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Autologous fractional full-thickness skin grafting is a method of harvesting full-thickness skin with reduced donor site morbidity compared with conventional skin grafting.To demonstrate that full-thickness skin microbiopsies can be harvested with minimal scarring or complications.In a nonrandomized, self-controlled, pilot trial, subjects ( n = 8) underwent tissue harvesting of full-thickness skin columns of 200, 400, 500, 600, 800 μm, 1, and 2 mm diameters. The extent of scarring was measured by using the Patient and Observer Scar Assessment Scale and blinded evaluation of photographs at 6 weeks postprocedure. Pain visual analog scale (VAS) and side effects were recorded.When present, scars were first observed after 2 to 4 weeks, much more often for wounds400 μm ( p.001). Blinded dermatologists increasingly identified clinical scarring on photographs with larger harvested microcolumn diameters ( p.001). Median VAS pain score was 0 (range 0-4). All subjects rated the procedure safe and tolerable.Harvesting full-thickness skin microcolumns is well-tolerated over a wide range of column diameters. At diameters of less than 500 μm, side effects including scarring are minimal.

Background and objectives Laser hair removal is the most common laser therapy and the third most commonly performed procedure with more than one million treatments in United States in 2016. This retrospective study was conducted to assess long-term efficacy and safety of the 755 nm laser for hair removal. Study design/materials and methods Nearly, 3,606 laser treatments were performed with the long-pulsed 755 nm wavelength laser equipped with an epidermal cooling device between 1997 and 2005 and were followed till 2013. Standardized assessments were conducted by two treating physicians and patients at two follow-up intervals. At first follow-up, clearance was assessed by two physicians and clearance and satisfaction by patients. At the second follow-up, patients were assessed if hair clearance sustained compared with the first follow-up. Results Nine hundred and forty-eight patients with Fitzpatrick skin types I-IV were treated with a total of 3,606 laser treatments in this study. The mean age at the beginning of the study was 35 years (±11), 95.1% of patients were female (n = 902) and 4.9% male (n = 46). Five hundred and seventy-four patients received a minimum of three treatments and an average of 5.31 (3-16) treatments on axilla, back, bikini, breast, abdomen, face, lower extremity, or upper extremity region. First, follow-up was conducted 3.9 (±1.5) years after the final laser treatment. Seventy-four percent of these patients received 75-100% clearance as reported by the physician and 48% clearance as reported by the patient. Fifty-two percent of patients reported slower hair growth and 42% change in hair texture. Ninety percent of patients treated on axilla, 82% treated on the bikini area, and 79% treated on lower extremities experienced 75% or more clearance after three treatments. Facial, as well as breast and abdomen treatments, only showed a 66% and 62%, respectively, after three treatments. For these locations, five and more treatments were needed to achieve a quote of 79% (face) or 80% (breast and abdomen) for a 75-100% clearance. Upper extremity and back treatments did not have enough physician ratings to draw conclusions. Long-term adverse events were minimal and were all located on the face (one patient scar, four patients herpes infection). Second follow-up of 173 patients was conducted after 11.5 years (±2.0) and 87.9% of patients reported that their improvement sustained. Conclusions The long-pulsed 755 nm alexandrite laser is a safe and efficacious treatment for the reduction of unwanted body hair with permanent results and high patient satisfaction. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

ObjectiveTo assess the reliability and variability of digital calipers, 3D photography, and high-frequency ultrasound (HFUS) for measurement of cutaneous neurofibromas (cNF) in patients with neurofibromatosis type 1 (NF1).BackgroundcNF affect virtually all patients with NF1 and are a major source of morbidity. Reliable techniques for measuring cNF are needed to develop therapies for these tumors.MethodsAdults with NF1 were recruited. For each participant, 6 cNF were assessed independently by 3 different examiners at 5 different time points using digital calipers, 3D photography, and HFUS. The intraclass correlation coefficient (ICC) was used to assess intrarater and interrater reliability of linear and volumetric measurements for each technique, with ICC values >0.90 defined as excellent reliability. The coefficient of variation (CV) was used to estimate the minimal detectable difference (MDD) for each technique.ResultsFifty-seven cNF across 10 participants were evaluated. The ICC for image acquisition and measurement was >0.97 within and across examiners for HFUS and 3D photography. ICC for digital calipers was 0.62–0.88. CV varied by measurement tool, linear vs volumetric measurement, and tumor size.ConclusionsHFUS and 3D photography demonstrate excellent reliability whereas digital calipers have good to excellent reliability in measuring cNF. The MDD for each technique was used to create tables of proposed thresholds for investigators to use as guides for clinical trials focused on cNF size. These criteria should be updated as the performance of these end points is evaluated.

Background and Objective Ablative fractional laser treatment uses thousands of very small laser beam wounds to damage a fraction of the skin, which stimulates tissue remodeling. Each open micro-wound heals without scarring, but the amount of skin tightening achieved is limited. This animal study was performed to test the hypothesis that immediate temporary closure of fractional laser wounds could increase skin tightening after fractional ablative laser treatment. Materials and Methods Four adult swine were used for the study; 98 square test sites (3 × 3 cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat the test areas. A laser micro-spot fluence of 375 J/cm2 was delivered in 150–250 microseconds pulses, resulting in an array of ablation channels extending 1.5 mm deep into the skin, with a spot size of 250 µm, with 10% treatment density. Immediately following laser exposure the resulting holes were closed using a stretched elastic adhesive dressing, which, when applied, recoiled and compressed the diameter of the ablation holes. The compressive dressings were removed after 7 days. This procedure was compared to removing the same amount of skin (10%) mechanically by specially designed 19 gauge coring needles, as well as to the same laser and coring methods without compression closure. Area and shape of test sites were measured by digital photography before and 28 days after treatment. Data analysis included compensation for animal growth, as measured by increase in the area of the untreated control sites. Results All treated and control sites healed within a week, without scarring evident at 28 days. Laser treatment combined with compressive wound closure caused significant shrinkage at 28 days compared with untreated control sites. The treated skin area was reduced by 11.5% (P = 0.0001). Needle coring with wound closure produced similar, significant shrinkage (8%, P

Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints.

We present evidence-based design principles for three different UV-C based decontamination systems for N95 filtering facepiece respirators (FFRs) within the context of the SARS-CoV-2 outbreak of 2019–2020. The approaches used here were created with consideration for the needs of low- and middle-income countries (LMICs) and other under-resourced facilities. As such, a particular emphasis is placed on providing cost-effective solutions that can be implemented in short order using generally available components and subsystems. We discuss three optical designs for decontamination chambers, describe experiments verifying design parameters, validate the efficacy of the decontamination for two commonly used N95 FFRs (3M, #1860 and Gerson #1730), and run mechanical and filtration tests that support FFR reuse for at least five decontamination cycles.

Background and Objective Skin changes are among the most visible signs of aging. Fractional ablative lasers improve skin quality by making small skin wounds that heal rapidly without scarring. While they improve skin texture and discoloration, there is minimal effect on skin laxity. This study was performed to assess skin shrinkage performed by removing multiple small full-thickness skin columns with coring needles combined with wound closure. Materials and Methods In 5 swine 116 squares (3 cm2) were demarcated for treatment and control sites. In treatment sites 10% of the skin was removed by full-thickness skin coring needles (19 gauge) and afterwards closed and compressed with an elastic adhesive dressing. This procedure was compared to puncturing the skin with standard hypodermic needles (without tissue removal) and subsequent closure with compressive dressing. Area and shape of sites were measured before and 28 days after treatment. Results Test and control sites healed within a week without scarring. Coring with wound closure caused significant shrinkage after 28 days. The treated skin area was reduced by 9% (P

Ablative fractional laser treatment uses thousands of very small laser beam wounds to damage a fraction of the skin, which stimulates tissue remodeling. Each open micro-wound heals without scarring, but the amount of skin tightening achieved is limited. This animal study was performed to test the hypothesis that immediate temporary closure of fractional laser wounds could increase skin tightening after fractional ablative laser treatment.Four adult swine were used for the study; 98 square test sites (3 × 3 cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat the test areas. A laser micro-spot fluence of 375 J/cmAll treated and control sites healed within a week, without scarring evident at 28 days. Laser treatment combined with compressive wound closure caused significant shrinkage at 28 days compared with untreated control sites. The treated skin area was reduced by 11.5% (P = 0.0001). Needle coring with wound closure produced similar, significant shrinkage (8%, P 0.0021), whereas laser and needle coring treatment without closure did not result in significant area reduction (P = 0.1289) compared with untreated control sites.Significant skin tightening can be achieved by immediate temporary non-invasive wound closure after short pulse Er:YAG fractional ablative laser treatment, as well as after mechanically removing skin with a coring needle. This approach may improve skin tightening after ablative laser treatments. Further clinical studies are necessary to confirm successful application in humans. Lasers Surg. Med. 50:64-69, 2018. © 2017 Wiley Periodicals, Inc.

Background and Objectives 5-Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) are porphyrin precursors used topically for photodynamic therapy (PDT). Previous studies have established that ablative fractional laser (AFXL) increases topical drug uptake. We evaluated kinetics and biodistribution of ALA- and MAL-induced porphyrins on intact and disrupted skin due to AFXL. Materials and Methods Two Yorkshire swine were exposed to CO2 AFXL (10.6 µm, 1,850 µm ablation depth) and subsequent topical application of ALA and MAL cream formulations (20%, weight/weight). Porphyrin fluorescence was quantified by digital fluorescence photography (30, 90, and 180 minutes) and fluorescence microscopy at specific skin depths (180 minutes). Results Porphyrins gradually formed over time, differently on intact and AFXL-disrupted skin. On intact skin (no AFXL), fluorescence photography showed that MAL initially induced higher fluorescence than ALA (t = 30 minutes MAL 21.1 vs. ALA 7.7 au, t = 90 minutes MAL 39.0 vs. ALA 26.6 (P

Background and Objectives Cryolipolysis is a noninvasive and well-tolerated treatment for reduction of localized subcutaneous fat. Although several studies demonstrate the safety and efficacy of this procedure, volumetric fat reduction from this treatment has not been quantified. This prospective study investigated the change in volume of fat after cryolipolysis treatment using three-dimensional (3D) photography. Materials and Methods A prospective study of subjects treated with cryolipolysis on the flank (love handle) was performed at Massachusetts General Hospital. Volume measurements were performed with a Canfield Scientific Vectra three-dimensional camera and software to evaluate the amount of post procedure volume change. Clinical outcomes were assessed with caliper measurements, subject surveys, and blinded physician assessment of photographs. Results Eleven subjects were enrolled in this study. Each subject underwent a single cycle of cryolipolysis to one flank. The untreated flank served as an internal control. The follow-up time after treatment was 2 months. The mean amount of calculated absolute fat volume loss using 3D photography from baseline to 2 months follow-up visit was 56.2 ± 25.6 from the treatment site and 16.6 ± 17.6 cc from the control (P

Conventional microscopy requires viewing a thin-cut “section” of fixed or frozen tissue, and therefore cannot be used to view thick tissue samples or for in vivo investigations. In vivo microscopy requires a virtual, rather than a physical, section of the specimen. Confocal microscopy, developed and patented by Marvin Minsky in 1955, uses optical imaging to create a virtual slice or plane, many micrometers deep, within the tissue. It provides very-high-quality images with fine detail and more contrast than conventional microscopy. In addition, the imaging technique allows for reconstruction of virtual 3-dimensional (3-D) images of the tissue when multiple sections are combined.

The success of permanent laser hair removal suggests that selective photothermolysis (SP) of sebaceous glands, another part of hair follicles, may also have merit. About 30% of sebum consists of fats with copious CH(2) bond content. SP was studied in vitro, using free electron laser (FEL) pulses at an infrared CH(2) vibrational absorption wavelength band.Absorption spectra of natural and artificially prepared sebum were measured from 200 to 3,000 nm, to determine wavelengths potentially able to target sebaceous glands. The Jefferson National Accelerator superconducting FEL was used to measure photothermal excitation of aqueous gels, artificial sebum, pig skin, human scalp, and forehead skin (sebaceous sites). In vitro skin samples were exposed to FEL pulses from 1,620 to 1,720 nm, spot diameter 7-9.5 mm with exposure through a cold 4°C sapphire window in contact with the skin. Exposed and control tissue samples were stained using HE, and nitroblue tetrazolium chloride staining (NBTC) was used to detect thermal denaturation.Natural and artificial sebum both had absorption peaks near 1,210, 1,728, 1,760, 2,306 and 2,346 nm. Laser-induced heating of artificial sebum was approximately twice that of water at 1,710 and 1,720 nm, and about 1.5× higher in human sebaceous glands than in water. Thermal camera imaging showed transient focal heating near sebaceous hair follicles. Histologically, skin samples exposed to ~1,700 nm, ~100-125 milliseconds pulses showed evidence of selective thermal damage to sebaceous glands. Sebaceous glands were positive for NBTC staining, without evidence of selective loss in samples exposed to the laser. Epidermis was undamaged in all samples.SP of sebaceous glands appears to be feasible. Potentially, optical pulses at ~1,720 or ~1,210 nm delivered with large beam diameter and appropriate skin cooling in approximately 0.1 seconds may provide an alternative treatment for acne.

Summary Background Photodynamic therapy (PDT) is a nonsurgical alternative to conventional tumour excision for nonmelanoma skin cancers (NMSCs). Objectives We evaluated whether patients with field cancerization (multiple NMSCs) treated with aminolaevulinic acid (ALA) or its methylester (MAL) for that indication had PDT-induced changes in surgical scars in the treatment field. Methods Six adult patients with multiple NMSCs and a total of 21 scars from previous excisions were studied in a retrospective blinded evaluation from clinical photographs of scar response to ALA/MAL-PDT. After a 3-h application of topical 20% ALA or 16·8% MAL under occlusion, each field was irradiated with 635-nm light-emitting diode light at the fluence of 200 J cm−2. Patients underwent one to three PDT sessions per field at ∼1 month intervals, to fields that included scars on the back, thigh, arms and neck. Pre- and post-treatment digital photographs of scars were combined into 92 pairs that were independently and blindly evaluated by three board-certified dermatologists. This study was performed at our academic practice at the Massachusetts General Hospital. Results PDT produced a statistically significant improvement in scar appearance. The degree of improvement correlated with the number of treatment sessions (two or three treatments; P

Background and Objective Basal Cell Nevus syndrome (BCNS) is characterized by numerous basal cell carcinomas (BCCs). Multiple treatments with the pulsed dye laser (PDL) have been shown, in small studies, to be effective for the treatment of superficial and nodular BCCs. Like PDL, the alexandrite laser can be vessel-selective, but has the added advantage of deeper tissue penetration. We evaluated the utility of the alexandrite laser in reducing the tumor burden in BCNS with a single treatment. Study Design/Materials and Methods A case report and review of the literature are presented. A 45-year-old man with BCNS and a history of radiation therapy presented with an extraordinarily high tumor burden (>250 BCCs). As a compassionate measure to reduce the tumor burden, we investigated the utility of a single treatment of the long-pulsed 755 nm alexandrite laser to several BCC lesions. The treated lesions were evaluated at 2-month and 7-month clinical follow-up. Histopathologic analysis of a treated lesion was performed at 7-month clinical follow-up. Results At 2-month, and 7-month clinical follow-up, 15 of 18 treated lesions or about 83% of the alexandrite laser treated lesions showed a complete clinical response and appeared as hypopigmented areas with scarring. Histopathologic analysis of a treated lesion at 7-month clinical follow-up showed no evidence of residual tumor. Conclusions The long-pulsed alexandrite laser may be helpful in significantly reducing tumor burden in difficult to manage BCNS patients with a single treatment. This provides a facile and practical treatment alternative for the management of challenging cases of BCNS. The limitation of this study is that it is a single case observation. Larger, prospective studies are needed to confirm these observations. Lasers Surg. Med. 42:68–71, 2011 © 2011 Wiley-Liss, Inc.

The first-line treatments for acne vulgaris are conventional topical and/or oral medications. However, many patients have contraindications, only partial response, significant adverse effects, or recurrence. Light-based treatments and photodynamic therapy (PDT) using topical precursors of porphyrins are off-label alternative treatments for acne vulgaris, with their own advantages and disadvantages. To date, there is no consensus on PDT methodology and parameters. An understanding of pathophysiology of acne, light-tissue interactions, and PDT mechanisms of action is helpful whenever PDT is considered as an alternative treatment. In general, blue light alone improves acne because of its antiinflammatory effects. PDT using 5-aminolevulenic acid (ALA) or ALA derivatives induces transient antimicrobial and antiinflammatory effects. At high doses, red light PDT may induce inhibition or destruction of sebaceous glands, resulting in clinical improvement. Learning objectives After completing this learning activity, participants should be able to compare different treatments of acne, recognize when photodynamic therapy may be a useful off-label treatment for acne vulgaris, and identify variables that may affect the efficacy of photodynamic therapy.

Background and Objectives: Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO2 laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug. Materials and Methods: Two Yorkshire swine were treated with single-hole CO2 laser AFR and subsequent topical application of MAL (Metvix 1 , Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800mm. AFR was performed with a 10.6mm wavelength prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse. Results: AFR created cone-shaped channels of approximately 300mm diameter and 1,850mm depth that were surrounded by a 70mm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P

The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AK) is lower on the distal extremities compared with head and neck areas. A recent pilot study demonstrated increased efficacy of ALA PDT when the skin is warmed during ALA incubation. Prolonged clearance rates on the heated extremity were noted in 3 subjects that were evaluated after the study ended. The aim of this study was to evaluate the longevity of clearance rates after temperature-modulated PDT for the treatment of AKs on the extremities.A total of 18 subjects (20 pairs of extremities) with at least 10 AKs on the upper or lower extremities were enrolled in the single-center study. Twenty percent ALA was applied to both extremities and heated during the 1-hour incubation period, followed by exposure to 10 J/cm 417-nm blue light. Lesions were photographed, counted, and templated at baseline, 1 week, and 3, 6, 9, and 12 months after treatment.A total of 17 subjects completed the 1-year study. The total number of lesions counted at baseline was 724 Grade 1 and 2 AKs (median 15 on each extremity). The lesion count at 3 and 12 months was 70 (9.6%) and 72 (9.9%), respectively. Grade 3 AKs did not resolve with treatment. The median baseline temperature of the treated extremities was 31.6°C. The median maximum temperature during the 1-hour incubation period was 41.2°C. The median clearance at 3 months was 90% and the same was maintained at 12 months. No new AK lesions formed in the treated areas within the 12-month follow-up period.Warming the skin after application of ALA is well tolerated, does not increase side effects, and increases the long-term efficacy of PDT for the treatment of AKs. The authors suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice.

We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat- or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (

Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints.

Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10-50 J cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1-2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris.

The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AKs) is lower on the distal extremities compared with the head and neck areas. The strong temperature dependence of porphyrin synthesis in biologic tissue suggests that heating skin during incubation may improve the efficacy of PDT, particularly in areas where biologic temperatures are naturally lower. The aim of this study was to evaluate the efficacy and tolerability of temperature-modulated PDT for the treatment of AKs on the extremities.In this IRB-approved, single-center study, the upper or lower extremities of 20 subjects were treated with 20% ALA under occlusion, followed by 10 J/cm, 417-nm blue light. One of the 2 extremities treated was heated during the 1-hour incubation. Outcome measures included lesion counts, tolerability, and global improvement at baseline, 1 week, and 2 and 6 months after treatment.The median temperatures of the heated and control sides were 38.8°C and 29.4°C, respectively. The median clearance for the heated side was significantly greater than the control side at 2 and 6 months (p.0001). Typical PDT side effects were greater on the heated side compared with the control yet were well tolerated by all subjects.Warming the skin during incubation of ALA seems to improve the efficacy of PDT in the treatment of AKs on the extremities and is well tolerated when heat application is controlled within the limits of safety.

As an alternative method to conventional split-thickness skin grafts (STSGs), we recently proposed fractional skin grafting (FSG), which consists in harvesting hundreds of microscopic skin tissue columns (MSTCs) to place them directly into the skin wound (Tam et al., 2013, “Fractional Skin Harvesting: Autologous Skin Graft Without Donor Site Morbidity,” Plast. Reconstructive Surgery–Global Open, 1(6)). This paper (i) introduces the concept and operational principles of a simple but robust fractional skin harvesting (FSH) device and (ii) presents the quantitative evaluation of the deployment of the FSH device with respect to different harvesting-needle sizes. The device utilizes a hypodermic needle with a specific cutting-geometry to core skin tissue mechanically. The tissue core is removed from the donor site into a collecting basket by air and fluid flows. The air flow transports the tissue core, while the fluid flow serves the purpose of lubrication for tissue transport and wetting for tissue preservation. The design and functionality of the device were validated in an animal study conducted to establish preclinical feasibility, safety and efficacy of the proposed FSH device and FSG method. The FSH device, operating at 55.16 kPa (8 psi) gauge pressure and 208 ml/min saline flow rate, cored 800 μm diameter × 2.5 mm length skin columns using a 1.05/0.81 mm outer/inner diameter needle. The MSTC harvesting rate was established by the user at 1 column/sec. For this columns size, about 50 MSTCs are required to cover a 1.5 cm × 1.5 cm wound. In comparison to STSGs, the proposed FSG method results in superior healing outcomes on the donor and wound sites. Most important, the donor site heals without morbidity by remodeling tissue, as opposed to scarring. The FSH device has the capability of extracting full-thickness skin columns while preserving its viability and eliminating the donor site morbidity associated with skin grafting.

5-Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) are porphyrin precursors used topically for photodynamic therapy (PDT). Previous studies have established that ablative fractional laser (AFXL) increases topical drug uptake. We evaluated kinetics and biodistribution of ALA- and MAL-induced porphyrins on intact and disrupted skin due to AFXL.Two Yorkshire swine were exposed to CO2 AFXL (10.6 µm, 1,850 µm ablation depth) and subsequent topical application of ALA and MAL cream formulations (20%, weight/weight). Porphyrin fluorescence was quantified by digital fluorescence photography (30, 90, and 180 minutes) and fluorescence microscopy at specific skin depths (180 minutes).Porphyrins gradually formed over time, differently on intact and AFXL-disrupted skin. On intact skin (no AFXL), fluorescence photography showed that MAL initially induced higher fluorescence than ALA (t = 30 minutes MAL 21.1 vs. ALA 7.7 au, t = 90 minutes MAL 39.0 vs. ALA 26.6 (P 0.009)) but reached similar intensities for long-term applications (t = 180 minutes MAL 56.6 vs. ALA 52 au, P = ns). AFXL considerably enhanced porphyrin fluorescence from both photosensitizers (P 0.05). On AFXL-exposed skin, MAL expressed higher fluorescence than ALA for short-term application (t = 30 minutes, AFXL-MAL 26.4 vs. AFXL-ALA 14.1 au, P 0.001), whereas ALA over time overcame MAL and induced the highest fluorescence intensities obtained (t = 180 minutes, AFXL-MAL 98.6 vs. AFXL-ALA 112.0 au, P 0.001). In deep skin layers, fluorescence microscopy showed higher fluorescence in hair follicle epithelium for ALA than MAL (t = 180 minutes, 1.8 mm, AFXL-MAL 35.3 vs. AFXL-ALA 46.7 au, P 0.05).AFXL changes kinetics and biodistribution of ALA and MAL. It appears that AFXL-ALA favors targeting deep structures.

Scrotal calcinosis has been classified as a form of idiopathic calcinosis cutis. However, the pathogenesis of the calcified nodules has not been fully elucidated: it is still unclear whether the condition is truly idiopathic, or the result of breakdown of calcified epithelial cysts. We describe a 29-year-old Japanese patient with scrotal calcinosis originating from epithelial cysts. Light microscopy revealed a large epithelial cyst containing von Kossa-positive material and several small dilated ductal structures beside the cyst. The epithelia of the cyst and ductal structures were connected, showing similar eccrine duct differentiation on immunohistochemical staining and electron microscopy. In the cyst lumen, calcium was present as needle-shaped crystals. The pathogenetic mechanism of calcium deposition seemed to be due to excessive production and discharge of matrical debris and sulphated mucopolysaccharides, which derived from luminal cells, and their accumulation in the lumina.

Basal Cell Nevus syndrome (BCNS) is characterized by numerous basal cell carcinomas (BCCs). Multiple treatments with the pulsed dye laser (PDL) have been shown, in small studies, to be effective for the treatment of superficial and nodular BCCs. Like PDL, the alexandrite laser can be vessel-selective, but has the added advantage of deeper tissue penetration. We evaluated the utility of the alexandrite laser in reducing the tumor burden in BCNS with a single treatment.A case report and review of the literature are presented. A 45-year-old man with BCNS and a history of radiation therapy presented with an extraordinarily high tumor burden (250 BCCs). As a compassionate measure to reduce the tumor burden, we investigated the utility of a single treatment of the long-pulsed 755 nm alexandrite laser to several BCC lesions. The treated lesions were evaluated at 2-month and 7-month clinical follow-up. Histopathologic analysis of a treated lesion was performed at 7-month clinical follow-up.At 2-month, and 7-month clinical follow-up, 15 of 18 treated lesions or about 83% of the alexandrite laser treated lesions showed a complete clinical response and appeared as hypopigmented areas with scarring. Histopathologic analysis of a treated lesion at 7-month clinical follow-up showed no evidence of residual tumor.The long-pulsed alexandrite laser may be helpful in significantly reducing tumor burden in difficult to manage BCNS patients with a single treatment. This provides a facile and practical treatment alternative for the management of challenging cases of BCNS. The limitation of this study is that it is a single case observation. Larger, prospective studies are needed to confirm these observations.

Background Optimal selective photothermolysis of a pigment particle requires pulse durations equal to or less than the particle's thermal relaxation time (t½). Since tattoo particles in skin range in diameter from 40 to 300 nm, picosecond pulses would approximate t½ more closely and, therefore, might be more effective at tattoo particle fragmentation. Materials and Methods India Ink (carbon) or iron oxide tattoos were placed on the back of a Yorkshire pig. Six weeks later, each tattoo was treated with either a 758 nm 500 picosecond laser (Cynosure), a 755 nm 30–50 nanoseconds laser, or left untreated. After 4 weeks, clinical responses were evaluated by three dermatologists based on pre- and post-treatment photographs; histopathologic findings were evaluated by a dermatopathologist; and electron microscopic findings were analyzed for treated and non-treated carbon tattoos. Results After a single treatment, picosecond-domain pulses at 758 nm produced a significantly greater degree of carbon tattoo clearance compared to nanosecond-domain pulses at 755 nm. For iron oxide tattoos, both modalities produced minimal-to-poor clearance that was generally comparable. Neither modality resulted in scarring, textural changes, or hypopigmentation, and there was no histopathologic evidence of scarring. Electron micrographs revealed the presence of amorphous material (treated pigment) in picosecond and nanosecond laser-treated tattoos, consistent with effective targeting of India Ink pigment. Conclusions The 758 nm 500 picosecond laser is more effective at carbon tattoo clearance after one session in a porcine model than the 30–50 nanosecond laser emitting at a similar wavelength. Both lasers cleared carbon tattoos more effectively than iron oxide tattoos. Both lasers have a comparable safety profile, and neither produced clinical or histopathologic scarring. Further studies in humans are necessary to evaluate whether repeated treatments with picosecond versus nanosecond domain modalities might yield superior tattoo pigment clearance with a comparable safety profile. Lasers Surg. Med. 42:640–646, 2010. © 2010 Wiley-Liss, Inc.

Background Q-switched lasers are the gold standard for tattoo treatment. Allergic tattoo reactions present a treatment dilemma. We present the application of ablative fractional resurfacing (AFR) as a novel method for tattoo removal. Objective We describe two patients with tattoo allergies, referred to us for treatment. Methods AFR was used in a series of treatments to remove the allergic-ink portion of a multicolored tattoo on the upper extremity of a 52-year-old man. In a 31-year-old woman with a red and black tattoo on her lower extremity, AFR was combined with a Q-switched neodymium:yttrium-aluminum-garnet laser. Results After a series of treatments, both patients experienced significant to complete removal of the offending tattoo inks with substantial or complete resolution of their symptoms. Limitations This uncontrolled observational series is based on two patients. Conclusions AFR appears to be safe and effective for removal of allergic tattoos. AFR can be combined with other treatments such as Q-switched lasers. The potential for a series of AFR treatments to remove tattoos, including allergic tattoos and inks of any color, merits further study.

Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO(2) laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug.Two Yorkshire swine were treated with single-hole CO(2) laser AFR and subsequent topical application of MAL (Metvix(R), Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 microm. AFR was performed with a 10.6 microm wavelength prototype CO(2) laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse.AFR created cone-shaped channels of approximately 300 microm diameter and 1,850 microm depth that were surrounded by a 70 microm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P0.0011) and dermis (P0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 microm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 microm from the holes (1,000, 1,800 microm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR.Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications.

Photodynamic therapy requires a photosensitizer, oxygen, and activating light. For acne, pilosebaceous units are "target" structures. Porphyrins are synthesized in vivo from 5-aminolevulinic acid (ALA), particularly in pilosebaceous units. Different photosensitizers and drug delivery methods have been reported for acne treatment. There are a variety of porphyrin precursors with different pharmacokinetic properties. Among them, ALA and methyl-ester of ALA (MAL) are available for possible off-label treatment of acne vulgaris. In addition, various light sources, light dosimetry, drug incubation time, and pre- and posttreatment care also change efficacy and side effects. None of these variables has been optimized for acne treatment, but a number of clinical trials provide helpful guidance. In this paper, we critically analyze clinical trials, case reports, and series of cases published through 2009.After completing this learning activity, participants should be able to analyze photodynamic therapy using 5-aminolevulinic acid and its derivates for acne treatment, predict the effectiveness and outcomes of photodynamic therapy using different parameters and/or different porphyrin-related photosensitizers, and assess and manage the side effects of porphyrin-based photodynamic therapy for acne.

The first-line treatments for acne vulgaris are conventional topical and/or oral medications. However, many patients have contraindications, only partial response, significant adverse effects, or recurrence. Light-based treatments and photodynamic therapy (PDT) using topical precursors of porphyrins are off-label alternative treatments for acne vulgaris, with their own advantages and disadvantages. To date, there is no consensus on PDT methodology and parameters. An understanding of pathophysiology of acne, light-tissue interactions, and PDT mechanisms of action is helpful whenever PDT is considered as an alternative treatment. In general, blue light alone improves acne because of its antiinflammatory effects. PDT using 5-aminolevulenic acid (ALA) or ALA derivatives induces transient antimicrobial and antiinflammatory effects. At high doses, red light PDT may induce inhibition or destruction of sebaceous glands, resulting in clinical improvement.After completing this learning activity, participants should be able to compare different treatments of acne, recognize when photodynamic therapy may be a useful off-label treatment for acne vulgaris, and identify variables that may affect the efficacy of photodynamic therapy.

Background and Objective: Aminolevulinic acid photodynamic therapy (ALA-PDT) depends on drug metabolism into porphyrins. Clinically, ALA-PDT has been used with a wide range of protocols for treating both epidermal and dermal targets, despite limited understanding of porphyrin biodistribution over time. We studied porphyrin accumulation after topical application of ALA in vivo, and also describe the porcine ear as a new animal model to study adnexal glands. Study Design/Materials and Methods: The microanatomy of anterior ear skin of swine was measured. Topical 20% ALA in water/ethanol was applied under occlusion. Biopsies taken after 5, 10, 15, and then every 15 minutes for a total of 3 hours were examined by fluorescence microscopy of frozen sections to assess accumulation and distribution of porphyrins. Results: Porphyrin fluorescence of digital photomicrograph images was not visually apparent until 30– 45 minutes after application, although quantitative pixel analysis showed a statistically significant increase in epidermal fluorescence only 15 minutes after ALA application. From 30 to 120 minutes, epidermis, hair follicles (HF), and sebaceous glands (SG) became progressively more fluorescent. Eccrine gland fluorescence began to be detected after 30 minutes; SG showed fluorescence starting at 45–75 minutes. Fluorescence in all sites reached maximum intensity from 75 to 180 minutes of incubation. There was a trend for HF and SG to express stronger fluorescence compared with epidermis and eccrine glands. Conclusion: Anterior pig ear skin is microanatomically similar to human sebaceous skin. The time-dependent accumulation of porphyrins in pilosebaceous units and eccrine glands in this model suggests other routes of uptake of topical ALA in addition to the trans-epidermal route. Apparently, time interval between ALA application and light exposure could be optimized for different uses of ALA-PDT. Lasers Surg. Med. 41:154–160, 2009. 2009 Wiley-Liss, Inc.

Adult T-cell leukemia/lymphoma (ATLL) is a malignant proliferation of mature helper T lymphocytes,(1) and is caused by human T-lymphotropic virus type I (HTLV-I);(2) an HTLV-I infection endemic in the Caribbean, south-western Japan, South America and Africa.(3,4) Seroepidemiological studies suggest that it is also endemic in Brazil.(5) Although carriers of HTLV-I show polyclonal integration of virus in T lymphocytes, only patients with ATLL of various subtypes show monoclonal integration of HTLV-I in tumor cells.(6,7) Cutaneous T-cell lymphomas (CTCL) are a group of primary cutaneous lymphoproliferative diseases(8) with unknown etiology.(9) The two most common presentations of CTCL are mycosis fungoides (MF) and Sezary syndrome (SS).(10-13) However, both CTCL categories can easily resemble ATLL. Therefore, in HTLV-I endemic areas, differentiation between ATLL and CTCL must be performed, as they have different prognoses and treatment approaches.(14).

Skin wounds that are too extensive to heal by primary closure often require reconstruction by autologous grafting or flap transplantation,1 which in turn requires harvesting of donor skin, causing morbidities—including pain, risk of infection, discoloration, and scarring—that are frequently more troublesome for patients than the primary wounds themselves.2,3 Split-thickness skin grafting (STSG), the current “gold standard” for closing large skin wounds,4 involves harvesting the epidermis and the upper portion of dermis from donor sites, and then transplanting the grafts onto the wound(s). STSGs are generally less damaging to donor sites (although donor-site morbidities are still substantial), and have higher “take” rates, than full-thickness grafts. However, because deep dermal structures such as hair follicles and sweat glands are not harvested, the STSG is aesthetically and functionally abnormal and scar-like. In addition, STSGs are usually meshed and expanded before grafting, which increases area coverage and facilitates fluid drainage but also causes a permanent, unsightly “fish-net” appearance in the grafted skin. Much effort has been invested in finding/developing exogenous graft materials, such as cadaveric skin, xenografts, and artificial skin substitutes.5 At present, these options can only provide temporary wound coverage, and eventual autologous grafting remains necessary. Alternative wound closure technologies that minimize donor-site morbidity, provide STSG-like graft reliability without unsightly texture, and can be performed easily in practice would be very beneficial. Scarring at the donor and/or graft site is one of the most problematic morbidities associated with autologous skin grafting. Scarring is nature’s way of quickly filling large voids in tissue, with a haphazard arrangement of connective tissue elements. Scar tissue is stiff, often painful, dysfunctional, and tends to contract over time, causing deformities. The arrangement of extracellular matrix and specialized dermal structures that confer function to normal tissue is missing.6 In contrast to scarring, a process that haphazardly replaces grossly missing tissue, remodeling is a process that replaces tissue while maintaining tissue architecture on the microscopic scale. Remodeling occurs in every organ as we age and grow, and it is abundantly clear that almost every tissue has the capacity for local remodeling without scarring. While scarring is stimulated by large-scale tissue damage, remodeling is stimulated by microscopic tissue damage. This principle became clear when we developed fractional photothermolysis (FP),7 which is now in widespread clinical use to improve photoaged skin and various lesions including wound scars.8 In FP, laser microbeams are used to produce hundreds to thousands of microscopic thermal burns per cm2 of skin surface, creating very thin columns of thermal damage or tissue removal, called “microthermal zones.” Microthermal zones less than about 300 µm in diameter heal rapidly without scarring.9 The differences between FP and third-degree skin burns are striking. Both involve extensive, full-thickness (ie, including complete epidermis and dermis) thermal damage, but third-degree burns heal slowly with scarring, whereas after FP the epidermis closes within 1 day, and the dermal injury is repaired in about 2 weeks, followed by continued tissue remodeling without scarring.9 Amazingly, up to 50% of the volume of normal skin can be killed or removed by FP—followed by rapid replacement of the lost tissue by remodeling, resulting in new skin tissue that is both functionally and aesthetically normal.9 Since our experience with FP established that millions of small, full-thickness columns of skin tissue can be removed without causing scarring, we hypothesized that similarly large numbers of full-thickness microscopic skin tissue columns (MSTCs) could be harvested from healthy skin with negligible donor-site morbidity and that these MSTCs could serve as a graft to improve skin wound healing. The current study was performed to test these hypotheses in the swine, a commonly used model for human skin.10,11

The distribution of immunoreactivity of bone morphogenetic protein (BMP), the glycosaminoglycans chondroitin 4-sulphate (C4SPG), chondroitin 6-sulphate (C6SPG), dermatan sulphate (DSPG) and keratan sulphate proteoglycans (KSPG), cytokeratin (K8.12), vimentin, glial fibrillary acidic protein (GFAP), actin, desmin, S-100 protein and neuron-specific enolase (NSE) in mixed tumour of the skin was investigated using immunohistochemical methods using monoclonal (MoAb) and polyclonal antibodies (PoAb). A strong BMP immunoreactivity was found characteristically in outer tumour cells of tubuloductal structures and modified myoepithelial cells. Modified myoepithelial cells and chondroidally changed cells showed positive immunoreactivity for C4SPG, C6SPG and DSPG; and KSPG was more pronounced in the modified myoepithelial cells. Vimentin, S-100 protein, GFAP and NSE, but not actin and desmin, were distribute in the outer tumour cells and modified myoepithelial cells in chondroidally changed tissue. Two factors show that chondrogenesis in mixed tumour of the skin is associated with the modified myoepithelial cells through the activity of BMP and biosynthesis of glycosaminoglycans as matrix substance. First, outer or basal tumour cells in mixed tumour of the skin is characterized by the presence of positive immunoreactivity for BMP, KSPG, vimentin, cytokeratin K8.12, S-100 protein, GFAP and NSE, and second, there is a matrix of chondroidally changed tissue containing the reaction products of C4SPG, C6SPG, DSPF and KSPG.

Plucked scalp hairs and hair roots of pili annulati were examined to understand their pathogenesis. Stereoscopic examinations of hairs in transmitted light and/or reflected light and light microscopic surveys of the cross-sections of hairs confirmed that the cortical empty spaces appeared to be responsible to the unique dotted shiny appearance of the hairs seen by the unaided eyes under a refracted light. By transmission electron microscope, small vacuoles and dense bodies were observed in the cytoplasm of the differentiating cortical cells; subsequently, with increasing number of tono-filaments, an uneven distribution of free ribosomes occurred and abnormal spaces containing fine granular substances were formed in the cytoplasm of the cortical cells. Occasionally, extremely large cortical trichohyaline granules were found. In the keratinized hair, irregular empty spaces were present in the cortex of the abnormal hair segments. Histochemically, the keratinized cortex of the affected hairs always had more residual SH groups than the controls. Pili annulati may be a disorder of protein metabolism involving a partial dysfunction of cytoplasmic ribosomes, resulting in a lack of cortical keratin formation.

Substance P is known to be a potent histamine liberator for mast cells. The influence of antianaphylactic agents, disodium cromoglycate (DSCG), ketotifen, and tranilast was studied on substance-P and compound 48/80-induced histamine release from rat peritoneal mast cells. Substance-P induced histamine release was inhibited by these agents, while compound 48/80-induced histamine release was not inhibited by tranilast. Our findings suggest that these antianaphylactic agents are assumed to be effective for cutaneous diseases which might be concerned with substance P and histamine.