Russian Journal of Skin and Venereal DiseasesRussian Journal of Skin and Venereal DiseasesРоссийский журнал кожных и венерических болезней1560-95882412-9097Eco-Vector63671110.17816/dv636711DERMATOLOGYДЕРМАТОЛОГИЯReview ArticleAssessment of genomic and non-genomic molecular indicators for the development of steroid resistance in dermatoses of various etiologiesОценка влияния геномных и негеномных молекулярных механизмов на развитие стероидной резистентности при дерматозах различной этиологии. Систематический обзорhttps://orcid.org/0000-0002-4365-30903261-3520LepekhovaAnfisa A.ЛепеховаАнфиса Александровна
Russian Federation

MD, Cand. Sci. (Medicine), Associate Professor

канд. мед. наук, доцент

anfisa.lepehova@yandex.ruhttps://orcid.org/0000-0003-2482-17542500-7989OlisovaOlga Y.ОлисоваОльга Юрьевна
Russian Federation

MD, Dr. Sci. (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences

д-р мед. наук, профессор, чл.-корр. РАН

olisovaolga@mail.ruhttps://orcid.org/0000-0002-5800-48008013-3256TeplyukNatalia P.ТеплюкНаталия Павловна
Russian Federation

MD, Dr. Sci. (Medicine), Professor

д-р мед. наук, профессор

teplyukn@gmail.comhttps://orcid.org/0000-0003-2433-77275028-6000DukhaninAlexander S.ДуханинАлександр Сергеевич
Russian Federation

MD, Dr. Sci. (Medicine), Professor

д-р мед. наук, профессор

das03du@mail.ruhttps://orcid.org/0009-0006-6798-881XBakasovaValeria E.БакасоваВалерия Евгеньевна
Russian Federation
valeria-bakasova@mail.ruThe First Sechenov Moscow State Medical University (Sechenov University)Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)The First Sechenov Moscow State Medical University (Sechenov University)Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)The Russian National Research Medical University named after N.I. PirogovРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова10122024231220242766306390410202426102024Copyright ©; 2024, Eco-VectorCopyright ©; 2024, Эко-Вектор2024Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://rjsvd.com/1560-9588/article/view/636711

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.

Устойчивость к системным глюкокортикоидам при различных дерматологических заболеваниях представляет серьёзную клиническую проблему, обусловливающую неэффективность лечения и обострение заболевания. Геномные факторы, включая полиморфизм глюкокортикоидных рецепторов и изменения ферментов метаболизма стероидов, способны изменять чувствительность пациентов к системным глюкокортикоидам.

Авторами обзора выполнен анализ влияния геномных и негеномных молекулярных механизмов на развитие стероидной резистентности у дерматологических больных, для чего в базах данных доказательной медицины (PubMed, ScienceDirect, Wiley Online Library, Google Scholar, Cochrane Library и MeSH) осуществлялся поиск опубликованной литературы по указанной тематике. Поиск исследований проводился по таким ключевым словам, как «glucocorticoid receptor», «glucocorticoid resistance», «macrophage migration inhibitory factor», «P-glycoprotein», «polymorphism NR3C1», «systemic lupus erythematosus», «bullous pemphigoid», «pemphigus vulgaris», «atopic dermatitis». Из 23 проанализированных источников было выбрано 8 исследований, описывающих различные геномные и негеномные факторы, которые потенциально могут влиять на формирование стероидной резистентности у пациентов с такими заболеваниями, как пузырчатка, буллёзный пемфигоид, атопический дерматит, нумулярная экзема, ограниченный нейродермит, красный плоский лишай, кожная форма системной красной волчанки.

Проведённая нами поисково-аналитическая работа позволила установить, что патогенез стероидной резистентности наиболее подробно изучен только для системной красной волчанки, в том числе с кожными проявлениями, при этом механизмы формирования стероидной резистентности при других дерматологических заболеваниях в настоящее время до конца не изучены. Кроме того, следует отметить, что механизмы её формирования при этих заболеваниях отличались. Исследование новых механизмов развития стероидной резистентности, а также разработка универсальных биомаркеров стероидной резистентности позволит усовершенствовать и оптимизировать терапию рассматриваемых дерматозов в будущем.

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