免疫抑制剂联合糖皮质激素治疗Behcet病葡萄膜炎患者85例的临床观察

Clinical observation of 85 patients with Behcet＇ s uveitis treated with immunosuppressive agentscombined with steroids

目的探讨免疫抑制剂联合糖皮质激素治疗Behqet病葡萄膜炎的有效性和安全性。方法系列病例研究。收集2010年6月至2011年6月北京同仁医院葡萄膜炎门诊确诊的85例（167只眼）Behcet病葡萄膜炎患者的临床资料。所有患者均接受免疫抑制剂联合糖皮质激素治疗，进行治疗前及治疗后每3个月随访1次，记录矫正视力、炎症情况、眼部并发症、药物不良反应。对阳性事件发生率采用“／人（眼）年”进行描述，对眼内炎症复发间隔进行Kaplan-Meier生存分析检验，对治疗前和治疗后未复发比例的比较采用对数秩检验。结果85例患者中，男性67例，女性18例，平均年龄为（30．4±9．5）岁。共随访255．5眼年，129．67人年。眼内炎症在3个月内未复发的比例为91．6％（153／167），1年内未复发的比例为22．3％（37／167），与药物治疗前[分别为34．7％（58／167）和1．0％（2／167）]相比，未复发比例明显提高（X^2=137．80，P〈0．01）。患眼视力提高发生率为0．22／眼年，患眼视力降低发生率为0．11／眼年。常见的并发症为并发性白内障（0．39／眼年）、眼压大于30mmHg（1mmHg=0．133kPa）（0．07／眼年）、玻璃体重度混浊（0．79／眼年）。醋酸泼尼松的常见不良反应包括肥胖（0．40／人年）、股骨头坏死（0．22／人年）、高血压（0．13／人年）。免疫抑制剂的常见不良反应包括可逆性中性粒细胞抑制（苯丁酸氮芥0．26／人年、甲氨蝶呤0．46／人年），肝脏毒性（复方环磷酰胺0．21／人年、硫唑嘌呤0．13／人年），镜下血尿（复方环磷酰胺0．21／人年），牙龈增生（环孢素A0．15／人年）。结论免疫抑制剂联合糖皮质激素全身治疗Behcet病葡萄膜炎可以有效控制眼内炎症反应复发，但Behqet病葡萄膜炎并发症发生率高，视力预后较差。在治疗过程中应注意高血压、肥胖、股骨头坏死等不良反应的监测。建议使用免疫抑制剂治疗替代长期大剂量糖皮质激素治疗，应注意药物相关不良反应的监测。

Objective To investigate the effect and safety of immunosuppressive treatment （IMT） combined with steroids in patients with Behcet＇s uveitis. Methods Case-series study. Eighty-five patients （167 eyes） were enrolled in this study from June 2010 to June 2011 at the Beijing Tongren Hospital. The patients were examined before the initiation of iMT and were followed up once every 3 months after the therapy. The corrected visual acuity, inflammation score, ocular complications and side effects of IMT and steroid use were recorded. The rate of positive outcomes was reported in person years （PY） or eye years （EY）. The intervals between the episodes of ocular inflammation were analyzed using Kaplan-Meier survival analysis. The difference of the proportion of stable cases before and after treatment was analyzed by Log-rank test. Results There were 67 males and 18 females. The mean age of diagnosis with Behcet＇s disease was （30. 4±9.5 ） years. The total follow-up period was 255.5 EY and 129.67 PY. The percentages of eyes with inflammation that had been stable for at least 3 months （91.6%, 153/167） or more than 1 year （22. 3%, 37/167） after treatment were significantly higher than those before treatment [ 34. 7% （58/167） and 1.0% （2/167） , respectively] （X^2 = 137.80,P 〈 0. 01 ）. The incident rate of a decrease in visual acuity was 0. 11per EY, and the incident rate of an increased in visual acuity was 0. 22 per EY. The incident rates of cataracts, an intraocular pressure greater than 30 mm Hg（ 1 mm Hg =0. 133 kPa） or a severe vitreous haze were 0. 39 per EY, 0. 07 per EY and 0. 79 per EY, respectively. The incident rates of obesity, osteoporosis and hypertension caused by steroid use were 0. 4 per PY, 0. 22 per PY and 0. 13 per PY, respectively. The common side effects of IMT were reversible leukopenia （0. 26 per PY by chlorambucil and 0. 46 per PY by methotrexate）, hepatotoxicity （0.21 per PY by cyclophosphamide, 0. 13 per PY by azathioprine）, hematuria （0. 21 per PY by cyclophosphamide） and gum hyperplasia caused by cyclosporine （0. 15 per PY）. Conclusions Although the use of IMT combined with steroids is effective for the control of intraocular inflammation in patients with Behcet＇s uveitis, the occurrence of complications is still high, and the vision prognosis is poor. We should pay attention to the side effects of the long-term use of steroids, such as hypertension, obesity and osteoporosis. The initiation of IMT is recommended over the long-term administration of large doses of steroids. The side effects of IMT should be monitored.