Primary (Early) Syphilis

• 21d incubation period (range 10-90 d)
• No constitutional symptoms
• Chancre:
  • Painless papule at site of inoculation
  • Clean based, circular, sharply defined borders:
    • Solitary lesions
    • Commonly on penis, vulva, and rectum
    • Bilateral regional lymphadenopathy
  • Heals spontaneously in 3-6 wk
• Rectal chancre:
  • Painful or painless
  • Rectal irritation/discharge
  • Painless enlargement of lymph nodes

Secondary (Early) Syphilis

• Occurs 3-6 wk after primary lesion
• Disseminated stage
• Rash (most common):
  • Symmetric, diffuse, polymorphous, papular, or maculopapular rash
  • Rash may be diverse and not fit a pattern
  • Starts on trunk and flexor extremities
  • Spreads to involve palms and soles:
    • Discrete, red/reddish-brown
    • 0.5-2 cm in diameter
• Condyloma lata:
  • Large raised gray/white lesions, painless, moist
  • Mucous membranes:
    • Oral cavity and perineum
    • Very contagious
    • Intertriginous areas
    • Flat rectal warts
• Systemic symptoms:
  • Fever, headache, malaise, anorexia, sore throat, myalgias, and weight loss
• Diffuse lymphadenopathy:
  • Palpable nodes at inguinal, axillary, posterior cervical, femoral, and /or epitrochlear regions
  • Painless, firm, and rubbery
• Less common:
  • “Moth-eaten” alopecia
  • Syphilitic meningitis
  • Scleritis
• Loss of lateral third of eyebrows
• Painless mucosal lesions (mucous patches)
• Secondary stage resolves spontaneously in 1-2 mo

Latent Secondary Syphilis

• Begins after primary and secondary symptoms resolve
• Period of no symptoms but positive serology:
  • CSF normal
• Late latent stage not infectious except for fetal transmission in pregnant women
• Persists for lifetime or develops into tertiary syphilis

Tertiary (Late) Syphilis

• Occurs in about 15% of patients with untreated latent secondary syphilis
• Can appear 10-20 yr after initial infection
• Neurologic and cardiovascular involvement:
  • Destructive stages of disease
• Neurosyphilis (most common):
  • Asymptomatic:
    • Positive CSF - Venereal Disease Research Laboratories (VDRL)
    • CSF pleocytosis (10-100 lymphocytes)
    • Elevated CSF protein at 50-100 mg/dL
  • Meningitis:
    • Aseptic; CSF with positive VDRL, higher protein, and lower glucose (compared with above)
    • Cranial nerve palsy, including isolated eighth nerve palsy
  • General paresis:
    • Loss of cortical function
    • Argyll Robertson pupils (small fixed pupils that do not react to strong light, but do react to accommodative convergence)
  • Tabes dorsalis (peripheral neuropathy)
• Degeneration of posterior columns/posterior or dorsal roots of spinal cord
• Dementia
• Paresthesias, abnormal gait, and lightning (sudden, severe) pain of extremities/trunk
• Progressive loss of reflexes, vibratory/position sensation
• Positive Romberg sign
• Vision: Optic atrophy
• Pupils: Argyll Robertson pupils
• Urinary incontinence
• Gummas:
  • Late benign syphilis of cutaneous skin/viscera:
    • Bone, brain, abdominal viscera, etc.
• Granulomatous, cellular hypersensitivity reaction:
  • Round, irregular, or serpiginous shape
  • “Great pox”
• Cardiovascular:
  • Thoracic aortic aneurysm (ascending most common):
    • Dilated aorta and aortic valve regurgitation
    • Aortic valve insufficiency
    • Coronary thrombosis
    • Destructive lesions of skeletal structures or skin
• HIV infected:
  • Strong association with syphilis
• Increased incidence of neurosyphilis

Congenital Syphilis

• In utero infection:
  • Age <2 yr:
    • Hepatosplenomegaly, rash, condyloma lata, rhinitis (snuffles), jaundice (nonviral hepatitis), osteochondritis
• Older children (syphilis stigmata):
  • Interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, Hutchinson teeth, saddle nose, etc.
  • Refer to CPS for possible sexual abuse evaluation

• Serology:
  • Nontreponemal test:
    • RPR
    • VDRL
    • Positive 14 d after chancre appears
    • Early false negatives, especially ≤7 d after primary chancre
    • Repeat negative test in 2 wk and correlate with disease activity
    • False positives in 1-2% of general population
    • Fourfold change in titer clinically significant
    • 100% sensitivity in secondary syphilis
    • Nonreactive after successful treatment
  • Treponemal antibody test:
    • Fluorescent treponemal antibody absorption (FTA-ABS)
    • Hemagglutination assay for antibody to T. pallidum (MHA-TP)
    • More sensitive and specific
    • 1% false-positive rate
    • Confirmatory test
    • Reactive for patient's lifetime
    • More costly and harder to perform
  • Reverse screening algorithm: Starts with treponemal test (EIA), then nontreponemal test is reflexively done if positive. Increased sensitivity for patients with latent syphilis
  • Dark-field microscopy:
    • Identifies treponemes from primary and secondary lesions
    • Suspicious early lesions with negative serology (early primary syphilis)
    • False negatives with ointments, creams
    • Oral specimen unsuitable
  • CSF analysis for tertiary neurosyphilis:
    • Tertiary syphilis
    • Positive VDRL/RPR
    • Lymphocytes >5/mL
    • Protein >45 mg/dL
    • Decreased glucose

• Neurosyphilis requires IV antibiotics
• Pregnant women allergic to penicillin requiring desensitization

Follow-up care:

• Measure for falling titers in 6 mo and 1 yr after treatment
• Tertiary/latent (>1 yr):
  • Measure for falling titers in 3, 6, 12, and 24 mo after treatment

• Infectious disease consultation for secondary and tertiary syphilis as well as congenital and neurosyphilis
• Refer patients with neurologic signs to ophthalmology for evaluation