A radiofrequência fracionada no tratamento de líquen escleroso vulvar: um relato de caso / Fractional radiofrequency in the treatment of vulvar lichen sclerosus: a case report

O líquen escleroso vulvar (LEV) é uma doença dermatológica crônica de etiologia incerta, caracterizada por prurido intenso e atrofia progressiva. O corticosteroide tópico de longo prazo é o tratamento de primeira linha para LEV. No entanto, esse tratamento requer a colaboração da paciente, está associado a efeitos colaterais adversos e algumas pacientes não respondem aos corticosteroides. O tratamento com tecnologias térmicas e fototérmicas tem sido estudado como terapia alternativa ou complementar para melhorar os sintomas de LEV e o trofismo cutâneo. A radiofrequência fracionada microablativa é usada em dermatologia para melhorar o trofismo tecidual. Também tem sido usada em pacientes ginecológicas para tratar a atrofia vulvovaginal, estimulando a neocolagênese dérmica e a neoelastogênese. Apresentamos o caso de uma mulher de 39 anos com LEV refratária que foi tratada com aplicações locais de radiofrequência fracionada microablativa. Ela apresentou melhora satisfatória dos sintomas e do trofismo vulvar em longo prazo, sem necessidade do uso de corticosteroides.(AU)

Vulvar lichen sclerosus (VLS) is a chronic dermatological disease of unclear etiology characterized by severe itching and progressive atrophy. Long-term topical corticosteroid is the first-line treatment for VLS. However, this treatment requires patient compliance, is associated with adverse side effects, and some patients do not respond to corticosteroids. Treatment with thermal and photothermal technologies have been studied as alternative or complementary therapies to improve VLS symptoms and skin trophism. Microablative fractional radiofrequency (MFR) is used in dermatology to improve tissue trophism. It has also been used in gynecological patients to treat vulvovaginal atrophy by stimulating dermal neocollagenesis and neoelastinogenesis. We present the case of a 39-year-old woman with refractory VLS who was treated with local applications of microablative fractional radiofrequency. She had satisfactory, long-term, improvement of symptoms and vulvar trophism, and stopped using corticosteroids.(AU)

UV-A1 phototherapy vs clobetasol propionate, 0.05%, in the treatment of vulvar lichen sclerosus: a randomized clinical trial.

IMPORTANCE: Topical corticosteroids are the current first-line therapy for vulvar lichen sclerosus (VLS). UV-A1 phototherapy may be a promising alternative treatment option, but controlled studies are lacking. OBJECTIVE: To compare the efficacy of high-potent topical corticosteroids with UV-A1 phototherapy in the treatment of VLS. DESIGN, SETTING, AND PARTICIPANTS: A 2-arm randomized clinical trial was conducted at a university hospital dermatology department according to the intention-to-treat principle with last observation carried forward. The study population comprised 30 female patients with VLS. INTERVENTIONS: Treatment of VLS with clobetasol propionate, 0.05%, ointment applied once daily for 3 months or medium-dose UV-A1 (50 J/cm²) home-based phototherapy, performed 4 times weekly for 3 months. MAIN OUTCOMES AND MEASURES: Mean relative reduction of the total clinician's score (TCS) was considered the primary outcome measure. Secondary outcome measures included the reduction of pruritus and burning and/or pain according to a visual analog scale (VAS), a health-related quality of life score (Skindex-29), 20-MHz ultrasonography, and histopathological analysis before and after 3 months of therapy. RESULTS: Fifteen patients were randomized in each treatment arm, and 2 patients dropped out in both treatment arms. After therapy, both therapies resulted in a significant decrease in mean TCS (51.4% [95% CI, 39.7% to 63.0%] for clobetasol ointment [P < .001] and 35.6% [95% CI, 18.2% to 53.1%] for UV-A1 phototherapy [P = .006]). No significant difference was found between both treatments (P > .05). The Skindex-29 (mean difference [MD], 29.6 [95% CI, 7.9 to 51.2] [P = .009]) and the VAS score for pruritus (MD, 4.6 [95% CI, 1.5 to 7.7] [P = .005]) and burning and/or pain (MD, 4.2 [95% CI, 1.9 to 6.6] [P = .001]) significantly decreased after clobetasol treatment. After UV-A1 phototherapy, the VAS score for burning and/or pain (MD, 3.2 [95% CI, 0.7 to 5.7] [P = .01]) was also significantly reduced; however, there was no significant reduction in pruritus (MD, 2.1 [95% CI, 0.5 to 3.7] [P = .16]) and in the Skindex-29 score (MD, 4.9 [95% CI, -12.6 to 22.4] [P > .99]). A significant reduction of the corium thickness and a significant increase in dermal density in 20-MHz ultrasonography as well as significant histopathological reduction of the inflammatory infiltrate was observed after clobetasol treatment but not after UV-A1 phototherapy. CONCLUSIONS AND RELEVANCE: Although resulting in a significant clinical improvement, UV-A1 phototherapy was inferior to the current gold standard treatment with topical high-potent corticosteroids with respect to practicability, relief of itch, and improvement in quality of life. UV-A1 phototherapy may be considered a potential second-line treatment for VLS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01400022.

Altered global methylation and hydroxymethylation status in vulvar lichen sclerosus: further support for epigenetic mechanisms.

BACKGROUND: Epigenetics refers to functionally relevant changes in the genome other than those of DNA sequence that can lead to changes in gene expression or cellular phenotype. There is evidence that epigenetics is relevant in the pathogenesis of autoimmune diseases such as vulvar lichen sclerosus (VLS), as well as in cancer, including cutaneous squamous cell carcinoma, which is frequently associated with VLS. OBJECTIVES: To study the global methylation and hydroxymethylation status in healthy controls and VLS lesions before and after long-term ultraviolet (UV)A1 treatment. METHODS: We studied 12 controls and 10 patients with VLS who were treated with medium-dose UVA1 four times weekly for 3 months. Immunohistochemistry and mutation analyses (polymerase chain reaction) were performed for 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), isocitrate dehydrogenases (IDHs) and the ten-eleven translocation (TET)2 enzyme. RESULTS: After 3 months of treatment, 5mC was significantly increased in VLS compared with baseline and controls. However, compared with controls 5hmC levels were significantly reduced in baseline VLS, but normalized after UVA1 treatment. Compared with controls, IDH1 expression was significantly higher in both treated and baseline VLS. By contrast, IDH2 levels were significantly reduced in baseline VLS compared with controls and UVA1-treated VLS. However, gene sequencing of the IDH1, IDH2 and TET2 genes did not reveal evidence of mutations. CONCLUSIONS: VLS is associated with altered expression of IDH enzymes and aberrant hydroxymethylation, indicating an epigenetic background for the pathogenesis of VLS. UVA1 phototherapy may cause normalization of 5hmC patterns, but also global DNA hypermethylation in VLS lesions, raising concerns with respect to an increased risk of photocarcinogenesis.