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

Abstract

<b><i>Background:</i></b> <i>Demodex</i> 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-<i>Demodex</i> strategies, we conducted this study, based on interventional clinical evidence with quantified <i>Demodex</i> mite data. <b><i>Methods:</i></b> 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 <i>Demodex</i> decrease rates. <b><i>Results:</i></b> 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 <i>Demodex</i> 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. <b><i>Conclusions:</i></b> We found ivermectin (topical and systemic), ivermectin-metronidazole (topical), and TTO (topical) are promising anti-<i>Demodex</i> interventions. In addition to traditional pharmacotherapy, light therapies, especially IPL and skin cleansing, could also be considered as effective methods to control <i>Demodex</i> mite infestation.

“Demodicosis” Mimicking PreSeptal Cellulitis: Severe Periocular and Facial Inflammation Caused by “Normal” Skin Flora

“…In the present case, topical metronidazole was chosen due to ease of use, wish to avoid further systemic therapy, and insurance coverage. Although “off-label,” the use of topical metronidazole is a long-accepted treatment of Demodex, for which there are a variety of treatment options (many off-label), from topical to systemic therapies, including systemic ivermectin.. 14 In July 2023, lotilaner ophthalmic solution became the first Food and Drug Administration (FDA)-approved therapeutic for Demodex blepharitis. Phase 3 trial of lotilaner ophthalmic solution versus vehicle control showed collarette cure at 56% versus 12.5% ( p < 0.0001) and mite eradication at 51.8% versus 14.6% ( p < 0.0001) after 6 weeks of twice-daily treatment in patients with Demodex blepharitis.…”

Rosacea, microbiome and probiotics: the gut-skin axis

“…Thus, the inflammatory reaction could be insufficient to eradicate Demodex mites as some of the infiltrating T-cells have become dysfunctional, so that polymorphisms in dendritic cells would explain the different susceptibility to Demodex antigens ( Forton, 2020 ). On the other hand, a recent meta-analysis evaluating the efficacy of different anti- Demodex treatments concluded that topical and systemic ivermectin, topical ivermectin-metronidazole, and topical tea tree oil, are promising anti- Demodex interventions ( Li et al, 2023 ). In addition, topical ivermectin 1% treatment for 12 weeks significantly decreased Demodex density and downregulated IL-8, LL-37, TLR-4, human β-defensin 3 (HBD3), and tumor necrosis factor α (TNF-α) gene expression, implicating anti-inflammatory effects along improving clinical course of rosacea ( Schaller et al, 2017b ).…”

Acne-like Eruptions: Disease Features and Differential Diagnosis

“…The determination of mite density can be conducted through direct microscopic examination or standardized skin surface biopsy [20]. Treatment options include topical and systemic ivermectin, topical and systemic metronidazole, and topical and light therapy, such as intense pulsed light (IPL) [11,27].…”