Stein Tomasz, Cieplewicz-Guźla Paulina, Iżykowska Katarzyna, Pieniawska Monika, Żaba Ryszard, Dańczak-Pazdrowska Aleksandra, Polańska Adriana
Department of Dermatology, Poznan University of Medical Sciences, 60-806 Poznan, Poland.
Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
J Clin Med. 2024 Nov 25;13(23):7134. doi: 10.3390/jcm13237134.
Morphea, also known as localized scleroderma, is an autoimmune chronic connective tissue disease. It is characterized by excessive collagen deposition in the dermis and/or subcutaneous tissue. The etiopathogenesis of this disease is not fully understood, with endothelial cell damage, immunological disorders, extracellular matrix disorders and factors such as infection, trauma and other autoimmune diseases being considered. As medicine advances, there is increasing evidence that genetic factors play a significant role in disease risk and progression. In addition to environmental factors and genetic predisposition, epigenetic factors may be potential triggers for morphea. Epigenetics studies changes that affect gene expression without altering the DNA sequence, such as microRNAs, long non-coding RNAs or DNA methylation. Understanding the pathogenesis of this disease is key to identifying potential new treatments. There are anecdotal reports of good therapeutic effects following the use of biological drugs such as tocilizumab, a humanized IgG monoclonal antibody; abatacept, a recombinant soluble fusion protein; JAK inhibitors, such as tofacitinib and baricitinib; and a drug used successfully in cancer treatment, imatinib, a tyrosine kinase receptor inhibitor. In this article, we aim to review up-to-date knowledge on the pathogenesis of morphea, with particular emphasis on genetic and epigenetic factors. In addition, we present the new options of morphea treatment based on several case series treated with new drugs that are potential targets for the development of therapies for this disease.
硬斑病，也称为局限性硬皮病，是一种自身免疫性慢性结缔组织疾病。其特征是真皮和/或皮下组织中胶原蛋白过度沉积。这种疾病的病因尚未完全明确，目前认为与内皮细胞损伤、免疫紊乱、细胞外基质紊乱以及感染、创伤和其他自身免疫性疾病等因素有关。随着医学的发展，越来越多的证据表明遗传因素在疾病风险和进展中起着重要作用。除了环境因素和遗传易感性外，表观遗传因素可能是硬斑病的潜在触发因素。表观遗传学研究的是在不改变DNA序列的情况下影响基因表达的变化，如微小RNA、长链非编码RNA或DNA甲基化。了解这种疾病的发病机制是确定潜在新疗法的关键。有一些轶事报道称，使用如托珠单抗（一种人源化IgG单克隆抗体）、阿巴西普（一种重组可溶性融合蛋白）、JAK抑制剂（如托法替布和巴瑞替尼）以及一种在癌症治疗中成功使用的药物伊马替尼（一种酪氨酸激酶受体抑制剂）等生物药物后，取得了良好的治疗效果。在本文中，我们旨在综述硬斑病发病机制的最新知识，特别强调遗传和表观遗传因素。此外，我们根据几个使用新药治疗的病例系列，介绍硬斑病治疗的新选择，这些新药是该疾病治疗开发的潜在靶点。
