• A 25-year-old malechancre of primary syphilis presents to the clinic with an ulcer on his penis. He denies pain, penile discharge, rash, and dysuria. Sexual history reveals that the patient has had six male partners over the past year. He infrequently uses condoms. Physical examination is unremarkable except for a 1-cm ulcer on the underside of the penis and bilateral inguinal lymphadenopathy. There is no discharge. HIV screen was negative, but both VDRL and FTA-ABS were positive.
  • Classification
    • bacteria
      • other bacteria
        • spirochetes
          • Treponema
            • T. pallidum
  • Pathogenesis
    • transmission 
      • sex
      • across the placenta
    • reservoir
      • GU tract
    • molecular biology
      • obligate pathogen
        • not intracellular
  • Syphilis (3 stages + congenital) 
    • primary syphilis
      • painless chancre  
        • due to ischemic necrosis
      • indurated edge
      • diagnose with dark-field or fluorescent microscopy of lesion at this stage
    • secondary syphilis
      • "secondary is systemic"
      • diffuse, copper-colored maculopapular rash 
      • condylomata lata
        • wartlike lesions in perianal area
        • highly infectious with many treponemes present
      • diagnose with VDRL or FTA-ABS at this stage
    • tertiary syphilis
      • gummas
        • granulomatous lesions of skin and bones
      • aortitis (vasa vasorum destruction) 
      • neurosyphilis (e.g., tabes dorsalis)
        • can lead to Charcot joint of knees, hip
      • Argyll-Robertson pupil
        • "prostitutes pupil"
          • "accommodates but does not react" (to light)
      • diagnose with FTA-ABS at this stage
    • congenital syphilis
      • stillbirth or hydrops fetalis
      • neurosyphilis (CN VIII deafness)
      • bone and teeth abnormalities
        • saddle nose (sunken appearance)
        • saber shins (bowing of tibia)
        • Hutchinson's teeth (notches in teeth with wide spacing between them)
        • mulberry molars (too many cusps on molars)
    • note that 3 different cutaneous lesions may occur during the 3 stages
      • stage 1 - chancre
      • stage 2 - condyloma lata
      • stage 3 - gumma
    • pathophysiology
      • all of syphilis is a vasculitis
        • Treponema infects
          • small vessels and arterioles
          • aortic arch
            • rich vasa vasorum
            • can lead to aortic regurgitation due to stretching of ring around aortic valve
  • Visualized using dark-field microscopy or fluorescent antibodies
    • reveals motile, helical organisms
  • Thin sphirochete
    • although gram-negative, not visualized on Gram-stain
      • too small to be seen by light microscopy
  • 2 types of screening tests are used to diagnose syphilis infection
    • VDRL (non-specific test; Note: RPR, or rapid plasma reagin, test is newer but very similar)
      • infection with syphilis results in cellular damage and release of specific lipids into the bloodstream, including cardiolipin
      • the body then produces antibodies against cardiolipin
        • cardiolipin is a glycerophospholipid also known as diphosphatidylglycerol
        • component of inner mitochondrial membrane and bacterial membranes
        • cardiolipin is the only antigenic human glycerophospholipid
      • Venereal Disease Research Laboratory (VDRL) test measures levels of these anti-cardiolipin antibodies using beef cardiolipin
        • note that test is looking for antibodies against a human cellular lipid, not antibodies against Treponema
      • VDRL becomes negative as disease is successfully treated
      • 1% of adults will have a false-positive VDRL
        • remember "VDRL" for causes of false-positives
          • Viruses (e.g. hepatitis)
          • Drugs
          • Rheumatic fever
          • Lupus and Leprosy
    • FTA-ABS (specific test)
      • treponemal antibody-absorption test (FTA-ABS) looks for antibodies against the spirochete itself
        • indirect immunofluorescence of patient serum mixed with whole killed T. pallidum
      • ↑ specificity
      • positive earlier and remains positive for life
      • "ABS will ABSolutely detect the antibodies"
  • Active infection
  • Probably false positive
  • Successfully treated
  • Note that T. pertenue also causes a VDRL positive result
    • T. pertenue causes the disease yaws
      • infection of bone, joints, and skin
      • keloids during healing lead to severe limb deformities
      • most prevalent in the tropics
      • not an STD
  • Herpes simplex virus
  • Haemophilus ducreyi
  • Chlamydia trachomatis
    • serotype L1, L2, or L3
  • Klebsiella granulomatis
  • IM benzathine penicillin for primary and secondary disease
  • IV penicillin G (for Gummas) for congenital and late disease
Prognosis, Prevention, and Complications
  • Prognosis
    • good if treated early
    • complications of late syphilis cannot be cured
  • Prevention
    • use of condoms
    • screening of at-risk groups
      • men who have sex with men
      • history of incarceration
      • commercial sex workers
      • pregnant women
  • Complications
    • Jarisch–Herxheimer reaction
      • resembles bacterial sepsis
      • occurs several hours after treatment with antibacterials
      • results from releases of bacterial cellular contents (endotoxin-like products)
      • self-limited
    • seen in tertiary syphilis
      • aortic insufficiency
      • tabes dorsalis
      • general paresis of the insane

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