Jamart Céline, Levesque Hervé, Thietart Sara, Fain Olivier, Rivière Sébastien, Benhamou Ygal, Mekinian Arsène
Service de Médecine Interne, Hôpital Rouen, Université de Rouen, Rouen, France.
Sorbonne Université, APHP, Service de Médecine Interne-DMU i3, Hôpital Saint-Antoine, Paris, France.
Front Med (Lausanne). 2022 Jul 6;9:878970. doi: 10.3389/fmed.2022.878970. eCollection 2022.
Ischemic digital ulcers (DUs) are frequent and severe complications of systemic sclerosis (SSc). Treatment options for SSc-related digital vasculopathy are based on aggressive vasodilation, with the objective to improve blood flow in ischemic areas. Intravenous prostanoids are recommended to treat active DUs. However, the level of evidence for the duration of 5 days is low. Therefore, the aim of this study was to determine whether prolonging the infusion beyond 5 days increases the rate of healing of active DUs in SSc.
This is an observational longitudinal retrospective bicenter study from 2000 to 2017. The objective was to compare the healing rate and time (defined by a healing of at least 50% of DUs) between two durations of iloprost administration: 5 days or less, or more than 5 days.
Forty-one patients, with a mean age of 47 ± 15 years at diagnosis and 32 (78%) females have been included. Systemic sclerosis was diffuse in 10 (24%) cases and 13 (32%) had an interstitial lung disease. A total of 243 iloprost infusions for DUs were performed: 140 infusions for 5 days or less, and 103 infusions for more than 5 days (prolonged duration). Patients with active DUs which received >5 days of iloprost had higher modified Rodnan skin scale at the time of iloprost infusion (median 33 vs. 15; < 0.05), more interstitial lung disease (44 vs. 27%; < 0.05), more anti-topoisomerase I antibody positivity (59 vs. 44%; < 0.05), and received more previous cyclophosphamide therapy (48 vs. 19%; < 0.05). While the number of active DUs before iloprost infusion was not significantly different among those who received ≤5 days and >5 days of iloprost, the time to healing after iloprost infusion significantly decreased in SSc patients who received >5 days iloprost infusion: 48 [7-392] vs. 91 [9-365] days ( < 0.05). The proportion of SSc patients with healed DUs tended to increase in patients with >5 days iloprost infusion (log rank = 0.06). The number of patients with complete DU healing at day 90 was significantly increased in SSc who received >5 days of iloprost: 53 (51%) vs. 52 (37%) ( < 0.05). In addition, the time to healing was not significantly associated with the use of calcium channel blockers, endothelin receptor antagonists or a combination of PDE-5 inhibitors.
Prolonging duration of iloprost >5 days could improve the healing rate and the time to healing of SSc-related DUs. Prospective randomized studies are needed to confirm these data and define the optimal duration of iloprost therapy.
缺血性指端溃疡（DU）是系统性硬化症（SSc）常见且严重的并发症。SSc相关指端血管病变的治疗方案基于积极的血管舒张，目的是改善缺血区域的血流。推荐静脉使用前列腺素治疗活动性DU。然而，证据显示5天疗程的有效性较低。因此，本研究旨在确定将输注时间延长至5天以上是否能提高SSc患者活动性DU的愈合率。
这是一项2000年至2017年的观察性纵向回顾性双中心研究。目的是比较伊洛前列素两种给药疗程（5天及以下或超过5天）的愈合率和愈合时间（定义为至少50%的DU愈合）。
共纳入41例患者，诊断时平均年龄为47±15岁，其中32例（78%）为女性。10例（24%）为弥漫性系统性硬化症，13例（32%）患有间质性肺病。共进行了243次针对DU的伊洛前列素输注：140次输注时间为5天及以下，103次输注时间超过5天（延长疗程）。接受伊洛前列素治疗超过5天的活动性DU患者在输注伊洛前列素时改良Rodnan皮肤评分更高（中位数33 vs. 15；P<0.05），间质性肺病更多（44% vs. 27%；P<0.05），抗拓扑异构酶I抗体阳性更多（59% vs. 44%；P<0.05），且接受环磷酰胺治疗的次数更多（48% vs. 19%；P<0.05）。虽然接受伊洛前列素治疗≤5天和>5天的患者在输注伊洛前列素前活动性DU的数量无显著差异，但接受伊洛前列素治疗>5天的SSc患者在输注伊洛前列素后的愈合时间显著缩短：48[7 - 392]天 vs. 91[9 - 365]天（P<0.05）。接受伊洛前列素治疗>5天的SSc患者中DU愈合的比例有增加趋势（对数秩检验=0.06）。接受伊洛前列素治疗>5天的SSc患者在第90天时完全愈合的DU数量显著增加：53例（51%） vs. 52例（37%）（P<0.05）。此外，愈合时间与使用钙通道阻滞剂、内皮素受体拮抗剂或PDE - 5抑制剂联合用药无显著相关性。
将伊洛前列素疗程延长至>5天可提高SSc相关DU的愈合率和缩短愈合时间。需要进行前瞻性随机研究以证实这些数据并确定伊洛前列素治疗的最佳疗程。
