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首页> 外文期刊>Rheumatology >Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis.
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Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis.

机译：局部硬皮病和全身性硬化症的局部治疗改善的发病机理和治疗方法。

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SSc is a chronic progressive disorder of unknown aetiology characterized by excess synthesis and deposition of collagen and other extracellular matrix components in a variety of tissues and organs. Localized scleroderma (LS) differs from SSc in that with LS only skin and occasionally subcutaneous tissues are involved. Although rarely life threatening, LS can be disfiguring and disabling and, consequently, can adversely affect quality of life. There is no known effective treatment for LS, and various options, including, as examples, corticosteroids and other immunomodulatory agents, ultraviolet radiation and vitamin D analogues, are of unproven efficacy. Clinical trials evaluating combination therapy such as corticosteroids with MTX or UVA1 exposure with psoralens have not been established as consistently effective. New immunomodulators such as tacrolimus and thalidomide are also being evaluated. A better understanding of the molecular and cellular mechanisms of LS has led to evaluation of new treatments that modulate profibrotic cytokines such as TGF-beta and IL-4, regulate assembly and deposition of extracellular matrix components, and restore Th1/Th2 immune balance by administering IL-12 or IFN-gamma. IFN-gamma acts by directly inhibiting collagen synthesis and by restoring immune balance. In this review, we evaluate current and future treatment options for LS and cutaneous involvement in SSc. Recent advances in therapy focus mainly on anti-fibrotic agents. Delivery of these drugs into the skin as the target tissue might be a key factor in developing more effective and safer therapy.
机译：SSc是一种病因不明的慢性进行性疾病，其特征是胶原蛋白和其他细胞外基质成分在多种组织和器官中过度合成和沉积。局部硬皮病（LS）与SSc的不同之处在于，局部硬皮病仅涉及皮肤，偶尔涉及皮下组织。尽管生活威胁很少，但生活保障可能会毁容和残废，因此可能对生活质量产生不利影响。尚无有效的LS治疗方法，各种选择的药效尚未得到证实，包括皮质类固醇和其他免疫调节剂，紫外线辐射和维生素D类似物。尚未评估评估联合治疗（如皮质类固醇与MTX或补骨脂素与UVA1接触）的持续疗效。还正在评估新的免疫调节剂，例如他克莫司和沙利度胺。对LS分子和细胞机制的更好理解导致对新疗法的评估，这些疗法可调节促纤维化细胞因子（例如TGF-beta和IL-4），调节细胞外基质成分的组装和沉积以及通过施用来恢复Th1 / Th2免疫平衡IL-12或IFN-γ。 IFN-γ通过直接抑制胶原蛋白合成和恢复免疫平衡发挥作用。在这篇综述中，我们评估了LS和SSc皮肤受累的当前和未来治疗方案。治疗方面的最新进展主要集中在抗纤维化药物上。这些药物作为目标组织进入皮肤可能是开发更有效，更安全的治疗方法的关键因素。

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