Genital Ulcers and Genial Lesions Flashcards

1
Q

Epidemiology of Syphilis

A
  • Infectious cases uncommon in NZ except MSM
    • smaller heterosexual component, mainly men-men
    • Some “imported” or from contaxt with imported
  • Late latent (non-infectious) syphilis has been previously over-diagnosed in NZ; eg, due to impact of immigration from pacific Islands
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2
Q

Describe the pathology of Syphilis, the pathogen, and how it evades the immune system….

A
  • T. pallidum; a spirochaete
  • Evasion of the Immune response is important in maintaining latency:
    • immunologically privledged sites; eye, brain etc
    • intra cellular sites
    • little evidence that antibody is lytic
    • surface of organism is immunologically inert
  • CMI is critical to the control of T.pallidum proliferation
  • Much of the clinical presentation is due to the immune response to the organism; eg; vasculitus → destruction, fibrosis
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3
Q

When do you get early manifestations of Syphilis and what are some of them?

A

9-90 days post exposure

Common features; anogenital ulceration, rash, ocular lesions, neurological issues

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4
Q

Primary Syphilis occurs when, and looks like

A
  • Onset is 14-21 days after inoculation
  • Initially papularr, then ulcerates
    • ulcer 1-2cm diameter
    • usually solitary and painless
    • less typical/unusual in non-genital types
  • Rubbery inguinal node(s) with genital lesions
  • Diagnosis by scraping lesion, doing DFA test (non-specific) or Direct fluorescent (specific) before serology positive
    • see the spirochaete moving around in solution, not actually that easy to do
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5
Q

Describe Secondary Syphilis

A
  • Appears 4-10 weeks after a primary lesion(s), may overlap primary lesion(s)
  • Due to haematogenous spread therefore may have systemic symptoms
  • Characteristic Rash (very variable!!)
    • ​macular → papular → paulosquamous
    • Trunk, extremeties, palms and soles
  • May also have mucus membrane lesions (look like warts!), alopecia (hair loss)
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6
Q

Late manifestations of Syphilis

A

Late Disease: defined as when no longer infectious (but can reactivate beyond this point in immune compromise)

Common features of late disease:

  • often NONE
  • Aortic disease
  • Papillary signs, optic atrophy
  • Long tract signs, yramidal signs
  • cognitive change
  • gummatous change (fibrosis with destruction often in skin or bones)
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7
Q

Congenital infection of Syphilis

A
  • Infection occurs as early as 9/40, but no inflammatory response until ~18/40 onwards
  • More then 50% undergo mid-trimester abortion or perinatal death
  • Early form
    • most changes appear 1-2months of age
  • Late forms
    • 80% of those liveborn who are infected are undetected early
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8
Q

Syphilis Tests

A
  • Predictive value of tests poor in low prevalence settings such as NZ
  • Pregnancy is a significant cause of of biological false positive (BFP) results
  • Screening with EIA
    • if positie then confirmed using RPR and TPPA (or TPHA, “h” is for haem)
    • False posiitive not associated with conventional BFP reactions
    • High sensitivity and speicificity EXCEPT in primary syphilis!
    • If you do too early the result wont be positive
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9
Q

What is the RPR of Syphilis

A
  • non-specific or non-treponemal test
    • detects ABs against lipoidal Ag
      • ​Liposomes in suspension + unattached charcoal
    • Flocculation type ie; not complement dependent
      • ​charcoal particules trapped in lattice of Ag-Ab complex
    • Quantitative: used to follow treatment
  • Positive: 3-5wk post-exposure
  • highly specifc in healthy people
    • ​false positive rate 1-10%
  • VDRL highly specific in CSF
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10
Q

TPPA test?

A
  • Treponema pallidum particle agglutination assay
  • Indirect agglutination assay
    • gelatin particles are sensitized with T pallidum Ag
    • Patient serum is mixed with these particles
    • In a positive assay the particles aggregate and clump
  • Confirmatory
  • Diagnosis early and late disease for BOTH primary and secondary syphilis
  • False positive reactions can occur due to presence of Ab against other treponemal organisms
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11
Q

Treatment of early syphilis is?

A

Benzathine Penicillin

  • If there is a penicillin allergy: Doxycycline 100mg twice daily for 14 days
  • Treat those in sexual contact with patient the same way
  • Still give benzthine penicillin if pregnant, if there is a penicillin allergy then desensitize before B-P, as they cannot usse doxycycline

Also used in rheumatic fever

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12
Q

What is a Jarisch-Herxheimer reaction

A

What can happen when you treat someone with early Ayphilis with benzthine penicillin.

Due to the systemic release of the breakdown products of infection cause this, eg; T.pallidum, and you get an exaggerated immune reaction.

Fever, chills

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13
Q

Describe the biology of the herpes virus, and the sub types

A

Herpesviridae

  • a subfamily
  • HSV-1 and HSV-2 closely related
    • morphologically indistinguishable; dense core containing genome, witha icosahedral capsid​
    • 50% homology of genomes
  • ​HSV-1 and HSV-2 have different site preference
    • commonly found in non-preffered site with altered natural history
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14
Q

Genital herpes:

Where does it transmit and then replicate. how does it then cause infection

A
  1. Transmission in mucosa: more vunerable then skin, why females are more at risk from male partner
  2. Replicates in the cells of the epidermis: causing cellular destruction and inflammation
  3. Travels via unmyelinated ensory nerves to sacral paraspinal ganglia​​​
    • ​​enters Latent phase: hidden from host immune system
  4. Reactivation in same nerve territory as initial infection
  • Dual genital infection with both HSV-1 and HSV-2 is possible
  • Duel orolabial and genital infection with HSV-1 is possible
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15
Q

Why can you never fully eliminate the genital herpes virus?

A

Because at any one time only some of the latently infected neurons are reactivated and there will always be some still latent and evading the immune system

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16
Q

How do you transmit HSV and what is the transmission risks?

A
  • Transmitted from direct contact with virions from
    • blister or ulcer
    • sexual contact shedding virus asymptomatically: can occur from genital/anal or oral sites.
  • Peak Shedding significant just before symptomatic episode but bad also when lesions are actually present
    • presents anxiety for patients as they don’t know when they’re actually infectious
  • Usually symptomatic new infections are from asymptomatic sexual partners
  • unsure how much virion is needed to cause infection
17
Q

Where and how to do a diagnostic test for Genital Herpes?

A
  • Best to test from a vesicle or ulcer
  • Herpes simplex PCR is performed using Rohe Lightmix kit HSV-1/2 assay
    • The use of HSV type specific serology is not routinel indicated and can be problematic if pitfalls are not well understood

Treatment:

  • First episode: Aciclovir 400 mg for 7 days
  • Recurrence : Aciclovir 800mg for 2 days
  • Suppression: Aciclocir 100mg for 9-12 months
18
Q

Aciclovir

A
  • Bioavailability 15-20% (low)
  • Once absorbed key step in acitvation involves thymidine kinase
  • Host cell kinases effect change to ACV-TP
  • ACV-TP competitively inhibits viral DNA polymerase; incorperates itself into viral DNA and causes chain termination
  • HSV resitance uncommon
  • Valaciclovir: aciclovir with L-valine ester added to ACV
    • 55% bioavailabilty
19
Q

Factors that reduce Transmission of herpes

A
  • condoms ~50%
  • Antiviral therapy:
    • reduces risk of transmission of symptomatic herpes by 75%
    • reduces overall acquisition of HSV-2 by 48%
    • Reduces total HSV acquisitions by 61%
    • Rates higher in women
20
Q

The L serovars of Chlamydia (L1, L2, L3)

A
  • Presentation depends on gender, site of acquisition and stage of disease
  • Predisposition in infecting lymphocytes and lymphatic tissue
  • Most relevant in developed nations in HIV+ MSM have high risk “serosorted’ sex
    • Should be tested for particularly in symptomatic MSM when rectal chlamydia is +
    • lots of sex with lots of different partners
    • doxycycline 100mg for 3 weeks
21
Q

Anogenital warts are due to ______. these rates are dropping due to the _________.

A

Anogenital warts are due to HPV. these rates are dropping due to the Gardasil vaccine.

  • can be difficult to treat
  • spontaneous regression can occur
  • can cause significant patient anxiety
  • some ass. with anogenital neoplasia
22
Q

what is HPV

A
  • DNA viruses
  • species and site specific
  • need differentiating epithelium to grow
  • warts are of clonal origin
  • infectiousness may vary with viral type
  • some types can transform or immortalise infected cells
  • get in with ‘cracks’, microabrasions in the eptithelium
23
Q

E6 and E7 of HPV do what?

A
  • Target Tumor suppresor genes and hence drive DNA replication
  • E7: binds to reticuloblastoma gene→ inhibits transcription factor E2F → transcription of genes involved in cell cycle progression and DNA synthesis
24
Q

Sexual transmission of HPV

A
  • Common infection in those whoe are recently sexually active (18-28 yr)
  • Most infections subclinical
  • Decreasing prevalence with age
  • incubation period: 3-8m for warts, 4-36m for cervical lesions
  • Visible lesions usually at sites of microtrauma byt HPV causes anogenital ‘field infection’
  • once one HPV infection resolved onlly have type specific immunity
  • evidence for perinatal transmission
25
Q

Types/stages of HPV

A
  • Latent, subclinical, clinical
  • Latent/subclinical 100x more common then clinical infection
  • long latency with periodic reactivation is the norm
26
Q

Treatment of HPV warts

A
  • mainly cosmetic (warts), or to prevent progression, ofr to remove pre/cancerous tissue
    • Physical or chemical ablation etc (70% efficacy, 30% reccurence)
    • have same levels of recurrence
27
Q

Intraepithelial neooplasia as a complication of HPV

A
  • uncommon, usually HPV infection is benign
  • smoking and immune status are important cofacotrs
  • Cervical and vulver IE neoplasia well described
  • Oro-pharyngeal and aanal cance becoming important
  • Prophylactixc vaccination vital
    • packaged in capsule from L1 gene of HPV DNA which is why it works so well