Glucocorticoid Receptor Beta and Its Prognostic Value on Treatment Response in Chronic Vulvar Dermatitis

Abstract

<b><i>Background:</i></b> Chronic vulvar dermatitis (CVD) is the most prevalent disease in gynecologic dermatology. The treatment mainly depends on topical glucocorticoids (TGC) but is challenged by insufficient treatment response. On a histological level, the upregulation of the glucocorticoid receptor β (GRβ), an inhibitor of the active glucocorticoid receptor α (GRα), is discussed as mechanism of glucocorticoid insensitivity. <b><i>Objectives:</i></b> To analyze whether the expression of GRβ protein at baseline in keratinocytes may predict responsiveness to TGC in patients with CVD. <b><i>Methods:</i></b> In this retrospective cohort study, clinical and biological data of 25 women with a histological diagnosis of chronic vulvar eczema were analyzed. Randomization was done according to the responsiveness to TGC treatment (responsive vs. nonresponsive). Clinical data and the expression of GRβ in the immunohistochemical stained biopsies were examined. <b><i>Results:</i></b> Fifty-two percent of women with CVD were nonresponsive to TGC. GRβ was abundantly expressed in the cytoplasma of keratinocytes of the vulvar epithelium, but no difference in the level of expression was found among GC responsive and nonresponsive patients in the semiquantitative (<i>p</i> = 0.376) and quantitative analysis (<i>p</i> = 0.894). <b><i>Conclusion:</i></b> GRβ is highly expressed in keratinocytes of the vulvar epidermis affected by CVD, but GRβ expression was not increased in patients nonresponsive to TGC compared to responsive patients. Thus, the failure mechanism in nonresponders still remains to be elucidated.

GR‐α and GR‐β mRNA levels in peripheral blood mononuclear cells of acute myelitis patients can assist in the identification of glucocorticoid sensitivity and are correlated with glucocorticoid therapeutic effect

“…The physiological response and sensitivity of GR to GCs vary with species, individual, tissue, cell type, and even cell cycle (Ali et al., 2019; Frohman & Wingerchuk, 2010). The two most important isoforms of GR, GR‐α and GR‐β are expressed in most human tissues and cell lines (Bernays et al., 2021). GR‐α is critical in corticosteroid therapy in interstitial lung diseases, and its expression is considered a potential biomarker for predicting corticosteroid sensitivity (Bin et al., 2019).…”