IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURES Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS 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 (T H 2; IL-4, IL-13, and chemokines CCL17 and CCL26), and T H 17/T H 22 (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 T H 2 (IL-33 and IL-4R) and T H 17/T H 22 (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). CONCLUSIONS AND RELEVANCE In this study, tape strips provide a minimally invasive alte...
Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis To the Editor:Atopic dermatitis (AD) affects 3% to 10% of adults. 1 Recently, the increased understanding of AD pathogenesis has led to development of new treatments, including dupilumab, the first US Food and Drug Administration-approved biologic for moderate-to-severe AD. Although T H 2 skewing is common across all AD subtypes, as suggested by the efficacy of dupilumab across populations with AD, it is a highly heterogeneous disease with diverse subtypes characterized by varying immune activation, perhaps requiring additional therapeutic approaches. 2,3 Recent studies have shown increased T H 17 skewing in several AD subtypes, including intrinsic, 3 Asian, 2 and pediatric AD, 4 and have also shown that T H 17-related markers are significantly correlated with AD severity. [2][3][4] An Asian patient with AD demonstrated clinical and tissue improvement with secukinumab, a selective IL-17A inhibitor. 5 However, controlled trials with IL-17 antagonists in patients with moderate-to-severe AD (including T H 17-high subtypes) are FIG 1. Epidermal thickness, epidermal hyperplasia markers, and clinical outcomes. A-C, Box plots depicting fold change (FCH) in epidermal thickness (A), Ki67 level (B), and K16 level (C) in lesional skin at week 4 (W4) and W16 versus at baseline (BL) (W0); red stars indicate significance of comparison with baseline. 1 P < .1 and **P < .01. D and E, Mean percentage change 6 SEM for the Scoring Atopic Dermatitis (SCORAD) (D) and the Eczema Area and Severity Index (EASI) (E) scores in all patients with AD receiving secukinumab or placebo from baseline to W16. Red and blue numbers in (D) and (E) represent numbers of patients receiving secukinumab and placebo remaining at each time point, respectively.
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