and processing, thus opening potential new windows for pharmacologic intervention.
In psoriasis, inflammatory skin lesions induced by interleukin 23-recruited Th17 lymphocytes are characterized by keratinocyte hyperproliferation and incomplete terminal differentiation leading to inefficient permeability barrier function.47 Although the immune cell subsets and cytokines involved in AD and psoriasis pathogenesis differ notably, the deleterious vicious circle of barrier disruption/inflammation is still present in the latter. The incomplete terminal differentiation of psoriatic lesional keratinocytes is induced by T-lymphocyte mediated skin inflammation, which has significant impact on the ceramide expression compared to normal or non-involved skin.13 Similar to AD, in psoriasis lesions, ceramide species show shorter fatty acid chains and the reduced levels of CER[EOS], CER[NP], CER [EOH]. CER [AS] and CER [AP].48 Clinical observations of improvement of psoriasis vulgaris lesions under simple occlusion and of AD lesions with topical emollient therapy alone clearly indicate that restoration of / compensation for the SC barrier helps to interrupt the vicious circle of pathogenic self-propagation.49,50 Medical doctors were first to study the question given the abundance of clinical examples, including rare dermatological syndromes, and the impact of the barrier integrity on disease history, and often, patients’ fate, eg, in severe burns or generalized blistering diseases.
Environmental Stressors
In order to perform its protective functions, epidermis must adapt continuously to the changes in environmental conditions. These encompass climate/season–related factors such as relative humidity, ambient temperature, and sun exposure, as well as environmental aggressions due to the wide-spread use of chemicals, presence of atmospheric pollutants and changes in the composition and importance of skin surface microbiota, the latter being largely related to the aforementioned factors.
Prolonged natural ultraviolet (UV) radiation induces increased epidermal and perifollicular keratinization, resulting in flares in patients suffering from acne, that occur after discontinuation of inflammation-suppressing sun baths. Instead, acute, highdose exposure to UVB, and also UVA, promotes permeation of the SC barrier. Yet, barrier disruption produced by UV does not necessarily result in enhanced skin absorption. It depends on such factors as the UV wavelength, irradiation energy, and physicochemical properties of the permeants.51 In a hairless mice model, Takagi et al investigated the effects of UVB induced perturbation of skin barrier.52 In their experiment, 75 mJ/cm2 UVB induced significant increase in transepidermal water loss (TEWL) and reduction in the level of covalently bound ceramide and of transglutaminase-1. Tight junctions were also shown to be disrupted by UVB irradiation in human skin xenografts and skin equivalent models.53 The deleterious effects of UVB on the mechanical properties of human frozen/thawed SC, ie, SC cohesiveness, were only observed with non-physiological energy doses, greater than 160 J/cm².54 The impact of physiologically relevant doses of UV irradiation in terms of barrier structure, ceramide profiles, and consumer perceivable changes remains to be further investigated.
Moisture influences SC turnover by changing the rate of corneocyte desquamation. Indeed, it promotes a rapid rise in the SC pH, resulting in an increase of activity of kallikreins, the major SC serine proteases involved in desquamation.44 Also, water exposure facilitates accessibility of corneodesmosomes to the proteolytic enzymes, which stay otherwise encased within the largely hydrophobic extracellular spaces, and thus promotes release of the cells at the skin surface.25 Conversely, there is an observed persistence of corneodesmosomes in the outer SC of xerotic winter skin compared to normal skin.7 A recent review of the literature indicated that low humidity and low temperatures lead to a general decrease in skin barrier function and to increased susceptibility towards mechanical stress.55 These findings remain in line with the clinical observations of winter xerosis and of skin dryness in the elderly. Moreover, cold and dry weather are known to increase the prevalence and risk of flares in patients with atopic dermatitis.
Environmental factors causing impairment of skin barrier function include exposure to irritants and allergens. In the industrialized societies, the skin barrier is affected by the everyday use of detergents and disinfectants, in combination with the deleterious action of atmospheric pollutants that vary with geographic location and source. These pollutants contain solid and liquid particles suspended in the air and various gases such as ozone, nitrogen oxides, volatile organic compounds, and carbon monoxide. Particles vary in number, size, shape, surface area, and chemical composition, while both particles and gases may vary in solubility and toxicity. Occupational factors also play a role since they increase the risks in specific subpopulations. In health care professions, the extensive use of gloves results in occlusion, which significantly worsens the negative effect on skin barrier function of detergents/soaps. The published data indicate that a dose–response relationship is important with respect to duration of occlusion. This is particularly relevant for workplaces where shifting between wearing of gloves and hand washing is common. In the present “COVID eraâ€, the problems once encountered by medical and paramedical staff may spread into lay populations due to the widespread and highly repetitive use of hydrogels and other protective means.
The growth of skin flora is favored by increased temperature and humidity and modified by body location, age, sex, and chronic diseases such as diabetes. Occupation, hospitalization, use of soaps, disinfectants, and medications exert promoting and
In psoriasis, inflammatory skin lesions induced by interleukin 23-recruited Th17 lymphocytes are characterized by keratinocyte hyperproliferation and incomplete terminal differentiation leading to inefficient permeability barrier function.47 Although the immune cell subsets and cytokines involved in AD and psoriasis pathogenesis differ notably, the deleterious vicious circle of barrier disruption/inflammation is still present in the latter. The incomplete terminal differentiation of psoriatic lesional keratinocytes is induced by T-lymphocyte mediated skin inflammation, which has significant impact on the ceramide expression compared to normal or non-involved skin.13 Similar to AD, in psoriasis lesions, ceramide species show shorter fatty acid chains and the reduced levels of CER[EOS], CER[NP], CER [EOH]. CER [AS] and CER [AP].48 Clinical observations of improvement of psoriasis vulgaris lesions under simple occlusion and of AD lesions with topical emollient therapy alone clearly indicate that restoration of / compensation for the SC barrier helps to interrupt the vicious circle of pathogenic self-propagation.49,50 Medical doctors were first to study the question given the abundance of clinical examples, including rare dermatological syndromes, and the impact of the barrier integrity on disease history, and often, patients’ fate, eg, in severe burns or generalized blistering diseases.
Environmental Stressors
In order to perform its protective functions, epidermis must adapt continuously to the changes in environmental conditions. These encompass climate/season–related factors such as relative humidity, ambient temperature, and sun exposure, as well as environmental aggressions due to the wide-spread use of chemicals, presence of atmospheric pollutants and changes in the composition and importance of skin surface microbiota, the latter being largely related to the aforementioned factors.
Prolonged natural ultraviolet (UV) radiation induces increased epidermal and perifollicular keratinization, resulting in flares in patients suffering from acne, that occur after discontinuation of inflammation-suppressing sun baths. Instead, acute, highdose exposure to UVB, and also UVA, promotes permeation of the SC barrier. Yet, barrier disruption produced by UV does not necessarily result in enhanced skin absorption. It depends on such factors as the UV wavelength, irradiation energy, and physicochemical properties of the permeants.51 In a hairless mice model, Takagi et al investigated the effects of UVB induced perturbation of skin barrier.52 In their experiment, 75 mJ/cm2 UVB induced significant increase in transepidermal water loss (TEWL) and reduction in the level of covalently bound ceramide and of transglutaminase-1. Tight junctions were also shown to be disrupted by UVB irradiation in human skin xenografts and skin equivalent models.53 The deleterious effects of UVB on the mechanical properties of human frozen/thawed SC, ie, SC cohesiveness, were only observed with non-physiological energy doses, greater than 160 J/cm².54 The impact of physiologically relevant doses of UV irradiation in terms of barrier structure, ceramide profiles, and consumer perceivable changes remains to be further investigated.
Moisture influences SC turnover by changing the rate of corneocyte desquamation. Indeed, it promotes a rapid rise in the SC pH, resulting in an increase of activity of kallikreins, the major SC serine proteases involved in desquamation.44 Also, water exposure facilitates accessibility of corneodesmosomes to the proteolytic enzymes, which stay otherwise encased within the largely hydrophobic extracellular spaces, and thus promotes release of the cells at the skin surface.25 Conversely, there is an observed persistence of corneodesmosomes in the outer SC of xerotic winter skin compared to normal skin.7 A recent review of the literature indicated that low humidity and low temperatures lead to a general decrease in skin barrier function and to increased susceptibility towards mechanical stress.55 These findings remain in line with the clinical observations of winter xerosis and of skin dryness in the elderly. Moreover, cold and dry weather are known to increase the prevalence and risk of flares in patients with atopic dermatitis.
Environmental factors causing impairment of skin barrier function include exposure to irritants and allergens. In the industrialized societies, the skin barrier is affected by the everyday use of detergents and disinfectants, in combination with the deleterious action of atmospheric pollutants that vary with geographic location and source. These pollutants contain solid and liquid particles suspended in the air and various gases such as ozone, nitrogen oxides, volatile organic compounds, and carbon monoxide. Particles vary in number, size, shape, surface area, and chemical composition, while both particles and gases may vary in solubility and toxicity. Occupational factors also play a role since they increase the risks in specific subpopulations. In health care professions, the extensive use of gloves results in occlusion, which significantly worsens the negative effect on skin barrier function of detergents/soaps. The published data indicate that a dose–response relationship is important with respect to duration of occlusion. This is particularly relevant for workplaces where shifting between wearing of gloves and hand washing is common. In the present “COVID eraâ€, the problems once encountered by medical and paramedical staff may spread into lay populations due to the widespread and highly repetitive use of hydrogels and other protective means.
The growth of skin flora is favored by increased temperature and humidity and modified by body location, age, sex, and chronic diseases such as diabetes. Occupation, hospitalization, use of soaps, disinfectants, and medications exert promoting and
