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Managing Vulvovaginal
      Disorders


           Michael Policar, MD, MPH
    Professor of Ob, Gyn, and Repro Sciences
            UCSF School of Medicine
           policarm@obgyn.ucsf.edu
• There are no relevant financial
  relationships with any commercial
  interests to disclose
Vulvovaginal Symptoms:
               Differential Diagnosis
Category        Condition
Infections      Vaginal trichomoniasis       (VT)
                Bacterial vaginosis          (BV)
                Vulvovaginal candidiasis (VVC)
Skin Conditions Fungal vulvitis (candida, tinea)
                Contact dermatitis (irritant, allergic)
                Vulvar dermatoses (LS, LP, LSC)
                Vulvar intraepithelial neoplasia (VIN)
Psychogenic     Physiologic, psychogenic
CDC 2010: Trichomoniasis
        Screening and Testing
• Screening indications
   – HIV positive women: annually
   – Consider if “at risk”: new/multiple sex partners, history of STI,
     inconsistent condom use, sex work, IDU
• New assays
   – Rapid antigen test:  sensitivity, specificity vs. wet mount
   – Aptima TMA T. vaginalis Analyte Specific Reagent (ASR)
• Other testing situations
   – Suspect trich but NaCl slide neg  culture or newer assays
   – Pap with trich  confirm if low risk
• Consider retesting 3 months after treatment
Trichomoniasis: Laboratory Tests
Test              Sensitivity   Specificity Cost   Comment

Aptima TMA        +4 (98%)      +3 (98%)    $$$ NAAT (like GC/Ct)
Culture           +3 (83%)      +4 (100%)   $$$ Not in most labs
Point of care
•Affirm VP III    +3            +4          $$$    DNA probe
•OSOM Rapid       +3 (90%)      +4 (100%)   $$     CLIA waived
NaCl suspension   +2 (56%)      +4 (100%)   ¢¢     1st line
Pap smear         +2            +3          n/a    Confirm if low
                                                   prevalence

                  Accuracy data: Huppert CID 2007
CDC 2010: Vaginal
   Trichomoniasis Treatment
• Recommended regimen
   – Metronidazole     2 grams PO single dose
   – Tinidazole        2 grams PO single dose
• Alternative regimen (preferred for HIV infected women)
   – Metronidazole 500 mg PO BID x 7 days
• Metronidazole safe at all gestational ages
   – Limited pregnancy data on Tinidazole
• Treat sex partner(s)
• Targeted screening for other STIs: GC, Ct, syphilis, HIV
CDC 2010: VT Treatment Failure
• Re-treat with either
   – Tinidazole 2 g PO single dose
   – Metronidazole 500 mg PO BID x 7 days
• If repeat failure, treat with
   – Metronidazole 2 grams po x 3-5 days
• If repeat failureTinidazole 2-3 g po plus 1-1.5 g vaginally
  x14 days
• Arrange for susceptibility testing: Call CDC!! (770-488-
  4115)
BV: Pathophysiology

• Non-inflammatory bacterial overgrowth
   – 100 x increase Gardnerella vaginalis
   – 1000 x increase in anaerobes
   – More pathogen types (Mobiluncus, Mycoplasmas)
• Suppression of H2O2-producing Lactobacillus crispatus and L.
  jensenii (L acidophilus is not present)
• >50% women carry G. vaginalis in their vaginal flora in the
  absence of BV
   – Bacterial “C/S” of vaginal fluid doesn’t help in the
     diagnosis of BV….or of any other vaginal infection
BV: Sexually Associated or Transmitted?
• “Sexually associated” in heterosexuals
   – Rare in virginal women
   – Greater risk of BV with multiple male partners
   – Condom use decreases risk,
   But
   – No BV carrier state identified in men
   – Treatment of partner does not affect recurrences
• Women having sex with women (WSW)
   – Infected vaginal fluid between women causes BV
   – Studies of concurrence in lesbian couples suggest
     horizontal transmission
BV: Clinical Diagnosis

• Amsel Criteria: 3 or more of
   – Homogenous white discharge
   – Amine odor (“whiff” test)
   – pH > 4.5 (most sensitive)
   – Clue cells > 20% (most specific)
• Spiegel criteria, Nugent score: Gram stain with
   – Few or no gram positive Lactobacillus spp.
   – Excess of other gram negative morphotypes
Characteristic Discharge With BV
BV: Clue Cells on Saline Suspension

                                >20% of
                                epithelial
                                cells are
                                clues


                                Reduced
                                Lactobacilli

                                 Ragged cell
                                 border
BV: Laboratory Tests
Test                    Sensit   Specif   Cost   Comment
Nugent score            +4       +4       ¢¢     Labor intensive
Point of care tests
 Affirm VP III         +4       +3       $$$    DNA probe
 OSOM BV Blue          +3       +3       $$     CLIA moderate
 G vag PIP             +2       +3       $$$    CLIA moderate
pH + amines             +2       +2       $      CLIA waived
Amsel criteria          +3       +2       ¢¢     1st line
Pap smear               +1       +2-3     n/a    Coccobacilli
Who Should Be Tested for BV?
• Routine screening (asymptomatic): not indicated
• Standard diagnostic testing
   – Check discharge, amines, vaginal pH, clue cells
• Microscopy not available or inconclusive
   – Affirm VP III
   – OSOM BV Blue
   – G vaginalis PIP, pH+amine test cards
• “Shift in vaginal flora” on Pap
   – No consensus, but poor correlation with BV…most experts
     recommend no further follow up
CDC 2010: BV Treatment
Recommended regimens
   – Metronidazole 500 mg PO BID x 7 days
   – Metronidazole gel 0.75% 5g per vagina QD x 5 days
   – Clindamycin 2% cream 5g per vagina QHS x 7 days
Alternative regimens
   – Tinidazole 2 g PO QD for 3 days
   – Tinidazole 1 g PO QD for 5 days
   – Clindamycin 300 mg PO BID x 7 days
   – Clindamycin ovules 100 mg per vagina QHS x 3 days
CDC 2010: Recurrent BV

• Consider suppression with metronidazole vaginal gel twice
  weekly for 4-6 months (after full initial treatment)
• No evidence yet to support use of probiotics
• Don’t douche…with anything!
• Use of condoms by male partners may reduce recurrences
• Clean sex toys (or use condoms) between uses
• Avoid vaginal insertion after anal insertion of a finger or penis
CDC 2010: VVC Classification
• Uncomplicated VVC (80-90%)
   – Sporadic or infrequent VVC, and
   – Mild-to-moderate VVC, and
   – Likely to be Candida albicans, and
   – Immunecompetant
• Complicated VVC (10-20%)
   – Recurrent VVC, or
   – Severe VVC, or
   – Non-albicans candidiasis, or
   – Uncontrolled DM, immunosuppression, pregnancy
VVC: Laboratory
• KOH suspension
   − C. albicans: pseudohyphae and blastospores (buds)
   − C. glabrata: blastospores only
• NaCl suspension: many WBC, normal lactobacillus
• pH: 4-6
• Amine test: negative
• Confirmatory tests
   - Point of care test: Affirm VP III
   - Candida culture (not: fungus culture)
   - Candida PCR
Treatments for VVC

       Drug           Over the Counter       Prescription
Length of Treatment   7d   3d     1d     7d     3d     1d
Butoconazole                                            X
Clotrimazole          X     X                           X
Miconazole            X     X     X
Terconazole                              X       X
Tioconazole                 X     X
Fluconazole (PO)                                        X
CDC 2010: Uncomplicated
                 VVC Treatments
• Non-pregnant women
   – 3 and 7 day topicals have equal efficacy and price
   – Offer either: 1 or 3 day topical or oral fluconazole
       • Topical: quickly soothing, but inconvenient
       • Oral: convenient, but effect is not immediate
• If first treatment course fails
   – Re-confirm diagnosis (r/o dual infection)
   – Treat with an alternate antifungal drug
   – Perform Candida culture to confirm and speciate
• No role for nystatin, candicidin
CDC 2010: Complicated
                 VVC Treatment
Severe VVC
• Advanced findings: erythema, excoriation, fissures
• Topical azole therapy for 7-14 days, or
Compromised host
• Topical azole treatment for 7-14 days
• Fluconazole 150 mg PO; repeat Q3 days 1-2 times
Pregnancy
• Topical azoles for 7 days
CDC 2010: Complicated
                 VVC Treatment
Recurrent VVC (RVVC)
• > 4 episodes of symptomatic VVC per year
• Most women have no predisposing condition
   – Partners are rarely source of infection
• Confirm with Candidal culture before maintenance
  therapy; also check for non-albicans species
• Early treatment regimen: self-medication 3 days with
  onset of symptoms
CDC 2010: Complicated
                 VVC Treatment
• Recurrent VVC: Treatment
   – Treat for 7-14 days of topical therapy or fluconazole
     150 mg PO q 72o x3 doses, then
   – Maintenance therapy x 6 months
      • Fluconazole 100-200 mg PO 1-2 per week
      • Itraconazole 100 mg/wk or 400 mg/month
      • Clotrimazole 500 mg suppos 1 per week
      • Boric acid 600 mg suppos QD x14, then BIW
      • Gentian violet: Q week x2, Q month X 3-6 mo
Vulvar Candidiasis

• Vulva will be very itchy; often excoriated
• Presentation
   – Erythema + satellite lesions
   – Occasionally: thrush, LSC thickening if chronic
• Diagnosis: skin scraping KOH, candidal culture
• Treatment
   – Topical antifungal therapy daily for 7-14 days, or
     fluconazole 150 mg PO repeat in 3 days
   – Plus: TAC 0.1% or 0.5% ointment QD-BID
Vulvar Candidiasis
Tinea Cruris: “Jock Itch”
• Asymmetric lesions on proximal inner thighs
   – Plaque rarely involves scrotum; not penile shaft
• Well demarcated red plaques with accentuation of scale
  peripherally; no satellite lesions
• Fungal folliculitis: papules, nodules or pustules within
  area of plaque
• Treatment
   – Mild: topical azoles BID x10-14d, terbinafine
   – Severe: fluconazole 150 mg QW for 2-4 weeks
   – If inflammatory, add TAC 0.1% on 1st 3 days
Intertrigo
• Background
   – Occlusion, rubbing of skin chafing, inflammation
   – If moist, often superinfection with candida or tinea
   – May lichenify to LSC
• Findings
   – Dull red, shiny skin fold; if moist, white surface
   – Follows clothing lines; under breasts, pannus
   – No satellites; border not sharp
• Treatment
   – Keep skin clean and dry; use cornstarch
   – Reduce friction with bland emollient
   – Treat secondary infection with topical azole
Contact Dermatitis
• Irritant contact dermatitis (ICD)
   – Elicited in most people with a high enough dose
   – Rapid onset vulvar itching (hours-days)
• Allergic contact dermatitis (ACD)
   – Delayed hypersensitivity
   – 10-14 days after 1st exposure; 1-7 d after repeat exposure
• ICD and ACD can present with
   – Itching, burning, swelling, redness
   – Small vesicles or bullae more likely with ACD
Contact Dermatitis
• Common contact irritants
   – Urine, feces, excessive sweating
   – Saliva (receptive oral sex)
   – Repetitive scratching, overwashing
   – Detergents, fabric softeners
   – Topical corticosteroids
   – Toilet paper dyes and perfumes
   – Hygiene pads (and liners), sprays, douches
   – Lubricants, including condoms
Contact Dermatitis

   Symmetric

  Raised,
  bright red,
  intense itching

  Extension to
  areas of irritant
  contact
Contact Dermatitis
• Common contact allergens
   – Poison oak, poison ivy
   – Topical antibiotics, esp neomycin, bacitracin
   – Spermicides
   – Latex (condoms, diaphragms)
   – Vehicles of topical meds: propylene glycol
   – Lidocaine, benzocaine
   – Fragrances
Contact Dermatitis: Treatment
• Exclude contact with possible irritants
• Restore skin barrier with sitz baths, compresses
• After hydration, apply a bland emollient
   – White petrolatum, mineral oil, olive oil
• Short term mild-moderate potency steroids
   – TAC 0.1% BID x10-14 days (or clobetasol 0.05%)
   – Fluconazole 150 mg PO weekly
• Cold packs: gel packs, peas in a “zip-lock” bag
• Doxypin or hydroxyzine (10-75 mg PO) at 6 pm
• If recurrent, refer for patch testing
Why Not Steroid-Antifungal
              Combination Drugs?
• Which products should be avoided?
  – Lotrisone: Clotrimazole and Betamethasone 0.5%
  – Mycolog II: Nystatin and Triamconolone acetonide
• Why avoid them?
  – Inflammation usually clears up before fungal infection
  – Steroid overshoot  skin atrophy
  – Local immunosuppression (from steroid) may blunt
    antifungal effect
ISSVD 1987: Vulvar Dermatoses
Type           ISSVD Term        Old Terms
Atrophic       Lichen            • Lichen sclerosus et atrophicus
               sclerosus         • Kraurosis vulvae
Hyper-         Squamous cell     • Hyperplastic dystrophy
plastic        hyperplasia       • Neurodermatitis
                                 • Lichen simplex chronicus
Systemic       Other             • Lichen planus
               dermatoses        • Psoriasis
Pre-           VIN               • Hyperplasic dystrophy/atypia
malignant                        • Bowen’s disease
                                 • Bowenoid papulosis
                                 • Vulvar CIS
       ISSVD: International Society for the Study of Vulvar Disease
ISSVD 2006 Classification of
                     Vulvar Dermatoses
• No consensus agreement on a system based upon
  clinical morphology, path physiology, or etiology
• Include only non-Neoplastic, non-infectious entities
• Agreed upon a microscopic morphology based system
• Rationale of ISSVD Committee
   – Clinical diagnosis  no classification needed
   – Unclear clinical diagnosis  seek biopsy diagnosis
   – Unclear biopsy diagnosis  seek clinic pathologic
     correlation
ISSVD 2006 Classification of
                   Vulvar Dermatoses
Path pattern      Clinical Corrrelates
Spongiotic        Atopic dermatitis, allergic contact dermatitis,
                  irritant contact dermatitis
Acanthotic        Psoriasis, LSC (primary or superimposed), (VIN)
Lichenoid         Lichen sclerosus, lichen planus
Dermal         Lichen sclerosus
homogenization
Vesicolobullous   Pemphigoid, linear IgA disease
Acantholytic      Hailey-Hailey disease, Darier disease, papular
                  genitocrural acantholysis
Granulomatous     Crohn disease
Vasculopathic     Apthous ulcers, Behcet disease, plasma c. vulvitis
Lichen Sclerosus: Natural History

• Most common vulvar dermatosis
• Prevalence: 1.7% in a general GYN practice
• Cause: autoimmune condition
• Bimodal age distribution: older women and children, but
  may be present at any age
• Chronic, progressive, lifelong condition
Lichen Sclerosus: Natural History

• Most common in Caucasian women
• Can affect non-vulvar areas
• Part (or all) of lesion can progress to VIN, differentiated
  type
• Predisposition to vulvar squamous cell carcinoma
   – 1-5% lifetime risk (vs. < 0.01% without LS)
   – LS in 30-40% women with vulvar squamous cancers
Lichen Sclerosus: Findings
• Symptoms
   – Most commoly, itching
   – Often irritation, burning, dyspareunia, tearing
   – 58% of newly-diagnosed patients are asymptomatic
• Signs
   – Thin white “parchment paper” epithelium
   – Fissures, ulcers, bruises, or submucosal hemorrhage
   – Loss of labia minora, fusion of labia and clitoral hood
   – Depigmentation (white) or hyperpigmentation in
     “keyhole” distribution: vulva and anus
   – Introital stenosis
Lichen Sclerosus: Treatment
• Biopsy mandatory for diagnosis, unless classic findings
• Preferred treatment
   – Clobetasol 0.05% ointment QD x4 weeks, then QOD x4
     weeks, then twice-weekly for 4 weeks
   – Taper to med potency steroid (or clobetasol) 2-4 times
     per month for life
   – Explain “titration” regimen to patient, including
     management of flares and recurrent symptoms
   – 30 gm tube of ultrapotent steroid lasts 3-6 mo
   – Monitor every 3 months twice, then annually
“Early”
Lichen Sclerosus

   Hyperpigmentation
   due to scarring

   Loss of labia minora
Later Lichen
Sclerosus

     Thin white
     epithelium

     Fissures
“Late” Lichen Sclerosus
     Agglutination of
     clitoral hood
     Loss of labia
     minora
     Introital
     narrowing

     Parchment paper
     epithelium
Lichen Sclerosus: Treatment
• Second line therapy
   – Pimecrolimus, tacrolimus
   – Retinoids, potassium para-aminobenzoate
• Testosterone (and estrogen or progesterone) ointment
  or cream no longer recommended
• Explain chronicity and need for life-long treatment
• Adjunctive therapy: anti-pruritic therapy
   – Antihistamines, especially at bedtime
   – Doxypin, at bedtime or topically
   – If not effective: amitriptyline, desipramine PO
• Perineoplasty may help dyspareunia, fissuring
Lichen Simplex Chronicus =
          Squamous Cell Hyperplasia
• Cause: an irritant initiates a “scratch-itch” cycle
• LSC classified as
   – Primary (idiopathic)
   – Secondary (superimposed upon lichen sclerosus,
     candida vulvitis; vulvar contact dermatitis)
• Presentation: always itching; burning, pain, tenderness
• Thickened leathery red (white if moisture) raised lesion
• In absence of atypia, no malignant potential
   – If atypia present , classified as VIN
Lichen Simplex Chronicus
L. Simplex Chronicus: Treatment

• Removal of irritants or allergens
• Treatment
   – Triamcinolone acetonide (TAC) 0.1% ointment BID x4-
     6 weeks, then QD
   – Other moderate strength steroid ointments
   – Intralesional TAC once every 3-6 months
• Anti-pruritics
   – Hydroxyzine (Atarax) 25-75 mg QHS
   – Doxepin 25-75 mg PO QHS
   – Doxepin (Zonalon) 5% cream; start QD, work up
Lichen Sclerosus + LSC
• “Mixed dystrophy” deleted in 1987
  ISSVD System
• 15% all vulvar dermatoses
• LS is irritant; scratching  LSC
• Consider: LS with plaque, VIN,
  squamous cell cancer of vulva
• Treatment
   – Clobetasol x12 weeks, then steroid
     maintenance
   – Stop the itch!!
Vulvar Intraepithelial Neoplasia (VIN):
                     Prior to 2004

• Grading of VIN-1 through VIN-3, based upon degree of
  epithelial involvement
• The mnemonic of the 4 P’s
   – Papule formation: raised lesion (erosion also
     possible, but much less common)
   – Pruritic: itching is prominent
   – “Patriotic”: red, white, or blue (hyperpigmented)
   – Parakeratosis on microscopy
ISSVD 2004: Squamous VIN

• VIN 1 is not a cancer precursor…abandon the term
  – Instead, use “condyloma” or “flat wart”
• Combine VIN-2 and VIN-3 into single “VIN” diagnosis
• Two distinct variants of VIN
   – VIN, usual type
      • Warty type
     • Basaloid type
     • Mixed warty-basaloid
  – VIN, differentiated (simplex) type
ISSVD 2004:VIN, Usual Type

•   Includes (old) VIN -2 or -3
•   Usually HPV-related (mainly type 16)
•   More common in younger women (30s-40s)
•   Often asymptomatic
•   Lesions usually elevated and have a rough surface,
•   Often multifocal; multicentric in 50%
•   Strongly associated with cigarette smoking
•   Regression is less likely and progression to invasion more
    likely with the basaloid type
VIN, Differentiated (Simplex) Type
• Includes (old) VIN 3 only
• Usually in older women with LS, LSC, or LP
• Not HPV related
• Less common than usual type
• Patients usually are symptomatic, with a long history of
  pruritus and burning
• Findings
   – Red, pink, or white papule; rough or eroded surfaces
   – A persistent, non-healing ulcer
• More likely to progress to SCC of vulva than usual VIN
White VIN,
Usual (warty) type
VIN, usual (basaloid)
type
VIN:
warty-
basaloid
type
Vulvar Intraepithelial Neoplasia
• Precursor to vulvar cancer, but low “hit rate”
   – Greater risk of invasion if immunocompromised
     (steroids, HIV), >40 years old, previous lower genital
     tract neoplasia
• Treatment
   – Wide local excision (few lesions), laser ablation
   – Topical agents: 5FU cream, imiquimod
   – Skinning or simple vulvectomy
• Recurrence is common (48% at 15 years)
   – Smoking cessation may reduce recurrence rate
Genital Skin: Dark Lesions
            (% are in women only)

•   36% Lentigo, benign genital melanosis
•   22% VIN
•   21% Nevi (mole)
•   10% Reactive hyperpigmentation (scarring)
•    5% Seborrheic keratosis
•    2% Malignant melanoma
•    1% Basal cell or squamous cell carcinoma
Vulvar Intraepithelial Neoplasia
Hyperpigmented
VIN, usual type
Indications for Vulvar Biopsy
• Papular or exophtic lesions, except obvious condylomata
• Thickened lesions (biopsy thickest region) to differentiate
  VIN vs. LSC
• Hyperpigmented lesions (biopsy darkest area), unless
  obvious nevus or lentigo
• Ulcerative lesions (biopsy at edge), unless obvious herpes,
  syphilis or chancroid
• Lesions that do not respond or worsen during treatment
• In summary: biopsy whenever diagnosis is uncertain
References
• Heller DS. Report of a new ISSVD classification of VIN. J Low Genit
  Tract Dis. 2007 Jan;11(1):46-7.
• Siderite M, et al. Squamous vulvar intraepithelial neoplasia: 2004
  modified terminology, ISSVD Vulvar Oncology Subcommittee J
  Reprod Med. 2005 Nov;50(11):807-10
• Wechter ME, Management of Bartholin duct cysts and abscesses: a
  systematic review Obstet Gynecol Surv. 2009 Jun;64(6):395-404.
• vanSeters, et al, Treatment of vulvar intraepithelial neoplasia with
  imiquimod. NEJM 2008;358:1465-73
• De Simone P Vulvar melanoma: a report of 10 cases and review of
  literature. Melanoma Res. 2008 Apr;18(2):127-33
References
• Lynch PJ, etal, 2006 ISSVD Classification of Vulvar Dermatoses.
  J Reprod Med 2007;52:3-9
• ACOG Practice Bulletin #93. Diagnosis and Management of
  Vulvar Skin Disorders. Ob Gynecol 2008;111 (5);1243-1253
• Smith YR, Haefner HK. Vulvar lichen sclerosus: pathophysiology
  and treatment. Am J Clin Dermatol. 2004;5(2):105-25.
• Edwards L, Vulvar fissures: causes and therapy. Dermatol Ther.
  2004;17(1):111-6.
• Foster DC, Vulvar disease. Ob Gynecol. 2002;100(1):145-63.

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Am 8.45 policar vulvovag

  • 1. Managing Vulvovaginal Disorders Michael Policar, MD, MPH Professor of Ob, Gyn, and Repro Sciences UCSF School of Medicine policarm@obgyn.ucsf.edu
  • 2. • There are no relevant financial relationships with any commercial interests to disclose
  • 3. Vulvovaginal Symptoms: Differential Diagnosis Category Condition Infections Vaginal trichomoniasis (VT) Bacterial vaginosis (BV) Vulvovaginal candidiasis (VVC) Skin Conditions Fungal vulvitis (candida, tinea) Contact dermatitis (irritant, allergic) Vulvar dermatoses (LS, LP, LSC) Vulvar intraepithelial neoplasia (VIN) Psychogenic Physiologic, psychogenic
  • 4. CDC 2010: Trichomoniasis Screening and Testing • Screening indications – HIV positive women: annually – Consider if “at risk”: new/multiple sex partners, history of STI, inconsistent condom use, sex work, IDU • New assays – Rapid antigen test:  sensitivity, specificity vs. wet mount – Aptima TMA T. vaginalis Analyte Specific Reagent (ASR) • Other testing situations – Suspect trich but NaCl slide neg  culture or newer assays – Pap with trich  confirm if low risk • Consider retesting 3 months after treatment
  • 5. Trichomoniasis: Laboratory Tests Test Sensitivity Specificity Cost Comment Aptima TMA +4 (98%) +3 (98%) $$$ NAAT (like GC/Ct) Culture +3 (83%) +4 (100%) $$$ Not in most labs Point of care •Affirm VP III +3 +4 $$$ DNA probe •OSOM Rapid +3 (90%) +4 (100%) $$ CLIA waived NaCl suspension +2 (56%) +4 (100%) ¢¢ 1st line Pap smear +2 +3 n/a Confirm if low prevalence Accuracy data: Huppert CID 2007
  • 6. CDC 2010: Vaginal Trichomoniasis Treatment • Recommended regimen – Metronidazole 2 grams PO single dose – Tinidazole 2 grams PO single dose • Alternative regimen (preferred for HIV infected women) – Metronidazole 500 mg PO BID x 7 days • Metronidazole safe at all gestational ages – Limited pregnancy data on Tinidazole • Treat sex partner(s) • Targeted screening for other STIs: GC, Ct, syphilis, HIV
  • 7. CDC 2010: VT Treatment Failure • Re-treat with either – Tinidazole 2 g PO single dose – Metronidazole 500 mg PO BID x 7 days • If repeat failure, treat with – Metronidazole 2 grams po x 3-5 days • If repeat failureTinidazole 2-3 g po plus 1-1.5 g vaginally x14 days • Arrange for susceptibility testing: Call CDC!! (770-488- 4115)
  • 8. BV: Pathophysiology • Non-inflammatory bacterial overgrowth – 100 x increase Gardnerella vaginalis – 1000 x increase in anaerobes – More pathogen types (Mobiluncus, Mycoplasmas) • Suppression of H2O2-producing Lactobacillus crispatus and L. jensenii (L acidophilus is not present) • >50% women carry G. vaginalis in their vaginal flora in the absence of BV – Bacterial “C/S” of vaginal fluid doesn’t help in the diagnosis of BV….or of any other vaginal infection
  • 9. BV: Sexually Associated or Transmitted? • “Sexually associated” in heterosexuals – Rare in virginal women – Greater risk of BV with multiple male partners – Condom use decreases risk, But – No BV carrier state identified in men – Treatment of partner does not affect recurrences • Women having sex with women (WSW) – Infected vaginal fluid between women causes BV – Studies of concurrence in lesbian couples suggest horizontal transmission
  • 10. BV: Clinical Diagnosis • Amsel Criteria: 3 or more of – Homogenous white discharge – Amine odor (“whiff” test) – pH > 4.5 (most sensitive) – Clue cells > 20% (most specific) • Spiegel criteria, Nugent score: Gram stain with – Few or no gram positive Lactobacillus spp. – Excess of other gram negative morphotypes
  • 12. BV: Clue Cells on Saline Suspension >20% of epithelial cells are clues Reduced Lactobacilli Ragged cell border
  • 13. BV: Laboratory Tests Test Sensit Specif Cost Comment Nugent score +4 +4 ¢¢ Labor intensive Point of care tests  Affirm VP III +4 +3 $$$ DNA probe  OSOM BV Blue +3 +3 $$ CLIA moderate  G vag PIP +2 +3 $$$ CLIA moderate pH + amines +2 +2 $ CLIA waived Amsel criteria +3 +2 ¢¢ 1st line Pap smear +1 +2-3 n/a Coccobacilli
  • 14. Who Should Be Tested for BV? • Routine screening (asymptomatic): not indicated • Standard diagnostic testing – Check discharge, amines, vaginal pH, clue cells • Microscopy not available or inconclusive – Affirm VP III – OSOM BV Blue – G vaginalis PIP, pH+amine test cards • “Shift in vaginal flora” on Pap – No consensus, but poor correlation with BV…most experts recommend no further follow up
  • 15. CDC 2010: BV Treatment Recommended regimens – Metronidazole 500 mg PO BID x 7 days – Metronidazole gel 0.75% 5g per vagina QD x 5 days – Clindamycin 2% cream 5g per vagina QHS x 7 days Alternative regimens – Tinidazole 2 g PO QD for 3 days – Tinidazole 1 g PO QD for 5 days – Clindamycin 300 mg PO BID x 7 days – Clindamycin ovules 100 mg per vagina QHS x 3 days
  • 16. CDC 2010: Recurrent BV • Consider suppression with metronidazole vaginal gel twice weekly for 4-6 months (after full initial treatment) • No evidence yet to support use of probiotics • Don’t douche…with anything! • Use of condoms by male partners may reduce recurrences • Clean sex toys (or use condoms) between uses • Avoid vaginal insertion after anal insertion of a finger or penis
  • 17. CDC 2010: VVC Classification • Uncomplicated VVC (80-90%) – Sporadic or infrequent VVC, and – Mild-to-moderate VVC, and – Likely to be Candida albicans, and – Immunecompetant • Complicated VVC (10-20%) – Recurrent VVC, or – Severe VVC, or – Non-albicans candidiasis, or – Uncontrolled DM, immunosuppression, pregnancy
  • 18. VVC: Laboratory • KOH suspension − C. albicans: pseudohyphae and blastospores (buds) − C. glabrata: blastospores only • NaCl suspension: many WBC, normal lactobacillus • pH: 4-6 • Amine test: negative • Confirmatory tests - Point of care test: Affirm VP III - Candida culture (not: fungus culture) - Candida PCR
  • 19. Treatments for VVC Drug Over the Counter Prescription Length of Treatment 7d 3d 1d 7d 3d 1d Butoconazole X Clotrimazole X X X Miconazole X X X Terconazole X X Tioconazole X X Fluconazole (PO) X
  • 20. CDC 2010: Uncomplicated VVC Treatments • Non-pregnant women – 3 and 7 day topicals have equal efficacy and price – Offer either: 1 or 3 day topical or oral fluconazole • Topical: quickly soothing, but inconvenient • Oral: convenient, but effect is not immediate • If first treatment course fails – Re-confirm diagnosis (r/o dual infection) – Treat with an alternate antifungal drug – Perform Candida culture to confirm and speciate • No role for nystatin, candicidin
  • 21. CDC 2010: Complicated VVC Treatment Severe VVC • Advanced findings: erythema, excoriation, fissures • Topical azole therapy for 7-14 days, or Compromised host • Topical azole treatment for 7-14 days • Fluconazole 150 mg PO; repeat Q3 days 1-2 times Pregnancy • Topical azoles for 7 days
  • 22. CDC 2010: Complicated VVC Treatment Recurrent VVC (RVVC) • > 4 episodes of symptomatic VVC per year • Most women have no predisposing condition – Partners are rarely source of infection • Confirm with Candidal culture before maintenance therapy; also check for non-albicans species • Early treatment regimen: self-medication 3 days with onset of symptoms
  • 23. CDC 2010: Complicated VVC Treatment • Recurrent VVC: Treatment – Treat for 7-14 days of topical therapy or fluconazole 150 mg PO q 72o x3 doses, then – Maintenance therapy x 6 months • Fluconazole 100-200 mg PO 1-2 per week • Itraconazole 100 mg/wk or 400 mg/month • Clotrimazole 500 mg suppos 1 per week • Boric acid 600 mg suppos QD x14, then BIW • Gentian violet: Q week x2, Q month X 3-6 mo
  • 24. Vulvar Candidiasis • Vulva will be very itchy; often excoriated • Presentation – Erythema + satellite lesions – Occasionally: thrush, LSC thickening if chronic • Diagnosis: skin scraping KOH, candidal culture • Treatment – Topical antifungal therapy daily for 7-14 days, or fluconazole 150 mg PO repeat in 3 days – Plus: TAC 0.1% or 0.5% ointment QD-BID
  • 26. Tinea Cruris: “Jock Itch” • Asymmetric lesions on proximal inner thighs – Plaque rarely involves scrotum; not penile shaft • Well demarcated red plaques with accentuation of scale peripherally; no satellite lesions • Fungal folliculitis: papules, nodules or pustules within area of plaque • Treatment – Mild: topical azoles BID x10-14d, terbinafine – Severe: fluconazole 150 mg QW for 2-4 weeks – If inflammatory, add TAC 0.1% on 1st 3 days
  • 27.
  • 28. Intertrigo • Background – Occlusion, rubbing of skin chafing, inflammation – If moist, often superinfection with candida or tinea – May lichenify to LSC • Findings – Dull red, shiny skin fold; if moist, white surface – Follows clothing lines; under breasts, pannus – No satellites; border not sharp • Treatment – Keep skin clean and dry; use cornstarch – Reduce friction with bland emollient – Treat secondary infection with topical azole
  • 29. Contact Dermatitis • Irritant contact dermatitis (ICD) – Elicited in most people with a high enough dose – Rapid onset vulvar itching (hours-days) • Allergic contact dermatitis (ACD) – Delayed hypersensitivity – 10-14 days after 1st exposure; 1-7 d after repeat exposure • ICD and ACD can present with – Itching, burning, swelling, redness – Small vesicles or bullae more likely with ACD
  • 30. Contact Dermatitis • Common contact irritants – Urine, feces, excessive sweating – Saliva (receptive oral sex) – Repetitive scratching, overwashing – Detergents, fabric softeners – Topical corticosteroids – Toilet paper dyes and perfumes – Hygiene pads (and liners), sprays, douches – Lubricants, including condoms
  • 31. Contact Dermatitis Symmetric Raised, bright red, intense itching Extension to areas of irritant contact
  • 32. Contact Dermatitis • Common contact allergens – Poison oak, poison ivy – Topical antibiotics, esp neomycin, bacitracin – Spermicides – Latex (condoms, diaphragms) – Vehicles of topical meds: propylene glycol – Lidocaine, benzocaine – Fragrances
  • 33. Contact Dermatitis: Treatment • Exclude contact with possible irritants • Restore skin barrier with sitz baths, compresses • After hydration, apply a bland emollient – White petrolatum, mineral oil, olive oil • Short term mild-moderate potency steroids – TAC 0.1% BID x10-14 days (or clobetasol 0.05%) – Fluconazole 150 mg PO weekly • Cold packs: gel packs, peas in a “zip-lock” bag • Doxypin or hydroxyzine (10-75 mg PO) at 6 pm • If recurrent, refer for patch testing
  • 34. Why Not Steroid-Antifungal Combination Drugs? • Which products should be avoided? – Lotrisone: Clotrimazole and Betamethasone 0.5% – Mycolog II: Nystatin and Triamconolone acetonide • Why avoid them? – Inflammation usually clears up before fungal infection – Steroid overshoot  skin atrophy – Local immunosuppression (from steroid) may blunt antifungal effect
  • 35. ISSVD 1987: Vulvar Dermatoses Type ISSVD Term Old Terms Atrophic Lichen • Lichen sclerosus et atrophicus sclerosus • Kraurosis vulvae Hyper- Squamous cell • Hyperplastic dystrophy plastic hyperplasia • Neurodermatitis • Lichen simplex chronicus Systemic Other • Lichen planus dermatoses • Psoriasis Pre- VIN • Hyperplasic dystrophy/atypia malignant • Bowen’s disease • Bowenoid papulosis • Vulvar CIS ISSVD: International Society for the Study of Vulvar Disease
  • 36. ISSVD 2006 Classification of Vulvar Dermatoses • No consensus agreement on a system based upon clinical morphology, path physiology, or etiology • Include only non-Neoplastic, non-infectious entities • Agreed upon a microscopic morphology based system • Rationale of ISSVD Committee – Clinical diagnosis  no classification needed – Unclear clinical diagnosis  seek biopsy diagnosis – Unclear biopsy diagnosis  seek clinic pathologic correlation
  • 37. ISSVD 2006 Classification of Vulvar Dermatoses Path pattern Clinical Corrrelates Spongiotic Atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis Acanthotic Psoriasis, LSC (primary or superimposed), (VIN) Lichenoid Lichen sclerosus, lichen planus Dermal Lichen sclerosus homogenization Vesicolobullous Pemphigoid, linear IgA disease Acantholytic Hailey-Hailey disease, Darier disease, papular genitocrural acantholysis Granulomatous Crohn disease Vasculopathic Apthous ulcers, Behcet disease, plasma c. vulvitis
  • 38. Lichen Sclerosus: Natural History • Most common vulvar dermatosis • Prevalence: 1.7% in a general GYN practice • Cause: autoimmune condition • Bimodal age distribution: older women and children, but may be present at any age • Chronic, progressive, lifelong condition
  • 39. Lichen Sclerosus: Natural History • Most common in Caucasian women • Can affect non-vulvar areas • Part (or all) of lesion can progress to VIN, differentiated type • Predisposition to vulvar squamous cell carcinoma – 1-5% lifetime risk (vs. < 0.01% without LS) – LS in 30-40% women with vulvar squamous cancers
  • 40. Lichen Sclerosus: Findings • Symptoms – Most commoly, itching – Often irritation, burning, dyspareunia, tearing – 58% of newly-diagnosed patients are asymptomatic • Signs – Thin white “parchment paper” epithelium – Fissures, ulcers, bruises, or submucosal hemorrhage – Loss of labia minora, fusion of labia and clitoral hood – Depigmentation (white) or hyperpigmentation in “keyhole” distribution: vulva and anus – Introital stenosis
  • 41. Lichen Sclerosus: Treatment • Biopsy mandatory for diagnosis, unless classic findings • Preferred treatment – Clobetasol 0.05% ointment QD x4 weeks, then QOD x4 weeks, then twice-weekly for 4 weeks – Taper to med potency steroid (or clobetasol) 2-4 times per month for life – Explain “titration” regimen to patient, including management of flares and recurrent symptoms – 30 gm tube of ultrapotent steroid lasts 3-6 mo – Monitor every 3 months twice, then annually
  • 42. “Early” Lichen Sclerosus Hyperpigmentation due to scarring Loss of labia minora
  • 43. Later Lichen Sclerosus Thin white epithelium Fissures
  • 44. “Late” Lichen Sclerosus Agglutination of clitoral hood Loss of labia minora Introital narrowing Parchment paper epithelium
  • 45. Lichen Sclerosus: Treatment • Second line therapy – Pimecrolimus, tacrolimus – Retinoids, potassium para-aminobenzoate • Testosterone (and estrogen or progesterone) ointment or cream no longer recommended • Explain chronicity and need for life-long treatment • Adjunctive therapy: anti-pruritic therapy – Antihistamines, especially at bedtime – Doxypin, at bedtime or topically – If not effective: amitriptyline, desipramine PO • Perineoplasty may help dyspareunia, fissuring
  • 46. Lichen Simplex Chronicus = Squamous Cell Hyperplasia • Cause: an irritant initiates a “scratch-itch” cycle • LSC classified as – Primary (idiopathic) – Secondary (superimposed upon lichen sclerosus, candida vulvitis; vulvar contact dermatitis) • Presentation: always itching; burning, pain, tenderness • Thickened leathery red (white if moisture) raised lesion • In absence of atypia, no malignant potential – If atypia present , classified as VIN
  • 48. L. Simplex Chronicus: Treatment • Removal of irritants or allergens • Treatment – Triamcinolone acetonide (TAC) 0.1% ointment BID x4- 6 weeks, then QD – Other moderate strength steroid ointments – Intralesional TAC once every 3-6 months • Anti-pruritics – Hydroxyzine (Atarax) 25-75 mg QHS – Doxepin 25-75 mg PO QHS – Doxepin (Zonalon) 5% cream; start QD, work up
  • 49. Lichen Sclerosus + LSC • “Mixed dystrophy” deleted in 1987 ISSVD System • 15% all vulvar dermatoses • LS is irritant; scratching  LSC • Consider: LS with plaque, VIN, squamous cell cancer of vulva • Treatment – Clobetasol x12 weeks, then steroid maintenance – Stop the itch!!
  • 50. Vulvar Intraepithelial Neoplasia (VIN): Prior to 2004 • Grading of VIN-1 through VIN-3, based upon degree of epithelial involvement • The mnemonic of the 4 P’s – Papule formation: raised lesion (erosion also possible, but much less common) – Pruritic: itching is prominent – “Patriotic”: red, white, or blue (hyperpigmented) – Parakeratosis on microscopy
  • 51. ISSVD 2004: Squamous VIN • VIN 1 is not a cancer precursor…abandon the term – Instead, use “condyloma” or “flat wart” • Combine VIN-2 and VIN-3 into single “VIN” diagnosis • Two distinct variants of VIN – VIN, usual type • Warty type • Basaloid type • Mixed warty-basaloid – VIN, differentiated (simplex) type
  • 52. ISSVD 2004:VIN, Usual Type • Includes (old) VIN -2 or -3 • Usually HPV-related (mainly type 16) • More common in younger women (30s-40s) • Often asymptomatic • Lesions usually elevated and have a rough surface, • Often multifocal; multicentric in 50% • Strongly associated with cigarette smoking • Regression is less likely and progression to invasion more likely with the basaloid type
  • 53. VIN, Differentiated (Simplex) Type • Includes (old) VIN 3 only • Usually in older women with LS, LSC, or LP • Not HPV related • Less common than usual type • Patients usually are symptomatic, with a long history of pruritus and burning • Findings – Red, pink, or white papule; rough or eroded surfaces – A persistent, non-healing ulcer • More likely to progress to SCC of vulva than usual VIN
  • 56.
  • 58. Vulvar Intraepithelial Neoplasia • Precursor to vulvar cancer, but low “hit rate” – Greater risk of invasion if immunocompromised (steroids, HIV), >40 years old, previous lower genital tract neoplasia • Treatment – Wide local excision (few lesions), laser ablation – Topical agents: 5FU cream, imiquimod – Skinning or simple vulvectomy • Recurrence is common (48% at 15 years) – Smoking cessation may reduce recurrence rate
  • 59. Genital Skin: Dark Lesions (% are in women only) • 36% Lentigo, benign genital melanosis • 22% VIN • 21% Nevi (mole) • 10% Reactive hyperpigmentation (scarring) • 5% Seborrheic keratosis • 2% Malignant melanoma • 1% Basal cell or squamous cell carcinoma
  • 62. Indications for Vulvar Biopsy • Papular or exophtic lesions, except obvious condylomata • Thickened lesions (biopsy thickest region) to differentiate VIN vs. LSC • Hyperpigmented lesions (biopsy darkest area), unless obvious nevus or lentigo • Ulcerative lesions (biopsy at edge), unless obvious herpes, syphilis or chancroid • Lesions that do not respond or worsen during treatment • In summary: biopsy whenever diagnosis is uncertain
  • 63. References • Heller DS. Report of a new ISSVD classification of VIN. J Low Genit Tract Dis. 2007 Jan;11(1):46-7. • Siderite M, et al. Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee J Reprod Med. 2005 Nov;50(11):807-10 • Wechter ME, Management of Bartholin duct cysts and abscesses: a systematic review Obstet Gynecol Surv. 2009 Jun;64(6):395-404. • vanSeters, et al, Treatment of vulvar intraepithelial neoplasia with imiquimod. NEJM 2008;358:1465-73 • De Simone P Vulvar melanoma: a report of 10 cases and review of literature. Melanoma Res. 2008 Apr;18(2):127-33
  • 64. References • Lynch PJ, etal, 2006 ISSVD Classification of Vulvar Dermatoses. J Reprod Med 2007;52:3-9 • ACOG Practice Bulletin #93. Diagnosis and Management of Vulvar Skin Disorders. Ob Gynecol 2008;111 (5);1243-1253 • Smith YR, Haefner HK. Vulvar lichen sclerosus: pathophysiology and treatment. Am J Clin Dermatol. 2004;5(2):105-25. • Edwards L, Vulvar fissures: causes and therapy. Dermatol Ther. 2004;17(1):111-6. • Foster DC, Vulvar disease. Ob Gynecol. 2002;100(1):145-63.