Funding sources The clinical and epidemiological aspects of the EAT birth cohort study are jointly funded by the UK Food Standards Agency (FSA, grant code T07051) and the Medical Research Council (MRC). The skin-related components of the study are supported by the National Institute for Health Research (NIHR). Carsten Flohr is funded by a Clinician Scientist Award from the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the FSA, MRC, the NHS, the NIHR or the UK Department of Health.
Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age
Article first published online: 18 NOV 2010
© 2010 The Authors. BJD © 2010 British Association of Dermatologists
British Journal of Dermatology
Volume 163, Issue 6, pages 1333–1336, December 2010
How to Cite
Flohr, C., England, K., Radulovic, S., McLean, W.H.I., Campbell, L.E., Barker, J., Perkin, M. and Lack, G. (2010), Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age. British Journal of Dermatology, 163: 1333–1336. doi: 10.1111/j.1365-2133.2010.10068.x
Conflicts of interest None declared.
- Issue published online: 18 NOV 2010
- Article first published online: 18 NOV 2010
- Accepted manuscript online: 27 SEP 2010 01:33PM EST
- Accepted for publication 7 September 2010
- atopic dermatitis;
- atopic eczema;
- transepidermal water loss
Background Filaggrin loss-of-function (FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in FLG mutation carriers.
Objectives To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age.
Methods A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared.
Results Thirty-three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5–31·0). TEWL (g m−2 h−1) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease (r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema [odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09–66·58, P = 0·042]. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34–13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG‘yes’ 21·59 vs. FLG‘no’ 11·24, P < 0·001), even without clinical eczema (FLG‘yes’ 15·99 vs. FLG‘no’ 10·82, P = 0·01).
Conclusions By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema.