Wigley F M, Seibold J R, Wise R A, McCloskey D A, Dole W P
Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ.
J Rheumatol. 1992 Sep;19(9):1407-14.
We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis.
Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks.
Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion.
Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.
我们开展本研究以评估静脉输注伊洛前列素对系统性硬化症继发雷诺现象患者的临床效用及生理影响。
35例系统性硬化症继发雷诺现象的患者，其中11例有手指缺血性溃疡，参与了在2个中心进行的双盲安慰剂对照平行研究。经过2周的洗脱期后，受试者连续5天每天接受6小时的静脉输注伊洛前列素（0.5 - 2.0纳克/千克/分钟）或生理盐水。在入组时、治疗5天时以及之后10周内每两周进行一次临床评估、手指溃疡状况评估、体内血小板活化指标检测以及外周血管对冷刺激反应的详细研究。
接受伊洛前列素治疗的7例患者中有6例在治疗10周后所有皮肤病变（溃疡、皲裂和甲沟炎）完全愈合，而接受安慰剂治疗的4例患者中无一例愈合（p = 0.015）。伊洛前列素组4例有溃疡的患者手指缺血性尖端溃疡均完全愈合，而安慰剂组无一例愈合（p = 0.029）。患者关于雷诺现象发作频率、持续时间及症状的日记显示两组均有改善。伊洛前列素组临界缺血温度（在控制性冷刺激期间手指温度，此时出现雷诺现象或可检测到的手指血流丧失）从基线时的21.3±7.3摄氏度逐渐降至治疗8周时的最低值16.1±3.2摄氏度（p = 0.076），而安慰剂组未观察到一致变化。治疗与冷刺激后皮肤温度恢复速率的改善相关。手指周围皮肤温度、手指总血流量、手指收缩压或体内血小板活化指标均未观察到变化。1例受试者因胸痛退出研究，但恶心、呕吐、头痛和颌痛等不良反应仅局限于药物输注的5天内。
伊洛前列素似乎对系统性硬化症患者的手指溃疡治疗有效，且有证据表明其可带来生理状况的长期改善，尽管这种作用机制尚不清楚。
