Rosacea pathogenesis and topical treatment options – a review
DOI:
https://doi.org/10.12775/QS.2025.39.58360Keywords
rosacea, demodex, topical treatment, pathogenesisAbstract
Introduction: Rosacea is a chronic inflammatory condition primarily affecting the central facial areas and eyes, with subtypes including erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea. While not life-threatening, rosacea significantly impacts quality of life, contributing to psychological distress.
Materials and methods: This article reviews the pathogenesis and treatment of rosacea, incorporating data from PubMed, Google Scholar, and Web of Science using keywords such as “rosacea,” “Demodex,” “topical treatment,” and “pathogenesis.”
Summary: Rosacea is driven by multifactorial mechanisms, including neurovascular hyperreactivity, immune system dysregulation, sebaceous gland dysfunction, microbial imbalances, and genetic predisposition. Triggers like UV radiation, stress, and certain foods exacerbate symptoms by activating pathways such as transient receptor potential (TRP) channels and inflammatory mediators like IL-6 and TNF-α. Effective treatments focus on symptom management and include topical agents like ivermectin, metronidazole, azelaic acid, calcineurin inhibitors, retinoids, alpha-adrenergic receptor agonists and sodium sulfacetamide. These therapies target inflammation, erythema, and microbial factors, with clinical trials demonstrating improvements in erythema, papules, and pustules.
Conclusions: While current treatments offer significant relief, the article emphasizes the importance of further research into the underlying mechanisms to develop more advanced therapeutic options.
References
[1] Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182(5):1269-1276. doi:10.1111/bjd.18420
[2] Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol. 2002;46(4):584-587. doi:10.1067/mjd.2002.120625
[3] van Zuuren EJ. Rosacea. N Engl J Med. 2017;377(18):1754-1764. doi:10.1056/NEJMcp1506630
[4] van Zuuren EJ, Fedorowicz Z, Tan J, et al. Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments. Br J Dermatol. 2019;181(1):65-79. doi:10.1111/bjd.17590
[5] Vieira AC, Höfling-Lima AL, Mannis MJ. Ocular rosacea--a review. Arq Bras Oftalmol. 2012;75(5):363-369. doi:10.1590/s0004-27492012000500016
[6] Del Rosso JQ, Thiboutot D, Gallo R, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 1: a status report on the disease state, general measures, and adjunctive skin care. Cutis. 2013;92(5):234-240.
[7] Heisig M, Reich A. Psychosocial aspects of rosacea with a focus on anxiety and depression. Clin Cosmet Investig Dermatol. 2018;11:103-107. Published 2018 Mar 6. doi:10.2147/CCID.S126850
[8] Tan J, Berg M. Rosacea: current state of epidemiology. J Am Acad Dermatol. 2013;69(6 Suppl 1):S27-S35. doi:10.1016/j.jaad.2013.04.043
[9] Alexis AF, Callender VD, Baldwin HE, Desai SR, Rendon MI, Taylor SC. Global epidemiology and clinical spectrum of rosacea, highlighting skin of color: Review and clinical practice experience. J Am Acad Dermatol. 2019;80(6):1722-1729.e7. doi:10.1016/j.jaad.2018.08.049
[10] Al-Dabagh A, Davis SA, McMichael AJ, Feldman SR. Rosacea in skin of color: not a rare diagnosis. Dermatol Online J. 2014;20(10):13030/qt1mv9r0ss. Published 2014 Oct 15.
[11] Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018;179(2):282-289. doi:10.1111/bjd.16481
[12] Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78(1):148-155. doi:10.1016/j.jaad.2017.08.037
[13] Holmes AD, Spoendlin J, Chien AL, Baldwin H, Chang ALS. Evidence-based update on rosacea comorbidities and their common physiologic pathways. J Am Acad Dermatol. 2018;78(1):156-166. doi:10.1016/j.jaad.2017.07.055
[14] Alia E, Feng H. Rosacea pathogenesis, common triggers, and dietary role: The cause, the trigger, and the positive effects of different foods. Clin Dermatol. 2022;40(2):122-127. doi:10.1016/j.clindermatol.2021.10.004
[15] Hu XM, Li ZX, Zhang DY, et al. Current research and clinical trends in rosacea pathogenesis. Heliyon. 2022;8(10):e10874. Published 2022 Oct 13. doi:10.1016/j.heliyon.2022.e10874
[16] Abram K, Silm H, Maaroos HI, Oona M. Risk factors associated with rosacea. J Eur Acad Dermatol Venereol. 2010;24(5):565-571. doi:10.1111/j.1468-3083.2009.03472.x
[17] Sarkar R, Podder I, Jagadeesan S. Rosacea in skin of color: A comprehensive review. Indian J Dermatol Venereol Leprol. 2020;86(6):611-621. doi:10.4103/ijdvl.IJDVL_769_19
[18] Aubdool AA, Brain SD. Neurovascular aspects of skin neurogenic inflammation. J Investig Dermatol Symp Proc. 2011;15(1):33-39. doi:10.1038/jidsymp.2011.8
[19] Schwab VD, Sulk M, Seeliger S, et al. Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15(1):53-62. doi:10.1038/jidsymp.2011.6
[20] Cui M, Honore P, Zhong C, et al. TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J Neurosci. 2006;26(37):9385-9393. doi:10.1523/JNEUROSCI.1246-06.2006
[21] Salamon M, Sysa-Jedrzejowska A, Lukamowicz J, Lukamowicz M, Swiatkowska E, Wozniacka A. Stezenie wybranych cytokin prozapalnych w surowicy chorych na tradzik rózowaty [Concentration of selected cytokines in serum of patients with acne rosacea]. Przegl Lek. 2008;65(9):371-374.
[22] Batycka-Baran A, Hattinger E, Marchenkov A, et al. Koebnerisin (S100A15): A novel player in the pathogenesis of rosacea. J Am Acad Dermatol. 2019;80(6):1753-1755. doi:10.1016/j.jaad.2018.06.012
[23] Buhl T, Sulk M, Nowak P, et al. Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1/Th17 Pathways. J Invest Dermatol. 2015;135(9):2198-2208. doi:10.1038/jid.2015.141
[24] Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55(2):77-81. doi:10.1016/j.jdermsci.2009.04.007
[25] Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015;72(5):749-760. doi:10.1016/j.jaad.2014.08.028
[26] Shi VY, Leo M, Hassoun L, Chahal DS, Maibach HI, Sivamani RK. Role of sebaceous glands in inflammatory dermatoses. J Am Acad Dermatol. 2015;73(5):856-863. doi:10.1016/j.jaad.2015.08.015
[27] Hoting E, Paul E, Plewig G. Treatment of rosacea with isotretinoin. Int J Dermatol. 1986;25(10):660-663. doi:10.1111/j.1365-4362.1986.tb04533.x
[28] Ní Raghallaigh S, Bender K, Lacey N, Brennan L, Powell FC. The fatty acid profile of the skin surface lipid layer in papulopustular rosacea. Br J Dermatol. 2012;166(2):279-287. doi:10.1111/j.1365-2133.2011.10662.x
[29] Kovács D, Lovászi M, Póliska S, et al. Sebocytes differentially express and secrete adipokines. Exp Dermatol. 2016;25(3):194-199. doi:10.1111/exd.12879
[30] Lee SH, Lee SB, Heo JH, et al. Sebaceous glands participate in the inflammation of rosacea. J Eur Acad Dermatol Venereol. 2020;34(3):e144-e146. doi:10.1111/jdv.16055
[31] Jarmuda S, O'Reilly N, Żaba R, Jakubowicz O, Szkaradkiewicz A, Kavanagh K. Potential role of Demodex mites and bacteria in the induction of rosacea. J Med Microbiol. 2012;61(Pt 11):1504-1510. doi:10.1099/jmm.0.048090-0
[32] Forton F, Germaux MA, Brasseur T, et al. Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice. J Am Acad Dermatol. 2005;52(1):74-87. doi:10.1016/j.jaad.2004.05.034
[33] Casas C, Paul C, Lahfa M, et al. Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation. Exp Dermatol. 2012;21(12):906-910. doi:10.1111/exd.12030
[34] Turgut Erdemir A, Gurel MS, Koku Aksu AE, Falay T, Inan Yuksel E, Sarikaya E. Demodex mites in acne rosacea: reflectance confocal microscopic study. Australas J Dermatol. 2017;58(2):e26-e30. doi:10.1111/ajd.12452
[35] Sarac G, Cankaya C, Ozcan KN, Cenk H, Kapicioglu YK. Increased frequency of Demodex blepharitis in rosacea and facial demodicosis patients. J Cosmet Dermatol. 2020;19(5):1260-1265. doi:10.1111/jocd.13150
[36] Ogrum A, Alim S. In which rosacea patients should Demodex in the eyelashes be investigated?. Niger J Clin Pract. 2020;23(8):1039-1043. doi:10.4103/njcp.njcp_590_18
[37] McMahon FW, Gallagher C, O'Reilly N, Clynes M, O'Sullivan F, Kavanagh K. Exposure of a corneal epithelial cell line (hTCEpi) to Demodex-associated Bacillus proteins results in an inflammatory response. Invest Ophthalmol Vis Sci. 2014;55(10):7019-7028. Published 2014 Oct 2. doi:10.1167/iovs.14-15018
[38] Yamasaki K, Kanada K, Macleod DT, et al. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol. 2011;131(3):688-697. doi:10.1038/jid.2010.351
[39] Segovia J, Sabbah A, Mgbemena V, et al. TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection. PLoS One. 2012;7(1):e29695. doi:10.1371/journal.pone.0029695
[40] Aldrich N, Gerstenblith M, Fu P, et al. Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins. JAMA Dermatol. 2015;151(11):1213-1219. doi:10.1001/jamadermatol.2015.2230
[41] Chang ALS, Raber I, Xu J, et al. Assessment of the genetic basis of rosacea by genome-wide association study. J Invest Dermatol. 2015;135(6):1548-1555. doi:10.1038/jid.2015.53
[42] Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Clustering of autoimmune diseases in patients with rosacea. J Am Acad Dermatol. 2016;74(4):667-72.e1. doi:10.1016/j.jaad.2015.11.004
[43] Odom R, Dahl M, Dover J, et al. Standard management options for rosacea, part 1: overview and broad spectrum of care. Cutis. 2009;84(1):43-47.
[44] van Zuuren EJ, Fedorowicz Z, Carter B, van der Linden MM, Charland L. Interventions for rosacea. Cochrane Database Syst Rev. 2015;2015(4):CD003262. Published 2015 Apr 28. doi:10.1002/14651858.CD003262.pub5
[45] Siddiqui K, Stein Gold L, Gill J. The efficacy, safety, and tolerability of ivermectin compared with current topical treatments for the inflammatory lesions of rosacea: a network meta-analysis. Springerplus. 2016;5(1):1151. Published 2016 Jul 22. doi:10.1186/s40064-016-2819-8
[46] Abokwidir M, Fleischer AB. An emerging treatment: Topical ivermectin for papulopustular rosacea. J Dermatolog Treat. 2015;26(4):379-380. doi:10.3109/09546634.2014.991672
[47] Stein L, Kircik L, Fowler J, et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13(3):316-323.
[48] Layton A, Thiboutot D. Emerging therapies in rosacea. J Am Acad Dermatol. 2013;69(6 Suppl 1):S57-S65. doi:10.1016/j.jaad.2013.04.041
[49] van Zuuren EJ, Kramer S, Carter B, Graber MA, Fedorowicz Z. Interventions for rosacea. Cochrane Database Syst Rev. 2011;(3):CD003262. Published 2011 Mar 16. doi:10.1002/14651858.CD003262.pub4
[50] Gooderham M. Rosacea and its topical management. Skin Therapy Lett. 2009;14(2):1-3.
[51] McGregor SP, Alinia H, Snyder A, Tuchayi SM, Fleischer A Jr, Feldman SR. A Review of the Current Modalities for the Treatment of Papulopustular Rosacea. Dermatol Clin. 2018;36(2):135-150. doi:10.1016/j.det.2017.11.009
[52] Schaller M, Schöfer H, Homey B, et al. Rosacea Management: Update on general measures and topical treatment options. J Dtsch Dermatol Ges. 2016;14 Suppl 6:17-27. doi:10.1111/ddg.13143
[53] Tomić I, Juretić M, Jug M, Pepić I, Cetina Čižmek B, Filipović-Grčić J. Preparation of in situ hydrogels loaded with azelaic acid nanocrystals and their dermal application performance study. Int J Pharm. 2019;563:249-258. doi:10.1016/j.ijpharm.2019.04.016
[54] Patel NU, Shukla S, Zaki J, Feldman SR. Oxymetazoline hydrochloride cream for facial erythema associated with rosacea. Expert Rev Clin Pharmacol. 2017;10(10):1049-1054. doi:10.1080/17512433.2017.1370370
[55] Del Rosso JQ, Kircik LH. Update on the management of rosacea: a status report on the current role and new horizons with topical azelaic acid. J Drugs Dermatol. 2014;13(12):s101-s107.
[56] Arman A, Demirseren DD, Takmaz T. Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline. Int J Ophthalmol. 2015;8(3):544-549. Published 2015 Jun 18. doi:10.3980/j.issn.2222-3959.2015.03.19
[57] Altinyazar HC, Koca R, Tekin NS, Eştürk E. Adapalene vs. metronidazole gel for the treatment of rosacea. Int J Dermatol. 2005;44(3):252-255. doi:10.1111/j.1365-4632.2004.02130.x
[58] Freeman SA, Moon SD, Spencer JM. Clindamycin phosphate 1.2% and tretinoin 0.025% gel for rosacea: summary of a placebo-controlled, double-blind trial. J Drugs Dermatol. 2012;11(12):1410-1414.
[59] Ertl GA, Levine N, Kligman AM. A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Arch Dermatol. 1994;130(3):319-324.
[60] Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part II. Topical and systemic therapies in the treatment of rosacea. J Am Acad Dermatol. 2015;72(5):761-772. doi:10.1016/j.jaad.2014.08.027
[61] Rahman MQ, Ramaesh K, Montgomery DM. Brimonidine for glaucoma. Expert Opin Drug Saf. 2010;9(3):483-491. doi:10.1517/14740331003709736
[62] Fowler J, Jarratt M, Moore A, et al. Once-daily topical brimonidine tartrate gel 0•5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies. Br J Dermatol. 2012;166(3):633-641. doi:10.1111/j.1365-2133.2011.10716.x
[63] Fowler J Jr, Jackson M, Moore A, et al. Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of two randomized, double-blind, and vehicle-controlled pivotal studies. J Drugs Dermatol. 2013;12(6):650-656.
[64] Gold LS, Papp K, Lynde C, et al. Treatment of Rosacea With Concomitant Use of Topical Ivermectin 1% Cream and Brimonidine 0.33% Gel: A Randomized, Vehicle-controlled Study. J Drugs Dermatol. 2017;16(9):909-916.
[65] Anderson MS, Nadkarni A, Cardwell LA, Alinia H, Feldman SR. Spotlight on brimonidine topical gel 0.33% for facial erythema of rosacea: safety, efficacy, and patient acceptability. Patient Prefer Adherence. 2017;11:1143-1150. Published 2017 Jul 6. doi:10.2147/PPA.S115708
[66] Jackson JM, Knuckles M, Minni JP, Johnson SM, Belasco KT. The role of brimonidine tartrate gel in the treatment of rosacea. Clin Cosmet Investig Dermatol. 2015;8:529-538. Published 2015 Oct 23. doi:10.2147/CCID.S58920
[67] Moore A, Kempers S, Murakawa G, et al. Long-term safety and efficacy of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: results of a 1-year open-label study. J Drugs Dermatol. 2014;13(1):56-61.
[68] Cline A, McGregor SP, Feldman SR. Medical Management of Facial Redness in Rosacea. Dermatol Clin. 2018;36(2):151-159. doi:10.1016/j.det.2017.11.010
[69] Del Rosso JQ. A status report on the medical management of rosacea: focus on topical therapies. Cutis. 2002;70(5):271-275.
[70] Abokwidir M, Feldman SR. Rosacea Management. Skin Appendage Disord. 2016;2(1-2):26-34. doi:10.1159/000446215
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Copyright (c) 2025 Aleksandra Okońska, Julia Kozakiewicz, Michał Ziemba, Joanna Kałuska, Tomasz Suprun, Aleksandra Sokół, Klaudia Mościszko, Katarzyna Nowicka, Wiktor Klimek, Maria Majewska

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