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 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 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 Selective sweep for an enhancer involucrin allele identifies skin barrier adaptation out of Africa

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Elizabeth Mathyer ◽  
Erin A. Brettmann ◽  
Alina D. Schmidt ◽  
Zane A. Goodwin ◽  
Inez Y. Oh ◽  
...  
Keyword(s):  
Selective Sweep ◽  
Skin Barrier ◽  
Human Migration ◽  
Epidermal Differentiation ◽  
Human Populations ◽  
Epidermal Differentiation Complex ◽  
Regulatory Module ◽  
Reporter Assays ◽  
Out Of Africa

AbstractThe genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.

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.

TRPV1 mediates itch‐associated scratching and skin barrier dysfunction in DNFB‐induced atopic dermatitis mice

2021 ◽  
Author(s):  
Liu Tang ◽  
Jiefang Gao ◽  
Xiaoqin Cao ◽  
Lu Chen ◽  
Huiling Wang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Barrier Dysfunction

scholarly journals Substantiation of Using Pimecrolimus 1% Cream in Proactive Therapy of Children with Atopic Dermatitis

2021 ◽  
Vol 20 (5) ◽  
pp. 376-382
Author(s):  
Nikolay N. Murashkin ◽  
Roman A. Ivanov ◽  
Eduard T. Ambarchian ◽  
Roman V. Epishev ◽  
Alexander I. Materikin ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Maintenance Therapy ◽  
Skin Disease ◽  
Pediatric Population ◽  
Efficacy And Safety ◽  
Inflammatory Skin Disease ◽  
High Prevalence ◽  
Proactive Therapy ◽  
Term Maintenance

Atopic dermatitis (AtD) is multifactorial inflammatory skin disease with high prevalence in pediatric population. It is crucial to implement long-term maintenance therapy to prevent AtD exacerbations according to current clinical guidelines and expert reports. The article summarizes the results of the major studies on using pimecrolimus 1% cream. Its efficacy and safety in long-term proactive therapy of children with AtD are presented.

scholarly journals Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

2020 ◽  
Vol 21 (8) ◽  
pp. 2867 ◽  
Author(s):  
Gabsik Yang ◽  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
Hye Suk Lee ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Systemic Disease ◽  
Skin Barrier ◽  
Immune Dysregulation ◽  
Food Allergies ◽  
Atopic Diseases ◽  
Barrier Dysfunction ◽  
Underlying Mechanisms ◽  
Chronic Pruritus ◽  
And Function

Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.

scholarly journals Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis

2020 ◽  
Vol 21 (20) ◽  
pp. 7607
Author(s):  
Hai Le Thanh Nguyen ◽  
Juan Valentin Trujillo-Paez ◽  
Yoshie Umehara ◽  
Hainan Yue ◽  
Ge Peng ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Antimicrobial Peptides ◽  
Tight Junction ◽  
Tight Junctions ◽  
Skin Barrier ◽  
Physical Barrier ◽  
Cutaneous Infections ◽  
Barrier Disruption ◽  
Barrier Repair ◽  
Skin Barrier Repair

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human β-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

Sign in / Sign up

Export Citation Format

Share Document