title: Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Paediatrics and Child Health, University College Cork, Cork, Ireland.
authors.forename: Maeve
authors.initials: M
authors.lastname: Kelleher
authors.affiliation: Paediatrics and Child Health, University College Cork, Cork, Ireland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dunn-Galvin
authors.affiliation: Paediatrics and Child Health, University College Cork, Cork, Ireland; National Children's Research Centre, Dublin, Ireland.
authors.forename: Jonathan O'B
authors.initials: JO
authors.lastname: Hourihane
authors.affiliation: Paediatrics and Child Health, University College Cork, Cork, Ireland; National Children's Research Centre, Dublin, Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Murray
authors.affiliation: Dermatology and Genetic Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Campbell
authors.affiliation: Dermatology and Genetic Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: W H Irwin
authors.initials: WHI
authors.lastname: McLean
authors.affiliation: 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.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Irvine
mesh_terms: D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D011379:Prognosis; D012306:Risk; D012867:Skin / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins
keywords: Infant; TEWL; atopic dermatitis; biomarker; filaggrin; predictor; skin barrier