Department of Dermatology, School of Medicine, Stanford University, Palo Alto, California, USA.
Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Lymphat Res Biol. 2023 Apr;21(2):101-110. doi: 10.1089/lrb.2021.0103. Epub 2022 Jul 18.
Genetic alterations in lymphatic development can lead to microcystic lymphatic malformations (micro LMs). LMs can have both microcystic and macrocytic components or be exclusively one or the other. LMs can result in serious, sometimes life-threatening, sequelae. Absent consensus guidelines, treatment has been largely empiric. Recent advances in our understanding of the pathogenesis of micro LMs have provided a foundation for novel therapeutic approaches. This review examines clinical data over the last 10 years on the role of sirolimus, an inhibitor of the PI3K/AKT/mTOR signaling pathway implicated in micro LM development, in the treatment of micro LM. Systematic review of published clinical studies from January 1, 2011, to July 15, 2021, using the PubMed, Google Scholar, and Cochrane Reviews databases, and utilizing delimiters to focus specifically on sirolimus in the treatment of micro LM. A total of 16 studies were identified (13 case studies or case reviews; 3 prospective) that included 52 subjects treated with topical ( = 15) or oral ( = 37) sirolimus for micro LM. Clinically meaningful, long-term improvement (up to 3 years) was noted in 92% (46/50), mostly previously treated subjects. Sirolimus yielded improvements in key manifestations such as lymphatic leakage, bleeding, vesicle bulk, pain, and skin discoloration. Some subjects experienced a rapid onset of effect (within 2 weeks). No unexpected adverse events were seen. Sirolimus appears to be an effective and safe option in the management of cutaneous and complex micro LM. However, prospective, controlled trials are clearly needed to accurately elucidate the benefits and risks of sirolimus in the management of micro LM. ClinicalTrials.gov Identifier: NCT05050149.
淋巴发育的遗传改变可导致微囊性淋巴管畸形（微 LMs）。LMs 可具有微囊和巨囊成分，或者仅具有其中一种。LMs 可导致严重的、有时危及生命的后遗症。由于缺乏共识指南，治疗主要是经验性的。我们对微 LMs 发病机制的理解的最新进展为新的治疗方法提供了基础。这篇综述检查了过去 10 年来关于雷帕霉素（一种参与微 LM 发育的 PI3K/AKT/mTOR 信号通路抑制剂）在治疗微 LM 中的作用的临床数据。对 2011 年 1 月 1 日至 2021 年 7 月 15 日发表的临床研究进行了系统评价，使用了 PubMed、Google Scholar 和 Cochrane Reviews 数据库，并利用限定符专门关注雷帕霉素在治疗微 LM 中的作用。确定了 16 项研究（13 项病例研究或病例综述；3 项前瞻性），其中 52 例微 LM 患者接受了局部（ = 15）或口服（ = 37）雷帕霉素治疗。92%（46/50）的患者，主要是以前治疗过的患者，观察到有临床意义的长期改善。雷帕霉素改善了淋巴漏、出血、水疱体积、疼痛和皮肤变色等关键表现。一些患者在 2 周内迅速起效。没有观察到意外的不良事件。雷帕霉素似乎是治疗皮肤和复杂微 LMs 的有效和安全选择。然而，显然需要前瞻性、对照试验来准确阐明雷帕霉素在治疗微 LMs 中的益处和风险。ClinicalTrials.gov 标识符：NCT05050149。
