Full-body blue light irradiation as treatment for atopic dermatitis: a randomized sham-controlled clinical trial (AD-Blue).

BACKGROUND: Visible blue light (wavelength 400-495 nm) is a promising new treatment option for both psoriasis and atopic dermatitis (AD). Whilst previous clinical trials featured various devices and blue light at a variety of wavelengths, none of these interventions were challenged in objective clinical criteria. PATIENTS AND METHODS: Eighty-seven patients diagnosed with AD were enrolled in AD-Blue, an international, prospective, double-blinded, three-armed (415 nm vs. 450 nm vs. sham control), randomized trial designed to investigate the safety and efficacy of prototype full-body blue light devices. RESULTS: Full-body irradiation with 450 nm blue light but not 415 nm had a significant impact on itch (Itch-VAS, -1.6 ± 2.3; p  =  0.023 vs. sham irradiation). PO-SCORAD values also decreased significantly in response to irradiation at 415 nm (-11.5 ± 18.4; p = 0.028 vs. sham irradiation). None of the other outcome measures (EASI, SCORAD, IGA, DLQI) changed significantly. No safety signals were observed. Evaluation of skin transcriptomes, cytokine levels in serum, and ELISpots from peripheral blood mononuclear cells isolated from a subset of patients revealed moderate decreases in IL-31 in response to irradiation with blue light. CONCLUSIONS: Despite its favorable safety profile and moderate reductions in itch and IL-31 levels, full-body blue light irradiation did not lead to an amelioration of any of the objective measures of AD.

Erbium:YAG fractional laser ablation improves cutaneous delivery of pentoxifylline from different topical dosage forms.

Topical application of pentoxifylline (PTX) would enable targeted treatment of radiation-induced skin fibrosis. However, PTX is hydrophilic with limited partitioning into the stratum corneum. The objective of this study was to investigate whether use of Erbium:YAG fractional laser ablation and different topical dosage forms (solution, hydrogel and patch) could be used to improve PTX cutaneous delivery as opposed to transdermal permeation. Initial results confirmed that fractional laser ablation significantly increased PTX delivery from each dosage form compared to passive controls. Delivery efficiencies of âˆ¼ 30% were achieved with each dosage form but a large proportion of PTX permeated across the skin; thus, fluences were decreased to create shallower micropores, their depth being linearly dependent on fluence. The hydrogel was selected as the optimal formulation and PTX delivery efficiencies were further increased (44%-67%) by reducing the amount of hydrogel applied (better mimicking conditions of use). As this resulted in PTX depletion in the formulation, a loss of dependence of delivery on laser fluence was observed. These findings suggest that fractional laser ablation at moderate fluences enables an effective and targeted cutaneous delivery of PTX from a hydrogel formulation, which can be easily produced without the need for complex equipment.

Fractional Photothermolysis for Treatment of a Residual Discoid Lupus Erythematosus Lesion: A Case Report.

Cutaneous discoid lupus erythematosus (CDLE) is a chronic inflammatory skin disease often resulting in permanent scarring of the affected area. Fractional photothermolysis (FP) is a well-known inducer of tissue regeneration by wounding the skin in a fractional pattern, hence inducing a well defined, wound healing response. It has been used clinically to treat atrophic as well as hypertrophic scars and also fibrotic diseases like morphea since more than a decade. We report a case of a young female patient treated with three sessions of ablative FP for stable atrophic scars due to CDLE affection of the upper left and right cheeks. After the last treatment, no side effects were observed. At the 13-month follow-up visit, the treated atrophic scars showed satisfying improvement for the patient. Skin texture, relief, color, and overall cosmetic appearance were all rated as improved by three independent dermatologists. No signs of unwanted side effects were observed at any time point. This case report should be followed up with a larger case series or ideally a prospective randomized clinical trial to better establish FP as a safe and effective tool to treat reminiscent scars after CDLE.

Laser-Induced Smoke in Dermatologic Practice: A Survey to Explore Hazard Perceptions, Safety Measures and Unmet Needs.

Introduction: Inhalation of laser-induced smoke is a potential health hazard to exposed physicians and laser operators. To date, little is known about the perception of health hazards related to laser-induced smoke exposure among physicians and the actual use of safety measures to mitigate these risks. Methods: In May 2020, 514 members of the European Society for Lasers and Energy-Based Devices (ESLD) were invited by email to participate in an online survey. The survey comprised 16 questions including multiple-choice and open-ended questions. Results: Responses were received from 109 participants. The majority (90%) were aware of potential hazards and highlighted a desire for better protective measures (60%). A smoke evacuation system was frequently used with ablative lasers (66%) and fractional ablative lasers (61%), but less the case with non-ablative lasers (30%) and hair removal lasers (28%). The COVID-19 outbreak had no clear effect on the use of smoke evacuation systems. Prior to the COVID-19 outbreak, mainly surgical masks were used (40-57%), while high filtration masks (FFP1, FFP2 or FFP3) were used by only a small percentage (15-30%). Post COVID-19 outbreak, the use of high filtration masks increased significantly (54-66%), predominately due to an increase in the use of FFP2 masks. Reasons mentioned for inadequate protective measures were sparse knowledge, limited availability, discomfort, excessive noise, high room temperatures, and financial costs. Conclusion: While there is considerable awareness of the hazards of laser-induced smoke among physicians and laser operators, a substantial number of them do not use appropriate protective measures. The implementation of regulations on safety measures is hampered by sparse knowledge, limited availability, discomfort, excessive noise, financial issues, and high room temperatures.

Generic outcome set for the international registry on Laser trEAtments in Dermatology (LEAD): a protocol for a Delphi study to achieve consensus on what to measure.

INTRODUCTION: While laser technology has expanded the armamentarium of treatment for various skin diseases during the past years, heterogeneity in study outcomes hampers comparability and appropriate evidence synthesis. Part of these issues can be addressed by developing a generic outcome set. Using the Delphi method, this study aims to seek consensus between key stakeholders on relevant generic outcomes (what to measure) for implementation in the international registry on Laser trEAtments in Dermatology (LEAD). The registry is focused on collecting research data on various laser treatments for skin disorders. METHODS AND ANALYSIS: By reviewing the literature and involvement of key stakeholder groups and adult patients in need or after laser surgery and health professionals, a preliminary list of outcomes will be generated and categorised into domains. Using these outcomes, an international three-round Delphi study will be performed to rate the importance of outcomes in the selection of a generic outcome set. Participants are allowed to provide new outcomes to the preliminary list for revisions during the first Delphi round. Finally, results will be discussed during a consensus meeting to agree on generic outcomes to be used in the LEAD registry. ETHICS AND DISSEMINATION: An ethics approval was not applicable (W19_290 # 18.336). The study is registered with the Cochrane Skin Core OUtcome Set INitiative) and the Core Outcome Measures in Effectiveness Trials initiative. Procedures will be conducted according to the Declaration of Helsinki. The findings will be disseminated through peer-reviewed publications and conference presentations.

Er:YAG fractional laser ablation for cutaneous co-delivery of pentoxifylline and d-α-tocopherol succinate: A new approach for topical treatment of radiation-induced skin fibrosis.

Radiation induced fibrosis is a common side-effect after radiotherapy. Pentoxifylline is reported to reverse radiation injuries when used in conjunction with D-α-tocopherol. However, pentoxifylline has a short half-life, limited oral bioavailability, and induces several systemic adverse effects. The objective of this study was to investigate the feasibility of using Er:YAG fractional laser ablation to enable simultaneous cutaneous delivery of pentoxifylline and D- α -tocopherol succinate from poly(lactide-co-glycolide) microparticles prepared using the freeze-fracture technique. In vitro release experiments demonstrated the different release profiles of the two molecules, which were influenced by their very different lipophilicities and aqueous solubilities. Experiments were then performed to investigate the effect of laser fluence on pore depth and so determine the pore volume available to host the topically applied microparticles. Application of the pentoxifylline and D-α-tocopherol succinate containing microparticles, prepared with RESOMER® RG 502H, to laser porated skin for 48 h, resulted in simultaneous delivery of pentoxifylline (69.63 ±â€¯6.41 µg/cm2; delivery efficiency 46.4%) and D-α-tocopherol succinate (33.25 ±â€¯8.91 µg/cm2; delivery efficiency 22.2%). After deposition into the micropores, the poly(lactide-co-glycolide) microparticles containing pentoxifylline and D-α-tocopherol succinate could serve as an intraepidermal depot to enable sustained drug delivery after micropore closure and thereby reduce the need for repeated microporation.

Treatment of Atopic Dermatitis Using a Full-Body Blue Light Device (AD-Blue): Protocol of a Randomized Controlled Trial.

BACKGROUND: Irradiation with visible blue light (wavelength 400-495 nm) is a promising, effective, and safe new treatment option for chronic inflammatory skin diseases such as psoriasis and atopic dermatitis. OBJECTIVE: We will perform a multicenter, placebo-controlled, double-blinded, 3-armed, prospective, randomized controlled trial to investigate the efficacy and safety of full-body blue light devices (wavelengths: 415 nm and 450 nm) compared with that of placebo irradiation for the treatment of atopic dermatitis. METHODS: We are planning to enroll a total of 150 patients at the University hospitals in Göttingen (Germany), Marburg (Germany), and Geneva (Switzerland). RESULTS: The trial was approved by the lead ethics committee of the medical faculty of the University of Göttingen (21/11/16). Further approvals were obtained from local and federal authorities (ethics committee Marburg, Cantonal Commission for Research Ethics Geneva, Suisse Medic, and Bundesinstitut für Arzneimittel und Medizinprodukte). CONCLUSIONS: We will disseminate the results in a peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT03085303; https://clinicaltrials.gov/ct2/show/NCT03085303 (Archived by WebCite at http://www.webcitation.org/73ucqkkA1). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11911.

Fractional photothermolysis for the treatment of facial wrinkles - searching for optimal treatment parameters in a randomized study in the split-face design.

BACKGROUND: Fractionated photothermolysis (FP) is used for the treatment of facial wrinkles. OBJECTIVES: Investigation of effects of different FP treatment parameters in the treatment of facial wrinkles. PATIENTS AND METHODS: In a randomized split-face controlled study 11 patients received 3 FP sessions in 4-week intervals. Keeping the total energy input for each facial side constant, one side was treated with 6 mJ/MTZ with relatively high MTZ density (up to 2,625 MTZ/cm(2) ) and the contralateral side with 70 mJ/MTZ with lower MTZ density (up to 230 MTZ/cm(2) ). Follow-up (FU) visits were performed 1, 3, and 6 months after the last treatment. The cosmetic evaluation was done by the patient self-assessments and by assessment of standardized photographs by 3 independent, blinded investigators. Post-treatment side effects were documented daily in a patient diary up to 7 days after the procedure. RESULTS: After 6 months, the patient self-assessments indicated significant improvements (p < 0.005) in wrinkle severity from 5.2 ± 1.5 to 3.8 ± 1.3 and 3.7 ± 1.3 for 6 and 70 mJ/MTZ, respectively, but without significant difference between the energy levels. In contrast, the photographic evaluation by the blinded investigators showed that wrinkle severity was rated significantly better at the sites treated with 70 mJ/MTZ than at the sites treated with 6 mJ/MTZ (p < 0.01). Treatment with 70 mJ/MTZ was significantly more painful than treatment with 6 mJ/MTZ. The typical local reactions to FP, erythema and edema, were also significantly more intense after 70 mJ/MTZ and lasted longer. CONCLUSIONS: FP with higher energy per MTZ at constant total energy input is more effective in the treatment of facial wrinkles than lower energy. The gain in effectiveness is, nonetheless, accompanied by an increase in adverse reactions. The treating physician may use this information to adjust treatment to the preferences of the individual patient.

Nevus of Ota in dark skin--an uncommon but treatable entity.

BACKGROUND: Nevus of Ota can be effectively and safely treated since the arrival of q-switched lasers in dermatology. However, available literature is scarce regarding the treatment of Nevus of Ota in skin types darker than IV. OBJECTIVES: We report about four Fitzpatrick phototype V patients treated for Nevus of Ota with a q-switched Nd:YAG laser at 1,064 nm. METHODS: Four patients with Fitzpatrick phototype V were treated for Nevus of Ota with a q-switched Nd:YAG laser at 1,064 nm in a private practice setting. Pulse diameter for the treatments was 2 mm and pulses were applied typically in a non-overlapping fashion. Treatment energies ranged from 4.1 to 9.5 J/cm(2) . RESULTS: All four patients of this case series showed significant cosmetic improvement. Improvement ratings, based upon pre- and post-treatment photographs rated by blinded investigators, were in between 6 and 10 with a mean of 8.5 on a 10-point scale. Side effects were mostly short termed and typical for this laser technique. No post-inflammatory hyperpigmentation was observed however one case of permanent drop-like hypopigmentation was encountered. CONCLUSIONS: A 1,064 nm q-switched Nd:YAG laser treatment could be an effective and reasonably safe treatment for patients with Nevus of Ota and Fitzpatrick skin type V. Patients should be counselled before treatment regarding the risk of permanent hypopigmentation.

Thermal injury causes DNA damage and lethality in unheated surrounding cells: active thermal bystander effect.

Direct heat exposure to cells causes protein degradation and DNA damage, which can lead to genetic alteration and cell death, but little is known about heat-induced effects on the surrounding tissue. After burns or laser surgery, loss of viability in the surrounding tissue has been explained by a temperature gradient due to heat diffusion. This study shows that, in the absence of any direct heating, heat diffusion, or cell-to-cell contact, "bystander" cells that share the medium with heat-exposed cells exhibit DNA damage, apoptosis, and loss of viability. We coin this phenomenon "active thermal bystander effect" (ATBE). Significant ATBE was induced by fibroblasts exposed for 10 minutes to a temperature range of 44-50 degrees C (all P<0.011). The ATBE was not induced by cells heated to lethality above 54 degrees C and immediate medium exchange did not suppress the effect. Therefore, the thermal bystander effect appears to be an active process in which viable, heat-injured cells induce a signal cascade and/or mediator that damages or kills surrounding bystander cells. The ATBE may have clinical relevance for acute burn trauma, hyperthermic treatments, and distant tissue damage after localized heat stress.

Effects of a 1,450 nm diode laser on facial sebum excretion.

BACKGROUND AND OBJECTIVE: Laser therapy with a 1,450 nm diode laser is a clinically effective treatment for acne vulgaris, although the mechanism of action is unknown. To investigate this, we conducted a small, prospective, controlled clinical trial to assess this laser's effects on the facial sebum excretion rate (SER). MATERIALS AND METHODS: Fourteen healthy volunteers without active acne were enrolled in this study and received three laser treatments on test areas of the nose and forehead. Nine subjects completed the treatment regimen and were available for follow-up. SER was measured with Sebumeter prior to the first treatment, and at 1 week and 1 month after the third treatment. Photographs were taken and subjective assessment of skin oiliness and pore size determined by questionnaires at 1 month follow-up. RESULTS: No significant reduction in SER was observed comparing treated with control on all treatment sites (P>0.05) on the nose. Reduction in the absolute SER was observed for both test and control sites on the forehead, reaching significance on the treatment site (P = 0.04) and marginal significance on the control site (P = 0.08). CONCLUSION: While our study was designed to detect only large changes in SER, we conclude that three 1,450 nm laser treatment sessions did not cause marked changes in SER compared to the control (i.e., >44%). Thus, major destruction of sebaceous glands as a result of this treatment is unlikely. However, reduced sebum production was observed on both treatment and control sides at 1 month. Therefore alternative mechanisms should also be considered to explain the clinical efficacy of this treatment for acne vulgaris.

In-vivo singlet oxygen dosimetry of clinical 5-aminolevulinic acid photodynamic therapy.

Photodynamic therapy (PDT) is a viable treatment option for a wide range of applications, including oncology, dermatology, and ophthalmology. Singlet oxygen is believed to play a key role in the efficacy of PDT, and on-line monitoring of singlet oxygen during PDT could provide a methodology to establish and customize the treatment dose clinically. This work is the first report of monitoring singlet oxygen luminescence in vivo in human subjects during PDT, demonstrating the correlation of singlet oxygen levels during PDT with the post-PDT photobiological response.

Skin responses to fractional photothermolysis.

BACKGROUND AND OBJECTIVE: Fractional photothermolysis (FP) is a new concept using arrays of microscopic thermal damage patterns to stimulate a therapeutic response. We analyzed epidermal and dermal response to FP with the aim of correlating histological and clinical response. STUDY DESIGN/MATERIALS AND METHODS: Twelve subjects received a single treatment with a prototype diode laser emitting at a wavelength of 1,500 nm, delivering 5 mJ per microscopic treatment zone (MTZ), and a density of 1,600 MTZs/cm(2) on the forearm. Biopsies were procured over a period of 3 months. The biopsies were analyzed by two blinded dermatopathologists using hematoxylin and eosin (Hematoxylin and Eosin Stain), Elastica von Gieson, nitro-blue-tetrazolium-chloride (NBTC) viability, and immunohistochemistry stains. Furthermore, the treatment sites were evaluated in vivo by confocal microscopy. RESULTS AND DISCUSSION: Twenty-four hours after fractional photothermolysis, the continuity of the epidermal basal cell layer is restored. Complete epidermal regeneration is obtained 7 days after the treatment. Microscopic epidermal necrotic debris (MENDs) are seen as early as 1 day after FP. MENDs contain melanin pigment, and are shed from the epidermis within 7 days. Evidence of increased collagen III production is shown with immunohistochemistry (IHC) staining 7 days after FP. IHC for heat shock protein 70 (HSP 70) shows the expression of HSP 1 day after FP, and IHC for alpha smooth muscle actin shows the presence of myofibroblasts 7 days after FP. These findings are concordant with the induction of a wound healing response by FP. There is no evidence of residual dermal fibrosis 3 months after treatment. CONCLUSION: A single treatment with fractional photothermolysis induces a wound healing response in the dermis. A mechanism for the precise removal of epidermal melanin is described, in which MENDs act as a melanin shuttle.