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International Journal of Molecular... Jul 2023Atopic dermatitis represents a complex and multidimensional interaction that represents potential fields of preventive and therapeutic management. In addition to the... (Review)
Review
Atopic dermatitis represents a complex and multidimensional interaction that represents potential fields of preventive and therapeutic management. In addition to the treatment armamentarium available for atopic dermatitis, novel drugs targeting significant molecular pathways in atopic dermatitis biologics and small molecules are also being developed given the condition's complex pathophysiology. While most of the patients are expecting better efficacy and long-term control, the response to these drugs would still depend on numerous factors such as complex genotype, diverse environmental triggers and microbiome-derived signals, and, most importantly, dynamic immune responses. This review article highlights the challenges and the recently developed pharmacological agents in atopic dermatitis based on the molecular pathogenesis of this condition, creating a specific therapeutic approach toward a more personalized medicine.
Topics: Humans; Dermatitis, Atopic; Precision Medicine; Biological Products
PubMed: 37511138
DOI: 10.3390/ijms241411380 -
Advances in Pediatrics Aug 2023Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a lifetime prevalence of up to 20% which can occur at any age but is most common among children.... (Review)
Review
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a lifetime prevalence of up to 20% which can occur at any age but is most common among children. There is a significant burden of pediatric AD in the primary care setting; thus, the ability to recognize and manage AD is of utmost importance to pediatricians. Treatment of AD requires a multifaceted approach based on a patient's severity including behavioral modifications, topical and systemic pharmacologic therapies, and phototherapy.
Topics: Humans; Child; Dermatitis, Atopic; Phototherapy; Behavior Therapy
PubMed: 37422293
DOI: 10.1016/j.yapd.2023.03.006 -
Journal of the American Academy of... Aug 2023Atopic dermatitis is a chronic inflammatory skin condition with a high prevalence that is increasing. The most universal symptom in patients with atopic dermatitis is... (Review)
Review
Atopic dermatitis is a chronic inflammatory skin condition with a high prevalence that is increasing. The most universal symptom in patients with atopic dermatitis is pruritus; it is often the most troublesome symptom. New insights on the mechanism of itch in patients with eczema have been elucidated, involving cross-talk between neural and immune systems, which have advanced our treatments significantly. In the last few years, there are emerging treatments currently undergoing investigation that yield a promising outlook in treating this symptom. In this review, we aimed to provide an updated overview of future treatments undergoing phase II and III clinical trials that may be used to treat pruritus of atopic dermatitis.
Topics: Humans; Dermatitis, Atopic; Pruritus
PubMed: 37156337
DOI: 10.1016/j.jaad.2023.04.057 -
Journal of the European Academy of... Oct 2023Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further...
BACKGROUND
Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further understanding of the abrocitinib long-term efficacy and safety profile is important for its appropriate use in treating chronic AD.
OBJECTIVE
To evaluate the abrocitinib efficacy up to 48 weeks and long-term safety in patients with moderate-to-severe AD.
METHODS
JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis focusses on patients from the phase 3 JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) studies who completed the full treatment period of placebo or abrocitinib (200 mg or 100 mg once daily) and subsequently entered JADE EXTEND. Efficacy endpoints included the proportion of patients achieving skin clearance (Investigator's Global Assessment [IGA] 0/1 [clear/almost clear]; ≥75% improvement in Eczema Area and Severity Index [EASI-75]) and itch response (Peak Pruritus Numerical Rating Scale [PP-NRS] severity ≥4-point improvement). Safety endpoints included treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation. Data cut-off: April 22, 2020.
RESULTS
As of the data cut-off, ~70% and ~45% of patients received abrocitinib for ≥36 and ≥48 weeks, respectively. Nasopharyngitis, atopic dermatitis, nausea and upper respiratory tract infections were the most frequent TEAEs. Serious TEAEs occurred in 7% and 5% and TEAEs leading to study discontinuation occurred in 9% and 7% of patients receiving abrocitinib 200 mg and 100 mg, respectively. Week 48 efficacy responses with abrocitinib 200 mg and 100 mg were as follows: IGA 0/1 52% and 39%; EASI-75 82% and 67%, and PP-NRS severity ≥4-point improvement 68% and 51%.
CONCLUSIONS
In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful skin and pruritus improvement. The long-term safety profile was manageable and consistent with previous reports.
Topics: Humans; Dermatitis, Atopic; Double-Blind Method; Immunoglobulin A; Pruritus; Severity of Illness Index; Treatment Outcome; Clinical Trials, Phase III as Topic
PubMed: 37335885
DOI: 10.1111/jdv.19280 -
The Journal of Investigative Dermatology Aug 2023Immunologically targeted therapies have revolutionized the treatment of inflammatory dermatoses, including atopic dermatitis and psoriasis. Although immunologic... (Review)
Review
Immunologically targeted therapies have revolutionized the treatment of inflammatory dermatoses, including atopic dermatitis and psoriasis. Although immunologic biomarkers hold great promise for personalized classification of skin disease and tailored therapy selection, there are no approved or widely used approaches for this in dermatology. This review summarizes the translational immunologic approaches to measuring treatment-relevant biomarkers in inflammatory skin conditions. Tape strip profiling, microneedle-based biomarker patches, molecular profiling from epidermal curettage, RNA in situ hybridization tissue staining, and single-cell RNA sequencing have been described. We discuss the advantages and limitations of each and open questions for the future of personalized medicine in inflammatory skin disease.
Topics: Humans; Dermatitis, Atopic; Precision Medicine; Dermatology; Psoriasis; Skin Diseases; Biomarkers
PubMed: 37341663
DOI: 10.1016/j.jid.2023.04.005 -
Veterinary Dermatology Feb 2024
Topics: Animals; Dogs; Dermatitis, Atopic; Dog Diseases
PubMed: 38095285
DOI: 10.1111/vde.13183 -
Journal of the European Academy of... Dec 2023Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta-analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk.
OBJECTIVES
To assess the potential causative link between AD and 14 site-specific cancers in a two-sample randomization study.
METHODS
From the largest genome-wide association study (GWAS) of AD (10,788 cases and 30,047 non-cases), genetic variants highly associated (p < 5 × 10 ) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n = 442,239) and the FinnGen study (n = 218,792), were employed to assess genetic associations with 14 site-specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta-analyses.
RESULTS
We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After the Benjamini-Hochberg correction, the inverse-variance weighted method indicated no association between AD and overall cancer risk in both the UK Biobank (OR, 1.00; 95% CI, 0.94-1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92-1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site-specific cancers.
CONCLUSIONS
Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes.
Topics: Adult; Humans; Dermatitis, Atopic; Drug-Related Side Effects and Adverse Reactions; Genome-Wide Association Study; Mendelian Randomization Analysis; Neoplasms; Polymorphism, Single Nucleotide
PubMed: 37478287
DOI: 10.1111/jdv.19380 -
The Medical Clinics of North America Jul 2024Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often...
Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.
Topics: Humans; Adrenal Cortex Hormones; Dermatitis, Atopic; Dermatologic Agents; Emollients; Phototherapy; Skin Care
PubMed: 38816108
DOI: 10.1016/j.mcna.2023.08.012 -
Advances in Experimental Medicine and... 2024Atopic dermatitis (AD) is a chronic relapsing condition that is characterized by itching and redness of the skin. Our modern usage of atopic dermatitis dates back to...
Atopic dermatitis (AD) is a chronic relapsing condition that is characterized by itching and redness of the skin. Our modern usage of atopic dermatitis dates back to 1933, when Wise and Sulzberger first coined the term to signify the disease's close association with other respiratory atopy, such as bronchial asthma and allergic rhinitis. A recent systematic review of 69 cross-sectional and cohort studies has confirmed that AD is now a worldwide phenomenon with lifetime AD prevalences of well over 20% in many affluent country settings. Although there is no obvious consistent overall global trend in the prevalence of AD, studies have shown that climate, urbanization, lifestyle, and socioeconomic class influence the prevalence of atopic dermatitis. Despite the pervasiveness of the disease, an understanding of atopic dermatitis has been hampered by a number of factors. Data suggests that extrinsic environmental factors work in concert with intrinsic immune mechanism and genetic factors to drive disease progression. With such a complex etiology, management of atopic dermatitis currently at best achieves symptomatic control rather than cure. This approach poses a significant burden on healthcare resources, as well as patients' quality of life. Current management methods of AD often involve a combination of non-pharmacologic modalities and prescription medications. Though they can be effective when employed, there are significant barriers to treatment for patients including time, costs, and medication side effects. Our aim, throughout this text, is to explore the complexities of AD, providing the healthcare provider with tips and tricks to improve patient care and satisfaction and the most current trends and treatment approaches on the horizon.
Topics: Humans; Dermatitis, Atopic; Prevalence; Quality of Life; Risk Factors
PubMed: 38724779
DOI: 10.1007/978-3-031-54513-9_1 -
Allergy Jan 2024Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast,...
BACKGROUND
Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape-stripping is a minimally invasive, nonscarring technique to collect skin samples.
METHODS
To construct a global AD skin transcriptomic profile comparing tape-strips to whole-skin biopsies, we performed RNA-seq on tape-strips and biopsies taken from the lesional skin of 20 moderate-to-severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold-change (FCH) ≥2.0 and false discovery rate <0.05.
RESULTS
We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape-strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape-strips showed higher FCHs for innate immunity (IL-1B, IL-8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL-13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL-22, S100As) and dermal cytokines (IFN-γ, CCL26). Itch-related genes (IL-31, TRPV3) were preferentially captured by tape-strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape-strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies.
CONCLUSIONS
Tape-strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD-related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies.
Topics: Humans; Dermatitis, Atopic; Transcriptome; Skin; Epidermis; Biopsy
PubMed: 37577841
DOI: 10.1111/all.15845