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J Allergy Clin Immunol. 2015 Apr;135(4):930-5.e1. doi: 10.1016/j.jaci.2014.12.013. Epub 2015 Jan 22.

Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.

Author information

1
Paediatrics and Child Health, University College Cork, Cork, Ireland.
2
Paediatrics and Child Health, University College Cork, Cork, Ireland; National Children's Research Centre, Dublin, Ireland.
3
Dermatology and Genetic Medicine, University of Dundee, Dundee, United Kingdom.
4
National Children's Research Centre, Dublin, Ireland; Paediatric Dermatology, Our Lady's Children's Hospital, Dublin, Ireland; Clinical Medicine, Trinity College Dublin, Dublin, Ireland. Electronic address: IRVINEA@tcd.ie.

Abstract

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.

KEYWORDS:

Infant; TEWL; atopic dermatitis; biomarker; filaggrin; predictor; skin barrier

PMID:
25618747
PMCID:
PMC4382348
DOI:
10.1016/j.jaci.2014.12.013
[Indexed for MEDLINE]
Free PMC Article

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