The Persistence of Atopic Dermatitis and Filaggrin (FLG) Mutations in a US Longitudinal Cohort

September 28, 2012

Since the beginning of this century several studies have been published that have helped to revolutionize our understanding of the pathophysiology of Atopic Dermatitis (AD). These studies have shown an association between genetic variation and AD. Genes that have been implicated include genes that code proteins associated with skin barrier and genes that code proteins involved in immune function. The most profound and consistent of studies described a change in the ability of the skin to work as a good barrier due to a mutation in a gene that makes a protein called filaggrin (FLG). Carrying a FLG mutation has since been estimated to increase the chance that a child will have AD by more than 3-fold. However, very few studies have evaluated whether a child carrying this gene will have more persistent and more difficult to treat AD. Mostly FLG mutations have been described in individuals with European or Asian ancestry. The mutations have not consistently been found in those of African ancestry.

Margolis et al studied a long-term US follow-up study of 6000 children diagnosed by a physician with mild to moderate AD. The goal of this NIH sponsored study recently published in the Journal of Allergy and Clinical Immunology (JACI) was to determine if children with AD and FLG mutations have more persistent (or severe) AD. Children in this study were followed every six months and they (or their parents) filled out questionnaires that asked for information on the presence of AD skin findings and whether they were using topical medication to treat their AD. The study team supplemented this information by obtaining DNA from about 850 children participants. At the time of the study, the average child had participated in the long-term study for about 4 years and in total there were 3684 person-years of follow up. Unlike other studies that measured the time until a child first reported no symptoms, Margolis et al used a statistical approach that allowed AD symptoms to wax and wane more like the natural clinical course. These authors studied the four most commonly reported FLG mutations in those of European ancestry.

These authors were able to show that about 28% of white children with AD had a FLG mutation. At any time during the study follow up, these children were about 50% less likely to have skin that was free of AD symptoms as compared to those who did not have a mutation. Interestingly, about 6% of African American children did have a FLG mutation too and they were also about 50% less likely to have skin that was free at any time during the study of AD symptoms as compared to children who did not have a FLG mutation. The authors further studied whether children required topical medications in order to clear their skin of AD symptoms. One mutation called R501X seemed to be the most likely to require the use of medications for full symptomatic relief. Margolis et al concluded that those who have AD and a FLG mutation were most likely to have persistent AD and a clinical course that more likely required the use of topical medications.


David J Margolis MD PhD
Professor of Dermatology
Professor of Epidemiology
University of Pennsylvania

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