Atopic Dermatitis: Etiology, Epigenetics, and Migration-Related Disease Patterns in Adults
Atopic dermatitis (AD), commonly referred to as eczema, is a chronic, relapsing inflammatory skin disorder characterized by pruritus, xerosis, and eczematous lesions. The pathophysiology of atopic dermatitis is complex, involving a combination of genetic predisposition, environmental factors, immune dysregulation, and epidermal barrier dysfunction. Understanding the diverse etiologies and patterns of disease expression, particularly in adult immigrants to the United States, has become increasingly significant in dermatological practice.
Etiology of Atopic Dermatitis
At its core, atopic dermatitis involves a dysregulated immune response, primarily driven by T-helper 2 (Th2) cells, leading to increased production of pro-inflammatory cytokines such as interleukin (IL)-4, IL-13, and IL-31. This immune dysregulation disrupts the skin barrier by reducing the expression of key structural proteins such as filaggrin (FLG), leading to increased transepidermal water loss (TEWL) and allowing for allergen penetration and microbial colonization, particularly Staphylococcus aureus.
Environmental factors such as allergens, irritants, and climate can exacerbate the condition. Urbanization and industrial pollution, which are more prevalent in developed countries like the United States, are associated with increased atopic dermatitis prevalence. Additionally, the hygiene hypothesis suggests that reduced exposure to infections early in life may skew immune responses toward atopic diseases, including atopic dermatitis.
Epigenetic Influences in Atopic Dermatitis
Recent advances have illuminated the role of epigenetics in the pathogenesis of atopic dermatitis. Epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNA regulation, can alter gene expression without changing the underlying DNA sequence. These modifications are influenced by environmental exposures and are thought to mediate the interaction between genetic predisposition and external factors.
In atopic dermatitis, studies have shown that epigenetic changes can affect immune cell function and skin barrier integrity. For instance, hypermethylation of the FLG gene has been associated with reduced filaggrin expression, contributing to impaired skin barrier function. Additionally, histone modifications in Th2 cells have been linked to the overexpression of cytokines involved in the inflammatory response.
These epigenetic alterations can be influenced by various environmental exposures, including allergens, pollutants, and diet. Importantly, epigenetic changes may be reversible, suggesting potential therapeutic avenues for atopic dermatitis through the modulation of gene expression.
Migration, Environmental Change, and Disease Onset
A striking observation is the development of atopic dermatitis in individuals who migrate to the United States as adults, particularly those from the Caribbean and Africa. This population often presents with atopic dermatitis patterns as though they had been "born" the day they immigrated, despite having no prior history of the disease.
This phenomenon can be explained by the sudden shift in environmental exposures, including increased exposure to industrial pollutants, altered diet, and new allergens, which may trigger latent atopic tendencies. Epigenetic modifications likely play a critical role in this transition, as the new environment may lead to changes in DNA methylation patterns, histone modifications, and non-coding RNA expression, resulting in the late onset of atopic dermatitis.
Additionally, people of color may have unique skin barrier characteristics, such as increased melanin production, which may influence how they respond to environmental triggers. The interplay between genetic predisposition, epigenetic changes, and new environmental exposures likely contributes to the onset of atopic dermatitis in this population.
If you need to book an appointment for your allergies or asthma, you can book your appointment online, or call (212) 247-7447.