Genital Warts And Genital Ulcer Disease Flashcards

1
Q

Papillomaviruses (HPV)

A
  • Papovavirus family
    • naked, icosahedral DNA virus (so will survive in the environment)
    • > 200 diff. Types of HPV have been recognized
    • > 40 are assoc. w/ genital infections
  • Latent and transforming infections
    • treatment will not clear latent infection
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2
Q

Papillomaviruses (HPV) Transmission

A
  • Breaks in skin
  • Sexually transmitted
  • Birth canal
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3
Q

HPV Wart Pathogenesis

A
  • Viral replication depends on epithelial cell differentiation
  • HPV infects basal cells
  • Induces cell proliferation and thickening in the basal layer, stratum spinosum and stratum granulosum
  • As cells differentiate, nuclear factors expressed in diff layers promote transcription of diff viral genes
  • The late genes encoding structural proteins are expressed only in terminally differentiated cells
  • New viral particles are shed w/ dead cells of the upper layer of skin
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4
Q

Risk factors for genital warts

A

Women

  • Young age (<25)
  • Multiple sex partners
  • Male partner sexual behavior

Men

  • Multiple sex partners
  • Being uncircumcised

Immunosuppressed

  • Larger and more treatment-resistant genital warts
  • Higher rates of recurrence
  • Higher rates of malignant transformation of anogenital warts

Persistent HPV infection (oncogenic subtype) is a risk factor for developing cervical cancer

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5
Q

Genital HPV infection Symptoms

A
  • Infection is often subclinical; only noticed during exam
  • Subclinical infection often resolves on its own
    • ~70% resolve 1 year
    • ~90% within 2 years
    • 20-30% of pts have a recurrence within a few months
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6
Q

HPV Genital Infection incubation period

A
  • 3wks to 8 months
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7
Q

HPV Transforming Infections

A
  • Viral DNA is usually integrated
  • Basal cells replace more differentiated epithelial cells
  • Clinical outcome = dysplasia and carcinomas
  • Integration inactivates an HPV early gene —> no viral DNA replication but express of some genes
  • Continued expression of HPV E6 and E7 genes
    • E6 protein binds p53 and targets it for degradation
    • E7 protein binds and inactivates retinoblastoma protein
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8
Q

HPV subtypes causing warts

A
  • 1, 2, 3, 4, 10
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9
Q

HPV subtypes causing genital warts

A
  • 6, 11
  • Also cause laryngeal papillomas
  • Low cancer risk subtypes
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10
Q

HPV Genital Warts Diagnosis

A
  • Usually made by clinical appearance
  • No FDA-approved serological or blood tests to detect HPV infection
    • not all ppl mount an antibody response to HPV and antibody titers may decline over time
    • HPV may become latent (undetectable) with the potential for reactivation, so neg. test does not rule out infection
  • Biopsy can be used to confirm the diagnosis and rule out malignancy
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11
Q

HPV Genital Warts Treatment

A
  • Main indication: alleviation of bothersome symptoms
    • pruritus, bleeding, burning, tenderness, vaginal discharge, pain, obstruction of the vagina, dyspareunia
  • No medical indication for treatment of asymptomatic warts
    • do not pose serious risks, may want to wait for spontaneous resolve
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12
Q

HPV cyto-destructive treatment

A
  • Podophyllotoxin
  • Trichloroacetic acid and bichloroacetic acid
  • 5-Fluorouracil
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13
Q

HPV immune-mediated treatment

A
  • Imiquimod
  • Interferons
  • HPV vaccines
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14
Q

HPV genital warts surgical treatment

A
  • Ablative procedures

- Excision

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15
Q

Herpes Simplex Viruses

A
  • Enveloped DNA virus
    • HSV-1 and 2 are closely related alpha herpesviruses
  • Potential for latency and reactivation
  • Reactivation may be asymptomatic, but virus is still shed
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16
Q

HSV Transmission

A
  • Sexually or perinatally
  • Sexual transmission from men to women is more efficient than women to men
  • Fomite transmission unlikely-sensitive to drying and detergents
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17
Q

Genital Herpes Clinical Course

A
  • Primary infection
    • both localized and systemic symptoms
    • mean duration ~3wks
  • Reactivation
    • prodrome
    • localized symptoms
    • duration ~5-10 days
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18
Q

HSV Primary Infection

A
  • Vesicular-ulcerative lesions on the penis, cervix, vagina or vulva
    • vesicles—>ulcers—>crusts
  • Fever, malaise, dysuria
  • Lymphadenopathy (inguinal lymph nodes)
  • HSV cervicitis
  • HSV proctitis
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19
Q

HSV Recurrent Disease

A
  • Frequency of recurrence depends on
    • severity and duration of the initial episode
    • infecting serotype- HSV-2 reactivates more often than HSV-1
    • host factors (immune status)
  • Reactivation becomes less common over time
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20
Q

Potential complication of genital herpes

A
  • Aseptic meningitis (assoc. w/ HSV-2)
    • more likely to occur w/ primary infection than reactivation
    • self resolves and neurological sequelae are unlikely
    • recurrent episodes of meningitis can occur (Mollaret’s meningitis); may not have evidence of genital lesions at time of meningitis
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21
Q

Genital herpes and HIV

A
  • HSV-2 genital ulcer disease assoc. w/ an increased risk for HIV-1 infection
    • HSV-2 genital lesions cause local inflammation and disruption of the genital mucosa
    • immune response to HSV-2 infection recruits CD4 T-cells to genital tract
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22
Q

Genital ulcer disease differential

A
  • Infectious causes = genital herpes, syphilis and chancroid
  • Genital herpes
    • multiple, shallow, tender ulcers that may be vesicular
    • recurrent disease
  • Primary syphilis
    • painless, indurated, clean-based ulcer, called a chancre
  • Chancroid
    • deep, purulent ulcer
    • may be assoc. w/ painful inguinal lymphadenitis
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23
Q

Herpes Treatment

A
  • Antiviral therapy
  • First clinical episode
    • Acyclovir
  • Treatment after primary infection
    • episodic treatment
    • continuous (suppression) treatment
  • Does NOT eliminate latent/asymptomatic shedding
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24
Q

Herpes Screening

A
  • Routine screening not recommended for asymptomatic pts
  • Screening asymptomatics assoc. w/ a low specificity and high false-pos rate
  • Serologic tests for HSV-1 cannot differentiate oral from genital infection
  • Asymptomatic individuals not treated
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25
HSV Diagnosis
- Based on appearance not accurate - Should be lab confirmed *Virologic tests +PCR or viral culture *type-specific serologic tests +western blots or ELISA +IgM assays do not differentiate b/w HSV-1 and 2
26
Type-specific Serologic Tests
- Type-specific and nonspecific antibodies to HSV develop within several weeks following infection and persist indefinitely * tests can differentiate b/w HSV-1 and 2 - Presence of HSV-2 antibody indicates genital infection - Presence of HSV-1 antibody does not distinguish genital from oral infection
27
Treponema pallidum
- Organism that causes syphilis - Humans only natural host - Think, coiled spirochete (no visualized under light microscopy) - Labile and cannot be spread by fomites - Lacks species-specific antigens on cell surface
28
Treponema pallidum transmission
- Organism that causes syphilis | - Transmitted through sexual, congenital, blood transfusion
29
Treponema pallidum pathogenicity
- Consequence of pts immune response - Can remain latent: lipid outer surface relative paucity of extruding proteins allow the organism to escape immune control and establish a chronic infection
30
Primary Syphilis Clinical Manifestations
Chancre - Early: macule/papule ---> erodes - Late: clean based, painless, indurated ulcer w/ smooth firm borders - Unnoticed in 15-30% of pts - Resolves in 1-5wks - HIGHLY INFECTIOUS
31
Syphilis Progression
- Primary: painless chancre - Secondary: Rash, fever, neuro symptoms (can even resemble chickenpox) - Latency: may got into latency - Tertiary Syphilis: 5-50yrs of infection, bone, cardiac, nerve disease
32
Syphilis Treatment
- Penicillin
33
Syphilis Diagnosis
- RPR lab test | - Followed by TPPA and FTA
34
Jarsich-Herxheimer reaction
- Immune reaction from massive release of treponemal antigens due to antibodies working and the organism being lysed - Manifested by fever, headache, myalgia - Occurs within 24hrs - Treatment = steroids
35
Malignant Syphilis Presentation
- Painful skin ulcers all over body, fever
36
Prozone Effect
- In syphilis refers to a false-neg response from overwhelming antibody titers that interfere w/ formation of the Ag-Ab network necessary to a pos reaction
37
Syphilitic Proctitis Presentation
- Painful bowel movements and rectal bleeding (dyschezia and hematochezia) - Rash on palms/soles
38
RPR Titer
- RPR measures the viral load | - 1:xx where x = the viral load (higher the number the more viral particles)
39
Tabes dorsalis
- Ataxia and loss of proprioception - Pupils do not react to light - Product of Ocular syphilis
40
Haemophilus ducreyi
- Causes chancroid | - Painful necrotizing genital ulcers that may be accompanied by lymphadenopathy
41
Chancroid Symptoms
- Caused by Haemophilus ducreyi - Starts as a tender papule-pustule-then ulcer w/ a ragged undermined edge; is friable and a grey-yellowish discharge - Painful, indurated, 'ragged' genital ulcers and tender suppurative inguinal adenopathy - Painful inguinal lymphadenopathy in 50%, fluctuant buboes may rupture spontaneously -
42
Chancroid Diagnosis
- Culture of material from the ulcer base or edges or aspirate (80% sensitive) - PCR
43
Chancroid Treatment
- Caused by Haemophilus ducreyi | - Treatment: Azithromycin 1g PO x1 OR Ceftriaxone 250mg IM x1 (erythromycin and ciprofloxacin may also be used)
44
Genital Ulcers Differentiation (Herpes vs. Chancroid vs. Primary syphilis)
- Genital Herpes: painful lesions w/ b/l painful inguinal adenopathy (pain, b/l) - Chancroid: painful lesions w/ unilateral painful adenopathy (pain, u/l) - Primary Syphilis: No painful lesions w/ b/l painless adenopathy (no pain, b/l)
45
Chancroid Transmission
- Microabrasion in skin during intercourse
46
Klebsiella granulomatis
- Granuloma inguinale or Donovanosis - Causes painless, progressive (destructive), "serpiginous" ulcerative lesions, w/o regional lymphadenopathy; beefy red w/ white border and highly vascular
47
Granuloma Inguinale OR Donovanosis Diagnosis
- Cause by Klebsiella granulomatis | - Dx: tissue biopsy
48
Granuloma Inguinale OR Donovanosis Treatment
- Caused by Klebsiella granulomatis | - Rx: Doxycycline 100mg PO BID x3wks
49
Granuloma Inguinale (Donovanosis)
- Chronic, progressively destructive infection, as beefy (velvety) red, friable and non-tender ulcers. Lesions are elevated w/ a smooth rolled edge. May have a serpiginous outline. - Kissing lesions- extension along skin folds and contact on opposed surfaces
50
Granuloma Inguinale (Donovanosis) Complications
- Elephantiasis, stricture and pelvic abscess, proctitis, lymphangitis, lymphadenitis, discharging sinuses
51
Lymohogranuloma venereum
- Chlamydia trachomatis | - "Groove sign"; painful elongated sausage-shaped swellings in inguinal area above and below the Poupart ligament
52
Chlamydia trachomatis Symptoms
- Lymphogranuloma Venereum - Short-lived painless genital ulcer accompanied by painful inguinal lymphadenopathy - Outbreaks in US assoc. w/ proctitis particularly among MSM (gays) - Rectal pain, tenesmeus, rectal bleeding/discharge - May be mistaken for IBD on biopsy
53
Lymphogranuloma Venereum Treatment
- Caused by Chlamydia trachomatis | - Rx: Doxycycline OR Erythromycin
54
Lymphogranulma Venereum Stages
- 1st stage: small painless papule/pustule at site of inoculation. May erode into small ulcer - 2nd stage: painful inflammation/infection of inguinal lymph nodes, may become fluctuant and rupture or may develop into hard, nonsuppurative masses' along w/ fever, arthralgia, malaise - 3rd stage: proctocolitis, perirectal abscesss, fistulas, strictures, stenosis and scarring, may lead to elephantiasis
55
Lymphogranuloma Venereum Diagnosis
- Caused by Chlamydia trachomatis | - Dx: culture and cell typing, serology, immunoflourescence, PCR
56
Chlamydia Risk Factors
- Women >25 who have a new sex partner, >1 sex partner, a sex partner w/ concurrent partner, or a sex partner who has a STI - Women <25 and older women w/ risk factors need testing every year (CDC)
57
Neurosyphilis
- Can occur at any stage of Infection
58
Mycoplasma genitalium
- Organism that can cause PID
59
Mycoplasma Genitalium Treatment
- Azithromycin | - Moxifloxacin
60
HPV Latent Infection
- Viral DNA is not integrated | - Treatment will not clear