系统性硬化症皮肤纤维化的诊断和治疗新挑战

IF 8.7 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
David Abraham , Alain Lescoat , Richard Stratton
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引用次数: 0

摘要

系统性硬化症(又称硬皮病,SSc)是一种慢性自身免疫性疾病,其特点是胶原蛋白过度沉积,导致皮肤纤维化和各种内脏器官表现。硬皮病的新兴诊断和治疗策略侧重于早期检测和有针对性的干预,以改善患者的预后和生活质量。近年来,在血清学标志物和成像技术进步的推动下,SSc 的诊断方法有了长足的发展。自身抗体分析,尤其是抗核抗体(ANA)和特定的硬皮病相关自身抗体,有助于识别硬皮病亚群和预测疾病进展。此外,高频超声波和光学相干断层扫描等新型成像模式能够早期发现皮肤纤维化和内脏器官受累,从而提高诊断的精确度,并进行有针对性的治疗。SSc 的治疗策略是多方面的,主要针对免疫失调、血管异常和纤维化过程。新出现的生物制剂已在临床试验中显示出前景,包括针对参与纤维化的关键细胞因子(如转化生长因子-β(TGF-β)和白细胞介素-6(IL-6))的单克隆抗体。此外,能破坏纤维化通路的小分子抑制剂,如酪氨酸激酶抑制剂,在限制胶原沉积和预防疾病进展方面也具有潜力。干细胞疗法、细胞消融和基因编辑技术在再生受损组织和阻止纤维化过程方面具有巨大潜力。由于不可逆的组织损伤往往发生在晚期,因此早期干预对于控制 SSc 依然至关重要。目前正在探索新的诊断方法,如生物标志物和基因表达谱分析,以确定罹患进展性严重疾病的高危人群,并进行积极干预。此外,还在研究针对患者的治疗方法,将免疫抑制剂和靶向抗纤维化疗法相结合,以提高疗效,同时最大限度地减少不良反应。新出现的硬皮病诊断和治疗策略正在改变这种具有挑战性疾病的治疗方法。然而,要优化这些新方法在复杂多样的 SSc 表现中的疗效和安全性,还需要持续的研究和临床试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Emerging diagnostic and therapeutic challenges for skin fibrosis in systemic sclerosis

Systemic sclerosis (also called scleroderma, SSc) is a chronic autoimmune disorder characterized by excessive collagen deposition leading to skin fibrosis and various internal organ manifestations. The emergent diagnostics and therapeutic strategies for scleroderma focus on early detection and targeted interventions to improve patient outcomes and quality of life. Diagnostics for SSc have evolved significantly in recent years, driven by advancements in serological markers and imaging techniques. Autoantibody profiling, especially antinuclear antibodies (ANA) and specific scleroderma-associated autoantibodies, aids in identifying subsets of scleroderma and predicting disease progression. Furthermore, novel imaging modalities, such as high-frequency ultrasonography and optical coherence tomography, enable early detection of skin fibrosis and internal organ involvement, enhancing the diagnostic precision and allowing for tailored management. Therapeutic strategies for SSc are multifaceted, targeting immune dysregulation, vascular abnormalities, and fibrotic processes. Emerging biologic agents have shown promise in clinical trials, including monoclonal antibodies directed against key cytokines involved in fibrosis, such as transforming growth factor-β (TGF-β) and interleukin-6 (IL-6). Additionally, small-molecule inhibitors that disrupt fibrotic pathways, like tyrosine kinase inhibitors, have exhibited potential in limiting collagen deposition and preventing disease progression. Stem cell therapy, cell ablation and gene editing techniques hold great potential in regenerating damaged tissue and halting fibrotic processes. Early intervention remains crucial in managing SSc, as irreversible tissue damage often occurs in advanced stages. Novel diagnostic methods, such as biomarkers and gene expression profiling, are being explored to identify individuals at high risk for developing progressive severe disease and intervene proactively. Furthermore, patient-tailored therapeutic approaches, employing a combination of immunosuppressive agents and targeted anti-fibrotic therapies, are being investigated to improve treatment efficacy while minimizing adverse effects. The emergent diagnostics and therapeutic strategies in scleroderma are transforming the management of this challenging disease. Nevertheless, ongoing research and clinical trials are needed to optimize the efficacy and safety of these novel approaches in the complex and diverse spectrum of SSc manifestations.

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来源期刊
Molecular Aspects of Medicine
Molecular Aspects of Medicine 医学-生化与分子生物学
CiteScore
18.20
自引率
0.00%
发文量
85
审稿时长
55 days
期刊介绍: Molecular Aspects of Medicine is a review journal that serves as an official publication of the International Union of Biochemistry and Molecular Biology. It caters to physicians and biomedical scientists and aims to bridge the gap between these two fields. The journal encourages practicing clinical scientists to contribute by providing extended reviews on the molecular aspects of a specific medical field. These articles are written in a way that appeals to both doctors who may struggle with basic science and basic scientists who may have limited awareness of clinical practice issues. The journal covers a wide range of medical topics to showcase the molecular insights gained from basic science and highlight the challenging problems that medicine presents to the scientific community.
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