Ritlecitinib, a JAK3 /TEC inhibitor, modulates the markers of celiac autoimmunity in alopecia areata and vitiligo patients.

Background: Celiac disease (CeD) has shown an association with autoimmune disorders including vitiligo and alopecia areata (AA). Ritlecitinib, a JAK3 and TEC kinase family inhibitor, has been approved for treatment of patients with AA and is in late-stage development for vitiligo. Ritlecitinib inhibits cytotoxic T cells, NK cells, and B cells which play a role in the pathogenesis of CeD.

Evolution of pathologic B-cell subsets and serum environment-specific sIgEs in patients with atopic dermatitis and controls, from infancy to adulthood.

Background: While B-cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B-cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined.

Objective: To compare the frequency of B-cell subsets in blood of 0-5, 6-11, 12-17, and ≥18 years old patients with AD versus age-matched controls.

Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years.

Background: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)-13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2-year impacts of IL-13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate-to-severe AD.

Methods: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long-term extension ECZTEND (NCT03587805) trials.

OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD.

Regulatory T-cell dysfunction and cutaneous exposure to Staphylococcus aureus underlie eczema in DOCK8 deficiency.

Background: Dedicator of cytokinesis 8 (DOCK8)-deficient patients have severe eczema, elevated IgE, and eosinophilia, features of atopic dermatitis (AD).

Objective: We sought to understand the mechanisms of eczema in DOCK8 deficiency.

Methods: Skin biopsy samples were characterized by histology, immunofluorescence microscopy, and gene expression.

The pathogenetic role of Th17 immune response in atopic dermatitis.

Purpose Of Review: As we continue to unravel the pathophysiology and immune mechanisms underlying atopic dermatitis (AD), the emergence of targeted treatments has provided new options for management. Although there are available therapies targeting various immune pathways in AD, the precise pathogenic role of interleukin (IL)-17 in AD pathogenesis remains unclear. The objective of this review is to examine the existing data pertaining to the role of IL-17 in AD and shed light on the potential of targeting this pathway as a therapeutic approach in AD treatment.

Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis.

Introduction: Atopic dermatitis (AD) is an inflammatory disease affecting over 20% of the pediatric population, with 85% of cases presenting before the age of five. Recently, therapeutic options in pediatric patients have evolved rapidly, following extensive development in adult treatments.

Areas Covered: This review will encompass relevant molecular drivers, along with an overlook on treatment modalities in pediatric AD, as well as a summary of pipeline treatments in clinical trials for pediatric patients from PubMed, Google Scholar, and Clinicaltrials.

Early intervention and prevention of allergic diseases.

Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic.

Vascular inflammation in moderate-to-severe atopic dermatitis is associated with enhanced Th2 response.

Background: In atopic dermatitis (AD), some studies have shown an association with increased cardiovascular disease in certain populations. However, other investigations found modest or no association. Despite conflicting results, molecular profiling studies in both AD skin and blood have demonstrated upregulation of atherosclerosis and cardiovascular risk-related markers.

High-dimensional analysis defines multicytokine T-cell subsets and supports a role for IL-21 in atopic dermatitis.

Background: Flow cytometry is a well-accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad-scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available.

Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).

Background: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms.

Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments.

Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis.

Background: Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials.

Objective: To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis.

Methods: PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis.

A Preliminary F-FDG-PET/MRI Study Shows Increased Vascular Inflammation in Moderate-to-Severe Atopic Dermatitis.

Background: Recent data suggest that patients with atopic dermatitis (AD) have increased systemic immune activation and cardiovascular risk. However, unlike psoriasis, evaluation of active vascular inflammation using state-of-the-art imaging is lacking in AD.

Objective: To assess aortic and carotid vascular inflammation using F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging (F-FDG-PET/MRI) imaging in moderate-to-severe AD versus healthy individuals.

Correction to: Qualitative Assessment of Adult Patients' Perception of Atopic Dermatitis Using Natural Language Processing Analysis in a Cross-Sectional Study.

The authors would like to correct the images in figures which are in wrong order and require swapping.

Qualitative Assessment of Adult Patients' Perception of Atopic Dermatitis Using Natural Language Processing Analysis in a Cross-Sectional Study.

Introduction: Atopic dermatitis (AD) is an incurable, inflammatory skin disease characterized by skin barrier disruption and immune dysregulation. Although AD is considered a childhood disease, adult onset is possible, presenting with daily sleep disturbance and functional impairment associated with itch, neuropsychiatric issues (anxiety and depression), and reduced health-related quality of life. Although such aspects of adult AD disease burden have been measured through standardized assessments and based on population-level data, the understanding of the disease experienced at the patient level remains poor.

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood.

Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored.

Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects.

Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4/CD8 T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA) versus systemic/CLA T cells.

Correction to: JAK Inhibitors for Atopic Dermatitis: An Update.

Page 7, Table 1, ASN002 row. The cell entry in column 4, "Manufacturer", which previously read.

Atopic dermatitis endotypes and implications for targeted therapeutics.

Recent research advancements indicate that atopic dermatitis (AD) is a complex disease characterized by different subtypes/phenotypes based on age, disease chronicity, ethnicity, filaggrin and IgE status, and underlying molecular mechanisms/endotypes. This heterogeneity advocates against the traditional "one-size-fits-all" therapeutic approaches still used to manage AD. Precision medicine approaches, striving for targeted, tailored, endotype-driven disease prevention and treatment, rely on detailed definitions of the disease's variability across different phenotypes.

Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases.

Background: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA) T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo.

Objective: We sought to measure cytokine production by circulating skin-homing (CLA) versus systemic (CLA) "polar" CD4/CD8 ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects.

JAK Inhibitors for Atopic Dermatitis: An Update.

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of T helper (Th) 2, Th22, and varying degrees of Th1 and Th17 among various subtypes. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and spleen tyrosine kinase (SYK) pathways are involved in signaling of several AD-related cytokines, such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17, mediating downstream inflammation and barrier alterations.

A randomized placebo-controlled single-center pilot study of the safety and efficacy of apremilast in subjects with moderate-to-severe alopecia areata.

Alopecia areata (AA) is a common autoimmune disease that results in non-scarring hair loss. AA pathogenesis is thought to involve multiple inflammatory cytokines. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that reduces pro-inflammatory cytokine production.