Epidermal Permeability May Increase Incidence of Eczema Symptoms
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 is most prevalent in the early years of life, with symptoms manifesting prominently during the first year or within the first five years.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.
Eczema Pathology: Skin Cells, Genetics, and Epidermal Permeability
Atopic dermatitis manifests due to an overactive immune system response and T-cell-driven systemic inflammation;4 however, the underlying pathology remains unclear. 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.4-5 Epidermal permeability—predisposed by individual genetics and exacerbated by environmental exposures—is believed to contribute to this disease process as 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. Phenotypic changes in DNA over time7 can sensitize skin to different allergenic triggers such as bacteria and environmental chemicals8 that may influence incidence and severity. Researchers believe that the deficient variants of the filaggrin gene contribute to epidermal dysfunction of the stratum corneum9—the outermost layer of skin—through the decreased presence and metabolism of protective skin lipids.8
Skin Lipids & Bacterial Entry
Lipid depletion of the stratum corneum may affect skin permeability and increase sensitization to allergens.10 The depletion of ceramides—the lipids responsible for regulating skin’s hydration and providing antimicrobial activity—was identified as a significant genetic risk factor associated with the mutant filaggrin gene type. Filaggrin also supports moisture regulation, skin protection, and pH balance;8 patients with a variant filaggrin gene may also be higher risk for allergic sensitization9 and decreased presence of overall ceramides4 when compared to those with a wild-type gene.
Depleted skin lipids and increased populations of Staphylococcus arceus on the skin are both frequently noted in clinical presentations of atopic dermatitis.11 Dry, chapped, or cracked skin from moisture or lipid dysregulation may enable the staphylococcus bacteria to breach the skin barrier more easily,11 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.11 Permeability during this timeframe is thought to contribute to prolonged states of inflammation and disease onset in the underlying epidermal cells.11 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. Some studies suggest that emollients containing botanical and plant-based oils, such as shea butter, aloe vera, and colloidal oatmeal, are as effective in replenishing skin lipids and restoring natural moisture factors to the stratum corneum as compared to prescription emollients.12-14
Products with the active ingredient linoleic acid may be used to enhance topical corticosteroid therapy or prove an effective alternative altogether with minimal adverse side effects.15,16 As a fatty acid, linoleic acid is considered a building block for ceramide production and essential for repopulating and stabilizing the skin-lipid barrier.15,17 Other cleansers and moisturizers containing ceramides are another therapeutic option for protecting the epidermal barrier and the day-to-day management and clearance of eczema symptoms.
Anti-inflammatory diets and avoiding food triggers to support gut and immune health may help to address underlying inflammation for patients with atopic dermatitis,18-19 and vitamin D supplementation has been found to decrease eczema severity.20 Specific nutrient considerations may also be appropriate for supporting skin function.
- Micronutrients, such as the vitamin spectrum A-E, have skin-protective properties against UV damage and other environmental exposures.21
- Dietary fat intake is closely linked to lipid composition and the skin’s ability to repair tissue damage.22
- Fatty acids found in omega-3-rich foods, which can decrease overall inflammation, also support the cell’s ability to synthesize and secrete lipids.22
As an adjuvant therapy, increased dosage of these nutrients through diet or supplementation can help downregulate inflammatory pathways and oxidative processes that may underpin the immune response of atopic dermatitis.
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 may inform the best overall approach for managing the occurrence of chronic, inflammatory skin conditions. Multimodal therapies including topical treatments and dietary interventions, especially early in life, can lessen the burden of atopy and other related allergenic disorders throughout a patient’s lifespan.
- Eczema prevalence, quality of life and economic impact. National Eczema Association. Published September 14, 2020. Accessed March 16, 2021. https://nationaleczema.org/research/eczema-facts
- Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4S):S65-S76. doi:1016/j.jaci.2017.01.011
- Langan SM, Irvine AD, Weidinger S. Atopic dermatitis [published correction appears in Lancet. 2020 Sep 12;396(10253):758]. Lancet. 2020;396(10247):345-360. doi:1016/S0140-6736(20)31286-1
- Agrawal R, Woodfolk JA. Skin barrier defects in atopic dermatitis. Curr Allergy Asthma Rep. 2014;14(5):433. doi:1007/s11882-014-0433-9
- Reynolds G, Vegh P, Fletcher J, et al. Developmental cell programs are co-opted in inflammatory skin disease. Science. 2021;371(6527):eaba6500. doi:1126/science.aba6500
- Li R, Hadi S, Guttman-Yassky E. Current and emerging biologic and small molecule therapies for atopic dermatitis. Expert Opin Biol Ther. 2019;19(4):367-380. doi:1080/14712598.2019.1573422
- Zaniboni MC, Samorano LP, Orfali RL, Aoki V. Skin barrier in atopic dermatitis: beyond filaggrin. An Bras Dermatol. 2016;91(4):472-478. doi:1590/abd1806-4841.20164412
- Mócsai G, Gáspár K, Nagy G, et al. Severe skin inflammation and filaggrin mutation similarly alter the skin barrier in patients with atopic dermatitis. Br J Dermatol. 2014;170(3):617-624. doi:1111/bjd.12743
- Tsakok T, Woolf R, Smith CH, Weidinger S, Flohr C. Atopic dermatitis: the skin barrier and beyond. Br J Dermatol. 2019;180(3):464-474. doi:1111/bjd.16934
- Lipsky ZW, Marques CNH, German GK.Lipid depletion enables permeation of Staphylococcus aureus bacteria through human stratum corneum. Tissue Barriers. 2020;8:2:1754706. doi:1080/21688370.2020.1754706
- Hon KL, Kung JSC, Ng WGG, Leung TF. Emollient treatment of atopic dermatitis: latest evidence and clinical considerations. Drugs Context. 2018;7:212530. doi:7573/dic.212530
- Hebert AA, Rippke F, Weber TM, Nicol NH.Efficacy of nonprescription moisturizers for atopic dermatitis: an updated review of clinical evidence. Am J Clin Dermatol. 2020;21(5):641-655. doi:1007/s40257-020-00529-9
- Nosrati A, Afifi L, Danesh MJ, et al. Dietary modifications in atopic dermatitis: patient-reported outcomes. J Dermatolog Treat. 2017;28(6):523-538. doi:1080/09546634.2016.1278071
- Kim MJ, Kim SN, Lee YW, Choe YB, Ahn KJ. Vitamin D status and efficacy of vitamin D supplementation in atopic dermatitis: a systematic review and meta-analysis. Nutrients. 2016;8(12):789. doi:3390/nu8120789