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23-04-2024 | Rosacea | Review Article

Rosacea in Older Adults and Pharmacologic Treatments

Authors: Jennifer J. Lee, Anna L. Chien

Published in: Drugs & Aging | Issue 5/2024

Abstract

Rosacea is a chronic inflammatory skin condition that is often more severe in older patients. The main clinical features are erythema, telangiectasia, and inflammatory lesions of the face. The pathogenesis of this condition is not fully understood but certainly multifaceted. Immune and inflammatory dysregulation, genetics, neurogenic dysregulation, microbiome dysbiosis, and systemic disease have all been implicated in rosacea pathogenesis. As we better understand the various pathways that lead to rosacea, we acknowledge that the different symptoms may have unique underlying triggers and mechanisms. Aging also impacts rosacea diagnosis and treatment. Older adults have more severe rosacea symptoms while also having more sensitive and fragile skin than younger patients; therefore, rosacea treatments for older patients require a balance between delivering adequate potency while also minimizing skin irritation and other adverse effects. Until recently, rosacea diagnoses were based on concrete subtypes that did not necessarily capture each patient’s manifestation of rosacea. There is now an emphasis on more personalized phenotype-based diagnoses and treatments, which allows for more emphasis on treating individual symptoms and accounting for the unique characteristics of older patients. Centrofacial erythema is best treated with brimonidine and oxymetazoline, while phymatous change and telangiectasia are best treated with surgery and laser ablation. Treatment for rosacea papules and pustules ranges from topicals, such as azelaic acid, ivermectin, metronidazole, minocycline, and encapsulated benzoyl peroxide, to systemics, such as doxycycline and isotretinoin. It is important to understand these treatments in relation to adverse effects and drug interactions that may specifically arise in older populations to provide optimal care. As we advance in understanding rosacea's pathogenesis and adopt personalized phenotype-based approaches, optimizing care for older patients becomes crucial. Continued research into novel treatments is essential to address their unique needs.

Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015;72:749–58. https://doi.org/10.1016/j.jaad.2014.08.028. (quiz 759-760).CrossRefPubMed

Aldrich N, Gerstenblith M, Fu P, Tuttle MS, Varma P, Gotow E, Cooper KD, Mann M, Popkin DL. Genetic vs environmental factors that correlate with rosacea: a cohort-based survey of twins. JAMA Dermatol. 2015;151:1213–9. https://doi.org/10.1001/jamadermatol.2015.2230.CrossRefPubMed

Ahn CS, Huang WW. Rosacea pathogenesis. Dermatol Clin. 2018;36:81–6. https://doi.org/10.1016/j.det.2017.11.001.CrossRefPubMed

Yamasaki K, Kanada K, Macleod DT, Borkowski AW, Morizane S, Nakatsuji T, Cogen AL, Gallo RL. TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes. J Invest Dermatol. 2011;131:688–97. https://doi.org/10.1038/jid.2010.351.CrossRefPubMed

Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018;40:249–59. https://doi.org/10.1007/s00281-018-0675-z.CrossRefPubMedPubMedCentral

Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol. 2007;157:474–81. https://doi.org/10.1111/j.1365-2133.2007.08028.x.CrossRefPubMed

Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C, Rivier M, Carlavan I, Rossio P, Metze D, et al. Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:53–62. https://doi.org/10.1038/jidsymp.2011.6.CrossRefPubMedPubMedCentral

Yamasaki K, Miyachi Y. Perspectives on rosacea patient characteristics and quality of life using baseline data from a phase 3 clinical study conducted in Japan. J Dermatol. 2022;49:1221–7. https://doi.org/10.1111/1346-8138.16596.CrossRefPubMedPubMedCentral

Rainer BM, Fischer AH, Felipe L, da Silva D, Kang S, Chien AL. Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study. J Am Acad Dermatol. 2015;73:604–8. https://doi.org/10.1016/j.jaad.2015.07.009.CrossRefPubMed

10.

Gallo RL, Granstein RD, Kang S, Mannis M, Steinhoff M, Tan J, Thiboutot D. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78:148–55. https://doi.org/10.1016/j.jaad.2017.08.037.CrossRefPubMed

11.

Tan J, Berg M, Gallo RL, Del Rosso JQ. Applying the phenotype approach for rosacea to practice and research. Br J Dermatol. 2018;179:741–6. https://doi.org/10.1111/bjd.16815.CrossRefPubMed

12.

Barakji YA, Ronnstad ATM, Christensen MO, Zachariae C, Wienholtz NKF, Halling AS, Maul JT, Thomsen SF, Egeberg A, Thyssen JP. Assessment of frequency of rosacea subtypes in patients with rosacea: a systematic review and meta-analysis. JAMA Dermatol. 2022;158:617–25. https://doi.org/10.1001/jamadermatol.2022.0526.CrossRefPubMedPubMedCentral

13.

Aponte JL, Chiano MN, Yerges-Armstrong LM, Hinds DA, Tian C, Gupta A, Guo C, Fraser DJ, Freudenberg JM, Rajpal DK, et al. Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes. Hum Mol Genet. 2018;27:2762–72. https://doi.org/10.1093/hmg/ddy184.CrossRefPubMedPubMedCentral

14.

Yang F, Wang L, Shucheng H, Jiang X. Differences in clinical characteristics of rosacea across age groups: A retrospective study of 840 female patients. J Cosmet Dermatol. 2023;22:949–57. https://doi.org/10.1111/jocd.15470.CrossRefPubMed

15.

Woo YR, Lim JH, Cho DH, Park HJ. Rosacea: molecular mechanisms and management of a chronic cutaneous inflammatory condition. Int J Mol Sci. 2016. https://doi.org/10.3390/ijms17091562.CrossRefPubMedPubMedCentral

16.

Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descargues P, Hovnanian A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13:975–80. https://doi.org/10.1038/nm1616.CrossRefPubMed

17.

De Y, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med. 2000;192:1069–74. https://doi.org/10.1084/jem.192.7.1069.CrossRef

18.

Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, Issbrucker K, Unterberger P, Zaiou M, Lebherz C, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111:1665–72. https://doi.org/10.1172/JCI17545.CrossRefPubMedPubMedCentral

19.

Bomba L, Walter K, Soranzo N. The impact of rare and low-frequency genetic variants in common disease. Genome Biol. 2017;18:77. https://doi.org/10.1186/s13059-017-1212-4.CrossRefPubMedPubMedCentral

20.

Deng Z, Chen M, Zhao Z, Xiao W, Liu T, Peng Q, Wu Z, Xu S, Shi W, Jian D, et al. Whole genome sequencing identifies genetic variants associated with neurogenic inflammation in rosacea. Nat Commun. 2023;14:3958. https://doi.org/10.1038/s41467-023-39761-2.CrossRefPubMedPubMedCentral

21.

Thompson KG, Rainer BM, Antonescu C, Florea L, Mongodin EF, Kang S, Chien AL. Comparison of the skin microbiota in acne and rosacea. Exp Dermatol. 2021;30:1375–80. https://doi.org/10.1111/exd.14098.CrossRefPubMed

22.

Rainer BM, Thompson KG, Antonescu C, Florea L, Mongodin EF, Bui J, Fischer AH, Pasieka HB, Garza LA, Kang S, et al. Characterization and analysis of the skin microbiota in rosacea: a case-control study. Am J Clin Dermatol. 2020;21:139–47. https://doi.org/10.1007/s40257-019-00471-5.CrossRefPubMedPubMedCentral

23.

Forton FMN. The pathogenic role of demodex mites in rosacea: a potential therapeutic target already in erythematotelangiectatic rosacea? Dermatol Ther (Heidelb). 2020;10:1229–53. https://doi.org/10.1007/s13555-020-00458-9.CrossRefPubMed

24.

Dahl MV, Ross AJ, Schlievert PM. Temperature regulates bacterial protein production: possible role in rosacea. J Am Acad Dermatol. 2004;50:266–72. https://doi.org/10.1016/j.jaad.2003.05.005.CrossRefPubMed

25.

Aghaei M, Aghaei S, Behshadnia F, Ghomashlooyan M, Khaghani A, Baradaran EH, Naeini FF, Iraji F, Shahmoradi Z, Hosseini SM, et al. Association between the Treatment of rosacea and eradication of Helicobacter pylori infection. Adv Biomed Res. 2023;12:173. https://doi.org/10.4103/abr.abr_236_22.CrossRefPubMedPubMedCentral

26.

Thompson KG, Rainer BM, Kang S, Chien AL. The skin microbiota as a link between rosacea and its systemic comorbidities. Int J Dermatol. 2020;59:513–4. https://doi.org/10.1111/ijd.14802.CrossRefPubMed

27.

Woo, Y.R., Lee, S.H., Cho, S.H., Lee, J.D., Kim, H.S. Characterization and analysis of the skin microbiota in rosacea: impact of systemic antibiotics. J Clin Med 2020, 9, doi:https://doi.org/10.3390/jcm9010185.

28.

Nam JH, Yun Y, Kim HS, Kim HN, Jung HJ, Chang Y, Ryu S, Shin H, Kim HL, Kim WS. Rosacea and its association with enteral microbiota in Korean females. Exp Dermatol. 2018;27:37–42. https://doi.org/10.1111/exd.13398.CrossRefPubMed

29.

Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A, Parodi A, Savarino V. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008;6:759–64. https://doi.org/10.1016/j.cgh.2008.02.054.CrossRefPubMed

30.

Drago F, De Col E, Agnoletti AF, Schiavetti I, Savarino V, Rebora A, Paolino S, Cozzani E, Parodi A. The role of small intestinal bacterial overgrowth in rosacea: A 3-year follow-up. J Am Acad Dermatol. 2016;75:e113–5. https://doi.org/10.1016/j.jaad.2016.01.059.CrossRefPubMed

31.

Gravina A, Federico A, Ruocco E, Lo Schiavo A, Masarone M, Tuccillo C, Peccerillo F, Miranda A, Romano L, de Sio C, et al. Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea. United European Gastroenterol J. 2015;3:17–24. https://doi.org/10.1177/2050640614559262.CrossRefPubMedPubMedCentral

32.

Lazaridou E, Korfitis C, Kemanetzi C, Sotiriou E, Apalla Z, Vakirlis E, Fotiadou C, Lallas A, Ioannides D. Rosacea and Helicobacter pylori: links and risks. Clin Cosmet Investig Dermatol. 2017;10:305–10. https://doi.org/10.2147/CCID.S121117.CrossRefPubMedPubMedCentral

33.

Diaz C, O’Callaghan CJ, Khan A, Ilchyshyn A. Rosacea: a cutaneous marker of Helicobacter pylori infection? Results of a pilot study. Acta Derm Venereol. 2003;83:282–6. https://doi.org/10.1080/00015550310016544.CrossRefPubMed

34.

Sharma VK, Lynn A, Kaminski M, Vasudeva R, Howden CW. A study of the prevalence of Helicobacter pylori infection and other markers of upper gastrointestinal tract disease in patients with rosacea. Am J Gastroenterol. 1998;93:220–2. https://doi.org/10.1111/j.1572-0241.1998.00220.x.CrossRefPubMed

35.

Hirschmann JV. Does Helicobacter pylori have a role in the pathogenesis of rosacea? J Am Acad Dermatol. 2000;42:537–9. https://doi.org/10.1016/s0190-9622(00)90242-1.CrossRefPubMed

36.

Gong H, Xu HM, Zhang DK. Focusing on Helicobacter pylori infection in the elderly. Front Cell Infect Microbiol. 2023;13:1121947. https://doi.org/10.3389/fcimb.2023.1121947.CrossRefPubMedPubMedCentral

37.

Chudzicka-Strugala I, Golebiewska I, Brudecki G, Elamin W, Zwozdziak B. Demodicosis in Different age groups and alternative treatment options—a review. J Clin Med. 2023. https://doi.org/10.3390/jcm12041649.CrossRefPubMedPubMedCentral

38.

Forton FMN, De Maertelaer V. Effectiveness of benzyl benzoate treatment on clinical symptoms and Demodex density over time in patients with rosacea and demodicosis: a real life retrospective follow-up study comparing low- and high-dose regimens. J Dermatolog Treat. 2022;33:456–65. https://doi.org/10.1080/09546634.2020.1770168.CrossRefPubMed

39.

Forton FMN, De Maertelaer V. Treatment of rosacea and demodicosis with benzyl benzoate: effects of different doses on Demodex density and clinical symptoms. J Eur Acad Dermatol Venereol. 2020;34:365–9. https://doi.org/10.1111/jdv.15938.CrossRefPubMed

40.

Yi JZ, Chen SX, Lukac D, McGee JS. Systemic comorbidities of rosacea: practice gaps among dermatologists. Arch Dermatol Res. 2022;314:995–7. https://doi.org/10.1007/s00403-021-02279-y.CrossRefPubMed

41.

Marchitto MC, Chien AL. Rosacea and associated comorbidities: a Google search trends analysis. J Clin Aesthet Dermatol. 2020;13:36–40.PubMedPubMedCentral

42.

Coumbe AG, Pritzker MR, Duprez DA. Cardiovascular risk and psoriasis: beyond the traditional risk factors. Am J Med. 2014;127:12–8. https://doi.org/10.1016/j.amjmed.2013.08.013.CrossRefPubMed

43.

Reinholz M, Ruzicka T, Schauber J. Cathelicidin LL-37: an antimicrobial peptide with a role in inflammatory skin disease. Ann Dermatol. 2012;24:126–35. https://doi.org/10.5021/ad.2012.24.2.126.CrossRefPubMedPubMedCentral

44.

Haber R, El Gemayel M. Comorbidities in rosacea: A systematic review and update. J Am Acad Dermatol. 2018;78:786-792e788. https://doi.org/10.1016/j.jaad.2017.09.016.CrossRefPubMed

45.

Hua TC, Chung PI, Chen YJ, Wu LC, Chen YD, Hwang CY, Chu SY, Chen CC, Lee DD, Chang YT, et al. Cardiovascular comorbidities in patients with rosacea: A nationwide case-control study from Taiwan. J Am Acad Dermatol. 2015;73:249–54. https://doi.org/10.1016/j.jaad.2015.04.028.CrossRefPubMed

46.

Egeberg A, Weinstock LB, Thyssen EP, Gislason GH, Thyssen JP. Rosacea and gastrointestinal disorders: a population-based cohort study. Br J Dermatol. 2017;176:100–6. https://doi.org/10.1111/bjd.14930.CrossRefPubMed

47.

Mohan A, Godugu S, Joshi SS, Shah KB, Vanka SC, Shakil H, P, D., Veliginti, S., Sure, P.S., Goranti, J,. Gut-brain axis: altered microbiome and depression - review. Ann Med Surg (Lond). 2023;85:1784–9. https://doi.org/10.1097/MS9.0000000000000573.CrossRefPubMed

48.

Wang X, Li Y, Wu L, Xiao S, Ji Y, Tan Y, Jiang C, Zhang G. Dysregulation of the gut-brain-skin axis and key overlapping inflammatory and immune mechanisms of psoriasis and depression. Biomed Pharmacother. 2021;137: 111065. https://doi.org/10.1016/j.biopha.2020.111065.CrossRefPubMed

49.

Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Exploring the Association between rosacea and Parkinson disease: a Danish nationwide cohort study. JAMA Neurol. 2016;73:529–34. https://doi.org/10.1001/jamaneurol.2016.0022.CrossRefPubMed

50.

Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Patients with rosacea have increased risk of dementia. Ann Neurol. 2016;79:921–8. https://doi.org/10.1002/ana.24645.CrossRefPubMed

51.

Egeberg A, Ashina M, Gaist D, Gislason GH, Thyssen JP. Prevalence and risk of migraine in patients with rosacea: a population-based cohort study. J Am Acad Dermatol. 2017;76:454–8. https://doi.org/10.1016/j.jaad.2016.08.055.CrossRefPubMed

52.

Hung CT, Chiang CP, Chung CH, Tsao CH, Chien WC, Wang WM. Risk of psychiatric disorders in rosacea: a nationwide, population-based, cohort study in Taiwan. J Dermatol. 2019;46:110–6. https://doi.org/10.1111/1346-8138.14705.CrossRefPubMed

53.

Rodgers JL, Jones J, Bolleddu SI, Vanthenapalli S, Rodgers LE, Shah K, Karia K, Panguluri SK. Cardiovascular risks associated with gender and aging. J Cardiovasc Dev Dis. 2019. https://doi.org/10.3390/jcdd6020019.CrossRefPubMedPubMedCentral

54.

Dumurgier J, Tzourio C. Epidemiology of neurological diseases in older adults. Rev Neurol (Paris). 2020;176:642–8. https://doi.org/10.1016/j.neurol.2020.01.356.CrossRefPubMed

55.

Dumic I, Nordin T, Jecmenica M, Stojkovic Lalosevic M, Milosavljevic T, Milovanovic T. Gastrointestinal tract disorders in older age. Can J Gastroenterol Hepatol. 2019;2019:6757524. https://doi.org/10.1155/2019/6757524.CrossRefPubMedPubMedCentral

56.

Petrova NN, Khvostikova DA. Prevalence, structure, and risk factors for mental disorders in older adults. Adv Gerontol. 2021;34:152–9.PubMed

57.

Gallo RL, Granstein RD, Kang S, Mannis M, Steinhoff M, Tan J, Thiboutot D. Rosacea comorbidities and future research: The 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;78:167–70. https://doi.org/10.1016/j.jaad.2017.06.150.CrossRefPubMed

58.

Elewski B. Rosacea treatment: a patient-centric approach. Br J Dermatol. 2020;182:1090–1. https://doi.org/10.1111/bjd.18616.CrossRefPubMed

59.

Cices A, Alexis AF. Patient-focused solutions in rosacea management: treatment challenges in special patient groups. J Drugs Dermatol. 2019;18:608–12.PubMed

60.

Helfrich YR, Maier LE, Cui Y, Fisher GJ, Chubb H, Fligiel S, Sachs D, Varani J, Voorhees J. Clinical, histologic, and molecular analysis of differences between erythematotelangiectatic rosacea and telangiectatic photoaging. JAMA Dermatol. 2015;151:825–36. https://doi.org/10.1001/jamadermatol.2014.4728.CrossRefPubMed

61.

Morgado-Carrasco D, Granger C, Trullas C, Piquero-Casals J. Impact of ultraviolet radiation and exposome on rosacea: Key role of photoprotection in optimizing treatment. J Cosmet Dermatol. 2021;20:3415–21. https://doi.org/10.1111/jocd.14020.CrossRefPubMedPubMedCentral

62.

Fowler J Jr, Jackson M, Moore A, Jarratt M, Jones T, Meadows K, Steinhoff M, Rudisill D, Leoni M. 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;12:650–6.PubMed

63.

Baumann L, Goldberg DJ, Stein Gold L, Tanghetti EA, Lain E, Kaufman J, Weng E, Berk DR, Ahluwalia G. Pivotal trial of the efficacy and safety of oxymetazoline cream 1.0% for the treatment of persistent facial erythema associated with rosacea: findings from the second REVEAL trial. J Drugs Dermatol. 2018;17:290–8.PubMed

64.

Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015;62:31–9. https://doi.org/10.2344/0003-3006-62.1.31.CrossRefPubMedPubMedCentral

65.

Fowler J, Jarratt M, Moore A, Meadows K, Pollack A, Steinhoff M, Liu Y, Leoni M, Brimonidine Phase, I.I.S.G. Once-daily topical brimonidine tartrate gel 05% 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;166:633–41. https://doi.org/10.1111/j.1365-2133.2011.10716.x.CrossRefPubMedPubMedCentral

66.

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;11:1143–50. https://doi.org/10.2147/PPA.S115708.CrossRefPubMedPubMedCentral

67.

Ringuet J, Houle MC. Case report: allergic contact dermatitis to topical brimonidine demonstrated with patch testing: insights on evaluation of brimonidine sensitization. J Cutan Med Surg. 2018;22:636–8. https://doi.org/10.1177/1203475418789020.CrossRefPubMed

68.

Cookson H, McFadden J, White J, White IR. Allergic contact dermatitis caused by Mirvaso(R), brimonidine tartrate gel 0.33%, a new topical treatment for rosaceal erythema. Contact Dermatitis. 2015;73:366–7. https://doi.org/10.1111/cod.12476.CrossRefPubMed

69.

Rajagopalan A, Rajagopalan B. Allergic contact dermatitis to topical brimonidine. Australas J Dermatol. 2015;56:235. https://doi.org/10.1111/ajd.12299.CrossRefPubMed

70.

Ilkovitch D, Pomerantz RG. Brimonidine effective but may lead to significant rebound erythema. J Am Acad Dermatol. 2014;70:e109-110. https://doi.org/10.1016/j.jaad.2014.01.853.CrossRefPubMed

71.

Swanson LA, Warshaw EM. Allergic contact dermatitis to topical brimonidine tartrate gel 0.33% for treatment of rosacea. J Am Acad Dermatol. 2014;71:832–3. https://doi.org/10.1016/j.jaad.2014.05.073.CrossRefPubMed

72.

Johnson AW, Johnson SM. The role of topical brimonidine tartrate gel as a novel therapeutic option for persistent facial erythema associated with rosacea. Dermatol Ther (Heidelb). 2015;5:171–81. https://doi.org/10.1007/s13555-015-0078-1.CrossRefPubMed

73.

Bowling CB, Lee A, Williamson JD. Blood pressure control among older adults with hypertension: narrative review and introduction of a framework for improving care. Am J Hypertens. 2021;34:258–66. https://doi.org/10.1093/ajh/hpab002.CrossRefPubMedPubMedCentral

74.

Shanler SD, Ondo AL. Successful treatment of the erythema and flushing of rosacea using a topically applied selective alpha1-adrenergic receptor agonist, oxymetazoline. Arch Dermatol. 2007;143:1369–71. https://doi.org/10.1001/archderm.143.11.1369.CrossRefPubMed

75.

Kircik LH, DuBois J, Draelos ZD, Werschler P, Grande K, Cook-Bolden FE, Weng E, Berk DR, Ahluwalia G. Pivotal trial of the efficacy and safety of oxymetazoline cream 1.0% for the treatment of persistent facial erythema associated with rosacea: findings from the first REVEAL trial. J Drugs Dermatol. 2018;17:97–105.PubMed

76.

DuBois J, Dover JS, Jones TM, Weiss RA, Berk DR, Ahluwalia G. Phase 2 Randomized, dose-ranging study of oxymetazoline cream for treatment of persistent facial erythema associated with rosacea. J Drugs Dermatol. 2018;17:308–16.PubMed

77.

Yuan X, Yin D. Benefits and safety of Oxymetazoline cream 1% on rosacea-associated erythema: A systematic review and analysis of clinical evidence. J Cosmet Dermatol. 2023;22:103–10. https://doi.org/10.1111/jocd.15467.CrossRefPubMed

78.

Draelos ZD, Gold MH, Weiss RA, Baumann L, Grekin SK, Robinson DM, Kempers SE, Alvandi N, Weng E, Berk DR, et al. Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: findings from the 52-week open label REVEAL trial. J Am Acad Dermatol. 2018;78:1156–63. https://doi.org/10.1016/j.jaad.2018.01.027.CrossRefPubMed

79.

Chauhan R, Loewenstein SN, Hassanein AH. Rhinophyma: prevalence, severity, impact and management. Clin Cosmet Investig Dermatol. 2020;13:537–51. https://doi.org/10.2147/CCID.S201290.CrossRefPubMedPubMedCentral

80.

Zhang H, Tang K, Wang Y, Fang R, Sun Q. Rosacea treatment: review and update. Dermatol Ther (Heidelb). 2021;11:13–24. https://doi.org/10.1007/s13555-020-00461-0.CrossRefPubMed

81.

van Zuuren EJ, Fedorowicz Z, Tan J, van der Linden MMD, Arents BWM, Carter B, Charland L. Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments. Br J Dermatol. 2019;181:65–79. https://doi.org/10.1111/bjd.17590.CrossRefPubMedPubMedCentral

82.

van Zuuren EJ, Fedorowicz Z. Interventions for rosacea. JAMA. 2015;314:2403–4. https://doi.org/10.1001/jama.2015.15287.CrossRefPubMed

83.

Coda AB, Hata T, Miller J, Audish D, Kotol P, Two A, Shafiq F, Yamasaki K, Harper JC, Del Rosso JQ, et al. Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel. J Am Acad Dermatol. 2013;69:570–7. https://doi.org/10.1016/j.jaad.2013.05.019.CrossRefPubMedPubMedCentral

84.

Juliandri J, Wang X, Liu Z, Zhang J, Xu Y, Yuan C. Global rosacea treatment guidelines and expert consensus points: The differences. J Cosmet Dermatol. 2019;18:960–5. https://doi.org/10.1111/jocd.12903.CrossRefPubMed

85.

Draelos ZD, Elewski BE, Harper JC, Sand M, Staedtler G, Nkulikiyinka R, Shakery K. A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea. Cutis. 2015;96:54–61.PubMed

86.

Draelos ZD, Elewski B, Staedtler G, Havlickova B. Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study. Cutis. 2013;92:306–17.PubMed

87.

Thiboutot DM, Fleischer AB Jr, Del Rosso JQ, Graupe K. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol. 2008;7:541–6.PubMed

88.

Deeks ED. Ivermectin: a review in rosacea. Am J Clin Dermatol. 2015;16:447–52. https://doi.org/10.1007/s40257-015-0150-8.CrossRefPubMed

89.

Abokwidir M, Fleischer AB. An emerging treatment: Topical ivermectin for papulopustular rosacea. J Dermatolog Treat. 2015;26:379–80. https://doi.org/10.3109/09546634.2014.991672.CrossRefPubMed

90.

Stein L, Kircik L, Fowler J, Tan J, Draelos Z, Fleischer A, Appell M, Steinhoff M, Lynde C, Liu H, 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;13:316–23.PubMed

91.

Stein Gold L, Kircik L, Fowler J, Jackson JM, Tan J, Draelos Z, Fleischer A, Appell M, Steinhoff M, Lynde C, et al. Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials. J Drugs Dermatol. 2014;13:1380–6.PubMed

92.

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;5:1151. https://doi.org/10.1186/s40064-016-2819-8.CrossRefPubMedPubMedCentral

93.

Sharma A, Kroumpouzos G, Kassir M, Galadari H, Goren A, Grabbe S, Goldust M. Rosacea management: a comprehensive review. J Cosmet Dermatol. 2022;21:1895–904. https://doi.org/10.1111/jocd.14816.CrossRefPubMed

94.

Narayanan S, Hunerbein A, Getie M, Jackel A, Neubert RH. Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system. J Pharm Pharmacol. 2007;59:1125–30. https://doi.org/10.1211/jpp.59.8.0010.CrossRefPubMed

95.

Wolf JE Jr, Del Rosso JQ. The CLEAR trial: results of a large community-based study of metronidazole gel in rosacea. Cutis. 2007;79:73–80.PubMed

96.

Miyachi Y, Yamasaki K, Fujita T, Fujii C. Metronidazole gel (0.75%) in Japanese patients with rosacea: A randomized, vehicle-controlled, phase 3 study. J Dermatol. 2022;49:330–40. https://doi.org/10.1111/1346-8138.16254.CrossRefPubMed

97.

Okamoto K, Kanayama S, Ikeda F, Fujikawa K, Fujiwara S, Nozawa N, Mori S, Matsumoto T, Hayashi N, Oda M. Broad spectrum in vitro microbicidal activity of benzoyl peroxide against microorganisms related to cutaneous diseases. J Dermatol. 2021;48:551–5. https://doi.org/10.1111/1346-8138.15739.CrossRefPubMed

98.

Stein Gold L, Kwong P, Draelos Z, Arekapudi KL, Levy-Hacham O, Erlich M, Desai SR. Impact of topical vehicles and cutaneous delivery technologies on patient adherence and treatment outcomes in acne and rosacea. J Clin Aesthet Dermatol. 2023;16:26–34.PubMedPubMedCentral

99.

Bhatia ND, Werschler WP, Baldwin H, Sugarman J, Green LJ, Levy-Hacham O, Nov O, Ram V, Stein Gold L. Efficacy and safety of microencapsulated benzoyl peroxide cream, 5%, in rosacea: results from two phase III, randomized, vehicle-controlled trials. J Clin Aesthet Dermatol. 2023;16:34–40.PubMedPubMedCentral

100.

Szymanski L, Arekapudi KL. Adverse-event reports in over-the-counter topical acne drug products containing benzoyl peroxide from a specific pharmaceutical company in the USA. Dermatol Ther (Heidelb). 2022;12:2397–400. https://doi.org/10.1007/s13555-022-00808-9.CrossRefPubMed

101.

Martins AM, Marto JM, Johnson JL, Graber EM. A review of systemic minocycline side effects and topical minocycline as a safer alternative for treating acne and rosacea. Antibiotics (Basel). 2021. https://doi.org/10.3390/antibiotics10070757.CrossRefPubMedPubMedCentral

102.

Gold LS, Del Rosso JQ, Kircik L, Bhatia ND, Hooper D, Nahm WK, Stuart I. Minocycline 1.5% foam for the topical treatment of moderate to severe papulopustular rosacea: Results of 2 phase 3, randomized, clinical trials. J Am Acad Dermatol. 2020;82:1166–73. https://doi.org/10.1016/j.jaad.2020.01.043.CrossRefPubMed

103.

Del Rosso JQ, Webster G, Weiss JS, Bhatia ND, Gold LS, Kircik L. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14–21.PubMedPubMedCentral

104.

Esterly NB, Koransky JS, Furey NL, Trevisan M. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol. 1984;120:1308–13.CrossRefPubMed

105.

Parenti A, Indorato B, Paccosi S. Minocycline affects human neutrophil respiratory burst and transendothelial migration. Inflamm Res. 2017;66:107–9. https://doi.org/10.1007/s00011-016-0999-x.CrossRefPubMed

106.

Erdogan HK, Bulur I, Kocaturk E, Saracoglu ZN, Alatas O, Bilgin M. Advanced oxidation protein products and serum total oxidant/antioxidant status levels in rosacea. Postepy Dermatol Alergol. 2018;35:304–8. https://doi.org/10.5114/ada.2018.76228.CrossRefPubMedPubMedCentral

107.

Del Rosso JQ, Webster GF, Jackson M, Rendon M, Rich P, Torok H, Bradshaw M. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol. 2007;56:791–802. https://doi.org/10.1016/j.jaad.2006.11.021.CrossRefPubMed

108.

Lim HG, Fischer A, Rueda MJ, Kendall J, Kang S, Chien AL. Prevalence of gastrointestinal comorbidities in rosacea: Comparison of subantimicrobial, modified release doxycycline versus conventional release doxycycline. J Am Acad Dermatol. 2018;78:417–9. https://doi.org/10.1016/j.jaad.2017.08.027.CrossRefPubMed

109.

Del Rosso JQ, Brantman S, Baldwin H. Long-term inflammatory rosacea management with subantibiotic dose oral doxycycline 40 mg modified-release capsules once daily. Dermatol Ther. 2022;35: e15180. https://doi.org/10.1111/dth.15180.CrossRefPubMed

110.

Valentin S, Morales A, Sanchez JL, Rivera A. Safety and efficacy of doxycycline in the treatment of rosacea. Clin Cosmet Investig Dermatol. 2009;2:129–40. https://doi.org/10.2147/ccid.s4296.CrossRefPubMedPubMedCentral

111.

van Zuuren EJ, Fedorowicz Z. Low-dose isotretinoin: an option for difficult-to-treat papulopustular rosacea. J Invest Dermatol. 2016;136:1081–3. https://doi.org/10.1016/j.jid.2016.03.003.CrossRefPubMed

112.

Shemer A, Gupta AK, Kassem R, Sharon N, Quinlan EM, Galili E. Low-dose isotretinoin versus minocycline in the treatment of rosacea. Dermatol Ther. 2021;34: e14986. https://doi.org/10.1111/dth.14986.CrossRefPubMed

113.

Chu S, Michelle L, Ekelem C, Sung CT, Rojek N, Mesinkovska NA. Oral isotretinoin for the treatment of dermatologic conditions other than acne: a systematic review and discussion of future directions. Arch Dermatol Res. 2021;313:391–430. https://doi.org/10.1007/s00403-020-02152-4.CrossRefPubMed

114.

Rosada A, Kassner U, Weidemann F, Konig M, Buchmann N, Steinhagen-Thiessen E, Spira D. Hyperlipidemias in elderly patients: results from the Berlin Aging Study II (BASEII), a cross-sectional study. Lipids Health Dis. 2020;19:92. https://doi.org/10.1186/s12944-020-01277-9.CrossRefPubMedPubMedCentral

115.

Kizilyel O, Metin MS, Elmas OF, Cayir Y, Aktas A. Effects of oral isotretinoin on lipids and liver enzymes in acne patients. Cutis. 2014;94:234–8.PubMed

116.

Andreas M, Fabczak-Kubicka A, Schwartz RA. Ocular rosacea: an under-recognized entity. Ital J Dermatol Venerol. 2023;158:110–6. https://doi.org/10.23736/S2784-8671.23.07484-4.CrossRefPubMed

117.

Sobolewska B, Doycheva D, Deuter C, Pfeffer I, Schaller M, Zierhut M. Treatment of ocular rosacea with once-daily low-dose doxycycline. Cornea. 2014;33:257–60. https://doi.org/10.1097/ICO.0000000000000051.CrossRefPubMed

118.

Sobolewska B, Doycheva D, Deuter CM, Schaller M, Zierhut M. Efficacy of topical ivermectin for the treatment of cutaneous and ocular rosacea. Ocul Immunol Inflamm. 2021;29:1137–41. https://doi.org/10.1080/09273948.2020.1727531.CrossRefPubMed

119.

Bilgin B, Karadag AS. Effects of combined oral doxycycline and topical cyclosporine treatment on ocular signs, symptoms, and tear film parameters in rosacea patients. Arq Bras Oftalmol. 2018;81:466–70. https://doi.org/10.5935/0004-2749.20180093.CrossRefPubMed

120.

Arman A, Demirseren DD, Takmaz T. Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline. Int J Ophthalmol. 2015;8:544–9. https://doi.org/10.3980/j.issn.2222-3959.2015.03.19.CrossRefPubMedPubMedCentral

121.

Schechter BA, Katz RS, Friedman LS. Efficacy of topical cyclosporine for the treatment of ocular rosacea. Adv Ther. 2009;26:651–9. https://doi.org/10.1007/s12325-009-0037-2.CrossRefPubMed

122.

Gold LS, Papp K, Lynde C, Lain E, Gooderham M, Johnson S, Kerrouche N. 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;16:909–16.PubMed

123.

Delara M, Murray L, Jafari B, Bahji A, Goodarzi Z, Kirkham J, Chowdhury M, Seitz DP. Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis. BMC Geriatr. 2022;22:601. https://doi.org/10.1186/s12877-022-03279-x.CrossRefPubMedPubMedCentral

124.

Tsai J, Chien AL, Kim N, Rachidi S, Connolly BM, Lim H, Alessi Cesar SS, Kang S, Garza LA. Topical timolol 0.5% gel-forming solution for erythema in rosacea: a quantitative, split-face, randomized, and rater-masked pilot clinical trial. J Am Acad Dermatol. 2021;85:1044–6. https://doi.org/10.1016/j.jaad.2021.01.098.CrossRefPubMedPubMedCentral

125.

Marchitto MC, Chien AL. Mast cell stabilizers in the treatment of rosacea: a review of existing and emerging therapies. Dermatol Ther (Heidelb). 2021;11:1541–9. https://doi.org/10.1007/s13555-021-00597-7.CrossRefPubMed

126.

Palmer SJ. Dermatological conditions in older adults: clinical overview. Br J Community Nurs. 2020;25:222–6. https://doi.org/10.12968/bjcn.2020.25.5.222.CrossRefPubMed

127.

Narla S, Heath CR, Alexis A, Silverberg JI. Racial disparities in dermatology. Arch Dermatol Res. 2023;315:1215–23. https://doi.org/10.1007/s00403-022-02507-z.CrossRefPubMed

Title: Rosacea in Older Adults and Pharmacologic Treatments
Authors: Jennifer J. Lee
Anna L. Chien
Publication date: 23-04-2024
Publisher: Springer International Publishing
Keywords: Rosacea
Brimonidine
Erythema
Ivermectin
Doxycycline
Minocycline
Published in: Drugs & Aging / Issue 5/2024
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI: https://doi.org/10.1007/s40266-024-01115-y

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