Connecting the Dots: From Skin Barrier Dysfunction to Allergic Sensitization, and the Role of Moisturizers in Repairing the Skin Barrier

June 2019 | Volume 18 | Issue 6 | Original Article | 581 | Copyright © June 2019

Tamara Lazic Strugar MD,a Alyce Kuo BS,a Sophie Seité PhD,b Ma Lin MD PhD,c Peter Lio MDd

 

aIcahn School of Medicine at Mount Sinai, New York, NY

bLa Roche-Posay Dermatological Laboratories, Levallois-Perret, France

cBeijing Children's Hospital of Capital Medical University, China

dMedical Dermatology Associates of Chicago, IL

step of the atopic march.13 In AD skin, Staphylococcus aureus is more abundant than normal, with reduced populations of other species. While exact mechanisms of dysbiosis contributing to barrier disruption have not been fully elucidated, several factors likely contribute, including the production of exotoxins by Staphylococcus aureus.14 The distribution of bacterial communities on the cutaneous surface depends on factors such as moisture content, temperature, environment, and sebaceous gland abundance.15 Regulating skin microbiota could be one way to control AD, restore the skin barrier, and potentially prevent subsequent development of IgE sensitization and atopic march.16-18

The Chemical Skin Barrier
The chemical layer includes antimicrobial compounds such as human β-defensins, NMF, and lipids. NMF includes hygroscopic compounds, amino acids, and their derivatives. Many of these are products of filaggrin breakdown, some of which may have antimicrobial properties.9 Human β-defensins, or host peptides in the skin known for their direct antimicrobial activity, have been shown to attract immune effector cells and induce cytokine and chemokine production in keratinocytes. They also regulate tight junction and epidermal barrier function.19,20 Cathelicidins are another group of antimicrobial peptides that play a similar role.21 Commensal skin bacteria also produce antimicrobial peptides that can protect against Staphylococcus aureus.18 In healthy individuals, the skin pH is generally maintained between 4-6, and deviation can result in abnormal permeability.9 Removal of natural antimicrobial peptides and elevation of skin pH from the use of alkaline products create an unfavorable environment for the healthy skin microbiota, further demonstrating the interdependence of the levels.22 Additionally, following experimental skin barrier disruption and provocation of irritant contact dermatitis (ICD), changes in skin lipid composition were reported.23 The sulfur-rich part of the SC may act as a redox barrier, buffering chemicals coming into contact with the skin.24

The Physical Skin Barrier
Disruption of the physical layer of the skin barrier enhances entry of foreign substances. Corneocytes, which are flattened and denucleated mature keratinocytes, constitute the “bricks” of the SC, while lipid-rich “mortar” fills the gaps between.25 Below the SC is the stratum granulosum, made of keratinocytes that have granules containing proteins such as filaggrin. Keratinocytes also produce lipids such as triglycerides and cholesterols functioning as part of the chemical level. Tight junction proteins connect adjacent keratinocytes within the stratum granulosum to form a barrier against water and solutes.9

Filaggrin, an important protein of the epithelial barrier, aggregates and organizes keratin filaments.26 Mutations in the gene for filaggrin are a major risk factor for developing AD.27 Defects in skin barrier result from a combination of factors including filaggrin defects and deficiency of other skin barrier proteins, enhancing allergen sensitization via the skin.28 Importantly, even for individuals with normal filaggrin genes, in the presence of inflammatory mediators, Th2 signaling increases susceptibility to AD.29 Specifically, keratinocytes differentiated in the presence of Th2 cytokines IL-4 and IL-13 demonstrate decreased filaggrin expression.30 This may be why individuals with AD are more likely to acquire CD.23,31 Mutations in the same gene have been linked to increased risk of developing food allergies.32

Chronic skin diseases including AD, ichthyosis, and psoriasis often present with a disturbed SC. Patients with these diseases are advised to avoid contact with irritants or allergens that can lead to CD.23