infectious. Indications for CSF examination: evidence of eye or nervous system involvement, evidence of tertiary disease (gummas or aortitis), suspected treatment failure (<4-fold decline in RPR titer 6 months after treatment), or HIV-infected persons. [ABX Guide] Some experts recommend CSF exam if RPR or VDRL titer greater or equal to 1:32. Some experts recommend CSF exam in HIV-infected persons only when the CD4+ T cell count <350/uL. [Harrison ID, p. 664t] Late latent syphilis is not infectious except in a pregnant woman to the fetus. [Cecil, p. 1985]

Neurosyphilis may be asymptomatic and may occur during any stage of infection. Findings include CNS impairment (cognitive, motor and sensory), cranial neuropathy, meningismus, and uveitis. CSF examination is recommended in all suspected cases. Positive CSF: pleocytosis, elevated protein, reduced glucose, and reactive VDRL. [ABX Guide]

Tertiary syphilis results in gummas, paresis, dementia, and aortic aneurysms. [ID, p. 899] Tertiary syphilis in industrialized countries during the antibiotic era has been nearly eliminated except for cases of neurosyphilis in AIDS patients. [Harrison ID, p. 660] Spinal cord disease is a complication of tertiary syphilis. Brassy cough and hoarseness may develop secondary to cardiovascular syphilis (aneurysm of ascending aorta). [Merck Manual, p. 1709] Neurosyphilis mimics other diseases of the spinal cord. Findings in neurosyphilis include absent reflexes, diminished vibration and position sensation, positive Romberg's test, Argyll-Robertson pupils, ptosis, urinary incontinence, megacolon, trophic ulcers, and osteoarthritis (Charcot joints). [ID, p. 1363] Tertiary syphilis is a destructive process that is inflammatory and noninfectious. It includes cardiovascular syphilis (>10 years post-infection), gummatous disease (> 5 years post-infection), general paresis (>15 years post-infection), and tabes dorsalis (>15 years post-infection). The last two conditions comprise late neurosyphilis. Tabes dorsalis is a demyelinating process of the posterior spinal cord. Findings include: ataxia, foot drop, shooting pains, bladder disturbances, fecal incontinence, impotence, loss of position/vibratory sensation, absent ankle/knee reflexes; and loss of deep pain/temperature sensations. [PPID, p. 2876-7] Meningovascular syphilis most commonly presents as a stroke in a relatively young person. [Harrison ID, p. 662] Tertiary syphilis lesions include irregular cutaneous plaques/nodules and gummas that destroy nasal cartilage. [Cohen, p. 562]
Initial RPR or VDRL, followed by FTA-ABS are being replaced by automated treponemal tests first. [ABX Guide] DFA on exudate does not depend on viable organisms & may be positive in 1st week, before positive serology; [Wallach, p. 1152]
  • >arthralgia
  • >fatigue, weakness
  • >fever
  • >myalgia
  • E pharyngitis
  • E stomatitis
  • G hepatomegaly
  • G liver function test, abnormal
  • G nausea, vomiting
  • H lymphadenopathy
  • H splenomegaly
  • N confusion, delirium
  • N headache
  • N muscle weakness
  • N paresthesia
  • N seizure
  • N stiff neck
  • O conjunctivitis, acute
  • O oculoglandular syndrome
  • R cough
  • S cellulitis or rash, circinate
  • S papules or plaques
  • S pustule
  • S rash (exanthem)
  • S rash on palms
  • S skin or subcutaneous nodule
  • S ulcer of skin
  • S warty growth of the skin
  • *arthritis
  • *cirrhosis
  • *cranial neuropathy
  • *encephalitis
  • *erythema nodosum
  • *glomerulonephritis
  • *hepatitis
  • *meningitis
  • *myelitis
  • *myocarditis
  • *osteomyelitis
  • *paralysis
  • *peripheral neuropathy
  • *uveitis
  • *weight loss




Needle (Includes Drug Abuse), Scalpel or Transfusion, Skin or Mucous Membranes (Includes Conjunctiva), Sexual Contact
  • AIDS patients
  • Have a blood transfusion
  • Injection drug users
Assess adequacy of treatment with follow-up VDRL or RPR titers. [Harrisons, p. 428] "Parenteral penicillin G is the preferred drug for all stages of syphilis. It’s the ONLY documented efficacious therapy for neurosyphilis and in pregnancy." [ABX Guide]
1. (US) Published in MMWR 2011 = 46042; Estimated 100,000 cases per year (reported rate X 2 similar to estimate of gonorrhea used by ABX Guide);
2. (Global) 1 million STIs /day; Each year 500 million cases of Chlamydia, Gonorrhea, Syphilis, and Trichomonas; [Fact sheets from WHO 2013] 10.6 million cases in 2008; [WHO: Baseline report on global sexually transmitted infection surveillance 2012] Estimated 11 million new cases per year; [Harrison ID, p. 659]