Sion Jung

Background: Rosacea is a chronic inflammatory skin disorder characterized by erythema, flushing, vasodilation, inflammatory papules, and ocular symptoms such as dryness and photophobia ^[1]. The pathogenesis of rosacea remains unclear, with UV exposure, genetic predisposition, and environmental triggers implicated ^[1]. Emerging evidence highlights alterations in the skin microbiome, particularly increased densities of Demodex folliculorum exceeding 5 mites/cm² in affected individuals ^[2]. These mites are associated with immune activation and inflammatory mediator release, as well as bacterial interactions that may influence microbiome composition ^[3][4][5][6]. However, it remains unclear whether Demodex directly drives inflammation or proliferates as a result of an already dysregulated skin environment.

Objective: This review aims to investigate the role of increased Demodex folliculorum density in modulating the skin microbiome and triggering inflammatory responses in rosacea. It further explores the associated immune pathways and microbial interactions that may contribute to disease progression.

Methods: A systematic online literature search was performed using PubMed and Google Scholar, focusing on studies published between 2014 and 2025. Keywords included “rosacea,” “Demodex folliculorum,” “Demodex,” “skin microbiome,” “ivermectin,” “Bacillus oleronius,” and “inflammation.”

Results: The reviewed literature consistently demonstrates increased densities of Demodex folliculorum in rosacea patients compared to healthy individuals ^{[1][2][3][4][5][6][7][8][9][10]}. Elevated Demodex levels are associated with activation of innate immune pathways, particularly Toll-like receptor 2 (TLR2), leading to increased expression of pro-inflammatory mediators such as KLK5, IL-8, and IL-22 ^[3][4][5]. In addition, the breakdown of Demodex mites is linked to the release of bacteria such as Bacillus oleronius, which may further amplify inflammatory responses ^[9]. Studies also report alterations in the skin microbiome composition in rosacea, suggesting a relationship between Demodex proliferation and microbial imbalance ^[6]. Furthermore, treatment with ivermectin has been shown to reduce Demodex density, decrease inflammatory markers, and partially restore microbiome balance ^[10].

Conclusion:The literature indicates that increased Demodex folliculorum density is associated with alterations in the skin microbiome and activation of inflammatory pathways in rosacea ^{[1][2][3][4][5][6][7][8][9][10]}. Clinically, treatments such as ivermectin that reduce Demodex density and inflammation may also help restore microbiome balance ^[10]. However, the precise mechanisms linking Demodex, microbial dysbiosis, and immune activation remain unclear. Future research should focus on clarifying these interactions, developing non-invasive diagnostic approaches, and exploring targeted therapies that address both microbial and inflammatory components of rosacea.

Works Cited:

[1] Geng, R. S. Q., Bourkas, A. N., Mufti, A., & Sibbald, R. G. (2024). Rosacea: Pathogenesis and Therapeutic Correlates. Journal of cutaneous medicine and surgery, 28(2), 178–189. https://doi.org/10.1177/12034754241229365

[2] Wei, F., Li, L., Kong, Y., Yan, X., Varghese, K. J., Zhang, S., Jiang, J., Chai, B., & Chen, H. (2023). Evidence for the Clinical Association between Demodex and Rosacea: A Review. Dermatology, 240(1), 95–102. https://doi.org/10.1159/000534245

[3] Martínez-Ortega, J. I., Medina Angulo, T. K., & Mut Quej, J. E. (2025). Unilateral Papulopustular Dermatosis: Demodex Mites Bridging Rosacea and Demodicosis. Cureus, 17(3), e79877. https://doi.org/10.7759/cureus.79877

[4] Forton F. M. N. (2020). The Pathogenic Role of Demodex Mites in Rosacea: A Potential Therapeutic Target Already in Erythematotelangiectatic Rosacea?. Dermatology and therapy, 10(6), 1229–1253. https://doi.org/10.1007/s13555-020-00458-9

[5] Xu, J., Zhang, Y., Ci, C., Lu, X., Hu, X., Zhao, J., & Li, Y. (2025). Relationship of the Specific Inflammatory Cytokines KLK5, IL-8, and IL-22 with Demodex Density and Risk Factors in Rosacea. Journal of inflammation research, 18, 15737–15748. https://doi.org/10.2147/JIR.S562730

[6] Nakatsuji, T., Cheng, J. Y., Butcher, A., Shafiq, F., Osuoji, O., Gallo, R. L., & Hata, T. R. (2024). Topical Ivermectin Treatment of Rosacea Changes the Bacterial Microbiome of the Skin. Journal of Investigative Dermatology, 145(5), 1226-1228.e5. https://doi.org/10.1016/j.jid.2024.10.592

[7] Rather, P. A., & Hassan, I. (2014). Human demodex mite: the versatile mite of dermatological importance. Indian journal of dermatology, 59(1), 60–66. https://doi.org/10.4103/0019-5154.123498

[8] Rainer, B. M., Kang, S., & Chien, A. L. (2017). Rosacea: Epidemiology, pathogenesis, and treatment. Dermato-endocrinology, 9(1), e1361574. https://doi.org/10.1080/19381980.2017.1361574

[9] Paichitrojjana A. (2022). Demodex: The worst enemies are the ones that used to be friends. Dermatology reports, 14(3), 9339. https://doi.org/10.4081/dr.2022.9339

[10] Paichitrojjana, A., & Chalermchai, T. (2024). Evaluating the Efficacy of Oral Ivermectin on Clinical Symptoms and Demodex Densities in Patients with Demodicosis. Drug design, development and therapy, 18, 5299–5306. https://doi.org/10.2147/DDDT.S498938