The Role of Epidermal Dysfunction in Atopic Dermatitis

The Eczema Association estimates that over 36 million Americans suffer from some form of atopic dermatitis, with approximately 10 million of those cases being children under 18 years old.¹ Atopic dermatitis, also called eczema, is most prevalent in the early years of life but can manifest throughout the lifespan.² Children with eczema are also more likely to develop other atopic conditions such as asthma, rhinitis, and food allergies.³ Though distinct, these disorders have common genetic risk factors and environmental triggers. Beyond genetics, new research has focused on the relationship between epidermal permeability and bacterial infection as a potential mechanistic cause of atopic dermatitis that may influence allergenic sensitization of the skin. What is the latest research, and how can lifestyle-based approaches for healthy skin help?

Eczema Pathology: Skin Cells, Genetics, and Epidermal Permeability

Atopic dermatitis appears to manifest due to combined epidermal barrier dysfunction and immune dysregulation; however, the underlying pathology remains unclear, with a range of contributors suggested such as genetic factors, dietary choices, environmental triggers (i.e., chemical and/or biological pollutants and allergens), and immune triggers.^2,4 In a 2021 study, researchers found that eczema-afflicted cells share similar molecular properties to those of healthy, developing cells and demonstrated the ability of both cell types to signal immune cells to form a protective layer on the skin.⁵ Signaling by the affected cells was attributed to overstimulation of the immune response and the subsequent occurrence of skin lesions and inflammation.⁵ Epidermal permeability—predisposed by individual genetics and exacerbated by environmental exposures—is believed to contribute to this disease process as a weakened skin barrier is more susceptible to topical infections that also trigger the immune response.⁶

The filaggrin gene, responsible for encoding a protein that supports skin barrier integrity and function, is often mutated in patients that present with atopic dermatitis.² The skin uses filaggrin metabolic byproducts to produce factors essential for skin hydration and skin microbial balance.^2,4 Mutations in filaggrin may lead to increased epidermal barrier permeability and the deeper passage of allergens, contributing to immune responses.² 

Skin Lipids & Bacterial Entry

Lipid depletion of the stratum corneum may affect skin permeability and increase sensitization to allergens.⁷ The depletion of ceramides—lipids found in the stratum corneum responsible for regulating skin’s hydration and providing antimicrobial activity—is linked to the pathogenesis of atopic dermatitis.² Research studies suggest that in patients with eczema, the amount of longer chained fatty acid ceramides is decreased while the amount of shorter ones is increased, negatively impacting the barrier function of the skin and the trans-epidermal water loss.²

Depleted skin lipids and increased populations of Staphylococcus aureus on the skin are both frequently noted in clinical presentations of atopic dermatitis.⁸ Dry, chapped, or cracked skin from moisture or lipid dysregulation may enable the staphylococcus bacteria to breach the skin barrier more easily,⁸ causing inflammation, lesions, plaque, and cutaneous infections in the underlying tissue. On skin with normal lipid presence, permeation of staph bacteria is not statistically significant; however, findings suggest that the bacteria can persist in lipid-compromised skin tissue for up to nine days.⁸ Permeability during this timeframe is thought to contribute to prolonged states of inflammation and disease onset in the underlying epidermal cells.⁸ Thus, skin barrier dysfunction may be a common precursor for eczema and other inflammatory skin conditions and may present a new therapeutic target for prevention.

Clinical Considerations for Eczema Management

Skincare regimens are often prescribed to help manage eczema symptoms and maintain skin barrier integrity. Emollients are a primary component of management,⁹ and studies continue to research the moisturizing benefits of emollients containing botanical and plant-based oils such as shea butter, colloidal oatmeal, and linolenic acid.^10-12 As a fatty acid, linoleic acid is considered a building block for ceramide production and essential for repopulating and stabilizing the skin-lipid barrier.¹²

Nutrition may also be an important consideration in a multimodal approach to eczema management. While the relationship between the gut-skin axis and atopic dermatitis continues to be studied,^13-15 avoiding food allergens and triggers¹⁶ to support overall gut and immune health may help to address some underlying inflammation for patients. In addition, specific nutrient considerations may be appropriate for supporting a patient’s overall skin function. For example:

• Micronutrients such as the vitamin spectrum A-E, polyphenolic compounds, and other plant-based antioxidants have skin-protective properties against UV damage and other environmental exposures.¹⁷
• Dietary fat intake is closely linked to lipid composition and the skin’s ability to repair tissue damage.¹⁸
• Fatty acids found in omega-3-rich foods also support the cell’s ability to synthesize and secrete lipids.¹⁸ 

As the largest organ in the body, the skin is a critical protective barrier against potential infection. Supporting skin health and minimizing potential environmental exposures holds promise for improving long-term outcomes for patients with eczema. Understanding a patient’s lifestyle and genetic risk factors helps inform a personalized therapeutic approach for managing the occurrence of chronic, inflammatory skin conditions. 

Learn more about the functional medicine approach to addressing chronic conditions and improving the health and well-being of your patients in IFM’s Applying Functional Medicine in Clinical Practice (AFMCP)^TM course.