Bacterial skin colonization and infections in patients with atopic dermatitis

Atopic Dermatitis is a chronic inflammatory skin disease that affects a large number of children and adults. The disease results from an interaction between genetic predisposition, host environment, skin barrier defects, and immunological factors. A major aggravating factor associated with Atopic Dermatitis is the presence of microorganisms on the patient's skin surface. Staphylococcus aureus and Streptococcus pyogenes, for instance, can exacerbate chronic skin inflammation. As a result, antimicrobials have often been prescribed to control the acute phase of the disease. However, increased bacterial resistance to antimicrobial agents has made it difficult for dermatologists to prescribe appropriate medication. In the presence of disseminated dermatitis with secondary infection, systemic antibiotics need to be prescribed; however, treatment should be individualized, in an attempt to find the most effective antibiotic with fewer side effects. Also, the medication should be used for as short as possible in order to minimize bacterial resistance.

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An untargeted investigation into the skin surface lipidome in the West Highland white terrier dog, with and without atopic dermatitis

10.21203/rs.3.rs-16633/v1 ◽

2020 ◽

Author(s):

Helen Louise Orbell ◽

Nick J Cave ◽

Katharina Parry ◽

Craig E Griffin

Keyword(s):

Atopic Dermatitis ◽

Lipid Analysis ◽

Critical Role ◽

Skin Barrier ◽

Disease Status ◽

Skin Surface ◽

Surface Lipids ◽

Skin Surface Lipids ◽

Secondary Hypothesis ◽

Unaffected Skin

Abstract Background – The skin barrier is important in the pathogenesis of atopic dermatitis and stratum corneum lipids have a critical role. Skin surface lipids have been largely overlooked but also contribute to barrier function. An untargeted approach was used to compare the skin surface lipids from atopic and non-atopic West Highland White terrier dogs. The primary hypothesis was that a difference in the lipidome of atopic and non-atopic dogs would be found and the secondary hypothesis was that affected and unaffected skin would differ in lipid profile.Results – Thirty-nine dogs were classified into one of four disease status groups based on strict criteria. Samples for lipid analysis were collected from affected and unaffected skin, and liquid chromatography/mass spectrometry found 421 lipid soluble features. Ten lipids were positively identified. Statistical analysis could not distinguish between non-atopic and atopic dogs. Partial least squares-discriminant analysis revealed a difference in the lipid profiles from affected and non-affected skin irrespective of disease status. Conclusions – An untargeted approach found a large array of unidentified lipids from the skin surface. There was a difference in the lipidome between affected and unaffected skin that was not related to disease status. Investigation into the lipidome of the skin surface in health and disease is an emerging area of research which could have clinical and therapeutic applications.

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Comparison of the Inhibitory Activities of 5,6-Dihydroergosterol Glycoside α- and β-Anomers on Skin Inflammation

Molecules ◽

10.3390/molecules24020371 ◽

2019 ◽

Vol 24 (2) ◽

pp. 371 ◽

Cited By ~ 1

Author(s):

Tae Kim ◽

Young Cho ◽

HoonGyu Park ◽

Tae Lee ◽

Hakwon Kim

Keyword(s):

Protein Expression ◽

Inflammatory Diseases ◽

Skin Barrier ◽

Skin Inflammation ◽

New Drugs ◽

Inflammatory Biomarker ◽

Cytokines And Chemokines ◽

Inflammatory Stimuli ◽

Mrna And Protein Expression ◽

Chronic Skin

Chronic skin inflammatory diseases, such as atopic dermatitis, are associated with a dysfunctional skin barrier due to an increase in various inflammatory stimuli, for instance inflammatory cytokines and chemokines. In particular, CCL17 and CCL22 expression is increased in patients with chronic skin inflammation. In this study, we synthesized several α- and β-anomers of dihydroergosterol (DHE)-glycosides and assessed their effects on CCL17 and CCL22 expression. We confirmed that the β-anomers of DHE-glycosides were superior to α-anomers of DHE-glycosides in inhibiting CCL17 and CCL22 mRNA and protein expression. In addition, we determined that DHE-glycoside β-anomers showed strong inhibitory activity towards pro-inflammatory cytokine mRNA and protein expression, including that of TNF-α, IL-6, and IL-1β- in stimulated HaCaT cells. These results imply that DHE-glycoside α- and β-anomers should be separated during synthesis of drugs for chronic skin inflammation. Our results also suggest that β-anomers of DHE-glycosides may play an important role as new drugs for chronic skin inflammation because of their ability to inhibit the skin inflammatory biomarker proteins CCL17 and CCL22.

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MicroRNA-146a alleviates chronic skin inflammation in atopic dermatitis through suppression of innate immune responses in keratinocytes

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2014.05.022 ◽

2014 ◽

Vol 134 (4) ◽

pp. 836-847.e11 ◽

Cited By ~ 85

Author(s):

Ana Rebane ◽

Toomas Runnel ◽

Alar Aab ◽

Julia Maslovskaja ◽

Beate Rückert ◽

...

Keyword(s):

Atopic Dermatitis ◽

Immune Responses ◽

Skin Inflammation ◽

Innate Immune ◽

Innate Immune Responses ◽

Chronic Skin

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Analisis Penyebab dan Edukasi Dokter Pada Penyakit Neurodermatitis Sirkumskripta

10.31227/osf.io/jhqs6 ◽

2019 ◽

Author(s):

Victoria Tasya Arifa Guardiola

Keyword(s):

General Practitioners ◽

Skin Inflammation ◽

Skin Surface ◽

Early Management ◽

Chronic Skin

nurodermatitis is a chronic skin inflammation, itchy cryptography, and is characterized by lichenification. Likenification arises secondary and histologically has the characteristics of acanthosis and hyperkeratosis, and clinically appears to be thickening of the skin, with an increase in skin surface lines in the area. Neurodermatitis therapy aims to break the cycle of itching, because basically the action of scratching an itchy lesion will actually aggravate the disease. Topical corticostreoid treatment is the treatment of choice. Administration of oral antihistamines is used to reduce complaints of pruritus.Based on the Indonesian Doctors Competency Standards (SKDI), general practitioners must be able to diagnose and provide early management of neurodermatitis patients then refer to skin and sex specialists

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Ex-Vivo Skin Explant Culture Is a Model for TSLP-Mediated Skin Barrier Immunity

Life ◽

10.3390/life11111237 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1237

Author(s):

Thomas Bauer ◽

Daniela Gubi ◽

Jörg Klufa ◽

Philipp Novoszel ◽

Martin Holcmann ◽

...

Keyword(s):

Atopic Dermatitis ◽

Ex Vivo ◽

Skin Barrier ◽

Skin Inflammation ◽

The Body ◽

Suitable Model ◽

Ex Vivo Model ◽

Egfr Inhibition ◽

Explant Cultures ◽

Barrier Immunity

The skin is the outermost barrier protecting the body from pathogenic invasion and environmental insults. Its breakdown initiates the start of skin inflammation. The epidermal growth factor (EGFR) on keratinocytes protects this barrier, and its dysfunction leads to atopic dermatitis-like skin disease. One of the initial cytokines expressed upon skin barrier breach and during atopic dermatitis is TSLP. Here, we describe the expression and secretion of TSLP during EGFR inhibition and present an ex-vivo model, which mimics the early events after barrier insult. Skin explants floated on culture medium at 32 °C released TSLP in parallel to the activation of the resident Langerhans cell network. We could further show the up-regulation and activation of the AP-1 family of transcription factors during atopic-like skin inflammation and its involvement in TSLP production from the skin explant cultures. Inhibition of the c-Jun N-terminal kinase pathway led to a dose-dependent blunting of TSLP release. These data indicate the involvement of AP-1 during the early stages of atopic-like skin inflammation and highlight a novel therapeutic approach by targeting it. Therefore, skin explant cultures mimic the early events during skin barrier immunity and provide a suitable model to test therapeutic intervention.

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EMOLLIENT MILK XEMOSE IN THERAPY OF ATOPIC DERMATITIS IN CHILDREN

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja629 ◽

2014 ◽

Vol 11 (4) ◽

pp. 59-63

Author(s):

E T KINDEEVA ◽

N G KOROTKII ◽

A N PAMPURA

Keyword(s):

Atopic Dermatitis ◽

Clinical Efficacy ◽

Combined Therapy ◽

Allergic Inflammation ◽

Skin Barrier ◽

Skin Surface ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Skin Barrier Function ◽

Epidermal Barrier

Background. Structural and functional damages of the epidermal barrier in patients with atopic dermatitis promote the entry of allergens and development of Th2-type allergic inflammation. Moisturizers containing lipids increase the physiological antiinflammatory effects of topical corticosteroids (TGKS), improve the epidermal barrier and reduce the duration of TGKS using preventing further infringement barrier. To evaluate the clinical efficacy of emollient milk Xemose in children with atopic dermatitis. Materials and methods. We examined 27 children with atopic dermatitis. Children were divided into 2 groups: patients in group 1 (n=14) used emollient milk Xemose twice a day on the skin lesions and limbs in the complex therapy, patients in the 2nd group (n=13) received combined therapy incorporating traditional dampening agents on the basis of lanolin (Unna cream) 3 times daily. All patients underwent measurement of transepidermal water loss (TEWl) (Tewameter TM 300, Multi Probe Adapter MPA 5/9, Courage + Khazaka) and the pH of the skin (Skin-pH-Meter, Multi Probe Adapter MPA 5/9, Courage + Khazaka) before and after 2 weeks of therapy. Results. Patients in groupthat used Xemose milk and children in group with Unna cream after 2 weeks showed a statistically significant decrease of TEWl (p=0,041 and p=0,04, respectively). TEWl was significantly lower in children treated for 2 weeks with milk Xemose (p=0,027) than in children treated with Unna cream. in both groups pH skin surface have not changed (р=0,22 and р=0,22 respectively). Conclusion. Clinical efficacy of milk Xemose as compound improving skin barrier function in children with atopic dermatitis was shown.

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Kallikrein 5 induces atopic dermatitis–like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome

Journal of Experimental Medicine ◽

10.1084/jem.20082242 ◽

2009 ◽

Vol 206 (5) ◽

pp. 1135-1147 ◽

Cited By ~ 322

Author(s):

Anaïs Briot ◽

Céline Deraison ◽

Matthieu Lacroix ◽

Chrystelle Bonnart ◽

Aurélie Robin ◽

...

Keyword(s):

Atopic Dermatitis ◽

Protease Inhibitor ◽

Adaptive Immune System ◽

Skin Barrier ◽

Skin Inflammation ◽

Nuclear Factor Κb ◽

Thymic Stromal Lymphopoietin ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Netherton Syndrome

Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy.

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Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis

Journal of Clinical Medicine ◽

10.3390/jcm9113741 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3741

Author(s):

Masutaka Furue

Keyword(s):

Atopic Dermatitis ◽

Barrier Function ◽

Coal Tar ◽

Calcineurin Inhibitors ◽

Skin Barrier ◽

Skin Inflammation ◽

Interleukin 4 ◽

Skin Barrier Function ◽

Barrier Dysfunction ◽

Therapeutic Implications

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD.

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The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype

Science Translational Medicine ◽

10.1126/scitranslmed.aav2685 ◽

2019 ◽

Vol 11 (480) ◽

pp. eaav2685 ◽

Cited By ~ 43

Author(s):

Donald Y. M. Leung ◽

Agustin Calatroni ◽

Livia S. Zaramela ◽

Petra K. LeBeau ◽

Nathan Dyjack ◽

...

Keyword(s):

Atopic Dermatitis ◽

Food Allergy ◽

Sampling Method ◽

Skin Barrier ◽

Skin Surface ◽

Transepidermal Water Loss ◽

Barrier Dysfunction ◽

Ceramide Content ◽

Immune Pathways

Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD FA+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD FA−) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD FA+. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD FA+ were substantially lower than in AD FA− and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD FA+ had increased abundance of Staphylococcus aureus compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD FA+. The skin transcriptome of AD FA+ had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD FA+, whereas filaggrin breakdown products were negatively correlated with AD FA+. These data suggest that the most superficial compartment of nonlesional skin in AD FA+ has unique properties associated with an immature skin barrier and type 2 immune activation.

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