Perilesional Skin Research Articles

Skin Barrier Function and Its Relationship With IL-17, IL-33, and Filaggrin in Malar Melasma.

The pathogenesis of melasma remains unclear. Interleukin (IL)-17, a proinflammatory mediator, disturbs barrier function. Filaggrin (FLG) is a protein involved in epidermal barrier homeostasis and may be affected by IL-17 and IL-33. To evaluate epidermal barrier function in malar melasma and its association with the expression of FLG, IL-17, and IL-33. Twenty patients with malar melasma were included in this study. Colorimetric and transepidermal water loss (TEWL) was measured in lesional and adjacent unaffected skin at baseline and 30 minutes after barrier disruption using the tape-stripping test. Biopsies from melasma and perilesional skin were performed to evaluate the presence of FLG by immunohistochemistry, and profilaggrin, IL-17, and IL-33 expression were analyzed by reverse transcription-qualitative polymerase chain reaction. After the stripping test, the erythema and TEWL values were higher in the melasma than in the unaffected skin ( P = 0.01). Thirty minutes later, TEWL diminished, but it remained higher than in the perilesional skin. Profilaggrin increased as TEWL gradually decreased (R = -0.68, P = 0.04). FLG and IL-17 were higher in the melasma than in the perilesional skin ( P = 0.003). IL-17 and profilaggrin expression were positively associated (R = 0.60, P = 0.04). IL-33 expression was higher in the adjacent normal skin than in the melasma ( P = 0.01). This study found subclinical inflammation in the skin adjacent to the melasma, dysfunction of the epidermal barrier in lesions associated with chronic inflammation, and an abnormal differentiation process promoting an increase in FLG. These findings highlight the need to preserve the integrity of the facial stratum corneum in these patients.

Intralesional Treatment of Basal Cell Carcinoma in a Genetically Inducible Mouse Model

Introduction: Patients with nevoid basal cell carcinoma syndrome (NBCCS), also termed Gorlin syndrome, develop numerous basal cell carcinomas (BCCs). Current treatment options include systemic hedgehog pathway inhibitors, with significant side effects when used long term, and multiple surgeries with the risk of scarring and sometimes even disfigurement over the long term. We have developed an intralesional treatment for BCC based on the intracellular delivery of an antisense oligonucleotide (ASO) targeting Gli1, the main protein active in the hedgehog pathway responsible for BCC. To test the efficacy of our treatment, we developed an inducible NBCCS-like mouse model, genetically modified at the level of the expression of the Ptch1 and p53 genes in the skin.
 Methods: The inducible mouse model uses Ptch1- and P53-knockdown mice irradiated with UVB three times a week until BCCs appear. These BCCs were treated once or twice a week with injections of an antisense oligonucleotide (ASO) targeting the production of the Gli1 protein, with and without the use of a peptide (the “Feldan shuttle") designed to introduce the ASO into the tumor cells. The evolution of the tumors was monitored several times a week with caliper measurements and photography. Following the treatments, the tumor site tissue was harvested and analyzed by both routine (H&E) and specialized (IHC, IF) histologic methods .
 Results: Intralesional treatment of BCCs in the inducible mouse model using the ASO and peptide combination (FLD103) resulted in rapid and marked tumor regression, and sometimes complete eradication, over a few weeks. In addition, healthy perilesional skin appeared unaffected by the treatment, demonstrating targeted treatment specificity. The healed skin appeared grossly normal. Histologic examination of the treated sites after recovery showed no residual BCC as well as complete healing of the epidermis, dermis and subcutaneous tissue. We also observed that intralesional treatment with the ASO alone is not associated with tumor regression and in fact permits continued tumor growth.
 Conclusion: We have demonstrated the utility of a specific intralesional treatment for BCC in a genetically inducible mouse model. This alternative and novel treatment produces rapid results with normal healing of the treated site. This treatment could offer an attractive option for patients with multiple BCCs who wish to avoid systemic treatments or multiple surgeries.

Dermoscopic Features of Perilesional Skin of Unstable Vitiligo: A Cross-Sectional Study

Objectives: Dermoscopy is a very useful tool in determining stability in vitiligo. Dermoscopic features of unstable vitiligo are trichrome appearance, comet tail appearance, star burst appearance, amoeboid pattern, nebular pattern, tapioca sago pattern and perifollicular hypopigmentation. Most studies are done on determining features of vitiligo lesions; however, there is lack of studies on dermoscopy in normal appearing perilesional skin. This would give an insight into the extent of the disease process, beyond the borders of skin lesions. We conducted a study on 100 unstable lesions of vitiligo and studied dermoscopic features in its perilesional skin. The objective of this study was to observe dermoscopic features of apparently normal perilesional skin in patients of unstable vitiligo. Materials and Methods: A cross-sectional study was conducted in a tertiary care centre in New Delhi. We evaluated perilesional skin of 100 unstable vitiligo lesions over a span of 1 year. The perilesional skin has been defined as area within 5 cm of the lesion. Dermoscopy was performed using DERMLITE 4 Dermoscope at 10X magnification with inbuilt white light and polarised light. Polarised light was used to study changes in the pigmentary network and other patterns. We looked for features such as pigment network, perifollicular pigmentation, presence of leukotrichia, microkoebner phenomenon and satellite lesions in the perilesional skin. Results: The study included a total of 100 unstable lesions. Majority of patients belonged to the age group of 18−30 years. Females outnumbered males (1.8:1). All cases had progressive disease and mean duration of disease was 12.07 ± 10. 85 years. Dermoscopic features of vitiligo were observed in 56% of patients even in normal appearing perilesional skin. The most common dermoscopic finding observed was reduced pigment network which was seen in 33% of cases. Perifollicular hypopigmentation and depigmentation were observed in 23 and two sites, respectively, while leukotrichia was seen at ten sites. Eight sites showed microkoebners phenomenon. Conclusion: The perilesional apparently normal skin also shows signs of disease activity in cases of unstable vitiligo. Hence, perilesional skin should also be examined carefully with the dermoscope and topical treatment and targeted phototherapy should aim at covering the normal looking perilesional skin as well, at least within 5 cm of the borders of the skin lesions. Importantly, the perilesional skin should also be examined before surgery.

Comparison between platelet-rich plasma (PRP) and mechanically emulsified fat grafts in management of chronic wounds

Backgroundchronic wounds represent a challenge in treatment, due to diverse pathogenesis, resistance to ordinary treatment complex and lack of direct methods of treatment In this study, the aim is to compare the effect of Platelet -rich plasma (PRP) and mechanically emulsified fat grafts on the outcome of the healing process of chronic wounds. Patients and methodsIn the current study, 30 patients with chronic wounds were divided into two groups (Group I, 15 patients had application of PRP on chronic wounds). Whereas (Group II, 15 patients had application of mechanically emulsified fat on chronic wounds). In both groups assessment of the healing rates and histopathological changes that were determined by observing the parameters of wound healing, including peri-lesional skin quality, observation of the wound size and depth, assessment of the pain indicated by Visual analog scale score. ResultsPatient were followed up for 6 months. Group II showed a better healing rate 64% in comparison to Group I 55%. Wound parameters and pain score were recorded in both groups with no statistically significant difference. ConclusionBoth PRP and mechanically emulsified fat grafts were found to be efficient treatment modalities in management of chronic “non-healing” wounds. But mechanically emulsified fat grafts represent a better treatment method for chronic wounds.

Pathogenesis of melasma

AbstractTo adequately guide future therapies, it is important to elucidate the pathogenesis of melasma. Chronic ultraviolet (UV) radiation exposure, hormonal stimulation, and genetic predisposition play a role in melasma. A widely accepted theory for the pathogenesis of melasma is the increase of melanin through UV, which leads to the upregulation of melanin stimulating receptors (MSR) such as melanocortin‐1 receptors (MC1R), resulting in increased hormone binding and melanin production. Furthermore, there are similarities between the histopathologic presentation of melasma and solar elastosis, a hallmark of photo‐aged skin. These overlaps include altered basement membrane, increased vascularization, and increased mast cell count. There is significant data showing greater degree of solar elastosis in the melasma skin compared to the perilesional skin. Additionally, an etiologic factor in the pathogenesis of melasma is hormonal exposure to estrogen. Melasma has increased prevalence among menstruating women, women on oral contraceptives, and pregnant women. In melasma lesions, studies have shown an increased number of estrogen receptors and progesterone receptors in the dermis and epidermis, respectively. Previously, increased melanogenesis was thought to be the sole contributing factor to the pathogenesis of melasma but more recently, aberrant vasodilation and angiogenesis have been found to play a role. Nitric oxide, a potent vasodilator, was found to be overexpressed at the dermal‐epidermal junction and was hypothesized to contribute to melasma through stimulation of tyrosinase and increasing vascularity. In conclusion, the various mechanisms implicated in melasma include melanocyte dysfunction, solar elastosis, mast cell dysfunction, hormonal influence, vascular transformation, and basement membrane damage.

Myofibroblast stroma differentiation in infiltrative basal cell carcinoma is accompanied by regulatory T-cells.

The implications of infiltrative compared to non-infiltrative growth of cutaneous basal cell carcinoma (BCC) on the tumor stroma and immune cell landscape are unknown. This is of clinical importance, because infiltrative BCCs, in contrast to other BCC subtypes, are more likely to relapse after surgery and radiotherapy. This descriptive cross-sectional study analyzed 38 BCCs collected from 2018 to 2021. In the first cohort (n=28), immune cells were characterized by immunohistochemistry and multiplex immunofluorescence staining for CD3, CD8, CD68, Foxp3, and α-SMA protein expression. In the second cohort (n=10) with matched characteristics (age, sex, location, and BCC subtype), inflammatory parameters, including TGF-β1, TGF-β2, ACTA2, IL-10, IL-12A, and Foxp3, were quantified via RT-qPCR after isolating mRNA from BCC tissue samples and perilesional skin. Infiltrative BCCs showed significantly increased levels of α-SMA expression in fibroblasts (p=0.0001) and higher levels of Foxp3+ (p=0.0023) and CD3+ (p=0.0443) T-cells compared to non-infiltrative BCCs. CD3+ (p=0.0171) and regulatory T-cells (p=0.0026) were significantly increased in α-SMA-positive tumor stroma, whereas CD8+ T-cells (p=0.1329) and CD68+ myeloid cells (p=0.2337) were not affected. TGF-β1 and TGF-β2 correlated significantly with ACTA2/α-SMA mRNA expression (p=0.020, p=0.005). Infiltrative growth of BCCs shows a myofibroblastic stroma differentiation and is accompanied by an immunosuppressive tumor microenvironment.

Quantification of human polyomaviruses MCPyV and HPyV6 in malignant and non-malignant skin lesions

BackgroundHuman Polyomaviruses such as MCPyV and HPyV6 are frequently found as part of healthy skin microbiota and have been associated with Merkel cell carcinoma (MCC), pruritic and dyskeratotic dermatoses, respectively. Their presence in other types of skin conditions varies greatly depending on lesion type and population. ObjectiveTo analyse comparatively the presence of MCPyV and HPyV6 in nonmelanoma skin cancers and healthy skin. MethodsThe authors utilized qPCR techniques to quantify these pathogens in NMSC, premalignant diseases, and healthy skin of 87 patients. ResultsMCPyV was detected in over 40% of samples, while HPyV6 was in 9.6%. MCPyV load was higher in squamous cell carcinomas (SCC) compared to basal cell carcinomas (BCC) (p=0.016) and HPyV6 showed a higher percentage of infected cells in areas of low solar exposure as well as normal skin (p=0.012). A fair agreement (kappa=0.301) was found between MCPyV detection in lesions and their respective perilesional skin, indicating a random process of local dissemination of the virus. Study limitationsThe lack of a larger sampling of different lesion types and protein expression analyses limits the correlation findings. ConclusionThis is the first report of HPyV6 detection in the healthy skin of a Brazilian population, but the role of both polyomaviruses in NMSC has yet to be demonstrated.

Immunoexpression of CD1a and Histopathology in Lesional and Non Lesional Skin in Psoriasis: A Cross-sectional Study

Introduction: Psoriasis is a long-lasting autoimmune disease mediated by T-lymphocytes and dendritic cells. Langerhans cells are a unique population of dendritic cells found in the epidermis, where they can be identified by Cluster of Differentiation 1a (CD1a) positivity. They play an important role in the pathogenesis of psoriasis. Aim: To evaluate the utility of immunoexpression of CD1a in the early diagnosis of psoriasis and to study the histopathology of skin biopsies from clinically diagnosed cases of psoriasis. Materials and Methods: A cross-sectional study was conducted from September 2017 to August 2019 at Gandhi Hospital, Secunderabad, Telangana, India. Skin biopsies were taken from 50 patients with psoriasis from the Outpatient Department (OPD). Histopathological features in early psoriasis were studied, and CD1a immunoexpression in lesional, perilesional, and distant skin was analysed. The data were analysed using Student’s t-test with the Statistical Package for the Social Sciences (SPSS) software. Results: Half of the cases were found in two age groups: 51-60 years (15 patients, 30%) and 11-20 years (10 patients, 20%). The majority of the cases were males (36 patients, 72%). Most of the biopsies were taken from the lower limb (24 patients, 48%), followed by the back (13 patients, 26%). In this study, the average number of CD1a positive Langerhans cells was highest (54.92±5.26) in perilesional skin compared to lesional skin (30±3.96), which was statistically significant (p-value=0.04). Conclusion: Based on the observations in this study, a strong positive reaction of CD1a in perilesional skin can be used to diagnose psoriasis in the early clinical stages, before full-blown clinical psoriatic plaques have appeared. Early diagnosis may prompt physicians to initiate treatment early

Immunobullous Disorder: A Diagnostic Dilemma Faced at a Tertiary Care Centre in Kanyakumari, Tamil Nadu, India

Introduction: Immunobullous disorders are morphologically heterogenous and hence the differentiation between various subtypes is essential for proper treatment and prognosis. Prompt diagnosis needs clinicopathological concordance added with Immunofluorescence (IF) in particular Direct Immunofluorescence (DIF) study to avoid discrepancies. Aim: To study the clinicopathological profile along with immunological features and to analyse the utility of IF in particular DIF of immunobullous disorders. Materials and Methods: The present study was a single institution based cross-sectional observational hospital study done in the department of pathology in SreeMookambika Institute of Medical Sciences, Tamil Nadu over a period of one year (July 2019-August 2020) involving 70 outpatients in the department of dermatology with clinical evidence of bullous disorders. Two biopsies were taken from the patient, one from a newly formed bulla or vesicle for Haematoxylin and Eosin (H&E) stain and the other from a perilesional normal looking skin for DIF study. Statistical analysis was done by using SPSS software. Chi-square test was used for statistical analysis. A p-value of less than 0.05 was considered as statistically significant. However, the final diagnosis was arrived after considering clinical, bedside investigations, histopathology and DIF study. Results: Out of seventy (70) patients included in this study, the most common age group of distribution was between 51-60 years in a frequency of 22 (31.4%). Out of 70 patients, 39 patients were diagnosed with intraepidermal bullous disorders and 31 patients were diagnosed with subepidermal bullous disorders. The most common disorder diagnosed was based on clinical findings was Pemphigus Vulgaris (PV) 31 (44.3%) followed by Bullous Pemphigoid (BP) 23 (32.9%). The common disorder diagnosed based on histopathology was PV 33 (47.1%). Clinical and histopathological concordance was conclusive in 31 cases of PV. The percentage of diagnosis of DIF was positive in 67 (95.71%). Patients which reached to inconclusive (DIF was not definite) diagnosis was in only three patients. Conclusion: Since, in most of the cases there occurs an overlap in clinical and histopathological features, IF in particular, DIF plays a sensitive tool in confirming diagnosis as well as distinguishing immunobullous disorders from other disorders.

MiRNA expression profiles of the perilesional skin of atopic dermatitis and psoriasis patients are highly similar

Atopic dermatitis (AD) and psoriasis vulgaris (PV) are chronic inflammatory skin diseases with heterogeneous molecular backgrounds. MicroRNAs (miRNAs) contribute to either development or regulation of many immune system related diseases. Only few miRNA profiling studies are available for AD and no comparisons between AD and PV skin miRNA profiles have been performed recently. We conducted a miRNA profiling analysis of skin, as well as serum, from adult AD and PV patients and control individuals. 130 miRNAs were differentially expressed in AD skin, of which 77 were common differentially expressed in AD and PV. No differentially expressed miRNAs were detected in serum. Pathway analyses revealed differentially expressed miRNAs to potentially target immune-system related pathways, including TNF-α, IL-2/STAT4 and IL-6/JAK/STAT3. Additional genetic analysis of published AD GWAS dataset detected association of several target genes of differentially expressed miRNAs in skin. Moreover, miR-28-5p, miR-31-5p, miR-378a-3p and miR-203a were validated as upregulated in the skin of AD and PV patients. All validated miRNAs were reliable predictive markers for AD or PV. In conclusion, miRNA expression pattern in the skin of adult AD patients is highly similar to that of PV with multiple differentially expressed miRNAs potentially involved in the regulation of immune responses in AD and PV.

Abnormal nuclear expression of aquaporin-3 in lesional and perilesional skin of vitiligo patients: A novel immunohistochemical finding.

Vitiligo is a skin disease characterized by a complex etiopathogenesis. Keratinocyte apoptosis may play a role in vitiligo pathogenesis. Aquaporin-3 (AQP-3) is an aqua-glyceroporin that controls keratinocyte proliferation and differentiation. To assess the immunohistochemical expression of AQP-3 in lesional and perilesional skin of vitiligo patients compared to healthy control skin. A total of 20 patients with generalized non-segmental vitiligo and 20 age- and sex-matched healthy controls were included. Lesional and perilesional skin of vitiligo patients, as well as normal skin of control subjects, were biopsied. The immunohistochemical expression of AQP3 in the epidermis was examined. Compared to control skin, both lesional and perilesional skin showed a significant reduction in the intensity of membranous staining of AQP-3 (p< 0.001, p= 0.002, respectively). Moreover, the membrano-cytoplasmic pattern of AQP-3 staining was significantly detected in 80% of lesions and 85% of perilesional biopsies, while it was absent in control skin (p< 0.001). Additionally, nuclear AQP-3 expression was significantly detected in 35% of lesions and 55% of perilesional biopsies, while it was not detected in control skin (p= 0.012, p< 0.001, respectively). No statistically significant difference was detected between lesional and perilesional skin. To our knowledge, this is the first immunohistochemical research to show a significant abnormal nuclear expression of AQP-3 in lesional and perilesional skin of vitiligo patients. This abnormality may reflect impaired functions of AQP-3, leading to keratinocyte apoptosis with subsequent melanocyte death and development of vitiligo.

Differential expression of C5aR1 and C5aR2 in innate and adaptive immune cells located in early skin lesions of bullous pemphigoid patients.

Bullous pemphigoid (BP), the by far most frequent autoimmune subepidermal blistering disorder (AIBD), is characterized by the deposition of autoantibodies against BP180 (type XVII collagen; Col17) and BP230 as well as complement components at the dermal-epidermal junction (DEJ). The mechanisms of complement activation in BP patients, including the generation of C5a and regulation of its two cognate C5aRs, i.e., C5aR1 and C5aR2, are incompletely understood. In this study, transcriptome analysis of perilesional and non-lesional skin biopsies of BP patients compared to site-, age-, and sex-matched controls showed an upregulated expression of C5AR1, C5AR2, CR1, and C3AR1 and other complement-associated genes in perilesional BP skin. Of note, increased expressions of C5AR2 and C3AR1 were also observed in non-lesional BP skin. Subsequently, double immunofluorescence (IF) staining revealed T cells and macrophages as the dominant cellular sources of C5aR1 in early lesions of BP patients, while C5aR2 mainly expressed on mast cells and eosinophils. In addition, systemic levels of various complement factors and associated molecules were measured in BP patients and controls. Significantly higher plasma levels of C3a, CD55, and mannose-binding lectin-pathway activity were found in BP patients compared to controls. Finally, the functional relevance of C5aR1 and C5aR2 in BP was explored by two in vitro assays. Specific inhibition of C5aR1, resulted in significantly reduced migration of human neutrophils toward the chemoattractant C5a, whereas stimulation of C5aR2 showed no effect. In contrast, the selective targeting of C5aR1 and/or C5aR2 had no effect on the release of reactive oxygen species (ROS) from Col17-anti-Col17 IgG immune complex-stimulated human leukocytes. Collectively, this study delineates a complex landscape of activated complement receptors, complement factors, and related molecules in early BP skin lesions. Our results corroborate findings in mouse models of pemphigoid diseases that the C5a/C5aR1 axis is pivotal for attracting inflammatory cells to the skin and substantiate our understanding of the C5a/C5aR1 axis in human BP. The broad expression of C5aRs on multiple cell types critical for BP pathogenesis call for clinical studies targeting this axis in BP and other complement-mediated AIBDs.

Effect of 30% Supramolecular Salicylic Acid Peel on Skin Microbiota and Inflammation in Patients with Moderate-to-Severe Acne Vulgaris.

Thirty-percent supramolecular salicylic acid (SSA), a modified salicylic acid preparation, is a safe and effective treatment for moderate-to-severe acne vulgaris (AV). However, its mechanism of action remains unclear. We aimed to analyze the role of 30% SSA peels on skin microbiota and inflammation in patients with moderate-to-severe AV. A total of 28 patients were enrolled and received 30% SSA peels biweekly for 2months. The Global Acne Grading System (GAGS) score, skin water content, transepidermal water loss (TEWL), pH, and sebum levels were assessed. Skin microbial samples and perilesional skin biopsies were obtained at the onset and 2weeks after treatment completion. Samples were characterized using a high-throughput sequencing approach targeting a portion of the bacterial 16S ribosomal RNA gene. After treatment, patients showed a significant improvement in their GAGS score and skin barrier indicators (P < 0.05). The GAGS score was positively associated with both the sebum concentration (R = 0.3, P = 0.027) and pH (R = 0.39, P = 0.003). Increased expression of caveolin-1 and decreased expression of interleukin (IL)-1a, IL-6, IL-17, transforming growth factor beta, and toll-like receptor 2 were observed in the skin tissue after treatment. The richness and evenness of the cutaneous microbiome decreased after treatment and the Staphylococcus proportion decreased significantly (P < 0.05), whereas the Propionibacterium proportion tended to decrease (P = 0.066). On the basis of analyses of the skin barrier and microbiota, we speculate that the 30% SSA peel may have a therapeutic effect in patients with moderate-to-severe AV by improving the skin microenvironment and modulating the skin microbiome, thus reducing local inflammation.

The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry.

Psoriasis is a common chronic inflammatory skin disease. The diversity and heterogeneity of immune cells in human skin have been studied in recent years, but the spatial distribution of immune cells at the single-cell level in the human psoriatic epidermis and dermis remains unclear. In this study, we mapped psoriatic skin immune cells from paired lesional, perilesional, and nonlesional skin samples using mass cytometry. Phenotypic dendritic cells (DCs) were found in the psoriatic epidermis and dermis. Psoriatic dermal CD1c+CD11b+ cDC2s migrated to the epidermis in the perilesional skin during the preinitiation stage. CD1c+CD11b+ cDC2s rapidly replaced EpCAM+CD11clow LC cells and initiated inflammation. Simultaneously, CD207+CD11chi LC and CD5+ T cells accumulated in the psoriatic epidermis and orchestrated epidermal inflammation in psoriasis. The immune cell pool in the psoriatic dermis primarily included APCs and T cells. However, unlike that in the dermis, the epidermal immune environment was more significant and coincided with the inflammation occurring during psoriasis.The epidermal immune microenvironment plays a dominant role in psoriasis. Langerhans cells, epidermis-resident memory T cells and macrophages together contribute to healthy epidermal immune homeostasis. However, psoriatic CD1c+CD11b+ epidermal cDC2s are positioned in the perilesional area, replacing EpCAM+CD11clow LCs rapidly and initiating inflammation. Epidermal CD141+ cDC1s, CD1c+ cDC2s, CD14+ moDCs, and BDCA2+ pDCs orchestrate psoriatic inflammation. Meanwhile, CD11chi LCs and CD5+ T cells accumulate in the psoriatic epidermis.

Videodermoscopic Changes of the Hair in Vitiligo Lesions in Relation to Disease Duration.

Vitiligo is an acquired disease of complex pathogenesis, in which the immunologic attack to the skin and hair follicle melanocytes leads to areas of depigmentation and leukotrichia, respectively. To study the dermoscopic features of the hair changes in vitiligo lesions in comparison to perilesional control areas and in relation to disease duration. Forty-seven patients with both old and recent vitiligo lesions were included. Dermoscopic features of hair within the lesions were examined and compared to those in perilesional non depigmented skin of the same patient. Hair density (P < 0.001), terminal hair rate (P = 0.011), terminal to vellus hair ratio (P = 0.029) and mean hair shaft thickness (P = 0.031) were significantly decreased, whereas vellus hair rate (P = 0.011) was significantly increased in old vitiligo lesions compared to their respective control areas. The frequency of broken hair was significantly higher in old lesions (P < 0.001), while that of upright re-growing hair was significantly higher in recent lesions (P = 0.016). Hair involvement in vitiligo lesions is not only limited to the development of leukotrichia. Other subtle changes in hair density, anagen and telogen hair rates, and mean hair thickness can be detected. These changes may serve as objective clues to the duration of the lesions.

Focal hypohidrosis in lesional skin in a probable case of confluent and reticulated papillomatosis: A case report with insight into the pathomechanism of recurrence.

Confluent and reticulated papillomatosis (CRP) is a rare skin disorder that develops in young adults and presents as persistent brown papules and plaques predominantly affecting the intertriginous areas, however, its etiopathogenesis remains elusive. Herein, we report a probable case of CRP with lesional hypohidrosis as detected by sweat test and provide insight into the pathomechanism. A 23-year-old man presented with nine-months history of painful sensation on his trunk without any skin change. The result of sweat test was compatible with acquired idiopathic generalized anhidrosis. Topical heparinoid and physical exercise improved the symptoms. However, he started to notice asymptomatic brownish reticulated macules on the trunk. Intriguingly, focal hypohidrosis, as detected by sweat test was evident on the macules. In histology, the lesional skin demonstrated hyperkeratosis, acanthosis, basal melanosis, mild papillomatosis, and obstruction of the sweat duct in the upper dermis, which were not observed in the peri-lesional skin. Accumulation of the sweat in the luminal aspect of the secretory portion and dilation of the sweat duct in the deeper dermis was detected in the lesional skin, as highlighted by anti-dermcidin staining. Aquaporin 5 expression in the secretory portion was more confined to the cell membrane in the lesional skin. Both brownish macules and lesional hypohidrosis simultaneously improved in summer and exacerbated in winter. Literature review found nine reports on recurrent CRP, and obesity was thought to be a major comorbidity in recurrent CRP cases. Obesity is often associated with sweat dysregulation. This, together with the findings in our case, implied the possible contribution of focal sweating abnormality in the pathogenesis of reticulated skin lesion in our case.

Autofluorescence identifies highly phagocytic tissue-resident macrophages in mouse and human skin and cutaneous squamous cell carcinoma.

Macrophages from human and mouse skin share phenotypic and functional features, but remain to be characterized in pathological skin conditions. Skin-resident macrophages are known to derive from embryonic precursors or from adult hematopoiesis. In this report, we investigated the origins, phenotypes and functions of macrophage subsets in mouse and human skin and in cutaneous squamous cell carcinoma (cSCC) using the spectral flow cytometry technology that enables cell autofluorescence to be considered as a full-fledged parameter. Autofluorescence identifies macrophage subsets expressing the CD206 mannose receptor in human peri-tumoral skin and cSCC. In mouse, all AF+ macrophages express the CD206 marker, a subset of which also displaying the TIM-4 marker. While TIM-4-CD206+ AF+ macrophages can differentiate from bone-marrow monocytes and infiltrate skin and tumor, TIM-4 identifies exclusively a skin-resident AF+ macrophage subset that can derive from prenatal hematopoiesis which is absent in tumor core. In mouse and human, AF+ macrophages from perilesional skin and cSCC are highly phagocytic cells contrary to their AF- counterpart, thus identifying autofluorescence as a bona fide marker for phagocytosis. Our data bring to light autofluorescence as a functional marker characterizing subsets of phagocytic macrophages in skin and cSCC. Autofluorescence can thus be considered as an attractive marker of function of macrophage subsets in pathological context.

Study on the correlation of high expression level of HuD with seborrheic keratosis and skin aging.

Currently, most studies of ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-like protein 4 (Hu antigen D, HuD) focus on nervous system-related diseases; the role of HuD in the occurrence of skin aging and seborrheic keratosis (SK) has not been reported. To explore the role of HuD in the occurrence of SK and skin aging and its related clinical significance. The expression levels of HuD in the skin and blood of healthy people at different ages, SK lesions, and perilesional skin of SK patients were detected by both immunohistochemistry and Western blotting. The mRNA expression levels of HuD in the skin and blood of healthy peoples at different ages were detected by quantitative real-time reverse transcription-polymerase chain reaction. The expression level of HuD was compared with the skin of healthy people, SK lesion, and perilesional skin of SK patients of the same age. The immunohistochemistry and Western blotting showed that the expression levels of HuD in SK lesions were higher than those in healthy skin and perilesional skin. The immunohistochemical staining intensity, protein and mRNA expression levels of HuD in the skin and blood of healthy people were correlated with age, which gradually increased with increasing age. HuD is highly expressed in SK lesion and aged skin, indicating that a higher HuD expression level is correlated with occurrence of SK and aging skin; however, its mechanism needs to be further studied.

Meta-Analysis of Alterations in Regulatory T Cells' Frequency and Suppressive Capacity in Patients with Vitiligo.

Vitiligo is a noncontagious autoimmune skin depigmenting disease. Regulatory T cells (Tregs) play a key role in maintaining peripheral tolerance; however, Tregs' number, suppressive function, and associated suppressive molecules (FOXP3, IL-10, and TGF-β) are found to be reduced in vitiligo patients. Although, the role of Tregs in vitiligo pathogenesis is well established, there are several contrary findings which suggest a controversial role of Tregs in vitiligo. Therefore, to clarify the role of Tregs in vitiligo pathogenesis, we aimed to study Tregs' frequency, suppressive capacity, and associated suppressive molecules (FOXP3, IL-10, and TGF-β) in vitiligo patients through meta-analysis approach. A total of 30 studies involving 1223 vitiligo patients and 1109 controls were included in the study. Pooled results from our meta-analysis suggested significantly reduced Treg cells' frequency in vitiligo patients (p = 0.002). Interestingly, Tregs' suppressive capacity was also significantly reduced in vitiligo patients (p = 0.0002); specifically, Treg-mediated suppression of CD8+T cells was impaired in vitiligo patients (p < 0.00001). Moreover, FOXP3, a key Tregs' transcription factor, was significantly reduced in blood and skin of vitiligo patients (p < 0.00001). Intriguingly, the FOXP3 expression was significantly reduced in the lesional skin as compared to perilesional and nonlesional skin (p = 0.007 and p = 0.04). Furthermore, the expression of key Treg-associated suppressive cytokines IL-10 and TGF-β were significantly reduced in vitiligo patients (p = 0.0005 and p = 0.01). The disease activity-based analysis suggested for reduced Tregs' frequency and FOXP3 expression in active vitiligo patients (p = 0.05 and p = 0.01). We also studied the effect of microRNA-based treatment, narrow band–UVB phototherapy, and Treg-associated treatments on Tregs' frequency, FOXP3, and IL-10 expression. Interestingly, we found increased Tregs' frequency, FOXP3, and IL-10 expression after the treatment (p = 0.007, p < 0.0001, and p = 0.002). Overall, our meta-analysis suggests that the Tregs play a crucial role in pathogenesis and progression of vitiligo, and hence, Treg-based therapeutic interventions could be effective in vitiligo patients.

31752 Inflammation in hidradenitis suppurativa extends to healthy-appearing perilesional skin and is therapeutically targetable with IL-17RA blockade

Introduction: Hidradenitis suppurativa (HS) is characterized by a dysregulation of the IL-17 axis. We recently reported a clinical benefit of brodalumab, a human anti-IL-17 receptor (IL-17RA) monoclonal antibody in moderate to severe HS.