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Cortisol Homeostasis in the Epidermis is Influenced by Topical Corticosteroids in Patients with Atopic Dermatitis.

ABSTRACT: The skin produces cortisol by itself and regulates its own proliferation and differentiation. There is a possibility that topical corticosteroids (TCSs) influence the cortisol homeostasis in the skin.The author described the density and distribution of cortisol and its parties in the epidermis after application of topical steroids immunohistologically.The forearm skin was biopsied before and after 2 weeks' application of clobetasol propionate 0.05% two times a day in one healthy volunteer. The biopsied skin was stained immunohistologically by ant-MLN64, StAR, CPY11A1, cortisol, HSD11B1, HSD11B2, glucocorticoid receptor alpha, glucocorticoid receptor beta (GRB), and mineralocorticoid receptor (MCR) antibodies. The skin biopsy was performed similarly in 19 adult patients with atopic dermatitis who had used TCS for a considerable period. They were 4 TCS present users (TCS+), 12 TCS nonusers with skin manifestation on the biopsied site (TCS-E+) and 3 TCS nonusers without skin manifestation on the biopsied site (TCS-E-).The staining density increased during TCS application in MLN64, cortisol and HSD11B2 in a healthy volunteer. The staining density was stronger in HSD11B2 of the basal layer and MCR of the spinous layer in the TCS-E+ patients than in the TCS+ and TCS-E- patients. The staining density was weaker in MLN64 of the basal and granular layers, HSD11B1 of the basal layer and GRB of the whole layer in the TCS-E+ patients than in the TCS+ and TCS-E- patients.The hypertrophy of the epidermis and insufficient keratinization recognized in the TCS-E+ patients might be caused by the decreased cortisol synthesis regulated by MLN64 and the increased cortisol inactivation by HSD11B2. Decreased GRB and increased MCR might enhance the reactivity of cortisol in the keratinocytes.

SUBMITTER: Fukaya M

PROVIDER: S-EPMC5527739 | biostudies-other | 2017 Jul-Aug

REPOSITORIES: biostudies-other

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Project description:ObjectiveAn umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema.MethodsEmbase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and Epistemonikos until 2 March 2021. Reviews were included if they assessed the safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality was assessed using version 2 of 'A MeaSurement Tool to Assess systematic Reviews' (AMSTAR 2 tool).Results38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up were usually short (2-4 weeks).Key findingsTCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4% to 5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased.TCS versus topical calcineurin inhibitors: Meta-analysis showed higher relative risk of skin thinning with TCS (4.86, 95% CI 1.06 to 22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares ('weekend therapy') versus vehicle: No meta-analyses identified. No evidence of skin thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).ConclusionsW e found no evidence of harm when TCS were used intermittently 'as required' to treat flares or 'weekend therapy' to prevent flares. However, long-term safety data were limited.Prospero registration numberCRD42018079409.

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Cortisol Homeostasis in the Epidermis is Influenced by Topical Corticosteroids in Patients with Atopic Dermatitis.

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