Atopic dermatitis (AD) is a common inflammatory skin disease highly attributable to genetic factors. Here, we report results from a genome-wide meta-analysis of AD in 37,541 cases and 1,056,519 controls with data from the FinnGen project, the Estonian Biobank, the UK Biobank, the EAGLE Consortium, and the BioBank Japan. We detected 77 independent AD-associated loci of which 10 were to our knowledge previously unreported. The associated loci showed enrichment in various immune regulatory processes ..read more

Loss-of-function (LoF) variants resulting in stop codons in FLG are causative for ichthyosis vulgaris (IV) (Smith et al, 2006). FLG LoF is also a major risk factor for developing atopic dermatitis (AD) (Palmer et al, 2006). However, reports of mild AD in compound heterozygote individuals suggest that these LoF may be in cis (same allele) and the other allele to be normal. To further complicate FLG genetics, each FLG allele is comprised of either 10, 11, or 12 repeats, with each additional repeat decreasing the odds of AD (Brown et al, 2012 ..read more

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A compromised permeability barrier is a hallmark of atopic dermatitis (AD). Localized to the outermost skin layer, the stratum corneum (SC) is critically dependent on terminal differentiation of epidermal keratinocytes, which transform into protein-rich corneocytes surrounded by extracellular lamellae of unique epidermal lipids, conferring permeability barrier function. These structures are disrupted in AD. A leaky barrier is prone to environmental insult, which in AD elicits type 2–dominant inflammation, in turn resulting in a vicious cycle further impairing the SC structure ..read more

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The progress in our understanding of atopic dermatitis (AD) (atopic eczema) in the last 10 years has been remarkable. Nearly half of the scientific papers ever published on AD have been written in the last 10 years. This contribution of knowledge, in parallel with technological and pharmaceutical progress, has transformed our ability to treat some of the most severe forms of AD. Notably, we have seen the advent of biologics such as the anti–IL-4 receptor biologic dupilumab (Simpson et al, 2016), 2 anti–IL-13 agents (tralokinumab [Wollenberg et al, 2021] and lebrikizumab [Silverberg e ..read more

Cutaneous T-cell lymphomas (CTCLs) comprise an incurable form of non-Hodgkin lymphoma, and advanced-stage forms of this disease, mycosis fungoides and Sezary syndrome, have poor prognosis. Previous case series documented long-lasting remission due to a graft-versus-lymphoma effect in patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). In these studies, lymphoma relapse was common, and treatment-related morbidity and mortality were noted, leading to weaker recommendations for HSCT in this patient population ..read more

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Schuler et al penned an in-depth review of atopic dermatitis (AD) to describe the intersection between the genetic features, immunopathogenesis, environmental influences, and relationship to other atopic diseases. Heritability of this disease is as high as 80%, stemming from null sequence variants in the skin barrier protein FLG as well as other epidermis-related factors. Dysfunction of immune cells (T helper [Th]2 cells, dendritic cells, mast cells, basophils, and keratinocytes) and cytokines (IL-2, IL-4, and IL-13) has also been rigorously explored in AD ..read more

The epidermis is the body’s first line of protection against dehydration and pathogens, continually regenerating the outermost protective skin layers throughout life. During both embryonic development and wound healing, epidermal stem and progenitor cells must respond to external stimuli and insults to build, maintain, and repair the cutaneous barrier. Recent advances in CRISPR-based methods for cell lineage tracing have remarkably expanded the potential for experiments that track stem and progenitor cell proliferation and differentiation over the course of tissue and even organismal developme ..read more