Intrinsic Effects of Exposome in Atopic Dermatitis: Genomics, Epigenomics and Regulatory Layers

Abstract

Atopic dermatitis (AD) or atopic eczema is an increasingly manifested inflammatory skin disorder of complex etiology which is modulated by both extrinsic and intrinsic factors. The exposome includes a person’s lifetime exposures and their effects. We recently reviewed the extrinsic exposome’s environmental risk factors that contribute to AD. The periods of pregnancy, infancy, and teenage years are recognized as crucial stages in the formation of AD, where the exposome leads to enduring impacts on the immune system. However, research is now focusing on the interactions between intrinsic pathways that are modulated by the extrinsic exposome, including genetic variation, epigenetic modifications, and signals, such as diet, stress, and microbiome interactions. As a result, immune dysregulation, barrier dysfunction, hormonal fluctuations, and skin microbiome dysbiosis are important factors contributing to AD development, and their in-depth understanding is crucial not only for AD treatment but also for similar inflammatory disorders.

Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis

“…The consistency of these findings across European and Asian populations highlights the universal importance of FLG in maintaining skin homeostasis and its relevance in AD [112]. The presence of significant heterogeneity concerning FLG rs558269137 and rs61816761 in European population was also observed in a prior meta-analysis of FLG polymorphisms in AD [113], which could be attributed to several demographic factors and environmental exposures that mediate the increased atopic eczema risk [111]. We further validate the 11q13.5 rs7927894 SNP as a risk locus, a variant localized within a non-coding genomic region.…”

“…The present meta-analysis confirms the pivotal role of the FLG locus in disease susceptibility, as LOF mutations disrupt the production of the filaggrin protein in the stratum corneum. The impaired barrier function facilitates loss of water, pH increase as well as the entry of irritants and allergens, contributing to the onset and exacerbation of allergic reactions [111]. The consistency of these findings across European and Asian populations highlights the universal importance of FLG in maintaining skin homeostasis and its relevance in AD [112].…”

“…In addition, discrepancies between the available data derived from the included studies, with the exemplars of disease activity, age of onset and relevant clinical information restricted further stratification and subgroup examination in our analysis. The predominant role of the exposome in the AD predisposition [111], and inclusion of such environmental risk factors in multivariate analyses is of paramount importance to gain a holistic understanding of AD etiopathology and thus unveil novel therapeutic targets.…”

The impact of glucocorticoids therapy on cutaneous wounds in Kawasaki disease: A meta‐analysis of randomized controlled trials

“…In KD, a diverse array of cutaneous manifestations contributes to the intricate clinical landscape of the disease. 7 Skin wounds characteristic of KD encompass an erythematous rash, desquamation and indurated edema. 8 The erythematous rash, initially diffuse and commonly appearing on the trunk, extremities and perineal region, exhibits a polymorphous nature, ranging from macular to morbilliform in appearance.…”

“…In KD, a diverse array of cutaneous manifestations contributes to the intricate clinical landscape of the disease 7 . Skin wounds characteristic of KD encompass an erythematous rash, desquamation and indurated edema 8 .…”