背景:瘢痕疙瘩的治疗仍然是一个棘手而复杂的临床问题,尤其是伤口诱发的多发性瘢痕疙瘩,严重烧伤,种族背景或文化行为,或无法解释的皮肤愈合。主流治疗在治疗多发性瘢痕疙瘩方面具有有限的功效。由于没有无痛苦和方便的口服治疗,应制定口腔治疗策略。
目的:本研究旨在探讨托法替尼口服治疗瘢痕疙瘩的疗效及机制。
方法:我们招募了7例瘢痕疙瘩患者,每天两次口服5mg托法替尼,最长随访12周。患者和观察者疤痕评估量表(POSAS)温哥华疤痕量表(VSS),ANTERA3D摄像机,和DUB皮肤扫描仪75用于评估病变的特征。进行免疫组织化学以评估胶原蛋白合成,扩散,和相对分子途径。此外,在体外评估了托法替尼对瘢痕疙瘩成纤维细胞的影响.
结果:口服托法替尼12周后,POSAS的显著改进,VSS,皮肤病学生活质量指数(DLQI)评分(p<0.05)。音量,病变高度,瘢痕疙瘩真皮厚度降低(p<0.05)。此外,胶原蛋白I的表达显着下降,给药12周后观察Ki67、p-STAT3和p-SMAD2。体外实验表明,托法替尼治疗通过抑制STAT3和SMAD2途径抑制成纤维细胞增殖和胶原蛋白I合成。
结论:托法替尼,一种治疗瘢痕疙瘩的新候选口服药物,可以通过抑制胶原蛋白合成和抑制成纤维细胞增殖来减少瘢痕疙瘩的体积,并减轻瘙痒和疼痛,以获得更好的生活质量。
BACKGROUND: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated.
OBJECTIVE: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients.
METHODS: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro.
RESULTS: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway.
CONCLUSIONS: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.