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Background: Baricitinib treatment in adults with moderate‐to‐severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest. Objectives: In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials. Methods: We analysed the percent change from baseline in individual EASI subscores from three phase‐III, double‐blind, 16‐week trials of baricitinib in monotherapy (BREEZE‐AD1/BREEZE‐AD2) and TCS combination therapy (BREEZE‐AD7) cohorts via mixed model repeated measures (MMRM). Results: Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near‐maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy. Conclusions: Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch‐scratch cycle. [ABSTRACT FROM AUTHOR]

This article, titled "Decoding atopic dermatitis: unveiling phenotypes through data-driven methods," discusses the use of data-driven methods, such as machine learning, to identify subtypes of atopic dermatitis (AD). The study analyzed a cohort of 1973 adult patients with AD and identified five distinct phenotypes based on disease severity. The study also found that factors such as itch intensity and flare patterns influenced phenotypic classification. While data-driven approaches have the potential to identify complex patterns, it is important to consider data quality and the integration of domain expertise to ensure accurate conclusions. Future research should focus on understanding the evolution of AD phenotypes over time and their correlation with treatment outcomes. [Extracted from the article]

Enrolled patients presented with either a newly diagnosed disease or a relapse of BP.[1] The primary endpoint was the cumulative rate of relapse-free patients after initiating therapy. Despite the fact that mepolizumab did not significantly affect the clinical outcome, we found significantly lower peripheral blood eosinophil levels in patients treated with mepolizumab compared to patients receiving placebo (Table). (b) Since we could not estimate the effect of mepolizumab in these elderly patients in advance, for ethical reasons, we chose an add-on therapy, that is, mepolizumab or placebo were administered in addition to the standardized therapy with OCS. Even after therapy, eosinophils were detectable in the skin both in patients with and without relapse of BP. [Extracted from the article]

The immune system has vital functions for homeostasis and host defense. Thus, imbalances of the immune system whether associated with allergy, hypersensitivity, or autoimmunity are of great importance, as is manifest from common diseases such as atopic diseases, urticaria, and angioedema, and drug hypersensitivity reactions. These can affect patients' quality of life and can generate high costs for health care. Epidemiological studies have provided evidence for changing patterns of allergic diseases caused by lifestyle and climate changes which have consequences for medical care. Deeper insights into the pathogenesis of allergic/immunologic diseases, combined with novel technologies, provide improved diagnostic options and treatment measures. This review will summarize novel aspects of the epidemiology, pathogenic mechanisms, as well as disease management in the fields of allergy and clinical immunology. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease presenting with recurrent eczematous lesions and intense pruritus. It is common and affects both children and adults, often beginning in infancy. Due to the unpredictable disease course, its visible skin lesions, itching and scratching followed by sleeplessness, other associated atopic diseases, and behavioral and psychiatric disorders, AD is an immense burden for patients and caregivers. AD is determined by a genetic predisposition characterized by an impaired skin barrier and a T-helper-2-predominant inflammation. Restoration of the skin barrier is the main approach for treating and preventing AD. In order to cope with acute flares, usually topical corticosteroids (TCS) are applied, while topical calcineurin inhibitors (TCI) are used mainly for maintenance therapy. There is a small group of patients who are refractory to TCS and TCI and require systemic immunosuppressive drugs such as ciclosporin. Novel, targeted therapies are under clinical investigation, among which an anti-IL-4/IL-13 receptor antibody has recently been approved in several countries. As we learn to understand the pathomechanisms of AD, the characteristics of the different patient subgroups, and the effectiveness of various targeted therapies, a personalized treatment ensuring the best efficacy and safety and, probably, a disease-modifying effect will result. [ABSTRACT FROM AUTHOR]

• The management of eosinophilic dermatoses should consider the underlying pathomechanism. • Causes of eosinophilia are either intrinsic (in eosinophils), or extrinsic (via cytokines). • Antibodies against IL-5 or its receptor target eosinophil numbers and activation. • Dexpramipexole efficiently reduces eosinophil numbers. • Tyrosine kinase inhibitors are effective in FIP1L1-PDGFRA positive hypereosinophilia. Eosinophil infiltration is observed in a broad spectrum of skin diseases of various origins. Eosinophils are thought to actively contribute to pathogenesis as they are able to defend against microbes, to regulate inflammation, cause tissue damage, promote remodeling and fibrosis, and initiate pruritus. Therefore, targeting eosinophils would seem a worthwhile therapeutic approach. A promising strategy is to target the production, activation and survival of eosinophils, example with antibodies directed against IL-5 or its receptor, and Siglec-8. Dexpramipexole and tyrosine kinase inhibitors have been shown to reduce eosinophil numbers in patients with hypereosinophilia. Janus kinase inhibitors block signal transduction and thus activation of inflammatory cells including eosinophils. A further approach is to target cells and cytokines acting on or mediators released by eosinophils, for example, CD52, IL-13, IL-31, TSLP, and eotaxins. This review summarizes current therapeutic strategies, including novel agents affecting eosinophils directly that are under clinical investigation. [ABSTRACT FROM AUTHOR]

Allergic diseases are of great concern because of their high prevalence, which is still rising in several regions, their impact on patients' physical and psychological health, the huge burden they place on patients' quality of life, as well as the socioeconomic consequences that they cause. Recent research has provided new data on both genetic and environmental risk factors of atopic/allergic diseases. The application of new technologies such as "omics" has allowed a better understanding of the pathogenesis and has helped with the identification of therapeutic targets. Immense progress has been made in developing and applying novel, targeted therapies, for example for asthma and urticaria. Intensive efforts are being made to find biomarkers that help to classify patients, to identify their potential responsiveness to specific therapies, and to monitor the disease severity. Based on recent insights in the pathogenesis of food allergy and drug hypersensitivity, novel strategies for diagnostics, allergen avoidance, and induction of tolerance have been developed. Here, we summarize important findings in the field of clinical allergy and immunology with a special focus on asthma, allergic rhinitis, atopic dermatitis, food allergy, urticaria, angioedema, and drug hypersensitivity. [ABSTRACT FROM AUTHOR]

Background: Hand eczema (HE) is common and may follow a chronic disease course. So far, prospective studies investigating the risk factors for disease progression as a prerequisite for targeted prevention are scarce. Objective: To evaluate the overall association of HE‐associated factors with clinical and quality of life (QoL) improvement during a follow‐up of 2 years. Methods: Data of the prospective patient cohort (N = 199) followed by the Swiss chronic HE (CHE) registry on long‐term patient management (CARPE‐CH) were analysed by means of both classic regression and semantic map analyses. Results: Both severity of HE and QoL significantly improved over the period of 2 years (P < .001). However, 20% of patients had moderate to severe HE after 2 years of follow‐up. As factors associated with an unfavourable CHE clinical course and QoL, environmental exposures, male sex, occupational skin disease, job loss or change at baseline, allergic contact dermatitis, a chronic disease course, palmar localization and widespread eczema were identified. Conclusions: Analysis of prospective data from CARPE‐CH shows a complex pattern of associations among variables as shown by semantic map and classic statistical analyses. Factors related to occupational exposure had the highest impact on CHE. [ABSTRACT FROM AUTHOR]

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid ( BP) is the most common autoimmune subepidermal blistering skin disease and is characterized by the presence of autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 that can be detected in the skin and serum of BP patients. Histologically, the dermal infiltration of eosinophils is obvious. The objective of this review was to present evidence that eosinophils play a key role in the pathogenesis of BP. Eosinophils, together with cytokines and chemokines regulating their production, recruitment and activation, are abundantly present in lesional skin, in blisters and in peripheral blood of patients with BP. Recently, using a cryosection model, eosinophils were demonstrated to induce dermal-epidermal separation in the presence of BP antibodies. Thus, eosinophils and their products, as well as mediators regulating their function, present promising targets for the treatment of BP. [ABSTRACT FROM AUTHOR]

During the last 20 years, science policy-making has taken to evaluation as an instrument for assessing research projects, programmes and even entire research institutes or faculties. This article examines key elements of the evaluation systems in the United Kingdom (Research Assessment Exercise), the Netherlands (Standard Evaluation Protocol) and Germany (Leibniz Association’s Evaluation Procedure) and the extent to which evaluations serve as an instrument of organizational development for the scientific bodies being evaluated. Evaluations are often mistrusted – particularly in Germany’s public discourse – as a Trojan horse of policy-making infiltrating the science system. However, our findings demonstrate that peer-review based evaluations can be an authoritative source of validation employed by scientific institutes to develop or optimize institutional strategies. Against this backdrop, we conclude with recommendations of how institutional evaluations may be further developed and how processes of organizational transformation can be supported in the research landscape. [ABSTRACT FROM PUBLISHER]

Eosinophil extracellular traps (EETs) are part of the innate immune response and are seen in multiple infectious, allergic, and autoimmune eosinophilic diseases. EETs are composed of a meshwork of DNA fibers and eosinophil granule proteins, such as major basic protein (MBP) and eosinophil cationic protein (ECP). Interestingly, the DNA within the EETs appears to have its origin in the mitochondria of eosinophils, which had released most their mitochondrial DNA, but were still viable, exhibiting no evidence of a reduced life span. Multiple eosinophil activation mechanisms are represented, whereby toll-like, cytokine, chemokine, and adhesion receptors can all initiate transmembrane signal transduction processes leading to the formation of EETs. One of the key signaling events required for DNA release is the activation of the NADPH oxidase. Here, we review recent progress made in the understanding the molecular mechanisms involved in DNA and granule protein release, discuss the presence of EETs in disease, speculate on their potential role(s) in pathogenesis, and compare available data on other DNA-releasing cells, particularly neutrophils. [ABSTRACT FROM AUTHOR]

Keratinocyte apoptosis mediated by Fas/Fas ligand molecular interactions and subsequent caspase activation is believed to play an important role in the pathogenesis of atopic dermatitis (AD), in particular for the formation of spongiosis. To estimate epidermal caspase activation in normal and AD skin under in vivo conditions, we analysed caspase-3 cleavage by immunohistology. In normal skin as well as non-lesional AD skin, we detected caspase-3 cleavage in single cells of the basal layer. In contrast, in acute lesional AD skin, we not only obtained evidence for increased expression of cleaved caspase-3 in keratinocytes of the basal layer but also observed caspase-3 cleavage in one or more layers of the spinous cell layer, in particular in spongiotic areas. Short-term topical treatment of the skin lesions with tacrolimus or pimecrolimus abolished the expression of cleaved caspase-3 in the spinous layer. Moreover, epidermal caspase-3 cleavage correlated with the numbers of dermal interferon-γ (IFN-γ)-expressing CD4+ and CD8+ lymphocytes in skin lesions of AD patients, supporting the view that IFN-γ is important for the activation of proapoptotic pathways in keratinocytes. This is also confirmed by the observation of increased Fas expression on keratinocytes in acute AD lesions that was markedly reduced following topical calcineurin inhibitor treatment. These data suggest that caspase-3 cleavage in the spinous layer of the epidermis is a pathologic event contributing to spongiosis formation in AD, whereas cleavage of caspase-3 in basal cells might represent a physiologic mechanism within the process of epidermal renewal. [ABSTRACT FROM AUTHOR]

Background: Although allergic mechanisms appear to be important, the pathogenesis of both extrinsic and intrinsic forms of atopic dermatitis (AD) is unknown. Methods: We compared the cytokine production of peripheral blood mononuclear cells of extrinsic AD (EAD) and intrinsic AD (IAD) patients and normal control individuals after stimulation with anti-CD3 and/or anti-CD28 monoclonal antibodies (mAbs) in the presence or absence of anti-CD2-blocking mAb. The cytokine production was measured by immunoassays in supernatants of 24-hour cultures. Results: EAD patients showed a decreased capacity to synthesize interferon gamma and granulocyte-macrophage colony-stimulating factor upon anti-CD3 mAb stimulation as compared with IAD patients. Both EAD and IAD patients demonstrated an increased production of interleukin (IL)-5 and IL-13. As expected, interferon gamma, granulocyte-macrophage colony-stimulating factor, and IL-5 levels were reduced in the presence of anti-CD2-blocking mAbs. CD28 costimulation restored the release in cultures with anti-CD2 mAbs added, suggesting that CD2 and CD28 have redundant functions in T cell activation and subsequent cytokine production. Strikingly, the IL-13 production was not blocked by anti-CD2 mAbs and also not increased by agonistic anti-CD28 mAb, in particular within the EAD patient group. Conclusion: The signalling pathway initiated by the T cell receptor complex leading to increased IL-13 production in AD patients appears to be highly sensitive and is largely independent on CD2 costimulatory signals.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The diagnosis of eczema (‘dermatitis’) is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co‐exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab‐associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. Methods: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non‐AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. Results: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL‐12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non‐AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. Conclusions: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD. [ABSTRACT FROM AUTHOR]

Pruritus is associated with various skin diseases, dry skin, and with it an impaired skin barrier function. The study objective was to investigate short‐term and long‐term effects of two emollients on symptoms and skin barrier functions in xerotic eczema. Randomized, double‐blind, study enrolling females/males, with bilateral itching. Two emollients, containing lactic acid and refined almond oil with/without polidocanol were administered on left versus right body sides. Itching severity, skin moisture, lipid content, and pH were assessed on Day 1, within 30–120 min after first administration, and on Days 7 and 14, and compared with baseline assessments. Severity of itching decreased 30 min after first administration of both emollients compared with baseline (p < .0001) and reached a maximum reduction of 63% (p < .0001) and 69% (p <.0001) on Day 14. Skin moisture and lipid content increased after first application, and further ameliorated within 14 days of treatment (p <.0001). Both emollients were tolerated well, and only a few adverse events were reported. This study confirmed the clinical efficacy of the two study emollients to substantially reduce itching already after first administration, and restore skin barrier integrity and thus should be considered as therapeutic approach for xerotic eczema. [ABSTRACT FROM AUTHOR]

Introduction: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. Methods: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. Results: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. Conclusion: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype. [ABSTRACT FROM AUTHOR]

Chronic pruritus profoundly affects patients' quality of life. The objective of this retrospective cross-sectional study was to characterize patients with chronic pruritus and identify patterns, in order to delineate a better diagnostic approach. Both semantic connectivity map and classical analysis were applied, linking demographic, clinical, laboratory and histopathological data with clinical and aetiological categories of 170 patients with chronic pruritus (median age 72 years, 58.2% women). The semantic map showed clinical categories separated in different hubs associated with distinct patterns concerning sex, aetiology, laboratory findings, and pharmacological treatment. Diabetes, diagnosis of cancer and psychiatric comorbidities were linked with certain clinical categories. Skin eosinophilia was a common finding of chronic pruritus, on both diseased and non-diseased skin. High frequencies of patients with chronic pruritus taking anti-arrhythmics, beta-blockers and AT-II receptor antagonists were noticed among those with underlying systemic, neurological and psychiatric diseases. This study provides a complex analysis of chronic pruritus and thus basic principles for a clinical work-up. [ABSTRACT FROM AUTHOR]

The newly observed nongenomic effects of glucocorticoids on signaling pathways operating in neutrophils in vitro will stimulate further investigations on pathogenic mechanisms and drug actions in bullous skin diseases. [ABSTRACT FROM AUTHOR]

Eosinophils are bone marrow‐derived granulocytes and are found in low numbers in the peripheral blood of healthy subjects. In type 2 inflammatory diseases, eosinopoiesis in the bone marrow is increased, resulting in a rise in the number of mature eosinophils released in the circulation. From the blood, eosinophils can migrate in multiple tissues and organs under both physiological and pathological conditions. Eosinophils exert their various functions through the synthesis and release of a variety of granule proteins and pro‐inflammatory mediators. Despite being present in all species of vertebrates, the functional role of eosinophils is still a matter of debate. Eosinophils may play a role in host defense against various pathogens. In addition, eosinophils have been reported to be involved in tissue homeostasis and exhibit immunomodulatory activities. In this review, we aim to provide a broad overview of eosinophil biology and eosinophilic diseases in a lexicon‐style format using keywords starting from A until Z with cross‐references to other chapters indicated in italics in the text or specified in parentheses. [ABSTRACT FROM AUTHOR]

The article discusses a new method called the Skin Redness Index (SRI) for quantifying skin redness in dermatology. The SRI is a practical and automated approach that uses image analysis to calculate a redness score based on the color of the skin. The study found that the SRI had excellent inter-rater reliability and a strong correlation with the Clinician Erythema Assessment (CEA) scale. The authors suggest that the SRI could be a useful tool for accurately assessing skin lesions, evaluating disease activity, and planning appropriate therapies. Further research is needed to validate the SRI, particularly in non-Caucasian patients. [Extracted from the article]

Background: Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. Objectives: To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. Methods: The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n = 46 652) in whom an occupational causation was refuted served as comparison group. Results: The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation‐related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. Conclusions: Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives. [ABSTRACT FROM AUTHOR]

Visions of and narratives about the future energy system influence the actual creation of innovations and are thus accompanying the current energy transition. Particularly in times of change and uncertainty, visions gain crucial relevance: imagining possible futures impacts the current social reality by both creating certain spaces of action and shaping technical artifacts. However, different actors may express divergent visions of the future energy system and its implementation. Looking at a particular innovation site involving multiple stakeholders over an 8-year period, we empirically analyze the collective negotiation process of vision making, its shifting over time, and how visions eventually unfold performativity. Adopting a process perspective, we identify four different phases and the respective functions of visions and visioneering related to the site's development by exploring the question: Why do certain visions gain importance and eventually lead to substantial changes of the project in process? Qualitative data from documents and interviews analyzed with reference to science and technology studies show the interweaving conditions that influence the visioneering and the linkage to the actual development of material artifacts. Against the backdrop of innovation projects, this paper explores visioneering as an ongoing, transformative and collective process and reveals its moments of (de)stabilization. [ABSTRACT FROM AUTHOR]

Background: Massage therapists are particularly exposed to constituents of massage preparations, wet work and mechanical strain and therefore, at high risk to develop occupational dermatitis (OD). Objectives: To describe the sensitization spectrum of massage therapists with OD. Patients and Methods: In a retrospective study, patch test data of patients with OD (128 massage therapists and 24 374 patients working in other professions) collected by the Network of Departments of Dermatology (IVDK, 2008–2020) were analysed. Results: Hand dermatitis (91.4%) and allergic contact dermatitis (34.4%) were common in massage therapists with OD. Most frequent were sensitizations to fragrances/essential oils which were found in 54 (42.2%) massage therapists and thus, more often than in other patients with OD. Concomitant positivity to several fragrances/essential oils was frequent. In 8 (14.8%) of the 54 massage therapists, sensitizations to fragrances/essential oils were not detected with the baseline series, but only with special fragrance series. Conclusions: Allergic contact dermatitis is common in massage therapists with OD and is mainly caused by fragrances and essential oils. Hence, massage therapists should be aware of this risk. When OD is suspected, not only the baseline series, but also special fragrance series should be patch tested in this occupational group. [ABSTRACT FROM AUTHOR]

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE‐induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non‐clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. Objectives: To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. Methods: Anonymised or pseudonymised individual data and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. Results: In 2019 and 2020, 22 581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 [19.2–20.4]% positivity [95% confidence interval]). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43–7.19)% and 6.62 (6.25–7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 [2.16–2.85]% vs. 1.59 [1.33–1.88]); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 [3.16–3.82]%), followed by 2‐hydroxyethyl methacrylate (2.32 [2.0–2.68]%). Conclusion: Ongoing surveillance on the prevalence of contact sensitization contributes to an up‐to‐date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe. [ABSTRACT FROM AUTHOR]

Objective: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants. Design: Patients from six EoE‐centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro‐esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)‐histological, and molecular features were determined and compared with EoE, GERD, and healthy controls. Results: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE‐like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non‐specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed—in contrast to EoE—no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE‐typical Th2‐response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE‐like (characterized by eotaxin‐3 expression), non‐specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression). Conclusion: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype. [ABSTRACT FROM AUTHOR]

Keywords: 2,4,6-Tris(dimethylaminomethyl)phenol; CAS 90-72-2; epoxy resin; patch testing; tris-DMP EN 2,4,6-Tris(dimethylaminomethyl)phenol CAS 90-72-2 epoxy resin patch testing tris-DMP 316 318 3 03/15/23 20230401 NES 230401 2,4,6-Tris(dimethylaminomethyl)phenol (tris-DMP; CAS No. 90-72-2) is a hardener/accelerator frequently used in epoxy resin systems (ERS), especially at low ambient temperature.[1] First cases of contact sensitization to tris-DMP have been observed at the Finnish Institute of Occupational Health (FIOH) around 1990.[2] Since then, contact sensitization to tris-DMP has been described in several case reports from various European countries.[1] In the FIOH, 14 cases of contact sensitization to tris-DMP have been registered from 1991 to 2013, rendering it the second most frequent sensitizer among epoxy resin hardeners.[1] Since 2016, tris-DMP is available as patch test preparation at 0.5% in pet. from Chemotechnique, Vellinge, Sweden. However, 9 out of 14 FIOH patients (64%) sensitized to tris-DMP, but only 3 of the 28 tris-DMP positive IVDK patients (11%), were painters. DISCUSSION Consistent with the FIOH data,[1] we found sensitizations to tris-DMP less frequently than sensitizations to MXDA, but with a similar frequency as sensitizations to IPDA. [Extracted from the article]

Background: Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. Objectives: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet. Patients and Methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010–2019. Results: Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol‐positive patients, compared to benzyl alcohol‐negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases. Conclusions: Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful. [ABSTRACT FROM AUTHOR]

Basophils are primarily associated with a proinflammatory and immunoregulatory role in allergic diseases and parasitic infections. Recent studies have shown that basophils can also bind various bacteria both in the presence and the absence of opsonizing Abs. In this report, we show that both human and mouse basophils are able to produce mitochondrial reactive oxygen species and to form extracellular DNA traps upon IL-3 priming and subsequent activation of the complement factor 5 a receptor or FceRI. Such basophil extracellular traps (BETs) contain mitochondrial, but not nuclear DNA, as well as the granule proteins basogranulin and mouse mast cell protease 8. BET formation occurs despite the absence of any functional NADPH oxidase in basophils. BETs can be found in both human and mouse inflamed tissues, suggesting that they also play a role under in vivo inflammatory conditions. Taken together, these findings suggest that basophils exert direct innate immune effector functions in the extracellular space. [ABSTRACT FROM AUTHOR]

Of 131 patch-test positive patients, 24 (18.3%) reacted to both preparations, 98 (74.8%) to FMI only, and 9 (6.9%) to OM and not to FMI, although OM is a constituent of FMI. Keywords: allergic contact dermatitis; delayed reactions; fragrance; fragrance mix I; late reactions; oak moss absolute; patch test; patch test active sensitization EN allergic contact dermatitis delayed reactions fragrance fragrance mix I late reactions oak moss absolute patch test patch test active sensitization 54 57 4 12/17/21 20220101 NES 220101 Patch test reactions that become positive de novo at around day 7 (D7) are called "late" patch test reactions,1 and are frequently seen after patch testing neomycin, for example.2 Reactions beyond D7 ("very late reactions") may indicate active sensitization.1,3 However, very late reactions (2 to 4 weeks after patch testing) without being linked to active sensitization have also been observed.4-6 We were interested in very late reactions (beyond D7) in patch testing fragrance mix I (FMI) and oak moss absolute (OM). Regarding all positive reactions, 11/136 (8.1%) of FMI-positive patients and 11/45 (24.4%) of OM-positive patients showed very late reactions (Table 1). 1 TABLEResults of reading fragrance mix I (FMI) and oak moss absolute (OM) in n = 1789 patients at different points of time HT