15: Syphilis

Question 1

What organism causes syphilis?

Answer 1

Troponema pallidum subsp. pallidum

Family spirochaetacae

Corkscrew-shaped, motile microaerophilic bacterium

Undulating movement at center distinguishes it from other treponemes

Lacks transposable elements; PCN-sensitive

Question 2

What are the various classifications of syphilis?

Answer 2

• Early (<1 year since infx)
  
  • Primary: chancre (macule –> papule –> ulcer; painless but highly infxs), regional lymphadenopathy, serological test may not be positive yet
  • Secondary: weeks-months; mucocutaneous lesions, papulosquamous/pustular rash (palmar/plantar highly diagnostic) lymphadenopathy, malaise, condylomata lata, nickel/dime lesions, alopecia, splenomegaly, serological tests have highest titers during this stage
  • Early latent (asymptomatic): host suppresses infx
• Late (>1 year since infx or unknown duration); not very contagious
  
  • Tertiary (1-20yrs): gummatous lesions (syphilitc tumors), cardiovascular syphilis (aortic dissection, aneurysms)
  • Late latent
• Neurosyphilis: T. pallidum invades CNS (any stage)
  
  • Months-years after infx
  • Sx: acute syphilitic meningitis, meningovascular syphilis, ocular involvement; neurologic involvement decades after infx (rare): general paresis, tabes dorsalis (loss of coordination), ocular involvement
• Congenital syphilis: T. pallidum transmitted pregnant woman to fetus
  
  • Stillbirth, neonatal death, infant disorders (deafness, neurologic impairment, bone deformities)
  • Risk highest during primary/secondary
  • Hutchinson’s teeth: small, irregular notches, spaced wider

Question 3

Describe T. pallidum pathophysiology.

Answer 3

• Penetration
  
  • Enters via skin and mucous membraes through abrasions during sexual contact
  • Transplacentally from mother to fetus during pregnancy
• Dissemination
  
  • Widespread via circulatory system, including lymphatic system and regional lymph nodes
• Infiltration
  
  • Early of PMNs –> replaced by T lymphocytes; secondary syphilis enriched for CD4+ and CD8+ T cells and dendritic cells
  • Huoral immune response early on
  • Invation of CNS at any stage

Question 4

Describe laboratory diagnosis of T. pallidum.

Answer 4

• ID in leson exudate or tissue using darkfield microscopy
• Serological tests (use both)
  
  • Nontreponemal tests (RPR, VDRL); qualitative and quantitative; titer; can tell if treatment is working or relapsing
  • Treponemal tests (FTA-ABS); qualitative; if treated, future test would be positive (“serofast”)

Question 5

What are the diagnosis criteria for latent syphilis?

Answer 5

• Early latent syphilis:
  
  • Seroconversion or 4-fold increase in comparison with serologic titer
  • Unequivocal sx of primary/secondary syphilis reported
  • Contact to infectious case of syphilis
  • Only possible exposure was in past 12 months
• Late latent syphilis
  
  • Unknown duration

Question 6

What are the indications for CSF examination?

Answer 6

• Neurologic/opthalmic signs/sx
• Evidence of active tertiary syphilis
• Treatment failure
• HIV infx w/ CD4 <350 or nontreponemal serologic test titer of > 1:32

Question 7

What is the treatment for syphilis?

Answer 7

• Benzathine penicillin
• If allergic and not pregnant, doxycycline or tetracycline (14 days or 28 days [LL, T])
• Neurosyphilis: IV penicillin G

Question 8

What is the Jarisch-Herxheimer Reaction?

Answer 8

• Self-limited rxn to antitreponemal therapy
• Sx: fever, malaise, nausea/vomiting; chills, secondary rash
• Occurs within 24 hours after therapy; not an allergic reaction
• Rx antipyretics
• May precipitate early labor

Question 9

What is the follow-up procedure for syphilis?

Answer 9

• Primary/secondary: Reexamine 6-12 months with titers
• Latent: Reexamine 6, 12 and 24 months
• HIV+: 3, 6, 9, 12, 24 months for primary/secondary, 6, 12, 18, 24 for latent
• Neurosyphilis: similar to primary, but with CSF exam at 6-month intervals until normal

If titer fails to show 4-fold decreae within 6-12 months, treatment failure.