Assessment of genomic and non-genomic molecular indicators for the development of steroid resistance in dermatoses of various etiologies

Resistance to systemic glucocorticosteroids in various dermatological conditions represents a serious clinical problem, often leading to treatment failure and exacerbation of the disease. The purpose of the review is to determine the relationships between association of genomic and non-genomic molecular factors and steroid resistance development in dermatoses of various etiologies. Genomic factors, including glucocorticoid receptor polymorphisms and changes in steroid metabolizing enzymes, may alter patient sensitivity to systemic glucocorticosteroids. All authors individually carried out a search of the available literature through PubMed, ScienceDirect, Wiley Online Library, Google Scholar, Cochrane Library, and MeSH using such key words "glucocorticoid receptor," and "glucocorticoid resistance," and "macrophage migration inhibitory factor," and "P-glycoprotein," and "polymorphism NR3C1," and "systemic lupus erythematosus," and "bullous pemphigoid," and "pemphigus vulgaris," and "atopic dermatitis." Out of 23 analyzed sources, 8 studies were selected that describe various genomic and nongenomic factors potentially influencing the development of steroid resistance in a vast variety of skin conditions including pemphigus, bullous pemphigoid, atopic dermatitis, nummular eczema, localized neurodermatitis, lichen planus, and cutaneous and systemic lupus erythematosus. We found that the mechanisms of steroid insensitivity were thoroughly studied in patients with systemic lupus erythematosus, including its cutaneous manifestations. Moreover, they differ in all these diseases. Meanwhile, the mechanisms underlying steroid resistance in other dermatological diseases are currently not fully understood. It is of a paramount importance to investigate mechanisms of steroid insensitivity and develop a panel of biomarkers which could predict steroid resistance in advance to optimize therapy of these conditions.