Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy*

Abstract

Summary Background Loss‐of‐function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. Objectives To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. Methods FLG mutations were analysed in 1836 infants in the Scandinavian population‐based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. Results FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m−2 h−1) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95–4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69–10·68) vs. 8·24 (95% CI 7·97–8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25–2·80; P = 0·002 and OR 2·44, 95% CI 1·51–3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04–2·22; P = 0·028 and OR 1·74, 95% CI 1·17–2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. Conclusions FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

Atopic dermatitis: filaggrin and skin barrier dysfunction

“…used, regardless of treatment assignment, the prospectively collected PreventADALL dataset for a post hoc evaluation of the association of filaggrin LoF with the prevalence of AD, eczema and skin barrier dysfunction. The latter was assessed by transepidermal water loss (TEWL), which can be technically difficult to measure 7,8 . Children from PreventADALL were genotyped for the most common European filaggrin LoF mutations – R501X, 2282del4 and R2447X – and were evaluated at 3, 6 and 12 months of age for the presence of dry skin, eczema, AD and skin barrier function (TEWL) 7 .…”

“…Filaggrin LoF variants were known to be relatively uncommon in the general population and more common in those with AD. 3,[5][6][7] However, if barrier dysfunction, as measured by TEWL, is the mechanism that drives the causal relationship between filaggrin LoF and AD, then TEWL should have been elevated at all timepoints and preceded the diagnosis of AD in infants. [7][8][9] It is possible that TEWL might not be a good measure of the causal pathway of filaggrin insufficiency and AD, but a better measure of AD severity.…”

“…What did we learn? Filaggrin LoF variants were known to be relatively uncommon in the general population and more common in those with AD 3,5–7 . However, if barrier dysfunction, as measured by TEWL, is the mechanism that drives the causal relationship between filaggrin LoF and AD, then TEWL should have been elevated at all timepoints and preceded the diagnosis of AD in infants 7–9 .…”

Corrigenda

“…In this Translational research paper by Hoyer et al ., 1 under the Study design section of Patients and method on page 545, the ethical number for The Swedish Ethical Review Authority in the last paragraph is incorrect.…”

Questionnaire use depends on the study goal, target group and phase of the condition

“…7,8 Children from PreventADALL were genotyped for the most common European filaggrin LoF mutations -R501X, 2282del4 and R2447Xand were evaluated at 3, 6 and 12 months of age for the presence of dry skin, eczema, AD and skin barrier function (TEWL). 7 About 9% of the cohort had filaggrin LoF, and all subsequent analyses compared patients with filaggrin LoF variants to those without. At all three timepoints filaggrin LoF was associated with eczema, and at the latter two timepoints with AD.…”