Supplementary Material for: Comparison of Different Anti-Demodex Strategies: A Systematic Review and Meta-Analysis

Background: Demodex mites are related to some inflammatory diseases such as rosacea and blepharitis and could be harmful in patients with immunodeficiency or immunosuppression, especially notable in patients using biologic like dupilumab. In order to have an objective observation of different anti-Demodex strategies, we conducted this study, based on interventional clinical evidence with quantified Demodex mite data. Methods: We used the PubMed, Embase, ClinicalTrials.gov, Medline, and International Clinical Trials Registry Platform (ICTRP) as databases. To assess the risk of bias, the RoB2 and ROBINS-I tools were used. The certainty of evidence was assessed following the GRADE guideline. Furthermore, the effect sizes (ESs) of different strategies were compared in different time periods (0–1, 1–2, 2–3, >3 months), as well as Demodex decrease rates. Results: 1,618 studies were identified in the databases, with 21 of which included in the final quantitative synthesis. Interventions in these studies included ivermectin, tea tree oil (TTO), permethrin, crotamiton, metronidazole, light therapies, combined therapies, and other therapies. During 0–1 month, the ES varied from 0.07 (cleanser) to 1.95 (systemic ivermectin-metronidazole). During 1–2 months, the ES varied from 0.88 (topical permethrin) to 4.40 (topical ivermectin). During 2–3 months, the ES varied from 0.79 (topical permethrin) to 8.37 (topical ivermectin). During the time of 3 months, the ES varied from 0.59 (topical permethrin) to 2.25 (intense pulsed light [IPL]). In terms of Demodex decrease rates, topical ivermectin, TTO, permethrin, IPL, and baby shampoo had achieved a nearly 100% decrease. The reported adverse events were mostly mild, without severe adverse events reported in any of the studies. Conclusions: We found ivermectin (topical and systemic), ivermectin-metronidazole (topical), and TTO (topical) are promising anti-Demodex interventions. In addition to traditional pharmacotherapy, light therapies, especially IPL and skin cleansing, could also be considered as effective methods to control Demodex mite infestation.背景：蠕形螨（Demodex mite）与玫瑰痤疮、睑缘炎等多种炎症性疾病相关，在免疫缺陷或免疫抑制患者中可造成危害，尤其在使用度普利尤单抗等生物制剂的患者中表现尤为显著。为客观评估不同抗蠕形螨干预策略的效果，本研究基于纳入量化蠕形螨数据的介入性临床证据开展。 方法：本研究检索的数据库包括PubMed、Embase、ClinicalTrials.gov、Medline以及国际临床试验注册平台（International Clinical Trials Registry Platform, ICTRP）。采用RoB2与ROBINS-I工具评估偏倚风险，依据GRADE指南评估证据确定性。此外，本研究还对比了不同干预策略在0~1个月、1~2个月、2~3个月及＞3个月四个时间段的效应量（effect size, ES）以及蠕形螨清除率。 结果：本研究共检索到1618项相关研究，最终纳入21项进行定量综合分析。纳入研究的干预措施包括伊维菌素、茶树油（tea tree oil, TTO）、扑灭司林、克罗米通、甲硝唑、光疗、联合治疗及其他疗法。在0~1个月时间段，效应量范围为0.07（洁面剂）至1.95（全身用伊维菌素-甲硝唑联合方案）；在1~2个月时间段，效应量范围为0.88（外用扑灭司林）至4.40（外用伊维菌素）；在2~3个月时间段，效应量范围为0.79（外用扑灭司林）至8.37（外用伊维菌素）；在3个月以上时间段，效应量范围为0.59（外用扑灭司林）至2.25（强脉冲光（intense pulsed light, IPL））。就蠕形螨清除率而言，外用伊维菌素、茶树油、扑灭司林、强脉冲光以及婴儿洗发水均实现了接近100%的螨体清除。所有研究报告的不良反应均以轻度为主，未出现严重不良反应案例。 结论：本研究发现，外用及全身用伊维菌素、外用伊维菌素-甲硝唑联合方案以及外用茶树油均为颇具前景的抗蠕形螨干预手段。除传统药物治疗外，光疗（尤其是强脉冲光）以及皮肤清洁也可作为控制蠕形螨感染的有效方法。