25 Jan Signal For Development of Atopic Dermatitis – Eczema – Seen In Early Infancy

MedicalResearch.com Interview with:
Dr. Alan Irvine, MD
Professor in Dermatology
Department of Clinical Medicine
Trinity College Dublin

Medical Research: What is the background for this study? What are the main findings?

Response: Atopic diseases include atopic dermatitis (AD, also know as eczema), food allergy, allergic rhinitis and asthma.  The prevalence of these diseases has increased in recent decades causing considerable morbidity in childhood. The putative “Atopic March” refers to the typical sequence of clinical manifestation of atopic disease, usually initiated by atopic dermatitis from early infancy.

Parental atopy is an independent risk factor for development of atopic disease. The genetic mechanisms and inheritance pattern of atopic diseases are not fully elucidated but recent candidate gene studies and Genome Wide Association Studies (GWAS) have yielded some insights. The most widely replicated and most significant gene to influence atopic dermatitis is Filaggrin (FLG). Filaggrin is a filament binding protein in the stratum Corneum. FLG loss-of-function mutations (FLG mut) occur in 10% of Europeans, imparting an increased risk of atopic dermatitis, food allergy and asthma.  The overall increase in risk of atopic dermatitis conferred by a single FLG loss-of-function mutation is approximately 3.3, with a significant additional and independent effect conferred by intragenic copy number variations in FLG. Importantly FLG mutations increase the risk of developing asthma only in the presence of atopic dermatitis.

While loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis, the pathogenic sequence of disturbances in skin barrier function prior to or during the early development of atopic dermatitis is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, non-invasive test to identify babies at high risk of atopic dermatitis would be important in planning early intervention and/or prevention studies.

We found that raised transepidermal water loss at birth and at two months in asymptomatic infants predates the development of atopic dermatitis. This signal is independent of FLG status and parental atopy.

Medical Research: What should clinicians and patients take away from your report?

Response: A signal for the development of atopic dermatitis/eczema is seen at 2 days and again at 2 months in asymptomatic infants. In other words the pathway to atopic dermatitis /eczema starts in some infants very shortly after birth. This is a needed mechanistic insight.

The clinical relevance of these insights is that interventions to potentially prevent atopic dermatitis could be targeted towards such infants, especially in families at high risk, such as those with a strong family history of these diseases. Early intervention, including intensive moisturizing therapies have come into focus recently and many studies are ongoing. Our findings, using the simple, painless test will help target those interventions to those most likely to benefit form them.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Insights into the pathogenesis of atopic dermatitis have highlighted the role of skin barrier dysfunction. This paper reinforces the fact that these changes occur very early, these changes need to be better understood with further mechanistic work.

Targeted intervention studies should be performed using our findings to identify those children most in need of intervention. This will make interventions more efficient and cost effective.

Citation:

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

Journal of Allergy and Clinical Immunology
Available online 22 January 2015
Maeve Kelleher | Audrey Dunn-Galvin | Jonathan O’B. Hourihane | Deirdre Murray | Linda E. Campbell | W.H. Irwin McLean | Alan D. Irvine

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Last Updated on January 25, 2015 by Marie Benz MD FAAD