Molecular Mechanisms of Atopic Dermatitis Pathogenesis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(8), P. 4130 - 4130

Published: April 16, 2021

Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature persistent itching of the skin. The relapsing course disease, economic burden, and whole family's involvement in treatment process immensely reduce quality life patients their families. disease emerges as social problem by increasing indirect costs, such visiting doctor, absenteeism from work school, avoiding interactions. Thepathophysiology atopic complex multifactorial. It includes genetic disorders, defect epidermal barrier, an altered immune response, anddisruption skin's microbial balance. numerous changes at thegenetic level innate adaptive immunity provide basis for characterizing various phenotypes endotypes dermatitis. Emerging therapies rely on action specific molecules involved disease's pathogenesis. may be starting point individualization treatment. This paper will try to present some molecular mechanisms clinical implications.

Language: Английский

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Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis

JAMA Dermatology, Journal Year: 2020, Volume and Issue: 156(4), P. 411 - 411

Published: Feb. 26, 2020

Interleukin 13 (IL-13) is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) pathophysiology.To evaluate the efficacy and safety lebrikizumab, novel, high-affinity, monoclonal antibody targeting IL-13 that selectively prevents formation IL-13Rα1/IL-4Rα heterodimer receptor signaling complex, in adults with moderate to severe AD.A phase 2b, double-blind, placebo-controlled, dose-ranging randomized clinical trial lebrikizumab injections every 4 weeks or 2 was conducted from January 23, 2018, May 2019, at 57 US centers. Participants were 18 years older AD.Patients 2:3:3:3 placebo subcutaneous following doses: 125 mg (250-mg loading dose [LD]), 250 (500-mg LD), LD baseline week 2).The primary end point percentage change Eczema Area Severity Index (EASI) (baseline 16). Secondary points for 16 included proportion patients achieving Investigator's Global Assessment score 0 1 (IGA 0/1); EASI improvement least 50%, 75%, 90% baseline; pruritus numeric rating scale (NRS) score; NRS points. Safety assessments treatment-emergent adverse events.A total 280 (mean [SD] age, 39.3 [17.5] years; 166 [59.3%] female) (n = 52) doses 73), 80), 75). Compared (EASI squares mean change, -41.1% [56.5%]), groups showed dose-dependent, statistically significant vs 16: (-62.3% [37.3%], P .02), (-69.2% [38.3%], .002), (-72.1% [37.2%], < .001). Differences placebo-treated (2 44 [4.5%]) seen as early day high-dose group (9 59 [15.3%]). Treatment-emergent events reported 24 52 (46.2%) follows: 42 73 (57.5%) weeks, 39 80 (48.8%) 46 75 (61.3%) weeks; most mild did not lead discontinuation. Low rates injection-site reactions (1 [1.9%] 228 [5.7%] all groups), herpesvirus infections [3.8%] 8 [3.5%]), conjunctivitis (0% 6 [2.6%]) reported.During treatment, provided rapid, dose-dependent across broad range manifestations adult AD demonstrated favorable profile. These data support role pathophysiology. If these findings replicate 3 studies, may meaningfully advance standard care AD.ClinicalTrials.gov Identifier: NCT03443024.

Language: Английский

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Staphylococcus epidermidis and its dual lifestyle in skin health and infection

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 21(2), P. 97 - 111

Published: Aug. 30, 2022

Language: Английский

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Atopic dermatitis: Role of the skin barrier, environment, microbiome, and therapeutic agents

Journal of Dermatological Science, Journal Year: 2021, Volume and Issue: 102(3), P. 142 - 157

Published: May 2, 2021

Language: Английский

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Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 388(12), P. 1080 - 1091

Published: March 15, 2023

Lebrikizumab, a high-affinity IgG4 monoclonal antibody targeting interleukin-13, prevents the formation of interleukin-4Rα-interleukin-13Rα1 heterodimer receptor signaling complex.We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included 16-week induction period and 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years age] adolescents [12 to <18 age, weighing ≥40 kg]) were randomly assigned in 2:1 ratio receive either lebrikizumab at dose 250 mg (loading 500 baseline week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for assessed up 16 weeks are this report. The primary outcome was an Investigator's Global Assessment (IGA) score 0 1 (indicating clear almost skin; range, 4 [severe disease]) reduction improvement) least points from 16. Secondary outcomes 75% improvement Eczema Area Severity Index (EASI-75 response) assessments itch interference sleep. Safety also assessed.In trial 1, met 43.1% 283 group 12.7% 141 placebo (P<0.001); EASI-75 response occurred 58.8% 16.2%, respectively (P<0.001). In 2, 33.2% 281 10.8% 146 52.1% 18.1%, Measures sleep indicated therapy. incidence conjunctivitis higher among who received than those placebo. Most adverse events during mild moderate severity did not lead discontinuation.In trials, treatment effective adults dermatitis. (Funded by Dermira; ADvocate1 ADvocate2 ClinicalTrials.gov numbers, NCT04146363 NCT04178967, respectively.).

Language: Английский

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Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate‐to‐severe atopic dermatitis: A network meta‐analysis

Dermatologic Therapy, Journal Year: 2022, Volume and Issue: 35(9)

Published: June 15, 2022

Janus kinase (JAK) inhibitors have become promising treatments for atopic dermatitis (AD), however no study directly comparing JAK with each other has been reported. We conducted this network meta-analysis to determine the comparative efficacy and safety of three common oral including abrocitinib, baricitinib, upadacitinib moderate-to-severe AD. first identified eligible studies from published meta-analyzes, then we searched PubMed obtain additional between February July 2021. Clinical were evaluated as primary secondary outcome, respectively. After extracting data assessing methodological quality, utilized ADDIS 1.4 software conduct pair-wise meta-analyzes. Ten included in final analysis. Pooled results that obtained higher investigator global assessment (IGA), eczema area, severity index (EASI) response, abrocitinib caused more treatment-emergent adverse events (TEAEs) regardless doses, compared placebo. Network meta-analyzes revealed 30 mg was superior all regimens 15 better than remaining except 200 terms IGA EASI response. Moreover, 100 mg, baricitinib 1 2 4 clinical efficacy. However, TEAEs. Abrocitinib, consistently effective therapies adult adolescent patients AD; however, may be optimal option short-term studies. More efforts should done reduce risk TEAEs by mg.

Language: Английский

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Electrospun fibers as carriers for topical drug delivery and release in skin bandages and patches for atopic dermatitis treatment

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2022, Volume and Issue: 15(1)

Published: July 11, 2022

Abstract The skin is a complex layer system and the most important barrier between environment organism. In this review, we describe some widespread problems, with focus on eczema, which are affecting more people all over world. Most of treatment methods for atopic dermatitis (AD) focused increasing moisture protecting from bacterial infection external irritation. Topical transdermal treatments have specific requirements drug delivery. Breathability, flexibility, good mechanical properties, biocompatibility, efficacy patches used skin. Up to today, electrospun fibers mostly wound dressing. Their however, meet AD. Active agents can be incorporated into by blending, coaxial or side‐by‐side electrospinning, also physical absorption post‐processing. Drug release membranes affected polymer properties technique combine them patch. We in detail vitro mechanisms, parameters transport, their kinetics, including theoretical approaches. addition, present current research patch design. This review summarizes extensive know‐how as delivery systems, while underlining advantages prospective use dermatitis. article categorized under: Implantable Materials Surgical Technologies > Nanomaterials Implants Nanotechnology Tissue Repair Replacement Therapeutic Approaches Discovery Emerging

Language: Английский

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Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2684 - 2684

Published: Feb. 28, 2022

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% children 10% adults in high-income countries. The prevalence incidence have increased recent years. onset mostly occurs childhood, although some cases may persist adult life or even manifest middle age (adult-onset AD). pathophysiology made a complex net, genetic background, barrier dysfunction, innate adaptive immune responses, as well itch contribute disease development, progression, chronicization. One important features dehydration, mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, antigen penetration. In accordance "outside-inside" theory pathogenesis, context an altered epidermal barrier, antigens encounter presentation cells (APCs), such Langerhans dendritic cells, leading their maturation Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), induce IgE-mediated sensitizations part pathogenic mechanisms AD. this review, we discuss role cytokines pathogenesis AD, considering patients various clinical phenotypes. Moreover, describe cytokine patterns at different phases evolution, relation phenotypes/endotypes, including age, race, intrinsic/extrinsic subtypes. We outcomes current biologics corroborate presence multiple axes involved background A deep insight into correlation between related forms crucial step towards increasingly personalized, therefore more efficient therapy.

Language: Английский

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Flavonoids as Promising Natural Compounds in the Prevention and Treatment of Selected Skin Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6324 - 6324

Published: March 28, 2023

Phytochemicals represent a large and diverse group of naturally occurring compounds, bioactive nutrients, or phytonutrients produced by plants, widely found in fruits, vegetables, whole grains products, legumes, beans, herbs, seeds, nuts, tea, dark chocolate. They are classified according to their chemical structures functional properties. Flavonoids belong the phenolic class phytochemicals with potential solid pharmacological effects as modulators multiple signal transduction pathways. Their beneficial effect on human body is associated antioxidant, anti-inflammatory, antimutagenic, anticarcinogenic also used various nutritional, pharmaceutical, medical, cosmetic applications. In our review, we discuss positive flavonoids chronic skin diseases such vitiligo, psoriasis, acne, atopic dermatitis.

Language: Английский

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Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 151(5), P. 1307 - 1316

Published: Feb. 23, 2023

Language: Английский

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