Project description:Canine atopic dermatitis (cAD) is a chronic and recurrent inflammatory and pruritic skin disease in dogs. Currently, allergen-specific immunotherapy (ASIT) is the only identified disease-modifying intervention for allergic diseases. It decreases the symptoms triggered by allergens and prevents recurrence of the disease in the long-term. The aim of our research was to determine how immunotherapy changes the proportion of lymphocyte subsets in dog peripheral blood and the levels of cytokines secreted by these cells during therapy. ASIT was applied for 6 months. Blood samples for further analyses were collected from patients in the third and sixth month of immunotherapy. Six out of seven dogs receiving ASIT showed a positive effect. A reduction in cytokine levels (IL-13, TNF-α) in peripheral blood of cAD patients and changes in the number of specific T cell subpopulations-reduction of Tc cells (CD8+) and increase of activated T cells (CD3+CD25+)-confirmed the beneficial effect of the applied ASIT. In addition, a significantly higher percentage of Treg cells (CD4+CD25+FOXP3+) was noted in cAD patients before treatment compared to healthy dogs. After 3 months of therapy, the percentage of Tregs significantly decreased, and after 6 months, it increased significantly again.
Project description:BACKGROUND:Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES:To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS:Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS:A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS:This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).
Project description:Background: Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Results: We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusion: Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Skin biopsies from normal ('normal') and lesional and patch-tested ('leisonal') skin from Atopic eczema patients sensitized to Malassezia sympodialis Organism Part: location of skin biopsy Keywords: disease state analysis
Project description:BackgroundAtopic eczema is an inflammatory skin condition, with a similar impact on health-related quality of life as other chronic diseases. Increasing pressures on resources within the National Health Service increase the importance of having good economic evidence to inform their allocation.ObjectivesTo educate dermatologists about economic methods with reference to currently available economic evidence on eczema.MethodsThe role of different types of economic evidence is illustrated by evidence found in a systematic literature search conducted across 12 online databases up to 22 May 2017. Primary empirical studies either reporting the results of a cost-of-illness study or evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema were included. Two reviewers independently assessed studies for eligibility and performed data abstraction, with disagreements resolved by a third reviewer. Evidence tables of results were produced for narrative discussion. The reporting quality of economic evaluations was assessed.ResultsSeventy-eight studies (described in 80 papers) were deemed eligible. Thirty-three (42%) were judged to be economic evaluations, 12 (15%) cost analyses, six (8%) utility analyses, 26 (33%) cost-of-illness studies and one a feasibility study (1%). The calcineurin inhibitors tacrolimus and pimecrolimus, as well as barrier creams, had the most economic evidence available. Partially hydrolysed infant formula was the most commonly evaluated prevention.ConclusionsThe current level of economic evidence for interventions aimed at preventing and treating eczema is limited compared with that available for clinical outcomes, suggesting that greater collaboration between clinicians and economists might be beneficial.
Project description:The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines.In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule.Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines.
Project description:The lack of standardized nomenclature for atopic dermatitis (AD) creates unnecessary confusion for patients, healthcare providers, and researchers. It also negatively impacts accurate communication of research in the scientific literature. We sought to determine the most commonly used terms for AD.A systematic review of the MEDLINE, EMBASE, and LILACS (1945-2016) for the terms AD, atopic eczema (AE), and multiple other eczematous disorders.In MEDLINE, 33 060 were identified, of which 21 299 (64.4%) publications used the term 'AD', 15 510 (46.9%) 'eczema', and only 2471 (7.5%) AE. Most of these publications used the term AD (82.0%) or eczema (70.8%) without additional nomenclature; only 1.2% used AE alone. Few publications used the terminology 'childhood eczema', 'flexural eczema', 'infantile eczema', 'atopic neurodermatitis', or 'Besnier's prurigo'. AD was rarely used until the late 1970s, after which it became the most commonly used of the three terms and continuously increased until 2015. Atopic eczema decreased between 2008 and 2015. Atopic dermatitis was the most commonly used term in studies across almost all publication types, languages, and journals.Atopic dermatitis is the most commonly used term and appears to be increasing in popularity. Given that eczema is a nonspecific term that describes the morphological appearance of several forms of dermatitis, we strongly suggest the use of a more specific term, AD, in publications, healthcare clinician training, and patient education. Support from researchers, reviewers, and editors is key to success.
Project description:Background: Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Results: We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusion: Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Skin biopsies from normal ('normal') and lesional and patch-tested ('leisonal') skin from Atopic eczema patients sensitized to Malassezia sympodialis Organism Part: location of skin biopsy Keywords: disease state analysis Computed