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Original Investigation |

UV-A1 Phototherapy vs Clobetasol Propionate, 0.05%, in the Treatment of Vulvar Lichen Sclerosus A Randomized Clinical Trial FREE

Sarah Terras, MD1; Thilo Gambichler, MD1; Rose K. C. Moritz, MD1; Markus Stücker, MD1; Alexander Kreuter, MD1
[+] Author Affiliations
1Department of Dermatology, Venereology, and Allergology, Ruhr-University Bochum, Bochum, Germany
JAMA Dermatol. 2014;150(6):621-627. doi:10.1001/jamadermatol.2013.7733.
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Published online

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

Figures in this Article

Lichen sclerosus (LS) is a connective tissue disease that predominantly affects the anogenital area. An autoimmune background is likely, given the high association with other autoimmune diseases and the presence of highly specific antibodies targeting extracellular matrix protein-1.1,2 Although vulvar lichen sclerosus (VLS) is relatively common and may have substantial psychological and emotional consequences, to date, only a few therapies have been evaluated in controlled studies. The “gold standard” of treatment for VLS consists of high-potent topical corticosteroids, such as clobetasol dipropionate applied once daily for 12 weeks.3 Other therapeutic options include topical calcineurin inhibitors or, in severe and recalcitrant disease, surgery or cryotherapy.35 UV-A1 phototherapy has been reported to be effective in the treatment of several sclerotic skin diseases including localized scleroderma and extragenital LS.611 UV-A1 irradiation increases collagenase activity and suppresses collagen synthesis, resulting in a softening of former sclerotic skin lesions.7 Moreover, UV-A irradiation has strong melanogenic properties, inducing a repigmentation of the hypopigmented lesions in LS.7,9 Currently, only few data are available on UV-A1 phototherapy in VLS. The present controlled study was therefore initiated to compare the efficacy of UV-A1 phototherapy with topical high-potent corticosteroids, the current gold standard for VLS.

Study Design, Setting, and Participants

The study protocol was approved by the ethics review board of Ruhr University Bochum (No. 3435-09) and registered at ClinicalTrials.gov (NCT01400022). All patients gave their written informed consent to participate in the study. This is an open 2-arm randomized clinical trial performed at a university hospital in Germany investigating UV-A1 phototherapy vs standard treatment (clobetasol propionate, 0.05%, ointment) in patients with VLS. From August 1, 2010, to January 31, 2012, 30 female patients older than 18 years were recruited from the outpatient clinic for connective tissue diseases of the Department of Dermatology, Venereology, and Allergology at Ruhr-University Bochum. Inclusion criteria were (1) active, histopathologically confirmed LS causing symptoms such as itch, burning, or pain present for less than 2 years and (2) age 18 years or older at study inclusion. If patients were treated with topical corticosteroids before initiation of the study, a washout period of 4 weeks was required. Exclusion criteria were (1) age younger than 18 years at study inclusion; (2) history of photoallergic reactions; (3) known genodermatoses with sensibility to UV light; (4) history of skin cancer; (5) notable sun exposure 3 months before inclusion; or (6) phototherapy in the last 4 weeks before study inclusion or planned phototherapy in the next 9 months.

Randomization and Allocation to Treatment

The randomization was performed using a random allocation software as described previously.12 A total of 51 patients with genital lichen sclerosus were assessed for eligibility in this study. Among those, 21 patients were excluded because they did not meet the inclusion criteria or refused to participate. Thirty patients were randomized, 15 to each of the 2 treatment arms (UV-A1 phototherapy or topical high-potent corticosteroid). Of these 30 patients, 26 were included in the final analysis (Figure 1).

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Figure 1.
Flow Diagram of the Study
Graphic Jump Location
Primary Outcome Measures

Clinical examinations during the treatment and follow-up period were performed at day 0 (T0 or baseline), after 1 month (T1), after 2 months (T2), after 3 months (T3, end of therapy), and at follow-up 3 months after the end of therapy. Photographic documentation was performed at each visit. Lesional skin biopsies were performed at baseline and after 3 months of therapy. Because there is currently no validated clinical score available for VLS, clinical assessment of efficacy was performed using our own score, the total clinician’s score (TCS). In this score, hypopigmentation, sclerosis, atrophy, hyperkeratosis, erosions, edema, and erythema are each assigned a value from 0 to 3, with 0 indicating “absent”; 1, “slight”; 2, “moderate”; and 3, “severe.” The total of these values was considered the TCS, with a maximum score of 21. The primary outcome measure was the mean reduction in TCS at T3 (after 3 months of treatment). The observer determining the TCS could not be blinded because of lesional tanning after UV-A1 phototherapy.

Secondary Outcome Measures

Secondary outcome measures were patients’ scores evaluating pruritus and burning and/or pain and the Skindex-29 score at T3. Pruritus and burning and/or pain were evaluated at each clinical visit by means of a visual analog scale (VAS) score on a 10-point scale, with 0 indicating “no sensation” and 10, “maximum intensity of sensation.” The Skindex-29 is a validated questionnaire in the German language to measure the health-related quality of life.13 Additional secondary outcome measures included the increase of dermal density and reduction of dermal thickness (corium thickness in micrometers), as measured by 20-MHz sonography (DUB 20; taberna pro medicum), as well as the reduction of lesional lymphocytic infiltrates in hematoxylin-eosin–stained samples as measured semiquantitatively (0, no lymphocytes; 1, slight lymphocytic infiltrate; 2, moderate lymphocytic infiltrate; and 3, strong lymphocytic infiltrate) before and after treatment. The examination of the ultrasonographic images and histological specimens was performed by a blinded observer (M.S.).

Interventions

UV-A1 phototherapy was performed with a specially designed Sellas irradiation unit (System Dr Sellmeier) emitting wavelengths mainly from 340 to 400 nm. All patients received a portable irradiation unit to take home and performed the radiation therapy in a comfortable environment at a suitable time for the patients. An example of this UV-A1 irradiation device (the so-called vulva lamp) is shown in Figure 2. Irradiation intensity at body distance was 24 mW/cm2. The distance between the irradiation unit and the irradiated genital area was approximately 25 cm. The UV-A1 doses were intensified during the first 5 treatment sessions. In the first session, a dose of 10 J/cm2 was used, resulting in a irradiation time of approximately 5 minutes. In the following 4 sessions, the radiation energy was successively increased to 20 J/cm2 (irradiation time approximately 10 minutes), 30 J/cm2 (irradiation time approximately 16 minutes), 40 J/cm2 (irradiation time approximately 22 minutes), and 50 J/cm2 (irradiation time approximately 27 minutes), respectively. From the fifth session until the end of the treatment period, 50-J/cm2 UV-A1 was applied, resulting in a medium-dose UV-A1 phototherapy.14 UV-A1 phototherapy was administered 4 times per week for a total of 12 weeks, resulting in 48 irradiations in total. Additional therapy was restricted to the use of emollients. Emollients were not applied shortly (within 60 minutes) before phototherapy. The comparative intervention was the use of topical high-potent corticosteroids. Clobetasol propionate, 0.05%, in white vaseline was applied once daily, preferably before bedtime, for 12 weeks.

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Figure 2.
Portable UV-A1 Sellas Irradiation Unit (System Dr Sellmeier) Used in This Study

All patients randomized to UV-A1 phototherapy received a portable irradiation unit to take home in order to perform the radiation therapy in a comfortable environment.

Graphic Jump Location
Sample Size Calculation

The null hypothesis was based on the assumption that there is no significant difference of efficacy between UV-A1 phototherapy and clobetasol propionate, 0.05%, ointment in the treatment of VLS. On the basis of an expected mean difference (MD) of 6.1 points in TCS (difference of mean relative TCS reduction of 33%) and a statistical power of 80% at the 5% α level, at least 26 patients were needed in this study, excluding a dropout rate of approximately 20%.15

Statistical Analysis

Data analysis was performed using the statistical package MedCalc Software. The primary outcome was analyzed on an intention-to-treat basis using baseline TCSs and last available TCSs of all randomized patients.16 Analysis of data distribution was assessed by the D’Agostino-Peason test. Means, standard errors, and 95% confidence intervals were calculated. Repeated measures analysis of variance including Bonferroni correction was used to detect significant differences of parameters assessed at baseline, at T3, and at follow-up.17 Primary and secondary outcome measures evaluated at T3 were analyzed using the F test, followed by the independent 2-sided t test (assuming equal variances) or Welch test (assuming unequal variances). Statistical significance was set at the 5% α level (2-sided).

A total of 30 patients were enrolled in the study, 15 in each of the 2 study arms. The median age was 60.3 years (range, 20-81 years). A flow diagram of patient treatment, including reasons for discontinuation, is shown in Figure 1. Of the 30 patients, 1 patient was excluded because the clinical diagnosis of VLS could not be histopathologically confirmed. One patient was excluded from the study because during the treatment phase, a systemic immunosuppressive therapy was initiated to treat another autoimmune disease. One patient dropped out of the study because of an acute bacterial skin infection in the genital area before initiation of the UV-A1 irradiation sessions. One patient was lost to follow-up. At baseline, both groups did not show any differences in any of the primary and secondary outcome measures (P > .50).

Primary Outcome

A summary of the results is detailed in the Table. After 3 months of treatment, 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]) (Figure 3). No significant difference in the relative reduction of the TCS was found between both treatments (P > .05; MD, −15.7% [95% CI, −35.2% to 3.7%]). Representative clinical pictures before and after both therapies are depicted in Figure 4.

Table Graphic Jump LocationTable.  Summary of the Results of the Primary and Secondary Outcome Measures Before and After Treatment With UV-A1 Phototherapy and Topical High-Potent Corticosteroids
Place holder to copy figure label and caption
Figure 3.
Outcome Measures Used in This Study

A, Total clinician’s score (TCS) by visit. B, Mean Skindex-29 scores by visit. C, Mean visual analog (VAS) scores for burning and/or pain by visit. D, Mean VAS scores for itching by visit. T0 indicates baseline; T1, after 1 month of therapy; T2, after 2 months of therapy; T3, at end of therapy; and F3, 3 months after the end of therapy. Error bars indicate the standard error of the mean.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Treatment of Vulvar Lichen Sclerosus With Topical Clobetasol Propionate, 0.05%, Ointment and UV-A1 Phototherapy

A, Extensive genital lichen sclerosus. B, Significant clinical improvement with complete clearance of all erosions and fissures following topical treatment with clobetasol ointment. C, Widespread genital lichen sclerosus. D, Marked clinical improvement with clearance of perilesional erythema and reduction of hyperkeratoses and erosions. The clinical pictures are representative of the outcome of the study, showing a significant improvement following therapy with clobetasol ointment (A and B) and UV-A1 phototherapy (C and D).

Graphic Jump Location
Secondary Outcome

After treatment with clobetasol ointment, the VAS score significantly decreased 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]), and also the Skindex-29 score significantly decreased (MD, 29.6 [95% CI, 7.9 to 51.2] [P = .009]). After UV-A1 phototherapy, the VAS score for burning and/or pain (MD, 3.2 [95% CI, 0.7 to 5.7] [P = .01]) reduced significantly; however, there was no significant reduction in pruritus (MD, 2.1 [95% CI, 0.5 to 3.7] [P = .16]) and Skindex-29 score (MD, 4.9 [95% CI, −12.6 to 22.4] [P > .99]; Figure 3). Three months after the end of the therapy, all primary and secondary outcome points returned to the baseline level, before initiation of the treatment.

The clinical improvement seen at T3 was confirmed by 20-MHz ultrasonography. Corium thickness was relatively high before therapy and significantly decreased into normal ranges after topical clobetasol therapy (MD, —786 [95% CI, —235 to 338] [P = .003]). There was also a statistically significant increase of dermal density after clobetasol treatment (MD, 15.0 [95% CI, 8.0 to 22.0] [P < .001]), correlating with a reduction of the edema. After treatment with UV-A1 phototherapy, a reduction of corium thickness and increase in dermal density could also be observed; however, it did not reach statistical significance (MD, −282 [95% CI, −1036 to 473] [P = .41], and MD, −0.1 [95% CI, −6.9 to 6.7] [P = .97], respectively).

In the histopathological evaluation of the lesional skin biopsy specimens before and after therapy, a significant reduction of lymphocytic infiltrates after topical corticosteroid therapy was observed (MD, 0.9 [95% CI, 0.2 to 1.7] [P = .02]), whereas after UV-A1 phototherapy, no significant reduction of lymphocytic infiltrates was seen (MD, 0.2 [−0.4 to 0.7] [P = .51]).

Tolerability

The predominantly reported short-term adverse effects of UV-A1 phototherapy include erythema, pruritus, xerosis cutis, and tanning.8 Patients treated with UV-A1 phototherapy in this study initially reported an increase of pruritus. We advised our patients to apply white vaseline directly (within 30 minutes) after the radiation session to prevent dehydration of the skin, which led to a marked subjective improvement. In total, there was only a slight, nonsignificant reduction of pruritus (P = .16) after 3 months of treatment with UV-A1 phototherapy. After UV-A1 treatment, a marked hyperpigmentation in the anogenital area was seen in all cases. However, this was not considered as a disturbing adverse effect by the patients. No erythema or sunburn following UV-A1 phototherapy was reported.

According to the British Association of Dermatologists’ guidelines for the management of LS, the first-line treatment for VLS is the use of topical high-potent corticosteroids.18 In this context, clobetasol propionate, 0.05%, cream is currently considered the gold standard, leading to a substantial decrease of inflammation and clinical symptoms.3 After therapy with high-potent corticosteroids, approximately 60% of patients experience a complete remission of their symptoms, resulting in a resolution of ecchymoses, fissures, erosions, and hyperkeratoses.19,20 Thus, the use of clobetasol propionate is safe and effective in VLS, and there is yet no evidence of notable steroid-related damage following its appropriate use.18 However, skin atrophy, scarring, and hypopigmentation are irreversible in VLS.

UV-A1 phototherapy was previously shown to be effective in a variety of sclerotic skin diseases including localized scleroderma, systemic sclerosis, eosinophilic fasciitis, necrobiosis lipoidica, chronic sclerodermic graft-vs-host disease, and scleroderma adultorum.6,7,2125 UV-A1 phototherapy is generally divided into the following 3 dosages: low-dose UV-A1 (10-20 J/cm2), medium-dose UV-A1 (20-70 J/cm2), and high-dose UV-A1 (70-130 J/cm2).14 The treatment of extragenital LS with low-dose UV-A1 was first reported by our study group in 2001.10,11 In a small prospective uncontrolled trial,7 we later treated 10 patients with extragenital LS using low-dose UV-A1 phototherapy (20 J/cm2; cumulative dose of 800 J/cm2). Low-dose UV-A1 phototherapy resulted in a marked reduction of the clinical score and a statistically significant decrease of ultrasonographically measured skin thickness as well as a statistically significant increase of dermal density. Most patients reported a remarkable softening and repigmentation of the affected skin.7 Rombold et al26 later confirmed the good response of extragenital LS lesions using medium-dose UV-A1 phototherapy.

The exact mechanism of action of UV-A1 phototherapy in sclerotic skin diseases is not fully understood.27 In general, UV-A1 phototherapy influences both lesional fibroblasts and inflammatory cells. UV-A1 irradiation leads to an increased collagenase production in fibroblasts with up-regulation of metalloproteinases, partly due to the increased production of hydrogen peroxide, as well as an up-regulation of α-melanocyte–stimulating hormone.28,29 UV-A1 phototherapy induces a down-regulation of interleukins 6 and 8, both cytokines that play a pivotal role in collagen metabolism.30 Moreover, UV-A1 phototherapy influences the expression of SMAD-7, a major inhibitory regulator of the key-fibrogenic cytokine tissue growth factor-β, and increases the expression of interferon-γ, an antifibrotic cytokine.3133

To our knowledge, UV-A1 phototherapy in VLS has only been reported once in a small case series of patients.34 In this study, 7 women with severe and progressive VLS not responding to ultrapotent topical corticosteroids were included. UV-A1 therapy led to a moderate improvement in 3 and to a minimal improvement in 2 of the 7 patients.

The present study was the first randomized clinical trial to assess the effectiveness and safety of UV-A1 phototherapy in the treatment of VLS. Moreover, it is one of the few controlled studies that have so far been conducted in LS. In general, we could confirm the high efficacy of clobetasol propionate, 0.05%, in VLS. On the basis of our results and those of others, topical corticosteroids should be considered the first-line approach for VLS.3,18 However, we also demonstrated that UV-A1 phototherapy is an effective and well-tolerated treatment for VLS as well. Although in this study UV-A1 phototherapy was not as effective as the gold standard therapy with high-potent corticosteroids, it resulted in a significant clinical improvement and reduction of burning and/or pain. Moreover, UV-A1 phototherapy was well tolerated, easy to deliver, and could be performed by the patient herself at an appropriate time and in a comfortable environment. Therefore, UV-A1 phototherapy can be considered as an alternative therapeutic option in the treatment of genital LS.

During follow-up, the primary and secondary end points in both therapies returned to the level before initiation of the therapy. This means that both treatments only transiently suppress the activity of disease. It also underlines the necessity to develop a long-term concept for treatment of VLS. Recently, it was published that once VLS has been stabilized with topical corticosteroids, the twice-weekly proactive application of mometasone furoate, 0.1%, ointment over 56 weeks was an effective and safe therapy option in maintaining VLS remission and in preventing the occurrence of relapse.35

Patients with VLS have an increased risk of developing squamous cell carcinoma (SCC). Although the overall risk for malignant transformation of VLS is low (<5% of all VLS cases), they should be regularly monitored for malignant transformation.18,36 UV irradiation has a major role in the pathogenesis of SCC because of its capacity to induce immunosuppression and DNA damage. However, in contrast to UV-B, UV-A1 irradiation in cell cultures neither induced measurable DNA damage nor induced cell death in the doses up to 15 J/cm2.37 Other studies, however, showed that the basal layer is more vulnerable to the carcinogenic effects of UV-A1 than would be predicted by mouse models.38 Sage et al39 recently discussed in detail the controversial data on the UV-A–induced mutational events obtained for various types of eukaryotic cells, including human skin cells. In the present study, no cases of SCC or precursor lesions occurred, but the follow-up period was very short. Accordingly, long-term follow-up has to be performed in these patients to assess the risk of SCC development following UV-A1 phototherapy in VLS. In accordance with Beattie et al,34 we think that UV-A1 phototherapy may have an acceptable risk-benefit ratio for the treatment of VLS. Nevertheless, more research is needed in the field of UV-A1–induced immunosuppression and carcinogenesis.39,40

The results reported herein should be viewed in light of the limitations of the study. The sample size calculation was based on a large effect size (mean difference between treatments). The 95% confidence interval of differences regarding the relative reduction of TCS was wide, indicating that the sample size was too small to detect smaller but still clinically meaningful differences between the 2 treatments assessed. Moreover, the observer determining the clinical response could not be blinded owing to the marked tanning after UV-A1 phototherapy, and this might have influenced the outcome of the study. Finally, the follow-up was relatively short given that chronic UV damage takes a relatively long period. These effects will be evaluated in a future long-term follow-up study.

Both topical high-potent corticosteroids and UV-A1 phototherapy significantly improved VLS. However, UV-A1 was inferior with respect to practicability, relief of itch, and improvement in quality of life. Therefore, high-potent corticosteroids remain the first-line treatment for VLS. Nevertheless, UV-A1 phototherapy may be considered an alternative second-line treatment option.

Corresponding Author: Alexander Kreuter, MD, Department of Dermatology, Venereology, and Allergology, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany (a.kreuter@derma.de).

Accepted for Publication: August 22, 2013.

Published Online: April 2, 2014. doi:10.1001/jamadermatol.2013.7733.

Author Contributions: Drs Terras and Kreuter had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Terras, Gambichler, Moritz, Kreuter.

Acquisition of data: Terras, Stücker, Kreuter.

Analysis and interpretation of data: Terras, Gambichler, Stücker, Kreuter.

Drafting of the manuscript: Terras, Kreuter.

Critical revision of the manuscript for important intellectual content: Terras, Gambichler, Moritz, Stücker, Kreuter.

Statistical analysis: Gambichler.

Administrative, technical, and material support: Terras, Moritz, Stücker.

Study supervision: Gambichler, Kreuter.

Conflict of Interest Disclosures: None reported.

Funding/Support: FoRUM (Forschungsförderung Ruhr University Bochum Medizinische Fakultat, project F615-2008) funded this work.

Role of the Sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Kim Allrich and Marina Skrygan, PhD, Department of Dermatology, Ruhr-University Bochum, provided technical assistance. They did not receive compensation for their contributions.

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Weber  HO, Schaller  M, Metzler  G, Röcken  M, Berneburg  M.  Eosinophilic fasciitis and combined UVA1—retinoid—corticosteroid treatment. Acta Derm Venereol. 2008;88(3):304-306.
PubMed
Beattie  PE, Dawe  RS, Ibbotson  SH, Ferguson  J.  UVA1 phototherapy for treatment of necrobiosis lipoidica. Clin Exp Dermatol. 2006;31(2):235-238.
PubMed   |  Link to Article
Grundmann-Kollmann  M, Behrens  S, Gruss  C, Gottlöber  P, Peter  RU, Kerscher  M.  Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy. J Am Acad Dermatol. 2000;42(1, pt 1):134-136.
PubMed   |  Link to Article
Ständer  H, Schiller  M, Schwarz  T.  UVA1 therapy for sclerodermic graft-versus-host disease of the skin. J Am Acad Dermatol. 2002;46(5):799-800.
PubMed   |  Link to Article
Eberlein-König  B, Vogel  M, Katzer  K,  et al.  Successful UVA1 phototherapy in a patient with scleredema adultorum. J Eur Acad Dermatol Venereol. 2005;19(2):203-204.
PubMed   |  Link to Article
Rombold  S, Lobisch  K, Katzer  K, Grazziotin  TC, Ring  J, Eberlein  B.  Efficacy of UVA1 phototherapy in 230 patients with various skin diseases. Photodermatol Photoimmunol Photomed. 2008;24(1):19-23.
PubMed   |  Link to Article
Kreuter  A, Breuckmann  F, Uhle  A,  et al.  Low-dose UVA1 phototherapy in systemic sclerosis. J Am Acad Dermatol. 2004;50(5):740-747.
PubMed   |  Link to Article
Brenneisen  P, Briviba  K, Wlaschek  M, Wenk  J, Scharffetter-Kochanek  K.  Hydrogen peroxide (H2O2) increases the steady-state mRNA levels of collagenase/MMP-1 in human dermal fibroblasts. Free Radic Biol Med. 1997;22(3):515-524.
PubMed   |  Link to Article
Kiss  M, Wlaschek  M, Brenneisen  P,  et al.  Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts. Biol Chem Hoppe Seyler. 1995;376(7):425-430.
PubMed   |  Link to Article
Kreuter  A, Hyun  J, Skrygan  M,  et al.  Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma. Br J Dermatol. 2006;155(3):600-607.
PubMed   |  Link to Article
Edwards  DR, Murphy  G, Reynolds  JJ,  et al.  Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 1987;6(7):1899-1904.
PubMed
Gambichler  T, Tomi  NS, Skrygan  M, Altmeyer  P, Kreuter  A.  Alterations of TGF-beta/Smad mRNA expression in atopic dermatitis following narrow-band ultraviolet B phototherapy: results of a pilot study. J Dermatol Sci. 2006;44(1):56-58.
PubMed   |  Link to Article
El-Mofty  M, Mostafa  W, Esmat  S,  et al.  Suggested mechanisms of action of UVA phototherapy in morphea: a molecular study. Photodermatol Photoimmunol Photomed. 2004;20(2):93-100.
PubMed   |  Link to Article
Beattie  PE, Dawe  RS, Ferguson  J, Ibbotson  SH.  UVA1 phototherapy for genital lichen sclerosus. Clin Exp Dermatol. 2006;31(3):343-347.
PubMed   |  Link to Article
Virgili  A, Minghetti  S, Borghi  A, Corazza  M.  Proactive maintenance therapy with a topical corticosteroid for vulvar lichen sclerosus: preliminary results of a randomized study. Br J Dermatol. 2013;168(6):1316-1324.
PubMed   |  Link to Article
Abramov  Y, Elchalal  U, Abramov  D, Goldfarb  A, Schenker  JG.  Surgical treatment of vulvar lichen sclerosus: a review. Obstet Gynecol Surv. 1996;51(3):193-199.
PubMed   |  Link to Article
Lisby  S, Gniadecki  R, Wulf  HC.  UV-induced DNA damage in human keratinocytes. Exp Dermatol. 2005;14(5):349-355.
PubMed   |  Link to Article
Tewari  A, Grage  MM, Harrison  GI, Sarkany  R, Young  AR.  UVA1 is skin deep. Photochem Photobiol Sci. 2013;12(1):95-103.
PubMed   |  Link to Article
Sage  E, Girard  PM, Francesconi  S.  Unravelling UVA-induced mutagenesis. Photochem Photobiol Sci. 2012;11(1):74-80.
PubMed   |  Link to Article
Schwarz  T, Schwarz  A.  Molecular mechanisms of ultraviolet radiation-induced immunosuppression. Eur J Cell Biol. 2011;90(6-7):560-564.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Flow Diagram of the Study
Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Portable UV-A1 Sellas Irradiation Unit (System Dr Sellmeier) Used in This Study

All patients randomized to UV-A1 phototherapy received a portable irradiation unit to take home in order to perform the radiation therapy in a comfortable environment.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Outcome Measures Used in This Study

A, Total clinician’s score (TCS) by visit. B, Mean Skindex-29 scores by visit. C, Mean visual analog (VAS) scores for burning and/or pain by visit. D, Mean VAS scores for itching by visit. T0 indicates baseline; T1, after 1 month of therapy; T2, after 2 months of therapy; T3, at end of therapy; and F3, 3 months after the end of therapy. Error bars indicate the standard error of the mean.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Treatment of Vulvar Lichen Sclerosus With Topical Clobetasol Propionate, 0.05%, Ointment and UV-A1 Phototherapy

A, Extensive genital lichen sclerosus. B, Significant clinical improvement with complete clearance of all erosions and fissures following topical treatment with clobetasol ointment. C, Widespread genital lichen sclerosus. D, Marked clinical improvement with clearance of perilesional erythema and reduction of hyperkeratoses and erosions. The clinical pictures are representative of the outcome of the study, showing a significant improvement following therapy with clobetasol ointment (A and B) and UV-A1 phototherapy (C and D).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Summary of the Results of the Primary and Secondary Outcome Measures Before and After Treatment With UV-A1 Phototherapy and Topical High-Potent Corticosteroids

References

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PubMed   |  Link to Article
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PubMed   |  Link to Article
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PubMed   |  Link to Article
Kreuter  A, von Kobyletzki  G, Happe  M,  et al.  Ultraviolet-A1 (UVA1) phototherapy in lichen sclerosus et atrophicus [in German]. Hautarzt. 2001;52(10):878-881.
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PubMed   |  Link to Article
Gambichler  T, Terras  S, Kreuter  A.  Treatment regimens, protocols, dosage, and indications for UVA1 phototherapy: facts and controversies. Clin Dermatol. 2013;31(4):438-454.
PubMed   |  Link to Article
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Cooper  SM, Gao  XH, Powell  JJ, Wojnarowska  F.  Does treatment of vulvar lichen sclerosus influence its prognosis? Arch Dermatol. 2004;140(6):702-706.
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Renaud-Vilmer  C, Cavelier-Balloy  B, Porcher  R, Dubertret  L.  Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol. 2004;140(6):709-712.
PubMed
Weber  HO, Schaller  M, Metzler  G, Röcken  M, Berneburg  M.  Eosinophilic fasciitis and combined UVA1—retinoid—corticosteroid treatment. Acta Derm Venereol. 2008;88(3):304-306.
PubMed
Beattie  PE, Dawe  RS, Ibbotson  SH, Ferguson  J.  UVA1 phototherapy for treatment of necrobiosis lipoidica. Clin Exp Dermatol. 2006;31(2):235-238.
PubMed   |  Link to Article
Grundmann-Kollmann  M, Behrens  S, Gruss  C, Gottlöber  P, Peter  RU, Kerscher  M.  Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy. J Am Acad Dermatol. 2000;42(1, pt 1):134-136.
PubMed   |  Link to Article
Ständer  H, Schiller  M, Schwarz  T.  UVA1 therapy for sclerodermic graft-versus-host disease of the skin. J Am Acad Dermatol. 2002;46(5):799-800.
PubMed   |  Link to Article
Eberlein-König  B, Vogel  M, Katzer  K,  et al.  Successful UVA1 phototherapy in a patient with scleredema adultorum. J Eur Acad Dermatol Venereol. 2005;19(2):203-204.
PubMed   |  Link to Article
Rombold  S, Lobisch  K, Katzer  K, Grazziotin  TC, Ring  J, Eberlein  B.  Efficacy of UVA1 phototherapy in 230 patients with various skin diseases. Photodermatol Photoimmunol Photomed. 2008;24(1):19-23.
PubMed   |  Link to Article
Kreuter  A, Breuckmann  F, Uhle  A,  et al.  Low-dose UVA1 phototherapy in systemic sclerosis. J Am Acad Dermatol. 2004;50(5):740-747.
PubMed   |  Link to Article
Brenneisen  P, Briviba  K, Wlaschek  M, Wenk  J, Scharffetter-Kochanek  K.  Hydrogen peroxide (H2O2) increases the steady-state mRNA levels of collagenase/MMP-1 in human dermal fibroblasts. Free Radic Biol Med. 1997;22(3):515-524.
PubMed   |  Link to Article
Kiss  M, Wlaschek  M, Brenneisen  P,  et al.  Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts. Biol Chem Hoppe Seyler. 1995;376(7):425-430.
PubMed   |  Link to Article
Kreuter  A, Hyun  J, Skrygan  M,  et al.  Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma. Br J Dermatol. 2006;155(3):600-607.
PubMed   |  Link to Article
Edwards  DR, Murphy  G, Reynolds  JJ,  et al.  Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 1987;6(7):1899-1904.
PubMed
Gambichler  T, Tomi  NS, Skrygan  M, Altmeyer  P, Kreuter  A.  Alterations of TGF-beta/Smad mRNA expression in atopic dermatitis following narrow-band ultraviolet B phototherapy: results of a pilot study. J Dermatol Sci. 2006;44(1):56-58.
PubMed   |  Link to Article
El-Mofty  M, Mostafa  W, Esmat  S,  et al.  Suggested mechanisms of action of UVA phototherapy in morphea: a molecular study. Photodermatol Photoimmunol Photomed. 2004;20(2):93-100.
PubMed   |  Link to Article
Beattie  PE, Dawe  RS, Ferguson  J, Ibbotson  SH.  UVA1 phototherapy for genital lichen sclerosus. Clin Exp Dermatol. 2006;31(3):343-347.
PubMed   |  Link to Article
Virgili  A, Minghetti  S, Borghi  A, Corazza  M.  Proactive maintenance therapy with a topical corticosteroid for vulvar lichen sclerosus: preliminary results of a randomized study. Br J Dermatol. 2013;168(6):1316-1324.
PubMed   |  Link to Article
Abramov  Y, Elchalal  U, Abramov  D, Goldfarb  A, Schenker  JG.  Surgical treatment of vulvar lichen sclerosus: a review. Obstet Gynecol Surv. 1996;51(3):193-199.
PubMed   |  Link to Article
Lisby  S, Gniadecki  R, Wulf  HC.  UV-induced DNA damage in human keratinocytes. Exp Dermatol. 2005;14(5):349-355.
PubMed   |  Link to Article
Tewari  A, Grage  MM, Harrison  GI, Sarkany  R, Young  AR.  UVA1 is skin deep. Photochem Photobiol Sci. 2013;12(1):95-103.
PubMed   |  Link to Article
Sage  E, Girard  PM, Francesconi  S.  Unravelling UVA-induced mutagenesis. Photochem Photobiol Sci. 2012;11(1):74-80.
PubMed   |  Link to Article
Schwarz  T, Schwarz  A.  Molecular mechanisms of ultraviolet radiation-induced immunosuppression. Eur J Cell Biol. 2011;90(6-7):560-564.
PubMed   |  Link to Article

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