Treat-to-target in dermatology:A scoping review and International Eczema Council survey on the approach in atopic dermatitis

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.</p

Skin resident T cells producing TNFalfa but not TH1, TH2, or Th17 cytokines: their posible role as immune sentinels in skin.

ABSTRACT BODY: The skin of a normal individual contains nearly 20 billion memory T cells, nearly twice as many as are present in the circulation. These T cells are polarized effector memory T cells that, from our current understanding, have arisen from recognition of their antigens within the skin. We previously reported that human skin contains significant numbers Th1, Th17 and Th2 cells. We report now that these T cell subsets are quiescent with respect to cytokine production when isolated from unstimulated skin and that additional signals (e.g., cellular proliferation) are required to unlock cytokine production. TNFα is a cytokine produced by both APC and subsets of effector T cells. We describe here a novel and previously undescribed population of skin resident T cells that produces TNFα alone, without concurrent production of IFNγ, IL-4 or IL-17. These cells comprise a mean 48% of the skin T cells resident in normal human skin. These T cells are CD45RO+ memory T cells, express CLA, CCR4 and CCR6 and have a diverse TCR repertoire. This T cell subset differs from the other cutaneous effector T cells in that half of these cells produce TNFα upon TCR triggering without a requirement for additional activating signals. TNFα T cells are the most numerous subset in normal human skin, outnumbering Th1, Th2 and Th17 T cells. TNFα has pleiotropic effects in the skin. TNFα induces maturation of dendritic cells, enhancing antigen presentation, and induces endothelial activation and chemokine production, leading to enhanced leukocyte recruitment. Skin TNFα T cells, specific for pathogens previously encountered in skin, may serve as antigen-specific immune sentinels. These T cells have the ability to rapidly produce TNFα upon re-exposure to cognate antigen, leading to activation and recruitment of both innate immune cells and other T cell subsets. Thus, they may serve to both initiate and amplify immune responses in skin

New Developments in Biomarkers for Atopic Dermatitis

The application of biomarkers in medicine is evolving. Biomarkers do not only give us a better understanding of pathogenesis, but also increase treatment efficacy and safety, further enabling more precise clinical care. This paper focuses on the current use of biomarkers in atopic dermatitis, new developments and future perspectives. Biomarkers can be used for many different purposes, including the objective determination of disease severity, confirmation of clinical diagnosis, and to predict response to treatment. In atopic dermatitis, many biomarkers have been investigated as a marker for disease severity. Currently serum thymus and activation-regulated chemokine (TARC) is the superior biomarker for assessing disease severity. However, we have recently shown that the use of a panel of serum biomarkers is more suitable for assessing disease severity than an individual biomarker. In this overview, we will discuss alternative sources for biomarkers, such as saliva and capillary blood, which can increase the user friendliness of biomarkers in atopic dermatitis (AD). Both methods offer simple, non-invasive and cost effective alternatives to venous blood. This provides great translational and clinical potential. Biomarkers will play an increasingly important role in AD research and personalized medicine. The use of biomarkers will enhance the efficacy of AD treatment by facilitating the individualization of therapy targeting the patients' specific biological signature and also by providing tools for predicting and monitoring of therapeutic response

New Developments in Biomarkers for Atopic Dermatitis

The application of biomarkers in medicine is evolving. Biomarkers do not only give us a better understanding of pathogenesis, but also increase treatment efficacy and safety, further enabling more precise clinical care. This paper focuses on the current use of biomarkers in atopic dermatitis, new developments and future perspectives. Biomarkers can be used for many different purposes, including the objective determination of disease severity, confirmation of clinical diagnosis, and to predict response to treatment. In atopic dermatitis, many biomarkers have been investigated as a marker for disease severity. Currently serum thymus and activation-regulated chemokine (TARC) is the superior biomarker for assessing disease severity. However, we have recently shown that the use of a panel of serum biomarkers is more suitable for assessing disease severity than an individual biomarker. In this overview, we will discuss alternative sources for biomarkers, such as saliva and capillary blood, which can increase the user friendliness of biomarkers in atopic dermatitis (AD). Both methods offer simple, non-invasive and cost effective alternatives to venous blood. This provides great translational and clinical potential. Biomarkers will play an increasingly important role in AD research and personalized medicine. The use of biomarkers will enhance the efficacy of AD treatment by facilitating the individualization of therapy targeting the patients’ specific biological signature and also by providing tools for predicting and monitoring of therapeutic response

Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell- attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis

BACKGROUND: Tissue infiltration of CD4(+) T cells plays an important role in the pathogenesis of allergic diseases. T-cell trafficking is mediated by specific chemokines and their receptors. OBJECTIVE: The purpose of this study was to investigate the participation of the chemokines thymus and activation-regulated chemokine (TARC) and cutaneous T cell-attracting chemokine (CTACK) in a large population of patients with allergic diseases. METHODS: Serum TARC and CTACK levels were measured in 455 patients with allergic disease. Patients were characterized as having atopic dermatitis (AD), allergic asthma, allergic rhinitis, or combinations or as healthy control subjects. Serum TARC and CTACK levels were correlated with disease activity in patients with AD. Furthermore, in 7 patients with AD, serum TARC and CTACK levels were studied after the start of systemic cyclosporin A treatment. Finally, TARC and CTACK localization was checked by immunohistochemistry in lesional skin biopsy specimens of patients with AD. RESULTS: Both TARC and CTACK serum levels in patients with AD were significantly higher than those in healthy control subjects and patients with allergic respiratory disease. Furthermore, serum TARC and CTACK levels significantly correlated with disease activity in patients with AD. Serum TARC levels paralleled clinical improvement in patients treated with cyclosporin A. Immunoreactive TARC was found in infiltrating cells and endothelial cells of the dermis but not in epidermal cells. CONCLUSIONS: The serum TARC level is an objective parameter for disease severity specific for AD. Furthermore, it is a promising tool for treatment monitorin