Cortisol homeostasis in the epidermis is influenced by topical corticosteroids in patients with atopic dermatitis

Abstract

Background: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.Aims and Objectives:The author described the density and distribution of cortisol and its parties in the epidermis after application of topical steroids immunohistologically.Materials and Methods: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−).Results: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.Conclusion: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.

Topical Steroid Withdrawal: A Case Series of 10 Children

“…Rapaport & Lebwohl proposed the mechanism for widespread erythema following TCS ceswww.medicaljournals.se/acta sation was secondary to the release of accumulated nitric oxide stores causing hyper-dilation of blood vessels (23) (TCSs suppress nitric oxide in the endothelium). Fukaya (24) proposed cortisol production by keratinocytes is suppressed by TCSs and so on cessation of TCSs there is relative cortisol insufficiency giving rise to some of the symptoms seen in TSW. It is possible disturbances at a cellular level -of which there may be several considering the multifactorial mode of action of TCSs -take considerable time to normalise.…”

Steroid Phobia: Is There a Basis? A Review of Topical Steroid Safety, Addiction and Withdrawal

“…Early cell models studies showed that exposure to glucocorticoids resulted in down-regulation of GR DNA and mRNA [50,51]. Subsequent studies have gone further to study variations in the two splicing variants of GR, the GRa and GRb isoform [52,53]. In 2009, Hagg [52] observed that following TCS treatment, patients with poor clinical response had upregulated GRb expression while this was unchanged in patients with good clinical response.…”

“…He hypothesised that TCS application causes a decrease in self-production of cortisol by keratinocytes. However, a second study by Fukaya in 2017 showed an increase in cortisol staining in the epidermis with TCS application, followed by a decrease after cessation in a single healthy volunteer after 2 weeks of clobetasol propionate application [53]. The evidence for this thus remains unclear.…”