Deciphering the Connection Between Atopic Dermatitis and Cardiovascular Diseases: Analysis of Clinical Associations and Cardiometabolic Proteins.

Background: There are conflicting data on a potential association between atopic dermatitis (AD) and cardiovascular diseases (CVD). The aim of this study was to further explore this connection and whether there are biomarkers indicating the risk for CVD in AD patients.

Methods: We included 677 AD patients and 79 nonatopic controls from an observational multicenter case-control study (ProRaD: Prospective longitudinal study investigating the remission phase in patients with atopic dermatitis and other allergy-associated diseases).

Immunoglobulin E autoantibodies in atopic dermatitis associate with Type-2 comorbidities and the atopic march.

Background: Autoreactive immunoglobulin E (IgE) antibodies to self-peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well-characterized patients with AD and controls (1.

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood.

Background: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls.

IL-13, periostin and dipeptidyl-peptidase-4 reveal endotype-phenotype associations in atopic dermatitis.

Background: The heterogeneous (endo)phenotypes of atopic dermatitis (AD) require precision medicine. Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI)≥16. Previous studies have demonstrated an improved treatment response to the anti-interleukin (IL)-13 antibody tralokinumab in AD subgroups with elevated levels of the IL-13-related biomarkers dipeptidyl-peptidase (DPP)-4 and periostin.

From Skin Barrier Dysfunction to Systemic Impact of Atopic Dermatitis: Implications for a Precision Approach in Dermocosmetics and Medicine.

Atopic dermatitis (AD) affects up to 20% of children and is considered the starting point of the atopic march with the development of food allergy, asthma, and allergic rhinitis. The heterogeneous phenotype reflects distinct and/or overlapping pathogenetic mechanisms with varying degrees of epidermal barrier disruption, activation of different T cell subsets and dysbiosis of the skin microbiome. Here, we review current evidence suggesting a systemic impact of the cutaneous inflammation in AD together with a higher risk of asthma and other comorbidities, especially in severe and persistent AD.

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status.

Circulating phospholipids have been considered as biomarkers and therapeutic targets in multiple disorders. Atopic dermatitis (AD) is the most common inflammatory skin disease. Although there are numerous studies having addressed stratum corneum lipids in the context of epidermal barrier, little is known about the circulating lipids in patients with AD.

Measuring Atopic Dermatitis Disease Severity: The Potential for Electronic Tools to Benefit Clinical Care.

Severity of atopic dermatitis (AD) correlates with impact on health-related quality of life (HRQoL), work productivity, and burden on health systems. Tools to measure severity inform regulatory approval, drug access, and value- or measurement-based care. A core set of instruments for measuring AD has been established.

Vitamin D-Induced Promotor Dissociation of PU.1 and YY1 Results in FcεRI Reduction on Dendritic Cells in Atopic Dermatitis.

Atopic dermatitis (AD) is a severe inflammatory skin disease. Langerhans cells and inflammatory dendritic epidermal cells (IDEC) are located in the epidermis of AD patients and contribute to the inflammatory processes. Both express robustly the high-affinity receptor for IgE, FcεRI, and thereby sense allergens.

JAK1/2 inhibition impairs the development and function of inflammatory dendritic epidermal cells in atopic dermatitis.

Background: Janus kinase (JAK) inhibitors are a new class of therapeutic compounds for dermatological diseases. In atopic dermatitis (AD), data of clinical phase III trials show rapid improvement of pruritus and significant reduction of inflammation within the first weeks with a favorable safety profile. However, their mode of action in AD is not fully understood.

Increased circulating levels of neurotrophins and elevated expression of their high-affinity receptors on skin and gut mast cells in mastocytosis.

Mastocytosis is a rare heterogeneous disease characterized by increase of mast cells (MCs) in different organs. Neurotrophins (NTs) have been shown to promote differentiation and survival of MCs, which in turn represent a major source of NTs. Thus, a contribution of NTs to mastocytosis seems highly conceivable but has not yet been investigated.

High-density genotyping study identifies four new susceptibility loci for atopic dermatitis.

Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency.

Attenuated TGF-β1 responsiveness of dendritic cells and their precursors in atopic dermatitis.

The responsiveness of DCs and their precursors to transforming growth factor beta1 (TGF-β1) affects the nature of differentiating DC subsets, which are essential for the severity of atopic dermatitis (AD). To evaluate TGF-β signaling in monocytes and monocyte-derived DCs of AD patients compared with that of controls, in vitro generated Langerhans cell (LC) like DCs, expression of TGF-β receptors, phospho-Smad2/3 and Smad7 were evaluated. Furthermore, TNF-α expression and synergistic effects of TNF-α upon TGF-β signaling and DC generation were evaluated.

Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2.

Background: Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs).

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis.

Background: Atopic dermatitis (AD) is characterized by a predominance of T(H)2 immune reactions but weaker T(H)1 immune responses in acute skin lesions.

Objectives: To evaluate whether enhanced T(H)2 immunity in patients with AD might impair T(H)1 immune responses by affecting the IFN-γ responsiveness of antigen-presenting cells, we investigated IFN-γ receptor and IL-4 receptor α chain expression, IFN-γ signaling, and the expression of IFN-γ-responsive mediators in dendritic cells (DCs) and their precursors from patients with AD compared with those from healthy subjects.

Methods: Skin biopsy specimens were obtained and both monocytes and monocyte-derived dendritic cells (MoDCs) from patients with AD (n = 86) and control subjects (n = 84) were analyzed by means of flow cytometry, real-time PCR, ELISA, and HPLC.

Modifications of the innate immune system in atopic dermatitis.

Atopic dermatitis (AD) is a frequent chronic inflammatory skin disease which is often complicated by recurrent microbial superinfections. Genetically based modifications which might have an impact on the innate immune system, such as impairment of the skin barrier, modifications of pattern recognition receptors, deficiency of antimicrobial peptides, antiviral natural killer cells and plasmacytoid dendritic cells, facilitate the entry of allergens and infectious microbes into the skin, where they encounter immunocompetent cells. The micromilieu in the skin of AD patients further potentiates dysfunctions of the innate immune system, leading to a vicious circle promoting the disease.

Head and neck squamous-cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair.

Tobacco smoking, alcohol drinking, and occupational exposures to polycyclic aromatic hydrocarbons are the major proven risk factors for human head and neck squamous-cell cancer (HNSCC). Major research focus on gene-environment interactions concerning HNSCC has been on genes encoding enzymes of metabolism for tobacco smoke constituents and repair enzymes. To investigate the role of genetically determined individual predispositions in enzymes of xenobiotic metabolism and in repair enzymes under the exogenous risk factor tobacco smoke in the carcinogenesis of HNSCC, we conducted a case-control study on 312 cases and 300 noncancer controls.