Clinical Review
Diet and Atopic Dermatitis
Dermatologists and pediatric dermatologists frequently treat patients with atopic dermatitis (AD), and patients and guardians often associate AD...
Nanette B. Silverberg, MD
From Mount Sinai St. Luke’s-Roosevelt Hospital and Beth Israel Medical Centers of the Icahn School of Medicine at Mount Sinai, New York, New York.
Dr. Silverberg has served as an investigator for Astellas Pharma US, Inc, and Novartis Corporation, and as a consultant for Anacor Pharmaceuticals, Inc; Johnson & Johnson Services, Inc; and Novartis Corporation.
This article is the first of a 3-part series. The second part will appear next month.
Correspondence: Nanette B. Silverberg, MD, 1090 Amsterdam Ave, Ste 11B, New York, NY 10025 (nsilverb@chpnet.org).
Barrier Defects Contributing to AD
The breakdown of the stratum corneum allows for antigen presentation to Langerhans cells, the dendritic antigen-presenting cells of the skin. Breaks in the stratum corneum may occur from scratching. These macroscopic breaks are large, whereas the breaks that otherwise occur due to barrier breakdown may be more microscopic in nature. Scratching causes aggravation of the helper T cell (TH2) response.29 For example, it allows the dendritic ends of Langerhans cells to be exposed to antigens. The dendritic ends capture allergens through IgE (may be elevated in AD29), which is bound to the high-affinity FCER1 receptors on Langerhans cells. Rather than causing a type I hypersensitivity reaction, these Langerhans cells are activated and move to the lymph nodes where they present antigen and initiate a cascade of proinflammatory activity. This TH2 cascade includes release of cytokines such as IL-2, IL-4, IL-8, IL-10, tumor necrosis factor α, and IFN-γ.26,29
Transepidermal water loss and barrier dysfunction contribute to disease activity and facilitate food/environmental allergen sensitization by allowing increased penetration of allergens through the skin to be presented by Langerhans cells to TH1 cells (sensitization phase). The Langerhans cells can reach their dendritic ends through tight junctions and into the stratum corneum, allowing them to reach surface allergens when the barrier is impaired. Ultimate expansion to systemic allergy (effector phase) occurs when dendritic cells move to draining lymph nodes, causing antigen presentation to CD4 and/or CD8 cells. Langerhans cells and dendritic cell sensitization through the weakened skin is believed to be the basis or role of barrier disruption as a trigger of atopic diseases, including AD and food and environmental allergies.
Many different forms of barrier disruption can cause a TH2 response in AD. The TH2 response triggers a constellation of proinflammatory activities including release of IL-4, associated with eosinophilia and elevated IgE levels, the latter being minor criterion in the diagnosis of AD.15 One mechanism by which the TH2 response is elicited may be the release of molecules such as danger-associated molecule patterns that may elicit recruitment of other inflammatory cells. Helper T cell (TH2) activity also can worsen barrier defects through IL-4 and IL-13 release, which can reduce filaggrin expression,29,41 and can aggravate barrier dysfunction in AD.
Inflammatory activation in AD also may involve inflammatory dendritic epidermal cells (IDECs). The IDECs can be tolerogenic or immunogenic mature phenotypes. The IDECs activate helper T cells (TH1), which may contribute to long-term AD activity.
Conclusion
Atopic dermatitis is a common skin condition worldwide and is characterized by the hallmark of pruritus and features that include a typical pattern, history of atopy (personal or family), and usually xerosis and early disease onset. Barrier dysfunction and immune dysregulation are prominent in AD, both of which aggravate the other and may encourage increased development of allergies and other forms of atopy over time.
Dermatologists and pediatric dermatologists frequently treat patients with atopic dermatitis (AD), and patients and guardians often associate AD...
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