Search

INTRODUCTION: Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control. In the CrisADe CONTROL phase III study (ClinicalTrials.gov: NCT04040192), participants aged ≥ 3 months with mild to moderate AD treated with once-daily (QD) crisaborole, following initial treatment success with crisaborole twice daily (BID), had longer periods of flare-free maintenance, a higher number of flare-free days, and a lower number of flares compared with those who received vehicle. The study was an exploratory analysis of data on the maintenance of response per Investigators Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear]) during the CrisADe CONTROL study through week 52. METHODS: Exploratory endpoints were the time to ISGA response during the open-label run-in period, and the maintenance of ISGA response and the severity and duration of flares during the double-blind maintenance period. Outcomes were stratified by age (participants aged 3 months to

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

INTRODUCTION: The 2021 US approval of ruxolitinib cream for treatment of atopic dermatitis (AD) in patients aged ≥ 12 years was based on the results of two pivotal phase 3 studies. Currently, real-world data to describe effectiveness of ruxolitinib cream and physician satisfaction with treatment remain limited. Our objective is to describe disease control among adults with mild to moderate AD prescribed ruxolitinib cream and physician satisfaction with treatment. METHODS: Data were from the Adelphi AD Disease Specific Programme™, a US real-world, cross-sectional survey of physician-reported data, undertaken between August 2022 and March 2023. For patients aged ≥ 18 years, physicians reported patient demographics, clinical characteristics, treatment patterns, and physician satisfaction with disease control. Descriptive analysis of data for patients with mild to moderate AD prior to the initiation of ruxolitinib cream and treated with ruxolitinib cream for ≥ 1 month was undertaken. RESULTS: Among physician-reported data from 1360 patients with AD, 149 patients had received ruxolitinib cream (in combination or as monotherapy) for ≥ 1 month, including 59 patients receiving monotherapy. Prior to treatment with ruxolitinib cream, 84.6% of patients had moderate AD (Investigators Global Assessment, IGA of 3), whereas after treatment (median duration, 26 weeks), only 21.5% had an IGA of 3, with 48.3% of patients having clear or almost clear skin (IGA of 0/1). For these patients, 81.2% were not currently experiencing a flare, and physicians were satisfied with disease control for 87.3%. Results were similar in patients receiving monotherapy. The most frequent physician-reported reasons for prescribing ruxolitinib cream included relieving itch, improving lesion redness/thickness, achieving disease control, and reducing/controlling flares. CONCLUSIONS: These real-world findings demonstrate effective disease control and physician satisfaction with ruxolitinib cream for the treatment of AD in adults in a clinical practice setting. Outcomes were similar whether ruxolitinib cream was prescribed as monotherapy or in combination regimens, suggesting a role for ruxolitinib cream across the spectrum of disease.

Itch (pruritus) is a sensation in the skin that provokes the desire to scratch. The sensation of itch is mediated through a subclass of primary afferent sensory neurons, termed pruriceptors, which express molecular receptors that are activated by itch-evoking ligands. Also expressed in pruriceptors are several types of Transient Receptor Potential (TRP) channels. TRP channels are a diverse class of cation channels that are responsive to various somatosensory stimuli like touch, pain, itch, and temperature. In pruriceptors, TRP channels can be activated through intracellular signaling cascades initiated by pruritogen receptors and underly neuronal activation. In this review, we discuss the role of TRP channels TRPA1, TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPC3/4 in acute and chronic pruritus. Since these channels often mediate itch in association with pruritogen receptors, we also discuss Mas-related G-protein-coupled receptors (Mrgprs) and protease-activated receptors (PARs). Additionally, we cover the exciting therapeutic targets amongst the TRP family, as well as Mrgprs and PARs for the treatment of pruritus.

BACKGROUND: For children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. OBJECTIVES: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). METHODS: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight

Staphylococcus epidermidis is a common microbe on human skin and has beneficial functions in the skin microbiome. However, under conditions of allergic inflammation, the abundance of S. epidermidis increases, establishing potential danger to the epidermis. To understand how this commensal may injure the host, we investigate phenol-soluble modulin (PSM) peptides produced by S. epidermidis that are similar to peptides produced by Staphylococcus aureus. Synthetic S. epidermidis PSMs induce expression of host defense genes and are cytotoxic to human keratinocytes. Deletion mutants of S. epidermidis lacking these gene products support these observations and further show that PSMs require the action of the EcpA bacterial protease to induce inflammation when applied on mouse skin with an intact stratum corneum. The expression of PSMδ from S. epidermidis is also found to correlate with disease severity in patients with atopic dermatitis. These observations show how S. epidermidis PSMs can promote skin inflammation.

Background: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. Methods: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. Results: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. Conclusion: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo‐controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta‐analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta‐analysis of SCORAD outcomes was conducted using random‐effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta‐analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well‐designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To describe disease burden in individuals with moderate‐to‐severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions.This multicentre, cross‐sectional, observational study (MEASURE‐AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life.This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non‐biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6–25.0) and Patient‐Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8–20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5–6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8–15.8). ADerm‐Impact sleep domain score was 15.1 (95% CI 13.2–16.9). ADerm‐Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3–5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self‐reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied.ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Chitinase‐3‐like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti‐CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action.The effect of CHI3L1 antibody on phthalic anhydride‐induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis‐related cytokines were determined using an enzyme‐linked immunosorbent assay, and RT‐qPCR, STAT3 and CXCL8 signalling were measured by western blotting.Anti‐CHI3L1 antibody suppressed phthalic anhydride‐induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride‐induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride‐treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis‐related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL‐4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein‐association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL‐1β, IL‐4, CXCL8, TSLP, and the expression of CHI3L1 and p‐STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p‐STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model.Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect longterm therapeutic effects of upadacitinib 15 mg or 30 mg. Methods: A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment. Results: Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment. Conclusion: The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD. [ABSTRACT FROM AUTHOR]

Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined. Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks. Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p < 0.01) and maltose (p < 0.05 and p < 0.01). Sleep disturbance was improved only in the FOS group (p < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p < 0.01). Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD. [ABSTRACT FROM AUTHOR]

Background: Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses. Methods and results: We examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls. Conclusions: We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted. [ABSTRACT FROM AUTHOR]

This study investigated the potential associations between allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) and the development of primary open-angle glaucoma. We utilized authorized data from the Korean National Health Information Database (KNHID), which provides comprehensive medical claims data and information from the National Health Screening Program. We compared the baseline characteristics of subjects with and without allergic diseases and calculated the incidence and risk of glaucoma development. Cox proportional hazard regression analysis was used to determine the risk of glaucoma development in subjects with allergic diseases. A total of 171,129 subjects aged 20–39 with or without allergic diseases who underwent a general health examination between 2009 and 2015 were included. Subjects with allergic diseases exhibited a higher incidence of glaucoma compared to the control group. The hazard ratio (HR) of glaucoma onset was 1.49 and 1.39 in subjects with at least one allergic disease before and after adjusting for potential confounding factors, respectively. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development (aHR 1.73) after adjusting for confounders. Allergic rhinitis showed an increased risk for incident glaucoma after adjustment (aHR 1.38). Asthma showed the lowest but still increased risk for glaucoma (aHR 1.22). The associations were consistent in all subgroup analyses stratified by sex, smoking, drinking, exercise, diabetes, hypertension, dyslipidemia, or history of steroid. In conclusion, allergic diseases are associated with increased risk of glaucoma development. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development followed by allergic rhinitis and asthma. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Meteorin‐like protein (METRNL)/Interleukin‐41 (IL‐41) is a novel immune‐secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD).METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903‐induced AD‐like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single‐cell RNA‐seq and RNA‐seq.METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced β‐Catenin activation, limited the expression of Th2‐related molecules that attract the accumulation of Arginase‐1 (Arg1)hi macrophages, dendritic cells, and activated mast cells.METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule β‐Catenin. [ABSTRACT FROM AUTHOR]

Atopic dermatitis patients and caregivers experience a high physical, mental and financial burden in Australia. We outline how the current care model impacts disease management and patients' quality of life via a survey of 265 Australian patients and caregivers to capture the experience of managing atopic dermatitis (AD) in Australia. Patients report an unsatisfactory quality of life and a high burden of disease with poor long‐term control and low treatment satisfaction. They also reported changing spending and saving patterns to fund medical care. Patient experience improves with more specialised care that incorporates shared decision‐making and patient/caregiver training beyond the clinic visit. These results highlight the need for improved general practitioner (GP) education, expedited access to medical specialists, greater patient involvement in treatment choices and more financial assistance to improve the experience of Australian patients and caregivers. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a multi-pathogenic disease characterized by chronic skin inflammation and barrier dysfunction. Therefore, improving the skin's ability to form an epidermal barrier and suppressing the production of cytokines that induce type 2 inflammatory responses are important for controlling atopic dermatitis symptoms. (-)-Blebbistatin, a non-muscle myosin II inhibitor, has been suggested to improve pulmonary endothelial barrier function and control inflammation by suppressing immune cell migration; however, its efficacy in atopic dermatitis is unknown. In this study, we investigated whether (S)-(-)-blebbistatin O-benzoate, a derivative of (-)-blebbistatin, improves dermatitis symptoms in a mite antigen-induced atopic dermatitis model using NC/Nga mice. The efficacy of the compound was confirmed using dermatitis scores, ear thickness measurements, serum IgE levels, histological analysis of lesions, and filaggrin expression analysis, which is important for barrier function. (S)-(-)-Blebbistatin O-benzoate treatment significantly reduced the dermatitis score and serum IgE levels compared to those in the vehicle group (p < 0.05). Furthermore, the histological analysis revealed enhanced filaggrin production and a decreased number of mast cells (p < 0.05), indicating that (S)-(-)-blebbistatin O-benzoate improved atopic dermatitis symptoms in a pathological model. In vitro analysis using cultured keratinocytes revealed increased expression of filaggrin, loricrin, involucrin, and ceramide production pathway-related genes, suggesting that (S)-(-)-blebbistatin O-benzoate promotes epidermal barrier formation. Furthermore, the effect of (S)-(-)-blebbistatin O-benzoate on type 2 alarmin cytokines, which are secreted from epidermal cells upon scratching or allergen stimulation and are involved in the pathogenesis of atopic dermatitis, was evaluated using antigens derived from mite feces. The results showed that (S)-(-)-blebbistatin O-benzoate inhibited the upregulation of these cytokines. Based on the above, (S)-(-)-blebbistatin O-benzoate has the potential to be developed as an atopic dermatitis treatment option that controls dermatitis symptoms by suppressing inflammation and improving barrier function by acting on multiple aspects of the pathogenesis of atopic dermatitis. [ABSTRACT FROM AUTHOR]

We present a case of a 47‐year‐old male with severe atopic dermatitis and metastatic renal cell carcinoma managed successfully with dupilumab. This case further supports the safety of dupilumab in patients with active malignancy, an area currently with limited data. [ABSTRACT FROM AUTHOR]

Background/Objectives: The evaluation of the efficacy and safety of new molecules for atopic dermatitis (AD) in real clinical practice is very important to obtain information that clinical trials (EECC) lack. The pattern of AD in the head and neck (H&N) continues to be a challenge in treatment today, despite the new molecules, and real‐life data on the use of tralokinumab is still missing. This is the first daily practice study of tralokinumab treatment in patients with H&N AD pattern. The objective is to evaluate the efficacy and safety of tralokinumab in the short term (16 weeks) in patients with AD with H&N pattern, for the first time. Methods: A multicentre prospective observational study was conducted, including patients with moderate‐severe AD and H&N pattern who started tralokinumab treatment in four hospitals in Andalusia. Values of severity and quality of life scales, as well as patient‐reported outcomes (PROs), were collected at baseline and at Weeks 4 and 16. Safety events were also recorded. Results: Twelve patients were included. An improvement was observed in all efficacy and quality of life parameters evaluated at 16 weeks with respect to the baseline. No serious adverse events were recorded. Conclusions: In real clinical practice, tralokinumab is demonstrated to be an effective and safe treatment for patients with AD and H&N pattern at short term. [ABSTRACT FROM AUTHOR]

Background: A significant association between atopic dermatitis and leaky gut syndrome has been demonstrated in humans. No studies have been conducted to determine whether there is an association between atopic dermatitis and intestinal damage in dogs. Objectives: This study aimed to determine whether there is an association between canine atopic dermatitis and intestinal damage using selected intestinal‐related biomarkers. Methods: Twenty‐six dogs with atopic dermatitis and 10 healthy dogs were included. Moderate‐to‐severe pruritus, erythema, erosion and alopecia on different parts of the body were sought in dogs to suspect atopic dermatitis. The presence of atopic dermatitis was confirmed by an allergic skin test. Serum biomarkers including intestinal fatty acid binding protein (I‐FABP), intestinal alkaline phosphatase (IAP), trefoil factor‐3 (TFF‐3), immunoglobulin E (IgE), interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13) concentrations were measured from venous blood samples. Results: Of the 26 dogs tested for allergens, 16 were found to be sensitive to mould mites, 10 to vernal grass, eight to house dust mites, five to wheat dust and five to grass pollen mix allergens. Significant increases in serum IAP, TFF‐3, IgE, IL‐4 and IL‐13 concentrations were determined. Conclusion: It was thought that the increase in TFF‐3 and IAP concentrations may be due to the presence of intestinal epithelial damage and the repair of this damage. In addition, the development of atopic dermatitis may be predisposed to the entry of allergens into the body through sites of intestinal damage. [ABSTRACT FROM AUTHOR]

Objective: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide–releasing medication) versus vehicle in MC patients with or without AD. Methods: Three Phase 3, multicenter, randomized, double‐blind, vehicle‐controlled, parallel‐group trials (B‐SIMPLE[berdazimer sodium in molluscum patients with lesions]1, −2, −4) enrolled patients 6 months and older with 3–70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta‐analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD− when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. Results: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD− (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7–2.5) and AD− (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4–2.4) subgroups. AEs in AD+ were application‐site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). Conclusions: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer‐induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum. [ABSTRACT FROM AUTHOR]

Many baby cleansers are promoted as hypoallergic products; however, these claims are not typically validated. This study assessed the 50 best‐selling baby cleansers from online retailer Amazon for potential allergens. We found that the presence of most marketing claims, including "hypoallergenic" or "allergy‐tested," did not correlate with the number of potential allergens in a cleanser. Furthermore, the total number of marketing claims of a cleanser was positively correlated with the number of allergens, highlighting the discordance between marketing claims and allergen content in baby cleansers. [ABSTRACT FROM AUTHOR]

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects children worldwide, with potential associations to metabolic syndrome (MetS) and non‐alcoholic fatty liver disease (NAFLD). Limited research exists on the interplay between AD, MetS, and NAFLD in the pediatric population. This study aimed to investigate the prevalence and potential relationships among AD, MetS, and NAFLD in children. Methods: A case–control study design was employed, recruiting 50 children with AD (median age: 9.5 years) and 50 age‐ and sex‐matched healthy controls (median age: 11.5 years, p =.051). Data on demographic characteristics, clinical features, disease severity, treatment history, anthropometric measurements, and laboratory evaluations were collected. MetS and NAFLD were diagnosed based on established criteria. Results: The prevalence of MetS was significantly higher in children with AD compared with controls (24% vs. 2%, p =.002). Significant differences for systolic blood pressure (p <.001), diastolic blood pressure (p =.012), and waist circumference (p =.040) were observed between AD patients and controls. Children with AD had higher triglyceride levels (p =.005). NAFLD was exclusively seen in moderate to severe AD cases (6% vs. 0%, p =.242). AD severity showed associations with increased body mass index (p =.020). Conclusion: This study highlights the increased prevalence of MetS and the potential association with NAFLD in children with AD. The findings suggest that AD may contribute to the development of metabolic abnormalities at an early age. Further research is needed to elucidate the underlying mechanisms and explore preventive strategies for these interconnected conditions. [ABSTRACT FROM AUTHOR]

Background: Allergy represents a major health problem of increasing prevalence worldwide with a high socioeconomic impact. Our knowledge on the molecular mechanisms underlying allergic diseases and their treatments has significantly improved over the last years. The generation of allergen-specific regulatory T cells (Tregs) is crucial in the induction of healthy immune responses to allergens, preventing the development and worsening of allergic diseases. Summary: In the last decades, intensive research has focused on the study of the molecular mechanisms involved in Treg development and Treg-mediated suppression. These mechanisms are essential for the induction of sustained tolerance by allergen-specific immunotherapy (AIT) after treatment discontinuation. Compelling experimental evidence demonstrated altered suppressive capacity of Tregs in patients suffering from allergic rhinitis, allergic asthma, food allergy, or atopic dermatitis, as well as the restoration of their numbers and functionality after successful AIT. Key Message: The better understanding of the molecular mechanisms involved in Treg generation during allergen tolerance induction might well contribute to the development of novel strategies for the prevention and treatment of allergic diseases. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a considerable impact on patients' quality of life. Its etiology is multifactorial and, among the predisposing factors, a role is played by oxidative stress. Pollution, recurrent infections, and psychological stress contribute to oxidative stress, amplifying the production of proinflammatory cytokines and worsening barrier damage. There are various oxidative stress mechanisms involved in the pathogenesis of AD. Moreover, AD often appears to be associated with psychological disorders such as alexithymia, depression, and anxiety due to severe itching and related insomnia, as well as social distress and isolation. The increasing incidence of AD requires the evaluation of additional therapeutic approaches in order to reduce the psychological burden of this condition. Our review aims to evaluate the role of some nutraceuticals in AD treatment and its related psychological comorbidities. The combination of some natural compounds (flavonoids, alkaloids, terpenes, isothiocyanates) with traditional AD treatments might be useful in improving the effectiveness of therapy, by reducing chronic inflammation and preventing flare-ups, and in promoting corticosteroid sparing. In addition, some of these nutraceuticals also appear to have a role in the treatment of psychological disorders, although the underlying oxidative stress mechanisms are different from those already known for AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a condition with a multifactorial aetiology that affects the skin. It most often begins at preschool age and involves the skin. The disease's main symptom is intense itching, which occurs especially at night and affects the child's sleep, negatively impacting the quality of life of affected children and, consequently, their families. The difficulty in resting during the night leads to many problems during the day, particularly behavioural disorders and difficulties in paying attention at school, which results in learning impairment. The unexpected symptoms of AD are caused by pathophysiological processes that include many molecular pathways and inflammatory cytokines such as IL-31, IL-1, IL-2, TNF-a, and IL-6. Drawing on a comprehensive review of the literature in PubMed/MedLine, our review offers an in-depth exploration of both the psychosocial impacts of AD and the molecular processes that contribute to this disorder. [ABSTRACT FROM AUTHOR]

The scientific article focuses on the role of azulene and its derivatives in the therapy of dermatological diseases, presenting the latest laboratory and clinical research as well as prospects for further studies. In a synthetic literature review, various databases such as PubMed, Scopus, Web of Science, and the Database of Polish Scientific Journals were queried to select relevant articles concerning azulene. The conclusions drawn from the thematic analysis of the studies emphasize the multifaceted pharmacological actions of azulene and its derivatives including their anti-inflammatory properties, potential anticancer effects, photoprotective abilities, alleviation of itching, management of atopic dermatitis, and treatment of erectile dysfunction. However, there are certain limitations associated with the application of unmodified azulene on the skin, particularly related to photodecomposition and the generation of reactive oxygen species under UV radiation. These effects, in turn, necessitate further research on the safety of azulene and azulene-derived substances, especially regarding their long-term use and potential application in phototherapy. The authors of this work emphasize the necessity of conducting further preclinical and clinical studies to fully understand the mechanisms of action. Incorporating azulene and its derivatives into the therapy of dermatological disorders may represent an innovative approach, thereby opening new treatment avenues for patients. [ABSTRACT FROM AUTHOR]

Derangement of the epidermal barrier lipids and dysregulated immune responses are key pathogenic features of atopic dermatitis (AD). The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signaling axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D epidermal equivalents. Tofacitinib, a low-molecular-mass JAK inhibitor, was used to screen for JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4 and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitoleic acid and caused depletion of triglycerides, in association with altered phosphatidylcholine profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very-long-chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by the halted homeostasis of FA metabolism. [ABSTRACT FROM AUTHOR]

This collection of articles from the Australasian Journal of Dermatology provides information on the efficacy and safety of various treatments for atopic dermatitis (AD). The studies discuss the results of clinical trials and real-world studies on targeted systemic therapies, including lebrikizumab and dupilumab, for moderate-to-severe AD in adults and adolescents. The studies show that both lebrikizumab and dupilumab are effective and safe treatment options for AD. Other articles in the collection explore topics such as the management of sleep disturbance in children with AD, the relationship between AD and mental health, and the association between AD and dementia. These findings provide valuable insights for patients and healthcare professionals seeking effective treatments and management strategies for AD. [Extracted from the article]

Atopic dermatitis (AD) has become a common childhood disease that affects a large number of children worldwide and has become a chronic skin disease that causes huge economical and psychological damage to the whole family. Despite the use of steroids, immunosuppressants, and various topical preparation, the prognosis is still poor. Hence, this review aimed to explore the potential of using essential oils (EO) as an active ingredient in managing AD. The review was completed by using Pubmed, Scopus, and Medline to search for relevant articles that study the pathophysiology of AD, the properties of EO, the use of EO in managing AD, and the suitable advanced formulation to incorporate EO. From the review conducted, it was concluded that EO have huge potential in managing AD and can be used as complimentary therapeutic agents in AD treatment. Scientists and industries should venture into commercializing more topical products with EO to help manage AD more effectively. [ABSTRACT FROM AUTHOR]

The CD1 and MR1 protein families present lipid antigens and small molecules to T cells, complementing well-studied major histocompatibility complex–peptide mechanisms. The CD1a subtype is highly and continuously expressed within the skin, most notably on Langerhans cells, and has been demonstrated to present self and foreign lipids to T cells, highlighting its cutaneous sentinel role. Alteration of CD1a-dependent T-cell responses has recently been discovered to contribute to the pathogenesis of several inflammatory skin diseases. In this review, we overview the structure and role of CD1a and outline the current evidence implicating CD1a in the development of psoriasis, atopic dermatitis and allergic contact dermatitis. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC). Objectives To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity. Methods We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped. Results Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm–1 (full width half maximum) and 1340 cm–1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = –0.59, carboxylate peak area r = –0.50). Conclusions ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a noteworthy pathogen in allergic diseases, as four staphylococcal exotoxins activate mast cells, a significant contributor to inflammation, in an IgE‐independent manner. Although the adhesion of mast cells is an essential process for their immune responses, only a small number of exotoxins have been reported to affect the process. Here, we demonstrated that staphylococcal superantigen‐like (SSL) 3, previously identified as a toll‐like receptor 2 agonist, induced the adhesion of murine bone marrow‐derived mast cells to culture substratum. SSL3‐induced adhesion was mediated by fibronectin in an Arg‐Gly‐Asp (RGD) sequence‐dependent manner, suggesting the integrins were involved in the process. Additionally, SSL3 was found to bind to an anti‐adhesive surface protein CD43. SSL3 induced the adhesion of HEK293 cells expressing exogenous CD43, suggesting that CD43 is the target molecule for adhesion induced by SSL3. Evaluation of SSL3‐derived mutants showed that the C‐terminal region (253–326), specifically T285 and H307, are necessary to induce adhesion. SSL3 augmented the IL‐13 production of mast cells in response to immunocomplex and SSL12. These findings reveal a novel function of SSL3, triggering cell adhesion and enhancing mast cell activation. This study would clarify the correlation between S. aureus and allergic diseases such as atopic dermatitis. [ABSTRACT FROM AUTHOR]

The article discusses the American Academy of Dermatology Annual Meeting that was held in San Diego, U.S. from March 8-12, 2024. Topics discussed include the efficacy and safety of different treatments for skin conditions like hidradenitis suppurativa and psoriasis. Attendees included experts such as Kimball AB, Papp KA, and Bissonnette R, who presented research findings on treatments like remibrutinib, lutikizumab, sonelokimab, ESK-001, and JNJ-77242113.

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]