scholarly journals Epidermal Barrier Dysfunction in Atopic Dermatitis

2021 ◽  
Vol 79 (3) ◽  
pp. 207-216
Author(s):  
Tiago Fernandes Gomes ◽  
Rebeca Calado ◽  
Margarida Gonçalo
Keyword(s):  
Atopic Dermatitis ◽  
Current Knowledge ◽  
Skin Barrier ◽  
Initial Step ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Atopic March ◽  
T Helper 2 ◽  
Barrier Repair

Impaired skin barrier is one of the hallmarks of atopic dermatitis (AD), with abnormalities in the cornified envelope, lipid lamellae, tight junctions and cutaneous microbiome. These findings are also present in nonlesional skin of AD individuals, suggesting that epidermal barrier defects may be the initial step towards the development of AD and eventually other atopic diseases (atopic march). It is currently known that pathophysiology of AD involves an interplay between this dysfunctional skin barrier and a predominantly type 2 skewed innate and adaptive immune responses, which further disrupt the skin barrier through type 2 cytokines. In this setting, there is enhanced penetration of environmental and food allergens through a deficient barrier, leading to an increased susceptibility to sensitization. During the sensitization process, thymic stromal lymphopoietin (TSLP) polarizes skin dendritic cells to a T-helper 2 response, and TSLP seems to be a key cytokine in the sensitization of food allergy, allergic asthma and rhinitis. In this review, the authors describe the current knowledge of the pathophysiology of the epidermal barrier, its disruption in AD and how it may be involved in the development of atopic comorbidities and the role of barrier repair therapy on the prevention of the atopic march progression.  

scholarly journals Barrier-Restoring Therapies in Atopic Dermatitis: Current Approaches and Future Perspectives

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Y. Valdman-Grinshpoun ◽  
D. Ben-Amitai ◽  
A. Zvulunov
Keyword(s):  
Atopic Dermatitis ◽  
Inflammatory Disease ◽  
Clinical Studies ◽  
Skin Barrier ◽  
Future Perspectives ◽  
Barrier Dysfunction ◽  
Gene Encoding ◽  
Promising Strategy ◽  
Topical Treatments ◽  
Barrier Repair

Atopic dermatitis is a multifactorial, chronic relapsing, inflammatory disease, characterized by xerosis, eczematous lesions, and pruritus. The latter usually leads to an “itch-scratch” cycle that may compromise the epidermal barrier. Skin barrier abnormalities in atopic dermatitis may result from mutations in the gene encoding for filaggrin, which plays an important role in the formation of cornified cytosol. Barrier abnormalities render the skin more permeable to irritants, allergens, and microorganisms. Treatment of atopic dermatitis must be directed to control the itching, suppress the inflammation, and restore the skin barrier. Emollients, both creams and ointments, improve the barrier function of stratum corneum by providing it with water and lipids. Studies on atopic dermatitis and barrier repair treatment show that adequate lipid replacement therapy reduces the inflammation and restores epidermal function. Efforts directed to develop immunomodulators that interfere with cytokine-induced skin barrier dysfunction, provide a promising strategy for treatment of atopic dermatitis. Moreover, an impressive proliferation of more than 80 clinical studies focusing on topical treatments in atopic dermatitis led to growing expectations for better therapies.

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

2019 ◽  
Vol 11 (480) ◽  
pp. eaav2685 ◽  
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.

scholarly journals Skin Barrier Function and Its Importance at the Start of the Atopic March

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mary Beth Hogan ◽  
Kathy Peele ◽  
Nevin W. Wilson
Keyword(s):  
Clinical Trials ◽  
Atopic Dermatitis ◽  
Food Allergy ◽  
Immune System ◽  
Barrier Function ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Allergen Sensitization ◽  
Epidermal Barrier ◽  
Atopic March

Atopic dermatitis can be due to a variety of causes from nonatopic triggers to food allergy. Control of egress of water and protection from ingress of irritants and allergens are key components of cutaneous barrier function. Current research suggests that a degraded barrier function of the skin allows the immune system inappropriate access to environmental allergens. Epidermal aeroallergen exposure may allow sensitization to allergen possibly initiating the atopic march. Further research into connections between epidermal barrier function and possible allergen sensitization will be important to undertake. Future clinical trials focused on skin barrier protection may be of value as a possible intervention in prevention of the initiation of the atopic march.

scholarly journals Current Insights into Atopic March

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1067
Author(s):  
Mitsuru Tsuge ◽  
Masanori Ikeda ◽  
Naomi Matsumoto ◽  
Takashi Yorifuji ◽  
Hirokazu Tsukahara
Keyword(s):  
Oxidative Stress ◽  
Environmental Pollutants ◽  
Skin Barrier ◽  
Allergic Diseases ◽  
Barrier Dysfunction ◽  
Atopic March ◽  
Inflammatory Conditions ◽  
And Oxidative Stress ◽  
Type 2 Inflammation

The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as “atopic march”. Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.

scholarly journals IgE Autoreactivity in Atopic Dermatitis: Paving the Road for Autoimmune Diseases?

Antibodies ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 47
Author(s):  
Christophe Pellefigues
Keyword(s):  
Atopic Dermatitis ◽  
Autoimmune Diseases ◽  
Current Knowledge ◽  
Skin Barrier ◽  
Allergic Diseases ◽  
Specific Ige ◽  
Barrier Dysfunction ◽  
The Road ◽  
Common Skin ◽  
Chronic Skin

Atopic dermatitis (AD) is a common skin disease affecting 20% of the population beginning usually before one year of age. It is associated with the emergence of allergen-specific IgE, but also with autoreactive IgE, whose function remain elusive. This review discusses current knowledge relevant to the mechanisms, which leads to the secretion of autoreactive IgE and to the potential function of these antibodies in AD. Multiple autoantigens have been described to elicit an IgE-dependent response in this context. This IgE autoimmunity starts in infancy and is associated with disease severity. Furthermore, the overall prevalence of autoreactive IgE to multiple auto-antigens is high in AD patients. IgE-antigen complexes can promote a facilitated antigen presentation, a skewing of the adaptive response toward type 2 immunity, and a chronic skin barrier dysfunction and inflammation in patients or AD models. In AD, skin barrier defects and the atopic immune environment facilitate allergen sensitization and the development of other IgE-mediated allergic diseases in a process called the atopic march. AD is also associated epidemiologically with several autoimmune diseases showing autoreactive IgE secretion. Thus, a potential outcome of IgE autoreactivity in AD could be the development of further autoimmune diseases.

scholarly journals The efficacy and safety of local therapy of atopic dermatitis in infants and school-age children

2020 ◽  
pp. 54-59
Author(s):  
O. I. Sidorovich ◽  
A. A. Tsyvkina ◽  
G. D. Abdullaeva
Keyword(s):  
Atopic Dermatitis ◽  
Local Therapy ◽  
Calcineurin Inhibitors ◽  
Skin Inflammation ◽  
School Age Children ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Atopic March ◽  
Age Related

Atopic dermatitis is a multifactorial genetic inflammatory skin disease associated with disturbances of skin barrier function affected by predisposition to IgE-mediated hypersensitivity, which is characterized by itching, chronic recurrent course of the disease, age-related features of localization and lesion morphology, and requires the long-term and permanent treatment.Treatment is based on the continuous use of emollients, topical calcineurin inhibitors, topical glucocorticoids, and hygienic skin care.The mechanisms of the atopic dermatitis development are primarily based on a genetic predisposition to allergies, failure of the normal development of congenital and acquired factors of the immune system, as well as the influence of environmental factors and various trigger factors, such as allergenic (food, indoor, epidermal, fungal allergens, etc.). and non-allergenic (tobacco smoke, pollutants, psycho-emotional stress, concomitant chronic and acute diseases, mainly ARVI, etc.).It has been established that atopic dermatitis is characterized by the epidermal barrier dysfunction leading to excessive tran-sepidermal water loss, increased permeability of the epidermis, the penetration of allergens and microbial agents via the skin and eventually to sensitization to allergens and the development of specific allergic skin inflammation and atopic march with the sequential development of other atopic diseases.Modern therapeutic strategies are actively aimed at repairing the epidermal barrier, preventing sensitization and atopic march development. This article describes the features of the epidermal barrier dysfunction in atopic dermatitis, lists the methods of its restoration and ways to prevent subsequent exacerbations using local therapy and emollients, and presents 3 clinical cases.

scholarly journals Role of skin microbiome in epidermal barrier dysfunction and development of atopic dermatitis in high risk infants

2019 ◽  
Vol 16 (1) ◽  
pp. 59-64
Author(s):  
N B Migacheva
Keyword(s):  
At Risk ◽  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Skin Microbiome ◽  
Children At Risk ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Microbiome Composition

Background. Colonization of skin with S. aureus in atopic dermatitis (AD) patients is a widespread phenomenon and a factor complicating the course of the disease. At present, it is not quite clear the role of S. aureus in the development of AD in children at risk. The aim of our study was to discribe the skin microbiome composition in young children at risk, as well as to investigate the role of S. aureus in skin barrier dysfunction and the development of AD. Material and methods. 12months follow-up study of 37 infants at risk has been performed. It included a general clinical examination, a microbiological investigation of skin microbiome (at 1 and 6 months), and investigation of epidermal barrier function by determining the transepidermal water loss (TEWL) at 1, 3, 6 and 12 months. Realization of AD during the observation period was considered as main outcome. Results. The prevalence of S. aureus colonization of infants aged 1 month was 45.9%, at the age of 6 months - 29.7%. Correlation analysis revealed an association between the skin colonization with S. aureus and a decrease of TEWL (p = 0.004), as well as the cumulative incidence of AD (p

scholarly journals New Treatments for Atopic Dermatitis Targeting Skin Barrier Repair via the Regulation of FLG Expression

2021 ◽  
Vol 10 (11) ◽  
pp. 2506
Author(s):  
Anna Dębińska
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Epidermal Differentiation ◽  
Barrier Dysfunction ◽  
New Therapeutic Approaches ◽  
Epidermal Differentiation Complex ◽  
High Prevalence ◽  
New Treatments ◽  
Barrier Repair

Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin disorders with a complex etiology and a broad spectrum of clinical phenotypes. Despite its high prevalence and effect on the quality of life, safe and effective systemic therapies approved for long-term management of AD are limited. A better understanding of the pathogenesis of atopic dermatitis in recent years has contributed to the development of new therapeutic approaches that target specific pathophysiological pathways. Skin barrier dysfunction and immunological abnormalities are critical in the pathogenesis of AD. Recently, the importance of the downregulation of epidermal differentiation complex (EDC) molecules caused by external and internal stimuli has been extensively emphasized. The purpose of this review is to discuss the innovations in the therapy of atopic dermatitis, including biologics, small molecule therapies, and other drugs by highlighting regulatory mechanisms of skin barrier-related molecules, such as filaggrin (FLG) as a crucial pathway implicated in AD pathogenesis.

scholarly journals Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Johny Bajgai ◽  
Jing Xingyu ◽  
Ailyn Fadriquela ◽  
Rahima Begum ◽  
Dong Heui Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Water Loss ◽  
Immunoglobulin E ◽  
Skin Barrier ◽  
Skin Lesions ◽  
Total Serum ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Complex Material ◽  
Mineral Complex

Abstract Background Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. Methods Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. Results Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. Conclusion Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

scholarly journals Update on Atopic Dermatitis

2019 ◽  
Vol 32 (9) ◽  
pp. 606 ◽  
Author(s):  
Tiago Torres ◽  
Eduarda Osório Ferreira ◽  
Margarida Gonçalo ◽  
Pedro Mendes-Bastos ◽  
Manuela Selores ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Clinical Manifestations ◽  
Skin Barrier ◽  
Future Research ◽  
Severe Atopic Dermatitis ◽  
Inadequate Response ◽  
Barrier Dysfunction ◽  
Therapeutic Goals ◽  
Global Health Issue

With an increasing prevalence during the past decades, atopic dermatitis has become a global health issue. A literature search following a targeted approach was undertaken to perform this non-systematic review, which intends to provide an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and current therapies for the treatment of atopic dermatitis. In sum, this is a heterogeneous skin disorder associated with variable morphology, distribution, and disease course. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis, and a strong genetic influence. Diagnosis is based on specific criteria that consider patient and family history and clinical manifestations. Overall disease severity must be determined by evaluating both objective signs and subjective symptoms. Therapeutic goals require a multistep approach, focusing on reducing pruritus and establishing disease control. Patients should be advised on basic skin care and avoidance of triggers. Topical anti-inflammatory agents should be considered in disease flares or chronic/recurrent lesions. In case of inadequate response, phototherapy, systemic immunosuppressants and, more recently, dupilumab, should be added. Nevertheless, the treatment of moderate-to-severe atopic dermatitis remains challenging and novel, efficacious, safe and targeted treatments are urgently needed. In conclusion, although the last few years have seen important improvement in the understanding of the disease, future research in atopic dermatitis will continue exploring gene-environment interactions and how it affects pathophysiology, disease severity, and treatment outcomes.

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