美洲不同治疗方法治疗黏膜利什曼病的治愈率：系统评价。

BACKGROUND: Mucosal or mucocutaneous leishmaniasis is the most severe form of tegumentary leishmaniasis due to its destructive character and potential damage to respiratory and digestive tracts. The current treatment recommendations are based on low or very low-quality evidence, and pentavalent antimonial derivatives remain strongly recommended. The aim of this review was to update the evidence and estimate the cure rate and safety profile of the therapeutic options available for mucosal leishmaniasis (ML) in the Americas. METHODOLOGY: A systematic review was conducted in four different databases and by different reviewers, independently, to evaluate the therapeutic efficacy and toxicity associated with different treatments for ML. All original studies reporting cure rates in more than 10 patients from American regions were included, without restriction of design, language, or publication date. The risk of bias was assessed by two reviewers, using different tools according to the study design. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. The protocol for this review was registered at the International Prospective Register of Systematic Reviews, PROSPERO: CRD42019130708. PRINCIPAL FINDINGS: Twenty-seven original studies from four databases fulfilled the selection criteria. A total of 1,666 patients with ML were treated predominantly with pentavalent antimonials in Brazil. Other interventions, such as pentamidine, miltefosine, imidazoles, aminosidine sulfate, deoxycholate and lipidic formulations of amphotericin B (liposomal, lipid complex, colloidal dispersion), in addition to combinations with pentoxifylline, allopurinol or sulfa were also considered. In general, at least one domain with a high risk of bias was identified in the included studies, suggesting low methodological quality. The pooled cure rate based on the latest cure assessment reported in the original studies was calculated grouping all study arms addressing the same intervention. It was confirmed that antimony is still the most used treatment for ML, with only moderate efficacy (possibly increased by combining with pentoxifylline). There is already evidence for the use of miltefosine for ML, with a cure rate similar to antimony, as observed in the only direct meta-analysis including 57 patients (OR: 1.2; 0.43-3.49, I2 = 0). It was possible to gather all descriptions available about adverse events reported during ML treatment, and the toxicity reflected the pattern informed in the manufacturers' technical information. CONCLUSIONS: This study provides an overview of the clinical experience in the Americas related to ML treatment and points out interventions and possible combinations that are eligible to be explored in future well-designed studies.

背景：黏膜或黏膜皮肤利什曼病是最严重的皮肤利什曼病形式，因为其具有破坏性特征和对呼吸道和消化道的潜在损害。目前的治疗建议基于低或极低质量的证据，仍强烈推荐使用五价锑衍生物。本综述的目的是更新黏膜利什曼病（ML）治疗方案的证据，并估计可用治疗方案的治愈率和安全性。

方法：在四个不同的数据库中，由不同的评审员进行了系统评价，以评估与 ML 相关的不同治疗方法的治疗效果和毒性。纳入了所有来自美洲地区的报告超过 10 例患者治愈率的原始研究，不受设计、语言或发表日期的限制。两名评审员使用不同的工具根据研究设计评估偏倚风险。根据原始研究中最新治愈率评估，将所有针对同一干预措施的研究组进行分组，计算基于治愈率的汇总。该综述的方案在国际前瞻性注册系统评价中注册，PROSPERO：CRD42019130708。

主要发现：从四个数据库中筛选出 27 项符合标准的原始研究。来自巴西的 1,666 例 ML 患者主要接受五价锑治疗。其他干预措施，如戊烷脒、米替福新、咪唑类、硫酸氨基多辛、去氧胆酸和两性霉素 B 的脂质制剂（脂质体、脂质复合物、胶体分散体），以及与己酮可可碱、别嘌呤醇或磺胺嘧啶联合使用，也被考虑在内。一般来说，纳入的研究中至少有一个领域存在高偏倚风险，表明方法学质量较低。根据原始研究中最新治愈率评估，将所有针对同一干预措施的研究组进行分组，计算基于治愈率的汇总。证实锑仍然是 ML 最常用的治疗方法，疗效仅为中等（可能通过与己酮可可碱联合使用而提高）。已经有证据表明米替福新可用于 ML 治疗，治愈率与锑相似，这在包括 57 例患者的唯一直接荟萃分析中得到了观察（OR：1.2；0.43-3.49，I2 = 0）。能够收集到 ML 治疗期间报告的所有不良反应描述，并反映了制造商技术信息中报告的毒性模式。

结论：本研究提供了有关美洲 ML 治疗临床经验的概述，并指出了有资格在未来精心设计的研究中进行探索的干预措施和可能的组合。