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The epidermis is composed of stratified cell layers, which undergo programmed differentiation to allow for constant renewal of the skin. Epidermal stem cells, which account for 1 to 10% of basal layer cells, give rise to transit-amplifying cells which yield terminally differentiated cells. Epidermal proliferative unit (EPU), 2 mm in size, is a functionally independent packet of self-renewing interfollicular epidermis, and one stem cell resides at the base of each EPU. Normal transit time from basal layer to desquamation is 28 days. Keratins, the cytoskeleton of keratinocytes, belong to intermediate filaments; mature keratin filaments contain types I & II keratins in a 1:1 molar ratio. Keratinocytes produce K5/K14 (K15) in the basal layer, K1/K10 in suprabasal layers, K2 in granular layer, and K9, K6a/b, K16, K17 in palmoplantar skin. Besides structural support, keratins are involved in cell and tissue growth, skin pigmentation, keratinocyte migration and immunomodulation. At plasma membrane, keratins are linked by adapter proteins to 2 types of anchoring junctions, desmosomes between adjacent cells, and hemidesmosomes between cell and dermal matrix. Adapter proteins in desmosomes include desmogleins, desmocollins, plakoglobin and plakophilin, and in hemidesmosomes, BPAG1, BPAG2, plectin, α6β4 integrin and laminin-332/laminin-311. In DE junction, anchoring fibrils consisting of type VII collagen is the strongest tie between epidermis and dermis, followed by hemidesmosome. Skin barrier is formed by corneocytes (“bricks”) reinforced by cornified envelope (CE), and intercellular lipids (“mortar”). CE is a covalently cross-linked protein polymer that forms underneath, and eventually replaces, keratinocyte membrane in the granular layer. The isopeptide bonds of CE are catalyzed by transglutaminases, a group of calcium-dependent enzymes. Among protein constituents of CE, involucrin synthesis begins in spinous layer; loricrin is the major structural component of CE; and filaggrin aggregates keratins into bundles and is eventually degraded to free amino acids, yielding natural moisturizing factors (NMF). Lamellar bodies, containing glycosylceramides, sphingomyelin, phospholipids, serine proteases, antimicrobial peptides and hydrolytic enzymes, are extruded to interface at SG/SC interface and form lipid bilayers in SC. Polar lipid precursors are “processed” into non-polar lipids (ceramides [45%], cholesterol [25%], free fatty acids [15%]) by specific hydrolytic enzymes and form the “mortar” of SC. Epidermal kallikreins are serine proteases that degrade corneodesmosomes and thus play a key role in desquamation. Tight junctions, located in SG2 layer, are second line barrier, and gap junctions formed by connexins are intercellular gatekeepers. Barrier insults stimulate not only repair responses, but also initiate cytokine cascade; IL-1, TNF and IL-6 are stimulators of lipid synthesis. Epidermal differentiation and lamellar body secretion is coordinately regulated by calcium and nuclear hormone receptors.
“Sensitive skin” is a self-diagnosed condition, a subjective cutaneous hyper-reactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions including itching, burning, stinging and tight sensation when their skin is in contact with cosmetics, soaps and sunscreens. Substances not commonly considered irritants may cause irritation. Patients with sensitive skin have very dry skin with low lipids, disturbed skin barrier function, increased transcutaneous penetration of water-soluble chemicals, hyperreaction of cutaneous blood vessels, enhanced immune responsiveness, reduced alkali resistance and increased neurosensory stimulation. Many have atopic background or concomitant rosacea. Materials that help sensitive skin include niacinamide (vitamin B3), panthenol (provitamin B5), vitamin E (tocopherol), ceramides, and metals such as zinc, copper, selenium, strontium and magnesium. On the other hand, vitamin A products, hydroxyl acids (esp. glycolic acid, lactic acid and salicylic acid), preservatives (formaldehyde, quaternium 15, paraben, etc.), fragrances (cinnamic acid compounds), propylene glycol, quaternary ammonium compounds, sodium lauryl sulfate, urea, scrubs/ exfoliants, vitamin C and oxybenzone should be avoided in these patients. Appropriate skin care for sensitive skin consists of gentle cleansing with mild, neutral products, effective moisturization, and UVA/UVB protection. For facial cleanser, mild liquid cleansers or self-foaming wash with pH similar to skin, high rinsibility, nonionic and silicone surfactants, and added emollients and humectants are best because they damage the skin barrier the least. Moisturizers should have occlusives and humectants in an ideal combination. Among occlusives, mineral oil and petrolatum are the most effective; silicone derivatives (dimethicone, cyclomethicone), lecithin, squalene, paraffin and soybean oil are also safe to use. Among humectants, glycerin and glycerol are the most effective. For sunscreen, physical (inorganic) filters such as zinc oxide and titanium dioxide are better than chemical (organic) filters because they are broad spectrum, safe, photostable and non-irritating. When consulting patients with sensitive skin, dermatologists should keep in mind the principle of and products for achieving skin barrier repair without irritation so that they can provide to these patients specific advice on which products to choose.