Connolly Mary Karin
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94115, USA.
Ann Transl Med. 2021 Mar;9(5):438. doi: 10.21037/atm-20-5449.
Despite progress in treating internal organ involvement in systemic sclerosis (scleroderma) (SSc), such as pulmonary disease, effective treatments for the hallmark of the disease, cutaneous fibrosis, remain elusive. None of the disease-modifying antirheumatic drugs (DMARDS) have shown proven efficacy for SSc skin fibrosis, and there remain no FDA-approved medications, all of which are off-label, for cutaneous fibrosis in SSc. This review article will briefly summarize conventional therapies, biologics and hematopoietic stem cell transplants and select ongoing clinical trials in SSc. The gold standard for measuring skin fibrosis in SSc is the modified Rodnan skin score (MRSSS). This is a validated test that measures skin thickness (0 to 3) at 17 locations for a total score of 51. Improvements in skin score over time are used in clinical trials to quantitate skin fibrosis. Although recording the Rodnan skin score is technically straightforward, requiring no special equipment, and noninvasive, the fluctuating natural history of the disease includes improvement over time without interventions, rendering meaningful trials difficult to assess. Understanding of the basic molecular mechanisms driving pathologic fibrosis in SSc remains lacking, and underpins the often empiric nature and likely the lack of efficacy of many therapeutics that have been tried. Although repeated skin biopsies might be a more precise way to follow disease progression and regression, this is necessarily invasive and requires special tools. Here, this review will look at conventional therapies, biologics, autologous hematopoietic stem cell transplantation, and catalog some of the ongoing clinical trials in SSc with a focus on cutaneous fibrosis.
尽管在治疗系统性硬化症（硬皮病）（SSc）的内脏器官受累方面取得了进展，如肺部疾病，但针对该疾病的标志性特征——皮肤纤维化，仍缺乏有效的治疗方法。没有一种改善病情抗风湿药（DMARDs）被证明对SSc皮肤纤维化有效，并且目前仍没有美国食品药品监督管理局（FDA）批准用于SSc皮肤纤维化的药物，所有用于该病症的药物都是未获批准的。这篇综述文章将简要总结传统疗法、生物制剂和造血干细胞移植，并介绍一些正在进行的SSc临床试验。测量SSc皮肤纤维化的金标准是改良Rodnan皮肤评分（MRSSS）。这是一项经过验证的测试，在17个部位测量皮肤厚度（0至3分），总分51分。临床试验中使用随时间推移皮肤评分的改善情况来量化皮肤纤维化。尽管记录Rodnan皮肤评分在技术上很简单，不需要特殊设备，且是非侵入性的，但该疾病波动的自然病程包括在无干预情况下随时间的改善，这使得有意义的试验难以评估。目前仍缺乏对驱动SSc病理性纤维化的基本分子机制的了解，这也是许多已尝试的治疗方法往往基于经验且可能缺乏疗效的原因。尽管重复进行皮肤活检可能是跟踪疾病进展和消退的更精确方法，但这必然是侵入性的，并且需要特殊工具。在此，本综述将探讨传统疗法、生物制剂、自体造血干细胞移植，并列举一些正在进行的SSc临床试验，重点关注皮肤纤维化。
