Priority research questions in atopic dermatitis : an International Eczema Council eDelphi consensus

Recent advances in understanding the complex pathogenesis of atopic dermatitis (AD, also known as eczema or atopic eczema), coupled with the development of new treatments, have led to increased interest from multiple stakeholders. There is a need to prioritize areas for research to inform a coordinated approach to advancing science and patient care

Phosphodiesterase Inhibition by Ro 20-1724 Reduces Hyper-IgE Synthesis by Atopic Dermatitis Cells In Vitro

Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis spontaneously produce large amounts of IgE in vitro. These cells also show markedly elevated levels of cAMP phosphodiesterase (PDE) which may be responsible for the observed abnormal cAMP responsiveness. Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10-4 M and 10-5 M concentrations. There was a close correlation between PDE inhibition and inhibition of IgE synthesis, r = 0.93, p <0.05. To define the cellular target of the drug, we used monoclonal antibodies directed toward MNL subsets (Lyt 3, OKT8, OKT4, monocyte-myeloid) in a modified “panning” method to perform experiments with purified subsets. With untreated subsets, removal of OKT4-positive cells significantly reduced IgE synthesis; readdition of OKT4-positive cells enhanced IgE synthesis. OKT8 cells and monocytes did not affect IgE synthesis. Pretreatment of T cell-depleted MNL with Ho 20-1724 resulted in significantly more inhibition of IgE synthesis than did pretreatment of T enriched cells prior to recombination with the reciprocal untreated subset and subsequent culture. Similarly, pretreatment of monocyte-depleted cells resulted in significantly more inhibition of IgE synthesis than pretreatment of monocyte-enriched cells prior to recombination and culture. The majority of the effect appeared to be mediated by a direct effect on the B cells. However, some inhibition of IgE synthesis was also achieved through pretreatment of T enriched cells. Since pretreatment of isolated suppressor/cytotoxic or helper/inducer T-cell subsets did not give the same degree of inhibition as with unfractionated T cells, a T-T interaction may be involved in this aspect. The imidazolidinone derivative, Ro 20-1724, significantly and consistently inhibited both the elevated cAMP phophodiesterase activity and the elevated spontaneous IgE synthesis of MNL from patients with atopic dermatitis. These findings demonstrate a previously indescribed link between cAMP PDE levels and in vitro IgE synthesis

Air Pollution and Atopic Dermatitis, from Molecular Mechanisms to Population-Level Evidence: A Review

Atopic dermatitis (AD) has increased in prevalence to become the most common inflammatory skin condition globally, and geographic variation and migration studies suggest an important role for environmental triggers. Air pollution, especially due to industrialization and wildfires, may contribute to the development and exacerbation of AD. We provide a comprehensive, multidisciplinary review of existing molecular and epidemiologic studies on the associations of air pollutants and AD symptoms, prevalence, incidence, severity, and clinic visits. Cell and animal studies demonstrated that air pollutants contribute to AD symptoms and disease by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, initiating a proinflammatory response, and disrupting the skin barrier function. Epidemiologic studies overall report that air pollution is associated with AD among both children and adults, though the results are not consistent among cross-sectional studies. Studies on healthcare use for AD found positive correlations between medical visits for AD and air pollutants. As the air quality worsens in many areas globally, it is important to recognize how this can increase the risk for AD, to be aware of the increased demand for AD-related medical care, and to understand how to counsel patients regarding their skin health. Further research is needed to develop treatments that prevent or mitigate air pollution-related AD symptoms

Air Pollution and Atopic Dermatitis, from Molecular Mechanisms to Population-Level Evidence: A Review

Atopic dermatitis (AD) has increased in prevalence to become the most common inflammatory skin condition globally, and geographic variation and migration studies suggest an important role for environmental triggers. Air pollution, especially due to industrialization and wildfires, may contribute to the development and exacerbation of AD. We provide a comprehensive, multidisciplinary review of existing molecular and epidemiologic studies on the associations of air pollutants and AD symptoms, prevalence, incidence, severity, and clinic visits. Cell and animal studies demonstrated that air pollutants contribute to AD symptoms and disease by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, initiating a proinflammatory response, and disrupting the skin barrier function. Epidemiologic studies overall report that air pollution is associated with AD among both children and adults, though the results are not consistent among cross-sectional studies. Studies on healthcare use for AD found positive correlations between medical visits for AD and air pollutants. As the air quality worsens in many areas globally, it is important to recognize how this can increase the risk for AD, to be aware of the increased demand for AD-related medical care, and to understand how to counsel patients regarding their skin health. Further research is needed to develop treatments that prevent or mitigate air pollution-related AD symptoms

Breaking the cycle: how I manage difficult atopic dermatitis Romper o ciclo: minha conduta em casos difíceis de dermatite atópica

This review summarizes the general approach and philosophy of managing difficult atopic dermatitis. There are as many regimens as there are physicians, but too many fail to provide patients with adequate relief. This leads to the wasteful alternative - an allergy-seeking behavior that makes caring for these patients even more complicated. If we, as dermatologists, provide rational counseling on prevention and skin care along with effective, stable, anti-inflammatory therapy, our patients may stop seeking irrational approaches. The new flood of information relating to epidermal barrier provides a basis for seeking and treating xerotic conditions earlier during infancy with the hope that the increasing problems with atopic dermatitis and asthma may be lessened with simple and safe measures.<br>Esta revisão resume a abordagem geral e a filosofia na conduta de casos difíceis de dermatite atópica. Existe uma variedade de tratamentos, assim como de médicos, mas muitos falham e não propiciam um alívio adequado aos pacientes, o que leva a uma alternativa dispendiosa, ou seja, um atitude que visa procurar alergias e complica ainda mais o tratamento desses pacientes. Se nós, como dermatologistas, oferecermos um aconselhamento racional sobre prevenção e cuidados com a pele, junto com uma terapia antiinflamatória eficaz e estável, nossos pacientes irão parar de procurar abordagens irracionais. O novo fluxo de informações sobre a barreira epidérmica propicia uma base para investigar e tratar as doenças xeróticas em uma fase mais precoce durante o primeiro ano de vida, com a esperança de que os problemas crescentes relacionados à dermatite atópica e asma possam ser atenuados com medidas simples e seguras