The Itching Vulva: Lichen Sclerosus and Vulvovaginal Atrophy

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 Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol 2013; 14: 27-47. 3

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

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 Cooper SM, Gao XH, Powell JJ, et al. Does treatment of vulvar lichen sclerosus influence its prognosis? 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. ACOG Practice Bulletin. Diagnosis and Management of Vulvar Skin Disorders. Obstetrics and Gynecology 2008; 11(5):1243-53 Cooper SM, Gao XH, Powell JJ, et al. Does treatment of vulvar lichen sclerosus influence its prognosis? 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 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 Cooper SM, Gao XH, Powell JJ, et al. Does treatment of vulvar lichen sclerosus influence its prognosis? Arch Dermatol 2004; 140: 702-6. Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol 2013; 14: 27-47. 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 Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: an update. Am J Clin Dermatol 2013; 14: 27-47.

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 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. 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. J Eur Acad Dermatol Vener 2015; 29: e1-43. 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 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. Cooper SM, Gao XH, Powell JJ, et al. Does treatment of vulvar lichen sclerosus influence its prognosis? 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 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. 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. 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. Kirtschig G, Becker K, Gunthert A, et al. Evidence based guideline on (anogenital) Lichen sclerosus. J Eur Acad Dermatol Vener 2015; 29: e1-43.

Vulvar LS: Treatment Intralesional steroids (esp. very hyperkeratotic) Other: retinoids, MTX, cyclosporin,cryotherapy, autologous platelet rich plasma not helpful 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. 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. 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. Kirtschig G, Becker K, Gunthert A, et al. Evidence based guideline on (anogenital) Lichen sclerosus. J Eur Acad Dermatol Vener 2015; 29: e1-43. 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 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. 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. 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: 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) Stika CS. Atrophic vaginitis. Dermatol Ther 2010; 23: 514-22.

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

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

Topical Estrogens Active ingredient Trade name Vehicle comments 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 Stika CS. Atrophic vaginitis. Dermatol Ther 2010; 23: 514-22. The Medical Letter on Drugs and Therapeutics. Imvexxy another estradiol vaginal insert for dyspareunia. 2018; 60: 147-8

Topical Estrogens Active ingredient Trade name Vehicle comments 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 Stika CS. Atrophic vaginitis. Dermatol Ther 2010; 23: 514-22.

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

Topical Estrogens: Use 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. 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. 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.

Topical Estrogens: Use 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. 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.

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 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.

Topical Estrogens: Alternatives Vaginal lubricants: for use prior to sex No long term therapeutic effect Stika CS. Atrophic vaginitis. Dermatol Ther 2010; 23: 514-22. 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.

Topical Estrogens: Alternatives 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.