Vulvar Lichen Sclerosus: Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser

Summary

Vulvar lichen sclerosus (VLS) is a lymphocyte-mediated disease of unknown etiology that can cause intense itching as well stenosis, hindering the evacuation and urination. It can also limit the sex life due to severe local pruritus, pain and dyspareunia (pain during sexual intercourse). The standard treatment for this disease is the use of topical corticosteroids to reduce the clinical symptoms and to try to increase disease-free intervals. Photodynamic therapy (PDT), a treatment that associates a light radiation with a photosensitizing agent and low-level laser therapy (LLLT) are therapies that can promote effective immunomodulatory responses at the application site by means of photophysical and photochemical phenomena from the molecular to the systemic level, which promote their use in chronic dermatoses. The aim is to study and compare the effects of PDT, LLLT, and topical corticosteroid in VLS evaluating clinical, histological, immunohistochemical and spectroscopic responses. The study will be prospective, randomized, and controlled, in a population of 60 women with histological diagnoses of VLS, enrolled on the outpatient clinic of Genitoscopy Department of the Pérola Byington Hospital in São Paulo. There will be 3 treatments groups: PDT, LLLT and topical corticosteroid, where will be allocated by randomization 20 patients in each one. The clinical course will be monitored by measuring local temperature, itching, clamping (atrophy), and the appearance of the lesion. Histologically, the slides will be classified according to the Hewitt grading and will have the ordering of collagen fibers quantified. Immunohistochemical analysis will be done using the markers IFN-γ, TGF-β, CD4, CD8, IL-1, p53 and Ki-67. Finally, the spectroscopic evaluation will be done by reflectance. Descriptive and inferential statistical analyses will be conducted to compare the groups and for associations between different responses.

Timeline

Start

2015-01

Primary completion

2016-08

Completion

2017-10

Publications

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• Background Oyama N, Chan I, Neill SM, Hamada T, South AP, Wessagowit V, Wojnarowska F, D'Cruz D, Hughes GJ, Black MM, McGrath JA. Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet. 2003 Jul 12;362(9378):118-23. doi: 10.1016/S0140-6736(03)13863-9.
• Background Gambichler T, Kammann S, Tigges C, Kobus S, Skrygan M, Meier JJ, Kohler CU, Scola N, Stucker M, Bechara FG, Altmeyer P, Kreuter A. Cell cycle regulation and proliferation in lichen sclerosus. Regul Pept. 2011 Apr 11;167(2-3):209-14. doi: 10.1016/j.regpep.2011.02.003. Epub 2011 Feb 15.
• Background Terlou A, Santegoets LA, van der Meijden WI, Heijmans-Antonissen C, Swagemakers SM, van der Spek PJ, Ewing PC, van Beurden M, Helmerhorst TJ, Blok LJ. An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155. J Invest Dermatol. 2012 Mar;132(3 Pt 1):658-66. doi: 10.1038/jid.2011.369. Epub 2011 Nov 24.
• Background Gambichler T, Terras S, Kreuter A, Skrygan M. Altered global methylation and hydroxymethylation status in vulvar lichen sclerosus: further support for epigenetic mechanisms. Br J Dermatol. 2014 Mar;170(3):687-93. doi: 10.1111/bjd.12702.
• Background Perez-Lopez FR, Ceausu I, Depypere H, Erel CT, Lambrinoudaki I, Rees M, Schenck-Gustafsson K, Tremollieres F, van der Schouw YT, Simoncini T; EMAS, Spanish Menopause society. EMAS clinical guide: vulvar lichen sclerosus in peri and postmenopausal women. Maturitas. 2013 Mar;74(3):279-82. doi: 10.1016/j.maturitas.2012.12.006. Epub 2013 Jan 3.
• Background Murphy R. Lichen sclerosus. Dermatol Clin. 2010 Oct;28(4):707-15. doi: 10.1016/j.det.2010.07.006.
• Background Selim MA, Hoang MP. A histologic review of vulvar inflammatory dermatoses and intraepithelial neoplasm. Dermatol Clin. 2010 Oct;28(4):649-67. doi: 10.1016/j.det.2010.07.005. Epub 2010 Aug 30.
• Background Monsalvez V, Rivera R, Vanaclocha F. [Lichen sclerosus]. Actas Dermosifiliogr. 2010 Jan-Feb;101(1):31-8. Spanish.
• Background Brodrick B, Belkin ZR, Goldstein AT. Influence of treatments on prognosis for vulvar lichen sclerosus: facts and controversies. Clin Dermatol. 2013 Nov-Dec;31(6):780-6. doi: 10.1016/j.clindermatol.2013.05.017.
• Background Hantschmann P, Sterzer S, Jeschke U, Friese K. P53 expression in vulvar carcinoma, vulvar intraepithelial neoplasia, squamous cell hyperplasia and lichen sclerosus. Anticancer Res. 2005 May-Jun;25(3A):1739-45.
• Background Thorstensen KA, Birenbaum DL. Recognition and management of vulvar dermatologic conditions: lichen sclerosus, lichen planus, and lichen simplex chronicus. J Midwifery Womens Health. 2012 May-Jun;57(3):260-75. doi: 10.1111/j.1542-2011.2012.00175.x.
• Background Lipkin D, Kwon Y. Therapies and nursing care of women with vulvar dermatologic disorders. J Obstet Gynecol Neonatal Nurs. 2014 Mar-Apr;43(2):246-52. doi: 10.1111/1552-6909.12286. Epub 2014 Feb 6.
• Background Burrows LJ, Creasey A, Goldstein AT. The treatment of vulvar lichen sclerosus and female sexual dysfunction. J Sex Med. 2011 Jan;8(1):219-22. doi: 10.1111/j.1743-6109.2010.02077.x. Epub 2010 Oct 18.
• Background Terras S, Gambichler T, Moritz RK, Stucker M, Kreuter A. UV-A1 phototherapy vs clobetasol propionate, 0.05%, in the treatment of vulvar lichen sclerosus: a randomized clinical trial. JAMA Dermatol. 2014 Jun;150(6):621-7. doi: 10.1001/jamadermatol.2013.7733.
• Background Olejek A, Steplewska K, Gabriel A, Kozak-Darmas I, Jarek A, Kellas-Sleczka S, Bydlinski F, Sieron-Stoltny K, Horak S, Chelmicki A, Sieron A. Efficacy of photodynamic therapy in vulvar lichen sclerosus treatment based on immunohistochemical analysis of CD34, CD44, myelin basic protein, and Ki67 antibodies. Int J Gynecol Cancer. 2010 Jul;20(5):879-87. doi: 10.1111/IGC.0b013e3181d94f05.
• Background Osiecka BJ, Nockowski P, Jurczyszyn K, Ziolkowski P. Photodynamic therapy of vulvar lichen sclerosus et atrophicus in a woman with hypothyreosis--case report. Photodiagnosis Photodyn Ther. 2012 Jun;9(2):186-8. doi: 10.1016/j.pdpdt.2012.02.002. Epub 2012 Mar 27.
• Background Romero A, Hernandez-Nunez A, Cordoba-Guijarro S, Arias-Palomo D, Borbujo-Martinez J. Treatment of recalcitrant erosive vulvar lichen sclerosus with photodynamic therapy. J Am Acad Dermatol. 2007 Aug;57(2 Suppl):S46-7. doi: 10.1016/j.jaad.2006.04.005. No abstract available.
• Background Hillemanns P, Untch M, Prove F, Baumgartner R, Hillemanns M, Korell M. Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid. Obstet Gynecol. 1999 Jan;93(1):71-4. doi: 10.1016/s0029-7844(98)00321-4.
• Background Sotiriou E, Panagiotidou D, Ioannidis D. An open trial of 5-aminolevulinic acid photodynamic therapy for vulvar lichen sclerosus. Eur J Obstet Gynecol Reprod Biol. 2008 Dec;141(2):187-8. doi: 10.1016/j.ejogrb.2008.07.027. Epub 2008 Sep 7. No abstract available.
• Background Biniszkiewicz T, Olejek A, Kozak-Darmas I, Sieron A. Therapeutic effects of 5-ALA-induced photodynamic therapy in vulvar lichen sclerosus. Photodiagnosis Photodyn Ther. 2005 Jun;2(2):157-60. doi: 10.1016/S1572-1000(05)00062-1. Epub 2005 Aug 3.
• Belotto RA, Chavantes MC, Tardivo JP, Euzebio Dos Santos R, Fernandes RCM, Horliana ACRT, Pavani C, Teixeira da Silva DF. Therapeutic comparison between treatments for Vulvar Lichen Sclerosus: study protocol of a randomized prospective and controlled trial. BMC Womens Health. 2017 Aug 10;17(1):61. doi: 10.1186/s12905-017-0414-y.

Drugs

Indications