Low-level laser therapy: an efficient supplement to treatments of vulvar Lichen sclerosus to improve quality of life.

BACKGROUND: Lichen sclerosus (LS) is a chronic, inflammatory disease of the genital and extra genital skin, causing pruritus, soreness, pain and dyspareunia. The aim of this study was to investigate whether Low Level Laser Therapy (LLLT) can improve the quality of life in women with Lichen sclerosus (LS) and insufficient topical treatment. METHODS: In a descriptive prospective observational study conducted between 02.01.2016 and 08.01.2018, we included 100 women with LS with insufficient topical treatment because of poor response of symptoms. All participants received ten LLLT treatments (808 nm and 500 mW) over a period of 8 weeks. The first four treatments were planned as two treatments per week. The remaining six treatments were planned as once a week. A Danish health-related quality of life tool (HRQoL test) monitored the effect. RESULTS: A total of 94 patients completed the study, median age of 62 [InterQuartile Range 53-69]. There was a statistically significant improvement in seven of the eight domains of the HRQoL test after ten LLLT. We found the results of DoloTest to be statistically significant in all of the groups except for smoking (p < 0.094). CONCLUSIONS: LLLT treatment can improve the quality of life in women with LS.

Lichen sclerosus is a chronic, inflammatory disease of the genital and extra genital skin, causing pruritus, soreness, pain and dyspareunia. This study aimed to investigate whether Low Level Laser Therapy can improve the quality of life in women with Lichen sclerosus and insufficient topical treatment. The study proposed a supplemental therapy to insufficient topical treatment in patients with Lichen sclerosus. This study indicated that Low Level Laser Therapy treatment can improve the quality of life in women with Lichen sclerosus.

LASER treatment in gynaecology -A randomized controlled trial in women with symptomatic lichen sclerosus.

OBJECTIVE: Aim of our study was to evaluate the therapeutic effect of laser treatment in vulvar lichen sclerosus, mainly the reduction of existing symptoms as itching, burning and pain. We asked about the different outcome by using different application doses. STUDY DESIGN: We conducted a prospective randomized double-blind dose-controlled trial in our dysplasia unit specializing vulvar disorders. 67patients with active LS were included. LS was confirmed by biopsy or by the validated CSS (clinical scoring system of vulvar LS). Computer generated randomization resulted in two groups, each group received a different application dose.(LDG- low dose group, NDG- normal dose group) During the study period of 18 weeks all participants received three laser applications in three subsequent sessions of three weeks. Two follow-ups six and twelve weeks after the first application was performed. At every visit, the participants filled in the VAS (visual analogue scale) for recording the actual vulvar symptoms as itching burning or pain on a range from 0 to 10. RESULTS: Before treatment the mean VAS-Score was 4.3 (STD ± 2.4) in the NDG and 5.1(±2.6) in the LDG. After 18 weeks, the mean reduction was -2.4 (±2.3) for NDG and -2.7 (±2.8) for LDG. Four patients (two of each group) reported more pain after than before treatment. Both groups show significant lower VAS-Scores 18 weeks after the treatment than before therapy (p < 0.0001). The reduction of symptoms after 18 weeks between NDG and LDG was not significant (p = 0.6244). CONCLUSION: Laser treatment with the microablative CO2 laser leads to a significant improvement for symptoms of LS. A higher dosage of laser radiation shows no benefit concerning the symptoms. We have not observed any serious adverse events during this study.

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)

Therapeutic comparison between treatments for Vulvar Lichen Sclerosus: study protocol of a randomized prospective and controlled trial.

BACKGROUND: 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 photobiomodulation (PBM) 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 compare the effects of PDT, PBM, and topical corticosteroid in VLS evaluating clinical, histological, immunohistochemical and spectroscopic responses. METHODS: The study is prospective, randomized and controlled, in a population of 60 women with histological diagnoses of VLS. There will be 3 treatments groups: PDT, PBM and topical corticosteroid (control group), where will be allocated by randomization 20 patients in each one. The clinical course will be monitored by measuring local temperature, itching, atrophy, and the area of the lesion. Histologically, the slides will be classified and will have the ordering of collagen fibers quantified. Immunohistochemical analysis will be done using the markers IFN-γ, TGF-ß, 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 make associations between different responses. The study is an open-label for patients with active symptomatic disease with a period of 1 year follow-up to determine the rate of recurrence in each groups. DISCUSSION: The immunological effects of PDT and PBM are described by several authors in inflammatory skin diseases, stimulating the production and organization of the associated collagen. Thus, it is reasonable to determine the efficacy and safety of these new treatments in VLS, in comparison to the control group, analyzing the recurrence time, the impact on the optical properties of the skin, and the benefit to patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02416531 .

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.

[Laser therapy of dystrophic diseases of the vulva]. / Lazernaia terapiia distroficheskikh protsessov vu'lvy.

The paper presents data of clinical and laboratory investigations performed in patients with vulvar leukoplakia or kraurosis before and after the helium-neon laser therapy. The impairment of adrenal performance (related to glucocorticoid, androgenic or mineralocorticoid functions) has been identified in the examinees. Employment of the laser therapy has normalized the impaired functions and beneficially affected local dystrophic processes in vulvar tissues. Local application of aerosol corticoid agents prolongs the response to the therapy.