the itching vulva: lichen sclerosus and vulvovaginal atrophy · lp and ls •elastic stain –...

The Itching Vulva:

Lichen Sclerosus and

Vulvovaginal Atrophy Miriam Keltz Pomeranz, M.D.

The Ronald O. Perelman Dept of Dermatology

NYU and NYC H+H/Bellevue

March 2, 2019

Forum F044: The Vulva: What do you know?

DISCLOSURE OF RELATIONSHIPS WITH INDUSTRY

Miriam Keltz Pomeranz Forum F044: Vulvar Disease: What do you know?

The Itching Vulvar: Lichen Sclerosus and Vulvovaginal Atrophy

March 2, 2019

DISCLOSURES

Proctor and Gamble: member of Scientific Advisory Board

UpToDate: Royalties

Vulvar Lichen Sclerosus

Nomenclature • Kraurosis Vulvae

• Vulvar Dystrophy

• White spot disease

• Guttate scleroderma

• Lichen sclerosus et atrophicus

3

Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol 2013; 14: 27-47.

Vulvar Lichen Sclerosus

epidemiology • Prevalence unknown – asymptomatic

• Margesson – 1/300 to 1/1000

• Age onset: girls mean 5.4yrs; women mean 55.1

yrs; Margesson women 30-40

• In women: 78% post menopausal ACOG Practice Bulletin. Diagnosis and Management of Vulvar Skin Disorders. Obstetrics and Gynecology 2008;

11(5):1243-53

Cooper SM, Ali I, Baldo M, et al. The association of lichen sclerosus and erosive lichen planus of the vulva

with autoimmune disease. Arch Dermatol 2008; 144(11) 1432-35.

Cooper SM, Gao XH, Powell JJ, et al. Does treatment of vulvar lichen sclerosus influence its prognosis?

Arch Dermatol 2004; 140: 702-6.

Margesson LJ. Vulvar disease pearls. Dermatologic clinics 2006; 24: 145-55.

Vulvar Lichen Sclerosus: epidemiology

• 28% of pts with other autoimmune dz:

• Alopecia areata

• Vitiligo

• Thyroid dz (most common)

• Pernicious anemia

• Morphea

• Family hx: 12% (likely underreported)

• ? Asst HLA DQ7, DQ8, DQ9 ACOG Practice Bulletin. Diagnosis and Management of Vulvar Skin Disorders. Obstetrics and Gynecology 2008;

11(5):1243-53




Arch Dermatol 2004; 140: 702-6.

Margesson LJ. Vulvar disease pearls. Dermatologic clinics 2006; 24: 145-55.


Vulvar Lichen Sclerosus - clinical •Signs – porcelain white papules/plaques; echymoses/purpura; “cigarette paper”; hyperkeratosis; ulceration; fusion of labia minora to majora; “phimosis” of clitoral hood (“burying of the clitoris”); “Closures of the commissures” (vestibule smaller – like zip closed from under clitoris);

ACOG Practice Bulletin. Diagnosis and Management of Vulvar Skin Disorders. Obstetrics and Gynecology 2008; 11(5):1243-53


Arch Dermatol 2004; 140: 702-6.

Ventolini G, Patel R, Vasquez R. Lichen Sclerosus: a potpourri of misdiagnosed cases based on atypical clinical presentations.

International journal of womens health 2015; 7: 511-15.

Vulvar Lichen Sclerosus - clinical

• 70% of women with some scarring • Symptoms – pruritus,irritation,burning,

dyspareunia, tearing; constipation in girls; can be asymptomatic Kirtschig G, Becker K, Gunthert A, et al. Evidence based guideline on (anogenital) Lichen sclerosus.

J Eur Acad Dermatol Vener 2015; 29: e1-43.



Arch Dermatol 2004; 140: 702-6.



Vulvar Lichen Sclerosus: clinical

• Distribution – 59% vulvar and perianal (figure of eight); vagina spared • Extragenital 11-13% (exclusively extragenital: 6%) • Rate of malignancy (SCCa) about 2-5 % as high as 6.7% (Bleeker) ACOG Practice Bulletin. Diagnosis and Management of Vulvar Skin Disorders. Obstetrics and Gynecology 2008; 11(5):1243-53


Arch Dermatol 2004; 140: 702-6.


Bleeker MCG, Nisser PJ, Overbeek LIH, et al. Lichen sclerosus: incidence and risk of vulvar squamous cell carcinoma.

Cancer Epidemiol Biomarkers Prev 2016; 25: 1224-30.

Vulvar Lichen Sclerosus: clinical

Hyperpigmentation: • vulvar lentiginosis: • can be dark and irregular • on bx clearly not melanoma

• nevi in LS:

• clinically suspicious for melanoma

• histologically suspicious for melanoma

• tell pathologist in setting of LS


Lichen Sclerosus: pathology

• Pathognomonic changes: in papillary dermis homogenization & sclerosis with atrophy of epidermis (not always present, esp in early lesions);bx center of white lesion

Fung M, LeBoit PE. Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus:

a comparison with lichen planus. The American Journal of Surgical Pathology 1998; 22(4): 473-478

Lichen Sclerosus: pathology

•Lymphocytic, lichenoid interface dermatitis in LP and LS •Elastic stain – marked decrease in papillary dermal elastic fibers in LS c/w LP

Fung M, LeBoit PE. Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus:

a comparison with lichen planus. The American Journal of Surgical Pathology 1998; 22(4): 473-478

Vulvar Lichen Sclerosus: etiology

• Unknown – thought to be autoimmune

• Sera of pts with auto antibodies: • 67% with antibody to extracellular matrix 1 protein

• 30% with antibody to BP180 and BP 230

• Another study: 4/149 had BP180 antibody (not significant)

• Expert opinion – antibodies secondary; likely T cell

mediated disease




Gambichler T, Höxtermann S, Skrygan M, Eberz B, Regauer S, Scola N, et al. Occurrence of circulating anti-bullous pemphigoid

antibodies in patients with lichen sclerosus. J Eur Acad Derm Venereol 2011; 25: 369–370

Vulvar Lichen Sclerosus: diagnosis

• Biopsy (except in prepubertal

child) vs clinical

• Biopsy may not be diagnostic • McCarthy et al 13/39 bx in clinically

certain LS not diagnostic

• Rebiopsy

• Response to treatment

• Look for other diseases ACOG Practice Bulletin. Diagnosis and Management of Vulvar Skin Disorders. Obstetrics and Gynecology 2008;

11(5):1243-53

Marren P, Walkden V, Mallon E, Wojnarowski F. Vulval cicatricial pemphigoid may mimic lichen sclerosus.

Br J Dermatol 1996; 134:522-524.

Kirtschig G, Becker K, Gunthert A, et al. Evidence based guideline on (anogenital) Lichen sclerosus.


McCarthy S, MacEoin N, O’Driscoll M, et al. Should we always biosy in clinically evident lichen sclerosus?

J Low Genital Tract Ds. 2019: ePub ahead of print doi: 10.1097/LGT.0000000000000457

Vulvar Lichen Sclerosus Treatment

• Ultra potent topical steroids:

• 96% partial-complete relief; (65%

women sx free)

• 23% return to normal skin exam

• If not responding, consider other

diagnosis



Br J Dermatol 1996; 134:522-524.


Arch Dermatol 2004; 140: 702-6.

Vulvar LS: Treatment

• Tacrolimus/pimecrolimus

• 50-94% at least partial improvement

• Pts failed topical steroids

• Burning/itching week(s); ?increase risk of SCCa



Br J Dermatol 1996; 134:522-524.

Cooper SM, Gao XH, Powell JJ, et al. Does treatment of vulvar LS influence its prognosis? Arch Dermatol 2004; 140: 702-6.

Goldstein AT, Thaci D, Luger T. Topical calcineurin inhibitors for the treatment of vulvar dermatoses. European J Obst Gynecol

and Reproductive Bio 2009; 146:22-9.





Vulvar LS: Treatment • Intralesional steroids (esp. very hyperkeratotic)

• Other: retinoids, MTX, cyclosporin,cryotherapy,

autologous platelet rich plasma – not helpful



Br J Dermatol 1996; 134:522-524.








Goldstein AT, King M, Runels C, et al. Intradermal injection of autologous platelet rich plasma for the treatment of Lichen Sclerosus.

JAAD 2017; 76: 158-160.

Goldstein AT, Mitchell L, Govind V, Heller D, A Randomized Double-Blind Placebo Controlled Trial of Autologous Platelet Rich Plasma

Intradermal Injections for the Treatment of Vulvar Lichen Sclerosus, Journal of the American Academy of Dermatology (2019),

doi: https:// doi.org/10.1016/j.jaad.2018.12.060.

Vulvar LS: Treatment • Lasers

• fractionated erbium yag – for hyperkeratotic

areas; adjunctive

• fractionated/ablative CO2 – hyperkeratotic;

adjunctive

• PDT – may be helpful but not proven

Prodromidou A, Chatziioannou E, Daskalakis G, Stergios K, Pergialiotis V. Photodynamic therapy for vulvar lichen sclerosus-a

systematic review. J Low Genit Tract Dis. 2018;22(1):58-65. doi:10.1097/LGT.0000000000000362

Lan T, Zou Y, Hamblin MR, Yin R. 5-Aminolevulinic acid photodynamic therapy in refractory vulvar lichen sclerosus et atrophicus:

series of ten cases. Photodiagnosis Photodyn Ther. 2018;21:234-238. doi:10.1016/j.pdpdt.2017.12.003

Lim A, Lee A, Fischer G. Fractional carbon dioxide laser in recalcitrant vulval lichen sclerosus. Aust J of Dermatol 2016; 57: 39-43.

Vulvar LS: Treatment

• Follow up q 6-12 months screening exam

• Never totally stop treatment



Br J Dermatol 1996; 134:522-524.






Vulvar Lichen Sclerosus: treatment

• Lee et al:

• suggest treatment 3 times/week

• lower strength of topical steroid if improved

• 0/357 compliant patients with SCCa/VIN

• 7/150 partially compliant patients SCCa/VIN

Lee A, Bradford J, Fischer G. Long-term management of adult vulvar lichen sclerosus: a

Prospective cohort study of 507 women. JAMA Dermatol 2015; 151: 1061-67.

Atrophic Vaginitis = Vulvovaginal Atrophy (VVA)

= Genitourinary Syndrome of Menopause

• Symptoms: • Dyspareunia

• Vulvovaginal dryness/itching/pain

• Urinary complaints

• After 4 years of menopause, > 60% have sxs

Stika CS. Atrophic vaginitis. Dermatol Ther 2010; 23: 514-22.

Sinha A, Ewies AAA. Non-hormonal topical treatment of vulvovaginal atrophy: an up-tp-date overview.

Climacteric 2013:16: 305-12.

Portman DJ, Gass ML; Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary

syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for

the Study of Women’s Sexual Health and The North American Menopause Society.

Climacteric 2014; 17: 557-63.

Vulvovaginal Atrophy

• Consequences of low estrogen: • Reduce mucosal elasticity

• Reduce mucosal hydration

• Vagina loses rugae; shorter; narrower

• Vagina, introitus, labia minora mucosa

thin and pale

• Loss of vasculature

• Decreased vaginal secretions

(transudate from vasculature)


Vulvovaginal Atrophy

• Post-menopausal vulva: • Labia majora-less fat and hair; gray

• Labia minora – smaller to absent

• Introitus (vestibule) – pale, shiny,dry

• +/- petechiae; fissures of post.

forchette

• Urethral caruncle (PG-like); urethral

prolapse


Topical Estrogens

Active ingredient Trade name Vehicle comments

Conjugated estrogens

0.625 mg/g

Premarin Vaginal

Cream

Cream 0.5-1gm PV 7 days

then BIW; 0.5gm 21

days off 7 days

Estradiol 0.1mg/g Estrace Vaginal Cream Cream 2-4 g cream PV 1-2

wks; taper to 1g 1-3/wk


Topical Estrogens


Estradiol 10 or 25 mcg Vagifem/Yuvifem

(generic)

Tablets 1 tab PV q day for 14

then 1 tab BIWk

Estradiol 4 or 10 mcg Imvexxy Insert tear shaped 1 insert PV q day for 14

then 1 insert BIWk


The Medical Letter on Drugs and Therapeutics. Imvexxy – another estradiol vaginal insert for dyspareunia. 2018; 60: 147-8

Topical Estrogens


Estradiol 7.5mcg/24 hr Estring Vaginal ring Place in upper vagina

for 90 days

Estradiol 50mcg/24 hr

or 100mcg/24 hr

Femring Vaginal ring Place in upper vagina

for 90 days; designed

to get systemic levels


Topical Estrogens: Use

• Most studies show no increase serum level

estrogens above menopausal norms

• Use lowest effective dose

• Safety data only up to 1 year

• Vaginal ring lowest systemic absorption and

highest pt satisfaction

• ?Screen endometrium with pelvic ultrasound or

endometrial biopsies


Rahn DD, Carberry C, Sanses TV, et al. Vaginal estrogen for genito-urinary syndrome of menopause:

a systematic review. Obstet Gynecol: 2014; 124: 1147-56.


• No increased risk of breast cancer, endometrial

cancer, stroke, venous thromboembolism with intra

vaginal estrogen in the women’s health initiative

observation study

• contraindicated in pts with genital bleeding,

“estrogen dependent neoplasm”, hx of VTE, active

arterial thromboembolic dz, thrombophilic dz, liver

dz, breast CJ Crandall et al. Breast cancer, endometrial cancer and cardiovascular events in participants who used vaginal estrogen

In the Women’s Health Initiative Observational Study. Menopause 2018; 25: 11.

The Medical Letter on Drugs and Therapeutics. Imvexxy – another estradiol vaginal insert for dyspareunia. 2018; 60: 147-8.

Topical Estrogens: Use • Suggest “clinician vigilance” varying depending on

patient

• “Data are insufficient to mandate endometrial

surveillance or dictate frequency or means of

surveillance.”

• “Data are insufficient to recommend annual

endometrial surveillance in asymptomatic women

using vaginal ET.”



The North American Menopause Society (no authors). Management of symptomatic vulvovaginal atrophy:

2013 position statement of The North American Menopause Society. The Journal of The North American

Menopause Society 2013; 20: 888-902.


• “Although these products generally appear safe, a

precise estimate of risk to the endometrium with

sustained vaginal estrogen use is not clear, and

additional long-term study with more consistent

assessment of the endometrium and more

sensitive assessment for changes in serum

estradiol is needed.”



Topical Estrogens: Alternatives • Selective estrogen receptor modulators:

ospemifene; PO med; helpful in studies for

vulvovaginal atrophy; FDA approved

• Topical DHEA (prasterone) – improves sexual

dysfunction due to vaginal atrophy; FDA approved

• Vitamin D – one study vit D improved sxs VVA Tan O, et al. Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: an

up-to-date review. Menopause: The Journal of the North American Menopause Society. 2012; 19: 109-117.

Yildirim B, et al. The effects of postmenopausal vitamin D treatment of vaginal atrophy.Maturitas 2004; 49: 334-7.

Portman, D.J.; Bachmann, G.A.; Simon, J.A. Ospemifene, a novel selective estrogen receptor modulator

for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 2013;

20: 623–630.

Pinkerton JV, Kagan R. Ospemifene for the treatment of postmenopausal vulvar and vaginal atrophy:

recommendations for clinical use. Expert Opin Pharmacother 2015; 16: 2703-14

Naumova J, Castelo-Branco C. Current treatment options for post-menopausal vaginal atrophy. Int J Women’s

Health. 2018; 10: 387-95.

Topical Estrogens: Alternatives • lasers:

• fractional CO2 laser (MonaLisa Touch™ (DEKA, Florence, Italy))

• others being studies

Tadir Y, Gaspar A, Lev-Sagie A, et al. Light and energy based devices for genitourinary syndrome of menopause:

Consensus and controversies. Lasers Surg Med. 2017 February ; 49(2): 137–159.

Topical Estrogens: Alternatives • Vaginal moisturizer as alternative for dryness:

• Replens (active ingredient polycarbophil carries water and stays for

2-3 days)

• Summer’s Eve (based on pectin)

• RepHresh

• Emerita

• Yes (from UK)

• Hyaluronic acid-based:

• Hyalo GY (US)

• Hyalofemme (UK)

• Repadina (UK) - ovules Stika CS. Atrophic vaginitis. Dermatol Ther 2010; 23: 514-22.

Tan O, et al. Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women:

an up-to-date review. Menopause: The Journal of the North American Menopause Society. 2012; 19: 109-117.

Sinha A, Ewies AAA. Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview.

Climacteric 2013:16: 305-12.

Topical Estrogens: Alternatives

• Use in patients with a history of breast or

endometrial cancer

• Equally effective as estrogens in patients with just

one symptom




• Vaginal lubricants: for

use prior to sex

• No long term therapeutic

effect


Sinha A, Ewies AAA. Non-hormonal topical treatment of vulvovaginal atrophy: an up-tp-dateoverview.

Climacteric 2013:16: 305-12.

Topical Estrogens: Alternatives Lubricants

• Water based:

• Astroglide liquid

• Astoglide gel liquid

• Astroglide

• Just like me

• K-Y jelly

• Pre-Seed

• Slippery Stuff

• Liquid Silk

• Silicone based • Astroglide X

• ID Millenium

• K-Y Intrigue

• Pink

• Pjur Eros

• Oil Based • Elegance Women’s

Lubricants

• Olive oil The North American Menopause Society (no authors). Management of symptomatic vulvovaginal atrophy:

2013 position statement of The North American Menopause Society.

The Journal of The North American Menopause Society 2013; 20: 888-902.


• Regular vaginal coital

activity • fewer sxs

• less shrinkage/stenosis of vagina

• thought because increase blood

flow, maintain vaginal

elasticity/pliability

Sinha A, Ewies AAA. Non-hormonal topical treatment of vulvovaginal atrophy: an up-tp-date overview.

Climacteric 2013:16: 305-12.

the itching vulva: lichen sclerosus and vulvovaginal atrophy · lp and ls •elastic stain –...

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