Ultraviolet A1 Research Articles

Laser and light therapies for the treatment of necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a rare, inflammatory granulomatous skin disorder involving collagen degeneration. In recent years, several light and laser therapies have been proposed and used in the treatment of NL with variable outcomes. The aim of the study was to investigate the efficacy and safety of lasers and light therapies for the treatment of NL. A review of PubMed was conducted to search for studies using laser and light therapies for the treatment of NL. Articles that employed a combination of treatment modalities were excluded. Twenty-four studies were reviewed. Light and laser therapies used in these studies included CO2 laser, pulsed dye laser, methyl aminolevulinate (MAL)-photodynamic therapy (PDT), aminolevulinic acid (ALA)-PDT, ultraviolet A1 (UVA1) phototherapy, and psoralen plus ultraviolet-A (PUVA). PUVA was identified as the modality with the most available evidence (7 studies), followed by MAL-PDT and ALA-PDT (5 studies each), pulsed dye laser and UVA1 (3 studies each), and lastly CO2 laser (2 studies). Most modalities demonstrated variable efficacies and side effects with the exception of PDL, which consistently showed successful outcomes. Multiple dermatologic light and laser therapies have been investigated for the treatment of NL, including PUVA, ALA-PDT, MAL-PDT, pulsed dye laser, UVA1, and CO2 laser. However, a clear consensus on the preferred treatment is yet to be addressed. Each treatment option demonstrates both advantages and disadvantages that should be discussed with patients when selecting the treatment modality.

Successful treatment of dyshidrotic palmoplantar eczema with ultraviolet A1 light-emitting diodes.

Successful treatment of dyshidrotic palmoplantar eczema with ultraviolet A1 light-emitting diodes.

A retrospective review of UVA1 treatment: An Australian experience from a single centre.

The therapeutic value of ultraviolet A1 (UVA1) phototherapy has been acknowledged for many years. Initially developed predominately for experimental and diagnostic purposes, it was subsequently recognised as a beneficial therapeutic modality in atopic dermatitis and localised scleroderma, and more recently a variety of sclerosing and fibrosing dermatoses, T-lymphocyte mediated disorders, both inflammatory and infiltrative, and several predominately dermal processes previously unresponsive to current therapies. We present a retrospective evaluation of outcomes and treatment tolerability in adult patients using a low dose (30 joules/cm2 ), regimen administered in our private dermatologic practice, between 2006 and December 2019. Major clinical groups represented include atopic dermatitis, localised and systemic sclerodermas, mycosis fungoides, urticarial dermatitis, generalised pruritus and granuloma annulare. Eighty-seven patients are included in this study with 92% of all patients experiencing a beneficial result, 54% having complete and 38% partial relief of presenting signs and/or symptoms. UVA1 therapy was well tolerated, with no patients ceasing treatment due to adverse effects. Ultraviolet A1 is an effective and safe treatment option in many hitherto recalcitrant cutaneous conditions.

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.

The effectiveness of high-dose ultraviolet A-1 phototherapy for acute exacerbation of atopic dermatitis in Asians.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by a chronic course of exacerbations and remissions. High-dose ultraviolet A-1 (UVA-1) phototherapy has been effective in the treatment of acute exacerbations of AD. However, there have been no case studies in Asian patients to date. We investigated the effectiveness of high-dose UVA-1 phototherapy for treating acute exacerbation of AD in Asian patients. This study included 16 patients with acute exacerbation of AD. High-dose (100J/cm2 ) regimens of UVA-1 therapy were employed. Therapeutic effectiveness was assessed based on the findings of clinical examinations and scoring of AD (SCORAD) index before treatment and after the 5th and 10th sessions of treatment. Additionally, side effects and recurrence during follow-up were retrospectively evaluated. The patients were between 7 and 50years of age, with a mean age of 25.8years. The SCORAD index was between 41 and 89.5, with a mean score of 64.9. Among the 16 patients, two patients discontinued treatment due to the aggravation of erythema and pruritus. Of the 14 patients who completed the 10 sessions of high-dose UVA-1 phototherapy, nine patients (64.3%) showed complete remission and five patients (35.7%) showed partial remission. The mean SCORAD index reduced from 64.9 (before treatment) to 23.3 (after the 10th session of treatment). This is the first case study of high-dose UVA-1 phototherapy for acute exacerbation of AD in Asian patients, suggesting that high-dose UVA-1 phototherapy can be a well-tolerated and effective treatment for acute exacerbated AD. Future large-scale prospective studies are needed.

Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P=.037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P=.032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P=.013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P=.626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.

Interventions for chronic palmoplantar pustulosis.

Interventions for chronic palmoplantar pustulosis.

Evidence-based, Skin-directed Treatments for Cutaneous Chronic Graft-versus-host Disease.

Chronic graft-versus host disease (cGVHD) occurs in 30% to 70% of patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cutaneous cGVHD affects 75% of cGVHD patients, causing discomfort, limiting the range of movement, and increasing the risk of wound infections. Furthermore, systemic immunosuppression is often needed to treat cGVHD and long-term use can lead to adverse events. Optimal use of skin-directed therapies is integral to the management of cutaneous cGVHD and may decrease the amount of systemic immunosuppression required.This study reviewed English-language articles published from 1990 to 2017 that evaluated the effect of skin-directed treatments for cutaneous cGVHD. A total of 201 papers were identified, 164 articles were screened, 46 were read, and 18 publications were utilized in the review. Skin-directed treatments for cGVHD included topical steroids, topical calcineurin inhibitors, psoralen with ultraviolet A (PUVA) irradiation, ultraviolet A1 (UVA1) irradiation, and ultraviolet B (UVB) irradiation. We report the number of complete remissions, partial remissions, and systemic immunosuppression reduction in each study, as available.Twenty-two out of 30 (73.3%) patients experienced overall improvement with topical calcineurin inhibitors. At least 26 out of 76 patients (34.2%) receiving PUVA experienced complete remission, and 30 out of 76 patients (39.5%) experienced partial remission. In UVA1 studies, 44 out of 52 (84.6%) patients experienced overall improvement. In UVB studies, nine out of 14 patients (64.3%) experienced complete remission and four out of 14 patients (28.6%) experienced partial remission.As more HCTs are performed, more individuals will develop cGVHD. Awareness and optimal use of skin-directed therapies for cutaneous cGVHD may help improve patient outcomes and quality of life.

Efficacy Evaluation of Products Against Long Wavelength Ultraviolet A1 and Visible Light Induced Biological Effects

Efficacy Evaluation of Products Against Long Wavelength Ultraviolet A1 and Visible Light Induced Biological Effects

Long-wavelength Ultraviolet A1 and Visible Light Photoprotection: A Multimodality Assessment of Dose and Response.

Human skin is exposed to visible light (VL; 400-700nm) and long-wavelength ultraviolet A1 (UVA1) radiation (370-400nm) after the application of organic broad-spectrum sunscreens. The biologic effects of these wavelengths have been demonstrated; however, a dose-response has not been investigated. Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. Subjects were irradiated with 2 light sources (80-480Jcm-2 ): one comprising VL with less than 0.5% UVA1 (VL+UVA1) and the other pure VL. Skin responses were evaluated for 2weeks using clinical and spectroscopic assessments. 4-mm punch biopsies were obtained from nonirradiated skin and sites irradiated with 480Jcm-2 of VL+UVA1 and pure VL 24h after irradiation. Clinical and spectroscopic assessments demonstrated a robust response at VL+UVA1 sites compared with pure VL. Histology findings demonstrated a statistically significant increase in the marker of inflammation (P<0.05) and proliferation (P<0.05) at the irradiated sites compared with nonirradiated control. Threshold doses of VL+UVA1 resulting in biologic responses were calculated. Results indicate that approximately 2h of sun exposure, which equates to VL+UVA1 dose (~400Jcm-2 ), is capable of inducing inflammation, immediate erythema and delayed tanning. These findings reinforce the need of photoprotection beyond the UV range.

Upcoming Therapeutic Modalities for the Treatment of Keloids: An Update

Introduction: Keloids are benign dermal tumors that generally form by local fibroblast proliferation and excessive collagen production following skin trauma. Several methods have been described for the treatment of keloid, often with suboptimal results and recurrences.&#x0D; Objective: To update literature that provides information regarding upcoming therapeutic modalities for the treatment of keloids, including lasers, radiofrequency (RF), photodynamic therapy (PDT), and ultraviolet A1 (UVA1) irradiation.&#x0D; Materials and Methods : A systematic review of the literature was performed for the original articles related to the treatment of keloids. The search terms ‘keloids’ and ‘lasers’ or ‘radiofrequency’ or ‘PDT’ or ‘UVA1’ was entered into a search of the National Library of Medicine’s PubMed Database.&#x0D; Result: The search returned a total of 188 sources, of which, 26 articles met our inclusion criteria.&#x0D; Conclusion: Combination approach is superior than solo therapy in the treatment of keloid. However, it is highly desirable that new emerging therapies undergo large-scale studies with long-term follow-up before being recommended conclusively as alternative therapies for the treatment of keloid. Moreover, lack of randomized clinical trials (RCTs) needs to be taken into consideration urgently.

Phototherapy of cutaneous T-cell lymphomas.

Cutaneous T-cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas arising in the skin. Mycosis fungoides (MF), the most common variant, is characterised by clonal proliferation of skin residing malignant T-cells. Initially appearing with erythematous patches and plaques it follows a chronic course with progression to cutaneous tumours and extracutaneous involvement in some patients. Phototherapy with ultraviolet A radiation combined with 8-methoxypsoralen (PUVA) and with narrow-band ultraviolet B radiation (NB-UVB) are among the first line options for the treatment of MF and can induce remission in most patients. Sézary syndrome (SS) is a rare and more aggressive CTCL variant with generalized skin involvement. Patients with SS and with erythroderma from MF can benefit from treatment with extracorporeal photochemotherapy (ECP) where peripheral blood is exposed to PUVA. Phototherapy can be safely combined with systemic agents, most notably interferon-alpha and retinoids. Another photoresponsive CTCL variant is lymphomatoid papulosis (LP), a CD30+ lymphoproliferative disease characterised by chronically recurring papules. The disease responds favourably to PUVA but low dose methotrexate might be preferred for long term disease control. Recently updated treatment guidelines have been published to provide evidence-based algorithms for the stage-oriented treatment of MF, SS and LP. Areas of uncertainty are treatment schedules that are currently not optimised for CTCL, the use of phototherapy for maintenance, and the value of ultraviolet A1 radiation, excimer lasers, and photodynamic therapy.

3D Bioprinting with UVA1 Radiation and Photoinitiator Irgacure 2959: Can the ASTM Standard L929 Cells Predict Human Stem Cell Cytotoxicity?

3D bioprinting often involves human mesenchymal stem cells (hMSC) that are differentiated into the desired cells to replace body parts like ears. Scaffolds of crosslinked hydrogels offer structural support during differentiation. Different photoinitiators are used to make free radicals that photocrosslink these hydrogels; the more penetrating ultraviolet A1 (UVA1) (340-400nm) wavelengths can be used because Irgacure 2959 only absorbs in the UV (100-400nm) region. We questioned if the L929 mouse fibroblast cells used in the American Society for Testing Materials standard cytotoxicity assays (F895&F813) can predict the viability of hMSC after exposure to UVA1 radiation alone and in combination with Irgacure 2959 (0.05-0.5% w/v usual range). We exposed both cell types to a high dose of LED UVA1 (370±5nm; 788kJm-2 ) and side by side to increasing UVA1 doses from a glass-filtered black light source combined with either 0.05% (w/v) or 0.5% (w/v) of Irgacure 2959 and monitored their viabilities using flow cytometry. We found UVA1 radiation alone killed ~50% of the hMSC cells compared to ~8% of the L929 cells and significantly more hMSC than L929 died after UVA1 with Irgacure 2959. Thus, L929 cannot be used to accurately predict the viability of hMSC after these specific 3D bioprinting conditions.

Ultraviolet A1 Phototherapy for Fibrosing Conditions.

In this article we describe efficacy and safety aspects of ultraviolet A1 (UV-A1) phototherapy in fibrosing conditions. UV-A1 is a specific phototherapeutic modality that is defined by a selective spectral range (340–400 nm). UV-A1 includes distinct modes of action qualifying this method for therapy of a variety of conditions, in particular fibrosing skin diseases. Concerning efficacy of UV-A1 phototherapy in fibrosing conditions, the best evidence obtained from randomized controlled trials exists for localized scleroderma. Moreover, fibrosing disorders such as lichen sclerosus and graft-vs.-host disease can be treated successfully by means of UV- A1. Regarding the optimal dosage regimen medium-dose UV-A1 seems to be linked to the best benefit/risk ratio. Possible acute adverse events of UV-A1 phototherapy include erythema and provocation of photodermatoses. Skin ageing and skin cancer formation belong to the chronic adverse events that may occur after long-term UV-A1 phototherapy.

Synergistic effects of long-wavelength ultraviolet A1 and visible light on pigmentation and erythema

SummaryBackground Visible light (VL) induces multiple cutaneous effects. Sunscreen testing protocols recommended by regulatory bodies throughout the world require the use of solar simulators with spectral output in ultraviolet (UV) domain only. However, sunlight contains VL and infrared radiation also. Objective This study aimed to evaluate the contributions of VL and UVA on pigmentation and erythema, and optimize parameters for in-vivo testing. Methods Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. Subjects were irradiated on their back with VL using two light sources: one containing pure VL and one containing VL with less than 0.5% UVA1 (VL+UVA1). Four different irradiances were administered to investigate reciprocity behaviour. Assessments, including photography, investigator's global assessment, colorimetry, and spectroscopy, were performed immediately, 24 hours, 7 days and 14 days post-irradiation. Results Pigmentation was observed with both light sources; however, pigment intensity was greater with VL+UVA1 than pure VL. Reciprocity was observed in pure VL sites, but not VL+UVA1. Variation in spectral output had greater impact on pigment intensity than irradiance. Clinical erythema was observed on the VL+UVA1 side, but not on the pure VL side. Protocol for testing photoprotection product efficacy against VL induced effects has been proposed. Conclusions The findings suggest a synergistic relationship between VL and UVA1 and emphasize the need for developing means of photoprotection against VL. This article is protected by copyright. All rights reserved.

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

There are few studies in the literature correlating the ultrasonographic findings, clinical scoring systems or histological findings in morphoea after ultraviolet (UV)A1 phototherapy. 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. In total, 17 patients with morphoea were studied. Initially and at study end, high-frequency ultrasonography (50MHz) 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. 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. Ultrasonographic pattern analysis of morphoea is a suitable technique for monitoring UVA1 phototherapy response.

Synergistic effects of long-wavelength ultraviolet A1 and visible light on pigmentation and erythema

Synergistic effects of long-wavelength ultraviolet A1 and visible light on pigmentation and erythema

1167 The impact of trace amounts of long wavelength UVA1 on visible light induced effects

Our skin is exposed to visible light (VL) and long wavelength ultraviolet A1 (UVA1) radiation (370-400 nm) present in sunlight even after application of organic broad spectrum sunscreens. The effects of these wavelengths on pigmentation and erythema have been demonstrated. However, a dose response has not been investigated which can provide insight on how skin responses can vary based on the duration of sun exposure. Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. On day 0, subjects were irradiated with two light source; one comprising pure VL and the other VL with less than 0.5% UVA1 (VL+UVA1) at a dose of 80 J/cm2, 160 J/cm2, 320 J/cm2 and 480 J/cm2. The irradiance was set at 175 mW/cm2. Skin responses were evaluated immediately, at 24 hours, 7 days, and 14 days after irradiation. Assessment methods included investigator’s global assessment (IGA), diffuse reflectance spectroscopy (DRS), and colorimetry. Clinical IGA scores suggest that 3/10 subjects for the 320 J/cm2 site, and 5/10 subjects for the 480 J/cm2 site had clinical erythema immediately after irradiation on the VL+UVA1 side only. No erythema was observed for the corresponding pure VL sites. Only the highest dose, 480 J/cm2,resulted in pigmentation response that was statistically significantly different at all time points between the two light sources (p<0.05). Pigmentation response from VL+UVA1 site was two times more intense than that of pure VL at the day 14 time point. Spectroscopy and histology data analysis are under progress. Wavelengths not covered by current broad spectrum sunscreens have implications on pigmentation and erythema. There appears to be a threshold dose of UVA1 which in combination with VL results in immediate erythema followed by darker and persistent pigmentation. The effects can be noticed at approximately two hours of outdoor sun exposure.

Synergistic effects of long-wavelength ultraviolet A1 and visible light on pigmentation and erythema

Visible light (VL) induces multiple cutaneous effects. Sunscreen testing protocols recommended by regulatory bodies throughout the world require the use of solar simulators with spectral output in the ultraviolet (UV) domain only. However, sunlight contains VL and infrared radiation also. This study aimed to evaluate the contributions of VL and UVA on pigmentation and erythema, and optimize parameters for in vivo testing. Ten subjects with Fitzpatrick skin phototype IV-VI were enrolled. Subjects were irradiated on their back with VL using two light sources: one containing pure VL and one containing VL with less than 0·5% UVA1 (VL+UVA1). Four different irradiances were administered to investigate reciprocity behaviour. Assessments, including photography, Investigator's Global Assessment, colorimetry and spectroscopy, were performed immediately, 24 h, 7 days and 14 days post-irradiation. Pigmentation was observed with both light sources; however, pigment intensity was greater with VL+UVA1 than with pure VL. Reciprocity was observed in pure VL sites, but not VL+UVA1. Variation in spectral output had greater impact on pigment intensity than irradiance. Clinical erythema was observed on the VL+UVA1 side, but not on the pure VL side. A protocol for testing photoprotection product efficacy against VL-induced effects has been proposed. The findings suggest a synergistic relationship between VL and UVA1 and emphasize the need for developing means of photoprotection against VL.

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

PurposeTo 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 methods42 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. ResultsSkin 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. ConclusionsThe 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.