Vulvar Lichen Sclerosus
Abstract
Lichen sclerosus is a chronic disorder of the skin and mucosal surfaces, and is most commonly seen on the female genital skin. It also occurs on other areas of the body. Any age group may be affected, although it is seen more often in elderly women. The exact cause of lichen sclerosus is unknown. There have been reports of family members with lichen sclerosus; thus it may have a genetic link. There is also the possibility of an autoimmune connection. Currently, ultra-potent topical corticosteroids are the medical treatment of choice. Other treatments that have been utilized for this condition include testosterone, progesterone, tacrolimus, surgery, and phototherapy. Surgery should be reserved for symptomatic patients who fail to respond to multiple medical treatments, as there is a high recurrence rate following surgery. The risk of developing squamous cell carcinoma of the vulva approaches 5% in women with vulvar lichen sclerosus, and therefore close surveillance by the healthcare provider and patient is needed. This review discusses the history, clinical features, pathophysiology, and treatment of lichen sclerosus of the vulva, as well as pregnancy issues and sexual function in patients with this condition. In addition, problems specific to children with lichen sclerosus are reviewed.
Keywords
Testosterone Topical Corticosteroid Lichen Planus Alopecia Areata Vulvar CancerNotes
Acknowledgments
The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.
References
- 1.Hallopeau H. Du Lichen plan, et particulièrement de sa forme atrophique. Un Méd (Par) 1887; 43: 729–33Google Scholar
- 2.Weir RF. Icthyosis of the tongue and vulva. NY State J Med 1875: 246Google Scholar
- 3.Darier J. Lichen plan sclereux. Ann Dermatol Syph 1892; 3: 833–7Google Scholar
- 4.Friedrich EG. Lichen sclerosus. J Reprod Med 1976; 17: 147–54PubMedGoogle Scholar
- 5.Meffert JJ, Davis BM, Grimwood RE. Lichen sclerosus. J Am Acad Dermatol 1995; 32: 393–416PubMedCrossRefGoogle Scholar
- 6.Tait SR. Serpiginous vascular degeneration of the nymphae. In: Tait RL. Diseases of Women. New York. William Wood & Co., 1877: 43–7Google Scholar
- 7.Breisky A. Ueber kraurosis vulvae, eine wenig beachtete Form von Hautatrophie an Pudendum muliebre. Ztschr f Heilk 1885; 6: 69–80Google Scholar
- 8.Unna PG. Karenblattförmige sklerodermie: lehrbuch der speziell path anatomie (8 lief). Berlin: A Hirschwald, 1894Google Scholar
- 9.Johnstone AW. Trachoma of the female genito-urinary tract. Tr Am Gynec Soc (Phila) 1895; 20: 427–34Google Scholar
- 10.Johnstone AW. Trachoma of the female genito-urinary tract. Am Gynaec Obstet J N Y 1895; 6: 764–9Google Scholar
- 11.Pichevin R, Pettit A. Leucoplasie vulvóvaginale. Semaine Gynéc Par 1897; 2: 257, 265, 276, 284Google Scholar
- 12.Westberg F. Ein Fall von mit weissen Flecken einhergehender, bisher nicht bekannter Dermatose. Monatschr Prakt Dermatol 1901; 33: 355–61Google Scholar
- 13.von Zumbusch LR. Über Lichen albus, eine bisher unbeschriebene Erkrankung. Arch Dermatol Syph (Berlin) 1906; 82: 339–50Google Scholar
- 14.Montgomery FH, Ormsby O. “White spot disease” (morphea guttata) and lichen planus sclerosus et atrophicus: a clinical and histological study of three cases, with a review of the literature. J Cutan Dis 1907; 25: 1–16Google Scholar
- 15.Csillag J. Dermatitis lichenoides chronica atrophicans [abstract]. Ikonographia Dermatol 1909; 4: 147Google Scholar
- 16.Veit J. Kraurosis vulvae (Leukoplakia vulvae). Handbuch der Gynakologie. 2nd ed. 1910; 4: 611–27Google Scholar
- 17.Berkeley C, Bonney V. Leucoplakic vulvitis and its relation to kraurosis vulvae and carcinoma vulvae. BMJ 1909; 2: 1739–44PubMedCrossRefGoogle Scholar
- 18.Graves WP. Kraurosis vulvae: gynecology. 4th ed. Philadelphia (PA): WB Saunders Co., 1928Google Scholar
- 19.Ormsby OS, Mitchell J. Lichen planus atrophicus et sclerosus and kraurosis vulvae. Arch Derm Syph 1922; 5: 786Google Scholar
- 20.Taussig FJ. Precancerous lesions of the skin of the vulva. Arch Dermatol Syph 1920; 38: 621–35Google Scholar
- 21.Kyrle J. Histo-biologie der menschichen haut und ihrer erkrankungen. Wien: Verlag von Julius Springer, 1927CrossRefGoogle Scholar
- 22.Kogoj FR. Lichen sclerosus (atrophicus) primitivus [paper]. Arch Derm Syph 1934; 169: 465Google Scholar
- 23.Kogoj FR. Ueber die Stellung des Lichen sclerosus im System [abstract]. Arch Derm Syph 1936; 173: 615–23Google Scholar
- 24.Swift BH. Achlorhydria as an aetiological factor in pruritis vulvae associated with kraurosis or leucoplakia. J Obstet Gynecol Br Emp 1936; 43: 1053–77Google Scholar
- 25.Cinberg BL. Postmenopausal pruritis vulvae. Am J Obstet Gynecol 1945; 49: 647–57Google Scholar
- 26.Oberfield RA. Lichen sclerosus et atrophicus and kraurosis vulvae. Arch Dermatol 1961; 83: 806–15PubMedCrossRefGoogle Scholar
- 27.Barker LP, Gross P. Lichen sclerosus et atrophicus of the female genitalia. Arch Dermatol 1962; 85: 362–73PubMedCrossRefGoogle Scholar
- 28.Jeffcoate TN. Chronic vulval dystrophies. Am J Obstet Gynecol 1966; 95: 61–74PubMedGoogle Scholar
- 29.Wallace HJ. Lichen sclerosus et atrophicus. Trans St Johns Hosp Dermatol Soc 1971; 57: 9–30PubMedGoogle Scholar
- 30.Friedrich EG. New nomenclature for vulvar disease. Obstet Gynecol 1976; 47: 122–4Google Scholar
- 31.Jasionowski EA, Jasionowski P. Topical progesterone in treatment of vulvar dystrophy. Am J Obstet Gynecol 1977; 127: 667–70PubMedGoogle Scholar
- 32.Jasionowski EA, Jasionowski PA. Further observations on the effect of topical progesterone on vulvar disease. Am J Obstet Gynecol 1979; 134: 565–7PubMedGoogle Scholar
- 33.Laude TA, Narayanaswamy G, Rajkumar S. Lichen sclerosus et atrophicus in an eleven year old girl. Report of a case. Cutis 1980; 26: 78–80PubMedGoogle Scholar
- 34.Harrington CI, Dunsmore IR. An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus et atrophicus. Br J Dermatol 1981; 104: 563–6PubMedCrossRefGoogle Scholar
- 35.Neuhofer J, Fritsch P. Treatment of localized scleroderma and lichen sclerosus with etretinate. Acta Derm Venereol (Stockh) 1984; 64: 171–4Google Scholar
- 36.Asbrink E, Hovmark A. Cutaneous manifestations in Ixodes-borne Borellia spirochetosis. Int J Dermatol 1987; 26: 215–23PubMedCrossRefGoogle Scholar
- 37.Tuffanelli D. Do some patients with morphea and lichen sclerosus et atrophicans have a Borrelia infection? Am J Dermatopathol 1987; 9: 371–3PubMedCrossRefGoogle Scholar
- 38.Clark JA, Muller S. Lichen sclerosus et atrophicus in children. Arch Dermatol 1967; 95: 476–82PubMedCrossRefGoogle Scholar
- 39.Taussig FJ. Chronic leukoplakic vulvitis followed by cancer. Surg Clin North Am 1922; 2: 1559–70Google Scholar
- 40.Friedrich EG. Vulvar disease. Philadelphia (PA): WB Saunders, 1983Google Scholar
- 41.Bousema MT, Romppanen U, Geiger J, et al. Acitretin in the treatment of severe lichen sclerosus et atrophicus of the vulva: a double-blind, placebo-controlled study. J Am Acad Dermatol 1994; 30: 225–31PubMedCrossRefGoogle Scholar
- 42.Thomas RH, Ridley CM, McGibbon DH, et al. Anogenital lichen sclerosus in women. J R Soc Med 1996; 89: 694–8PubMedGoogle Scholar
- 43.Lorenz B, Kaufman RH, Kutzner SK. Lichen sclerosus: therapy with clobetasol propionate. J Reprod Med 1998; 9: 790–4Google Scholar
- 44.Ox2019Keefe RJ, Scurry JP, Dennerstein G, et al. Audit of 114 non-neoplastic vulvar biopsies. Br J Obstet Gynaecol 1995; 102: 780–6PubMedCrossRefGoogle Scholar
- 45.Ball SB, Wojnarowska F. Vulvar dermatoses: lichen sclerosus, lichen planus, and vulvar dermatitis/lichen simplex chronicus. Semin Cutan Med Surg 1998; 17: 182–8PubMedCrossRefGoogle Scholar
- 46.Rodke G, Friedrich Jr EG, Wilkinson EJ. Malignant potential of mixed vulvar dystrophy lichen sclerosus associated with squamous cell hyperplasia. J Reprod Med 1988; 33: 545–50PubMedGoogle Scholar
- 47.Carlson JA, Lamb P, Malfetano J, et al. Clinicopathologic comparison of vulvar and extragenital lichen sclerosus: histologic variants, evolving lesions, and etiology of 141 cases. Mod Pathol 1998; 11: 844–54PubMedGoogle Scholar
- 48.Marren P, Wojnarowska F, Powell S. Allergic contact dermatitis and vulvar dermatoses. Br J Dermatol 1992; 126: 52–6PubMedCrossRefGoogle Scholar
- 49.Fung MA, LeBoit PE. Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. Am J Surg Pathol 1998; 22: 473–8PubMedCrossRefGoogle Scholar
- 50.Goolamali SK, Barnes EW, Irvine WJ, et al. Organ specific antibodies in patients with lichen sclerosus. BMJ 1974; 4: 78–9PubMedCrossRefGoogle Scholar
- 51.Meyrick Thomas RH, Ridley CM, McGibbon DH, et al. Lichen sclerosus et atrophicus and autoimmunity: a study of 350 women. Br J Dermatol 1988; 118: 41–6PubMedCrossRefGoogle Scholar
- 52.Meyrick Thomas RH, Ridley CM, Black MMK. The association of lichen sclerosus et atrophicus and autoimmune-related diseases in males. Br J Dermatol 1983; 109: 661–4PubMedCrossRefGoogle Scholar
- 53.Lipscombe TK, Wayte J, Wojnarowska F, et al. A study of clinical and aetiological factors and possible associations of lichen sclerosus in males. Australas J Dermatol 1997; 38: 132–6PubMedCrossRefGoogle Scholar
- 54.Sahn EE, Bluestein EL, Oliva S. Familial lichen sclerosus et atrophicus in childhood. Pediatr Dermatol 1994; 11: 160–3PubMedCrossRefGoogle Scholar
- 55.Meyrick Thomas RH, Kennedy CT. The development of lichen sclerosus et atrophicus in monozygotic twin girls. Br J Dermatol 1986; 114: 377–9PubMedCrossRefGoogle Scholar
- 56.Cox NH, Mitchell JN, Morley WN. Lichen sclerosus et atrophicus in non-identical female twins. Br J Dermatol 1986; 115: 743–6PubMedCrossRefGoogle Scholar
- 57.Shirer Jr JA, Ray MC. Familial occurrence of lichen sclerosus et atrophicus. Arch Dermatol 1987; 123: 485–8PubMedCrossRefGoogle Scholar
- 58.Murphy FR, Lipa M, Haberman HF. Familial vulvar dystrophy of lichen sclerosus type. Arch Dermatol 1982; 118: 329–31PubMedCrossRefGoogle Scholar
- 59.Powell J, Wojnarowksa F, Winsey S, et al. Lichen sclerosus premenarche: autoimmunity and immunogenetics. Br J Dermatol 2000; 142: 481–4PubMedCrossRefGoogle Scholar
- 60.Marren P, Yell J, Charnock FM, et al. The association between lichen sclerosus and antigens of the HLA system. Br J Dermatol 1995; 132: 197–203PubMedCrossRefGoogle Scholar
- 61.Azurdia RM, Luzzi GA, Byren I, et al. Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease. Br J Dermatol 1999; 140: 79–83PubMedCrossRefGoogle Scholar
- 62.Farrell AM, Marren PM, Wojnarowska F. Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical and HLA characteristics. Br J Dermatol 2000; 143: 598–603PubMedCrossRefGoogle Scholar
- 63.Meyrick Thomas RH, Ridley CM, Sherwood F, et al. The lack of association of lichen sclerosus et atrophicus with HLA-A and B tissue antigens. Clin Exp Dermatol 1984; 9: 290–2PubMedCrossRefGoogle Scholar
- 64.Schwartz BD. The major histocompatibility complex and disease susceptibility. In: Wyngaarden JB, Smith Jr LH, Bennett JC, editors. Cecil textbook of medicine. Philadelphia (PA): Saunders, 1992: 1470–9Google Scholar
- 65.Dinarello CA, Thompson RC. Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. Immunol Today 1991; 12: 404–10PubMedCrossRefGoogle Scholar
- 66.Clay FE, Cork MJ, Tarlow JK, et al. Interleukin 1 receptor antagonist gene polymorphism association with lichen sclerosus. Hum Genet 1994; 94: 407–10PubMedCrossRefGoogle Scholar
- 67.Betti R, Lodi A, Marmini A, et al. T cell peripheral subsets in lichen sclerosus et atrophicus. Br J Dermatol 1986; 11: 569–73Google Scholar
- 68.Carli P, Bracco G, Taddei G, et al. Vulvar lichen sclerosus immunohistologic evaluation before and after therapy. J Reprod Med 1994; 39: 110–4PubMedGoogle Scholar
- 69.Farrell AM, Marren P, Dean D, et al. Lichen sclerosus: evidence that immunological changes occur at all levels of the skin. Br J Dermatol 1999; 140: 1087–92PubMedCrossRefGoogle Scholar
- 70.Carlson JA, Grabowski R, Chichester P, et al. Comparative immunophenotypic study of lichen sclerosus: epidermotropic CD57+ lymphocytes are numerous: implications for pathogenesis. Am J Dermatopathol 2000; 22: 7–16PubMedCrossRefGoogle Scholar
- 71.Gross T, Wagner A, Ugurel S, et al. Identification of TIA-1+ and granzyme B+ cytotoxic T cells in lichen sclerosus et atrophicus. Dermatol 2001; 202: 198–202CrossRefGoogle Scholar
- 72.Scrimin F, Rustja S, Radilo O, et al. Vulvar lichen sclerosus: an immunologic study. Obstet Gynecol 2000; 95: 147–50PubMedCrossRefGoogle Scholar
- 73.Farrell AM, Dean D, Charnock M, et al. Distribution of transforming growth factor-beta isoforms TIF-beta1, TGF-beta2 and TGF-beta 3 and vascular endothelial growth factor in vulvar lichen sclerosus. J Reprod Med 2001; 46: 117–24PubMedGoogle Scholar
- 74.Carli P, Moretti S, Spallanzani A, et al. Fibrogenic cytokines in vulvar lichen sclerosus. J Reprod Med 1997; 42: 161–5PubMedGoogle Scholar
- 75.Friedrich Jr EG, Kalra PS. Serum levels of sex hormones in vulval lichen sclerosus and the effect of topical testosterone. N Engl J Med 1984; 310: 488–91PubMedCrossRefGoogle Scholar
- 76.Kohlberger PD, Joura EA, Bancher D, et al. Evidence of androgen receptor expression in lichen sclerosus: an immunohistochemical study. J Soc Gynecol Investig 1998; 5: 331–3PubMedCrossRefGoogle Scholar
- 77.Clifton MM, Garner I, Kohler S, et al. Immunohistochemical evaluation of androgen receptors in genital and extragenital lichen sclerosus: evidence for loss of androgen receptors in lesional epidermis. J Am Acad Dermatol 1999; 41: 43–6PubMedCrossRefGoogle Scholar
- 78.Hodgins MB, Spike RC, Mackie RM, et al. Immunohistochemisty of steroid receptors in vagina and vulvar skin: evidence for loss of androgen and estrogen receptor in the lesional epidermis of vulvar lichen sclerosus [abstract]. Br J Dermatol 1991; 125: 486Google Scholar
- 79.Carlson JA, Murphy M. Androgen receptors and lichen sclerosus. J Am Acad Dermatol 2000; 43: 559–60PubMedCrossRefGoogle Scholar
- 80.Marren P, Cherry C, Day A, et al. Lichen sclerosus: the patient, the hormonal influences and disease impact [abstract]. Br J Dermatol 1995; 21: 133Google Scholar
- 81.Zarcone R, Vicinanza G, Bellini P, et al. Drug treatment in vulvar lichen sclerosus. Minerva Ginecolog 1996; 48: 441–4Google Scholar
- 82.Cantwell AR. Histologic observations of variably acid-fast bacteria in scleroderma, morphoea and lichen sclerosus et atrophicus. Int J Dermatol 1984; 23: 45–52PubMedCrossRefGoogle Scholar
- 83.Drut RM, Gomez MA, Drut R, et al. Human papillomavirus is present in some cases of childhood penile lichen sclerosus: an in situ hybridization and SP-PCR study. Pediatr Dermatol 1998; 15: 85–90PubMedCrossRefGoogle Scholar
- 84.Rohwedder A, Philips B, Malfetano J, et al. Vulvar malignant melanoma associated with human papillomavirus DNA. Am J Dermatopathol 2002; 24: 230–40PubMedCrossRefGoogle Scholar
- 85.Boulinguez S, Bernard P, Lacour JP, et al. Bullous lichen sclerosus with chronic hepatitis C virus infection. Br J Dermatol 1997; 137: 474–5PubMedCrossRefGoogle Scholar
- 86.Ross SA, Sanchez JL, Taboas JO. Spirochetal forms in the dermal lesions of morphea and lichen sclerosus et atrophicus. Am J Dermatopathol 1990; 12: 357–62PubMedCrossRefGoogle Scholar
- 87.Aberer E, Stanek G. Histological evidence for spirochetal origin of morphea and lichen sclerosus et atrophicans. Am J Dermatopathol 1987; 9: 374–9PubMedCrossRefGoogle Scholar
- 88.Weide B, Walz T, Garbe C. Is morphoea caused by Borellia burgdorferi? A review. Br J Dermatol 2000; 142: 636–44PubMedCrossRefGoogle Scholar
- 89.Wallace HJ, Whimster I. Vulval atrophy and leukoplakia. Br J Dermatol 1951; 63: 241–57PubMedCrossRefGoogle Scholar
- 90.Hunt E. Diseases affecting the vulva. London: H Kimpton, 1954Google Scholar
- 91.Bottger H, Dittman E. Pruritus, kraurosis vulvae, and vulvakarzinom. Geburtshilfe Frauenheilkd 1957; 12: 1097–109Google Scholar
- 92.Suurmond D. Lichen sclerosus et atrophicus of the vulva. Arch Dermatol 1964; 90: 143–53PubMedCrossRefGoogle Scholar
- 93.Gardner HL. Benign diseases of the vulva and vagina. St Louis (MO): CV Mosby Co, 1969Google Scholar
- 94.Hart WR, Norris HJ, Helwig EB. Relation of lichen sclerosus et atrophicus of the vulva to development of carcinoma. Obstet Gynecol 1975; 45: 369–77PubMedGoogle Scholar
- 95.Kini U. Squamous cell carcinoma of the vulva in association with mixed vulvar dystrophy. Indian J Cancer 1997; 34: 92–5PubMedGoogle Scholar
- 96.Carlson JA, Ambros R, Malfetano J, et al. Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective: implications for chronic inflammation and sclerosis in development of neoplasia. Hum Pathol 1998; 29: 932–48PubMedCrossRefGoogle Scholar
- 97.Haefner HK, Tate JE, McLachlin CM, et al. Vulvar intraepithelial neoplasia: age, morphological phenotype, papillomavirus DNA, and coexisting invasive carcinoma. Hum Pathol 1995; 26: 147–54PubMedCrossRefGoogle Scholar
- 98.Taussig FJ. Cancer of the vulva: an analysis of 155 cases. Am J Obstet Gynecol 1940; 40: 764–9Google Scholar
- 99.Langley II, Hertig A, Smith G. Relation of leukoplakic vulvitis to squamous cell carcinoma of the vulva. Am J Obstet Gynecol 1951; 62: 167–9PubMedGoogle Scholar
- 100.Weghaupt K. die Krauosis vulvae und ihre Behandlung mit Elecktrocoagulation. Geburtshilfe Frauenheilkd 1954; 14: 705PubMedGoogle Scholar
- 101.Green TH, Ulfelder H, Meigs JV. Epidermoid carcinoma of the vulva: an analysis of 238 cases [paper]. Am J Obstet Gynecol 1958; 75: 834–47PubMedGoogle Scholar
- 102.Lundwall F. Cancer of the vulva: clinical review [thesis]. Copenhagen: University of Copenhagen, 1961Google Scholar
- 103.Buscema J, Stern J, Woodruff JD. The significance of the histologic alterations adjacent to invasive vulvar carcinoma. Am J Obstet Gynecol 1980; 137: 902–9PubMedGoogle Scholar
- 104.Zaino RJ, Husseinzadeh N, Nahhas W, et al. Epithelial alterations in proximity to invasive squamous carcinoma of the vulva. Int J Gynecol Pathol 1982; 1: 173–84PubMedCrossRefGoogle Scholar
- 105.Choo YC. Invasive squamous carcinoma of the vulva in young patients. Gynecol Oncol 1982; 13: 158–64PubMedCrossRefGoogle Scholar
- 106.Hacker NF, Berek JS, Lagasse LD, et al. Individualization of treatment for stage I squamous cell vulvar carcinoma. Obstet Gynecol 1984; 63: 155–62PubMedGoogle Scholar
- 107.Hewitt J. Conditions étiologiques du carcinome invasif d’emblée de la vulve: possibilité d’un traitement prophylactique? J Gynecol Obstet Biol Reprod (Paris) 1984; 13: 297–303Google Scholar
- 108.Borgno G, Micheletti L, Barbero M, et al. Epithelial alterations adjacent to 111 vulvar carcinomas. J Reprod Med 1988; 33: 500–2PubMedGoogle Scholar
- 109.Leibowitch M, Neill S, Pelisse M, et al. The epithelial changes associated with squamous cell carcinoma of the vulva: a review of the clinical, histological and viral findings in 78 women. Br J Obstet Gynaecol 1990; 97: 1135–9PubMedCrossRefGoogle Scholar
- 110.Toki T, Kurman RJ, Park JS, et al. Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction. Int J Gynecol Pathol 1991; 10: 107–25PubMedCrossRefGoogle Scholar
- 111.MacLean AB. Precursors of vulval cancers. Curr Obstet Gynecol 1993; 3: 149–56CrossRefGoogle Scholar
- 112.Ansink AC, Krul MR, De Weger RA, et al. Human papillomavirus, lichen sclerosus, and squamous cell carcinoma of the vulva: detection and prognostic significance. Gynecol Oncol 1994; 52: 180–4PubMedCrossRefGoogle Scholar
- 113.Hording U, Junge J, Daugaard S, et al. Vulvar squamous cell carcinoma and papillomaviruses: indications for two different etiologies. Gynecol Oncol 1994; 52: 241–6PubMedCrossRefGoogle Scholar
- 114.Gomez Rueda N, Garcia A, Vighi S, et al. Epithelial alterations adjacent to invasive squamous carcinoma of the vulva. J Reprod Med 1994; 39: 526–30PubMedGoogle Scholar
- 115.Sagerman PM, Choi YJ, Hu Y, et al. Human papilloma virus, vulvar dystrophy, and vulvar carcinoma: differential expression of human papillomavirus and vulvar dystrophy in the presence and absence of squamous cell carcinoma of the vulva. Gynecol Oncol 1996; 61: 328–32PubMedCrossRefGoogle Scholar
- 116.Vilmer C, Cavelier-Balloy B, Nogues C, et al. Analysis of alterations adjacent to invasive vulvar carcinoma and their relationship with the associated carcinoma: a study of 67 cases. Eur J Gynaecol Oncol 1998; 19: 25–31PubMedGoogle Scholar
- 117.Derrick EK, Ridley CM, Kobza-Black A, et al. A clinical study of 23 cases of female anogenital carcoma. Br J Dermatol 2000; 143: 1217–23PubMedCrossRefGoogle Scholar
- 118.Al-Ghamdi A, Freedman D, Miller D, et al. Vulvar squamous cell carcinoma in young women: a clinicopathologic study of 21 cases. Gynecol Oncol 2002; 84: 94–101PubMedCrossRefGoogle Scholar
- 119.Carli P, Cattaneo A, De Magnis A, et al. Squamous cell carcinoma arising in vulval lichen sclerosus: a longitudinal cohort study. Eur J Cancer Prevention 1995; 4: 491–5CrossRefGoogle Scholar
- 120.Bart RS, Kopf AW. Tumor conference no 18: squamous-cell carcinoma arising in balanitis xerotica obliterans. J Dermatol Surg Oncol 1978; 4: 556–8PubMedGoogle Scholar
- 121.Pride HB, Miller III OF, Tyler WB. Penile squamous cell carcinoma arising from balanitis xerotica obliterans. J Am Acad Dermatol 1993; 29: 469–73PubMedCrossRefGoogle Scholar
- 122.di Paola GR, Rueda-Leverone NG, Belardi MG. Lichen sclerosus of the vulva recurrent after myocutaneous graft: a case report. J Reprod Med 1982; 27: 666–8PubMedGoogle Scholar
- 123.Thomas RH, McGibbon DH, Munro DD. Basal cell carcinoma of the vulva in association with vulval lichen sclerosus et atrophicus. J R Soc Med 1985; 78 Suppl. 11: 16–8PubMedGoogle Scholar
- 124.Friedman RJ, Kopf AW, Jones WB. Malignant melanoma in association with lichen sclerosus on the vulva of a 14-year-old. Am J Dermatopathol 1984; 6: 253–6PubMedGoogle Scholar
- 125.McAdams AJ, Kistner RW. The relationship of chronic vulvar disease, leukoplakia, and carcinoma in situ to carcinoma of the vulva. Cancer 1958; 11: 740–57PubMedCrossRefGoogle Scholar
- 126.Egan CA, Bradley RR, Logsdon VK, et al. Vulvar melanoma in childhood. Arch Dermatol 1997; 133: 345–8PubMedCrossRefGoogle Scholar
- 127.Regauer S, Reich O, Beham-Schmid C. Monoclonal gamma-T-cell receptor rearrangement in vulvar lichen sclerosus and squamous cell carcinomas. Am J Pathol 2002; 160: 1035–45PubMedCrossRefGoogle Scholar
- 128.Carlson JA, Amin S, Malfetano J, et al. JS. Concordant p53 and mdm-2 protein expression in vulvar squamous cell carcinoma and adjacent lichen sclerosus. Appl Immunohistochem Mol Morphol 2001; 9: 150–63PubMedCrossRefGoogle Scholar
- 129.Carlson JA, Healy K, Tran TA, et al. Chromosome 17 aneusomy detected by fluorescence in situ hybridization in vulvar squamous cell carcinomas and synchronous vulvar skin. Am J Pathol 2000; 157: 973–83PubMedCrossRefGoogle Scholar
- 130.Pinto AP, Lin MC, Sheets EE, et al. Allelic imbalance in lichen sclerosus, hyperplasia, and intraepithelial neoplasia of the vulva. Gynecol Oncol 2000; 77: 171–6PubMedCrossRefGoogle Scholar
- 131.Rolfe KJ, Crow JC, Benjamin E, et al. Cyclin D1 and retinoblastoma protein in vulvar cancer and adjacent lesions. Int J Gynecol Cancer 2001; 11: 381–6PubMedCrossRefGoogle Scholar
- 132.Tate JE, Mutter GL, Boynton KA, et al. Monoclonal origin of vulvar intraepithelial neoplasia and some vulvar hyperplasias. Am J Pathol 1997; 150: 315–22PubMedGoogle Scholar
- 133.Neill SM, Tatnall FM, Cox NH. Guidelines for the management of lichen sclerosus. Br J Dermatol 2002; 147: 640–9PubMedCrossRefGoogle Scholar
- 134.Willliams GA, Richardson AC, Hathcock EE. Topical testosterone in dystrophic diseases of the vulva. Am J Obstet Gynecol 1966; 96: 21–30Google Scholar
- 135.Zelle K. Treatment of vulvar dystrophies with topical testosterone propionate. Am J Obstet Gynecol 1971; 109: 570–3PubMedGoogle Scholar
- 136.Friedrich EG. Topical testosterone for benign vulvar dystrophy. Obstet Gynecol 1971; 37: 677–86PubMedGoogle Scholar
- 137.Kaufman RH, Gardner H, Brown D, et al. Vulvar dystrophies: an evaluation. Am J Obstet Gynecol 1974; 120: 363–7PubMedGoogle Scholar
- 138.Ayhan A, Urman B, Yuce K, et al. Topical testosterone for lichen sclerosus. Int J Gynaecol Obstet 1989; 30: 253–5PubMedCrossRefGoogle Scholar
- 139.Paslin D. Treatment of lichen sclerosus with topical dihydrotestosterone. Obstet Gynecol 1991; 78: 1046–9PubMedGoogle Scholar
- 140.Wright AJ. Testosterone pellet implant therapy for lichen sclerosus. Mo Med 1993; 90: 711–3PubMedGoogle Scholar
- 141.Paslin D. Androgens in the topical treatment of lichen sclerosus. Pharmacol Ther 1996; 35: 298–301Google Scholar
- 142.Joura EA, Zeisler H, Bancher-Todesca D, et al. Short-term effects of topical testosterone in vulvar lichen sclerosus. Obstet Gynecol 1997; 89: 297–9PubMedCrossRefGoogle Scholar
- 143.Dalziel KL, Millard PRP, Wojnarowska F. The treatment of vulval lichen sclerosus with a very potent topical steroid (clobetasol propionate 0.05%) cream. Br J Dermatol 1991; 124: 461–4PubMedCrossRefGoogle Scholar
- 144.Cattaneo A, De Marco A, Sonni L, et al. Clobetasol versus testosterone in the treatment of lichen sclerosus of the vulvar region. Minerva Ginecol 1992; 44: 567–71PubMedGoogle Scholar
- 145.Dalziel KL, Wojnarowska F. Long-term control of vulval lichen sclerosus after treatment with a potent topical steroid cream. J Reprod Med 1993; 38: 25–7PubMedGoogle Scholar
- 146.Bracco GL, Carli P, Sonni L, et al. Clinical and histologic effects of topical treatments of vulvar lichen sclerosus: a critical evaluation. J Reprod Med 1993; 38: 37–40PubMedGoogle Scholar
- 147.Sideri M, Origoni M, Spinaci L, et al. Topical testosterone in the treatment of vulvar lichen sclerosus. Int J Gynaecol Obstet 1994; 46: 53–6PubMedCrossRefGoogle Scholar
- 148.Cattaneo A, Carli P, De Marco A, et al. Testosterone maintenance therapy: effects on vulvar lichen sclerosus treated with clobetasol propionate. J Reprod Med 1996; 41: 99–102PubMedGoogle Scholar
- 149.Bornstein J, Heifetz S, Kellner Y, et al. Clobetasol dipropionate 0.05% versus testosterone propionate 2% topical application for severe vulvar lichen sclerosus. Am J Obstet Gynecol 1998; 178: 80–4PubMedCrossRefGoogle Scholar
- 150.Sinha P, Sorinola O, Luesley DM. Lichen sclerosus of the vulva: long-term steroid maintenance therapy. J Reprod Med 1999; 44: 621–4PubMedGoogle Scholar
- 151.Parker LU, Bergfeld WF. Virilization secondary to topical testosterone. Cleve Clin J Med 1991; 58: 43–6PubMedGoogle Scholar
- 152.Punch MR, Ansbacher R. Autogenic masculinization. Am J Obstet Gynecol 1990; 163: 114–6PubMedGoogle Scholar
- 153.Ridley CM. Lichen sclerosus. Dermatol Clin 1992; 10: 309–23PubMedCrossRefGoogle Scholar
- 154.Mazdisnian F, Degregorio F, Mazdisnian F, et al. Intralesional injection of triamcinolone in the treatment of lichen sclerosus. J Reprod Med 1999; 44: 332–4PubMedGoogle Scholar
- 155.Dutton WA. The use of local injections of triamcinolone into chronic inflammatory lesions of the vulva. J Obstet Gynaecol Br Commonw 1962; 69: 891–2CrossRefGoogle Scholar
- 156.Neill SM, Ridley CM. Management of anogenital lichen sclerosus. Clin Exp Dermatol 2001; 26: 637–43PubMedCrossRefGoogle Scholar
- 157.Tosti A, Guerra L, Manuzzi P, et al. Contact dermatitis from clobetasol propionate. Contact Dermatitis 1987; 17: 256–7PubMedCrossRefGoogle Scholar
- 158.Torok E, Orley J, Goracz G, et al. Lichen sclerosus et atrophicus in children: clinical and pathological analysis of 33 cases. Mod Probl Paediatr 1975; 17: 262–71PubMedGoogle Scholar
- 159.Bohm M, Frieling U, Luger TA, et al. Successful treatment of anogenital lichen sclerosus with topical tacrolimus. Arch Dermatol 2003; 139 (7): 922–4PubMedCrossRefGoogle Scholar
- 160.Kunstfeld R, Kirnbauer R, Stingl G, et al. Successful treatment of vulvar lichen sclerosus with topical tacrolimus. Arch Dermatol 2003; 139 (7): 850–2PubMedCrossRefGoogle Scholar
- 161.Assmann T, Becker-Wegerich P, Grewe M, et al. Tacrolimus ointment for the treatment of vulvar lichen sclerosus. J Am Acad Dermatol 2003; 48: 935–7PubMedCrossRefGoogle Scholar
- 162.Morrison L, Kratochvil III FJ, Gorman A. An open trial of topical tacrolimus for erosive oral lichen planus. J Am Acad Dermatol 2002; 47: 617–20PubMedCrossRefGoogle Scholar
- 163.Bergman J, Rico MJ. Tacrolimus clinical studies for atopic dermatitis and other conditions. Semin Cutan Med Surg 2001; 20: 250–9PubMedCrossRefGoogle Scholar
- 164.Nasr IS. Topical tacrolimus in dermatology. Clin Exp Dermatol 2000; 25: 250–4PubMedCrossRefGoogle Scholar
- 165.Wakelin SH, Marren P. Lichen sclerosus in women. Clin Dermatol 1997; 15: 155–69PubMedCrossRefGoogle Scholar
- 166.Parsad D, Saini R. Oral stanozolol in lichen sclerosus et atrophicus. J Am Acad Dermatol 1998; 38: 278–9PubMedCrossRefGoogle Scholar
- 167.Kaufman RH, Faro S, Friedrich E, et al. Benign diseases of the vulva and vagina. St Louis (MO): Mosby Year Book Inc., 1994Google Scholar
- 168.Virgili A, Corazza M, Bianchi A, et al. Open study of topical 0.025% tretinoin in the treatment of vulvar lichen sclerosus: one year of therapy. J Reprod Med 1995; 40: 614–8PubMedGoogle Scholar
- 169.Penneys N. Treatment of lichen sclerosus with potassium para-aminobenzoate. J Am Acad Dermatol 1984; 10: 1039–42PubMedCrossRefGoogle Scholar
- 170.Everett MA, Coffey CM. Intradermal administration of chloroquine for discoid lupus erythematous and lichen sclerosus et atrophicus. Arch Dermatol 1961; 83: 977–9PubMedCrossRefGoogle Scholar
- 171.NZ Dermatological Society [online]. Available from URL: http://dermnetnz.org/index.html [Accessed 2004 Feb 12]Google Scholar
- 172.Vulvar Health lichen sclerosis 2002 [online]. Available from URL: http://www.vulvarhealth.org/LS.html [Accessed 2004 Mar 25]Google Scholar
- 173.National Lichen Sclerosus Support Group [online]. Available from URL: http://www.lichensclerosus.org [Accessed 2004 Feb 12]Google Scholar
- 174.Wakelin SH, James MP. Extensive lichen sclerosus et atrophicus with bullae and ulceration: improvement with hydroxychloroquine. Clin Exp Dermatol 1994; 19: 332–4PubMedCrossRefGoogle Scholar
- 175.Garcia-Doval I, Peteiro C, Sanchez-Aguilar D, et al. Extensive bullous lichen sclerosus et atrophicus unresponsive to hydroxychloroquine [letter]. Clin Exp Dermatol 1996; 21: 247PubMedCrossRefGoogle Scholar
- 176.Kreuter A, Gambichler T, Sauermann K, et al. Extragenital lichen sclerosus successfully treated with topical calcipotriol: evaluation by in vivo confocal laser scanning microscopy. Br J Dermatol 2002; 146: 332–3PubMedCrossRefGoogle Scholar
- 177.Carli P, Cattaneo A, Taddei G, et al. Topical cyclosporine in the treatment of vulvar lichen sclerosus: clinical, histologic, and immunohistochemical findings. Arch Dermatol 1992; 128: 1548–9PubMedCrossRefGoogle Scholar
- 178.Origoni M, Ferrari D, Rossi M, et al. Topical oxatomide: an alternative approach for the treatment of vulvar lichen sclerosus. Int J Gynaecol Obstet 1996; 55: 259–64PubMedCrossRefGoogle Scholar
- 179.Abramov Y, Elchalal U, Abramov D, et al. Surgical treatment of vulvar lichen sclerosus: a review. Obstet Gynecol Surv 1996; 51: 193–9PubMedCrossRefGoogle Scholar
- 180.Woodruff JD, Baens J. Interpretation of atrophic and hypertrophic alterations in the vulvar epithelium. Am J Obstet Gynecol 1963; 86: 713–23PubMedGoogle Scholar
- 181.Paniel BJ. Chapter II: surgical procedures in benign vulval disease. In: Ridly CM, Neill SM, editors. The vulva. Oxford: Blackwell Science, 1999: 288–90Google Scholar
- 182.Candiani GB, Mangioni C, Molteni P, et al. Long-term results of surgical treatment of chronic vulvar dystrophies [in Italian]. Ann Ostet Ginecol Med Perinat 1981; 102: 5–9PubMedGoogle Scholar
- 183.Rettenmaier MA, Braly P, Roberts W, et al. Treatment of cutaneous vulvar lesions with skinning vulvectomy. J Reprod Med 1985; 30: 478–80PubMedGoogle Scholar
- 184.Breech LL, Laufer M. Surgicel in the management of labial and clitoral hood adhesions in adolescents with lichen sclerosus. J Pediatr Adolesc Gynecol 2000; 13: 21–2PubMedCrossRefGoogle Scholar
- 185.Rouzier R, Haddad B, Deyrolle C, et al. Perineoplasty for the treatment of introital stenosis related to vulvar lichen sclerosus. Am J Obstet Gynecol 2002; 186: 49–52PubMedCrossRefGoogle Scholar
- 186.Holzgreve W, Schmidt EH. Surgical treatment of therapy refractory pruritus vulvae in lichen sclerosus. Med Welt 1982; 33: 1323–6PubMedGoogle Scholar
- 187.Paniel BJ, Truc JB, Robichez B, et al. Vulvoperineoplasty [in French]. Presse Med 1984; 13: 1895–8PubMedGoogle Scholar
- 188.van Straalen WR, Hage JJ, Bloemena E, et al. Plastic surgery as a last resort in lichen sclerosus. Ned Tijdschr Geneeskd 1997; 141: 992–8PubMedGoogle Scholar
- 189.Maessen-Visch MB, Neumann HA. Plastic surgery as a last resort in lichen sclerosus [in Dutch]. Ned Tijdschr Geneeskd 1997; 141: 1583PubMedGoogle Scholar
- 190.Ovadia J, Levavi H, Edelstein T. Treatment of pruritus vulvae by means of CO2 laser. Acta Obstet Gynecol Scand 1984; 63: 265–7PubMedCrossRefGoogle Scholar
- 191.Davis AJ, Goldstein DP. Treatment of pediatric lichen sclerosus with CO2 laser. Adolesc Pediatr Gynecol 1989; 2: 103–5Google Scholar
- 192.Stuart GC, Nation J, Malliah V, et al. Laser therapy of vulvar lichen sclerosus et atrophicus. Can J Surg 1991; 34: 469–70PubMedGoogle Scholar
- 193.Rabinowitz LG. Lichen sclerosus et atrophicus treatment with the 585-nm flashlamp-pumped pulsed dye laser. Arch Dermatol 1993; 129: 381–2PubMedCrossRefGoogle Scholar
- 194.Kartamaa M, Reitamo S. Treatment of lichen sclerosus with carbon dioxide laser vaporization. Br J Dermatol 1997; 136: 356–9PubMedCrossRefGoogle Scholar
- 195.Hillemanns P, Untch M, Prove F, et al. Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid. Obstet Gynecol 1999; 93: 71–4PubMedCrossRefGoogle Scholar
- 196.Hackenjos K, Schroder W, Schopf E, et al. Therapy of lichen sclerosus et atrophicus vulvae with the CO2 silk touch laser. Hautarzt 2000; 51: 502–4PubMedCrossRefGoogle Scholar
- 197.Zderkiewicz B. Lichen sclerosus et atrophicus hemorrhagicus treated by a new method. Przegl Dermatol 1972; 59: 55–9PubMedGoogle Scholar
- 198.August PJ, Milward TM. Cryosurgery in the treatment of lichen sclerosus et atrophicus of the vulva. Br J Dermatol 1980; 103: 667–70PubMedCrossRefGoogle Scholar
- 199.Kreuter A, Gambichler T, Avermaete A, et al. Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study. J Am Acad Dermatol 2002; 46: 251–5PubMedCrossRefGoogle Scholar
- 200.Haefner HK, Pearlman MD, Barclay ML, et al. Lichen sclerosus in pregnancy: presentation of two cases. J Lower Genital Tract Dis 1999; 3: 260–3Google Scholar
- 201.Dalziel KL. Effect of lichen sclerosus on sexual function and parturition. J Reprod Med 1995; 40: 351–4PubMedGoogle Scholar
- 202.Schatz M, Hoffman C, Zeiger R, et al. The course and management of asthma and allergic diseases during pregnancy. In: Middleton Jr E, Reed CE, Ellis EF, editors. Allergy: principles and practice. 3rd ed. St Louis (MO): Mosby, 1988: 1124–5Google Scholar
- 203.Scott J. Fetal growth retardation associated with maternal administration of immunosuppressive drugs. Am J Obstet Gynecol 1977; 128: 668–76PubMedGoogle Scholar
- 204.Katz V, Thorp Jr J, Bowes Jr W. Severe symmetric intrauterine growth retardation associated with the topical use of triamcinolone. Am J Obstet Gynecol 1990; 162: 396–7PubMedGoogle Scholar
- 205.Robert E, Scialli A. Topical medications during pregnancy. Reprod Toxicol 1994; 8: 197–202PubMedCrossRefGoogle Scholar
- 206.Laymon CW. Lichen sclerosus et atrophicus in children. Arch Dermatol Syph 1945; 52: 353Google Scholar
- 207.Fischer G, Rogers M. Vulvar disease in children: a clinical audit of 130 cases. Pediatr Dermatol 2000; 17: 1–6PubMedCrossRefGoogle Scholar
- 208.Powell JJ, Wojnarowska F. Childhood vulvar lichen sclerosus: an increasingly common problem. J Am Acad Dermatol 2001; 44: 803–6PubMedCrossRefGoogle Scholar
- 209.Berth-Jones J, Graham-Brown RA, Burns DA. Lichen sclerosus et atrophicus: a review of 15 cases in young girls. Clin Exp Dermatol 1991; 16: 14–7PubMedCrossRefGoogle Scholar
- 210.Fivozinsky KB, Laufer M. Vulvar disorders in prepubertal girls. J Reprod Med 1998; 43: 763–73PubMedGoogle Scholar
- 211.Gibbon KL, Bewley AP, Salisbury JA. Labial fusion in children: a presenting feature of genital lichen sclerosus. Pediatr Dermatol 1999; 16: 388–91PubMedCrossRefGoogle Scholar
- 212.Warrington SA, de San Lazaro C. Lichen sclerosus et atrophicus and sexual abuse. Arch Dis Child 1996; 75: 512–6PubMedCrossRefGoogle Scholar
- 213.Handfield-Jones SE, Hinde FRJ, Kennedy CTC. Lichen sclerosus et atrophicus in children misdiagnosed as sexual abuse. BMJ 1987; 295: 1404–5CrossRefGoogle Scholar
- 214.Wood PL, Bevan T. Lesson of the week: child sexual abuse enquiries and unrecognised vulvar lichen sclerosus et atrophicus. BMJ 1999; 319: 899–900PubMedCrossRefGoogle Scholar
- 215.Ridley CM. Genital lichen sclerosus in childhood and adolescence. J R Soc Med 1993; 86: 69–75PubMedGoogle Scholar
- 216.Fischer G, Rogers M. Treatment of childhood vulvar lichen sclerosus with potent topical corticosteroid. Pediatr Dermatol 1997; 14: 235–8PubMedCrossRefGoogle Scholar
- 217.Garzon MC, Paller AS. Ultrapotent topical corticosteroid treatment of childhood genital lichen sclerosus. Arch Dermatol 1999; 135: 525–8PubMedCrossRefGoogle Scholar
- 218.Smith YR, Quint EH. Clobetasol propionate in the treatment of premenarchal vulvar lichen sclerosus. Obstet Gynecol 2001; 98: 588–91PubMedCrossRefGoogle Scholar
- 219.Serrano G, Millan F, Fortea J, et al. Topical progesterone as a treatment of choice in genital lichen sclerosus et atrophicus in children. Pediatr Dermatol 1993; 10: 201PubMedCrossRefGoogle Scholar
- 220.Kreuter A, Jansen T, Stucker M, et al. Low-dose ultraviolet-A1 phototherapy for lichen sclerosus et atrophicus. Clin Exp Dermatol 2001; 26: 30–2PubMedCrossRefGoogle Scholar