Oxidative Stress, Environmental Factors, and Pollutants

Introduction

When we consider the variety of external factors that may influence the development of atopic dermatitis (AD), it is logical that environmental pollution comes to the forefront, as it has been strongly associated with the development of other atopic diatheses, including asthma, allergic rhinitis, and food allergies.

Before we discuss the impact of pollution, however, it would be prudent that we first define the term pollution . According to the Merriam-Webster Dictionary online , is “the action of polluting, especially by environmental contamination with man-made waste.” (Merriam-Webster). Thus human activities, whether intentional or unintentional, produce waste and byproducts that can become triggering factors for the development of AD. Having defined pollution, let us now delineate its impact on AD by examining published data in the literature.

The prevalence of AD has been steadily rising in recent decades, particularly in certain regions. Despite a global increase in the number of children with AD, developed countries such as New Zealand and the United Kingdom that previously reported high rates of AD have experienced a plateau at around 10% to 15% ( ). However, AD prevalence is growing in lower income developing nations, with rates higher than 15% and up to 24.6% reported in countries of Southeast Asia, Africa, and Latin America ( ). The increased incidence of AD parallels expansion in urbanization and industrialization worldwide, and investigation of the role of airborne pollution in relation to AD has become increasingly relevant. One of the major areas of study centers on the role of pollution in skin barrier dysfunction.

General mechanism of pollution-induced barrier dysfunction

The general mechanisms of pollution-induced skin barrier dysfunction result from excess oxidative stress that in turn induces inflammation. Airborne pollution generates reactive oxygen species, which deplete the skin’s antioxidant defenses. This pro- versus antioxidant imbalance, favoring prooxidants, results in oxidative damage to keratinocytes, decreased cell adhesion, and barrier dysfunction as indicated by increased transepidermal water loss (TEWL), decreased hydration, and increased pH ( ). Compromised skin barrier integrity allows for easy entry of pathogens, irritants, and immunogens ( ), fueling inflammation and the itch-scratch cycle in AD ( ). Signaling cascades involved in pollutant-induced skin barrier damage include the NFκB inflammatory pathway ( ) and aryl hydrocarbon receptor (AhR) ( ). Airborne pollutants have been found to increase NFκB signaling and promote expression of proinflammatory cytokines that lead to skin redness, swelling, itch, and pain. AhR acts as a chemical sensor in keratinocytes, leading to downstream activation of inflammation and itch mediators as well as epidermal antioxidant defense mechanisms ( ).