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INTRODUCTION: Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52 weeks was assessed in a subset of patients with moderate and/or more extensive disease. METHODS: This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigators Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed. RESULTS: Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period: 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week 8 (continuous-use), IGA-treatment success (IGA 0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use: week 8) to 18/23 patients (78.3%; as-needed use: week 52) in patients applying ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population. CONCLUSION: Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy. TRIAL REGISTRATION NUMBER: NCT03745638/NCT03745651.

Abrocitinib, an oral, once-daily, Janus kinase (JAK) 1-selective inhibitor, is approved for the treatment of adults and adolescents with moderate-to-severe atopic dermatitis (AD). Abrocitinib has shown rapid and sustained efficacy in phase 3 trials and a consistent, manageable safety profile in long-term studies. Rapid itch relief and skin clearance are more likely to be achieved with a 200-mg daily dose of abrocitinib than with dupilumab. All oral JAK inhibitors are associated with adverse events of special interest and laboratory changes, and initial risk assessment and follow-up monitoring are important. Appropriate selection of patients and adequate monitoring are key for the safe use of JAK inhibitors. Here, we review the practical use of abrocitinib and discuss characteristics of patients who are candidates for abrocitinib therapy. In general, abrocitinib may be used in all appropriate patients with moderate-to-severe AD in need of systemic therapy, provided there are no contraindications, e.g., in patients with active serious systemic infections and those with severe hepatic impairment, as well as pregnant or breastfeeding women. For patients aged ≥ 65 years, current long-time or past long-time smokers, and those with risk factors for venous thromboembolism, major adverse cardiovascular events, or malignancies, a meticulous benefit-risk assessment is recommended, and it is advised to start with the 100-mg dose, when abrocitinib is the selected treatment option.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patients quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD. METHODS: Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. RESULTS: Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 - 7.8 vs - 2.8; ADvocate2 - 7.3 vs - 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 - 7.43 vs - 1.51; ADvocate2 - 4.95 vs - 0.82) and PROMIS Depression (ADvocate1 - 7.42 vs - 2.46; ADvocate2 - 4.28 vs - 2.00). CONCLUSIONS: Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline. TRIAL REGISTRATION: ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

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.

ABSTRACT Background Objective Methods Results Conclusion Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder presenting in childhood. Dupilumab is the first approved biologic agent for the treatment of moderate‐to‐severe AD in pediatric populations. While generally well‐tolerated, dupilumab‐associated ocular surface disease (DAOSD) is a known complication. In severe cases, this may necessitate discontinuation of treatment.We aim to describe DAOSD in our cohort of Asian pediatric patients with moderate‐to‐severe AD on dupilumab.We performed a single‐center retrospective review of children and adolescents on dupilumab for moderate‐to‐severe AD who developed ophthalmological complications from 2019 to 2024. Most patients had prophylactic lubricant eyedrops. Data collected and analyzed included demographics, ophthalmologic findings, treatment, and outcomes of eye condition.Of 216 patients treated with dupilumab, 16 (7.4%) developed ophthalmologist‐diagnosed DAOSD. All patients had co‐existing eyelid or head and neck eczema while 31.3% of these patients had pre‐existing eye conditions. Eye redness (87.5%) was the most common presenting symptom, followed by pruritus (43.8%) and eye discharge (25%). The most common eye finding was conjunctivitis (87.5%), followed by limbitis (62.5%) and papillary reaction (62.5%). Two patients required temporary interruption of dupilumab. No patients required discontinuation of dupilumab treatment. The median time to resolution of eye complications was 14 weeks.In a real‐world setting, the incidence and severity of DAOSD in pediatric patients appears to be lower than that of adults. Prophylactic use of lubricant eye drops, close monitoring and early referral to pediatric ophthalmologists can help reduce the incidence of severe eye disease requiring discontinuation of dupilumab. [ABSTRACT FROM AUTHOR]

Background: The increase in allergic diseases in children has coincided with the westernization of lifestyles. Although clustering of modifiable lifestyles has been frequently reported in children, there is limited research on how lifestyle factors collectively contribute to allergic conditions. Our aim was to identify lifestyle clusters among Finnish school-aged children and explore their associations with the prevalence of allergic disease symptoms and sensitization. Methods: We used cross-sectional data from the international ISCOLE survey and its Finnish ancillary allergy study conducted in 2012–2013. We studied 148–461 children aged 9–11 years living in the metropolitan area of Finland. Parents completed a questionnaire on their child's allergic disease symptoms, and specific IgE responses from blood samples were analyzed to determine allergic sensitization. Lifestyle factors considered in clustering were moderate-to-vigorous-physical activity (MVPA) and nighttime sleep recorded by accelerometers, screen time inquired via a questionnaire, and healthy and unhealthy dietary patterns from food frequency questionnaire data. Lifestyle clusters were identified using K-means cluster analysis, and their associations with allergic disease symptoms and sensitization were explored using logistic regression models. Results: Two distinct and stable clusters were identified: 'healthier lifestyle & lower MVPA' and 'unhealthier lifestyle & higher MVPA'. After adjustments, children in the 'unhealthier lifestyle & higher MVPA' cluster did not show significantly different odds for symptoms of asthma (OR: 0.80, 95% CI: 0.46–1.37), allergic rhinitis (OR: 1.32, 95% CI: 0.77–2.24), or eczema (OR: 0.89, 95% CI: 0.43–1.77) as compared to those in the 'healthier lifestyle & lower MVPA' cluster. Similar results were observed for sensitization to ≥ 1 inhaled allergen (OR: 1.27, 95% CI: 0.53–3.10) and sensitization to ≥ 1 food allergen (OR: 0.91, 95% CI: 0.30–2.60). Conclusions: The results suggest that modifiable lifestyle factors may not play a significant role in allergic conditions within the examined age group. Lifestyle behaviors established in earlier childhood may serve as more credible predictors of allergic outcomes. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved cellular self-digestive process that underlies the maintenance of cellular homeostasis. Autophagy is classified into three types: macrophage, chaperone-mediated autophagy (CMA) and microphagy, which maintain cellular homeostasis through different mechanisms. Altered autophagy regulation affects the progression of various skin diseases, including psoriasis (PA), systemic lupus erythematosus (SLE), vitiligo, atopic dermatitis (AD), alopecia areata (AA) and systemic sclerosis (SSc). In this review, we review the existing literature focusing on three mechanisms of autophagy, namely macrophage, chaperone-mediated autophagy and microphagy, as well as the roles of autophagy in the above six dermatological disorders in order to aid in further studies in the future. [ABSTRACT FROM AUTHOR]

Obesity is a prevalent metabolic disease that reduces bacterial diversity, colonizes the epidermis with lipophilic bacteria, and increases intestinal pro-inflammatory species, all of which lead to impaired epithelial barriers. Adipose tissue secretes immunomodulatory molecules, such as adipokines, leptin, and adiponectin, which alters the morphology of adipocytes and macrophages as well as modulates T cell differentiation and peripheral Th2-dominated immune responses. Atopic dermatitis (AD) and obesity have similar pathological manifestations, including inflammation as well as insulin and leptin resistance. This review examines the major mechanisms between obesity and AD, which focus on the effect on skin and gut microbiota, immune responses mediated by the toll like receptor (TLR) signaling pathway, and changes in cytokine levels (TNF-a, IL-6, IL-4, and IL13). Moreover, we describe the potential effects of adipokines on AD and finally mechanisms by which PPAR-γ suppresses and regulates type 2 immunity. [ABSTRACT FROM AUTHOR]

Inflammatory dermatologic diseases have long been viewed as a "skin limited" disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms. Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1. The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally "skin limited" inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Pediatric cow milk allergies (CMA) can occur in immunoglobulin (Ig) E and non-IgE-mediated forms. Unlike IgE-mediated allergies, the mechanisms of disease pathogenesis in non-IgE-mediated food allergy and an association with microbiome has not been well established. Previous studies have identified the presence of altered humoral responses to gut bacteria in IgE mediated allergies. Here, we analyzed IgA, IgE and IgG responses to gut bacteria in subjects with either IgE or non-IgE mediated CMA to identify relative proportions of Ig-coated bacteria and characterize unique disease specific microbial signatures. Methods: Multi-parametric flow cytometry analysis was used to identify IgA, IgE and IgG responses to gut bacteria in CMA patients. Cell sorting of Ig coated gut bacteria was subsequently performed followed by high throughput 16S rRNA gene sequencing and specific patterns of humoral responses to gut bacteria assessed in each study group. Results: We identified significant alterations in IgA and IgG gut bacterial coating patterns in CMA subjects. Proportions of IgA-coated bacteria were decreased in IgE mediated CMA subjects without atopic dermatitis (ALL) and non-IgE mediated CMA subjects (ENP), compared to healthy controls (CON). In comparison, IgG-coated bacteria was significantly elevated in CMA subjects with atopic dermatitis (AD). Alpha and beta diversities displayed significant differences in IgA-, IgE-, and IgG-coated bacteria in AD and ENP groups. Significant differences in bacteria coated by IgA, IgE and IgG were detected at Phyla, Genus and Species levels and associated bacterial dysbiosis in IgE and non-IgE mediated allergies were identified. Linear discriminant analysis (LDA) effect size (LEFse) revealed unique disease associated bacterial signatures, including several pathogenic bacteria namely Bacteroides fragilis, Ruminococcus gnavus, Eubacterium dolichum, Fusobacterium, Clostridium neonatale and Robinsoniella peoriensis. Receiver operating characteristic curve analysis confirmed the efficiency of using the bacterial signatures identified as biomarkers for disease. Conclusions: Altered IgA and IgG responses to gut bacteria were identified in CMA subjects. The disease-specific responses were associated with alterations in bacterial diversity and concomitant dysbiosis of Ig-coated bacteria in IgE-mediated and non-IgE-mediated CMA pediatric subjects. The identification of pathogenic bacteria uniquely associated with different classes of allergic disease indicates a role of these bacteria in driving disease-specific pathological phenotypes. [ABSTRACT FROM AUTHOR]

\nIntroduction: So far, no definitive conclusions have been reached regarding the preventive effect of moisturizers on atopic dermatitis (AD). The variability in results may be due to differences in skin care methods, including bathing and washing, among studies and study design. In hot and humid Japan, bathing and gauze washing have been routinely practiced from the neonatal period, but this may impair the skin barrier function. To address this gap, we determined whether a combination of minimally invasive cleaning methods and moisturizing may prevent AD in infants in Japan. Methods: Mothers of children born between January and September 2019 were instructed in traditional skin care methods (control group; 132 subjects), and mothers of children born between January and September 2020 were instructed in a new skin care method combining less invasive washing and moisturizing (intervention group; 140 subjects). Mothers and babies with and without a history of allergy were recruited, and the incidence of AD at 1 year of age was investigated by questionnaire. Results: Skin care-related behaviors such as face washing, hand washing, and use of moisturizers were more frequent in the intervention group than in the control group. At 6 and 12 months of age, there was no difference in the incidence of AD between the two groups. However, for children born between January and March, the prevalence of AD at 12 months was significantly lower in the intervention group than in the control group (2.9% vs. 21.2%, p = 0.0253). Conclusions: This study suggests that for children born during dry and cold seasons, strengthening the skin barrier function early in life through routine skin care with less invasive washing and moisturizing may prevent AD in Japan. Appropriate skin care practices for newborns and infants may vary in regions and environments. Impaired skin barrier function is one of the main causes of atopic dermatitis (AD). European guidelines recommend reducing the frequency of bathing so as not to impair the skin barrier function. In addition, to date, many studies have attempted to prevent AD by using moisturizers starting in infancy, with conflicting results. The variation in these results may be due to differences in skin care methods such as washing and moisturizing. In Japan, frequent bathing and gauze washing are commonly used from the neonatal period. The purpose of this study was to determine whether a combination of less invasive washing methods and moisturizing could prevent AD in infants. Mothers of infants born between January and September 2019 were instructed in conventional skin care methods (control group; 132 subjects), and mothers of infants born between January and September 2020 were instructed in a new, less invasive skin care regimen combining washing and moisturizing (intervention group; 140 mothers). Mother/infant dyads with and without a history of allergies were recruited and the incidence of AD at 1 year of age was investigated. The prevalence of AD at 12 months was significantly lower in the intervention group than in the control group for infants born between January and March (2.9% vs. 21.2%). This study suggests that for children born during the dry, cold season, strengthening the skin barrier function early in life with less invasive cleaning and moisturizing skin care may prevent AD. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions. Tozorakimab is a high‐affinity human monoclonal antibody that neutralizes interleukin‐33, a broad‐acting alarmin cytokine that is over‐expressed in keratinocytes of patients with AD.This Phase 2a study (FRONTIER‐2; NCT04212169) evaluated the safety and efficacy of tozorakimab in adults with moderate‐to‐severe AD.FRONTIER‐2 was a randomized, placebo‐controlled, parallel‐group, double‐blind study conducted from 9 December 2019 to 20 September 2022 at 32 centres across six countries. Patients were randomized 3:1:1:3 to receive placebo, tozorakimab 60 mg, tozorakimab 300 mg or tozorakimab 600 mg by subcutaneous injection once every 4 weeks for four doses. The primary endpoint was percentage change from baseline to Week 16 in the Eczema Area and Severity Index (EASI) score in patients treated with tozorakimab versus placebo. Secondary outcomes included EASI‐75 responders (patients achieving ≥75% reduction from baseline in EASI score), Investigator's Global Assessment (IGA) responders (patients achieving an IGA score of 0 or 1), pharmacokinetics, immunogenicity and safety.Overall, 148 patients were randomized. There was no statistically significant difference in the primary endpoint (60 mg difference of 1.3 [90% confidence interval (CI): −13.7, 16.2], p = 0.888; 300 mg: difference of 5.9 [90% CI: −10.4, 22.1], p = 0.549; 600 mg: difference of − 1.7 [90% CI: −13.4, 10.0], p = 0.807). The proportion of EASI‐75 and IGA 0/1 responders at Week 16 was numerically higher in the tozorakimab 600 mg group than in the placebo group (EASI‐75: 18.2% vs. 7.1%, p = 0.094; IGA 0/1: 9.1% vs. 1.8%, p = 0.113). Serum pharmacokinetics were dose‐dependent, immunogenicity incidence was low and tozorakimab was well tolerated.FRONTIER‐2 did not show a statistically significant difference in the primary endpoint for tozorakimab compared with placebo. However, numerical increases in responder rates were observed. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion To evaluate long‐term infection rates in children aged 6 months to 5 years with moderate‐to‐severe atopic dermatitis (AD) treated with dupilumab.This was a post hoc analysis of an ongoing open‐label extension (OLE) study of dupilumab. Pediatric patients aged 6 months to 5 years with moderate‐to‐severe AD who had previously taken part in the LIBERTY AD PRESCHOOL phase 2 and 3 clinical trials received weight‐based subcutaneous dupilumab every 2 or 4 weeks. Exposure‐adjusted infection rates after a median dupilumab exposure of 52 weeks are compared with data from the earlier randomized, placebo‐controlled, 16‐week LIBERTY AD PRESCHOOL phase 3 trial.Infection rates were overall lower in the OLE study compared with the dupilumab and placebo groups in the earlier 16‐week trial, including total infections (101.0 patients/100 patient‐years [PY]), nonherpetic skin infections (22.7 patients/100PY), herpetic infections (7.3 patients/100PY), and nonskin infections (92.9 patients/100PY). The frequency of severe and serious infections was low (3.1 patients/100PY), compared with 17.1 placebo‐treated patients/100PY and 0 dupilumab‐treated patients in the earlier 16‐week trial, and no infections leading to treatment discontinuation were observed. Systemic anti‐infective medication use (58.9 patients/100PY) was lower in the OLE study compared with both the dupilumab and placebo groups in the 16‐week trial.Overall, reduced infection rates are observed in infants and young children with moderate‐to‐severe AD treated with dupilumab long‐term, supporting the known safety profile of dupilumab. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion The use of blood specific IgE or skin prick tests (SPT) to guide dietary exclusions for disease control in children with atopic dermatitis (AD) is controversial. We undertook a consensus exercise on how to interpret SPT results and dietary history for cow's milk, hen's egg, wheat, and soy in children < 2 years old with AD.Fourteen clinicians from general practice, pediatrics, pediatric dermatology, pediatric allergy, and pediatric dietetics from UK and Ireland took part in an online modified Delphi study. Over three rounds, participants gave their anonymous opinions and received individualized and group feedback, based on the premise that all children had SPTs. The findings were discussed in an online workshop.Of 18 symptoms, 12 were identified as relevant to immediate and 7 to delayed allergy. Regarding SPTs, there was consensus over which allergens to use for wheat and soy but not cow's milk or hen's egg; for all study foods, wheal size was determined as 0–1 mm negative, ≥ 5 mm sensitized, but between 2 and 4 mm, categorization varied by food. During the final workshop, consensus was reached on dietary advice for nine combinations of SPT results and dietary history.We attained consensus on how SPTs and dietary history for four common food allergens should be interpreted in young children under 2 years of age with AD. These pragmatic recommendations may support clinician education, consistency of decision‐making, and future research. [ABSTRACT FROM AUTHOR]

Backgrounds: Dupilumab has demonstrated remarkable efficacy and safety in clinical trials for moderate-to-severe atopic dermatitis (AD). However, long-term real-world evidence, especially in the Chinese population, remains limited. Objective: To investigate the long-term efficacy and safety of dupilumab for moderate-to-severe AD in a real-world clinical setting in China and analyze factors that may influence its long-term treatment outcomes. Methods: This prospective, observational real-world study included moderate-to-severe AD patients from the AD cohort of the dermatology department of Chongqing Hospital of Traditional Chinese Medicine who received dupilumab treatment for≥52 weeks. Efficacy and adverse events were assessed at baseline, weeks 4, 16, 24, and 52. Multivariate logistic regression analysis was used to identify predictive factors for achieving EASI 50 and EASI 75 at week 52. Results: A total of 124 patients were included. At week 52, EASI, SCORAD, IGA, NRS, and DLQI scores were significantly improved compared to baseline. The proportions of patients achieving EASI-50/75 were 50.81%/29.84%, 72.58%/42.74%, 75%/53.23%, and 67.74%/41.94% at weeks 4, 16, 24 and 52, respectively. Female sex, absence of atopic comorbidities, higher baseline EASI, and medication compliance were positive predictive factors for 52-week EASI-50/75. Eosinophil elevation predicted lower EASI-50 attainment. Nineteen adverse events occurred during the 52-week period (incidence rate: 14.52%), mostly mild and manageable. Conclusions: Dupilumab demonstrated significant efficacy and a low incidence of adverse events over 52 weeks in Chinese patients with moderate-to-severe AD, making it an effective and safe long-term treatment option. Predictive factors were identified to guide treatment optimization. [ABSTRACT FROM AUTHOR]

Background: In the current study, we evaluated whether atopic dermatitis (AD) affects the entire body rather than being limited to skin barrier damage and inflammation. We hypothesized that medium-term exposure of distant organs to systemic inflammatory cytokines in sub-chronic inflammatory skin diseases has detrimental effects on distant tissues. Results: Our findings demonstrated the dysregulation of genes and pathways associated with inflammation and the skin barrier, as well as genes and pathways involved in muscle development that respond to chemicals or stress in muscle tissues, all of which were reversed by hydrocortisone (Hc) administration. The expression of Ces1d showed significant differences during disease onset and after treatment in both skin and skeletal muscle, suggesting that Ces1d is likely responsible for the alleviation of subchronic AD. Conclusions: Using NC/Nga mice with AD-like symptoms, we compared the transcriptomes of the skeletal muscle (a tissue that is relatively distant from the skin) with those of the skin (the lesion induction site) before and after disease induction, after which Hc was administered. Although further study is needed to better understand the effects of Ces1d on AD, skeletal muscle was associated with AD pathogenesis, and AD-like symptoms appeared to affect the body in a systemic manner. Given the importance of evidence-based medicine and the development of precision medicine, our findings provide insights into the mechanisms of AD onset and progression. [ABSTRACT FROM AUTHOR]

Herpes Simplex Virus-1 (HSV-1) Kaposi varicelliform eruption (KVE) is a rare and severe cutaneous manifestation, clinically characterized by the presence of widespread vesicles and pustules. A case report details a patient with a history of Atopic Dermatitis (AD) and recent SARS-CoV-2 infection who developed a severe KVE subsequent to the viral illness. The patient, a 35-year-old male, presented with severe atopic dermatitis (AD) subsequent to a SARS-CoV-2 infection. In a period of four months, the dermatological eruption underwent a rapid progression to a severe state, characterised by the presence of extensive vesicles and pustules, in addition to the emergence of symptoms. In conjunction with a chest CT scan, plasma and antigen testing, the patient was confirmed to be positive for HSV-1 positive. The patient exhibited elevated levels of IgE and a notable reduction in the absolute number of immune cells. The patient was treated with valaciclovir, piperacillin-tazobactam, IVIG at the same time. Within seven days of treatment, the blisters had dried up and the scabs had fallen off without any pain, pruritus, or fever. This case highlights the potential for severe viral eruptions, such as KVE in individuals with underlying dermatological conditions following viral infections. [ABSTRACT FROM AUTHOR]

To date, the pathogenesis of Kimura's disease remains unclear, there is no unified diagnostic criterion, the clinical phenotype shows considerable heterogeneity, and there is a lack of optimal treatment strategies. Due to its rarity, treatment strategies for KD are still under exploration. This paper reports a case of a 37-year-old Chinese female presenting with generalized erythematous papules and pruritic eruptions for 12 years, followed by the onset of limb swellings 3 years later, ultimately diagnosed as Kimura's disease. Considering the patient's multiple lymphadenopathies and limb swellings with concurrent atopic dermatitis, the treatment regimen included initial dupilumab dosage of 600 mg (300 mg administered in two injections), followed by subcutaneous injections of 300 mg every two weeks for four months. Concurrent oral corticosteroid therapy (methylprednisolone, initial dose 16 mg/kg/day, gradually tapered with tumor regression) was also administered. Following treatment, the patient did not experience severe adverse effects, and the multiple nodules markedly decreased in size. Additionally, serum IgE levels, eosinophil, and basophil counts showed significant reductions. These results demonstrate the significant efficacy of dupilumab combined with oral corticosteroids in treating Kimura's disease with concurrent atopic dermatitis. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to assess the causality of allergic diseases and celiac disease.We collected summary-level data from publicly available genome-wide association studies to conduct our bidirectional two-sample and multivariable Mendelian randomization analysis. Furthermore, a series of sensitivity analyses were applied to validate our findings.In bidirectional two-sample MR analyses, we found a significant causal effect of atopic dermatitis (AD) on CD (Inverse-variance weighted (IVW): odds ratio [OR] = 1.302, 95% confidence interval [CI] = 1.152–1.471, p < 0.001). We also found a significant causal effect of allergic rhinitis (AR) on CD (IVW: OR = 4.181, 95% CI = 1.495–11.697, p = 0.006). However, the MR-Egger method indicated a different causal effect direction compared to the IVW and weighted median method. After Bonferroni correction, the result of asthma on CD is suggestive of a causal effect (IVW: OR = 1.186, 95% CI = 1.021–1.378, p = 0.026). No causal effects were found when CD was considered as an exposure variable. In MVMR analyses, after separately and jointly adjusting for the influence of smoking and BMI, the causal effect of AD on CD remained robust.Our study suggests that AD is a risk factor for CD and it is considered suggestive of a causal relationship between asthma and CD. Further research is needed to explore the potential mechanisms underlying this causal effect. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objectives Methods Results Conclusions Basic skin care education holds the potential to improve clinical outcomes in pediatric atopic dermatitis (AD). However, evidence is lacking on the efficacy of video education for patient guardians in Thailand to reduce AD disease severity.To compare the efficacy of a video education program for guardians of pediatric AD patients versus a control group by assessing the severity score of AD (SCORAD), transepidermal water loss (TEWL), and skin hydration (SH).A single‐blinded, randomized controlled trial was conducted at a tertiary hospital from June 2023 to February 2024, involving AD patients aged < 18 years and their guardians. Both groups received standard treatment, and the educational group received an additional video education program. SCORAD, TEWL, SH, pruritus, sleeplessness, and parental/guardian confidence and knowledge accuracy were assessed at enrollment and a 4‐week follow‐up.Seventy patients (educational:control group, 34:36) with a median age of 3.1 years were enrolled. The groups exhibited no significant demographic or disease severity differences between them. At follow‐up, the educational group showed significant SCORAD improvement compared to the control group (mean difference −10.93 [95% CI −16.92–−4.95]; p < 0.001). SH (mean difference 3.82 [95% CI −2.7–10.33]; p = 0.25) and TEWL (mean difference −1.24 [95% CI −5.72–3.24]; p = 0.58) did not differ significantly.Video education demonstrated efficacy in significantly reducing SCORAD. While there were improvements in SH and TEWL in patients in the education group, these improvements were not statistically significant. Further investigation with a larger sample size is warranted.Trial Registration: Thai Clinical Trials Registry (TCTR): TCTR20230524001 [ABSTRACT FROM AUTHOR]

ABSTRACT Topical steroid withdrawal syndrome (TSW) is a debated condition marked by burning erythema, severe itching, and dry skin following the discontinuation of topical corticosteroids (TCS). This study reviewed reported pediatric TSW cases. With a total of 21 cases reported (inconsistent data provided), 60% (6/10) used TCS on the face; 69% (9/13) were associated with an escalation in potency of TCS and 75% (3/4) were the erythematoedematous variant. Overall, data on TSW in children is lacking and standardized diagnostic criteria are needed. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion The role of autoimmune IgE responses in atopic dermatitis (AD) is highly debated. While IgE targeting self‐proteins has been extensively studied, IgE responses induced by human‐homologous exogenous molecular allergens (HEMAs) remains less understood.To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.We enrolled 3325 participants with a history of allergic diseases, including 577 (17.3%) diagnosed with AD. Serum IgE antibodies against 183 exogenous allergenic molecules were measured using the IgE microarray (Allergy Explorer‐ALEX‐2®, MADX, Vienna). Based on international classification criteria, participants were stratified by AD severity and clinical phenotypes. For each patient, we developed an ‘IgE molecular‐mimicry index’ (IgE‐MMI), calculated from IgE reactivity to a panel of five HEMA protein families: arginine kinase, enolase (ENO), cyclophilin (CYP), lipocalin, and MnSOD. Logistic regression was employed to assess the association between IgE to HEMAs or IgE‐MMI and AD, its severity, and response to dupilumab.IgE sensitization to most HEMAs (32/48, 67%), but only to a small fraction of non‐HEMAs (3/135, 2.2%), was significantly more common in patients with severe AD compared to other patient groups. The IgE‐MMI was positive in 295/2748 (10.7%) of allergic patients without AD, and in 58/283 (20%), 52/134 (39%), and 86/160 (54%) of patients with remitting, moderate, or severe AD, respectively. It was strongly associated with specific phenotypes, such as flexural dermatitis (OR 8.4, 95% CI: 6.3–11.2), head and neck dermatitis (OR: 16.5, 95% CI: 7.4–37.2), and generalized eczema (OR: 8.6, 95% CI: 4.9–15.6). Poor response to dupilumab was associated with IgE antibodies to ENO (OR: 22.7, 95% CI: 1.7–302.9), but inversely associated with IgE antibodies to MnSOD (OR: 0.1, 95% CI: 0.02–0.8) and NPC‐2 from dust mites (OR: 0.1, 95% CI: 0.01–0.9).IgE microarrays are useful for broadly assessing IgE to HEMAs in allergic patients. IgE reactivity to HEMAs and a positive IgE‐MMI may serve as valuable biomarkers for severe AD, its clinical phenotypes, and the response to dupilumab. [ABSTRACT FROM AUTHOR]

Beyond Th2 cells and various immune cells, M2 macrophages have been identified in lesional skin of atopic dermatitis (AD) indicating their involvement in the disease's underlying mechanisms. MMP12, a matrix-degrading enzyme, which is predominantly produced by macrophages, is increased in skin lesions of AD patients. In this study we investigated the expression of MMP12 mRNA in lesional AD skin at single cell level through RNA sequencing (scRNA-seq) and the expression of MMP12 in M2 macrophages from healthy individuals and AD patients in response to Th2 cytokines and histamine using quantitative PCR and ELISA. Additionally, we analyzed macrophages from dupilumab-treated AD patients using the same methods to assess the influence of Th2 cytokines on MMP12 expression ex-vivo. ScRNA-seq identified macrophages as the primary producers of MMP12 in lesional AD skin. In-vitro, both MMP12 mRNA and protein expression were significantly increased in monocytes during differentiation to M2 macrophages in the presence of histamine, of Th2 cytokines or of Th2 cytokines in combination with histamine. In M2 macrophages obtained from dupilumabtreated AD patients, the upregulation of MMP12 expression by IL-4 and IL-13 was attenuated. Our findings unveil a novel mechanism whereby Th2 cytokines and histamine regulate MMP12 expression, potentially impacting skin barrier homeostasis in AD. [ABSTRACT FROM AUTHOR]

Aim: Atopic dermatitis is a popular allergy disease among children, adolescents and adults. The risk of depression in patients with atopic dermatitis can be evaluated using an updated systemic review and meta‐analysis of observational and cross‐sectional studies. Methods: The log odds ratio (OR) was transformed using the OR and 95% confidence interval (CI) to assess the risk of depression in patients with atopic dermatitis across the children, adolescent and adult groups. After a restricted selection, 39 studies of 234 306 patients with atopic dermatitis and 10 935 459 reference individuals were enrolled. The focused outcome was the OR and 95% CI of depression risk in each included study, assigned according to the age for the children, adolescent and adult groups. Results: In adult patients with atopic dermatitis, a significantly higher risk of depression was observed. In addition, the similar significantly higher risk of depression was observed in children and adolescent patients with atopic dermatitis, respectively. However, the significantly high heterogeneity was observed across children, adolescent and adult groups. Conclusions: In the current meta‐analysis, the patients with atopic dermatitis had a higher risk of depression across the children, adolescent and adult groups, respectively. However, substantial heterogeneity should be considered during the interpretation of our meta‐analysis results. [ABSTRACT FROM AUTHOR]

Introduction: Difamilast has proven to be an effective treatment for the treatment of atopic dermatitis (AD) in Japan, but its cost-effectiveness remains unknown. Therefore, the objective of the current study was to determine the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in Japanese adult patients with all-severity AD from a Japanese public health-care perspective. Methods: The analysis was conducted using a cost-effectiveness model from the Japanese public health-care perspective. This model had four health states ("clear," "mild," "moderate," and "severe") defined according to the Eczema Area and Severity Index score. The time horizon of the analysis was 1 year. Because the analysis period was short, no discount rate was applied. The proportions of patients previously estimated by the anchored matching-adjusted indirect comparison were implemented in the model. The model was further populated with data from the literature. The main model outcomes were quality-adjusted life-years (QALY), costs, and outcomes, including the incremental cost-effectiveness ratio. All prices were stated in JPY at the price level from 2018 April to 2019 March. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the results. Results: In the base case, the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% and placebo was JPY 827,054/QALY and JPY 1,518,657/QALY, respectively. The PSA showed that the cost-effectiveness of difamilast 1% compared with delgocitinib 0.5% and placebo had a 66.6% and 99.6% probability of being below the JPY 5 million/QALY threshold, respectively. Conclusion: The results suggest that difamilast 1% is a more cost-effective treatment option compared with delgocitinib 0.5% in Japanese adult patients with moderate-to-severe AD and compared with placebo in adult patients with all-severity AD from a Japanese public health-care perspective. [ABSTRACT FROM AUTHOR]

Introduction: For some patients with atopic dermatitis (AD), topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and systemic therapies are inadequate to control disease or are associated with adverse events (AEs). Ruxolitinib cream monotherapy demonstrated anti-inflammatory and anti-pruritic effects among patients enrolled in two pivotal phase 3 studies (TRuE-AD1/TRuE-AD2); most patients had long-term disease control with as-needed use during the 44-week long-term safety (LTS) period. This post hoc analysis explored efficacy and safety of 1.5% ruxolitinib cream by previous medication use. Methods: Patients aged ≥ 12 years enrolled in TRuE-AD1/TRuE-AD2 were randomized 2:2:1 to twice-daily 0.75% or 1.5% ruxolitinib cream or vehicle cream for 8 weeks, followed by a 44-week LTS period; patients initially on vehicle were re-randomized 1:1 to either ruxolitinib cream strength. Results: Within 12 months of enrollment (N = 1249), previous AD therapies were used by 89.4% of efficacy-evaluable patients applying vehicle or ruxolitinib cream (n = 725); of these, 80.4% received TCS (n = 583), 22.2% TCI (n = 161), 20.3% TCS + TCI (n = 147), and 18.9% systemic therapies (n = 137). Across previous medication subgroups, achievement of Investigator's Global Assessment (IGA)-treatment success (IGA 0/1 with ≥ 2-grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index from baseline, and ≥ 4-point improvement in Itch numerical rating scale score from baseline at Week 8 did not substantially differ among patients who applied ruxolitinib cream. Outcomes were similar to those in the overall study population. At all study visits during the LTS period, > 70% of patients in each subgroup had IGA 0/1 and a low percentage (generally < 3%) of affected body surface area. Treatment-related AEs across subgroups were reported in 7.3% (n = 35/481) to 17.4% (n = 19/109) of patients. Conclusions: Continuous-use ruxolitinib cream monotherapy for 8 weeks followed by as-needed use was effective and well tolerated, regardless of previous topical or systemic therapy, with outcomes similar to those achieved in the overall study population. Trial Registration: ClinicalTrials.gov Identifier, NCT03745638/NCT03745651. Plain Language Summary: Atopic dermatitis (AD) is a skin condition resulting in itchy, dry, and inflamed skin. For some patients, medication applied to the skin (topical treatment) or medication taken by mouth or injection (systemic treatment) may not control disease or may have side effects. In the TRuE-AD1/TRuE-AD2 trials in patients with mild to moderate AD aged 12 years and older, ruxolitinib cream used twice daily for 8 weeks reduced itch and redness. As-needed ruxolitinib cream use for another 44 weeks maintained long-term disease control. Here, we assessed disease control with 1.5% ruxolitinib cream in patients with AD based on their previous AD treatments. Of the 725 patients who had used previous AD treatments, most (80.4%) used topical corticosteroids (TCS). After 8 weeks, disease control outcomes were similar across all previous treatment subgroups (i.e., TCS, topical calcineurin inhibitors [TCI], TCS + TCI, systemic treatments) and were similar to the outcomes in the overall study population. After 44 weeks of as-needed ruxolitinib cream use, over two-thirds of patients still had clear or almost clear skin. The percentage of affected body surface area also remained low. Regardless of the AD treatments previously used, twice-daily ruxolitinib cream use for 8 weeks and then as needed for 44 weeks was generally well tolerated. These results show that twice-daily 1.5% ruxolitinib cream for 8 weeks, followed by as-needed treatment for 44 weeks, provides long-term control of AD in patients regardless of previous topical or systemic treatment received. [ABSTRACT FROM AUTHOR]

Introduction: The skin is the largest and most visible organ of the human body. As such, skin infections can have a significant impact on overall health, social wellbeing and self‐image. In 2019, we published a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource‐limited settings where skin infections are endemic. This current review serves as an update to assess the evidence for treatment of these conditions as well as atopic dermatitis, molluscum contagiosum and head lice in endemic settings. The data from this systematic review have supported an update to the Australian National Healthy Skin guidelines. Methods: A systematic review was conducted using two separate searches in MEDLINE, PubMed, Embase, CINAHL, Cochrane and Web of Science. The first search was an update of the 2018 systematic review using the same search strategy for the same skin conditions to identify emerging literature from 2018 to 2022. The second search strategy used the same key terms but with the addition of atopic dermatitis, head lice and molluscum contagiosum from 1960 to 2022. Eligible studies included Indigenous peoples and populations in resource‐limited settings with a diagnosis of impetigo, scabies, crusted scabies, tinea capitis, atopic dermatitis, molluscum contagiosum or who presented with head lice. Studies conducted in high‐income countries were excluded. Articles were screened for inclusion independently by one author with a second group of reviewers independently double screening. Data extraction and an in‐depth quality assessment conducted by one author and checked by two others. Results: Of 1466 original articles identified, 68 studies were included and key findings outlined for impetigo, scabies, crusted scabies, atopic dermatitis, head lice and molluscum contagiosum. Recommendations for each condition based on the available evidence are provided. Conclusion: The importance of assessing literature relevant to the populations with heavy burden of skin infections is outlined in this systematic review. We have summarised updates to this literature, which may benefit in developing guidelines for skin infection management similar to the National Healthy Skin Guidelines for Australia. [ABSTRACT FROM AUTHOR]

Oclacitinib is a novel Janus kinase (JAK) inhibitor that potently inhibits JAK1‐dependent cytokines involved in allergy, inflammation, and pruritus (IL‐2, IL‐4, IL‐6, IL‐13, and IL‐31). Oclacitinib (Apoquel®, Zoetis Inc, Parsippany, NJ) is approved for the treatment/control of pruritus associated with allergic dermatitis and treatment/control of clinical manifestations of atopic dermatitis in dogs at least 12 months of age. To evaluate the effectiveness of oclacitinib in dogs with flea allergy dermatitis, the JAK1 selective inhibitor was tested in a placebo‐controlled, masked, single‐dose (0.4 mg/kg) or repeat‐dose (0.4 mg/kg, twice daily for 2 weeks) study. Pruritic behaviors were quantitated by video recording, and erythema and skin lesions were assessed using a 10‐cm visual analog scale (VAS). Results showed that oclacitinib reduced pruritus by 61% as early as 1.5 h after a single oral dose compared to placebo, with an average reduction (compared to placebo) of 85% 1–5 h after dosing (0.4 mg/kg; p <.0001). Oclacitinib also significantly reduced erythema (p <.0001) and skin lesion (p <.0005) VAS scores on Day 14 compared to placebo in a repeat dose study. No adverse events were noted during the conduct of these studies. IL‐31 concentrations were elevated in the majority of dogs after flea infestation, suggesting JAK1‐dependent cytokines may drive clinical signs of flea allergy dermatitis. These findings show that oclacitinib, an inhibitor of JAK1‐dependent cytokines involved in allergy and inflammation can rapidly reduce clinical signs associated with flea allergic dermatitis in dogs. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is an inflammatory dermatological disease characterized by persistent scratching and recurrent eczema. Due to the influence of environmental variables on the cause of this disease, there remains an ongoing interest in the development of therapeutic interventions. Previous studies have shown that various plants of the genus Aster and its derived phytochemicals possess efficacy in treating inflammatory-mediated diseases, including atopic dermatitis. Therefore, the present study investigated a potential compound with anti-atopic dermatitis properties derived from Aster koraiensis leaves, specifically targeting HaCaT keratinocyte cells. First, we isolated eleven compounds with three unknown compounds, including two polyacetylenes (1 and 3) and a benzoic acid derivative (4). The chemical structures of the isolates were elucidated by 1D and 2D NMR, specific rotation, acid hydrolysis, and quantum chemical calculations. Next, we treated an A. koraiensis extract and all isolates to HaCaT keratinocyte, followed by stimulation with TNF-α/IFN-γ. Among bioactive compounds, astersaponin J (7) exhibited a significant reduction in the levels of inflammatory cytokines associated with atopic dermatitis at a concentration of 2.5 μM. These findings suggest that chemicals obtained from an A. koraiensis 95% ethanol extract and derived compounds are potential therapeutics to help reduce the immunological response driven by atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Moderate to severe (M2S) atopic dermatitis (AD) is a chronic condition impacting individuals, society, and healthcare systems. Considering the changing M2S-AD treatment landscape, this study assesses the M2S-AD burden in patients reaching referral centers in Greece. Methods: This was a multicenter, cross-sectional study. Patients aged 12 years or older with clinically diagnosed M2S-AD were enrolled. Data collected included clinical practice assessments and the following validated patient-reported instruments: Dermatology Life Quality Index (DLQI); EuroQol-5 Dimensions-3 Level scale (EQ-5D-3L); Patient Oriented Eczema Measure (POEM); Peak Pruritus Numerical Rating Scale (PP-NRS); and Work Productivity and Activity Impairment: General Health (WPAI:GH). A pain frequency/intensity/cause questionnaire and a sleep disturbance scale were also used. Results: Outcomes of 184 adults (51.1% female) with M2S-AD based on the Eczema Area and Severity Index (EASI) are presented (n = 117 moderate; n = 67 severe). Among the patients, 14.8% were obese, 59.2% had allergic comorbidities, and 88.0% were receiving AD-specific therapy (systemic: 38.6%). The median age, disease duration, body surface area, and total EASI scores were 38.8 years, 11.8 years, 30.0%, and 16.9, respectively. The median DLQI score was 12.0, with 'symptoms/feelings' being the most affected domain. EQ-5D dimensions 'anxiety/depression' and 'pain/discomfort' were also affected (65.2% and 64.1% reporting problems, respectively). The median POEM score was 17.0. Pain, severe pruritus (PP-NRS ≥ 7), and sleep disturbance were reported by 80.4%, 62.0%, and 88.5%, respectively. The median WPAI:GH 'work productivity loss' and 'activity impairment' scores were 23.8% and 30.0%, respectively. Conclusions: Both moderate and severe AD patients reaching Greek specialized centers experience significant symptom burden and impairments in quality of life, sleep, work, and daily activities. [ABSTRACT FROM AUTHOR]

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients' quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine's impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ. [ABSTRACT FROM AUTHOR]

Children and adolescents suffering from moderate‐to‐severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p‐value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08–8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71–10.02), EASI 50 (OR 8.89; 95% CI 6.18–12.78) and EASI 90 (8.30; 95% CI 4.81–14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34–9.90) or 4 points or more (OR 8.09; 95% CI 5.19–12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58–1.07), and conjunctivitis (OR 2.08; 95% CI 1.00–4.33). In this meta‐analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of eczema among children in New Zealand. Methods: Population‐based retrospective observational study utilising national pharmaceutical dispensing records for topical corticosteroids and emollients for all New Zealand children aged 0–14 years from 1st January 2006 to 31st December 2019. Data are reported using descriptive statistics, with comparisons between ethnicities and socioeconomic quintiles undertaken with rate ratios. Results: Based on dispensing data, the prevalence of eczema for New Zealand children aged 0–14 years in 2018 was 14.0% (95% CI 14.0%–14.1%), with prevalence decreasing in older age groups (children aged <1 year 26.0% (25.6%–26.4%); children aged 10–14 years 8.8% (8.7%–8.9%)). Prevalence was higher in Pacific children (23.6% (23.3%–24.0%)), but slightly lower in Māori children (13.2% (13.0%–13.3%)). Conclusion: Eczema is a common condition affecting a considerable proportion of children in New Zealand. This study provides nationwide paediatric prevalence data for New Zealand, and highlights the increased burden of eczema in Pacific children. Inequity in dispensing of topical corticosteroids is postulated to explain the reduced rates found for Māori children compared to previous studies. These results support the need for further research to determine factors contributing to differing eczema prevalence rates in New Zealand. [ABSTRACT FROM AUTHOR]

Introduction: Allergic diseases remain of concern due to their increasing prevalence worldwide. Intrinsic and environmental risk factors have been implicated in the pathogenesis of allergic disease. Among the possible risk factors, migration has been associated with the manifestation of allergic diseases. We aimed to consolidate the existing evidence, review the hypotheses for the relationship between environmental factors and allergic disease, and provide a direction for future work. Methods: This systematic review and meta-analysis complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Web of Science database was searched in September 2023 to retrieve publications investigating the relationship between allergic rhinitis (AR), atopic dermatitis (AD), or asthma and the following factors: (i) migrant status (i.e., migrants vs. natives) or (ii) duration since migration among migrants. Risk of bias was assessed using the JBI critical appraisal tool. Details and findings from the included studies were also summarized and meta-analyses were conducted where appropriate. Results: Fifty studies encompassing an estimated 3,755,248 individuals were reviewed. Articles investigated asthma (n = 46), AR (n = 16), and AD (n = 14). A variety of migration-related factors were also studied: movement of individuals across regions (n = 40), duration since immigration (n = 12), age at immigration (n = 9), and acculturation (n = 2). Migration status was not significantly associated with AD (pooled odds ratio [pOR] = 0.68, 95% confidence interval (CI) = 0.31, 1.49). Although AR prevalence was lower among immigrants than natives (pOR = 0.58, 95% CI = 0.45, 0.74), immigrants who had resided at least 10 years in the destination country had a higher risk of AR than immigrants with a duration of residence of less than 10 years (pOR = 8.36, 95% CI = 4.15, 16.81). Being an immigrant was also associated with a decreased risk of asthma (pOR = 0.56, 95% CI = 0.44, 0.72). Among immigrants, residing in the host country for at least 10 years was associated with increased asthma manifestation (pOR = 1.85, 95% CI = 1.25, 2.73). Immigrants who migrated aged 5 and below did not exhibit a significantly higher likelihood of asthma than migrants who immigrated older than 5 years (pOR = 1.01, 95% CI = 0.68, 1.50). Conclusion: This review was limited by the primarily cross-sectional nature of the included studies. Objective diagnoses of allergic disease, such as using the spirometry of bronchodilator reversibility test for asthma rather than questionnaire responses, could add to the reliability of the outcomes. Furthermore, immigrant groups were mostly nonspecific, with little distinction between their country of origin. Overall, migration appears to be a protective factor for allergic diseases, but the protection subsides over time and the prevalence of allergic diseases among the immigrant group approaches that of the host population. [ABSTRACT FROM AUTHOR]

Aim of our study is to analyse the sensitisation profile to molecular components of latex and of food allergens with the use of ALEX2 Allergy Xplorer test and to compare these results with the anamnestical data after latex exposure and with the anamnestical data after exposure to food allergens in atopic dermatitis patients. 100 patients were included in the study (49 men and 51 women with the average age 40.6 years). The specific IgE was examined with the use of ALEX2 Allergy Xplorer test. A detailed personal history of allergic reaction to latex and allergic reaction to food allergens was taken in all included patients. The sensitisation to latex was recorded in 17 % of patients, majority of patients have positive results of specific IgE to Hev b 8 without clinical reaction to latex. In 7 % of patients with positive results of specific IgE to Hev b 1, Hev b 3, Hev b 5, Hev b 6.02 and Hev b 11 the contact urticaria or contact dermatitis were recorded. The latex fruit syndrome was recorded in 7 % of patients; in another 10 % of patients we recorded no clinical reaction to latex, but the positive results to molecular components of latex and the clinical symptoms after ingestion of different kinds of fruits. The significant relation between the results of specific IgE to molecular components Hev b 3, Hev b 5 and Hev b 6.02 and the clinical reaction to latex was confirmed; these components significantly imply clinical reactivity to latex. • The positive results of specific IgE to molecular components of latex were confirmed in 17 % of patients suffering from atopic dermatitis. • Atopic dermatitis patients with positive results of specific IgE to Hev b 8 are usually without clinical reaction to latex. • In atopic dermatitis patients with positive results of specific IgE to Hev b 1, Hev b 3, Hev b 5, Hev b 6.02 and Hev b 11 the contact urticaria or contact dermatitis were recorded. • The molecular components Hev b 3, Hev b 5 and Hev b 6.02 significantly imply clinical reactivity to latex. [ABSTRACT FROM AUTHOR]

Introduction Psoriasis and atopic dermatitis are chronic, immune-mediated skin disorders that are disqualifying for entrance into the military. Both conditions can cause difficulty wearing body armor and other protective equipment when poorly controlled, limiting a service member's ability to train and deploy worldwide. In addition, these conditions may be exacerbated by military service because of increased exposure to austere environments, extreme temperatures, stress, skin injury, bug bites, and vaccinations Service members have limited treatment options because of restrictions on systemic medications that can be used while deployed. Newer systemic medications—in particular, biologics and oral immunomodulators—have evolved to be both extremely effective and safe. We review more recent treatment options for psoriasis and atopic dermatitis in the context of DoD's regulations guiding entry and retention of personnel with psoriasis and eczema and make recommendations regarding updating DoD policy for systemic treatment options. Materials and Methods A literature search was performed using PubMed, Embase, and Ovid with the last search done in the fall of 2023 from all years to date. These articles were further screened based on inclusion and exclusion criteria. In total, 25 articles were included in this review. An Internet search was also performed on the DoD's regulations guiding entry and retention of personnel with psoriasis and eczema. In addition, we examined medical requirements for deployment to the U.S. Central Command and U.S. European Command. Results Currently, U.S. Central Command and U.S. European Command do not allow the use of medications with special storage and handling requirements on deployments. Newer biologics are safe and efficacious but require refrigeration, although other immunomodulators like deucravacitinib and apremilast are oral pills and do not have cold-storage requirements. However, the use of biologics in austere environments may be feasible because of increased intervals between dosing and the ability to store refrigerated medical supplies in most deployed environments. For military service members with psoriasis, risankizumab and deucravacitinib are excellent options given their favorable safety and efficacy profiles. Of the biologics available for atopic dermatitis, dupilumab is the safest and effective systemic medication available. The Janus kinase inhibitors have also demonstrated excellent efficacy in treating atopic dermatitis, but more safety data are needed because of potential adverse events to include heart-related events, blood clots, and cancers. Conclusions Systemic treatments have evolved to become highly specific for both eczema and psoriasis. These newer biologics and immunomodulators may be compatible with use in the deployed setting, especially those that have long dosing intervals and proven efficacy and safety. Of the biologics, dupilumab and risankizumab offer the best efficacy, safety, and dosing intervals for atopic dermatitis and psoriasis, respectively. Deucravcitinib is a recently FDA-approved oral immunomodulator for psoriasis that has an excellent safety profile and efficacy. Allowing the use of these medications on deployments will enable more people with moderate to severe psoriasis and eczema to join and remain in the military while receiving effective treatment. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) are key orchestrators of development, tissue homeostasis and repair. FGF receptor (FGFR) deficiency in mouse keratinocytes causes an inflammatory skin phenotype with similarities to atopic dermatitis, but the human relevance is unclear. Therefore, we generated human keratinocytes with a CRISPR/Cas9-induced knockout of FGFR2. Loss of this receptor promoted the expression of interferon-stimulated genes and pro-inflammatory cytokines under homeostatic conditions and in particular in response to different inflammatory mediators. Expression of FGFR2 itself was strongly downregulated in cultured human keratinocytes exposed to various pro-inflammatory stimuli. This is relevant in vivo, because bioinformatics analysis of bulk and single-cell RNA-seq data showed strongly reduced expression of FGFR2 in lesional skin of atopic dermatitis patients, which likely aggravates the inflammatory phenotype. These results reveal a key function of FGFR2 in human keratinocytes in the suppression of inflammation and suggest a role of FGFR2 downregulation in the pathogenesis of atopic dermatitis and possibly other inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background and Aim: Atopic dermatitis (AD) impacts the quality of life of patients and their families. This survey‐based study aimed to understand the perspectives of physicians in Egypt and Lebanon regarding available educational initiatives and support programs for patients with AD, which was complemented by the social analytics study, offering a more comprehensive understanding of the perceptions of AD among social media users. Methods: The survey included 200 physicians, comprising primary care physicians, family medicine physicians, pediatricians, and dermatologists from Egypt and Lebanon. The social analytics study leveraged artificial intelligence to analyze 100 million websites across the region, identifying mentions of AD‐related terminologies. Results: The physician survey uncovered gaps in AD awareness and education in Egypt and Lebanon, with limited educational initiatives and digital applications available for patients. The perceptions of physicians varied regarding the use of telemedicine in dermatological disease management. According to the social analytics study, online discussions about AD predominantly originated from Egypt, featuring educational content on causes, diagnosis, management, and AD patient journey. Discussions included news about training programs, AD‐related healthcare initiatives, and drug approvals. Some authors, beauty clinics, and manufacturers actively promoted their services and products. Patients actively engaged in online discussions on self‐care and natural remedies, sharing their experiences of living with AD. Notably, there were substantial volumes of incorrect and inaccurate information being shared and promoted by some authors. Conclusion: Education about AD is crucial for patients and healthcare professionals. While social media offers opportunities for increased patient engagement, the prevalence of misinformation poses a significant challenge. Addressing issues related to education and discerning misinformation is essential for achieving optimal outcomes in the management of AD within the region. [ABSTRACT FROM AUTHOR]

Introduction: Eblasakimab, a first-in-class monoclonal antibody with a unique mechanism to target the interleukin (IL)-13 receptor alpha 1 (IL-13Rα1), inhibits IL-4/IL-13 signaling in the pathophysiology of atopic dermatitis (AD). This study investigates the impact of eblasakimab on type 2 inflammatory biomarkers in patients with moderate-to-severe AD. Methods: A double‑blind, multiple ascending dose, phase Ib study evaluated the effect of eblasakimab (200, 400, 600 mg) or placebo administered subcutaneously once weekly for 8 weeks in patients with moderate‑to‑severe AD. Serum levels of thymus and activation-regulated chemokine (TARC), total immunoglobulin E (IgE), and lactate dehydrogenase (LDH) were assessed. Results: Eblasakimab suppressed TARC, IgE, and LDH in the 400-mg and 600-mg groups over 8 weeks of treatment. Patients in the 400-mg and 600-mg groups experienced a reduction of 72.8% (p = 0.004) and 62.9% (p = 0.003), respectively, for TARC, 35.1% (p = 0.006) and 20.9% (not significant; NS), respectively, for IgE, and 24.6% (NS) and 23.1% (NS), respectively, for LDH between baseline and Week 8. Reduction in serum TARC in the 400-mg group was significantly greater than placebo as early as Week 1, whereas reductions in total IgE were more gradual. Serum TARC and total IgE remained suppressed in the 400-mg and 600-mg eblasakimab groups for 4–6 weeks following the last administered dose. Conclusion: The effect of eblasakimab on circulating AD‑associated biomarker levels was accompanied by improvements in signs and symptoms of AD, consistent with the inhibition of IL-13 and IL-4 signaling via the type 2 receptor. Trial Registration Number: NCT04090229. [ABSTRACT FROM AUTHOR]

ABSTRACT Previous observational studies focused on the association of tea intake and allergic diseases. However, it is not known whether these associations are causal. We used a bidirectional Mendelian randomization (MR) study to assess the causal relationship of tea intake with the risk of allergic diseases, such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). Single‐nucleotide polymorphisms (SNPs) which had genetic statistical significance with tea intake were used as instrumental variables (IVs). We employed heritable IVs of tea intake from the UK Biobank, which included 447,485 samples. Sensitivity analyses were further performed using MR Egger and MR‐PRESSO. Inverse variance weighted (IVW) method was used as the main approach. In this MR study, 40 independent SNPs were selected for tea intake. The MR analysis revealed that an increase in genetically predicted tea intake was associated with a lower risk of AD (OR = 0.709, 95% CI = 0.546–0.919, p = 0.009). Furthermore, we observed a causal effect of genetically predicted tea intake on the risk of AA (OR = 0.498, 95% CI = 0.320–0.776, p = 0.002). However, no significant causal relationship was found between genetically predicted tea intake and AR (OR = 1.008, 95% CI = 0.998–1.017, p = 0.115). Our MR analysis suggested that increased tea intake may reduce the risk of AD and AA in European population. This suggests that tea intake is likely a trigger or a prevention strategy for AD and AA. [ABSTRACT FROM AUTHOR]

Objective: The daily lives of adolescents have changed significantly because of COVID-19 pandemic. We investigated the effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents. Methods: Data from the 2021 Korea Youth Risk Behavior Survey were used. In total, 54,848 survey participants were included in the analysis. Allergic diseases included allergic rhinitis, atopic dermatitis, and asthma. Changes attributed to COVID-19 included family economic difficulties, physical activity, breakfast skipping frequency, alcohol consumption, smoking, and depressive moods. Chi-square tests and multiple logistic regression analyses were conducted to examine the impact of changes in daily life attributed to COVID-19 on allergic diseases. Results: Among the Korean adolescents surveyed, 29.8% experienced a deterioration in their economic status due to COVID-19, 49.1% reported decreased physical activity, 2.8% reported increased alcohol consumption, 1.0% reported an increase in their smoking behavior, and 36.9% reported an increase in depressive moods. Those diagnosed with atopic dermatitis, allergic rhinitis, or asthma within the previous 12 months accounted for 17.1%, 6.2%, and 1.0% of the population, respectively. Adolescents who were significantly affected by COVID-19 in their daily lives were frequently diagnosed with allergic diseases within the last 12 months. Conclusion: Changes in daily life due to COVID-19, including decreased physical activity and increased depressive mood, were common in adolescents and were associated with an increased prevalence of allergic diseases. Since changes in daily life due to the pandemic may increase the burden of allergic disease, additional interventions for disease management should be considered. [ABSTRACT FROM AUTHOR]

Atopic diseases, including atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis (AR) are closely related to inflammatory diseases involving different body sites (i.e. the skin, airway, and digestive tract) with characteristic features including specific IgE to allergens (so-called "atopy") and Th2 cell-mediated inflammation. It has been recognized that AD often precedes the development of other atopic diseases. The progression from AD during infancy to FA or asthma/AR in later childhood is referred to as the "atopic march" (AM). Clinical, genetic, and experimental studies have provided evidence that allergen sensitization occurring through AD skin could be the origin of the AM. Here, we provide an updated review focusing on the role of the skin in the AM, from genetic mutations and environmental factors associated with epidermal barrier dysfunction in AD and the AM to immunological mechanisms for skin sensitization, particularly recent progress on the function of key cytokines produced by epidermal keratinocytes or by immune cells infiltrating the skin during AD. We also highlight the importance of developing strategies that target AD skin to prevent and attenuate the AM. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), a prevalent Th2-dominant skin disease, involves complex genetic and environmental factors, including mutations in the Filaggrin gene and dysbiosis of skin microbiota characterized by an increased abundance of Staphylococcus aureus. Our recent findings emphasize the pivotal role of the skin barrier's integrity and microbial composition in infantile AD and allergic diseases. Early skin dysbiosis predisposes infants to AD, suggesting targeted skincare practices as a preventive strategy. The effects of skincare interventions, particularly the application of moisturizers with the appropriate molar concentration of ceramides, cholesterol, and fatty acids, play a crucial role in restoring the skin barrier. Notably, our study revealed that appropriate skincare can reduce Streptococcus abundance while supporting Cutibacterium acnes presence, thus directly linking skincare practices to microbial modulation in neonatal skin. Despite the mixed outcomes of previous Randomized Controlled Trials on the efficacy of moisturizers in AD prevention, our research points to the potential of skincare intervention as a primary preventive method against AD by minimizing the impact of genetic and environmental factors. Furthermore, our research supports the notion that early aggressive management of eczema may reduce the incidence of food allergies, highlighting the necessity for multifaceted prevention strategies that address both the skin barrier and immune sensitization. By focusing on repairing the skin barrier and adjusting the skin's microbiome from birth, we propose a novel perspective on preventing infantile AD and allergic diseases, opening new avenues for future studies, and practices in allergy prevention. [ABSTRACT FROM AUTHOR]

Allergy is a complex array of diseases influenced by innate and adaptive immunity, genetic polymorphisms, and environmental triggers. Atopic dermatitis is a chronic inflammatory skin disease characterized by barrier defects and immune dysregulation, sometimes leading to asthma and food allergies because of the atopic march. During atopic skin inflammation, Langerhans cells and dendritic cells (DCs) in the skin capture and deliver allergen information to local lymph nodes. DCs are essential immune sensors coordinating immune reactions by capturing and presenting antigens to T cells. In the context of allergic responses, DCs play a crucial role in instructing two types of helper T cells—type 2 helper T (Th2) cells and follicular helper T (TFH) cells—in allergic responses and IgE antibody responses. In skin sensitization, the differentiation and function of Th2 cells and TFH cells are influenced by skin-derived factors, including epithelial cytokines, chemokines, and signalling pathways to modify the function of migratory DCs and conventional DCs. In this review, we aim to understand the specific mechanisms involving DCs in allergic responses to provide insights into the pathogenesis of allergic diseases and potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Clinical trials and real‐life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation. Objectives: (1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors. Methods: This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3–6 months after inclusion) and at visit 3 (corresponding to the last medical visit). Results: After multivariate analysis, the only factors associated with a complete resolution of dupilumab‐associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47–55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82–62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94–99.66) (p = 0.002). Conclusions: Although uncommon, severe dupilumab‐associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered. [ABSTRACT FROM AUTHOR]