Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis (AD). The pathogenic sequence of disturbances in skin barrier function before or during the early development of AD is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, noninvasive test to identify babies at high risk of AD would be important in planning early intervention and/or prevention studies.
OBJECTIVES: To ascertain whether a noninvasive measurement of skin barrier function at day 2 after birth and at 2 months predicts the development of AD at 1 year. Furthermore, to determine whether increases in transepidermal water loss (TEWL) predate the development of clinical AD.
METHODS: A total of 1903 infants were enrolled in the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study from July 2009 to October 2011. Measurements of TEWL were made at birth (day 2) and at 2 and 6 months. The presence of AD was ascertained at 6 and 12 months, and disease severity was assessed by using the SCORing Atopic Dermatitis clinical tool at 6 months and by using both the SCORing Atopic Dermatitis clinical tool and Nottingham Severity Score at 12 months. A total of 1300 infants were genotyped for FLG mutations.
RESULTS: At 6 months, 18.7% of the children had AD, and at 12 months, 15.53%. In a logistic regression model, day 2 upper quartile TEWL measurement was significantly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.81; P < .05). Lowest quartile day 2 TEWL was protective against AD at 12 months. An upper quartile 2 month TEWL was also strongly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.84; P < .05). At both ages, this effect was independent of parental atopy, FLG status, or report of an itchy flexural rash at 2 months. Associations were increased when parental atopy status or child FLG mutation status was added into the linear regression model.
CONCLUSIONS: Impairment of skin barrier function at birth and at 2 months precedes clinical AD. In addition to providing important mechanistic insights into disease pathogenesis, these findings have implications for the optimal timing of interventions for the prevention of AD.
| Errataetall: |
CommentIn: Br J Dermatol. 2017 Sep;177(3):e35-e37. - PMID 27808403 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:135 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 135(2015), 4 vom: 05. Apr., Seite 930-935.e1 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kelleher, Maeve [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.06.2015 Date Revised 08.04.2022 published: Print-Electronic CommentIn: Br J Dermatol. 2017 Sep;177(3):e35-e37. - PMID 27808403 Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2014.12.013 |
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| Förderinstitution / Projekttitel: |
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NLM245631518 |
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| 245 | 1 | 0 | |a Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year |
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| 500 | |a CommentIn: Br J Dermatol. 2017 Sep;177(3):e35-e37. - PMID 27808403 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis (AD). The pathogenic sequence of disturbances in skin barrier function before or during the early development of AD is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, noninvasive test to identify babies at high risk of AD would be important in planning early intervention and/or prevention studies | ||
| 520 | |a OBJECTIVES: To ascertain whether a noninvasive measurement of skin barrier function at day 2 after birth and at 2 months predicts the development of AD at 1 year. Furthermore, to determine whether increases in transepidermal water loss (TEWL) predate the development of clinical AD | ||
| 520 | |a METHODS: A total of 1903 infants were enrolled in the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study from July 2009 to October 2011. Measurements of TEWL were made at birth (day 2) and at 2 and 6 months. The presence of AD was ascertained at 6 and 12 months, and disease severity was assessed by using the SCORing Atopic Dermatitis clinical tool at 6 months and by using both the SCORing Atopic Dermatitis clinical tool and Nottingham Severity Score at 12 months. A total of 1300 infants were genotyped for FLG mutations | ||
| 520 | |a RESULTS: At 6 months, 18.7% of the children had AD, and at 12 months, 15.53%. In a logistic regression model, day 2 upper quartile TEWL measurement was significantly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.81; P < .05). Lowest quartile day 2 TEWL was protective against AD at 12 months. An upper quartile 2 month TEWL was also strongly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.84; P < .05). At both ages, this effect was independent of parental atopy, FLG status, or report of an itchy flexural rash at 2 months. Associations were increased when parental atopy status or child FLG mutation status was added into the linear regression model | ||
| 520 | |a CONCLUSIONS: Impairment of skin barrier function at birth and at 2 months precedes clinical AD. In addition to providing important mechanistic insights into disease pathogenesis, these findings have implications for the optimal timing of interventions for the prevention of AD | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Filaggrin Proteins |2 NLM | |
| 650 | 7 | |a Intermediate Filament Proteins |2 NLM | |
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| 700 | 1 | |a Murray, Deirdre |e verfasserin |4 aut | |
| 700 | 1 | |a Campbell, Linda E |e verfasserin |4 aut | |
| 700 | 1 | |a McLean, W H Irwin |e verfasserin |4 aut | |
| 700 | 1 | |a Irvine, Alan D |e verfasserin |4 aut | |
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