ZINC THERAPY FOR SCLERODERMA--PHASE I STUDY

硬皮病是一种平均预期寿命不到10年的疾病，目前还没有被证明可以改变其病程的治疗方法。实验证据表明，缺血再灌注诱导的损伤、金属催化的自身抗原结构修饰和成纤维细胞胶原蛋白的过量产生与该疾病的发病机制有关。锌在体外已被证明可以抑制这些过程。锌已被安全地用于治疗其他疾病，特别是威尔逊氏病，但锌治疗硬皮病患者的安全性仍有待确定。本研究的目的是评估口服硫酸锌对硬皮病患者的安全性和生物利用度。在为期6周的试验中，采用威尔逊氏病治疗常用的给药方案，对弥漫性硬皮病患者进行临床不良事件监测，作为主要研究结果。6名患者参加了这项研究。没有明显的不良事件，也没有方案退出。血清锌水平从79.6+/- 11.2ug/dl（平均+/-标准差）上升到129.6 +/- 35.1 ug/dl，差异有统计学意义（学生t检验p=0.0163）。血清锌水平的增加与之前报道的正常受试者的结果一致。锌治疗对患者和医生整体视觉模拟量表评分、健康评估问卷评分和改良罗德曼皮肤评分的平均改善，但未达到统计学意义。6名患者中有3名在研究方案结束时选择继续服用锌，因为主观感觉有益。本研究结果提示锌疗法对硬皮病患者是安全且生物可利用的。一项II期试验评估锌治疗硬皮病的临床益处是必要的。

No treatments exist which have been proven to modify the course of scleroderma, a disease with median life expectancy of less than 10 years. Experimental evidence has implicated ischemia-reperfusion- induced injury, metal-catalyzed modifications of autoantigen structure, and excess fibroblast collagen production in the pathogenesis of this disease. Zinc has been shown in vitro to inhibit each of these processes. Zinc has been used safely for the treatment of other conditions, notably Wilson's Disease, but the safety of zinc therapy in scleroderma patients remains to be established. The aim of this study was to assess the safety and bioavailability of oral zinc sulfate in scleroderma patients. Using a dosing regimen common to Wilson's Disease therapy, patients with diffuse scleroderma were montiored clinically for adverse events as the primary study outcome over a 6-week trial. Six patients entered the study. There were no significant adverse events, and no protocol dropouts. Serum zinc levels increased from 79.6+/- 11.2ug/dl (mean +/- standard deviation) to 129.6 +/- 35.1 ug/dl, a statistically significant difference (Student's t test p=0.0163). This increase in serum zinc levels was consistent with results previously reported for normal subjects. Mean improvements in patient and physician global visual analog scale scores, health assessment questionnaire scores, and modified Rodnan skin scores were observed with zinc therapy, but did not reach statistical significance. Three of the six patients elected to continue taking zinc at the conclusion of the study protocol due to a subjective sense of benefit. The results of this study suggest that zinc therapy is safe and bioavailable in scleroderma patients. A Phase II trial to assess for clinical benefits of zinc therapy in scleroderma is warranted.