Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.
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ABSTRACT:
SUBMITTER: Ma X
PROVIDER: S-EPMC9301047 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Atopic dermatitis (AD) is the most common atopic disease in young children and most common skin disease in childhood. In the Polish population, the incidence of AD in the group of children aged 6-14 is about 4% and it is underestimated. The disease is chronic and recurrent, and the leading symptom is skin pruritus that in the mechanism of the vicious circle is accompanied by scratching that causes generalized infections. The overall problems lead to a decrease in the quality of life of the child and its parents and to an increased risk of psychosomatic diseases. The complex pathomechanism of AD is due to chronic inflammation of the skin, in which various cell phenotypes are involved. The management is comprehensive and it is aimed at reducing inflammation, improving the skin barrier function, reducing the symptoms of dryness and itching of the skin and secondarily improving the quality of life. The treatment includes intensive skincare, anti-inflammatory treatment based on the proactive use of topical glucocorticosteroids and topical calcineurin inhibitors. Periods of exacerbation of lesions require intensified treatment. In particularly severe, recurrent cases, treatment options can be extended to systemic immunosuppressive drugs, with awareness of their adverse effects. Previous year has brought significant progress in the current treatment of AD in the form of biological treatment. Cytokines and other mediators that play an important role in the pathogenesis of skin inflammation have become a target for new forms of therapy. Drugs for which interleukin (IL)-4 and IL-13 are the targets are particularly represented. Dupilumab is the first biological drug approved for the general treatment of children aged >12 years with moderate to severe AD. Another therapeutic option for topical use is crisaborole, a phosphodiesterase-4 inhibitor. This study presents the current state of research on biological drugs in AD.
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Project description:Atopic dermatitis (AD) is an inflammatory skin disorder affecting up to 20% of the paediatric population worldwide. AD patients commonly exhibit dry skin and pruritus and are at a higher risk for developing asthma as well as allergic rhinitis. Filaggrin loss-of-function variants are the most widely replicated genetic risk factor among >40 genes associated with AD susceptibility. The prevalence of AD has tripled in the past 30 years in industrial countries around the world. This urgent public health issue has prompted the field to more thoroughly investigate the mechanisms that underlie AD pathogenesis amidst environmental exposures. Epigenetics is the study of heritable, yet reversible, modifications to the genome that affect gene expression. The past decade has seen an emergence of exciting studies identifying a role for epigenetic regulation associated with AD and at the interface of environmental factors. Such epigenetic studies have been empowered by sequencing technologies and human genome variation and epigenome maps. miRNAs that post-transcriptionally modify gene expression and circRNAs have also been discovered to be associated with AD. Here, we review our current understanding of epigenetics associated with atopic dermatitis. We discuss studies identifying distinct DNA methylation changes in keratinocytes and T cells, eQTLs as DNA methylation switches that impact gene expression, and histone modification changes associated with AD-related microbial dysbiosis. We further highlight the need for integrative and collaborative analyses to elucidate the impact of these epigenetic findings as potential drivers for AD pathogenesis and the translation of this new knowledge to develop newer targeted treatments.
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