Vaginitis Cases: From the common to the challenging - PowerPoint Presentation

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Vaginitis Cases: From the common to the challenging

Caroline Mitchell, MD, MPH

Vincent Center for Reproductive Biology, MGH

Assistant Professor, Harvard Medical School

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Caroline Mitchell, MD, MPHDr. Mitchell is a consultant for

Scynexis

,

Inc and receives research funding from MerckAdditional disclosure: Some of the treatment regimens discussed are not FDA approved for the specific indication for which they are mentioned.

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Learning Objectives

At the end of this presentation, the participant will be able to:

Describe the differential diagnosis for vaginal discharge and the clinical signs and symptoms associated with each of the major causes.

Outline the tests needed to confirm diagnosis and appropriate treatments.Explain the challenges of recurrent and resistant infections.

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Case 1

SC is a 27-year-old G1P1 woman who presents with 3 day history of worsening vulvovaginal

pruritis

, thick vaginal discharge and some dysuria. She has had one sexual partner for the past 3 years. She reports a history of gestational diabetes in her pregnancy a year ago. She relies on birth control pills for contraception. She tried to douche to relieve her symptoms, but to no avail. Her BMI is 26 kg/m2. On exam, her vulva is erythematous, edematous and somewhat excoriated. Speculum exam reveals thick adherent white clumpy discharge. Cervix has no mucopurulent discharge and there is no CMT.

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Sensitivity/Specificity

BV

Yeast

Trichomonas

Sensitivity

Specificity

Sensitivity

Specificity

Sensitivity

Specificity

Wet mount65%97%61%89%60%100%BD Affirm90.1%67.6%58.1%100%46.3-63%99.9%BD Max90.5%85.8%90.9 (75.9*)94.1(99.7*)93.199.3PCR96.9**92.6**97.7%93.2%--Antigen----82-95%97-100%NAAT--98.1%95-100%

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Gaydos Obstet Gynecol 2017; Cartwright JCM 2013; Huppert CID 2007; Schwebke JCM 2011; Andrea JCM 2011;Brown H IDOG 2004; Hobbs STI 2013

*C.

glabrata

; ** A.

vaginae

, BVAB2, Mega Type 1

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Yeast

Clinical

pH

WBCBacteriaOtherDischarge, Itching

Normal

+/-

Lactobacilli

usually present

Hyphae, buds

96% Candida

albicans

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Is it really yeast?Patient self-diagnosis

:

95 women purchasing OTC yeast meds

Evaluated within 24h

Ferris Obstet Gynecol 2002

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Vulvovaginal Candidiasis: OTC IntravaginalClotrimazole 1% cream 5g intravaginally for 7-14 daysMiconazole 2% cream 5g intravaginally daily for 7 days

Miconazole 100 mg vaginal suppository daily for 7 days

Miconazole 4% cream 5g intravaginally daily for 3 days

Miconazole 200 mg vaginal suppository daily for 3 daysMiconazole 1200 mg vaginal tablet onceTioconazole 6.5% ointment 5g intravaginally oncehttp://www.cdc.gov/std/tg2015/

Comparable efficacy

Irritation

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Vulvovaginal Candidiasis: Rx Intravaginal Butoconazole 2% cream (bioadhesive product), 5g intravaginally in a single application

Tioconazole 6.5% ointment 5 g intravaginally once

Terconazole 0.4% cream 5 g intravaginally nightly for 7 days

Terconazole 0.8% cream 5 g intravaginally nightly for 3 daysTerconazole 80 mg suppository nightly for 3 dayshttp://www.cdc.gov/std/tg2015/

Comparable efficacy

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Vulvovaginal Candidiasis: Oral AgentsFluconazole 150 mg oral tablet once for mild to moderate infections1Moderate to severe cases may require extra dosing:

CDC recommendation: days 1 and 4

Common practice: days 1, 4 and 7

http://www.cdc.gov/std/tg2015/

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Case 1

She comes back a year later, having self-treated symptoms several times with OTC products. She went to an urgent care where they did an exam but no testing, and she was given a single dose of fluconazole, which helped. She again has symptoms of itching, vaginal discharge and pain with sex.

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Recurrent: Weekly Fluconazole

Recurrent = 3+/year

91%

36%

43%

22%

Stop therapy

Sobel NEJM 2004

150-200 mg weekly

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Resistant Yeast VulvovaginitisCase series, 2000-2010

4000 new vaginitis patients

25 women with resistant

C. albicans

Resistance = MIC > 2mcg/mL

Median MIC 8 mcg/mL

(range 2-128 mcg/mL)

Marchaim Ob Gyn 2012

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Treating resistant C. albicans

Initial: Boric acid 600mg PV

qhs

x 14 daysMaintenance:Low MIC (2-4 mcg/mL): Twice weekly FluconazoleHigher MICKetoconazoleItraconazoleBoric acid 3x/weekVaginal amphotericinVaginal gentian violet (Q 3-7 days)

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Marchaim Ob Gyn 2012

C. albicans

maintains sensitivity to medications at low pH, but not all isolates do.

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Non-albicans species

C.

glabrata

C. tropicalisC. krusei*C. parapsilosis

C.

lusitaniae

Responsible for symptoms ~ 46% cases

Responsible for symptoms ~ 50% cases

Kennedy Curr Infect Dis Rep

10-16.3%

0.8%

4-8.9%

0.8-1%

Look for another cause for symptoms

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Non-albicans

vulvovaginitis

> 50% C. glabrata resistant to azoles:Boric acid 600mg pv qHS x 14d

Fluconazole 400mg daily for 7d + topical azole

Compounded Amphotericin B 4%/

flucytosine

17% vaginal cream, 70 grams, 4 grams nightly for 14 days

C.

glabrata

Sobel Lancet 2007

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Yeast - Modifiable risk factors?

Risk factor

Risk

Oral contraceptives4 studies no difference5 studies increased risk (1.4-10.15)Diabetesrisk with poorly controlled diabetes

Diet

Higher

gtt

values in women with RVVC



risk with fewer

servings of milkrisk with more servings of dairyrisk with 2+ servings of breadSexual practicesrisk with frequent oral sexrisk with frequent sexClothing choiceNo clear association with +culture, but worse symptoms with tight clothes18Van de Wijgert AIDS 2013; Donders AJOG 2002; Reed B Jl Womens Health Gender Based Medicine 2000; Reed BD Jl womens health 2003

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Yeast – should you recommend probiotics?Yeast and lactobacilli: friend or foe?

151 HIV- sex workers in

Mombassa

13,863 pregnant US women

McClelland JID 2009; Cotch AJOG 1998

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Yeast and pregnancy1.4 million pregnancies in Denmark

Linked administrative databases

Each fluconazole-exposed case matched with 4 controls (1 of whom had topical azole exposure)

SAB between 7-23 weeks

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Molgaard-Nielsen JAMA 2016

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What if. . .Her history was slightly different. What would you think of if all she had ever complained of was intense

pruritis

and post scratching burning without discharge and this is what you saw on your exam?

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Case 2A 23-year-old heterosexual woman presents with classic symptoms of foul smelling vaginal discharge for about a week. Douching did not resolve symptoms for long. She denies any new sexual partners or any unprotected sex. She and her partner use external condoms fairly regularly.

Vaginal pH is 6.0. On microscopy this is what you see. . .

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Bacterial vaginosis

Amsel

’

s criteria (3/4)Elevated pHClue cellsDischarge+ whiff test

Clinical

pH

WBC

Bacteria

Other

Discharge,

OdorElevated (> 4.5)NoneMany, small rodsClue cells > 20%+ whiffGram stain

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Question

Which of the images below shows clue cells?

1

2

3

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Question

Which of the images below shows clue cells?

1

2

3

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Treatment efficacy for BV

Drug

Dose

Cure at 1

mo

- A /- N

0/4 Amsel

Not BV

Metronidazole

500 mg PO bid x 7d

60%

54-57%

48%-82%

0.75% gel PV x 5d

30%

66%

47-78%

1.3% gel PV x 1

30%

37%

-

Clindamycin

2% cream PV x 7d

42%

63%

61-79%

300 mg PO bid x 7d

-

-

90%

Tinidazole

1g PO daily x 5d

36%

-

-

2g PO daily x3d

27%

-

-

Secnidazole

2g PO x 1

60%

68%

77%

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Bacterial vaginosis - recurrent

Its (probably) all about sex

Risk

# studies

Condom use

0.8*

43

New/multiple male partner(s)

1.6*

43

Consistent partner

1.91

2

Douching

1.17-1.21

2 (2 no)

Hormonal contraceptive use

0.78**

55

Female partner w/sx

HR 7.92

1

* From meta-anaysis, Fethers CID 2008

**from meta-analysis, Vodstrcil PLoS One 2013

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Twice weekly Metrogel

Sobel AJOG 2006

Recurrent BV = 3+ episodes/year

75%**

41%

39%

25%

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Bacterial vaginosis – boric acid?

7 days oral MTZ or TDZ

21 days of nightly vaginal boric acid

16 weeks twice weekly vaginal MTZ

Reichman STD 2009

Case series; n = 51

MTZ suppression alone

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Boric acid-based therapy: TOL-463Phase 2 RCT: Gel vs. Insert

BV: All 4

Amsel

criteriaCure: 0 Amsel criteria, d9-1253 women with BVSymptoms resolved by the end of 7d treatment in 88% of women using gel, and 93% using insert

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Marrazzo

CID 2018

Cure (d9-12)

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Probiotics - Prevention

N

125

450

95

215

65

100

49

64

19025012098Tx30d12d5dvar6d10d+6m28d7d7m14d14dmF/u30d30d30d60d14d30d30d28d28d60d60d120dRoutePOVVVVVVPOVVPOV

L.

Rhamnosus

GR

L.

crispatus

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Should we treat male partners?

Women

7d vs 1d

7d vs 1d2g, 2 doses2g, 2 doses

2g

TDZ

Vag

clinda

Men

None, 7d, 1dNone, 7d, 1dNone vs. 2g x2None vs. 2g x2None vs. 2gNone vs. 7d PON39/12/1371/33/3453/53118/127125/12540/6980% Power80% effect23% effect60% effect68% effect26% effect63% effectMehta STD 2012

Purell treatment of penis also ineffective

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Case 3CC is a 42-year-old woman presents with complaints of large amounts of vaginal discharge; some vulvar irritation and some post coital bleeding. She has had two sex partners in the past six months. She uses an IUD for contraception.

On exam, she has copious amounts of discharge around introitus, erythema of vaginal walls, petechiae on cervix and bubbles in the nonadherent discharge pooled in posterior vault. No cervical motion tenderness.

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Trichomoniasis

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TrichomonasMetronidazole 2g PO x1

(1/2 life 7 hours)

Tinidazole

2g PO x1 (1/2 life 12.5 hours)Partner treatment (60 days!)Abstinence until 7d after therapy for both

Clinical

pH

WBC

Bacteria

Other

Discharge

Elevated+No associationStrawberry cervix60% sensitivity

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Trichomoniasis in HIV+ women

RCT of HIV+ women with

trichomoniasis

2833 screened: 16.9% + for trich270 randomized to either 2g x1 or 500mg BID x 7d92% African American

Single dose

7 day

RR

TOC (8-12d)

21/125 (16.8%)

11/130 (8.5%)

0.5 (0.25, 1.0)

3 month f/u

19/79 (24.1%)

8/73 (11%)

0.46 (0.21, 0.98)

Treatment Failure or Recurrence

Kissinger et al JAIDS 2010

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A 47-year-old woman presents with persistent complaints of vulvovaginal irritation, non-malodorous discharge and dyspareunia. On exam you note vulvar swelling, copious discharge, vaginal erythema with ecchymotic lesions or erosions. On wet mount you note increased inflammatory cells, parabasal epithelial cells, no lactobacilli.

Hr

vaginal discharge has a pH > 4.5.

Case 4

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Desquamative Inflammatory Vaginitis

Treatment:

2% clindamycin

4-5g dailyVaginal hydrocortisone100g/day suppository10% cream, 3-5g dailyInitial Rx 4-6 weeksMaintenance 1-2 times weekly

Clinical

pH

WBC

Bacteria

Other

Pain, erythema

Elevated

Copious, sheets

Parabasal

cells

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Vaginal discomfort NOS

Discharge

Irritation

Burning

Itching

Pain

Pain with sex

Vulvodynia

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Thank youVincent Center for Reproductive Biology

David Eschenbach

Jeanne

MarrazzoLisa ManhartIna ParkKatherine HsuRochelle Walensky