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Moisturizing treatment of patients with atopic dermatitis and ichthyosis vulgaris improves dry skin, but has a modest effect on gene expression regardless of FLG genotype
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
Karolinska Institutet, Solna.
Karolinska Institutet, Solna.
Karolinska Institutet, Solna.
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2015 (English)In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 29, no 1, 174-177 p.Article in journal (Refereed) Published
Abstract [en]

Background

Loss-of-function mutations in FLG (encoding filaggrin) are a predisposing factor for atopic dermatitis (AD) and cause ichthyosis vulgaris (IV). Patients with AD and IV display impaired skin barrier and dry skin, and altered epidermal expression of genes in pro-inflammatory and lipid metabolic pathways are often evident.

Objectives

To evaluate the effect of three different moisturizers on skin barrier function and epidermal gene expression in patients with AD/IV in relation to FLG mutation status.

Methods

Patients (n = 43) were classified according to their FLG status: AD with FLG+/+ (n = 14), AD with FLG+/− (n = 14), and AD/IV with FLG−/− (n = 15). Dryness score and transepidermal water loss (TEWL) were monitored on volar forearms, and punch biopsies were taken for analysis of gene expression. Measurements were repeated after 4 weeks of treatment with either of two moisturizers on each forearm.

Results

Treatment with any of the three moisturizers significantly reduced dryness score and TEWL in the group as a whole. FLG−/− patients displayed the largest reduction in dryness score. Only minute changes occurred in the mRNA expression of 15 selected epidermal genes.

Conclusions

Moisturizing treatment improves dry skin and certain aspects of abnormal skin barrier function, especially in patients with AD/IV and dual FLG mutations, but does not normalize the epidermal gene expression profile.

Place, publisher, year, edition, pages
2015. Vol. 29, no 1, 174-177 p.
National Category
Dermatology and Venereal Diseases
Identifiers
URN: urn:nbn:se:uu:diva-191808DOI: 10.1111/jdv.12333ISI: 000346733800028PubMedID: 24330146OAI: oai:DiVA.org:uu-191808DiVA: diva2:587069
Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Skin Barrier Function and mRNA Expression Profiles in Patients with Atopic Dermatitis, Ichthyosis Vulgaris, and X-linked Recessive Ichthyosis: Aetiopathogenic Differences and the Impact of Moisturizing Treatment
Open this publication in new window or tab >>Skin Barrier Function and mRNA Expression Profiles in Patients with Atopic Dermatitis, Ichthyosis Vulgaris, and X-linked Recessive Ichthyosis: Aetiopathogenic Differences and the Impact of Moisturizing Treatment
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atopic dermatitis (AD), ichthyosis vulgaris (IV), and X-linked recessive ichthyosis (XLRI) are characterized by dry skin and impaired skin barrier. AD and IV are related to loss-of-function mutations in FLG (encoding filaggrin), whereas XLRI is caused by deletions or inactivating mutations in the steroid sulphatase gene (STS). Patients regularly use moisturizing creams, but little is known about the creams’ effects on the skin barrier.

The present work combines objective scorings, non-invasive techniques, and molecular analyses of skin biopsies to characterize the skin in 57 patients with AD, IV, or XLRI, and in 14 healthy controls. Patients were classified according to their FLG and STS mutation status: AD with FLG+/+ (n = 14), AD with FLG+/– (n = 14), AD/IV with FLG–/– (n = 15), and XLRI with STS– (n = 14), as well as one man with a novel point mutation. Assessments were conducted at baseline and after four weeks of treatment with three different moisturizers applied to volar forearm skin.

At baseline, dryness scoring and non-invasive assessments verified impaired skin barrier function in all patients. In patients with AD/IV, microarray analysis identified 300–3000 up- or downregulated mRNA transcripts involved in signalling pathways important for inflammation and barrier repair. The skin phenotype and number of altered transcripts were correlated with the FLG mutation status, with FLG–/– patients displaying the highest transepidermal water loss (TEWL) and the most altered transcript levels. In contrast, despite an equally dysfunctional skin barrier, only limited changes in mRNA transcripts occurred in XLRI patients. Treatment with moisturizers improved skin dryness similarly in all groups, but TEWL behaved differently: it decreased slightly in the AD/IV group and increased in the XLRI group, especially after urea treatment. Only minute effects on skin pH and mRNA expression were observed.

In conclusion, FLG mutations elicit pro-inflammatory mechanisms probably aimed at restoring barrier competence. This does not occur in patients with XLRI, presumably because STS deficiency automatically increases the barrier thickness. Moisturizing treatment improves skin dryness in patients with AD, IV, or XLRI, but does not seem to normalize the altered epidermal gene expression profile in AD/IV patients.

 

 

 

 

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 859
Keyword
atopic dermatitis, ichthyosis vulgaris, X-linked recessive ichthyosis, skin barrier function, moisturizers, transepidermal water loss, gene expression
National Category
Dermatology and Venereal Diseases
Research subject
Dermatology and Venerology
Identifiers
urn:nbn:se:uu:diva-192396 (URN)978-91-554-8583-2 (ISBN)
Public defence
2013-03-08, Rosénsalen, Ingång 95/96, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
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Available from: 2013-02-15 Created: 2013-01-20 Last updated: 2013-04-02

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Hoppe, TorborgVahlquist, AndersTörmä, HansBerne, Berit

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