Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis

Zhou, Lisa; Leonard, Alexandra; Pavel, Ana B.; Malik, Kunal; Raja, Aishwarya; Glickman, Jacob W.; Estrada, Yeriel; Peng, Xiangyu; Duca, Ester Del; Sanz-Cabanillas, Juan Luís; Ruano, Juan; Xu, Hui; Zhang, Ning; Wen, Huei‐Chi; Gonzalez, Juana; Garcet, Sandra; Krueger, James G.; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2019.01.015

Cited by 106 publications

(124 citation statements)

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“…In addition, the results start to define age-specific differences between pediatric patients with AD and age-matched control subjects as a complement to our recent data showing differences between elderly versus young AD adult endotypes. 3 Our data suggest that even adolescents have a different profile from adults, possibly contributing to the somewhat lower response to the recently approved IL-4 receptor a antagonist dupilumab in adolescents versus adults. 30,31 Immune responses at birth are immature, 10 with decreases in frequencies of naive T cells in healthy children with increasing age paralleled by increases in Tcm/Tem cell counts.…”

Section: Discussionmentioning

confidence: 68%

“…83 Additionally, AD has a highly varied endotype repertoire, with different immune polarizations. 3,84,85 Despite common features, particularly increased T H 2 expression, AD is endotypically different across ages, and treatments should be tailored to the unique age endotype. Although one could hypothesize that the immune changes merely reflect developmental phenomena that are age related, the lack of clear clustering in control subjects implicates AD as the driver of the distinct, progressive, age-related endotypic characteristics rather than age alone.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, 85% of patients with atopic dermatitis (AD) present before 5 years of age. 2 Although young adults have a different AD phenotype from elderly patients, 3 immune changes in patients with AD between early childhood and adulthood are unknown. 4 Blood studies that dissect developmental changes from infancy through adulthood are limited and primarily focused on T H 1/T H 2 subsets.…”

Section: Il-9mentioning

confidence: 99%

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Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Czarnowicki

Canter

et al. 2020

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Il-9mentioning

confidence: 99%

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Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Czarnowicki

Canter

et al. 2020

Journal of Allergy and Clinical Immunology

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“…In elderly AD, phenotypic analyses of peripheral blood cytokine concentrations demonstrated the dominance of a Th2 cytokine profile, i.e., IL-4, IL-5, and IL-13, in older patients with IgE-allergic AD, whereas dominance of a Th1 cytokine profile, i.e., IFN-γ, was observed in older patients with AD and low serum total IgE levels [6]. In a recent study on age-specific changes in the molecular phenotype of patients with AD, serum total IgE levels and eosinophil counts were negatively correlated with age in patients with AD, and patients with elderly AD tended to show immune skewing with decreased Th2 and Th22 cytokines and increased Th1 cytokines in lesional skin compared with patients with adult AD [9]. The participation and role of allergen-specific IgEs in the development of skin lesions of AD has been controversial [26], but immunohistopathological analysis in our previous studies indicated that, at least in patients with IgE-allergic elderly AD, IgE-mediated allergic inflammation (composed of IgE-bearing cells, including mast cells, dermal dendritic cells, inflammatory dendritic epidermal cells, and Langerhans cells) accompanied by specific allergens (e.g., HDMs) play a critical role in the features of skin lesions [7,16,21].…”

Section: Histopathology and Pathophysiology Of Skin Lesionsmentioning

confidence: 97%

“…However, the paradigm has recently changed. The number of cases of AD remaining or first appearing in adulthood [4,5], and even in older adults [3,6], have increased and the characteristics of elderly AD have become apparent [7][8][9][10]. Hence, this newly defined subgroup of elderly AD (age > 60 or ≥ 60 years) was recently added into the classification of AD as a fourth subtype [11,12].…”

Section: Introductionmentioning

confidence: 99%

Atopic Dermatitis in Older Adults: A Review of Treatment Options

Tanei

2020

Drugs Aging

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Atopic dermatitis (AD) in older adults (elderly AD) has recently emerged as a newly defined subgroup of AD. When selecting treatment options, clinical characteristics of elderly AD and age-specific factors of older patients must be considered. As in other age groups, regular application of moisturizers in combination with topical corticosteroids and calcineurin inhibitors, adjunctive administration of oral antihistamines/anti-allergic drugs, and avoidance of exacerbating factors comprise basic treatments for elderly AD. For moderate-to-severe cases and/or in those with a decreased ability to use topical treatments, powerful anti-inflammatory treatments may become necessary as additional treatment options. While low-dose oral corticosteroids may be useful for cases of elderly AD, careful attention should be paid to adverse effects. Oral cyclosporine (ciclosporin) is less commonly used due to the increased risk of malignancy and organ toxicity in older patients with AD.

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Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis

et al. 2019

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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...

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Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis

Cited by 106 publications

References 73 publications

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Atopic Dermatitis in Older Adults: A Review of Treatment Options

Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis

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