Abstract
Atopic dermatitis (AD) is a complex disease characterized by dry, pruritic skin and significant atopic and psychological sequelae. Although AD has always been viewed as multifactorial, early research was dominated by overlapping genetic determinist views of either innate barrier defects leading to inflammation or innate inflammation eroding skin barrier function. Since 1970, however, the incidence of AD in the United States has increased at a pace that far exceeds genetic drift, thus suggesting a modern, environmental etiology. Another implicated factor is Staphylococcus aureus; however, a highly contagious microorganism is unlikely to be the primary etiology of a noncommunicable disease. Recently, the roles of the skin and gut microbiomes have received greater attention as potentially targetable drivers of AD. Here too, however, dysbiosis on a population scale would require induction by an environmental factor. In this review, we describe the evidence supporting the environmental hypothesis of AD etiology and detail the molecular mechanisms of each of the AD-relevant toxins. We also outline how a pollution-focused paradigm demands earnest engagement with environmental injustice if the field is to meaningfully address racial and geographic disparities. Identifying specific toxins and their mechanisms can also inform in-home and national mitigation strategies.