Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, China.
Research Unit of Key Technologies of Immune-Related Skin Diseases Diagnosis and Treatment, Chinese Academy of Medical Sciences, Changsha, China.
Clin Rev Allergy Immunol. 2022 Apr;62(2):273-291. doi: 10.1007/s12016-020-08831-4. Epub 2021 Jan 15.
There are two major clinical subsets of scleroderma: (i) systemic sclerosis (SSc) is a complex systemic autoimmune disorder characterized by inflammation, vasculopathy, and excessive fibrosis of the skin and multiple internal organs and (ii) localized scleroderma (LoS), also known as morphea, is confined to the skin and/or subcutaneous tissues resulting in collagen deposition and subsequent fibrosis. SSc is rare but is associated with significant morbidity and mortality compared with other rheumatic diseases. Fatal outcomes in SSc often originate from organ complications of the disease, such as lung fibrosis, pulmonary artery hypertension (PAH), and scleroderma renal crisis (SRC). Current treatment modalities in SSc have focused on targeting vascular damage, fibrosis, and regulation of inflammation as well as autoimmune responses. Some drugs previously used in an attempt to suppress fibrosis, like D-penicillamine (D-Pen) or colchicine, have been disappointing in clinical practice despite anecdotal evidence of their advantages. Some canonical medications, including glucocorticoids, immunosuppressants, and vasodilators, have had some success in treating various manifestations in SSc patients. Increasing evidence suggests that some biologic agents targeting collagen, cytokines, and cell surface molecules might have promising therapeutic effects in SSc. In recent years, hematopoietic stem cell transplantation (HSCT), mostly autologous, has made great progress as a promising treatment option in severe and refractory SSc. Due to the complexity and heterogeneity of SSc, there are currently no optimal treatments for all aspects of the disease. As for LoS, local skin-targeted therapy is generally used, including topical application of glucocorticoids or other immunomodulatory ointments and ultraviolet (UV) irradiation. In addition, systemic immunosuppressants are also utilized in several forms of LoS. Here, we comprehensively discuss current treatment options for scleroderma, encompassing old, new, and future potential treatment options. In addition, we summarize data from new clinical trials that have the potential to modify the disease process and improve long-term outcomes in SSc.
（i）系统性硬化症（SSc）是一种复杂的系统性自身免疫性疾病，其特征为炎症、血管病变以及皮肤和多个内部器官的过度纤维化；（ii）局限性硬皮病（LoS），也称为硬斑病，局限于皮肤和/或皮下组织，导致胶原蛋白沉积和随后的纤维化。SSc 较为罕见，但与其他风湿性疾病相比，其发病率和死亡率都较高。SSc 患者的死亡结局通常源于疾病的器官并发症，如肺纤维化、肺动脉高压（PAH）和硬皮病肾危象（SRC）。目前 SSc 的治疗方法侧重于靶向血管损伤、纤维化以及炎症和自身免疫反应的调节。一些以前用于试图抑制纤维化的药物，如 D-青霉胺（D-Pen）或秋水仙碱，尽管有其优势的传闻证据，但在临床实践中却令人失望。一些经典药物，包括糖皮质激素、免疫抑制剂和血管扩张剂，在治疗 SSc 患者的各种表现方面取得了一些成功。越来越多的证据表明，一些针对胶原蛋白、细胞因子和细胞表面分子的生物制剂在 SSc 中可能具有有前途的治疗效果。近年来，造血干细胞移植（HSCT），主要是自体 HSCT，作为一种严重和难治性 SSc 的有希望的治疗选择取得了很大进展。由于 SSc 的复杂性和异质性，目前尚无针对该疾病所有方面的最佳治疗方法。对于 LoS，通常使用局部皮肤靶向治疗，包括局部应用糖皮质激素或其他免疫调节软膏和紫外线（UV）照射。此外，还在几种形式的 LoS 中使用全身性免疫抑制剂。在这里，我们全面讨论了硬皮病的当前治疗选择，包括旧的、新的和未来潜在的治疗选择。此外，我们总结了具有改变疾病进程和改善 SSc 长期结局潜力的新临床试验数据。
