Clinical and laboratory characterization of patients with localized scleroderma and response to UVA-1 phototherapy: In vivo and in vitro skin models.

BACKGROUND/PURPOSE: Localized scleroderma (LS) is a rare disease leading to progressive hardening and induration of the skin and subcutaneous tissues. LS is responsive to UVA-1 phototherapy, though its exact mechanism of action dermal fibrosis is yet to be fully elucidated. We aimed to investigate the molecular changes induced by UVA-1 rays in human primary fibroblasts cultures. METHODS: A total of 16 LS patients were treated with medium-dose UVA-1 phototherapy. At baseline, during and after therapy, Localized Scleroderma Assessment Tool, Dermatology Life Quality Index and lesions' staging and mapping were performed along with high-frequency ultrasound (HFUS) examination for dermal thickness assessment. Gene expression analysis for 23 mRNA transcripts, in vitro UVA-1 irradiation and viability tests were realized on lesional fibroblasts' primary cultures, before and 3 months after therapy. RESULTS: The dermal thickness, the LoSCAT and the DLQI progressively decreased starting from the last phototherapy session up to the 6 and 9 month follow-ups (-57% and -60%, respectively). Molecular gene analysis (rt-PCR) revealed that UVA-1 phototherapy exerts multiple effects: the activation of specific anti-fibrotic pathways (e.g., overexpression of CTHRC1 and metalloproteases 1, 2, 7, 8, 9, 12, suppression of TIMP-1), the downregulation of peculiar pro-fibrotic pathways (e.g., downregulation of TGF-ß, TGF-ßrII, Grb2, SMAD 2/3, TNRSF12A, CTGF) through a significant overexpression of IL-1ß; the stabilization of collagen synthesis acting on genes COL1A1, COL3A1, COL8A1, COL10A1, COL12A1. CONCLUSION: UVA-1 phototherapy adds significant benefits in local tissue remodeling, rebalancing the alteration between pro-fibrotic and anti-fibrotic pathways; these changes can be well monitored by HFUS.

Biological effects of a new ultraviolet A1 prototype based on light-emitting diodes on the treatment of localized scleroderma.

Ultraviolet A1 (UVA1 ) phototherapy (spectral range 340-400 nm) is a well-established treatment option for various skin diseases such as localized scleroderma. Recent improvements of conventional UVA1 light sources (metal-halide or fluorescent lamps) have brought attention to a new light-emitting diode (LED) technology with remarkable advantages in handling and clinical routine. This study provides a preclinical histological and molecular evaluation of an LED-based UVA1 prototype with a narrower spectral range (360-400 nm) for treating localized scleroderma. Scleroderma mouse models and fibroblasts in vitro were exposed to LED-based UVA1 phototherapy or to irradiation with a commercially available metal-halide lamp emitting low-dose (20, 40 J/cm2 ), medium-dose (60 J/cm2 ) and high-dose (80, 100 J/cm2 ) UVA1 light. Both UVA1 light sources affected inflammatory genes (IL-1α and IL-6) and growth factors (TGFß-1 and TGFß-2). Increased collagen type 1 was reduced after UVA1 phototherapy. Matrix metalloproteinase-1 was more enhanced after a medium dose of LED-based UVA1 phototherapy than after conventional treatment. In vivo, dermal thickness and the amount of collagen were reduced after both treatment methods. Remarkably, myofibroblasts were more effectively reduced by a medium dose of LED-based UVA1 phototherapy. The study indicates that LED-based UVA1 phototherapy yields similar or even better results than conventional treatment. In terms of biosafety and patient comfort, LED-based UVA1 phototherapy offers clear advantages over conventional treatment because of the use of a narrower and less harmful UVA1 spectrum, less heat generation and shorter treatment times at the same irradiation intensity. Clinical studies are required to confirm these results in patients with localized scleroderma.

Clinical, histological and high-frequency ultrasonographic evaluation (50 MHz) of morphoea treated with ultraviolet A1 phototherapy.

BACKGROUND: There are few studies in the literature correlating the ultrasonographic findings, clinical scoring systems or histological findings in morphoea after ultraviolet (UV)A1 phototherapy. AIMS: To evaluate the quantitative and morphological aspects of high-frequency ultrasonography in the treatment of plaque morphoea in response to UVA1 phototherapy, and to correlate these with clinical and histological scores. METHODS: In total, 17 patients with morphoea were studied. Initially and at study end, high-frequency ultrasonography (50 MHz) was performed on the edge of a morphoea lesion treated with UVA1 phototherapy. A quantitative and qualitative analysis of dermal features was performed and compared with the features of healthy skin. Skin biopsy specimens were obtained from lesions analysed at the beginning and end of the study, assessing dermal sclerosis and dermal inflammatory infiltrate and their distribution. RESULTS: All affected skin showed a statistically significant increase in dermal thickness and hypoechogenicity, corresponding to a reduction in dermal density by ultrasonography compared with healthy skin. Morphological evaluation identified undulations of the dermis in 11 of 17 lesions (64.7%) and in 5 healthy skin areas (29.4%) (P = 0.08), while 'yoyo' figures were identified in 8 lesions (47%) but only 1 healthy skin area (5.9%) (P = 0.02). Ultrasonographic morphological analysis highlighted an improvement in dermal hyperechogenic bands and disappearance of yoyo figures after UVA1 treatment. Histology revealed a reduction in dermal sclerosis and inflammation, although this was not statistically significant. CONCLUSIONS: Ultrasonographic pattern analysis of morphoea is a suitable technique for monitoring UVA1 phototherapy response.

Ultraviolet phototherapy for cutaneous diseases: a concise review.

Phototherapy is the use of non-ionizing radiation, primarily in the ultraviolet spectrum, to treat disease. In dermatology, ultraviolet (UV) phototherapy remains an established, lower cost, and often preferred option for many common skin conditions, despite the introduction of newer potent biologics. This article introduces a principal therapeutic modality in the treatment of psoriasis, atopic dermatitis (eczema), vitiligo, and morphea among other diseases where oral manifestations may be present, providing basic information about the use of UVA, UVB, and PUVA. Practical considerations and side effects of phototherapy are described. Phototherapy is an effective treatment for many illnesses and carries a relatively benign side-effect profile.

Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment of localized scleroderma: a clinical and immunohistochemical randomized controlled study.

Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm2) UVA-1 phototherapy (340-400 nm) or 3 sessions of fractional CO2 laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO2 laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

Recurrence of morphea after successful ultraviolet A1 phototherapy: A cohort study.

BACKGROUND: Studies support efficacy of ultraviolet (UV)A1 phototherapy, but little is known about recurrence after successful UVA1 treatment. OBJECTIVE: We sought to determine the frequency of recurrent activity after UVA1 phototherapy and variables associated with recurrence. METHODS: This was a case series and prospective cohort study of patients treated with UVA1 phototherapy with minimum 6 months of follow-up. Demographics, clinical features, and cumulative UVA1 dose were analyzed for association with recurrence. RESULTS: Of 37 patients, 46% (n = 17) had recurrence of active morphea lesions after successful UVA1 phototherapy. Two-year and 3-year (after the last UVA1 phototherapy treatment) recurrence rates were 44.5% (95% confidence interval 30.1%-62.2%) and 48.4% (95% confidence interval 33.2%-66.1%), respectively. The only variable associated with recurrence was duration of morphea before UVA1 (P value = .02, hazard ratio 1.15, 95% confidence interval 1.06-1.27). LIMITATIONS: The sample size limits conclusions. CONCLUSION: With the exception of increased duration of morphea, risk of recurrence is no different in adults and children, or between morphea subtypes, skin types, and medium- to high-dose regimens. This indicates treatment doses in the medium-high UVA1 range are adequate with respect to frequency of recurrence.

Radiation-induced morphoea treated with UVA-1 phototherapy.

Morphoea is a localized inflammatory disorder of the dermis and subcutaneous fat and radiotherapy is a rarely reported cause (estimated incidence of 2 per 1000). Morphoea is commonly mistaken for an inflammatory recurrence of breast cancer, resulting in unnecessary investigations and treatment. We report the case of a 40-year-old woman who developed radiation-induced morphoea of the breast 7 months following adjuvant radiotherapy. She was treated with topical and systemic steroids as well as psoralen plus ultraviolet (UV)A before proceeding to UVA1 phototherapy. We also review the literature and discuss other management options.

"Assessment of chronic sclerodermoid Graft-versus-Host Disease patients, using 20 MHz high-frequency ultrasonography and cutometer methods".

The development of an adverse graft-versus-host disease (GvHD) is a major complication of stem cell transplantations, which are widely used to cure increasing number of hematologic malignancies. Patients with chronic GvHD are at risk of joint contractures secondary to sclerodermatous skin changes. Several clinical scores or serologic markers have been used to assess skin sclerosis in scleroderma patients. Evaluation of sclerotic skin changes using biometric tools remains to be challenging. The purpose of this study was to illustrate and exemplify ultrasound measurement and measurement of skin elasticity of five chronic sclerodermoid GvHD patients. There is still a substantial lack of studies using objective and non-invasive methods helpful in assessment of patients with skin involvement of GvHD. Although ultrasound is not the ideal method, it is worth emphasizing that it is still useful, non-invasive, and repeatable device in monitoring patients suffering from GvHD. It should also be added, that it seems to be advisable to repeat USG examination at an interval of 3 months after the treatment. In addition, skin echogenicity may be a more sensitive parameter than skin thickness in assessment of cGvHD patients.

UVA1 irradiation attenuates collagen production via Ficz/AhR/MAPK signaling activation in scleroderma.

Scleroderma is an autoimmune disease mainly characterized by progressive fibrosis of the skin. There are two types of scleroderma, namely localized scleroderma (LS) and systemic sclerosis (SSc); skin lesions in both types of scleroderma are histologically identical. Progressive skin sclerosis induces psychological and ecological burden for scleroderma patients. However, there is no effective treatment for scleroderma due to its unclear etiology. Aryl hydrocarbon receptor (AhR) is recognized as an environmental chemical effector that can respond to ultraviolet radiation, which has been demonstrated to participate in the pathogenesis of SSc in our previous study. In this study, we verify whether the anti-fibrosis effect of ultraviolet A1 (UVA1) phototherapy could be partially induced through Ficz/AhR/MAPK signaling activation for fibrotic lesions in both SSc and LS patients. This is the first study to show the association between the AhR pathway and the anti-fibrotic mechanism of UVA1 phototherapy, which provides additional evidence of the role of AhR in the fibrotic mechanism of systemic scleroderma from different perspectives. Ficz and other AhR agonists may replace UVA1 phototherapy as anti-fibrotic agents in scleroderma.

A systematic review of morphea treatments and therapeutic algorithm.

BACKGROUND: Morphea (localized scleroderma) is a skin disorder with significant morbidity. No consistent recommendations exist for therapy, impeding patient care. OBJECTIVE: We sought to create an evidence-based therapeutic algorithm. METHODS: We reviewed English-language literature using search engines and hand searches for therapeutic interventions in morphea. Results were summarized. RESULTS: Narrowband ultraviolet B is appropriate for progressive or widespread superficial dermal lesions; broadband ultraviolet A/ultraviolet A-1 is appropriate for widespread or progressive deeper dermal lesions. Systemic treatment with methotrexate, corticosteroids, or both is indicated for deep or function-impairing lesions and rapidly progressive or widespread (severe) disease. Topical treatment with calcipotriene or tacrolimus is supported for limited, superficial, inflammatory lesions. Use of oral calcipotriol, D-penicillamine, interferon gamma, and antimalarials is not supported. LIMITATIONS: Limitations are publication bias; lack of adequately powered, controlled trials; and no validated outcome measures. CONCLUSION: Phototherapy, methotrexate/systemic corticosteroids, calcipotriene, and topical tacrolimus have the most evidence for efficacy in morphea. Treatment works best in inflammatory disease. Disease activity, severity, progression, and depth should play a role in therapeutic decision making.

Successful ultraviolet A1 phototherapy in the treatment of localized scleroderma: a retrospective and prospective study.

BACKGROUND: Ultraviolet (UV) A1 phototherapy is an effective anti-inflammatory treatment modality that influences fibroblast functions. OBJECTIVES: To document the effects of UVA1 treatment in patients with localized scleroderma (LS) in a retrospective study (at least 6 months after UVA1 treatment) and in a prospective study before and immediately after medium-dose UVA1 irradiation. METHODS: In total, 30 patients (retrospective study n = 17, prospective study n = 13) with LS receiving UVA1 phototherapy five times weekly (for 3-6 weeks) were investigated. Improvement was documented using standardized questionnaires and clinical evaluation (using modified Rodnan skin score, Cutometer and 7.5-MHz ultrasound measurements). Levels of collagen I and collagen III metabolites were measured in serum and urine. RESULTS: In the retrospective study, medium-dose UVA1 phototherapy had been performed 6 months-3 years earlier (cumulative dose 750-1400 J cm(-2); mean + or - SD number of irradiations 19.3 + or - 3.8). Fourteen of 17 patients (82%) reported an improvement in symptoms following UVA1 therapy. In the prospective study, skin elasticity increased in 77% of the patients following medium-dose UVA1 phototherapy (cumulative dose 750-1250 J cm(-2); mean + or - SD number of irradiations 20.8 + or - 4.0). 7.5-MHz ultrasound measurements showed a mean reduction of lesional skin thickness of 13% compared with skin thickness before UVA1 phototherapy. The ratio of deoxypyridinoline to creatinine was significantly elevated in about two-thirds of the patients. CONCLUSIONS: This open study showed a positive short- and long-term efficacy of UVA1 phototherapy in patients with LS, with a reduction in sclerotic plaques, an increase in skin elasticity and a reduction of lesional skin thickness. UVA1 phototherapy had a significant effect on collagen metabolism. UVA1 phototherapy can be regarded as a safe treatment modality for patients with LS.

Ultraviolet A1 phototherapy for the treatment of localized scleroderma.

Ultraviolet (UV)A1 phototherapy is effective for T-cell-mediated skin diseases such as atopic dermatitis and mast cell-mediated skin diseases such as mastocytoma. UVA1 phototherapy is also effective against the sclerotic lesions of systemic sclerosis and morphea. Currently, in Japan, access to UVA1 phototherapy is limited because the UVA1 phototherapy device has not yet been approved. On the basis of our experience, we report three patients with localized scleroderma who responded successfully to UVA1 phototherapy. Efficacy was assessed by histological analysis and elastography. UVA1 successfully ameliorated sclerotic lesions, including morphea, linear scleroderma and morphea lesions in a patient with limited cutaneous systemic sclerosis. No side-effects were observed during UVA1 phototherapy.

Medium-dose is more effective than low-dose ultraviolet A1 phototherapy for localized scleroderma as shown by 20-MHz ultrasound assessment.

BACKGROUND: Recent studies suggest that ultraviolet (UV) A1 phototherapy is an effective treatment for localized scleroderma (LS); however, the optimum UVA1 dose remains to be determined. OBJECTIVE: We sought to compare the immediate and long-term efficacy of low- versus medium-dose UVA1 phototherapy for plaque-type LS. METHODS: Three comparable plaques in 16 patients were treated with 20 J/cm2 UVA1, 70 J/cm2 UVA1, or no irradiation. In total, 30 treatments were given. Skin thickness was determined by high-frequency ultrasound examination and clinical scoring. Assessments were done at baseline, immediately after treatment, and 3, 6, and 12 months thereafter. RESULTS: Ultrasound measurement showed a significantly greater reduction of skin thickness with 70 J/cm2 than with 20 J/cm2 at all time points of the study except immediately after UVA1 treatment. The clinical score of the irradiated plaques also decreased substantially but failed to detect a significant difference between the two dose regimens. LIMITATIONS: Our results only pertain to plaque-type LS and are limited by a small sample size. CONCLUSION: Medium-dose provides for better long-term results than low-dose UVA1 in LS as shown by ultrasound assessment. With clinical scoring, no significant difference between the two UVA1 dose regimens was detected, indicating that ultrasound measurement is a more sensitive method for quantifying treatment-induced skin changes in patients with LS.

Ultraviolet A phototherapy for sclerotic skin diseases: a systematic review.

BACKGROUND: Ultraviolet (UV) A-1 phototherapy is now available for a variety of skin diseases. Increasingly since 1995, there have been investigations of the efficacy of UVA-1 (340-400 nm) therapy for sclerotic skin diseases. Most studies undertaken treated patients who had localized scleroderma, but UVA-1 phototherapy is currently also used for other sclerotic skin conditions. OBJECTIVE: We sought to assess the efficacy, biological effects, and side effects of UVA-1 in a variety of sclerotic skin diseases (localized scleroderma, eosinophilic fasciitis, chronic graft-versus-host disease, lichen sclerosus et atrophicus, scleredema adultorum, necrobiosis lipoidica, POEMS disease, pansclerotic porphyria cutanea tarda, and drug-induced scleroderma-like disorders). METHODS: The authors searched for publications dated between January 1996 and November 2007 in the computerized bibliographic database, PubMed. PubMed was searched using medical subject heading terms and open searches to retrieve the latest reports. RESULTS: The evidence based on research concerning the effect of full-spectrum UVA (320-400 nm) and UVA-1 on these skin diseases is still growing, and appears promising. Up until now, good results are shown for all different doses (low, medium, and high) UVA-1 and UVA. There are insufficient data regarding use of high-dose UVA-1 and there are no comparative studies to make a clear assessment regarding the superiority of low-, medium-, or high-dose UVA-1 therapy. Although UVA-1 has various effects on, for instance, fibroblasts and inflammatory cells, the precise mode of action remains obscure. The main short-term side effects of UVA-1 therapy are erythema, pruritus, xerosis cutis, tanning, and recrudescence of herpes simplex infection. More studies are warranted to investigate the potential long-term risk of photoaging and skin cancer. Currently, UVA-1 is considered to be less carcinogenic than psoralen plus UVA (PUVA). LIMITATIONS: Because of the limited availability of randomized controlled trials and large cohort studies, it is difficult to draw firm conclusions on the long-term efficacy, optimum dose, and best treatment regimens for UVA-1 when administered to patients with sclerosing skin disorders. CONCLUSIONS: Full-spectrum UVA and UVA-1 phototherapy seem effective in the treatment of sclerotic skin diseases based on data retrieved from the literature. UVA-1 treatment can shorten the active period of localized scleroderma and pseudoscleroderma and prevent further disease progression, including contractures. Further investigations will be needed to determine any additional biological effects of UVA-1. Although long-term side effects are not yet known, UVA-1 might develop into a promising beneficial and well-tolerated treatment in the therapeutic armamentarium for sclerotic skin diseases. Long-term studies in large groups of patients are clearly needed.

Period of remission after treatment with UVA-1 in sclerodermic skin diseases.

BACKGROUND: Sclerodermic skin diseases can cause severe morbidity and disability. UVA-1 has shown to be an effective therapy for sclerodermic skin diseases. However, the period of remission in these patients is not clear. In this study, the effect and remission period of UVA-1 phototherapy in various sclerotic skin diseases is described using a semiquantitative clinical score combined with the durometer score as an objective apparatus to measure the hardness of the skin. OBJECTIVE: Our purpose was to determine the effectiveness of UVA-1 phototherapy and the duration of remission in sclerodermic skin diseases. METHODS: In this prospective study, 10 patients with various sclerodermic skin diseases were treated with UVA-1 phototherapy. The durometer was used to observe the hardness of the skin. Hardness of the skin was measured by one investigator at 10 locations, distributed evenly on the representative sclerotic skin. Each spot was measured three times, and the average of each of these measurements was summed to give the total durometer score. Durometer scores were recorded weekly until the final treatment date and 4 weeks after treatment. Clinical scores were carried out at the end date of the treatment using a 6-point scale semiquantitative score. Long-term effects were evaluated up to 29-46 months. RESULTS: The patients were treated with UVA-1 in a cumulative dose of 1286 +/- 58.8 (SEM) J/cm(2) (range, 846-1470 J/cm(2)) divided over five times a week for 4 weeks. In all patients studied, the sclerotic skin lesions were markedly softer after UVA-1 treatment. All durometer scores improved highly significant during the first 3 weeks of treatment and borderline significant during the last week of treatment. There was no significant improvement between the end of UVA-1 phototherapy and 1 month after ending the therapy (P > 0.05). All patients noted improvement of the semiquantitative clinical score during treatment. Clinical improvement was associated with improvement of the durometer score (95% confidence interval). With a follow-up until 46 months, the remission period was stable up to 26 months in six patients. The duration of sclerodermic skin diseases before start of treatment did not influence improvement in the clinical or durometer score. One patient had an acute side effect of minimal erythema. No other side effects, except tanning and fatigue, were noted. LIMITATIONS: This is an open-label uncontrolled study. CONCLUSION: UVA-1 is an effective treatment for sclerodermic skin diseases with a long period of remission and clinical improvement even in patients with a long history of a sclerotic skin disease. UVA-1 should be considered among the first approaches in the management of sclerotic skin diseases.

The safety and efficacy of light emitting diodes-based ultraviolet A1 phototherapy in bleomycin-induced scleroderma in mice.

PURPOSE: To define the efficacy and safety of narrowband ultraviolet A1 (UVA1) for the treatment of dermal fibrosis in bleomycin-induced mouse model of scleroderma. MATERIALS AND METHODS: 42 DBA/2 strain mice were included in the study: healthy mice and mice with established scleroderma, treated with high or medium dose of UVA1. Non-treated groups served as control. The equipment emitting 365±5nm UVA1 radiation was used in the study. The average cumulative doses were 1200J/cm2 for high and 600J/cm2 for medium dose course. Histological analysis was performed for the evaluation of the dermal thickness and mast cells density. The expressions of p53 and Ki-67 proteins were assessed by immunohistochemical analyses. RESULTS: Skin thickness of mice with scleroderma, treated with high and medium dose of UVA1, were lower (272.9±113.2µm and 394±125.9µm, respectively) in comparison to the dermal thickness of non-treated animals (599±55.7µm). The dermal mast cells count in mice with scleroderma was reduced after high and medium dose treatment to 11±1.7 and 13±2.2, respectively, as compared to that in non-treated mice (23±3.0). No significant upregulation of p53 nor Ki-67 proteins was observed in the skin of healthy mice and mice with scleroderma after high- and medium-dose of UVA1. CONCLUSIONS: The results of this study indicate that 365nm UVA1 with the cumulative doses of 1200J/cm2 and 600J/cm2 is safe and effective for the dermal fibrosis treatment.

Familial linear scleroderma (en coup de sabre) responsive to antimalarials and narrowband ultraviolet B therapy.

A 32-year-old woman and her 35-year-old sister presented with plaques of scleroderma en coup de sabre. The younger sister's disease was more severe and preceded the older sister's by 10 years. This is the second reported case of familial en coup de sabre, and the first case of horizontal transmission. Treatment of the younger sister with antimalarials and narrow-band ultraviolet B (NB-UVB) phototherapy slowed disease progression and reversed hair loss. The observation that NB-UVB was effective in this case of linear scleroderma suggests that it may be indicated as a therapy for cutaneous scleroderma.

The impact of high-dose narrowband ultraviolet A1 on dermal thickness, collagen and matrix-metalloproteinases in animal model of scleroderma.

OBJECTIVE: The main purpose of the present study was to define the impact of high-dose of 365±5nm ultraviolet A1 (UVA1) on dermal fibrosis in the pre-established, bleomycin-induced mouse model of scleroderma. METHODS: DBA/2 strain mice with the pre-established, bleomycin-induced scleroderma were irradiated with cumulative UVA1 dose of 1200J/cm2 and in parallel were challenged with prolonged administration of bleomycin. Non-treated groups served as the control. Light source emitting a narrow band UVA1 light of 365±5nm and 21mW/cm2 power density was used in the study. Histological analysis was performed for the evaluation of dermal thickness. The expressions of matrix-metalloproteinase-1 (MMP-1), matrix-metalloproteinase-3 (MMP-3), collagen types I and III were evaluated by immunohistochemical analyses. The Mann - Whitney U test was used for statistical analysis. RESULTS: Dermal thickness in mice injected with bleomycin during all the experiment (8weeks) and irradiated with UVA1 for the last 5weeks was significantly lower than that in mice challenged only with bleomycin for 8weeks (253.96±31.83µm and 497.43±57.83µm, respectively; P=0.002). The dermal thickness after phototherapy was lower as compared with the pre-existing fibrotic changes observed after 3weeks of bleomycin injections (253.96±31.83µm and 443.87±41.76µm, respectively; P=0.002). High-dose of UVA1 induced the 5.8- and 5.2-fold increase in MMP-1 and MMP-3 expressions, respectively, and the 1.2- and 1.4-fold decrease in collagen type I and collagen type III expressions in the pre-established, bleomycin-induced scleroderma model as compared to that in the control non-irradiated mice (P=0.002). CONCLUSIONS: Our study has demonstrated that a cumulative 365±5nm UVA1 radiation dosage of 1200J/cm2 not only prevents the progression of dermal fibrosis, but also induces a regression of pre-existing fibrotic changes.

A randomized controlled study of low-dose UVA1, medium-dose UVA1, and narrowband UVB phototherapy in the treatment of localized scleroderma.

BACKGROUND: In previous trials, UV therapy has been demonstrated to be effective in the treatment of localized scleroderma (LS). To date, a randomized comparison study to evaluate the efficacy and safety of different, commonly used phototherapeutic modalities in LS is still outstanding. OBJECTIVE: The aim of this study was to compare the safety and efficacy of low-dose (LD) UVA1, medium-dose (MD) UVA1, and narrowband (NB) UVB phototherapy in the treatment of LS. METHODS: Sixty four patients with LS were consecutively included in a prospective, open, randomized controlled 3-arm study. Severity of LS was determined by means of a clinical score, and clinical improvement was also monitored by histopathologic analysis and 20-MHz ultrasound. RESULTS: A total of 27 patients were treated with LD UVA1 (20 J/cm2), 18 patients received MD UVA1 (50 J/cm2), and 19 patients were treated with NB UVB dependent on their skin type. Phototherapy was performed 5 times weekly for 8 weeks. Two of the 64 patients included in this trial discontinued therapy. Skin status significantly improved in all patients who finished the treatment protocol, resulting in a reduction of the clinical score in all groups (LD UVA1, 7.6-5.0 [P < .001, 95% confidence interval 1.6-3.4]; MD UVA1, 11.1-6.6 [P < .001, 95% confidence interval 2.5-6.2]; NB UVB, 7.3-4.9 [P < .001, 95% confidence interval 1.6-3.2]). The reduction of the score was accompanied by an improvement of the visual analog scale for itching and tightness, histologic score, and 20-MHz ultrasound. MD UVA1 was significantly more effective than NB UVB (P < .05). There were no significant differences between LD UVA1 and NB UVB and the former and MD UVA1 (P > .05). LIMITATIONS: We had a relatively small study sample and nonblinded assessment of primary outcome. CONCLUSION: Phototherapy, as previously reported in several noncontrolled trials, is an effective therapeutic option in LS, with a favorable risk/benefit ratio. UVA1 phototherapy should be considered among the first approaches in the management of LS.