Inflammatory Skin Lesions Research Articles

Hidradenitis Suppurativa Leads to Increased Risk of Wound-Related Complications following Total Joint Arthroplasty

BackgroundHidradenitis suppurativa (HS) is a skin disorder characterized by inflammatory skin lesions that are most commonly in the inguinal and axillary regions. These skin lesions are common sites of bacterial growth and are thus a potential risk factor for infection following procedures such as total hip arthroplasty (THA) or total knee arthroplasty (TKA). Material and methodsAdult patients undergoing THA or TKA for degenerative etiologies were identified from PearlDiver datasets. For THA and TKA, HS patients were matched 1:4 with non-HS patients based on age, sex, and Elixhauser Comorbidity Index. The incidence of 90-day any, severe, minor, and specific adverse events was compiled and compared with multivariate analyses. Five-year revision rates were plotted on Kaplan-Meier survival curves and compared with log-rank tests. ResultsFor THA, 331,627 patients were identified, of which HS was noted for 481 patients (0.15%). For TKA, 274,161 patients were identified, of which HS was noted for 290 patients (0.11%). Following THA, HS patients had increased odds of wound dehiscence (odds ratio = 2.55, P = .002). Following TKA, HS patients had increased odds of surgical site infection (odds ratio = 1.95, P = .006). All other 90-day adverse events were not significantly different. There was no significant difference in 5-year implant survival in either procedure. ConclusionsHS is a rare but identified comorbidity for those undergoing THA or TKA. Although most 90-day adverse events and 5-year implant survival were similar to those without this condition, specific wound-related issues were elevated by roughly twofold. These findings could help inform patients and surgeons.

Oral Administration of East Asian Herbal Medicine for Inflammatory Skin Lesions in Plaque Psoriasis: A Systematic Review, Meta-Analysis, and Exploration of Core Herbal Materials.

Psoriasis is an inflammatory autoimmune skin disease with various clinical manifestations. The aim of this review was to systematically evaluate the efficacy and safety of oral administration of East Asian herbal medicine (EAHM) for inflammatory skin lesions in psoriasis and to explore core herbal materials for drug discovery. A comprehensive search was conducted in 10 electronic databases for randomized controlled trials from their inception until 29 July 2021. Statistical analysis was performed in R version 4.1.2 and R studio. When heterogeneity in studies was detected, the cause was identified through sensitivity analysis, meta-regression, and subgroup analysis. Methodological quality was independently assessed using the revised tool for risk of bias in randomized trials. A total of 56 trials with 4966 psoriasis patients met the selection criteria. Meta-analysis favored EAHM monotherapy on Psoriasis Area Severity Index (PASI) 70 (RR: 1.2845; 95% CI: 1.906 to 1.3858, p < 0.0001), PASI 60 (RR: 1.1923; 95% CI: 1.1134 to 1.2769, p < 0.0001), continuous PASI score (MD: −2.3386, 95% CI: −3.3068 to −1.3704, p < 0.0001), IL-17, IL-23, TNF-α, and Dermatology Life Quality Index. Patients treated with EAHM monotherapy had significantly reduced adverse events incidence rate. In addition, based on additional examination of the herb data included in this meta-analysis, 16 core materials were identified. They are utilized in close proximity to one another, and all have anti-inflammatory properties. The findings in this study support that oral EAHM monotherapy may be beneficial for inflammatory skin lesions in psoriasis. Meanwhile, the identified core materials are expected to be utilized as useful drug candidate hypotheses through follow-up studies on individual pharmacological activities and synergistic effects.

Development of a comprehensive method for the dermatoscopic images analysis of the facial skin with acne

Background: One of the most common inflammatory chronic and recurrent skin diseases is acne (“acne vulgaris”), which appears itself as open or closed comedones and inflammatory skin lesions in the form of papules, pustules, nodes, etc. It has been established that acne is one of the most common dermatoses, since, according to modern data, it affects about 9.4% of the population. During adolescence, up to 90% of people suffer, and in adulthood — about 20% with varying degrees of severity. Currently, there are many approaches to treating this disease through various cosmetic treatments such as phototherapy, ultrasonic skin cleansing, Mesotherapy, chemical peels, and medication. Therefore, the development of methods and means of differential diagnosis of acne is one of the urgent tasks in the field of biomedical engineering, dermatology, and clinical medicine, since this allows timely identification of the localization of the disease, its causes, and prescribing appropriate treatment. However, the solution to the problem of monitoring the dynamics of external manifestations of the disease is possible only with the use of combined mathematical methods for image analysis. Objectives: To develop a comprehensive method for analyzing dermatoscopic images for monitoring the external manifestations of acne disease during treatment and isolating the affected areas of the facial skin. Materials and Methods: Dermatological preclinical researches of the skin were conducted in the laboratory of 3D-biomedical technologies of the Department of Biomedical Engineering of the Kharkiv National University of Radio Electronics, using a digital videodermatoscope BIO Bm6+ in daylight and a portable skin analyzer Skin Scope F-102 in the ultraviolet range. Clinical researches were conducted based on the Department of Pediatric Propaedeutics #2 of the Kharkiv National Medical University. The development of a software tool for image analysis was conducted out in Python programming using the libraries OpenCV, Scikit-image, Numpy, PIL, Mathplotlib. Determination of the affected skin areas and calculation of the parameters of inflammation were carried out using multi-Otsu methods and morphological segmentation of digital dermatoscopic images. Results: During the research, automated software was developed that allows to analyze in dynamics the nature of inflammatory processes and the area of facial skin lesions, as well as to carry out a differential diagnosis of acne disease. The proposed method for the analysis of dermatoscopic images makes it possible to perform color segmentation and obtain a map of the gradations of skin inflammations to control the dynamics during the prescribed treatment. Conclusions: The comprehensive method of analysis of dermatoscopic images of the skin of the face makes it possible to effectively control the condition of the skin of the face from acne during treatment, while analyzing the degree of inflammatory processes and the area of lesions, where, using the developed software, in an automated mode, red gradations are calculated to detect the boundaries of inflammation, geometric parameters and percentage of lesions in relation to healthy facial skin.

Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature.

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two‐step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding ‘AND (epilum* or dermosc* or dermatosc*)’. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine‐eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine‐eccrine ATs and details possible differential dermoscopic features.

Control of Foxp3+ Treg Production, Stability and Function by the Nuclear Co‐regulator, Sin3A

PurposeFoxp3+ T‐regulatory (Treg) cells are well established as a crucial component of immune homeostasis and self‐tolerance. Histone/protein deacetylase (HDAC) activity within Foxp3+ Tregs plays an important role in regulation of gene expression. HDAC1 and ‐2 regulate Foxp3 expression and play critical roles in the control of Treg functions and properties. Less understood, are the contributions made by proteins which form large complexes with HDAC1 and ‐2, such as the paired amphipathic helix protein, Sin3a.MethodsWe sought to evaluate the contributions Sin3a makes to Tregs by undertaking its conditional deletion in Foxp3+ cells.ResultsSin3a‐/‐Foxp3Cre mice developed severe, systemic autoimmunity, leading to death within 2‐3 weeks of birth. These mice had greatly enlarged superficial lymph nodes, massive inflammatory lesions in lungs, skin, livers and kidneys and developed autoantibodies to islet cells, striated muscles, keratin, endomysium and gastric parietal cells. Percentages of Foxp3+ Tregs in the secondary lymphoid organs of Sin3a‐/‐Foxp3Cre mice were vastly lower than in controls (p values ranging from &gt;0.01 to &gt;0.0001). Further, the amount of Foxp3 mRNA expression (&gt;20‐fold) and Foxp3 protein per Treg (&gt;3‐fold) were also significantly reduced within Sin3a deficient animals. The ratios of T effectors to Tregs, and follicular T effectors to follicular Tregs were drastically increased within the spleens and superficial lymph nodes (ranging from 87‐154% and 152‐160%, respectively). Sin3a deficient Tregs produced significant amounts of pro‐inflammatory cytokines, including Granzyme B, IFN‐γ and IL‐2 (ranging from 12‐45% of cells). Tregs lacking Sin3a had impaired suppressive function against CD4+ and CD8+ responders (p&lt;0.01 and p&lt;0.05 respectively, compared to WT Tregs) in vitro. In addition, we found that Sin3a was essential for peripheral iTreg conversion since conventional CD4+CD25‐ cells from Sin3a‐/‐FoxP3Cre mice completely lacked the ability to convert to Foxp3+ iTregs ex vivo in the presence of IL‐2, TGFb, and CD3/CD28 beads. Consistent with impaired Treg function, CD4+ and CD8+ T cells from Sin3a‐/‐Foxp3Cre mice showed increased activation ex vivo (Ki67+ and CD69+ increased 120% and 230%, respectively) and enhanced production of Granzyme B and cytokines IFN‐γ and IL‐2 upon stimulation in vitro. To gain a more complete understanding of the regulatory role of Sin3a in Tregs, we are in the process of performing RNAseq. To address the vast reduction of Foxp3+ Tregs within Sin3a‐/‐FoxP3Cre mice we are investigating methylation of the CNS2 intronic region of Foxp3 by bisulphite conversion and determining the fate of Tregs in vivo by lineage tracing.ConclusionsThese data show that the nuclear co‐regulator, Sin3a, functions in modulating Treg gene expression and helps maintain the unique properties of these key immune cells. Our results indicate a potential for therapeutic modulation of Treg functions by pharmacologic targeting of components within the Sin3a complex.

Do We Have a New Psoriasis Drug?

Pentadekapeptide BPC 157 was used in numerous laboratory rat animal models with proven cytoprotective and organ protective properties. In different wound therapy (incisional/excisional wound, deep burns, diabetic ulcer, alkali burns) fast and complete tissue restitution was achieved. BPC 157 was found to rapidly stimulate the expression of various genes involved in the healing process of the skin and mucosal lesions in these models. Psoriasis is a chronic, relapsing, immune‐mediated skin disease pathogenically driven by proinflammatory cytokines of which: TNF‐alpha, IL‐12, IL‐17, IL‐23 play a key role. Since BPC 157 has shown a significant anti‐inflammatory effect in several studies, the aim of this study is to show that it has the same role in the regression of inflammatory skin lesions such as those in psoriasis. An experimental model of psoriasis in laboratory animals is easily feasible, using 5% imiquimod topically.MATERIALS AND METHODS The experiment is done on male Wistar Albino rats. Animals are divided into groups of 6. „Psoriasis‐like” lesions are induced in all animals applying 5% imiquimod cream topically on shaved skin on their backs for 7 consecutive days. On the 7th day, 3 hours after applying imiquimod cream treatment starts usage BPC 157 in cream (conc. 1μg/g neutral cream) or only neutral cream (Belobaza) in control groups. Animals are treated and observed daily, video documentation was made. Animals are treated until the sacrifice day according to schedule. The severity of skin lesions is measured clinically using a modified version of Psoriasis Area Severity Index‐PASI score. Modified PASI includes scoring the following lesion features: erythema, infiltration, desquamation on scale 1‐4; maximum modified PASI value is 12. Two way ANOVA and Bonferroni post hoc test were used for statistical analysis. Data represented as mean SD for N=6/group.RESULTS Animals treated using BPC 157 conc.1μg/g in a cream had significantly lower values of PASI score when compared to control group. Faster resolution of imiquimod induced „psoriasis‐like” lesions was achieved using BPC 157 when compared to control group.CONCLUSION BPC 157 is well‐known peptide used in various experimental models without any side effects of it's use, with proven effects on the NO‐system, and excellent results in wound healing. Psoriasis is a rather common immune‐mediated skin disease driven by proinflammatory cytokines. TNF‐alpha, IL‐12, IL‐17, IL‐23 play a key role in the pathogenesis of psoriasis. It is undisputably that the use of BPC 157 topically successfully neutralizes the effects of imiquimod and induces regression of „psoriasis‐like“ lesions, the question that needs to be answered yet is whether BPC 157 has an impact on one of the above‐mentioned cytokines. It is yet to be explored which mechanism is the key to it´s beneficial effects in treating „psoriasis‐like“ lesions in experimental models.

Ultraviolet light induces HERV expression to activate RIG-I signalling pathway in keratinocytes.

Skin inflammation and photosensitivity are common in lupus erythematosus (LE) patients, and ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) patients. Type I interferons (IFN) are upregulated in LE skin after UV exposure; however, the mechanisms to explain UVB-induced inflammation remain unclear. Here, we demonstrated that UVB irradiation-induced activation of human endogenous retroviruses (HERVs) plays a major role in the immune response. UVB-induced HERV-associated dsRNA transcription and subsequent activation of the innate antiviral RIG-I/MDA5/IRF7 pathway led to downstream transcription of interferon-stimulated genes, which promotes UVB-induced apoptosis and proliferation inhibition in keratinocytes through RIG-I and MDA5 pathways. Our findings indicate that UVB irradiation induces HERV-dsRNA overexpression, and the dsRNA-sensing innate immunity pathway promotes type I IFN production, which may be a potential mechanism of skin inflammatory response and skin lesion of SLE/DLE.

T cells in the skin: Lymphoma and inflammatory skin disease

T cells are established contributors to the pathogenesis of atopic dermatitis and psoriasis; yet, whether they are the key drivers or simply unwitting participants remains incompletely understood. Conversely, malignant T cells are the undisputed culprits of cutaneous T-cell lymphoma (CTCL), a group of diseases that share key clinical, histopathologic, and molecular features with inflammatory skin disease (ISD). Here, we compare the pathogenesis of ISD and CTCL and discuss the resulting insights. Recurrent, skin-limited disease implicates skin-resident memory T cells in both ISD and CTCL. In CTCL, malignant T cells recruit benign T cells into inflammatory skin lesions, a disease-amplifying function that has also been proposed for pathogenic T cells in ISD. Mechanistically, cytokines produced by malignant T cells in CTCL and by pathogenic T cells in ISD, respectively, are likely both necessary and sufficient to drive skin inflammation and pruritus, which in turn promotes skin barrier dysfunction and dysbiosis. Therapies for ISD target T-cell effector functions but do not address the chronicity of disease, whereas treatments for CTCL target malignant T cells but not primarily the symptoms of the disease. Integrating our understanding of ISD and CTCL can result in important insights into pathogenesis and therapy that may improve the lives of patients in both of these disease groups.

Attention Mechanism Guided Deep Regression Model for Acne Severity Grading

Acne vulgaris is the common form of acne that primarily affects adolescents, characterised by an eruption of inflammatory and/or non-inflammatory skin lesions. Accurate evaluation and severity grading of acne play a significant role in precise treatment for patients. Manual acne examination is typically conducted by dermatologists through visual inspection of the patient skin and counting the number of acne lesions. However, this task costs time and requires excessive effort by dermatologists. This paper presents automated acne counting and severity grading method from facial images. To this end, we develop a multi-scale dilated fully convolutional regressor for density map generation integrated with an attention mechanism. The proposed fully convolutional regressor module adapts UNet with dilated convolution filters to systematically aggregate multi-scale contextual information for density maps generation. We incorporate an attention mechanism represented by prior knowledge of bounding boxes generated by Faster R-CNN into the regressor model. This attention mechanism guides the regressor model on where to look for the acne lesions by locating the most salient features related to the understudied acne lesions, therefore improving its robustness to diverse facial acne lesion distributions in sparse and dense regions. Finally, integrating over the generated density maps yields the count of acne lesions within an image, and subsequently the acne count indicates the level of acne severity. The obtained results demonstrate improved performance compared to the state-of-the-art methods in terms of regression and classification metrics. The developed computer-based diagnosis tool would greatly benefit and support automated acne lesion severity grading, significantly reducing the manual assessment and evaluation workload.

Disturbed expression of vitamin D and retinoic acid-related orphan receptors α and γ and of megalin in inflammatory skin diseases.

The pathogenesis of inflammatory skin diseases is associated with the abnormal activity of keratinocytes and immune cells infiltrate. Vitamin D3 deficiency can correlate with the increased incidence, severity and duration of inflammatory skin disorders. The exact mechanism on how vitamin D3 influences inflammatory skin diseases still requires clarification. However, it can be associated with the disturbances in transmembrane glycoprotein-LRP2/megalin, which is implicated in vitamin D3 transport to the cell, and defects in vitamin D-signalling through the nuclear receptors. Therefore, by using immunohistochemistry, we analysed the expression of LRP2/megalin, VDR, RORα and RORγ in allergic contact dermatitis, lichen simplex chronicus, sarcoidosis and psoriasis in comparison with the normal skin. We observed decreased expression of LRP2/megalin in all inflammatory lesions in comparison with the normal skin. Significant differences were also noticed in VDR, RORα and RORγ levels between inflammatory lesions and normal skin. Our research indicates disturbed expression of LRP2/megalin, VDR, RORα and RORγ in inflammatory skin lesions in comparison with normal skin. Therefore, we suggest that changes in the activity of these proteins may play role in pathogenesis of inflammatory skin disorders. Furthermore, we suggest that LRP2/megalin, VDR, RORα and RORy may serve as targets in therapy of these diseases.

Automated segmentation of epidermis in high-frequency ultrasound of pathological skin using a cascade of DeepLab v3+ networks and fuzzy connectedness.

This study proposes a novel, fully automated framework for epidermal layer segmentation in different skin diseases based on 75MHz high-frequency ultrasound (HFUS) image data. A robust epidermis segmentation is a vital first step to detect changes in thickness, shape, and intensity and therefore support diagnosis and treatment monitoring in inflammatory and neoplastic skin lesions. Our framework links deep learning and fuzzy connectedness for image analysis. It consists of a cascade of two DeepLab v3+models with a ResNet-50 backbone and a fuzzy connectedness analysis module for fine segmentation. Both deep models are pre-trained on the ImageNet dataset and subjected to transfer learning using our HFUS database of 580 images with atopic dermatitis, psoriasis and non-melanocytic skin tumors. The first deep model is used to detect the appropriate region of interest, while the second stands for the main segmentation procedure. We use the softmax layer of the latter twofold to prepare the input data for fuzzy connectedness analysis: as a reservoir of seed points and a direct contribution to the input image. In the experiments, we analyze different configurations of the framework, including region of interest detection, deep model backbones and training loss functions, or fuzzy connectedness analysis with parameter settings. We also use the Dice index and epidermis thickness to compare our results to state-of-the-art approaches. The Dice index of 0.919 yielded by our model over the entire dataset (and exceeding 0.93 in inflammatory diseases) proves its superiority over the other methods.

Atopic dermatitis: Current standards of diagnosis and treatment, including the latest methods of management

AbstractAtopic dermatitis (AD) is a chronic relapsing disease which causes characteristic eczematous skin lesions. The most common symptoms of atopic dermatitis are persistent pruritus, xerosis, and skin lesions with a typical location and appearance that changes with the patient’s age. The prevalence of the disease in the pediatric population is estimated at 10% to 30%, while in adults it ranges from 1% to 3%. The number of people who suffer from AD is rising every year. The pathophysiology of the disease is complex and multifactorial. It involves elements of epidermal barrier dysfunction, alterations in cellular immune response, IgE hypersensitivity, and environmental factors. AD significantly reduces the quality of life of both patients and their families. Patients with AD are at higher risk for neuropsychiatric disorders such as depression, attention-deficit/hyperactivity disorder, and headaches. The decreased quality of life of AD patients and their families is associated with the discomfort of recurrent and chronic inflammatory skin lesions, persistent pruritus, and the inconvenience of long-term therapy. It also affects the psychological development of children, contributes to behavioral disorders (hyperactivity, hypersensitivity) and impacts many areas of family life such as sleep, leisure activities, and relationships between family members. The basic treatment of AD is avoidance of potential harmful factors, proper care in the treatment of exacerbations, topical corticosteroids, and calcineurin inhibitors in proactive therapy. In some patients who meet age criteria, phototherapy and cyclosporine should be considered. In individuals with severe AD who do not respond to topical treatment and who will not benefit from general therapy, dupilumab, a biologic drug, is the treatment of choice. Biologic treatment has an increasingly important place in the effective and modern therapy of AD. Currently, new biologic drugs are being researched, which may bring a therapeutic revolution in AD in the future. Allergen immunotherapy in patients with AD should be carefully evaluated on an individual basis, as proper selection of patients with documented IgE-dependent sensitization is important for the success of this therapy. Close collaboration with the patient and their caregivers, education, and psychological support as appropriate are integral to the treatment.

EFFICIENCY OF FIRST GENERATION RETINOIDS IN THE TREATMENT OF III AND IV GRADE OF ACNE FOR IMPROVING EMOTIONAL STATUS

Acne (acne vulgaris) is a chronic, widespread, multifactorial disease manifested by open and closed comedones, inflammatory skin lesions in the form of papules, pustules and nodes. Emotional reactions are the most characteristic manifestations of human mental activity, which are accompanied by autonomic and endocrine changes associated with the release of various hormones: primarily stress hormones and androgens. Antibiotics have been effective and widely used for the past four decades. However, worldwide, there is an increase in antibiotic resistance due to their frequent and prolonged use. Retinoids are currently one of the most effective groups of drugs used to treat acne. The aim of our study is to investigate the efficacy of the first generation retinoids (isotretinoin) in the treatment of third and fourth degree acne in order to improve emotional status of patients. Patients received Isotretinoin in a starting dose of 0.5 mg / kg of body weight during meals, dose adjustment was carried out after 1 month at the rate of 0.5-0.75 1.0 mg / kg of body weight, the duration of treatment was assessed by gaining the commutative dose of 120 mg / kg of body weight, and the treatment duration lasted 16-24 weeks. After 3 months, the majority of patients 26 (89.66%) noted the disappearance of the rash completely, and 3 (10.34%) found only single papular-pustular elements. At the end of the therapy course with isotretinoin, complete clinical remission was achieved in all patients and the emotional load completely disappeared, self-esteem increased, disbelief in a positive result faded in 25 (96.15%) of 26 patients in the "Depressive" category.

Acute Vascular Reactive Inflammatory Acral Skin Lesions and SARS-CoV-2

&#x0D; &#x0D; &#x0D; Introduction: Coronavirus disease 2019 (COVID-19) predominantly affects the respiratory system, but there have been many reports of skin involvement. Several cutaneous manifestations associated with COVID-19 have been identified, including acral lesions (pernio-like), which we intend to better characterize in this study.&#x0D; Methods: Demographic, clinical and major histopathologic characteristics of acral skin lesions occurring during the acute infection stage of COVID-19 disease were evaluated in this survey conducted in the Dermatology Division of Santa Casa Hospital Complex, Federal University of Health Sciences, Porto Alegre, Brazil.&#x0D; Results: In the present study, we evaluated eight female patients with acute SARS-CoV-2 infection confirmed by PCR with acral skin lesions including pernio-like. The mean age was 43.6 and with no other acute disease, who had a good outcome with need for hospitalization only in 2 cases. Pernio-like lesions were observed under hot weather conditions in patients who denied any previous history of similar cutaneous manifestations. Some acral lesions resembled those of lupus erythematosus and of herpes simplex paronychia, but laboratory tests were negative for those conditions. Unusual nail involvement was present, characterized by half-moon shaped erythematous bands at the distal margin of the lunula.&#x0D; Conclusion: Recognition of these skin lesions is important in that they could be potential markers, aiding in the diagnosis and prognosis of COVID-19 disease.&#x0D; &#x0D; &#x0D;

Emerging topical drug delivery approaches for the treatment of Atopic dermatitis.

Atopic dermatitis is a chronic, relapsing skin inflammation disease that generally affects 20% of children and 1-3% of adults. It is characterized by pruritus, inflammatory skin lesions, and skin barrier defect. The pillar treatment is topical therapies that have shown great adherence and incredible results in alleviating symptoms of atopic dermatitis. Topical corticosteroids and calcineurin inhibitors have shown improvement in the symptoms of atopic dermatitis but have certain side effects. There is need to develop new therapies or novel drug delivery approaches which can overcome drawbacks of the conventional formulation and increase the therapeutic efficacy. The scope of this review is to describe the new topical therapies including phosphodiesterase inhibitors, Janus kinase inhibitors, and nano-formulations such as nanoemulsion, polymeric and lipid nanoparticles, vesicular system, and micelles. The article reviews and discusses the published literature of the topical drug delivery approaches for treatment of Atopic dermatitis. The reported literature highlighted the benefits of novel topical formulations exhibiting targeted drug delivery, better penetration, enhanced therapeutic efficacy, and overcome systemic side effects. Literature indicated that the new therapies and novel drug delivery approaches found to be the therapeutically more effective in increasing the efficacy of drugs and reducing the side effects in comparison with the conventional treatments for Atopic dermatitis. This has provided a way to modify and develop more such formulations for dermal delivery.

Establishing diagnostic criteria for mastocytosis in skin biopsies

The diagnosis of mastocytosis in skin biopsies can be challenging - particularly in cases with very few mast cells. More diagnostic criteria are needed. We analyzed 103 skin biopsies from patients with mastocytosis and compared them with biopsies from inflammatory skin lesions and normal skin. Using CD117 immunostaining, we determined the mast cell distribution pattern, the percentage of mast cells in the inflammatory infiltrate, and the mast cell count per mm². We found that a sheet-like or subepidermal distribution of mast cells was specific for mastocytosis. The most significant feature was the percentage of mast cells and not the mast cell count. We found that a mast cell percentage above 40% was fully specific in both adults and children but lacked sensitivity, especially in adults. In children, all cases with a percentage below 40% harbored a number of mast cells above 90 per mm², allowing a straightforward diagnosis. In adults, the diagnosis was more challenging and cases with less than 40% of mast cells could be diagnosed on account of a number of mast cells above 40 per mm², with 88.5% sensitivity and 95.2% specificity. Additional signs might be useful in difficult cases. However, CD25 immunostaining was not useful. We confirmed that the criteria currently applied in the bone marrow were not appropriate for the skin. Accordingly, we developed an algorithm for the diagnosis of mastocytosis in skin biopsies with a high level of interrater reproducibility (mean kappa 0.8).

Inflamed skin lesions along the course of a nerve as patient self-help proxy indicator of nerve abnormalities in leprosy

Objectives This study sought to determine the acceptability and utility of a self-assessment tool using inflamed skin lesions as proxy indicator of nerve abnormalities; and if nerve proximity to these skin lesions increases the risk of nerve abnormality and deformity in leprosy. Methods A cohort of 200 Filipino patients were monitored before and during reaction. Using a self-assessment tool, skin lesions were independently scored by the patient and a clinician, while the nerves were assessed by a clinical staff. Skin lesions and nerves were scored on a 0–15 severity scale; and nerves were noted as near or distant from the skin lesion. Skin lesions with type-1 or type-2 reactions were included. Results A total of 314 inflamed skin lesions matched with the same number of nerves near and distant from skin lesions were studied. There was no significant difference (P = 0.1771) in skin lesion scores independently determined by the patient and the clinician. Mean skin lesion score was 2 in the absence of a reaction; and 5 at the peak of a reaction. Nerve scores remained low in the absence of a reaction, and when a reaction occurred in the skin lesion distant from the nerve. However, nerve scores were significantly higher when a skin lesion near the nerve became inflamed (0.24 vs 1.03; P &lt; 0.0001). Among these skin lesions, 15% had nerve findings before the skin reaction; 32% had both nerve and skin findings, while 53% had skin reaction without nerve findings. At the peak of a reaction, seven new episodes of visible disability were recorded with skin lesion and nerve scores ≥3; and all nerves involved were located near inflamed skin lesions. No deformity was associated with nerves distant from inflamed skin lesions. Ninety-five percent (95%) of patients considered the tool highly acceptable, important and beneficial. Conclusion and recommendation This study demonstrates the acceptability and utility of a self-assessment tool using inflamed skin lesions as proxy indicator of nerve abnormality; and that with adequate training, patients can reliably be delegated to monitor their own skin lesions. This study also demonstrates the higher risk of deformity and abnormality among nerves near inflamed skin lesions.

Angiogenesis in Chronic Inflammatory Skin Disorders.

Angiogenesis, the growth of new blood vessels from preexisting vessels, is associated with inflammation in various pathological conditions. Well-known angiogenetic factors include vascular endothelial growth factor (VEGF), angiopoietins, platelet-derived growth factor, transforming growth factor-β, and basic fibroblast growth factor. Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) have recently been added to an important angiogenic factor. Accumulating evidence indicates associations between angiogenesis and chronic inflammatory skin diseases. Angiogenesis is deeply involved in the pathogenesis of psoriasis. VEGF, angiopoietins, tumor necrosis factor-a, interleukin-8, and interleukin-17 are unregulated in psoriasis and induce angiogenesis. Angiogenesis may be involved in the pathogenesis of atopic dermatitis, and in particular, mast cells are a major source of VEGF expression. Angiogenesis is an essential process in rosacea, which is induced by LL-37 from a signal cascade by microorganisms, VEGF, and MMP-3 from mast cells. In addition, angiogenesis by increased VEGF has been reported in chronic urticaria and hidradenitis suppurativa. The finding that VEGF is expressed in inflammatory skin lesions indicates that inhibition of angiogenesis is a useful strategy for treatment of chronic, inflammatory skin disorders.

Comparison of non-invasive Staphylococcus aureus sampling methods on lesional skin in patients with atopic dermatitis

There is evidence that Staphylococcus aureus colonisation is linked to severity of atopic dermatitis. As no gold standard for S. aureus sampling on atopic dermatitis skin lesions exists, this study compared three commonly used methods. In addition, effectiveness of standard skin disinfection to remove S. aureus colonisation from these inflamed skin lesions was investigated. In 30 atopic dermatitis patients, three different S. aureus sampling methods, i.e. detergent scrubbing, moist swabbing and tape stripping, were performed on naïve and disinfected skin lesions. Two different S. aureus selective media, mannitol salt agar and chromID agar, were used for bacterial growing. Quantifying the S. aureus load varied significantly between the different sampling methods on naïve skin lesions ranging from mean 51 to 1.5 × 104 CFU/cm2 (p < 0.001). The qualitative detection on naïve skin was highest with the two detergent-based techniques (86% each), while for tape stripping, this value was 67% (all on chromID agar). In comparison, mannitol salt agar was less sensitive (p < 0.001). The disinfection of the skin lesions led to a significant reduction of the S. aureus load (p < 0.05) but no complete eradication in the case of previously positive swab. The obtained data highlight the importance of the selected sampling method and consecutive S. aureus selection agar plates to implement further clinical studies for the effectiveness of topical anti-staphylococcal antibiotics. Other disinfection regimes should be considered in atopic dermatitis patients when complete de-colonisation of certain skin areas is required, e.g. for surgical procedures.

TEMP - Therapy Escalation in M. Parkinson - A German Regional Multicenter Survey

Objective: To characterize socio-demographic and disease-specific data of Parkinson’s disease patients before and 1 year after therapy escalation with subcutaneous apomorphine (APO), levodopa/carbidopa intestinal gel (LCIG), or subthalamic deep brain stimulation (STN-DBS) in an observation trial under real life conditions. Methods: Between 2014-2015, patients undergoing therapy escalation were consecutively included in 5 movement disorders centers. Motor and nonmotor symptoms were scored before and 1 year following initiation of invasive treatments. Therapy adherence, changes of scores and oral medication were evaluated. Results: In this open-label, prospective, 12-months, multicenter real-lifestudy 63 patients were included. 31 received DBS, 19 were commenced on LCIG, 15 received treatment with APO. 16 patients were lost for follow-up. Therapy adherence after one year in the STN-DBS-group was 100%, in the LCIG-group 87.5%, and in the APO-group 47%. Therapy termination in the APO-cohort was due to onset of hallucinations, orthostatic hypotension and inflammatory skin lesions and necrosis. After one year, UPDRS-III scores improved for STN-DBS patients. All groups gained ON-time with no differences between the 3 arms. STN-DBS patients had less ON-time with dyskinesia compared to APO- and LCIG-patients. Levodopa daily dose was decreased by 50% in STN-DBS patients, and 33% in APO patients, respectively. Conclusion: All three escalation options improved ON-time. Therapy adherence in the APO-group was less than 50% after 1 year, making it a potential bridging option while awaiting a more invasive treatment.