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Background: Current treat‐to‐target recommendations for atopic dermatitis (AD) may not include high enough treatment targets and do not fully consider patient needs. Objective: To develop recommendations for optimized AD management, including disease severity assessments, treatment goals and targets, and guidance for treatment escalation/modification. Methods: An international group of expert dermatologists drafted a series of recommendations for AD management using insights from a global patient study and 87 expert dermatologists from 44 countries. Experts voted on recommendations using a modified eDelphi voting process. Results: The Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations establish a novel approach to AD management, incorporating shared decision‐making and a concept for minimal disease activity (MDA). Consensus (≥70% agreement) was reached for all recommendations in 1 round of voting; strong consensus (≥90% agreement) was reached for 30/34 recommendations. In the AHEAD approach, patients select their most troublesome AD feature(s); the clinician chooses a corresponding patient‐reported severity measure and objective severity measure. Treatment targets are chosen from a list of 'moderate' and 'optimal' targets, with achievement of 'optimal' targets defined as MDA. Conclusions: Patient and expert insights led to the development of AHEAD recommendations, which establish a novel approach to AD management. Patients were not involved in the eDelphi voting process used to generate consensus on each recommendation. However, patient perspectives were captured in a global, qualitative patient research study that was considered by the experts in their initial drafting of the recommendations. [ABSTRACT FROM AUTHOR]

Background: Treatment optimization may require dosing flexibility. The Phase 3 JADE REGIMEN trial (NCT03627767) evaluated maintenance of abrocitinib 200 mg‐induced response in patients with moderate‐to‐severe atopic dermatitis (AD) randomly assigned to subsequent maintenance with continuous‐dose abrocitinib (200 mg), reduced‐dose abrocitinib (100 mg) or placebo. Maintenance with continuous‐dose abrocitinib was associated with a stronger prevention of disease flares, but also with a higher occurrence of adverse events, compared with the reduced dose. Objective: This post hoc analysis of JADE REGIMEN aimed to identify predictors of not flaring during the maintenance period and to generate tools that can be used to assess probability of not flaring. Methods: Data were analysed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 mg or 100 mg) or placebo in the 40‐week maintenance period. Demographic and baseline disease characteristics and level of response to induction were evaluated for association with not flaring using logistic regression. Parameters with a significant (p < 0.15) interaction with the treatment arm were fitted into a multivariable regression model, which was used to assess probability of not flaring. Results: Lower percentage body surface area affected at baseline (p = 0.09), absence of prior exposure to systemic agents (p = 0.02) and greater percentage change in EASI from baseline to randomization (p < 0.001) were identified as predictors of not flaring with abrocitinib. In both abrocitinib arms, percentage change in EASI from baseline to end of induction (Week 12) was the major contributor to the probability of not flaring in the maintenance period. Conclusions: Maintenance of response using reduced‐dose abrocitinib 100 mg may be feasible for patients with lower baseline disease severity and strong response to abrocitinib 200 mg induction treatment. [ABSTRACT FROM AUTHOR]

The article discusses a case of primary localized cutaneous amyloidosis (PLCA) associated with atopic dermatitis (AD) successfully treated with nemolizumab. The patient, a 67-year-old Japanese man with AD and PLCA, experienced significant itch and skin lesions. Treatment with nemolizumab led to a marked improvement in symptoms, including reduced itch and improved skin appearance. The study highlights the potential of nemolizumab as an effective treatment for PLCA associated with AD, although further research is needed to determine the best approach for managing this condition. [Extracted from the article]

Atopic dermatitis (AD) is a genetically predisposed allergic inflammatory dermatosis with chronic, pruritic, and recurrent features. Patients with AD have dry and itchy skin, often accompanied by chronic eczematous lesions, allergic rhinitis, or asthma, which has a considerable impact on their daily lives. With advances in genome sequencing technology, it has been demonstrated that microorganisms are involved in this disease, and the microorganisms associated with AD are attracting considerable research attention. An increasing number of studies conducted in recent years have demonstrated that an imbalanced microbiome in AD patients has substantial impact on disease prognosis, and the causes are closely tied to various immune mechanisms. However, the involvement of microorganisms in the pathogenesis of AD remains poorly understood. In this paper, we review the advances in research on the immunological mechanisms of the skin microbiome, intestinal microbiome, and lung microbiome that are related to AD prognosis and immunotherapy protocols. It is hoped that this approach will lay the foundation for exploring the pathogenesis of and emerging treatments for AD. [ABSTRACT FROM AUTHOR]

Background Systemic glucocorticosteroids (SGCs) are used in the short-term treatment of atopic dermatitis (AD), but are not recommended for long-term use because they are associated with severe side-effects. Objectives This study aimed to characterize the utilization and potentially negative effects of SGC use for AD in German statutory health insurance (SHI) claims data. Methods Cross-sectional and longitudinal analysis of a large nationwide SHI dataset. SGC drug prescriptions and incidences of predefined comorbidities after drug initiation that were known to be potentially harmful side-effects were analysed. SGC use was quantified by (-definition 1) the number of quarters with at least one SGC prescription and (definition 2) the defined daily doses (DDD). Comparisons were adjusted for age, sex and morbidity. Results The AD prevalence was 4.07% in 2020 (4.12% women, 3.42% men). During this period 9.91% of people with AD were prescribed SGCs compared with 5.54% in people without AD (P < 0.01). Prescribing of SGCs was significantly higher in women (10.20% vs. 9.42% in men, P < 0.01) and in the elderly. AD and SGC prevalence varied regionally. In a 3-year follow-up period, 58% of people with AD receiving a SGC were prescribed SGCs in > one quarter and 15% in > six quarters. The odds of developing osteoporosis [odds ratio (OR) 3.90 -(definition 1) and 1.80 (definition 2)] and diabetes [OR 1.90 (definition 1) and 1.38 (definition 2)] were significantly higher in people with AD on SGCs, especially in the frequently prescribed group compared with the rarely prescribed group, regardless of quantified use. Conclusions A considerable number of people with AD in Germany are prescribed long-term SGCs. The onset of medical conditions known to be harmful effects of steroids was significantly more frequent in those who were frequently prescribed SGCs, indicating the need for optimized healthcare. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real‐world data on its efficacy and safety in treating moderate‐to‐severe atopic dermatitis (AD) remains limited. Objectives: This study aimed to evaluate the short‐term effectiveness and safety of abrocitinib in a real‐life setting for patients with moderate‐to‐severe AD. Methods: We conducted a retrospective multicenter study involving adult patients with moderate‐to‐severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. Results: The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. Conclusions: This first Spanish series assessing abrocitinib in real‐world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well‐tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the level of burden in pediatric and adolescent atopic dermatitis (AD) patients in Japan, the associated burden on caregivers/families, and whether this burden varied with age. Methods: Data were drawn from the Adelphi Pediatric AD Disease Specific Programme (DSP)™, a cross‐sectional survey of physicians and their patients conducted in Japan between July and December 2022. Physicians reported patient demographics, clinical characteristics, disease burden, and current/previous therapies. Patients and/or caregivers reported perceived disease severity and impact of AD, including the Children's Dermatology Life Quality Index (CDLQI) and Dermatitis Family Impact questionnaire (DFI). Results: Overall, 55 physicians provided data for 537 AD patients aged ≤17. Mean (SD) overall scores for CDLQI, POEM, and DFI were 9.3 (6.3), 8.3 (6.8), and 11.7 (7.2), respectively. Age was associated with higher patient and/or caregiver‐reported CDLQI scores, which increased by 0.543 points per year of age (P = 0.01). Patients with severe disease reported a more significant impact on quality of life factors compared with mild patients (P < 0.001). Age was associated with higher caregiver‐reported burden, with DFI scores increasing by 0.325 per year (P = 0.01). Physician‐reported impact on caregivers showed that age was significantly associated with increased burden on sleep, daily activities, work, and mood (P < 0.05), with disease severity associated with impact across all factors (P < 0.01). Conclusions: Both increasing age and disease severity were associated with the increased impact of AD on patients and their caregivers. Disease control/modification through appropriate therapeutic intervention at a younger age may relieve the burden of pediatric AD on patients and their families. [ABSTRACT FROM AUTHOR]

Purpose: To identify potential factors associated with keratoconus. Methods: This cross‐sectional study included data from Israel's largest healthcare provider for the years 2005–2020. Keratoconus patients and age‐matched controls were identified. Demographic factors and comorbid conditions, including smoking, diabetes mellitus, asthma, myalgia, mental retardation, Down syndrome, atopic dermatitis and allergy/allergic rhinitis, were compared between the two cohorts. The independent risk factors associated with keratoconus were determined using a multivariable conditional logistic regression model. Results: Overall, 145 508 subjects were reviewed of which 13 228 were keratoconus patients. A ten‐fold group (n = 132 280) of age‐matched control subjects served as controls for comparisons. In multivariable analysis, several factors were found to be significantly associated with keratoconus. Male gender (OR = 1.27, p < 0.001), Arab ethnicity (OR = 1.50, p < 0.001), diabetes (OR = 1.19, p < 0.001), asthma (OR = 1.50, p < 0.001), myalgia (OR = 1.09, p = 0.02), mental retardation (OR = 2.63, p < 0.001), atopic dermatitis (OR = 1.35, p < 0.001) and allergic rhinitis (OR = 1.21, p < 0.001) were significantly associated with keratoconus. Smoking was significantly protective of keratoconus (OR = 0.66, p < 0.001). Conclusions: This population‐based study reports male gender, Arab ethnicity, diabetes, asthma, myalgia, mental retardation/Down syndrome, atopic dermatitis and allergic rhinitis as factors associated with keratoconus while smoking demonstrates a protective effect. The results of this study could guide enhanced screening strategies and early interventions, particularly for high‐risk groups. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. Objectives: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. Methods: We analysed two groups (AD and non‐AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. Results: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non‐AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age‐adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61–0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non‐AD individuals. Conclusions: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non‐AD population, except for a negative relationship between AD and sensitisation to nickel sulphate. [ABSTRACT FROM AUTHOR]

Background: Neomycin is an aminoglycoside antibiotic that may cause contact allergy. It was withdrawn as a medicine for human use in Denmark in October 2009 but is still found in some vaccines. Objectives: To identify time trends in contact allergy to neomycin in the period from 2000 to 2023. Methods: A cross‐section study of patients ≥18 years consecutively patch‐tested with neomycin sulfate (20% in pet.) at Gentofte Hospital, Denmark, during the period 2000–2023 was conducted. Results: The overall prevalence of contact allergy to neomycin was 1.4%. The prevalence was significantly lower in the period '2010–2023' (1.2%) than in '2000–2009' (1.8%) (p < 0.005). Contact allergy to neomycin was significantly positively associated with facial dermatitis and age >40 years, and significantly negatively associated with occupational dermatitis and hand dermatitis. No changes in sex, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, or age > 40/≤40 (the MOAHLFA‐index) were identified when comparing neomycin contact allergic‐patients in the two periods '2010–2023' and '2001–2009'. Conclusion: Neomycin is a rare cause of contact allergy in Denmark with a significantly lower prevalence following its withdrawal as a medicinal product for human use in Denmark in 2009. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in childhood. Interleukin 17 (IL17) is one of the pro-inflammatory cytokines that has an important role in the pathogenesis of many skin diseases including AD. Ischemia modified albumin (IMA) is an indicator of oxidative stress, inflammation and ischemia. The aim of the study was to assess the IL-17 and IMA serum levels in the children patients with AD in comparison to a control group. Additionally, the study seeks to examine the correlation between these biomarkers and their association with disease severity, disease stages, and other clinical characteristics. Methods: The case-control study enrolled two groups: (patient group: 50 children with AD) and (control group: 50 healthy age and sex-matched children). Full history was taken from all cases along with full dermatologic examination. The assessment of AD severity was conducted by using Eczema Area and Severity Index (EASI). Evaluation of IL-17 and IMA was performed by using ELISA technique. Results: There was a statistically significant elevation in the mean levels of IL-17 and IMA in patients with AD compared to the control group. A strong positive correlation was observed between IL-17 and IMA levels. Additionally, both IL-17 and IMA levels exhibited a statistically significant negative correlation with the duration of the disease and the age of the patients. Conclusion: The elevated serum levels of IL17 and IMA and their positive correlation confirm that AD is a systemic inflammatory disease influenced and associated with increased oxidative stress. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common allergic skin disease characterized by eczema, dryness, and severe itching, which has a significant impact on patients' quality of life. Its pathogenesis involves immune dysregulation and impaired skin barrier function. In this study, the therapeutic potential of Ampelopsis brevipedunculata (Maxim.) Trautv for alleviating atopic dermatitis symptoms was investigated using the NC/Nga mouse model. A. brevipedunculata (Maxim.) Trautv was effective in attenuating the atopic dermatitis-like epidermal thickening and the immune cell infiltration in the skin lesions induced by the atopic dermatitis ointment. Additionally, A. brevipedunculata (Maxim.) Trautv suppressed the production of inflammatory mediators and chemokines associated with atopic dermatitis progression. In addition, A. brevipedunculata (Maxim.) Trautv exhibited restorative effects on skin barrier dysfunction by increasing the expression of key barrier proteins. Mechanistically, A. brevipedunculata (Maxim.) Trautv modulated the mitogen-activated protein kinase pathway and inhibited nuclear factor-kappa B activation. These findings highlight the potential of A. brevipedunculata (Maxim.) Trautv as a promising therapeutic agent for treating atopic dermatitis and provide insight into its mechanisms of action. [ABSTRACT FROM AUTHOR]

The use of medications which target the JAK-STAT signaling pathway, also known as janus kinase (JAK) inhibitors, has rapidly increased in recent years. Patient perceptions, opinions, and concerns regarding the use of JAK inhibitors are largely uninvestigated. Our objective is to better understand patient concerns, reported side effects, and sentiments regarding the use of JAK inhibitors for dermatologic disease. The authors performed a cross-sectional analysis of the most frequented subreddits for dermatologic disease in which JAK inhibitors have obtained FDA approval (r/atopic dermatitis, r/psoriasis, r/alopecia areata, r/vitiligo, and r/eczeJAKS). The sentiment, central theme, and engagement level of each post was evaluated using previously utilized methods. Nine hundred twenty-three posts were analyzed, with the majority focusing on efficacy (433, 47%) and medication-related side effects (150, 16%). Other themes of interest to patients were Payment/Insurance (84, 9%), Study Results/News (69, 7%), Administration/Dosage (33, 4%), and Medication Interactions (31, 3%). The most frequently reported side effects were acne/folliculitis (24, 22%), nausea/gastrointestinal disturbance (11,10%), and fatigue/muscle aches (10, 9%). At the same time, the medication interactions garnering the most concern were sunscreens/facial moisturizers (5, 16%), topical calcineurin inhibitors (4, 13%), and Marijuana/THC (3, 9.%). This analysis highlights that patients are most concerned about the efficacy and side effects of JAK inhibitors in addition to issues regarding access to JAK inhibitors. Providers can use the insights gained from this study to address hesitancy better and guide comprehensive, patient-centered discussions with patients regarding JAK inhibitor use. [ABSTRACT FROM AUTHOR]

[Display omitted] Systemic Janus kinase inhibitors (JAKi) and dupilumab both have emerged as promising therapeutics for atopic dermatitis (AD). Dupilumab has a favorable safety profile, but oral JAKi therapy has been established in other diseases that carry potential comorbid susceptibilities that influence safety. We sought to provide real-world evidence of the comparative safety of oral JAKi versus dupilumab in patients with AD. The study used observational data from multiple healthcare organizations in the US. Patients with AD treated with either oral JAKi (upadacitinib, abrocitinib, and baricitinib) or dupilumab were enrolled. The 2 treatment groups were propensity score matched 1:1 on the basis of demographics, comorbidities, and prior medications. Safety outcomes within 2 years after the initiation of medications were measured by hazard ratios (HRs) with 95% confidence intervals (CIs). A total of 14,716 patients were included, with 942 patients treated with oral JAKi and 13,774 with dupilumab. The 2 treatment groups respectively included 938 patients after matching. Treatment with oral JAKi was not associated with increased risks of mortality, malignancies, major adverse cardiovascular events, venous thromboembolism, renal events, or serious gastrointestinal events. However, patients receiving oral JAKi showed significantly higher risks of skin and subcutaneous tissue infection (HR = 1.35, 95% CI = 1.07-1.69), herpes infection (herpes simplex, HR = 1.64, 95% CI = 1.03-2.61; herpes zoster, HR = 2.51, 95% CI = 1.14-5.52), acne (HR = 2.09, 95% CI = 1.54-2.84), cytopenia (anemia, HR = 1.83, 95% CI = 1.39-2.41; neutropenia, HR = 4.02, 95% CI = 1.91-8.47; thrombocytopenia, HR = 1.76, 95% CI = 1.08-2.89), and hyperlipidemia (HR = 1.45, 95% CI = 1.09-1.92); the risk of ophthalmic complications was higher in those receiving dupilumab (HR = 1.49, 95% CI = 1.03-2.17). Oral JAKi did not exhibit concerning safety issues in treating patients with AD but increased the risk of infections and abnormalities in laboratory findings. Long-term follow-up data are required to validate these results. [ABSTRACT FROM AUTHOR]

A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, an mAb targeting the IL-4 receptor α (IL-4Rα) subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B cells, critical in atopic diseases. Recent studies indicate IgG+CD23hiIL-4Rα+ type 2 memory B cells (MBC2s) as IgE-producing B-cell precursors, linked to total IgE serum levels in atopic patients. Total IgE serum levels decreased during dupilumab treatment in previous studies. We sought to assess the effects of dupilumab treatment in comparison with alternative therapies on the frequency of MBC2s and the correlation to total IgE levels in pediatric patients with AD. Pediatric patients with AD, participating in an ongoing trial, underwent randomization into 3 treatment groups: dupilumab (n = 12), cyclosporine (n = 12), and topical treatment (n = 12). Plasma samples and PBMCs were collected at baseline (T0) and at 6 months after starting therapy (T6). Flow cytometry was used for PBMC phenotyping, and ELISA was used to assess total IgE levels in plasma. Our findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. In addition, a significant correlation was observed between MBC2s and total IgE levels. Systemic blocking of the IL-4Rα subunit leads to a decrease in circulating MBC2 cells and total IgE levels in pediatric patients with AD. Our findings unveiled a novel mechanism through which dupilumab exerts its influence on the atopic signature. [ABSTRACT FROM AUTHOR]

Background: Ocular surface disorders have been reported among patients with various medical conditions, including atopic dermatitis (AD). Nonetheless, validated algorithms to identify conjunctivitis and keratitis in claims data are lacking. Objective: Develop validated, claims‐based algorithms for conjunctivitis and keratitis among patients with AD using medical records. Methods: Patients with AD were identified in a claims database between March 2017 and November 2019. Among these patients, candidate algorithms were developed that included diagnosis codes for conjunctivitis or keratitis, alone and in combination with ophthalmic treatments. Among patients who met ≥ 1 candidate algorithms, a subset was randomly selected for medical record review. Additionally, records from a random sample of patients with AD were reviewed to assess sensitivity. Overall, 341 records were sought and 262 adjudicated by an expert ophthalmologist. The positive predictive value (PPV) of each algorithm was calculated and compared to a pre‐specified threshold of ≥ 70%. Results: For conjunctivitis, the final algorithm was ≥ 1 conjunctivitis diagnosis (PPV = 81%, 95% confidence interval [CI]: 73%–87%). For keratitis, the final algorithm combined the following 2 candidate algorithms: ≥ 1 keratitis diagnosis and ≥ 1 dispensing of a topical antibiotic or antibiotic–steroid combination (PPV = 91%); and ≥ 1 keratitis diagnosis and ≥ 1 dispensing of an ophthalmic corticosteroid, topical immune‐modulator, or topical NSAID (PPV = 68%) for an overall PPV of 80% (95% CI: 55%–93%). Conclusion: The first claims‐based algorithms to identify conjunctivitis and keratitis among AD patients were developed and validated. They are available for use in future studies, particularly to better understand conjunctivitis and keratitis occurrence among patients with AD. [ABSTRACT FROM AUTHOR]

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream 1% in Japanese patients aged ≥12 years with atopic dermatitis (AD) in two phase 3 trials, ZBB4‐1 and ZBB4‐2. ZBB4‐1 (N = 216) consisted of an 8‐week, double‐blind, vehicle‐controlled treatment period (period 1) and a 16‐week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who enrolled in period 2 received tapinarof. ZBB4‐2 (N = 291) was a 52‐week, open‐label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBB4‐1, the proportion of patients who achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with ≥2‐grade improvement from baseline at week 8 (IGA treatment success, the primary end point) was 20.24% in the tapinarof group and 2.24% in the vehicle group (p = 0.0007). The proportion of patients with ≥75% improvement from baseline in Eczema Area and Severity Index (EASI) score at week 8 (EASI‐75 response, the key secondary end point) was 40.3% in the tapinarof group and 4.3% in the vehicle group (p < 0.0001). In ZBB4‐2, IGA treatment success rate was 28.1% at week 16, 32.3% at week 24, and 41.3% at week 52, and EASI‐75 response rate was 53.3% at week 16, 63.7% at week 24, and 76.6% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis, acne, and headache. In summary, tapinarof cream 1% was effective and generally safe for up to 52 weeks of treatment in Japanese patients with AD. [ABSTRACT FROM AUTHOR]

Background: Epidemiological evidence suggests that particulate matter (PM) exposure can trigger or worsen atopic dermatitis (AD); however, the underlying mechanisms remain unclear. Recently, pregnane X receptor (PXR), a xenobiotic receptor, was reported to be related to skin inflammation in AD. Objectives: This study aimed to explore the effects of PM on AD and investigate the role of PXR in PM-exposed AD. Methods: In vivo and in vitro AD-like models were employed, using BALB/c mice, immortalized human keratinocytes (HaCaT), and mouse CD4+ T cells. Results: Topical application of PM significantly increased dermatitis score and skin thickness in AD-likemice. PM treatment increased themRNA and protein levels of type 17 inflammatorymediators, including interleukin (IL)-17A, IL-23A, IL-1b, andIL-6, in AD-like mice and human keratinocytes. PM also activated PXR signaling, and PXR knockdown exacerbated PM-induced type 17 inflammation in human keratinocytes and mouse CD4+ T cells. In contrast, PXR activation by rifampicin (a human PXR agonist) reduced PM-induced type 17 inflammation. Mechanistically, PXR activation led to a pronounced inhibition of the nuclear factor kappa B (NF-kB) pathway. Conclusion: In summary, PM exposure induces type 17 inflammation and PXR activation in AD. PXR activation reduces PM-induced type 17 inflammation by suppressing the NF-kB signaling pathway. Thus, PXR represents a promising therapeutic target for controlling the PM-induced AD aggravation. [ABSTRACT FROM AUTHOR]

Objective: We review the prevalence of allergic diseases in children across prenatal exposures to heavy metals. Methods: This systematic review and meta-analysis is registered in the PROSPERO database (CRD42023478471). A comprehensive search of PubMed, Web of Science, Medline and Cochrane library was conducted from the database inception until 31 October 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of included studies. We used a random-effects model to summarize the effects from the studies. Results: A total of 16 studies were included, 120,065 mother-child pairs enrolled. The NOS scores indicated that the quality of the literature included in the study was of a high standard. Conclusion: The final results indicate that prenatal exposure to Pb increased the incidence of wheeze and Eczema in infants, and exposure to Ni and CD increased the incidence of AD in infants. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic disease characterized by relapsed eczema and intractable itch, and is often triggered by house dust mites (HDM). PAR2 is a Gprotein coupled receptor on keratinocytes and may be activated by HDM to affect AD processes. We first established a HDM-derived AD mouse model in wild-type (WT) and Par2-/-mice. Single cell RNA sequencing of the diseased skins found a stronger cellular communication between the ligand macrophage migration inhibitory factor (MIF) from keratinocytes and its receptors on antigen-presenting cells, suggesting the critical role of MIF in AD. HDM-WT mice showed severer skin lesions and pathological changes with stronger immunofluorescence MIF signals in skin sections than HDM-Par2-/- mice. Primary keratinocytes from WT mice stimulated with HDM or SLIGRL (PAR2 agonist) secreted more MIF in cultured medium and induced stronger immunofluorescence MIF signals than those from Par2-/- mice. The skin section of HDM-WT mice showed higher immunofluorescence signals of P115 (relating to MIF secretion) and KIF13B (possibly relating to intracellular trafficking of MIF) than that of HDM-Par2-/- mice. Acetylation of a-tubulin increased after stimulation by SLIGRL in WT keratinocytes but not in Par2-/- keratinocytes. HDMWT mice treated with the MIF antagonist ISO-1 displayed improvement of ADlike presentations and lower expressions of IL-4, IL-13, TSLP and Arg1 (a biomarker of M2 macrophage) mRNAs. We conclude that MIF is an important cytokine and is significantly increased in the AD model. PAR2 affects AD changes by regulating the expression, intracellular trafficking, and secretion of MIF in epidermis. [ABSTRACT FROM AUTHOR]

Introduction: Several current therapies for autoimmune diseases do not provide sustained remission. Therapies that focus on the restoration of homeostasis within the immune system (i.e., immune resolution) could overcome the limitations of current therapies and provide more durable remission. However, there is no established consensus on appropriate clinical trial designs and endpoints to evaluate such therapies. Therefore, we conducted a systematic literature review (SLR) focusing on five index diseases (asthma, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus [SLE], and ulcerative colitis) to explore published literature on 1) expert opinion on immune-resolution outcomes that should be measured in clinical trials; and 2) quantification of immune resolution in previous clinical trials. Methods: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase and MEDLINE databases were systematically searched (2013–2023) for published English language articles. Conference proceedings (2020–2022) from American Academy of Dermatology, American College of Rheumatology, Digestive Disease Week, European Alliance of Associations for Rheumatology, and European Academy of Dermatology and Venereology were searched to include relevant abstracts. The study protocol was registered in PROSPERO (CRD42023406489). Results: The SLR included 26 publications on 20 trials and 12 expert opinions. Expert opinions generally lacked specific recommendations on the assessment of immune resolution in clinical trials and instead suggested targets or biomarkers for future therapies. The targets included thymic stromal lymphopoietin (TSLP) in asthma; T helper (Th)2 and Th22 cells and their respective cytokines (interleukin [IL]-4R and IL-22) in atopic dermatitis; inhibitory/regulatory molecules involved in T-cell modulation, and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) in rheumatoid arthritis; low-dose IL-2 therapy in SLE; and pro-resolution mediators in ulcerative colitis and asthma. In the interventional studies, direct biomarker assessments of immune resolution were the number/proportion of regulatory T-cells (Treg) and the ratio Th17/Treg in SLE and rheumatoid arthritis; the number of T follicular helper cells (Tfh), Th1, Th2, Th17, and Th22 in atopic dermatitis, rheumatoid arthritis, and SLE; and mucosal proinflammatory gene signatures (tumor necrosis factor [TNF], interleukin 1 alpha [IL1A], regenerating family member 1 alpha [REG1A], IL8, interleukin 1 beta [IL1B], and leukocyte immunoglobulin-like receptors A [LILRA]) in ulcerative colitis. Several studies reported a statistically significant relationship between clinical remission and immune-resolution biomarkers, suggesting a link between T-cell homeostasis, cytokine production, and disease activity in autoimmune diseases. Discussion: Existing literature does not offer clear guidance on the evaluation of immune resolution in interventional studies. Further research and consensus are needed to assess a treatment’s ability to induce long-term remission or low disease activity [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate‐to‐severe atopic dermatitis (AD).In this randomized, double‐blind, placebo‐controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate‐to‐severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo‐treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF‐α, and total IgE in serum. By contrast, the expression levels of IL‐12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4‐dihydroxy‐6‐naphthoate biosynthesis II.FMT was a safe and effective therapy in moderate‐to‐severe adult patients with AD; the treatment changed the gut microbiota compositions and functions. [ABSTRACT FROM AUTHOR]

Background Hypothesis/Objectives Animals Materials and Methods Results Conclusions and Clinical Relevance Canine atopic dermatitis (cAD) is a common skin disorder in dogs, wherein allergens are presumed to exert a significant influence. The prevalence of allergen sensitisation in dogs with suspected cAD remains inadequately investigated in France.This study aimed to analyse allergen‐specific immunoglobulin (Ig)E test results from French dogs with suspected cAD, exploring potential risk factors influencing sensitisation.The study included 25,451 client‐owned dogs presented with clinical signs of cAD between January 2016 and December 2022. The study population consisted of 226 pure breeds and 915 cross‐bred dogs of both sexes, with a mean age of 4.4 (±2.8) years.Data collection involved the compilation of results from canine serological allergen‐specific IgE ELISA tests, using a 23 allergen composite panel. The influence of breed, sex, age, geographical area and sampling season on IgE test outcomes subsequently was analysed.Of the 25,451 analysed samples, 75.6% exhibited significant serum IgE concentrations in response to at least one of the tested allergens, with 67.9% testing positive for mites and 39.8% for pollens. Breed, sex, age, geographical area and sampling season were identified as significant risk factors influencing sensitisation patterns.This study provides insights into the prevalence and risk factors associated with allergen sensitisation in dogs with suspected cAD. Understanding these factors is crucial for effective diagnosis and tailored management strategies in veterinary practice. The findings underscore the need for personalised approaches in addressing cAD, considering individual patient characteristics. [ABSTRACT FROM AUTHOR]

Background Hypothesis/Objectives Materials and Methods Results Conclusions and Clinical Relevance Few studies have investigated optimal storage conditions or expiration dates for sublingual immunotherapy (SLIT) formulations prepared from glycerinated allergen extracts.The objective of this study was to compare concentrations of short ragweed major allergen (Amb a 1) and total protein in SLIT formulations stored at two different temperatures. It was hypothesised that protein concentrations would show greater decline over time in a formulation stored at room temperature (RT) than in one stored under refrigeration.Two SLIT samples containing equal volumes of 20,000 PNU Amb a 1 extract were prepared and stored at refrigerated cold (CT) (2–8°C) or RT (20–24°C) for 140 days. Changes in total protein and major allergen concentration and composition were measured by Bradford assay, two‐site enzyme‐linked immunosorbent assay and SDS–PAGE. Presence of Amb a 1 was confirmed with Western immunoblot. Data were analysed using an analysis of covariance, with p < 0.05 considered significant.SDS–PAGE showed compositional changes in a ~26–30 kDa protein band under RT and not CT storage. The Amb a 1 concentration of the RT SLIT sample declined significantly over time, compared to that of the CT SLIT sample (F(1,8) = 47.69, p < 0.0001). There was no significant difference in total protein concentration over time between groups (F(1,8) = 1.79, p = 0.22).These results demonstrate that storage of glycerinated SLIT formulations in refrigerated CT preserved the highest concentration of the specific allergen Amb a 1, suggesting that SLIT formulations containing short ragweed should be stored under refrigeration. [ABSTRACT FROM AUTHOR]

Objective To comprehensively evaluate the association between Thymic Stromal Lymphopoietin (TSLP) and atopic dermatitis (AD). Methods Six databases were searched for relevant studies. For studies on TSLP levels, the standardized mean difference (SMD) was used. For studies involving gene polymorphisms, evaluation was performed using odds ratios (ORs) and 95% confidence intervals (95% CIs). Based on the between-study heterogeneity, a fixed- or random-effects model was chosen. Analyses were performed using RevMan 5.3 software and R 4.3.0 software. Trial sequential analysis was conducted to evaluate whether the number of cases was sufficient. Results A significant relationship between TSLP rs1898671 polymorphism and AD was found under homozygous (DD vs dd), and dominant contrasts (DD + Dd vs dd), with OR = 0.47 (95% CI: 0.24, 0.92) and 0.46 (95% CI: 0.24, 0.88), respectively (p < 0.05). Whereas under allele (D vs d), heterozygous (Dd vs dd) and recessive contrasts (DD vs Dd + dd), no significant relationship was found. No significant relationship was found for rs1837253 or rs11466749. Serum TSLP levels were significantly higher in patients with AD, with the SMD = 1.45 (95% CI: 0.65, 2.25) (p < 0.05). Conclusions TSLP gene rs1898671 polymorphism was associated with AD, and TSLP levels were elevated in patients with AD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the distribution characteristics of specific immunoglobulin E (IgE) to dust mite components in patients with atopic dermatitis (AD), aiming to provide a reference basis for the development of microarray protein chips for allergen component discrimination diagnosis and personalized desensitization therapy. Methods: A total of 55 patients who visited Huishan District People's Hospital of Wuxi City, Xishan People's Hospital of Wuxi City, and People's Hospital of Wuxi City from January 2023 to December 2023 were selected. The results of serum total IgE (total IgE) and specific IgE detection were analyzed. Results: Among the 55 patients, 54 (98.2%) were positive (cutoff value > 0.35 Ua/mL, the normal value for serum total IgE is under 150–400 IU/mL) for serum total IgE antibodies, 52 (94.6%) were positive for Dermatophagoides pteronyssinus (Dp)–specific IgE antibodies, and 50 (90.9%) were positive for Dermatophagoides farinae (Df)–specific IgE antibodies. The protein chip results were consistent with the existing Phadia detection results. Conclusion: The development of chips based on CRD (component‐resolved diagnosis) cannot only rely on IgE binding rate to assist in precise treatment of patients but also choose personalized desensitization therapy, providing more practical recommendations for preventing cross‐allergy, avoiding allergic environments, or ingesting sensitizing foods for susceptible individuals. [ABSTRACT FROM AUTHOR]

Background: Oclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4+ and CD8+ T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28. Results: The study showed that the mean percentage and absolute count of CD4+ and CD8+ T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4+ T cells and the mean percentage and absolute count of CD8+ T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25+CD4+ and CD25+CD8+ T cells were significantly decreased; the reduction in the percentage of CD25+CD4+ T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3+CD4+ T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils. Conclusions: The findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4+ and CD8+ T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4+ Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4+ regulatory T cells - resulting in the shift of the CD4+ Treg cell (i.e. Foxp3+CD4+)/activated Teff (i.e. CD25+CD4+) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Management of moderate‐to‐severe atopic dermatitis (AD) needs long‐term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin‐4 receptor α subunit (IL‐4Rα), a shared receptor for IL‐4 and IL‐13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI‐75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2‐point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long‐term (52 weeks) efficacy and safety of stapokibart from this trial.After 16‐week double‐blind treatment completed, patients in both stapokibart and placebo groups entered a 36‐week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period.Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI‐75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2‐point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4‐point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP‐NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52‐week treatment period, 88.1% of patients reported treatment‐emergent adverse events, most were mild or moderate.Long‐term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician's Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control. Impaired interleukin-2 production and regulatory T cell dysfunction is implicated in multiple autoimmune diseases. Here, in two phase lb trials, the authors show that rezpegaldesleukin, a Treg-selective pegylated IL-2, is safe and improves symptoms in patients with atopic dermatitis or psoriasis. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Materials and Methods Results Conclusions and Clinical Relevance Epicutaneously house dust mite‐sensitised (HDM‐S) healthy dogs are commonly used as canine atopic dermatitis (cAD) models; however, the exact mechanisms of HDM‐induced AD immune activation in HDM‐S and HDM‐nonsensitised (NS) dogs remain unclear.To characterise the inflammatory and pruritogenic transcriptome of acute epicutaneous HDM‐induced skin lesions at 6 h and 24 h in HDM‐NS and HDM‐S dogs; untreated skin at 0 h from each dog served as control.Six HDM‐S and six HDM‐NS laboratory beagles.Processed expression data from GEO deposited by Schamber et al. (G3 (Bethesda), 2014, 4 and 1787) (GSE58442) were downloaded and analysed using R and the Bioconductor package. Significance analysis was performed with the limma package; genes with false discovery rate <0.05 and fold‐change ≤/≥1.5 were considered significantly differentially expressed (DEGs).A 2D principal component analysis revealed no clear separation between HDM‐NS and HDM‐S dogs at 6 h and 24 h time points. HDM‐induced skin lesions in sensitised and nonsensitised dogs at the 24 h time point showed significant upregulation of T helper cell (Th)2 genes (interleukin [IL]‐4R, IL‐5, IL‐13, CCL13 and CCL17), as well as proinflammatory‐ (LTB, IL‐1A and IL‐18), Th1‐ (CXCL10, OASL and MX‐1) and Th17‐related markers (IL‐17B, IL‐17F, CCL19 and CCL20). The key Th22‐related maker, IL‐22, was upregulated only in the HDM‐S group at the 24 h time point. Both groups at 24 h featured significant upregulation of several noncytokine pruritogens, such as trypsin, chymase, cathepsin S, periostin and neuromedin B.Taken together, we establish that epicutaneous HDM patch application induces immune changes in HDM‐NS dogs with Th2 dominance and activates several itch‐promoting pathways. [ABSTRACT FROM AUTHOR]

In the treatment process of atopic dermatitis, pompholyx may occurs on palms and soles. However, there is limited knowledge about which patients are more likely to develop pompholyx and when it is expected to occur. Therefore, this study investigated the occurrence of pompholyx after the start of induction remission treatment. We collected medical information from48 AD patientswho visited Hiroshima University Hospital for the first time between January 2019 and December 2020, from the time of their first visit to 12 months later. In the initial group of 48 patients, 10 individuals developed pompholyx within 1 year after their first visit. There was no clear connection between the occurrence of pompholyx and treatment received. Most of the patients who developed pompholyx were above the age of 30. Serum thymus and activation-regulated chemokine (TARC) levels tended to be higher at the first visit in the group that later developed pompholyx compared to the group that did not. In conclusion, patients over the age of 30 with higher serum TARC levels may develop pompholyx while their AD is improving. It is crucial to provide these patients with information about the possibility of developing pompholyx during the course of their AD treatment and that it would be cured in the course of treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT Biological agents are widely used across medicine, including for immune‐mediated skin conditions such as psoriasis and atopic dermatitis. When used to treat a relevant pathological process, they demonstrate impressive efficacy and credible safety, helping to achieve remission and improved function and quality of life. However, with their expanded use, awareness and understanding of adverse reactions to biologicals have also increased. Herein, we discuss the pathomechanism of adverse reactions to biological agents used to treat skin conditions and apply these to Pichler's classification system. This classification differentiates five distinct types, namely overstimulation (type α), hypersensitivity or immunogenicity (β), immunodeviation (γ), cross‐reactivity (δ) and nonimmunologic adverse reactions (ε). This classification covers most types of adverse reactions associated with use of biological agents and could be used to better understand the reaction pathogenesis and manage the clinical features of biological adverse effects. [ABSTRACT FROM AUTHOR]

Autoimmune diseases, a disease characterized by immune imbalance caused by the human immune system mistakenly attacking its own components, include vitiligo, psoriasis and atopic dermatitis (AD). Previous studies on autoimmune diseases have focused mainly on immune cells, keratinocytes and endothelial cells. Fibroblasts, the main cells that secrete the extracellular matrix (ECM) in the dermis, have been studied thoroughly in terms of fibrosis and wound healing. However, an increasing number of studies have shown that fibroblasts play an important role in nonfibrotic autoimmune skin diseases. In this article, the previously reported role of fibroblasts in nonfibrous autoimmune skin diseases such as psoriasis, vitiligo and AD is summarized to provide new ideas for the treatment of this disease. [ABSTRACT FROM AUTHOR]

ABSTRACT Hyperimmunoglobulin E syndrome (HIES) is a group of rare genetic disorders characterized by severe atopic dermatitis and recurrent skin and pulmonary infections. The efficacy of dupilumab in pediatric patients with HIES‐associated severe atopic dermatitis is relatively understudied. Here, we present a series of three children with HIES, two with AD‐HIES caused by STAT3 mutations, and one with AR‐HIES caused by biallelic mutations in ZNF341. In all cases, dupilumab treatment led to sustained clearance of severe atopic dermatitis over multiple years, as well as improvements in systemic symptoms of HIES. [ABSTRACT FROM AUTHOR]

Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was examined. Methods: We conducted a retrospective review of mandatory medical questionnaires administered during legally mandated freshman medical checkups between 2017 and 2019 at the University of Tokyo, Japan. Out of 9376 total responses, 9098 cases involving individuals under the age of 20 were included in the analysis. Respondents were classified into three groups based on their daily toothbrushing frequency: "1 time or less", "twice", and "3 times or more". For the duration of each toothbrushing session, they were classified into three groups: "1 min or less", "2–3 min", and "4 min or more". A statistical analysis was performed by Pearson's χ2 test and multinomial logistic regression analysis. Results: Regarding frequency of daily toothbrushing: The χ2 test showed no significant relationship between frequency of toothbrushing and 17 systemic diseases/disorders. A multivariate analysis found that gingival bleeding and sex were independent factors. The risk of gingival bleeding decreased dramatically with increased frequency of toothbrushing (odds ratio (OR): 0.428; 95% confidence interval (CI), 0.366–0.501; p < 0.001). Regarding the amount of time spent on toothbrushing: The χ2 test showed atopic dermatitis and arrhythmia were significantly associated with the duration of toothbrushing (p = 0.032 and p = 0.016, respectively). In the multivariate analysis, atopic dermatitis, gingival bleeding, and sex were independent factors regarding the duration of toothbrushing; longer brushing time was associated with a lower risk of atopic dermatitis (OR: 0.731, 95% CI: 0.578–0.924, p = 0.009) and a lower risk of gingival bleeding (OR: 0.643, 95% CI: 0.567–0.729, p < 0.001). Conclusions: Dental self-care was most strongly associated with gingival bleeding, while the risk of atopic dermatitis was found to increase with shorter toothbrushing times. The results suggest that dental self-care during adolescence is important not only for oral health but also for general health. [ABSTRACT FROM AUTHOR]

Simple Summary: Intralymphatic immunotherapy is a treatment used for allergic diseases in both humans and animals. While ultrasound-guided injections were initially common, palpation-based injections have become more popular in veterinary dermatology. Precise injection into the lymph node seems crucial for the treatment's effectiveness; therefore, this study aimed to evaluate the impact of injection method (ultrasound guidance vs. palpation-based) on clinical responses in dogs with atopic dermatitis. The retrospective analysis of 129 canine atopic dermatitis cases treated with ILIT between 2014 and 2022 found that dogs receiving ILIT via ultrasound guidance had a significantly higher success rate compared to palpation-based injections. These findings suggest that injection quality may influence treatment outcomes. Further research is needed to validate these findings. Background: Intralymphatic immunotherapy (ILIT) has been used successfully in both human and veterinary medicine as a safe and effective treatment for allergic diseases. Initially, ILIT was administered by ultrasound guidance, but palpation-based injections have become more popular among veterinary dermatologists. Data from human medicine, however, show that precise injection into the lymph node is mandatory, and injection quality clearly correlates with clinical response. Hypothesis: Our aim was to assess the impact of the injection method (ultrasound guidance versus palpation-based guidance) on clinical response in dogs with atopic dermatitis. Methods: A total of 129 canine atopic dermatitis (CAD) cases treated with ILIT between 2014 and 2022 were retrieved from the hospital clinical database. The included dogs had to receive at least three intralymphatic injections administered either by palpation or ultrasound guidance. Those cases were retrospectively assessed and compared regarding clinical response to ILIT. Results: In total, 84 dogs received ILIT by ultrasound guidance, and in 25 dogs, ILIT was injected based on palpation. The success rate of ILIT was significantly higher in the ultrasound guidance group when compared to palpation-based injections. Conclusions: Low-quality injections must be considered as a possible reason for ILIT failure in dogs. Further prospective and controlled studies are necessary to confirm these results. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases. Topical treatments are recommended for all patients regardless of severity, making it essential to develop an effective topical AD treatment with minimal side effects; We investigated the efficacy of topical application of naringin in AD and explored the possible mechanisms using an AD mouse model induced by 1-chloro-2,4-dinitrobenzene (DNCB). Clinical, histological, and immunological changes related to AD and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling proteins in the skin tissues were measured as outcomes; Naringin treatment resulted in a significant improvement in dermatitis severity score and reduced epidermal thickness and mast cell count in the skin (p < 0.05). Naringin also demonstrated the ability to inhibit DNCB-induced changes in interleukin (IL) 4, chemokine (C-C motif) ligand (CCL) 17, CCL22, IL1β, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels by quantitative real-time polymerase chain reaction (qRT-PCR) and IL13 by enzyme-linked immunosorbent assay (ELISA) (p < 0.05). Western blot results exhibited the decreased JAK1, JAK2, STAT1, STAT3, phospho-STAT3, and STAT6 expression in the naringin-treated groups (p < 0.05); The findings of this study suggest that topical naringin may effectively improve the symptoms of AD and could be used as a therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

Immunodeficiency 11B with atopic dermatitis (IMD11B, OMIM:617638) is rare primary immunodeficiency disease caused by germline dominant negative (DN) mutations in the CARD11 gene. Affected patients present with immune dysfunction, recurrent infections and atopic dermatitis. In this study, we sought to identify and characterize the genetic variant in one patient with periodic fever, recurrent infections, and eczema. Trio whole-exome sequencing (WES) was employed in this patient and her parents, and Sanger sequencing validated the potential pathogenic variant. In vitro functional study was performed to evaluate the pathogenicity of genetic variant identified. A very rare missense mutation (c.2324C > T, p.S775L) in CARD11 gene (NM_032415) was identified by WES in the patient but not her parents. Luciferase reporter assays and co-immunoprecipitation demonstrated mutation exerts a dominant-interfering effect on wild-type CARD11, inhibiting the activity of NF-κB. RNA sequencing analysis also confirmed that mutant CARD11 inhibited down-stream transcriptional activity of NF-κB. A review of literature doesn't found significant genotype–phenotype correlation. We identified a vary rare DN CARD11 mutation, expanding the genetic and phenotypic spectrum of CARD11. [ABSTRACT FROM AUTHOR]

OX40/OX40L are costimulatory molecules in the tumor necrosis factor superfamily. Numerous studies have shown that OX40/OX40L are involved in immune regulation, especially in the proliferation and differentiation of T cells and the generation of memory T cells, which play important roles in allergic diseases. In recent years, the use of OX40/OX40L as therapeutic targets for treating T‐cell‐mediated diseases has attracted the interest of scholars. This paper reviews the role of OX40/OX40L in allergic diseases and the progress in clinical treatments targeting this signaling pathway. [ABSTRACT FROM AUTHOR]

Background Objective Animals Materials and Methods Results Conclusions and Clinical Relevance Intradermal allergen testing (IDAT) is commonly used to formulate allergen‐specific immunotherapy, a pillar treatment for canine atopic dermatitis. Many sedatives have shown histaminergic or anti‐histaminergic effects and thus been deemed unsuitable for IDAT.The goal of this study was to determine whether, in healthy dogs, dexmedetomidine (Dexdomitor) or a 1:20 combination of medetomidine and vatinoxan (Zenalpha) will affect intradermal reactions compared to unsedated dogs.Ten privately owned healthy dogs were enrolled in this equivalence study.Wheal formation was subjectively and objectively assessed in conscious then sedated dogs. Dogs were randomly sedated with either Dexdomitor (dexmedetomidine [0.5 mg/m2]) or Zenalpha (medetomidine [1 mg/m2/vatinoxan] 20 mg/m2) intramuscularly. Once sedated, five 10‐fold histamine (100–0.01 μg/mL) and compound 48/80 (200–0.02 μg/mL) dilutions were intradermally injected into the lateral thorax. The study was repeated on the opposite side with the alternative sedation 1 week later. Quality of sedation, cardiorespiratory function and rectal temperature were recorded every 5 min.There was no difference in the median values of the reactions with either sedative when compared to unsedated dogs. Dexdomitor and Zenalpha achieved an equivalence in both subjective and objective scoring systems for all concentrations tested. A faster median time to sedation (10 vs. 18 min, p = 0.013) was seen with Zenalpha compared to Dexdomitor. Although both sedatives depressed the cardiovascular function, such parameters were less affected by Zenalpha than by Dexdomitor (p ≤ 0.001).Owing to the lack of effects on wheal formation, both sedatives are appropriate for sedating dogs undergoing IDAT. Although, such results should be validated in allergic dogs. Zenalpha may induce more rapid and reliable sedation than Dexdomitor. [ABSTRACT FROM AUTHOR]

Introduction Objectives Methods Results Conclusions Patch test results may be influenced by age‐related factors. However, there is still discordant evidence between age and patch test results.We aim to evaluate the patch test results reflecting skin sensitisation, their relevance and association with clinical features by age group.Prospective multicentric study of all patients patch tested with the Spanish baseline series in participating centres. Age groups were pre‐defined as children (0‐ to 11‐years), adolescents (12‐ to 18‐years), young adults (19‐ to 30‐years), middle‐aged adults (31‐ to 65‐years) and older adults (≥66‐years). Occurrence of sensitisation, relevance and clinical features were compared by age group. Factors associated with skin sensitisation were investigated with multivariate logistic regression.A total of 13 368 patients were patch‐tested. Differences in positive patch test results and relevance by age were detected with the highest proportion in middle‐aged adults. Age‐related trend differences were found for nickel, potassium dichromate, caines, colophony, Myroxylon pereirae resin, 2‐hydroxyethyl methacrylate and limonene hydroperoxide. The multivariate logistic analysis (adjusted for sex, atopic dermatitis, body location and occupational dermatitis) showed an association between the age group of 31–65 (OR: 1.41, 95% CI: 1.26–1.58) and above 66‐years (OR: 1.15, 95% CI: 1.01–1.32) with a higher proportion of positive results, compared with young adults.Positive patch test results vary according to age, with the highest occurrence in middle‐aged adults. Most haptens did not present age‐related differences, reinforcing the use of baseline series regardless of age. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies. Results: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions. Conclusions: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required. [ABSTRACT FROM AUTHOR]

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Atopic dermatitis is the most common inflammatory skin condition with a severe negative impact on patients' quality of life. The etiology of AD is complex and depends on age, genetics, the immune system, environmental factors, and the skin microbiome, with a key role for pathogenic Staphylococcus aureus in the development of severe AD. However, the composition of the skin microbiome in mild AD is understudied. Here, using metagenomic shallow shotgun sequencing, we showed that mild AD lesions did not show a significant difference in the diversity of the skin microbiome compared to samples from non-AD patients and that the relative abundance of S. aureus did not differ in these mild AD lesions. However, when we assessed other taxa, Mycobacterium ostraviense, Pedobacter panaciterrae_A and four Streptomyces species were identified with higher abundances in mild AD lesions and species of 15 genera were decreased in abundance. The highest fold decreases were observed for Paracoccus marcusii, Microbacterium lacticum, Micrococcus luteus, and Moraxella sp002478835. These microbiome compositional insights are a first step towards novel microbiome-based diagnostics and therapeutics for early intervention at the stage of mild AD and provide a path forward for the functional study of species involved in this often-overlooked patient population. [ABSTRACT FROM AUTHOR]

Canine atopic dermatitis (CAD) is a common skin disease in dogs. Various pathogenic factors contribute to CAD, with dust mites, environmental pathogens, and other substances being predominant. This research involved comprehensive statistical analysis and prediction of CAD in China, using data from 14 cities. A distributed lag nonlinear model (DLNM) was developed to evaluate the impact of environmental factors on CAD incidence. Additionally, a seasonal auto-regressive moving average (ARIMA) model was used to forecast the monthly number of CAD cases. The findings indicated that CAD mainly occurs during June, July, August, and September in China. There was a positive correlation found between CAD incidence and temperature and humidity, while a negative correlation was observed with CO, PM2.5, and other pollutants. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify key genes and investigate the immunological mechanisms of atopic dermatitis (AD) at the molecular level via bioinformatics analysis. Gene expression profiles (GSE32924, GSE107361, GSE121212, and GSE230200) were obtained for screening common differentially expressed genes (co-DEGs) from the gene expression omnibus database. Functional enrichment analysis, protein–protein interaction network and module construction, and identification of common hub genes were performed. Hub genes were validated using receiver operating characteristic curve analysis based on GSE130588 and GSE16161. NetworkAnalyst was used to detect microRNAs (miRNAs) and transcription factors (TFs) associated with the hub genes. The immune cell infiltration was analyzed using the CIBERSORT algorithm to further analyze the correlation between hub genes and immune cells. A total of 146 co-DEGs were obtained, showing significant enrichment in cytokine–cytokine receptor interaction and JAK-STAT signaling pathway. Seven hub genes were identified by Cytoscape and validated with external datasets. Subsequent prediction of miRNAs and TFs targeting these hub genes revealed their regulatory roles. Analysis of immune cell infiltration and correlation revealed a significant positive correlation between CCL22 expression and the number of dendritic cells activated. The identified hub genes represent potential diagnostic and therapeutic targets in the immunological pathogenesis of AD. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion Trial Registration Adherence to pediatric atopic dermatitis (AD) treatment regimens can be complex and a major challenge to optimizing treatment outcome. We aimed to review factors associated with nonadherence in pediatric AD and propose interventions to improve adherence.PubMed and EMBASE databases were systematically searched for articles from 2000 to February 2023 related to AD and adherence, with an additional update in December 2023. Non‐human studies, reviews, commentaries, and meta‐analyses were excluded. Articles were sorted into pediatric versus adult study population based on volume. Herein, we examine the results of papers discussing adherence factors related to pediatric patients.A total of 62 studies met inclusion criteria. Thirty‐six studies surveyed patients and caregivers (N = 10,268) to identify barriers to treatment adherence. None of the included studies were specific to systemic medications. Barriers included poor caregiver quality of life, inadequate AD‐related education, topical corticosteroid (TCS) phobia, unclear therapy‐related instructions, and dissatisfaction with physician interaction. Five studies solely measured adherence using medication electronic monitoring systems, Morisky medication adherence scale, or self‐reported adherence to measure adherence to topical medications. Twenty‐one studies described interventions involving nurse‐led or web‐based education programs, text message or email reminders, and TCS education. Adherence was improved with caregiver education programs, daily text‐message reminders, eczema action plans, TCS potency “traffic light” color system, and frequent follow‐up visits.Adherence to pediatric AD treatment poses a multifactorial challenge for caregivers and patients. This study provides an index of strategies to optimize adherence, as it is essential for prevention of long‐term sequela associated with AD in children. As the AD treatment landscape rapidly expands, further studies are vital to assess pediatric adherence to new topical, oral, and injectable medications.PROSPERO: CRD42023488557 [ABSTRACT FROM AUTHOR]

Cold atmospheric plasma (CAP) technology has emerged as a revolutionary therapeutic technology in dermatology, recognized for its safety, effectiveness, and minimal side effects. CAP demonstrates substantial antimicrobial properties against bacteria, viruses, and fungi, promotes tissue proliferation and wound healing, and inhibits the growth and migration of tumor cells. This paper explores the versatile applications of CAP in dermatology, skin health, and skincare. It provides an in-depth analysis of plasma technology, medical plasma applications, and CAP. The review covers the classification of CAP, its direct and indirect applications, and the penetration and mechanisms of action of its active components in the skin. Briefly introduce CAP's suppressive effects on microbial infections, detailing its impact on infectious skin diseases and its specific effects on bacteria, fungi, viruses, and parasites. It also highlights CAP's role in promoting tissue proliferation and wound healing and its effectiveness in treating inflammatory skin diseases such as psoriasis, atopic dermatitis, and vitiligo. Additionally, the review examines CAP's potential in suppressing tumor cell proliferation and migration and its applications in cosmetic and skincare treatments. The therapeutic potential of CAP in treating immune-mediated skin diseases is also discussed. CAP presents significant promise as a dermatological treatment, offering a safe and effective approach for various skin conditions. Its ability to operate at room temperature and its broad spectrum of applications make it a valuable tool in dermatology. Finally, introduce further research is required to fully elucidate its mechanisms, optimize its use, and expand its clinical applications. [ABSTRACT FROM AUTHOR]

Protease-activated receptor 2 (PAR2) is a cell-surface receptor expressed in various cell types, including keratinocytes, neurons, immune and inflammatory cells. Activation of PAR2, whether via its canonical or biased pathways, triggers a series of signaling cascades that mediate numerous functions. This review aims to highlight the emerging roles and interactions of PAR2 in different skin cells. It specifically summarizes the latest insights into the roles of PAR2 in skin conditions such as atopic dermatitis (AD), psoriasis, vitiligo and melasma. It also considers these roles from the perspective of the cutaneous microenvironment in relation to other inflammatory and autoimmune dermatological disorders. Additionally, the review explores PAR2's involvement in associated comorbidities from both cutaneous and extracutaneous diseases. Therefore, PAR2 may serve as a key target for interactions among various cells within the local skin environment. [ABSTRACT FROM AUTHOR]