A Survey of Experts Regarding the Treatment of Adult Vulvar Lichen Sclerosus Amanda Selk, MD, MSc Objective: The objective of this work was to survey physician members and fellows of the International Society for the Study of Vulvovaginal Disease to determine current expert opinion regarding the management of adult vulvar lichen sclerosus. Materials and Methods: A cross-sectional design was used. An electronic survey was emailed to all members and fellows of the International Society for the Study of Vulvovaginal Disease. Responses were analyzed using univariate methods. Subgroup analyses were performed to report treatment differences between gynecologists and dermatologists and between physicians in the United States and Europe. Results: In total, 128 (42%) of 305 providers responded to the survey. Analysis was confined to the 114 physician respondents who treat patients with lichen sclerosus. Clobetasol propionate 0.05% is the most common first-line agent used in lichen sclerosus (85%). The most common second-line agents used are tacrolimus (39%), other topical steroids (28%), and intralesional steroids (13%). Most physicians (59%) start all patients with lichen sclerosus on drug therapy at an initial visit, regardless of symptoms. Dermatologists are more likely to treat all patients (both symptomatic and asymptomatic) than gynecologists (p < .01). Most physicians (64%) continue maintenance therapy in all patients. Gynecologists are more likely than dermatologists to treat only when patients are symptomatic versus using maintenance therapy (p = .03). Physicians practicing in the United States are more likely than those practicing in Europe to treat all patients with maintenance therapy (p < .01). Conclusions: Lichen sclerosus management varies among experts. Variations exist between physician specialties and between those practicing in different geographic locations. Uncertainty regarding optimal treatment remains, especially regarding long-term management. Key Words: lichen sclerosus et atrophicus, vulvar lichen sclerosus, lichen sclerosus (J Lower Gen Tract Dis 2015;19: 244–247)

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ichen sclerosus is a chronic inflammatory skin condition that most commonly occurs in postmenopausal women. It predominantly affects the vulva but can have extragenital manifestations in up to 20% of patients, most commonly on the trunk and proximal extremities.1–3 The etiology of lichen sclerosus remains unknown.4 The disease can be extremely debilitating, with patients typically complaining of vulvar itch or irritation.1 In addition, lichen sclerosus can cause vulvar anatomical changes that can lead to pain, sexual difficulties, and voiding problems.1,5,6 Since some cases are asymptomatic, the exact prevalence of lichen sclerosus

Department of Obstetrics and Gynecology, Women's College Hospital, Toronto, Ontario, Canada and Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada Correspondence to: Amanda Selk, MD, MSc, Department of Gynecology, Women's College Hospital, 76 Grenville St, Toronto, ON, M5S 1B2 Canada. E-mail: [email protected] This study received no financial support. The author has declared that there are no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site. © 2015, American Society for Colposcopy and Cervical Pathology

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remains unknown, with estimates ranging from 1 in 30 nursing home residents to 1 in 300 patients presenting to a general gynecology clinic.7,8 These numbers will likely increase as the population ages. Unfortunately, there are few published randomized controlled trials (RCTs) regarding the treatment of lichen sclerosus.9 The published RCTs examine initial treatment, but studies regarding long-term management and the role of maintenance therapy are lacking.4 Approximately 5% of patients with lichen sclerosus develop squamous cell cancer of the vulva,10,11 and it remains unclear whether or not topical steroid treatment will decrease the likelihood of cancer development.1,4–6 This study surveyed experts in the management of adult vulvar lichen sclerosus by approaching physician members and fellows of the International Society for the Study of Vulvovaginal Disease (ISSVD). An abstract with the results of this study was previously published.12

MATERIALS AND METHODS An Internet-based survey of 23 questions was created to better understand physician management of adult vulvar lichen sclerosus. Research ethics board approval was received (Women's College Hospital, Toronto Research Ethics Board No. 20120045-E). The survey was developed specifically for this study. To determine face validity and completeness, the survey was developed in consultation with 3 clinical colleagues and was pretested in 5 physicians for comprehension and completeness. The questionnaire included 7 demographic questions, 8 questions regarding management (multiple choice and short answer to elaborate on treatment regimens), and 8 questions regarding measurement of treatment outcomes (see Supplemental Digital Content, Appendix, available at http://links.lww.com/LGT/A16). The typical time to complete the survey was less than 15 minutes. The survey was distributed via e-mail link to all members and fellows of the ISSVD in November 2012. The study was conducted in English, the primary language of communication of the ISSVD. Two reminder e-mails were sent 1 week and 3 weeks after the initial invitation, and the survey closed 4 weeks after the initial invitation was sent. The data were transferred from the Web site www. surveymonkey.com into an Excel spreadsheet. Informed consent was obtained from all participants. Analysis of results was confined to the responses of physicians actively treating patients with lichen sclerosus. Subgroup analyses were preplanned, comparing management between (1) dermatologists and gynecologists and (2) physicians working in the United States and physicians working in Europe (as these are the geographic regions with the most members in the ISSVD). Any respondents with missing data for a question were excluded from analysis of that question. Univariate methods of analysis were used to analyze data with the program IBM SPSS Statistics version 21 (Armonk, NY). The Fisher exact test (2-sided) was used to compare proportions between groups.

Journal of Lower Genital Tract Disease • Volume 19, Number 3, July 2015

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Journal of Lower Genital Tract Disease • Volume 19, Number 3, July 2015

RESULTS A total of 305 surveys were sent via Survey Monkey, with 128 responses recorded (128/305), for a 42% response rate. Of those who responded, 124 of the 128 consented to participate and 4 of 128 declined. Of those who consented to participate, 114 of the 124 were physicians, and analysis was confined to those respondents whose baseline characteristics are displayed in Table 1. For the subgroup analyses, there were 24 dermatologists, 11 practicing in the United States and 9 practicing in Europe; and 81 gynecologists, 30 practicing in the United States and 29 practicing in Europe. Clobetasol propionate 0.05% (clobetasol) is the most commonly used first-line therapy, whereas tacrolimus is the most commonly used second-line therapy for patients not responding to initial treatment (Table 2). At an initial visit, 66 (59%) of 114 of respondents start all patients on medical treatment for lichen sclerosus, including both symptomatic and asymptomatic patients, whereas 35 (31%) of 114 treat only those patients who are symptomatic, and 11 (10%) of 114 do not treat patients until after taking a biopsy and TABLE 1. Baseline Characteristics of Respondents Characteristic Physician specialty, n (%) Gynecology Dermatology Pathology General practice Other Sex, n (%) Female Male Number of years since completing medical school, n (%) 21 Geographic location, n (%) Australia/New Zealand Africa Asia The Middle East South America Central America Canada United Kingdom (UK) Europe (non-UK) United States of America Practice Setting, n (%) Mix of public and private Public Hospital Private/community practice (non–university affiliated) Combined university and private practice University practice

Respondents (N = 114) 81 (71%) 24 (21%) 3 (3%) 2 (1%) 4 (3%) 72 (63%) 42 (37%)

1 (1%) 6 (5%) 14 (12%) 12 (11%) 81 (71%) 11 (10%) 0 (0%) 4 (4%) 4 (4%) 5 (4%) 0 (0) 5 (4%) 10 (9%) 31 (27%) 44 (39%) 18 (16%) 16 (14%) 25 (22%) 24 (21%) 31 (27%)

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Opinions Regarding Lichen Sclerosus

TABLE 2. First-Line and Second-Line Treatments for Adult Vulvar Lichen Sclerosus First-line therapies (n, %) Clobetasol propionate 0.05% Betamethasone dipropionate 0.5% Mometasone furoate 0.1% Other Second-line therapies (n, %) Tacrolimus Other topical steroids Intralesional steroids Pimicrolimus Other

Respondents (n = 104) 88/104 (85%) 9/104 (9%) 5/104 (5%) 2/104 (1%) Respondents (n = 95) 37/95 (39%) 27/95 (28%) 12/95 (13%) 5/95 (5%) 14/95 (15%)

receiving those biopsy results. Dermatologists, 20 (83%) of 24, are more likely to treat all patients compared with gynecologists, 41 (50%) of 82 (p < .01). Gynecologists, 32 (39%) of 82, are more likely than dermatologists, 2 (8%) of 24, to treat symptomatic patients only (p < .01). A wide variety of initial steroid treatment regimens are used. The 3 most common regimens for clobetasol are once daily for 4 weeks, 34 (32%) of 105; twice daily for 2 weeks, 20 (19%) of 105; and twice daily for 4 weeks, 19 (18%) of 105; whereas 32 (32%) of 105 use other regimens. Gynecologists, 12 (19%) of 62, are more likely than dermatologists, zero (0%) of 21, to treat twice daily for 2 weeks initially (p = .03). Physicians in the United States, 12 (30%) of 40, are more likely than those in Europe, 1 (3%) of 32, to start a twice-daily clobetasol regimen (p < .01). The clinical situations that lead to biopsies are listed in Table 3. Maintenance therapy is used in various circumstances, with most respondents treating all patients with maintenance therapy (Table 4). Gynecologists, 25 (30%) of 82, are more likely than dermatologists, 2 (8%) of 24, to treat only if there are symptoms/flares,

TABLE 3. When Are Biopsies Performed in Adult Vulvar Lichen Sclerosus Patients? (Multiple Responses Allowed) Patients' characteristics, n (%)

Respondents by specialty Respondents Dermatology Gynecology (n = 113) (n = 24) (n = 82)

At the initial visit to establish a diagnosis in all cases At the initial visit if the diagnosis is unclear At follow-up visits in patients not responding to treatment At follow-up visits if any suspicious lesion is present to rule out dysplasia or malignancy

39 (35%)

7 (29%)

28 (34%)

62 (55%)

14 (58%)

45 (55%)

54 (48%)

10 (42%)

43 (52%)

76 (67%)

18 (75%)

52 (63%)

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Journal of Lower Genital Tract Disease • Volume 19, Number 3, July 2015

Selk

versus putting all patients on maintenance therapy (p = .03). Physicians in the United States, 33 (79%) of 42, were more likely than those in Europe, 16 (43%) of 37, to treat all patients with maintenance therapy (p < .01). The most commonly used steroid for maintenance therapy is clobetasol, 70 (69%) of 102, followed by betamethasone dipropionate, 10 (10%) of 102. When used as maintenance therapy, the most commonly reported regimens for clobetasol are once weekly, 25 (45%) of 54; twice weekly, 20 (37%) of 54; or another regimen, 12 (22%) of 54. Gynecologists, 18 (50%) of 36, are more likely than dermatologists, 3 (18%) of 17, to use clobetasol once weekly for maintenance versus another regimen (p = .04). The most common goal of using maintenance therapy is to prevent symptoms/flares (Table 5). Dermatologists, 15 (63%) of 24, use maintenance therapy with the goal of decreasing the risk of developing squamous cell carcinoma more often than gynecologists, 31 (38%) of 82 (p = .04).

DISCUSSION This survey found that a high-potency topical steroid, specifically clobetasol, is the most commonly used first-line therapy in lichen sclerosus followed by mometasone. A recent systematic review of RCTs found efficacy in treating genital lichen sclerosus with clobetasol propionate, mometasone furoate, and pimecrolimus.13 Since this survey was conducted, recent RCTs have been published comparing mometasone to clobetasol, finding similar efficacy and good tolerability for mometasone.14,15 This survey found a variation in initial treatment regimens using clobetasol, with survey respondents most commonly starting a twice-daily steroid regimen. This differs from guidelines, which recommend a 3-month initial regimen of once-daily ultrapotent topical steroid treatment for 4 weeks, which is then tapered.1,5 Once-daily steroid regimens are recommended over twice-daily steroid regimens owing to pharmacodynamic studies showing equal efficacy on extragenital skin.16 It is unclear why many practitioners use twice-daily regimens. It was found that only 35% of practitioners recommend biopsy to patients initially to establish a diagnosis of lichen sclerosus. Both the British dermatology guidelines and the American gynecology practice bulletin on vulvar skin disorders recommend biopsy to confirm the diagnosis in adults.1,5 Since lichen sclerosus has a 5% risk of malignancy,10,11 biopsies should be encouraged to ensure that these patients are followed long term. In this study, maintenance therapy was used in most of the patients, with many practitioners responding that the goals of

TABLE 4. When Is Maintenance Therapy Used in Adult Vulvar Lichen Sclerosus Patients? (Multiple Responses Allowed) Patients' characteristics (n, %)

Respondents by specialty Respondents Dermatology Gynecology (n = 108) (n = 24) (n = 82)

In all patients (symptomatic and asymptomatic) When patients are symptomatic, i.e., during flares In asymptomatic patients with skin changes

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69 (64%)

17 (71%)

47 (57%)

28 (26%)

2 (8%)

25 (30%)

24 (22%)

4 (17%)

19 (23%)

TABLE 5. Goals of Using Maintenance Therapy in Adult Vulvar Lichen Sclerosus (Multiple Responses Allowed) Respondents by Specialty Goals, n (%) To decrease the risk of developing squamous cell carcinoma To prevent anatomic changes To prevent symptoms/flares Not applicable (i.e., do not use maintenance therapy)

Respondents Dermatology Gynecology (n = 111) (n = 24) (n = 82) 48 (43%)

15 (62%)

31 (38%)

67 (60%)

15 (62%)

45 (55%)

74 (67%)

16 (67%)

51 (62%)

16 (14%)

1 (4%)

15 (18%)

maintenance therapy are to decrease the risk of squamous cell carcinoma, prevent anatomic changes, and/or prevent symptoms/ flares of the disease. There is epidemiologic evidence linking chronic inflammation to the development of skin cancers.17 However, it has not been shown that treating lichen sclerosus with maintenance steroids will prevent cancer, scarring, or symptomatic disease.4 This survey found that practitioners in the United States were more likely than those in Europe to put all patients with lichen sclerosus on maintenance therapy. In addition, this study found that dermatologists and gynecologists treat lichen sclerosus differently, with dermatologists more commonly treating all patients, including those who are asymptomatic. The use of maintenance therapy and the treatment of asymptomatic patients are areas that deserve further study to understand whether preventing inflammation prevents scarring, prevents cancer, or improves quality of life. One strength of this survey is its exploration of understudied areas of lichen sclerosus management. Although the response rate was only 42%, only responses from physicians treating patients with lichen sclerosus were included. Data regarding absolute numbers of physicians in the ISSVD are not available, suggesting that this response rate is an underestimate. By administering the survey exclusively in English, participation from some geographic areas may have been limited, leading to a potential bias in responses.

CONCLUSIONS Lichen sclerosus is one of the best-studied vulvar dermatoses, and yet there are very few published RCT data to guide treatment in this area, especially regarding long-term therapy.9 This study showed that even among a very experienced group of international experts, significant practice variations exist. REFERENCES 1. Neill SM, Lewis FM, Tatnall FM, et al. British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010. Br J Dermatol 2010;163:672–82. 2. Powell JJ, Wojnarowska F. Lichen sclerosus. Lancet 1999;353:1777–83. 3. Kreuter A, Kryvosheyeva Y, Terras S, et al. Association of autoimmune diseases with lichen sclerosus in 532 male and female patients. Acta Derm Venereol 2013;93:238–41.

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4. Moyal-Barracco M, Wendling J. Vulvar dermatosis. Best Pract Res Clin Obstet Gynaecol 2014;28:946–58. 5. Boardman LA, Kennedy CM; ACOG Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 93: diagnosis and management of vulvar skin disorders. Obstet Gynecol 2008;111: 1243–53. 6. Pugliese JM, Morey AF, Peterson AC. Lichen sclerosus: review of the literature and current recommendations for management. J Urol 2007;178:2268–76. 7. Goldstein AT, Marinoff SC, Christopher K, et al. Prevalence of vulvar lichen sclerosus in a general gynecology practice. J Reprod Med 2005;50:477–80. 8. Leibovitz A, Kaplun VV, Saposhnicov N, et al. Vulvovaginal examinations in elderly nursing home women residents. Arch Gerontol Geriatr 2000;31:1–4. 9. Chi CC, Kirtschig G, Baldo M, et al. Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus. J Am Acad Dermatol 2012;67:305–12. 10. Wallace HJ. Lichen sclerosus et atrophicus. Trans St Johns Hosp Dermatol Soc 1971;57:9–30.

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11. Hart WR, Norris HJ, Helwig EB. Relation of lichen sclerosus et atrophicus of the vulva to development of carcinoma. Obstet Gynecol 1975;45: 369–77. 12. Selk A. A survey of members of the International Society for the Study of Vulvovaginal Disease Regarding the Treatment of Vulvar Lichen Sclerosus. JLGTD 2013;17(suppl 2):S104. 13. Chi CC, Kirtschig G, Baldo M, et al. Topical interventions for genital lichen sclerosus. Cochrane Database Syst Rev 2011:CD008240. 14. Funaro D, Lovett A, Leroux N, et al. A double-blind, randomized prospective study evaluating topical clobetasol propionate 0.05% versus topical tacrolimus 0.1% in patients with vulvar lichen sclerosus. J Am Acad Dermatol 2014;71:84–91. 15. Virgili A, Borghi A, Toni G, et al. First randomized trial on clobetasol propionate and mometasone furoate in the treatment of vulvar lichen sclerosus: results of efficacy and tolerability. Br J Dermatol 2014;171:388–96. 16. Lagos BR, Maibach HI. Frequency of application of topical corticosteroids: an overview. Br J Dermatol 1998;139:763–6. 17. Maru GB, Gandhi K, Ramchandani A, et al. The role of inflammation in skin cancer. Adv Exp Med Biol 2014;816:437–69.

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A Survey of Experts Regarding the Treatment of Adult Vulvar Lichen Sclerosus.

The objective of this work was to survey physician members and fellows of the International Society for the Study of Vulvovaginal Disease to determine...
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