Events in Normal Skin Promote Early-Life Atopic Dermatitis—The MPAACH Cohort

Myers, Jocelyn M. Biagini; Sherenian, Michael G.; Kyzy, Asel Baatyrbek; Alarcón, Rubén; An, Amen; Flege, Zachary; Morgan, David; Gonzalez, Tammy; Stevens, Mariana L.; He, Hua; Kroner, John; Spagna, Daniel; Grashel, Brittany; Martin, Lisa J.; Herr, Andrew B.; Hershey, Gurjit K. Khurana

doi:10.1016/j.jaip.2020.03.048

Cited by 28 publications

(48 citation statements)

References 28 publications

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“…We tested the hypotheses that staphylococcal colonization and biofilm propensity are associated with increased AD severity. The presence of culturable S aureus on the subject's skin was associated with increased AD severity as defined by SCORAD ( P = .05) but was not significantly associated with TEWL, as previously described for the MPAACH study 55 (Figure 3A). The presence of S epidermidis had no significant associations with either SCORAD or TEWL (Table ).…”

Section: Resultssupporting

confidence: 71%

“…In the MPAACH cohort, we observed that both lesional and nonlesional FLG expression levels varied significantly with staphylococcal colonization pattern (Table ). As reported in a companion study, 55 the presence of S aureus was associated with decreased FLG expression levels in nonlesional and lesional skin. Furthermore, we show here that in the Spearman's rank correlation test, increased mean biofilm propensity of S aureus was associated with decreased nonlesional ( P = .02) and lesional ( P = .02) FLG expression (Table 2).…”

Section: Resultssupporting

confidence: 70%

“…Furthermore, FLG expression by keratinocytes is reduced in AD lesional skin, likely due to inflammatory cytokines including IL‐4, IL‐13, and IL‐31 62,63 . Colonization by S aureus is associated with decreased FLG expression in both nonlesional and lesional skin, 55 similar to the report by Clausen et al 64 that increased S aureus colonization was observed in AD patients with FLG mutations. These findings are consistent with results from a tissue culture model of human epidermis, in which knockdown of FLG expression led to increased colonization by S aureus 63 .…”

Section: Discussionsupporting

confidence: 68%

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Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort

Gonzalez

Stevens

Kyzy

et al. 2020

Allergy

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Background: Atopic dermatitis (AD) patients are often colonized with Staphylococcus aureus, and staphylococcal biofilms have been reported on adult AD skin lesions. The commensal S epidermidis can antagonize S aureus, although its role in AD is unclear. We sought to characterize S aureus and S epidermidis colonization and biofilm propensity and determine their associations with AD severity, barrier function, and epidermal gene expression in the first US early-life cohort of children with AD, the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH). Methods: The biofilm propensity of staphylococcal isolates was assessed by crystal violet assays. Gene expression of filaggrin and antimicrobial alarmins S100A8 and S100A9 was measured in keratinocyte RNA extracted from skin tape strips. Staphylococcal biofilms sampled from MPAACH skin were visualized using scanning electron microscopy. Results: Sixty-two percent of staphylococcal isolates (sampled from 400 subjects) formed moderate/strong biofilms. Sixty-eight percent of subjects co-colonized with both staphylococcal species exhibited strains that formed cooperative mixed-species biofilms. Scanning electron microscopy verified the presence of staphylococcal biofilms on the skin of MPAACH children. Staphylococcus aureus strains showing higher relative biofilm propensity compared with S epidermidis were associated with increased AD severity (P = .03) and increased lesional and nonlesional transepidermal water loss (P = .01, P = .03). Conclusions: Our data suggest a pathogenic role for S aureus biofilms in AD. We found that strain-level variation in staphylococcal isolates governs the interactions between | 303 GONZALEZ Et AL.

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Section: Resultssupporting

confidence: 71%

Section: Resultssupporting

confidence: 70%

Section: Discussionsupporting

confidence: 68%

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Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort

Gonzalez

Stevens

Kyzy

et al. 2020

Allergy

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“…The MPAACH study design and methods are discussed in full detail in the manuscripts by Biagini et al 24 and Kroner et al 25 ; for complete description, please refer to these manuscripts. Briefly, MPAACH subjects were identified from the electronic medical record at Cincinnati Children's Hospital Medical Center (CCHMC) or from the general public through direct advertising.…”

Section: Methodsmentioning

confidence: 99%

Sensitization to peanut, egg or pets is associated with skin barrier dysfunction in children with atopic dermatitis

Sherenian

Kothari

Biagini

et al. 2021

Clin Experimental Allergy

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Background: Children with atopic dermatitis (AD) are often sensitized to food and aeroallergens, but sensitization patterns have not been analysed with biologic measures of disease pathogenicity. Objective:We sought to define allergen sensitization grouping(s) using unbiased machine learning and determine their associations with skin filaggrin (FLG) and transepidermal water loss (TEWL) (assesses skin barrier integrity), S100A8 and S100A9 expression (assesses skin inflammation) and AD severity. Methods:We studied 400 children with AD in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort to identify groupings of food and aeroallergen sensitizations. MPAACH is a paediatric AD cohort, aged 1-2, recruited through hospital/community settings between 2016 and 2018. We analysed these groupings' associations with AD biomarkers: skin FLG, S100A8 and S100A9 expression, total IgE, TEWL and AD severity.Results: An unbiased machine learning approach revealed five allergen clusters. The most common cluster (N = 131), SPT PEP, had sensitization to peanut, egg and/or pets. Three low prevalence clusters, which included children with allergen sensitization other than peanut, egg or pets, were combined into SPT Other . SPT NEG included children with no sensitization(s). SPT PEP children had higher median non-lesional TEWL (16.9 g/m 2 /h) and IgE (90 kU/L) compared with SPT OTHER (8.8 g/m 2 /h and 24 kU/L; p = .01 and p < .001) and SPT NEG (9 g/m 2 /h and 26 kU/L; p = .003 and p < .001). SPT PEP children had lower median lesional (0.70) and non-lesional (1.09) FLG expression compared with SPT OTHER (lesional: 0.9; p = .047, non-lesional: 1.78; p = .01) and SPT NEG (lesional: 1.47; p < .001, non-lesional: 2.21; p < .001). There were no differences among groupings in S100A8 or S100A9 expression. Conclusions and clinical relevance:In this largely clinic-based cohort of young children with AD, allergic sensitization to peanut, egg, cat or dog was associated with more severe disease and skin barrier function but not markers of cutaneous inflammation. These data need replicating in a population-based cohort but may have important implications for understanding the interaction between AD and allergic sensitization. | 667 SHERENIAN Et Al.

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“…AD is characterized by compromised epidermal barrier integrity. Even the skin of a patient that is not flaring is compromised and has imperfect barrier function [ 10 – 14 ]. The purpose of daily moisturization is to repair and support the skin barrier, thereby reducing the risk of flares.…”

Section: Clinical Evidence That Moisturizers Can Improve Outcomes In mentioning

confidence: 99%

Efficacy of Nonprescription Moisturizers for Atopic Dermatitis: An Updated Review of Clinical Evidence

Hebert¹,

Rippke

Weber³

et al. 2020

Am J Clin Dermatol

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Twice-daily moisturization is recommended by international guidelines as the bedrock of the management of atopic dermatitis (AD). Moisturizers should be selected based on proven clinical effectiveness in improving the skin barrier and improving the symptoms of AD. We searched the PubMed database for clinical trials assessing daily moisturization for the treatment of AD published between 2006 and 2019. Studies had to assess the efficacy of commercially available moisturizers using objective measures of corneometry, transepidermal water loss, or incidence of flare as endpoints, and treatments had to be currently available to patients. Clinical studies showed that moisturization (typically twice daily) significantly improved the skin barrier in adults and children with AD. Longer-term flare studies showed that daily moisturization reduced the incidence of flares and extended the time between flares. Proactive moisturization of infants at high risk of developing AD may reduce its manifestation. Therapeutic moisturizers for AD are specifically formulated with ingredients that target symptoms of AD, such as itch, inflammation, or compromised skin barrier. The US FDA requires that any moisturizer available in the USA and claiming to treat AD must contain colloidal oatmeal. Healthcare providers can maximize compliance and outcomes by educating patients on the benefits of liberally applying a therapeutic moisturizer twice daily to support the skin barrier and help reduce the incidence of flares. Specific recommendations should be for clinically tested moisturizers evaluated using objective, validated skin assessments.

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Events in Normal Skin Promote Early-Life Atopic Dermatitis—The MPAACH Cohort

Cited by 28 publications

References 28 publications

Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort

Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort

Sensitization to peanut, egg or pets is associated with skin barrier dysfunction in children with atopic dermatitis

Efficacy of Nonprescription Moisturizers for Atopic Dermatitis: An Updated Review of Clinical Evidence

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