Japanese guidelines for atopic dermatitis 2020.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice

Variants of C-C Motif Chemokine 22 (CCL22) Are Associated with Susceptibility to Atopic Dermatitis: Case-Control Studies

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD

Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site

ABSTRACT Atopic dermatitis (AD) shows frequent recurrence. Staphylococcus aureus is the primary microbial component in AD and is associated with disease activity. However, traditional typing methods have failed to characterize virulent AD isolates at the clone level. We conducted a comprehensive genomic characterization of S. aureus strains isolated from the skin of AD patients and healthy donors, comparing the whole-genome sequences of the 261 isolates with anatomical and lesional (AD-A)/nonlesional (AD-NL)/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. Sequence type (ST) diversity was lost with worsening disease activity; ST188 was the most frequently detected ST in AD-A and had the strongest correlation with AD according to the culture rate and proportion with worsening disease activity. ST188 and ST20 isolates inhabited all skin conditions, with significantly higher proportions in AD skin than in healthy skin. ST8, ST15, and ST5 proportions were equivalent for all skin conditions; ST30 was detected only in healthy skin; and ST12 was detected only in AD skin. ST97 detected in AD-A and healthy skin was clearly branched into two subclades, designated ST97A and ST97H. A comparison of two genomes led to the discovery that only ST97A possessed the complete trp operon, enabling bacterial survival without exogenous tryptophan (Trp) on AD skin, where the Trp level was significantly reduced. Primary STs showing an AD skin inhabitation trend (ST188, ST97A, ST20, and ST12) were all trp operon positive. The predominant clones (ST188 and ST97) possessed almost no enterotoxin genes, no mecA gene, and few other antimicrobial resistance genes, different from the trend observed in Europe/North America. IMPORTANCE While Staphylococcus aureus is a member of the normal human skin flora, its strong association with the onset of atopic dermatitis (AD) has been suggested. However, previous studies failed to assign specific clones relevant to disease activities. Enterotoxins produced by S. aureus have been suggested to aggravate and exacerbate the inflammation of AD skin, but their role remains ambiguous. We conducted a nuanced comprehensive characterization of isolates from AD patients and healthy donors, comparing the whole-genome sequences of the isolates with anatomical and lesional/nonlesional/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. We demonstrate that specific clones are associated with disease severity and clinical manifestations, and the dominant clones are devoid of enterotoxin genes and antimicrobial resistance genes. These findings undermine the established notion of the pathophysiological function of S. aureus associated with AD and introduce a new concept of S. aureus colonization in AD

Inflammation-free, gas-permeable, lightweight, stretchable on-skin electronics with nanomeshes

Thin-film electronic devices can be integrated with skin for health monitoring and/or for interfacing with machines. Minimal invasiveness is highly desirable when applying wearable electronics directly onto human skin. However, manufacturing such on-skin electronics on planar substrates results in limited gas permeability. Therefore, it is necessary to systematically investigate their long-term physiological and psychological effects. As a demonstration of substrate-free electronics, here we show the successful fabrication of inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time, realized with a conductive nanomesh structure. A one-week skin patch test revealed that the risk of inflammation caused by on-skin sensors can be significantly suppressed by using the nanomesh sensors. Furthermore, a wireless system that can detect touch, temperature and pressure is successfully demonstrated using a nanomesh with excellent mechanical durability. In addition, electromyogram recordings were successfully taken with minimal discomfort to the user.1