Consider the shift from an aqueous to an arid environment, like moving from the sterile, xenobiotic womb to enter the world. This transition triggers a rapid breakdown of filaggrin (FLG) in the skin, as it senses the absence of an aqueous environment and metabolizes FLG to produce natural moisturizing factors. FLG is stored as a reserve and built up over time. For premature infants, this transition is relatively smooth, but for full-term babies, the breakdown of FLG begins within the first 24 hours as the skin recognizes it is no longer in a dry environment. Humans also undergo this process seasonally albeit less dramatically when moving from dry to humid environment. This could explain why some people’s skin worsens in winter, particularly in terms of atopic dermatitis (AD). The most significant changes occur between the prenatal and postnatal stages. Therefore, when a baby is born, it is important to consider all the environmental influences they may be exposed to.
Impact of Tar and Air Pollution Through Aryl Hydrocarbon Receptor (AhR)
The AhR receptor, a complex and intriguing receptor, plays a pivotal role in skin barrier maturity and is part of the dioxin pathway. Various factors influence it, for instance, cold air inhibits the AhR receptor, while pollution exerts different pressures. Companies are actively targeting the AhR receptor for drug development. The microbiome also plays a role here. Research by Joost Schalkwijk, published years ago in the Journal of Clinical Investigation, demonstrated that external pressures like tar could enhance the strength of FLG, which is also influenced by the type 2 immunity.
Link Between Water Hardness and AD
There is a notable link between water hardness and AD, with compelling data from England showing a strong interaction with odds ratios of 28%. This interaction becomes more pronounced when considering individuals with and without FLG mutations. The interplay between hard water, rich in calcium carbonate, and FLG mutation contributes to these differences. A weaker skin barrier, lacking the reserve of FLG to adapt to its environment, leads to a higher incidence of AD in those with this genetic defect. Current studies are exploring the use of water softeners for individuals with FLG mutations as a preventative measure against AD. However, this is a costly intervention in England and complicates the water system to the point where the water becomes non-potable. Despite the complexity, it exemplifies how environmental factors interact with the skin barrier in different contexts.
Site of Predilection
There was a Danish study that examined the sites of predilection for AD which are the cheeks, forearms, and hands. What these all have in common is that they are areas that interact with the environment. You are dealing with people who have less of a reserve, less of a threshold to interact with the outside world.
There is a significant interaction between FLG mutations and environmental exposures on the skin barrier which was shown in this series. There are also other elements that have not been mentioned like older siblings and fatalities exposures and more. There are a lot of genes environmental exposures worked out such as older siblings, water hardness, phthalate exposure (higher urinary phthalate metabolite level, all increase AD risk additional to FLG null genotype).
In conclusion, it has been established that there is an intricate interplay between various environmental factors and their impact on the skin barrier. Understanding the transition from prenatal to postnatal stages, the role of AhR receptor in skin barrier maturity, and the influence of water hardness lead to a better grasp of the prevalence of AD in the population.
Want to learn more about skin barrier dysfunction in AD? Follow this link to access the full webinar.
About the Author
Alan D. Irvine, MD, DSc
A key leader in dermatology research, he is a professor of Dermatology at Trinity College in Ireland. Dr. Irvine is the founding president of the Irish Skin Foundation and the International Eczema Council. His research focuses on molecular genetics of skin disease including rare skin disorders.
