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Characterization of the effects on pruritus by novel treatments for atopic dermatitis.

Chronic pruritus is a common and debilitating symptom in patients with atopic dermatitis and contributes to impairment of quality of life. Effective treatment of pruritus should therefore be one of the main treatment goals in patients with atopic dermatitis. Pathophysiologically, the histamine-independent pruritogens interleukin-31, interleukin-13, and interleukin-4, have been shown to play a major role in atopic dermatitis. All three cytokines can mediate chronic pruritus via Janus kinase 1/2 signaling pathways. Novel drugs target these pathways and have shown rapid and sustained reduction of pruritus in patients with atopic dermatitis in clinical use and in phase II and III clinical trials. Here we summarize the published data on the effects of these drugs on itch parameters such as overall reduction in pruritus intensity and percent of patients with atopic dermatitis achieving a relevant reduction in itch. Each of the novel drugs shows very good effects on pruritus. These data offer hope for an even better and possibly more specific treatment of pruritus in patients with atopic dermatitis in the future. In addition, the different pharmacological approaches give us the chance to learn more about the pathophysiology of pruritus in atopic dermatitis.

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Deacetylasperulosidic Acid Ameliorates Pruritus, Immune Imbalance, and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice.

The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.

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Multilineage-differentiating stress-enduring cells alleviate atopic dermatitis-associated behaviors in mice.

Pruritus is a recurring, long-lasting skin disease with few effective treatments. Many patients have unsatisfactory responses to currently available antipruritic treatments, and effective therapeutics are urgently needed to relieve symptoms. A previous study reported that mesenchymal stem cell (MSC)-mediated immune regulation could be used to treat skin inflammatory diseases. Multilineage-differentiating stress-enduring (Muse) cells are a new type of pluripotent stem cell that may also have the potential to treat inflammatory skin diseases.

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Treatment Outcomes Associated With Dupilumab Use in Patients With Atopic Dermatitis: 1-Year Results From the RELIEVE-AD Study.

Clinical trial populations may not reflect clinical practice: knowledge generated in other settings can inform clinical decision-making.

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Worst Itch Numerical Rating Scale for Prurigo Nodularis: A Psychometric Evaluation.

Study TR03 evaluated the safety and efficacy of nalbuphine ER for prurigo nodularis (PN) (NCT02174419).

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The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds.

Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish.

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Role of TRP Ion Channels in Pruritus.

The transient receptor potential (TRP) channel superfamily responds to various physical, chemical, and environmental stimuli including the detection of sensations both harmful and non-harmful. Among these sensations is pruritus, or itch. There are at least 27 different TRP channels and about six of them are involved in pruriception. The function of these six receptors is primarily seen in the skin and the dorsal root ganglia. Identification and biological insights provided by these receptors in pruriception is important for human health as mutations and activations of many of these channels cause discomfort and disease. This review will focus on involvement of TRP channels in pruriception that may render these channels as the targets of many antagonistic topical medications, which may help patients' better cope with the pruritus that results from various cutaneous and systemic diseases.

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DMSO: an aid to combat pain and pruritus.

Dimethyl sulfoxide (DMSO) is a highly reactive by-product of paper production in the form of an odorless, colorless liquid that has been studied since the 1860s. Initially it was utilized as a solvent, but more recently it is being investigated for therapeutic applications. Owing to its versatility, the use of DMSO has been proposed in many different medical fields for a variety of applications, with possibly the widest use being in the field of dermatology. The clinical interest in the use of DMSO for dermatology conditions stems from this solution's efficacy as a vehicle to deliver pharmacological agents across the stratum corneum and its ability to penetrate biological membranes. Currently there is only one FDA approval for the use of DMSO, and it is not in the dermatologic field but rather for interstitial cystitis. Outside of the FDA scope of usage, DMSO is used frequently to treat osteoarthritis in humans and animals, as well as other chronic pain conditions. This suggests the possible utility of DMSO being applicable to other inflammatory conditions such as pruritus. Further research is necessary to explore the promising utilization opportunities of DMSO in dermatology.

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Symptoms of Depression and Anxiety are Associated with Poorer Functional Outcomes in Chronic Pruritus.

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Estrogens influence female itch sensitivity via the spinal gastrin-releasing peptide receptor neurons.

There are sex differences in somatosensory sensitivity. Circulating estrogens appear to have a pronociceptive effect that explains why females are reported to be more sensitive to pain than males. Although itch symptoms develop during pregnancy in many women, the underlying mechanism of female-specific pruritus is unknown. Here, we demonstrate that estradiol, but not progesterone, enhances histamine-evoked scratching behavior indicative of itch in female rats. Estradiol increased the expression of the spinal itch mediator, gastrin-releasing peptide (GRP), and increased the histamine-evoked activity of itch-processing neurons that express the GRP receptor (GRPR) in the spinal dorsal horn. The enhancement of itch behavior by estradiol was suppressed by intrathecal administration of a GRPR blocker. In vivo electrophysiological analysis showed that estradiol increased the histamine-evoked firing frequency and prolonged the response of spinal GRP-sensitive neurons in female rats. On the other hand, estradiol did not affect the threshold of noxious thermal pain and decreased touch sensitivity, indicating that estradiol separately affects itch, pain, and touch modalities. Thus, estrogens selectively enhance histamine-evoked itch in females via the spinal GRP/GRPR system. This may explain why itch sensation varies with estrogen levels and provides a basis for treating itch in females by targeting GRPR.

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