Adjacent Skin Research Articles

Expression Profile of CD10, BCL-2, p63, and EMA in the Normal Skin and Basal Cell Carcinomas: An Immunohistochemical Reappraisal

BackgroundBasal cell carcinoma (BCC) is common cutaneous malignancy. AimsTo examine the expression patterns of CD10, p63, BCL-2, and epithelial membrane antigen (EMA) proteins in BCC. Materials and methodsWe used immunohistochemistry to evaluate the expression pattern of these proteins in 45 BCC specimens and their adjacent normal skin. ResultsWe found variations in the expression pattern of these proteins among normal skins and BCC. In normal skins, we found strong EMA cytoplasmic expression (adnexal structures). A strong nuclear p63 protein expression was found in basal and some suprabasal keratinocytes, external root sheath cells of the hair follicles, basal cells of the sebaceous glands, and in sweat glands.CD10 protein expression was seen in peri-adnexal mesenchymal spindle cells and myoepithelial cells of sweat glands.BCL-2 protein expression was confined to the basal cell keratinocytes, epidermal melanocytes, outer root sheath, and infundibulum of the hair follicle. In BCC, we found p63 (diffuse, strong nuclear staining), CD10 (focal, moderate cytoplasmic reactivity), and BCL-2 (focal, moderate cytoplasmic reactivity) protein expression in the neoplastic cells. BCC was consistently negative for EMA (except in areas of squamous differentiation). ConclusionsThere is an altered expression of these proteins in BCC. The underlying molecular mechanisms are open to further investigations.

AB0958 The relationship between the extensor tendon enthesis and the nail in distal interphalangeal joint disease in psoriatic arthritis: ultrasound study

BackgroundIt has been shown that there is an anatomical link between the distal interphalangeal joint (DIP) extensor tendon enthesitis and the nail changes in psoriatic arthritis (PsA) [1].ObjectivesTo evaluate the relationship between nail involvement and enthesopathy at DIP level in PsA patients using ultrasonography (US).MethodsWe included patients with PsA. According to OMERACT, the following elemental lesions were dichotomously (presence/absence) evaluated on greyscale US assessment at extensor tendon insertion at distal phalanx of DIP joints: abnormally hypoechoic, enthesophytes, and erosions. We also measured the tendon thickness. Increased abnormal vascularization at entheseal level was also assessed using PD technique. We also performed an US assessment of the finger nails that included the study of morphological changes and measurement of the thickness of nail bed (NBT), nail plate (NPT) and adjacent skin (ST).ResultsWe included 33 PsA patients (323 DIP). Eleven patients (34 %) presented psoriatic onychopathy (45 fingernails) with a mean NAPSI 7 (IQR (25,75)) [2 -18]. US study of the nails revealed dystrophy in 75 nails (23%).At patient level, the mean NPT, NBT and SK were 1.90±0.22, 0.38±0.09, and 2.33±0.62, respectively.None of the patients had clinical involvement of DIP.Using US, we examined 325 extensor tendon. The mean thickness of the tendon was 0.63mm ±0.1 mm. The tendon was abnormally hypoechoic in two fingers (0.61%).Erosions were present in 16 DIP (4.9%).We found enthesophytes in 82 DIP joints at insertion of extensor digitorum tendon (25.23%).We did not observe increased abnormal vascularization at entheseal level.At finger level, the extensor tendon thickness was higher in the presence of US nail dystrophy (0.70 mm vs 0.60, p=0.01). Erosions were more common in fingers with US nail involvement (14.6 % vs 1.9%, p=0.00).Osteophytes were present in 20% of fingers with US nail involvement and 26.3% of fingers without US nail involvement (p=0.166).The thickness of DIP digital extensor tendons was correlated with the NBT(r = 0.412, p = 0.00), the NPT (r = 0.310, p = 0.00), and the thickness of the adjacent skin (r = 0.509, p = 0.00).ConclusionThe presence of US nail dystrophy was associated with thicker extensor tendon and more erosions. The thickness of the tendon was correlated with the thickness of the nail parts.This might be explained by the close relationship between nail and enthesis and supports the theory of the enthesis as an extended organ beyond the tendon bony attachment.

A pilot study of using thermal imaging to assess hand hygiene technique

Background: Although substantial efforts have been made to improve hand hygiene (HH) compliance among healthcare personnel (HCP), much less attention has been devoted to improving HH technique. To date, no standard method for assessing HH technique has been widely adopted by hospitals. Because applying an alcohol-based hand sanitizer (ABHS) transiently reduces adjacent skin temperature, we explored the feasibility of using thermal imaging to determine whether ABHS has been applied to fingertips and thumbs, areas often missed by HCP. Methods: A convenience sample of 12 Quality and Safety staff volunteered for the study. A FLIR One Pro thermal camera attached to an iPhone was used to obtain thermal images of the palmar aspect of each volunteer’s dominant hand before applying ~1.8 mL ABHS gel, immediately after hands felt dry, and at 1 minute and 2 minutes later. Spot temperature readings of the mid-palm area and middle finger were recorded at each time point. The sex and estimated hand surface area (HSA in cm2) of each volunteer were recorded. Results: In 11 of 12 volunteers, thermal imaging showed a significant decrease in mid-palm and middle finger skin temperatures after performing HH (paired t test P < .01 for both), especially for the fingers and thumb, indicating that ABHS was applied to these areas (Fig. 1). When HH was performed with ABHS and the thumb was purposefully excluded, the lack of colorimetric change in the thumb was visible (Fig. 2). The palmar area showed the least drop in temperature and reverted to normal temperature more quickly. Immediate post-HH mid-palm temperature change ranged from +0.5 to −2.7°C, with a significantly greater mean temperature drop with small or medium hands than with large hands (Mann-Whitney U test P = .048). With some volunteers, the color changes lasted 1 minute or longer. However, for persons with “cold” fingers at baseline, it was more difficult to draw conclusions from the gross assessment for colorimetric change. Conclusions: Thermal imaging of HH performance shows promise as an HH assessment technique and may be useful to determine whether HCP have applied ABHS to their fingertips and thumbs. Additional studies involving a much larger number of HCP under varying conditions are needed to determine whether thermal imaging can be a practical modality for teaching HH technique, for routinely monitoring HH technique, or as a research tool for studying the dynamics of HH using ABHS.Funding: NoneDisclosures: None

Регенеративные эффекты пептидов Gly-His-Lys и Gly-His-Lys-D-Ala при кожной инфицированной ране

Skin wound healing mechanisms and new ways of improving their efficiency represent an important focus in medicine. In this regard, regulatory peptides, which exhibit physiological polyfunctionality and modulate cell growth and differentiation, are of special interest. This study evaluates the effects of Gly-His-Lys (GHK) and Gly-His-Lys-D-Ala (GHK-D-Ala) peptides in the infected skin wound healing. The wounds were modeled in rats (n=150) by full-thickness dorsal skin defects. The peptides were administered intracutaneously at daily doses of 0.5 or 1.5 µg/kg. The healing was assessed on days 3, 7, and 10 by histomorphometric examination of the wounds with adjacent intact skin. GHK-D-Ala administered at daily doses of 0.5 µg/kg had pronounced positive effect on regeneration processes in the wound, as indicated by significantly reduced numbers of granulocytes and lymphocytes with increased representation of fibroblastic lineages and macrophages, and the resulting higher cellular index (p < 0.05–0.001). At higher doses of GHK-D-Ala (1.5 µg/kg), the beneficial effects were less pronounced. According to the comparative morphological examination, the highest positive effect was achieved with 0.5 µg/kg of GHK-D-Ala. Thus, local administration of the GHK peptide with extra D-alanine at carboxy-terminus significantly mitigated the inflammatory reaction and facilitated the healing of infected skin wounds in rat model.

Imaging features of dermatofibrosarcoma protuberans

The study highlights diffusion-weighted imaging (DWI) and dynamic enhancement features of DFSP and characterizes unenhanced and enhanced computed tomography (CT) and magnetic resonance imaging (MRI) scans. Image findings and clinical histories of 23 patients with DFSP were reviewed. Nine patients underwent CT before and after intravenous administration of contrast material. MRI was performed for 17 patients. CT and MRI findings were analyzed using location, size, edge, shape, infiltration sign, density and signal enhancement mode, and degree. Patients showed 26 superficial and one deep lesion. Ten superficial lesions bulged onto the skin surface. Fourteen lesions were well-defined and 13 ill-defined. All lesions were nodular, with nine being multilobular. Thirteen showed infiltration to adjacent skin, fat, and fascia. Seven lesions on CT were iso- or hypo-dense to muscle without calcification. Contrast-enhanced CT showed inhomogeneous moderate and progressive enhancement in the arterial phase. Small tortuous vessels were seen in the arterial phase in one case. Sixteen tumors displayed signals that were similar to muscle by T1WI. Ten lesions were either hyper-intense to muscle or iso-intense to fat; the deep DFSP was hypo-intense by T2WI. All lesions were hyper-intense homogeneously or heterogeneously under fat-suppressed T2WI. Twelve superficial lesions showed high-intermediate signal, and one deep lesion showed low-intermediate signal with DWI. Seven cases showed low signal diffusion coefficient (ADC) images. Dynamic enhancement and signal intensity-time (SI-T) curves of four tumors showed rapid SI increases followed by steady or slightly rising SI. All lesions showed inhomogeneous, progressive enhancement in the arterial phase. This report is the first on dynamic curves and highlights DWI and T2WI features of DFSP. DFSP can be correctly diagnosed by combining a patient's clinical manifestations with imaging characteristics.

Hiding in Plain Sight: A Retrospective Review of Unrecognized Tumors During Dermatologic Surgery.

Background: Mohs micrographic surgery requires focused attention that may lead to tunnel vision bias, contributing to not recognizing skin cancer at nearby sites.Objective: It is to determine if a subsequently diagnosed skin cancer was visible at the time of Mohs surgery.Methods: A retrospective chart review was performed at a single academic center from 2008 to 2020. Patients who underwent at least two distinct MMS procedures, separated in time to capture subsequent tumors, were included.Results: Four hundred and four individual patients were identified with at least two distinct Mohs procedures, which generated 1,110 Mohs sequences. Fifty-one (4.6%) clinically apparent tumors went unrecognized and 127 (11.4%) tumors were identified and biopsied during the visit. High-risk tumor histology was identified in 10 (20%) unrecognized tumors and 31 (24%) recognized tumors (p-value 0.491).Conclusion: Our study suggests that Mohs surgeons may be overlooking adjacent skin cancers when focusing only on the tumor being surgically treated. Tunnel vision bias may account for part of this phenomenon.

533 Human Case Characterizations of Skin Burn Using Novel Multi-Spectral Short Wave Infrared Imaging

IntroductionDetermining the depth of skin burns in patients is critical for surgical decision making, but currently lacks accuracy in clinical practice. Short-wave infrared (SWIR) light penetrates tissue more than visual or near-infrared light and is very sensitive to water content. We have shown in animal models that imaging of skin burns in the SWIR range distinguishes between superficial and deep tissue necrosis. Here we present the first 2 cases of multi-spectral SWIR imaging of human burn injury as a first step toward a non-invasive, label-free, technique for burn depth determination.MethodsTwo subjects admitted for mixed depth, thermal, 6% and 7% total body surface area (TBSA), burns were studied. Prior to burn excision, a novel system, based on a specialized camera, imaged the burn areas and normal skin at 4 different SWIR bands. Standard photographs from imaged areas were collected and presented for 5 independent, blinded, surgeons’ assessments. In SWIR images, 3-5 regions of interest (ROIs) were selected in burned and adjacent normal skin and the reflected light intensity in each ROI was averaged.ResultsVisual and SWIR images were collected for 9 burn areas in the hands, arms, and shoulder of 2 patients (Panel A). Fifty ROIs from the burn areas were assessed by the surgeons and 30 (60%) ROIs were agreed as being superficial or superficial partial thickness (n=5), deep partial thickness (n=11), or full thickness (n=14) burns by a majority (60% or above consensus together with a possible disagreement only between deep partial and full thickness burn). In Panel B the cumulative SWIR reflectance intensity at the 4 SWIR bands for the 3 burn groups, determined by expert surgeon evaluation, and normal skin are compared. The reflectance from superficial and superficial partial thickness burns (yellow) were 102.7±1.2%, 102.3±0.7% and 103.4±1.4% of the normal skin reflectance for 1200, 1650 and 1940 nm, respectively. On the other hand, the reflectance from deep partial thickness burns (grey) were 96.7±0.1% and 94.7±0.1%, and for full thickness burn (red) were 96.1±1.4% and 93.7±1.6% of normal skin reflectance for 1650 and 1940 nm, respectively.ConclusionsWe present the first human SWIR study demonstrating a distinct reflectance intensity of SWIR wavelengths for different burn depths based on surgeon assessments. The results motivate further studies of SWIR imaging of burns in the hope to non-invasively and accurately identify operative versus non-operative burns.

Digital melanoma in Caucasians: a descriptive and survival study according to sublocation.

Digital melanoma is an uncommon form of acral melanoma that is anatomically restricted to the finger. The aim of this study is to provide specific epidemiological and clinical information about this subtype of melanoma, as well as to identify differences in recurrence and survival depending on the anatomical sublocation. We describe a group of 45 Caucasian patients with digital melanoma divided into three groups: nail unit melanoma (group A), finger skin melanoma (group B), and those melanomas that involve both nail and adjacent skin (group C). The mean tumor thickness was 4.66 mm, and the most common histological subtype is acral lentiginous melanoma. Group C was more frequent in older men and was thicker and more frequently ulcerated (P < 0.05). In addition, patients in group C developed distant metastases more frequently and had a significantly lower median disease-free survival (26.60 months) compared with group A (69.47 months) and group B (89.81 months) (P < 0.05). According to our results, digital melanoma limited to nail apparatus or finger skin was associated with a better prognosis, while those affecting both nail apparatus and skin showed lower melanoma-specific survival.

NRF2 and Key Transcriptional Targets in Melanoma Redox Manipulation.

Simple SummaryMelanocytes are the pigment-producing cells in the skin that help to protect it against damaging solar ultraviolet radiation. As they engage in this function, they are subject to an inordinate amount of oxidative stress. To protect themselves, they utilize numerous antioxidant systems to reduce the amount of reactive oxygen and nitrogen species present in the cells, and this activity then contributes towards the prevention of cancer formation. However, after the formation of melanomas these same antioxidant systems are often co-opted by the cancer in order to promote its uncontrolled growth and metastasis. The purpose of this review is to highlight how the melanocyte’s antioxidant systems, regulated by the transcription factor NRF2 and its targets, are co-opted in melanomas and, therefore, could be targeted for novel therapies to treat melanomas going forward.Melanocytes are dendritic, pigment-producing cells located in the skin and are responsible for its protection against the deleterious effects of solar ultraviolet radiation (UVR), which include DNA damage and elevated reactive oxygen species (ROS). They do so by synthesizing photoprotective melanin pigments and distributing them to adjacent skin cells (e.g., keratinocytes). However, melanocytes encounter a large burden of oxidative stress during this process, due to both exogenous and endogenous sources. Therefore, melanocytes employ numerous antioxidant defenses to protect themselves; these are largely regulated by the master stress response transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2). Key effector transcriptional targets of NRF2 include the components of the glutathione and thioredoxin antioxidant systems. Despite these defenses, melanocyte DNA often is subject to mutations that result in the dysregulation of the proliferative mitogen-activated protein kinase (MAPK) pathway and the cell cycle. Following tumor initiation, endogenous antioxidant systems are co-opted, a consequence of elevated oxidative stress caused by metabolic reprogramming, to establish an altered redox homeostasis. This altered redox homeostasis contributes to tumor progression and metastasis, while also complicating the application of exogenous antioxidant treatments. Further understanding of melanocyte redox homeostasis, in the presence or absence of disease, would contribute to the development of novel therapies to aid in the prevention and treatment of melanomas and other skin diseases

Elevated non-coding promoter mutations are associated with malignant transformation of melanocytic naevi to melanoma

Evolution from a benign naevus to a melanoma results principally from the stepwise accumulation of mutations. We used a custom next generation sequencing (NGS) panel targeting specific melanoma associated genes to analyse and compare differences between melanomas and their precursor naevi in coding and non-coding mutations and copy number aberrations, with a view to implementing this technique as an ancillary test to assist in the interpretation of difficult to diagnose melanocytic tumours. Fifteen cases of cutaneous melanoma with an adjacent morphologically benign (presumed precursor) naevus were selected. A custom NGS panel was used to sequence 54 melanoma associated genes in both the melanoma and the associated naevus for each case. In three cases, two morphologically distinct regions of the melanoma were sequenced. The adjacent (non-lesional) skin was also tested in nine cases. One case was excluded following molecular testing and clinicopathological reclassification as an epidermotropic melanoma metastasis. Twelve of the 14 tumours showed either BRAF or NRAS driver mutations. The melanomas harboured significantly more mutations than the adjacent naevi, particularly in non-coding promoter regions (p=0.002). There were significantly more non-coding promotor mutations in NRAS-mutant melanomas than BRAF-mutant melanomas (p=0.004). Mutations in TERT promoter regions were found preferentially in melanomas. Oncogenic events found exclusively in melanomas included PTEN loss in two BRAF-mutant melanomas and RAC1 P29S hyperactivating mutations in two NRAS-mutant melanomas. Higher numbers of mutations were present in melanomas compared to their precursor naevi. These findings support the further evaluation of this melanoma custom NGS panel as an ancillary test for interpreting difficult borderline melanocytic lesions.

Novel design for local full-thickness skin graft: optimizing donor sites of radial forearm free flap.

Donor site deformities remain the primary issues after radial forearm free flap (RFFF) translocations. This study introduced a local full-thickness skin graft (FTSG) from an adjacent cutaneous area to manage RFFF donor sites and evaluated the esthetic and functional outcomes post-operatively. This was a retrospective study among patients undergoing ablative surgery for head and neck tumors followed by defect reconstruction using a RFFF. The RFFF donor site defects were covered by local FTSGs from the adjacent skins whose harvesting was assisted by a forearm model or traditional FTSGs from abdomen. The color matching degree, surgical scars, ranges of wrist movement, and grip strengths in donor forearms were assessed in two groups at twelve months after surgery. Patients undergoing local FTSGs recovery exhibited better color matching than those repaired by traditional FTSGs from the abdomen. In forearm model, the local FTSGs width should be less than 22% of the forearm circumference located 5cm away from the center of Fossa cubitalis. All the local FTSGs transplanted with this technique showed primary or secondary healing. This study demonstrated using this innovatively designed local FTSGs to close RFFF donor sites was more advantageous than traditional methods.

Morphological and transcriptional evaluation of multiple facial cutaneous hyperpigmented spots.

BackgroundMorphological characteristics of major facial hyperpigmented spots have been well documented. However, detailed alterations of respective transcriptional profile for each spot and in‐depth comparisons across multiple spot types have not been reported.ObjectivesTo comprehensively assess and compare multiple facial hyperpigmented spot types at the morphological and molecular levels by utilising transcriptional expression profiling with correlation to quantified histological features.MethodsMultiple types of facial spot biopsies were collected from Chinese women and compared to additional biopsies taken from adjacent healthy skin. The types of spots included Solar Lentigos with both elongated dermal‐epidermal junction (DEJ) (SL[E]) and flat DEJ (SL[F]), Seborrhoeic Keratosis (SK), Melasma, Freckles, Post‐inflammatory hyperpigmentation of resolving acne (PIH[A]) and other stimuli (PIH[O]). Combined histomorphometry, immunohistology, and transcriptome analysis for suprabasal‐epidermis, basal‐epidermis, and dermal compartments dissected by Laser Capture Microdissection (LCM) were conducted and compared across different spot types.ResultsEach spot type was confirmed to have the unique histological pathology already documented elsewhere. Most of the spot types except Melasma and PIH (A) revealed similar melanocyte density to adjacent skin. All spots exhibited increased melanin synthesis, melanosome transportation, as well as enhanced melanocyte dendricity, however, each spot revealed a distinct transcriptome regulation pattern in pigmentation pathways. Upregulation of pigmentation genes was also observed in the dermis of SL(F), SL(E), SK and PIH(O), associated with significant modulation of DEJ related genes in basal‐epidermis and/or dermal compartments, suggesting potential melanocyte infiltration into the dermis due to impaired DEJ quality. Beyond upregulated pigmentation, for most spots, gene expression in the suprabasal‐epidermis regulating keratinisation was significantly upregulated in conjunction with thickened stratum corneum. Furthermore, downregulation of tight junction related genes represented by claudin‐1 was observed in majority of spot types, suggesting compromised barrier function could be a similarity across spots. Additionally, Cyclin‐Dependent Kinase Inhibitor 2A (CDKN2A) was upregulated in all types of spots, indicating involvement of cell senescence as a common theme.ConclusionThis comprehensive and comparative study based on the histological and transcriptional analysis of three skin compartments provided unique insights into specific causations as well as differences and similarities across multiple hyperpigmented spot types.

Unveiling idiopathic guttate hypomelanosis: pathology, immunohistochemistry, and ultrastructural study.

AbstractBackgroundIdiopathic guttate hypomelanosis (IGH) is a pigment disorder of unknown etiology. Despite its high prevalence and the unaesthetic appearance of the lesions, there are relatively few histological studies on this disorder. This is an important gap to understanding its pathogenesis.ObjectivesTo assess the microscopic structure of IGH lesions compared to normal adjacent skin areas and the possible interaction between melanocytes and the subjacent dermis.MethodsIn this cross‐sectional study, we took biopsy specimens of hypochromic lesions and adjacent normal skin from 20 patients with IGH. We analyzed the fragments using routine stains, immunohistochemistry, and electron microscopy.ResultsWe found superficial dermal fibrosis in 90% (18/20) of our IGH cases and unreported keratinocyte cytoplasmic changes on electron microscopy.ConclusionOur results suggest an interaction between melanocytes and the subjacent dermis in IGH. These findings can help to understand melanocyte biology and the pathogenesis of other achromic lesions.

Observational evaluation of global climate model simulations of arctic sea ice and adjacent land pertaining to the radiative effects of frozen hydrometeors

This study explores the linkage of frozen hydrometeors (cloud ice and falling ice/snow) with sea ice and adjacent lands through surface energy budget using model-observation comparisons to quantify the roles of the falling ice radiative effects (FIREs) in determining the extent and thickness of Arctic sea ice and adjacent land surface radiation budget and land surface skin (Ts) and surface (SAT) temperatures. The Coupled Model Intercomparison Project Phase 5 (CMIP5) models without FIREs tend to produce underestimated downward longwave radiation, and overestimated shortwave downward radiation and surface albedo, resulting in too-cold skin temperature (TS) and surface air temperature (SAT) and overestimated sea ice concentration (SIC) and thickness (SIT). By comparing two simulations of late 20th Century climate from CESM1-CAM5 model with inclusion and exclusion of FIREs, it is found that TS, SAT, radiation, SIC, and SIT and their seasonal cycles are improved with the inclusion of FIREs. Exclusion of FIREs results in underestimated net downward longwave radiative flux, which is highly correlated with overestimated surface albedo, colder TS, and SAT with a confidence level at 99% (p < 1%). These biases in CESM1-CAM5 resemble those in CMIP5 models without FIREs. With the inclusion of FIREs, the SIC bias is reduced by 2%–15% in summer, while the SIT is improved up to 90% in winter despite little improvement in SIC. These findings suggest a potential link among the increased downward longwave flux, decreased downward shortwave flux, and decreased surface air and land surface temperatures locally, which then drives SIC melting and SIT thinning when FIREs are included relative to when FIREs are excluded. It is suggested that the roles played by FIREs over the Arctic regions are of the same order of importance as those over the Southern Oceans despite the differences in geography and impact of human activity.

Detection of Potential Markers for Lip Vermilion Epithelium in Japanese Macaques Based on the Results of Gene Expression Profile

Development of effective in vitro human lip models, specific to the vermilion epithelium, has not progressed as much as that of skin and oral mucosa/gingiva models in vitro. Our histologic examination demonstrated that a Japanese macaque (male, 7 years and 9 months old) had vermilion in the lip distinct from adjacent skin and oral mucosa, resembling histological characteristics of the human lip. Therefore, in this study, we examined the gene expression profile of the three distinct epithelia (skin/vermilion/oral mucosa) within the lip of a Japanese macaque to explore a single potential marker of human vermilion epithelium. Six pairwise comparisons in the skin/vermilion/oral mucosa epithelium in vitro and in vivo revealed 69 differentially up-regulated genes in vermilion epithelium in vivo, in which a few unique genes were highly expressed when compared with both skin and oral mucosa epithelium in vivo using clustering analysis. However, we could not detect a single marker specific to vermilion epithelium supported by the gene expression profile of a Japanese macaque. Instead, the pair of keratin 10 and small proline-rich protein 3 resulted in a potential marker of vermilion epithelium in the human lip (female, 53-year-old) via a double-immunostaining technique. Nonetheless, our result may provide further clues leading to other potential markers of the vermilion epithelium.

Use of a novel Indentometer to evaluate skin induration in localized scleroderma and psoriasis vulgaris.

Diseased skin in localized scleroderma (LS) and plaque psoriasis (PPs) is characterized by induration that can be evaluated by non-invasive bioengineering methods. In this study, we applied a new measurement device based on indentometry to determine the changes of skin mechanical properties in patients with LS and PPs. A total of 30 sclerodermatous plaques in 12 patients with LS and 46 psoriatic plaques in 19 patients with PPs were measured with Indentometer IDM 800 (Courage + Khazaka, Cologne, Germany). The device measures the penetration depth of the probe indenter (pin) into the skin in mm. We used two probes with pin diameters 3 and 5mm, respectively. The stiffer the skin, the less deep is the displacement by the indenter. The smaller the diameter, the deeper the pin will go into the skin when using the same force. The measurements were made on diseased skin and in adjacent normal skin served as control.In addition, the psoriatic plaques were measured before and after treatment. The sclerodermatous skin and the psoriatic skin showed lower Indentometer values compared to adjacent normal skin as measured with both probes. This suggests that diseased skin is stiffer than healthy skin. The values of psoriatic plaques increased after treatment applied that correlates with the clinical improvement. The Indentometric readings significantly negatively correlated with clinical scores of skin induration. There was a significant correlation between the measurements with probe 3mm and probe 5mm. The non-invasive method used is appropriate for objective and quantitative determination of the degree of skin induration in LS and PPs as well as for assessment of the disease evaluation and treatment efficacy.

The combination of sucrose dilaurate and sucrose laurate suppresses HMGB1: an enhancer of melanocyte dendricity and melanosome transfer to keratinocytes.

Hyperpigmented spots are common issues in all ethnicities, involving multiple intrinsic and extrinsic factors such as UVB exposure, hormone balance, inflammatory status and ageing. To determine (i) melanocyte dendricity in multiple facial spot types, (ii) impact of High Mobility Group Box1 (HMGB1), and the combination of sucrose dilaurate and sucrose laurate (SDL) on melanogenesis and melanocyte dendricity, and (iii) SDL effect on facial spots in a human use test. Facial spot and adjacent non-spot skin biopsies were collected from Chinese women (age 20-70). Histological assessment of melanocyte dendricity was performed for 3 spot types (solar lentigo, melasma and postinflammatory hyperpigmentation) by immunofluorescent staining for c-kit/MITF. Keratinocyte, melanocyte and melanocyte-keratinocyte co-culture models were used to assess HMGB1 release by UVB radiation, the effects of HMGB1 and SDL on melanin production, melanocyte dendricity and melanosome transfer. The effect of an SDL-containing moisturizer on appearance of facial hyperpigmented spots was assessed against a vehicle control in an 8-week human use test. Melanocytes in spot areas are more dendritic than melanocytes in adjacent non-spot skin across three investigated spot types. In cell culture models, a moderate UVB-radiation exposure caused release of HMGB1 from keratinocytes. HMGB1 did not alter melanin production in melanocytes, but enhanced melanocyte dendricity and melanosome transfer. SDL reduced HMGB1 release from keratinocytes, inhibited melanin production, reversibly suppressed melanocyte dendricity and reduced melanosome transfer. In the human use test, SDL-containing moisturizer reduced appearance of spots versus vehicle. Increased melanocyte dendricity was observed in multiple types of facial spots. Addition of HMGB1 protein increased melanocyte dendricity and melanosome transfer in cell cultures, implicating potential involvement in spot formation. SDL suppressed melanin production, melanocyte dendricity and melanosome transfer invitro and reduced appearance of spots in the use test, suggesting SDL is an effective solution to address hyperpigmented spot concerns.

Study of management of postburn flexion contracture of finger by glabrous versus nonglabrous split skin graft

Aims and Objectives: This prospective study was designed to determine the outcome of split-thickness glabellar and nonglabellar skin graft for the coverage of defects on palmar aspect of hand after release of postburn contracture in terms of graft take, complications, recurrence, and patient satisfaction for color and texture match. Materials and Methods: This prospective comparative study was carried out on patients from December 2018 to December 2020. Fifty patients were randomly divided into two groups by simple randomization method. Group A was offered treatment with split-thickness graft from glabellar region and other Group B was offered treatment with split-thickness graft from nonglabellar skin. Frequencies and percentages of both recipient and donor sites complications such as infection, hypertrophic scarring on the Vancouver scar assessment scale, recurrence, and difficulty in walking were noted. Patient satisfaction for colour and texture match to neighboring skin at recipient site were assessed 3 months after the operation using five points Likert scale. Results: At follow-up of the Group A, the donor areas were completely healed in all the cases 100%. The grafted area showed excellent color and texture match with the adjacent palmer skin. The graft was mobile, stable and without any pigmentation. There was also no hypertrophic scarring, hyperpigmentation or pain at the donor site as compared to ordinary skin graft. Walking and weight bearing were smooth and the instep curvature appeared normal. In Group B, 100% of patients had hyperpigmentation, 20% had marginal scarring and scar hypertrophy at hand. While 40% had scar hypertrophy at 80% had hyperpigmentation over the donor site. Recurrence was noted in 32% of patients in Group B as compared to 8% in Group A. Conclusions: Glabellar skin of the instep is the best replacement for the palmar skin of the digits and hand because of the similarities in their characteristics. Results are excellent in terms of color and texture match, no hyperpigmentation, less marginal scarring, scar hypertrophy, and less recurrence of contracture in patients with area grafted with glabellar skin. Donor site morbidity is very low and hardly any donor site scar is visible. So in conclusion for the management of postburn flexion contracture of the finger. An ideal skin substitute is glabellar skin grafts from the instep region of foot.

Histopathological Changes Induced by Malassezin: A Novel Natural Microbiome Indole for Treatment of Facial Hyperpigmentation.

Malassezin is a natural indole compound produced by the fungus Malassezia furfur and preclinical investigations have demonstrated an ability to suppress melanogenesis. To investigate the histopathological effects of malassezin for treatment of facial hyperpigmentation. In this proof-of-concept study, seven subjects with facial hyperpigmentation caused by melasma or photodamage applied topical malassezin twice daily for 14 weeks, followed by eight weeks of observation. At baseline, 2 mm punch biopsies were taken from hyperpigmented areas and adjacent uninvolved skin. Skin biopsies from hyperpigmented areas were repeated at 8, 14, and 22 weeks. Paraffin-embedded sections were cut and stained with H&amp;E, Fontana Masson, and MART 1 and assessed for histopathological changes. Increased epidermal melanin and dermal melanophages were observed in all biopsies at baseline in the hyperpigmented compared to uninvolved skin of all subjects. Eight and 14 week biopsies of involved skin revealed decreased epidermal melanin in all subjects treated with malassezin. Melanocytes appeared less dendritic compared to baseline, and numbers were slightly reduced at eight weeks. Biopsies at 22 weeks showed no significant difference in epidermal melanin levels compared to baseline hyperpigmented skin, and melanocytes were comparable in number and dendricity to baseline. There was no evidence of melanocyte atypia in any of the biopsies. These features were similar in melasma and photo-damaged skin. This study documents the histopathological features and ability of malassezin, a novel agent unique to the skin microbiome, to decrease epidermal pigmentation and the temporary and revisable nature of the process. J Drugs Dermatol. 2022;21(2):141-145. doi:10.36849/JDD.6596.

Downregulation of hsa_circ_0002198 inhibits keloid fibroblast activities in vitro by reducing NLRP3 inflammasome activity

The levels of hsa circular RNA_0002198 (hsa_circ_0002198) have been found to be significantly upregulated in keloid dermal fibroblasts. However, the functional role of hsa_circ_0002198 in keloid fibroblasts and the underlying molecular mechanism for its effects have not been reported. In this study, the levels of hsa_circ_0002198 and nucleotide-binding and oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) expression in keloid scar tissues and adjacent normal skin tissues were determined by quantitative real-time PCR and western blotting, respectively. In vitro models of keloid tissue were created by culturing primary keloid fibroblasts obtained from patients. A series of functional experiments, including CCK-8 assays, Transwell assays, and ELISA assays were performed to analyze the functional role of hsa_circ_0002198/NLRP3. Our data showed that hsa_circ_0002198 and NLRP3 were upregulated in keloid scar tissues when compared with adjacent normal tissues. Knockdown of hsa_circ_0002198 expression significantly suppressed cell proliferation, migration, and invasion, and those effects could be partially reversed by forced NLRP3 overexpression in keloid fibroblasts. At the molecular level, knockdown of hsa_circ_0002198 downregulated the levels of Col I, α-SMA, and NLRP3 proteins, as well as the levels of TGF-β, IL-1ß, and IL-33, but upregulated caspase 3 expression in keloid fibroblasts. All those effects were partially reversed after NLRP3 overexpression. In conclusion, our results suggest hsa_circ_0002198 as a potential target for treating keloid lesions.