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BACKGROUND: Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early-onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent-onset, moderate-to-severe AD using tape strips. METHODS: Sixteen tape strips were collected for RNA-seq profiling from 19 infants/toddlers (

BACKGROUND: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis/AD, but chronologic changes in blood of AD infants and children through adolescence have not been explored. OBJECTIVE: To compare immune activation and cytokine polarization in blood of 0–5y/o (n=39), 6–11y/o (n=26), 12–17y/o (n=21) and ≥18y/o (n=43) patients with AD vs. age-matched controls. METHODS: Flow cytometry was used to measure interferon-γ, interleukin (IL)-9, IL-13, IL-17, and IL-22 cytokines in CD4(+)/CD8(+) T-cells, with ICOS and HLA-DR defining mid- and long-term T-cell activation, respectively, within skin-homing/CLA(+) vs. systemic/CLA(−) T-cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. RESULTS: While CLA(+) Th1 frequencies were significantly lower in infants with AD vs. all older patients (P

BACKGROUND: Although atopic dermatitis (AD) often presents in infancy and persists into adulthood, comparative characterization of AD skin among different pediatric age groups is lacking. OBJECTIVE: We sought to define skin biopsy profiles of lesional and nonlesional AD across different age groups (0-5-year-old infants with disease duration

BACKGROUND Transepidermal water loss (TEWL) is a surrogate measure of skin barrier dysfunction. Historically, devices that measure TEWL are expensive, complex, and require connection to a computer and energy source. Consequently, measurement of skin's TEWL has been limited to the research setting. OBJECTIVES Evaluate the accuracy of the handheld device gpskin Barrier Light® in comparison with a standardly used device, AquaFlux AF200® , for measuring TEWL. METHODS Transepidermal water loss measurements by gpskin Barrier Light® and AquaFlux AF200® in ichthyotic and healthy skin were compared. RESULTS AquaFlux AF200® TEWL readings were consistently higher than those from gpskin Barrier Light® . In the pooled cohort, TEWL values were strongly correlated and both devices had excellent reliability. When subjects and controls were examined separately, there was moderate correlation between devices, with stronger agreement at higher TEWL values. LIMITATIONS Transepidermal water loss was determined at one time point. There is no formally established industry standard TEWL-assessing device. CONCLUSION Although gpskin Barrier Light® and AquaFlux AF200® devices cannot be used interchangeably, correlation in measuring TEWL was strong in patients with skin disease. This finding suggests that the low-cost, handheld device can accurately capture change in TEWL to track disease improvement.

PURPOSE: Localized autosomal recessive hypotrichosis (LAH) has been associated with pathogenic variants in DSG4, encoding a desmosomal protein as well as in LIPH and LPAR6, encoding respectively lipase H, which catalyzes the formation of 2-acyl-lysophosphatidic acid (LPA), and lysophosphatidic acid receptor 6, a receptor for LPA. LPA promotes hair growth and differentiation. In this study we aimed at delineating the genetic basis of LAH in patients without pathogenic variants in these three genes. METHODS: Variant analysis was conducted using exome and direct sequencing. We then performed quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence staining, immunoblotting, enzymatic, and coimmunoprecipitation assays to evaluate the consequences of potential etiologic variants. RESULTS: We identified homozygous variants in C3ORF52 in four individuals with LAH. C3ORF52 was found to be coexpressed with lipase H in the inner root sheath of the hair follicle and the two proteins were found to directly interact. The LAH-causing variants were associated with decreased C3ORF52 expression and resulted in markedly reduced lipase H–mediated LPA biosynthesis. CONCLUSION: LAH can be caused by abnormal function of at least three proteins which are necessary for proper LPA biosynthesis.

Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking.To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies.This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018.Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry.A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools).In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.