Glucocorticoids have anti-inflammatory effects and are used to treat conditions that involve inflammation.
Synthetic or semisynthetic glucocorticoids, derived chiefly from cortisol, include prednisone, prednisolone, dexamethasone, methylprednisolone, triamcinolone, and betamethasone.
Glucocorticoids-mediated skin atrophy involves thinning of the epidermis and dermis (and even hypodermis), resulting in increased water permeability and, thus, in increased transepidermal water loss. The thinning is caused by a decreased proliferative rate of keratinocytes and dermal fibroblasts. The origin of the decreased proliferation lies in collagen turnover. Transforming growth factor β (TGF-β) is a signaling molecule that, among other actions, promotes production of collagen, using Smad proteins as second messengers. Activated GR negatively regulates Smad3 through a protein-protein interaction, in this way, blocking expression of the COL1A2 gene, which encodes a type I collagen chain. Type I collagen represents roughly 80% of the total share of skin collagen. Therefore, glucocorticoids reduce collagen turnover through blocking of TGF-β actions.
Glucocorticoids also diminish synthesis of epidermal lipids. Furthermore, glucocorticoids reduce collagenases, which are part of the matrix metalloproteinases (MMPs) and tissue inhibitors of the metalloproteinases TIMP-1 and TIMP-2. Striae formation, which occurs in hypercortisolism and may occur after long-term topical treatment with glucocorticoids, may be explained by the skin tensile strength determined by type I and type III collagens.
The thinning of epidermis caused by glucocorticoids’ long-term topical treatment appears also to be related with the repression of K5–K14 keratin genes, which are markers of the basal keratinocytes. Additionally, these drugs inhibit K6–K16 keratin genes, markers of activated keratinocytes, therefore promoting impaired wound healing.
Special attention should be paid when applying topical corticosteroids in the presence of an infection, as there is a risk of exacerbation. Topical corticosteroids can inhibit the skin’s ability to fight against bacterial or fungal infections.
Int J Endocrinol. 2012
Mechanisms of Action of Topical Corticosteroids in Psoriasis
Luís Uva, Diana Miguel, Catarina Pinheiro