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Eczema (dermatitis)
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
A marked decrease in skin barrier function is observed in AD patients due to the downregulation of cornified envelope genes (filaggrin and loricrin), reduced ceramide levels in epidermis, enhanced transepidermal water loss, and increased levels of endogenous proteolytic enzymes. Frequent use of alkaline soap and detergents raise the pH of skin, increasing the activity of endogenous protease enzymes, leading to further decrease of epidermal barrier function. Exogenous proteases from Staphylococcus aureus (S. aureus) and house dust mites also take a toll on the epidermal barrier. Deficiency of few endogenous protease inhibitors in atopic skin worsens the situation. The defective epidermal barrier leads to increased allergen absorption and microbial colonization of the skin. Epicutaneous sensitization to these environmental allergens, chemicals, and antigens results in inflammatory responses and a high level of immunologic memory, thus predisposing these children to the development of respiratory allergy and food allergy later in life.
Endocrine and Metabolic Side Effects
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Ayse Serap Karadag, Emin Ozlu, Bodo C. Melnik
Daily oral application of 30 mg alitretinoin in patients with chronic hand eczema increased Ki-67-positive cells in the suprabasal layer and a normalized dysregulated expression of various skin barrier genes (claudin 1, loricrin, filaggrin, and cytokeratin 10) and TSLP (175). Alitretinoin is also negative regulator of TSLP expression in airway epithelial cells (176). Inhibition of IL-1β-dependent genes by active RXRs involves antagonism of NF-κB signaling (177).
Xerosis, Itching, and Fissures
Published in Gabriella Fabbrocini, Mario E. Lacouture, Antonella Tosti, Dermatologic Reactions to Cancer Therapies, 2019
Gabriella Fabbrocini, Tiziana Peduto, Mariateresa Cantelli
It should also be taken into consideration that dryness can also occur in the mucous membranes, especially the vaginal, and the perineum, with discomfort during urination. Skin xerosis predisposes to the onset of itching, a symptom almost entirely reported by patients. It is usually generalized and exacerbated by heat, and presents at day and at night causing an interrupted sleep. There is often no primary rash; however, there may be numerous linear excoriations on the skin secondary to scratching (5). It tends to persist even after the suspension of the therapy (8). The pathogenesis of xerosis is linked to the alteration of skin barrier integrity highlighted during therapy with EGFRis. Indeed, numerous studies have shown that knock-out mice for EGFR tend to develop drier skin, with decreasing production of loricrin in the granular epidermis layer. This molecule plays a key role in maintaining the epidermis barrier function, as it represents the most abundant protein of the stratum corneum, which, in addition to serving as an important barrier protein, also contributes to counteract transepidermal water loss and electrolysis (4).
The Epidermal Barrier Structure and Function of Re-Harvested Skin from Non-Scalp Donor Sites
Published in Journal of Investigative Surgery, 2023
Bohan Zhang, Peng Luo, Jiachen Sun, Dawei Li, Zhaoxing Liu, Xinzhu Liu, Hongqing Zhao, Zhisheng Li, Xiaoye Xie, Jianqiu Yang, Chuan’an Shen
The structural proteins of CE include filaggrin, loricrin, involucrin, SPRR, etc., which play a key role in providing resistance to external mechanical tension, preventing the invasion of pathogens and allergens, and preventing excessive water loss in the body.11 Filaggrin is mainly expressed in the granular layer and the transparent layer of the epidermis, which interacts with keratin intermediate filaments and aggregates to form dense keratin fiber bundles, thereby forming a flat and tough scaffold structure of keratinocytes.12 With the participation of SPRR, loricrin and involucrin cross-link with each other to form an abnormally water-insoluble CE, wrapping keratin fiber bundles and forming the unique stratum corneum barrier structure of the epidermis.12 In this study, these proteins were analyzed by IHC staining. The results revealed that the expression of CE structural proteins in the skin tended to decrease as the skin was re-harvested. As a result, the connection between keratin proteins was weakened, thus impairing the barrier function.
Baricitinib for the treatment of atopic dermatitis
Published in Journal of Dermatological Treatment, 2022
Amelia Melo, Jose Manuel Carrascosa, Tiago Torres
AD is found to present a biphasic inflammation, concerning its immune response. In the initial acute phase, a Th2-biased immune response dominates, with eosinophils, TSLP, IL-4, IL-5, IL-13, IL-31 and CCL18, associated with Th22 responses, like IL-22 and S100A proteins. These seem to downregulate terminal differentiation genes and tight junction products which causes skin barrier dysfunction (49–57). IL-4 and IL-13 are known to play a significant part in the pathogenesis of this condition and AD has been proven to be genetically related to IL-4 and IL-13 polymorphisms (58–61). In addition, in the presence of IL-4 and IL-13, keratinocytes show an appreciably decrease in filaggrin gene expression (62). IL-4 and IL-13 also downregulate loricrin and involucrin in the skin of patients with AD (53). On the other hand, there seems to be a Th1/Th0 dominance, with IL-12, IL-5, IFN-γ and GM-CSF, in the chronic phase (49,63).
Portulaca oleracea extract relieves skin barrier damage induced by increased photosensitivity after GA peeling
Published in Cutaneous and Ocular Toxicology, 2022
Jing Wei, Qianghua Quan, Peiyu Wang, Yiming Wang, Tong Huo, Quan An
Modern studies have revealed that P. oleracea extract is capable of regulating the TNF-α-induced NF-κB signalling pathway as well as suppressing the overexpression of pro-inflammatory factors25. Zhao et al.26 reported that with the use of a cream containing calcipotriol ointment and P. oleracea extract for four consecutive weeks, the protein expression levels of Keratin 10 (K10), loricrin (LOR), and FLG were significantly downregulated in psoriatic lesions and TEWL values were significantly decreased. Keratins are the major proteins in the epidermis. They build the intermediate filament (IF) cytoskeleton, which provides epidermal stability because they are highly crosslinked with the cornified envelope. Keratin 1 (K1) and K10 are among the first keratins to be expressed during cornification27. LOR is synthesized and subsequently crosslinked by several transglutaminases to reinforce epidermal stability28. These studies have shown that P. oleracea has effects on inhibiting inflammation and repairing the skin barrier. Our research also confirmed that P. oleracea can relieve damage to the skin barrier and inflammation induced by GA + UVB.