GENITAL ULCER DISEASE

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GENITAL ULCER DISEASE

• STEPHANIE N. TAYLOR, MD
• LSUHSC SECTION OF INFECTIOUS DISEASES
• MEDICAL DIRECTOR,
• DELGADO PERSONAL HEALTH CENTER
• NEW ORLEANS, LA

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DISCLOSURE

• I have no financial interests or other
  relationship with manufacturers of commercial
  products, suppliers of commercial services, or
  commercial supporters. My presentation will not
  include any discussion of the unlabeled use of a
  product or a product under investigational use.

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GENITAL ULCER DISEASE

• Differential Diagnosis
• STDs
• Syphilis, Herpes, Chancroid
• LGV, Granuloma inguinale, Ectoparasites
  (infected)
• Non-STDs
• Trauma, fixed drug eruption, neoplasia
• Aphthous ulcers, non-STD infection, Crohns Ds.
• Behçets Syndrome Oral and/or genital ulcers
  (not alone), cutaneous lesions, uveitis,
  arthritis, phlebitis
• Reiters Syndrome arthritis, conjunctivitis,
  urethritis, circinate balanitis, keratoderma
  blennorrhagicum

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Primary and secondary syphilis Rates by state
United States and outlying areas, 2008
Note The total rate of PS syphilis for the
United States and outlying areas (Guam, Puerto
Rico and Virgin Islands) was 4.5 per 100,000
population. The Healthy People 2010 target is 0.2
case per 100,000 population.
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Primary and secondary syphilis Age- and
sex-specific rates United States, 2008
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Primary and secondary syphilis Male-to-female
rate ratios United States, 19812006
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Primary and secondary syphilis Reported cases
by stage and sexual orientation, 2008
20 of reported male cases with PS syphilis
were missing sex of sex partner information.
MSM denotes men who have sex with men.
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Primary and secondary syphilis Cases by sexual
orientation and race/ethnicity, 2008
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SYPHILIS STAGING
INFECTION
(3 WEEKS)
PRIMARY CHANCRE
(1-3 MONTHS)
SECONDARY
(1-3 MONTHS / 60-90)
LATENCY
(2-50 YEARS)
70 30
LIFETIME LATENCY TERTIARY
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PRIMARY SYPHILIS
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PRIMARY SYPHILIS


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Manifestations of Secondary Syphilis

• Rash (may be anywhere or look like
  anything)
• Mucous patches condylomata lata
• Lymphadenopathy
• Moth eaten alopecia
• Systemic symptoms (fever, headache, fatigue,
  arthralgia/myalgia)

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SECONDARY SYPHILIS

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SECONDARY SYPHILIS


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SECONDARY SYPHILIS


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SECONDARY SYPHILIS


Adenopathy Patchy Alopecia
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SECONDARY SYPHILIS


Condyloma lata
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LATENT SYPHILIS

• Period during which there is no clinical evidence
  of disease
• Serological tests are positive
• Arbitrarily divided into early latent
  (infection occurred within the last year) or
  late latent

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TERTIARY SYPHILIS

• Slowly progressive disease - affects any organ
  system and produces clinical illness years after
  initial infection
• NEUROSYPHILIS - meningitis, general paresis,
  optic neuritis ( ? WBCs, CSF VDRL, ? Prot.)
• CARDIOVASCULAR - aortic aneurysm, aortic
  regurgitation
• GUMMATOUS - large indurated lesions of skin, GI
  tract, mouth

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DIAGNOSIS

• Darkfield examination of material from a moist
  lesion 70-80 sensitive
• Serologic Tests
• Non-treponemal (Non-specific) RPR, VDRL, ART
• Treponemal (Specific) FTA-ABS, TPHA, IgG
• Silver stain of biopsy material
• DNA Methods (PCR, etc.)

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(No Transcript)
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Specific Serologic Tests (IgG, MHA-TP, FTA-Abs,
etc)

• Detect antibody to specific treponemal antigens
  (fewer false positives)
• May be negative in primary syphilis (70 80
  sensitive)
• Remain positive for life

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Non-specific Serologic Tests(RPR, VDRL, ART, etc)

• Detect antibody to cardiolipin, cholesterol and
  lecithin (false positives are possible)
• May be negative in primary syphilis (70 80
  sensitive) but almost always positive in
  secondary syphilis
• Reported as reactive, weakly reactive,
  non-reactive or may be quantified

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Non-specific Serologic Tests(RPR, VDRL, ART, etc)

• Quantification
• 11 12 14 18 116 132 164 .
  1512 etc.
• Titers decrease after successful therapy
  (re-check at 6 and 12 months)
• A fourfold decrease (2 dilutions) 6 months after
  treatment is considered a sign of successful
  treatment

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Non-specific Serologic Tests(RPR, VDRL, ART, etc)

• Titers should eventually fall to zero
  (non-reactive) after treatment
• 10 15 of patients remain serofast at a low
  titer - This can result in problems with
  test interpretation years later

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Syphilis2006 CDC STD Treatment Guidelines

• Primary, Secondary, and Early Latent
• Benzathine penicillin 2.4 MU IM
• PCN allergic Doxy. 100 mg po bid for 14 days
• Late Latent
• Benzathine penicillin 2.4 MU IM q wk. x 3
  injections
• PCN allergic Doxy. 100 mg po bid x 4 weeks
• Neuro-Syphilis
• Aqueous crystalline PCN 3-4 MU IV q 4 hrs 10-14
  days PCN Allergic need to be desensitized
• Special Circumstances
• Pregnant and PCN allergic desensitize and treat
• HIV Same tx. for stage of syphilis in non-HIV
  pt.

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CHANCROID

• ETIOLOGY
• Haemophilus ducreyi
• Fastidious organism difficult to isolate
• Requires supplemented chocolate agar and 5 CO2
  for growth

• EPIDEMIOLOGY
• Seen more commonly in third world countries
• Only 25 cases reported in the U.S. in 2008, but
  outbreaks have been seen in the past

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CLINICAL MANIFESTATIONS

• Incubation period 5-7 days
• A papule develops initially but goes on to erode
  into a painful, soft, and non-indurated ulcer
• 50 of patients will develop painful local
  adenopathy which may suppurate or rupture

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CHANCROID

Genital Ulcer with Inguinal Buboes in 50
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Chancroid2006 CDC STD Treatment Guidelines

• Azithromycin 1 gm orally single dose
• Ceftriaxone 250 mg IM single dose
• Ciprofloxacin 500 mg po bid for 3 days
• Erythromycin base 500 mg po qid for 7 days

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Herpes Simplex Virus - Pathophysiology

• Mucocutaneous infection retrograde migration
  along sensory nerves latency in dorsal spinal
  root or trigeminal ganglia re-activation and
  recurrent outbreaks.
• HSV1 most infections are orolabial 20 of
  new genital herpes cases
• HSV-2 almost always genital infection orolabia
  l infection is rare

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GENITAL HERPES

• Most common cause of genital ulcer disease in
  N.A.
• Primary Infection
• 80-90 due to HSV-2
• Typically most severe, systemic symptoms common
• Mult. painful vesicles, shallow ulcers, heal 2-3
  wks
• Recurrences
• Less severe lesions
• Shorter duration
• Most patients with HSV-2 asymp. or do not
  recognize symptoms
• Asymptomatic viral shedding occurs without
  outbreaks

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Genital herpes Initial visits to physicians
offices United States, 19662005
Note The relative standard error for genital
herpes estimates range from 20 to 30.
SOURCE National Disease and Therapeutic Index
(IMS Health)
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Disease Spectrum in HSV-2 Seropositive Persons

• 20 - Clinical manifestations are recognized as
  genital herpes
• 60 - Clinical manifestations are not recognized
  as genital herpes
• 20 - Subclinical

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Genital Herpes Initial Presentations for Care

• 20 - True primary infection
• 40 - Non-primary first episode of genital
  HSV
• 40 - First clinical manifestations of a prior
  genital HSV infection (recurrence)

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Features of Primary HSV-2 Infection

• 3-week illness
• Many lesions, frequently bilateral
• Mucosal involvement is common
• Pain may be severe
• Lymphadenopathy is common
• Systemic symptoms are common

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HERPES SIMPLEX


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Features of Recurrent Genital Herpes

• 5 10 days
• Fewer lesions, usually unilateral
• Mucosal involvement is uncommon
• Lymphadenopathy is uncommon
• Systemic symptoms are uncommon

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RECURRENT HERPES SIMPLEX
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Recurrence of Herpes Outbreaks

• Mean number of outbreaks in first year after
  initial genital HSV-2 infection
• - men 5.2 outbreaks/year - women 4.0
  outbreaks/year
• Rate declines over time
• Rates are lower in genital HSV-1 infection
• ? Precipitating factors

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Subclincal Shedding of HSV

• Seen in gt 95 of persons with HSV-2 (much less
  common in genital HSV-1)
• More frequent in first year after infection
  (detected on 5 10 of days by culture and 20
  30 of days by PCR)
• Less frequent over time (2 3 of days)
• Responsible for most transmission

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Diagnosis of Genital Herpes

• Clinical diagnosis has good specificity in
  classic cases but lacks sensitivity due to
  atypical and subclinical cases
• Culture (or DFA) 50 70 sensitivity
• Type specific serologic assays with good
  sensitivity and specificity are now available

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Treatment of Genital Herpes

• Primary and Non-primary Initial Infections
• Treat most patients

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CDC 2006 STD Treatment GuidelinesTreatment of
First Episode

• Acyclovir 400 mg TID for 7-10 days
• Acyclovir 200 mg 5x/day for 7 10 days
• Valacyclovir 1 g BID for 7 10 days
• Famciclovir 250 mg TID for 7 10 days

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Treatment of Genital Herpes

• Primary and Non-primary Initial Infections
• - treat most patients
• Episodic Recurrences
• - treatment may have minimal benefit

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CDC 2006 STD Treatment GuidelinesTreatment of
Episodic Recurrences

• Acyclovir 400 mg TID for 5 days
• Acyclovir 800 mg BID for 5 days
• Acyclovir 800 mg TID for 2 days
• Valacyclovir 500 mg BID for 3 days
• Valacyclovir 1000 mg q day for 5 days
• Famciclovir 125 mg BID for 5 days
• Famciclovir 1000 mg BID for 1 day

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Treatment of Genital Herpes

• Primary and Non-primary Initial Infections
  - treat most patients
• Episodic Recurrences - treatment may
  have minimal benefit
• Suppressive Therapy - indicated when
  outbreaks are frequent - should be
  discussed with all patients

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CDC 2006 STD Treatment GuidelinesSuppressive
Therapy

• Acyclovir 400 mg BID
• Valacyclovir 1 g q day
• Valacyclovir 500 mg q day
• Famciclovir 250 mg BID
• Reassess the need for continued therapy

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HSV - 2006 STD Treatment Guidelines

• Initial Episode
• Acyclovir, famcicloivir, or valacyclovir X 7-10
  days
• Recurrences
• Acyclovir, famcicloivir, or valacyclovir X 5 days
• 2006 STD Guidelines add 1, 2 and 3-day regimens
• Suppressive Therapy
• Indicated for patients with 6 outbreaks a year
• Reduces the frequency and asymptomatic shedding

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Approach to the Patient with GUD

• History and exam - if the presentation is
  classic then treat based on your clinical
  diagnosis
• Testing - syphilis serology and darkfield
  (if available) - culture or serology for herpes
  (if available) - HIV testing
• If diagnosis is not clear, treat for primary
  syphilis