A genetic factor for the persistence of atopic dermatitis

Published Online: August 29, 2012

Atopic dermatitis (AD), commonly known as eczema,  is a chronic, relapsing skin disease that often begins in early childhood and is characterized by recurrent episodes of itching. AD affects between 10 to 20% of all children. Many with AD also suffer from asthma and allergic rhinitis.

Starting in 2006, several seminal studies were published that revolutionized our understanding of the pathophysiology of AD. These 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 ancestry. The mutations have not uncommonly been found in those of African ancestry. The goal of this NIH sponsored study by Margolis et al published in The Journal of Allergy and Clinical Immunology (JACI) was to determine if children who have AD and FLG mutations have more persistent (or severe) AD.

Margolis et al studied a long-term US follow-up study of 6,000 children diagnosed by a physician with mild to moderate 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. They 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 statistical approach that allowed AD symptoms to wax and wane like the normal clinical course. These authors studied the four most commonly reported FLG mutations in Europe.

The authors were able to show that about 28% of Caucasian children with AD had a FLG mutation and at any time during the study 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 symptoms 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 requires the use of topical medications.


The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology