245
Views
0
CrossRef citations to date
0
Altmetric
Review

Treatment strategies, including antibiotics, to target the immune component of rosacea

, &
Pages 1239-1251 | Received 18 Jun 2022, Accepted 21 Sep 2022, Published online: 27 Sep 2022

References

  • Rainer BM, Kang S, Chien AL. Rosacea: epidemiology, pathogenesis, and treatment. Dermatoendocrinol. 2017;9(1).
  • Alexis AF, Callender VD, Baldwin HE, et al. 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.
  • Mikkelsen CS, Holmgren HR, Kjellman P, et al. Rosacea: a clinical review. Dermatol Reports. 2016; 8(1). DOI: 10.4081/dr.2016.6387
  • van Zuuren EJ, Arents BWM, van der Linden MMD, et al. Rosacea: new concepts in classification and treatment. Am J Clin Dermatol. 2021;22(4):457–465.
  • 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.
  • Oussedik E, Bourcier M, Tan J. Psychosocial burden and other impacts of rosacea on patients’ quality of life. Dermatol Clin. 2018;36(2):103–113.
  • Johnson SM, Berg A, Barr C. Managing rosacea in the clinic: from pathophysiology to treatment-a review of the literature. J Clin Aesthet Dermatol. 2020;13(4 Suppl 1):S17–S22.
  • Huynh TT. Burden of disease: the psychosocial impact of rosacea on a patient’s quality of life. Am Health Drug Benefits. 2013;6(6):348–354.
  • Lim HW, Collins SAB, Resneck JS, et al. The burden of skin disease in the United States. J Am Acad Dermatol. 2017;76(5):958–972.e2.
  • 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.
  • 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.
  • Awosika O, Oussedik E. Genetic predisposition to rosacea. Dermatol Clin. 2018;36(2):87–92.
  • Plewig G, Melnik B, Chen W. Acne Epidemiology and Genetics. Plewig and Kligman´s Acne and Rosacea. 4th ed. Springer Cham; 2019.
  • Kim HS. Microbiota in rosacea. Am J Clin Dermatol [Internet]. 2020;21:25–35.
  • Thompson KG, Rainer BM, Antonescu C, et al. Comparison of the skin microbiota in acne and rosacea. Exp Dermatol. 2021;30(10):1375–1380.
  • Thompson KG, Rainer BM, Kang S, et al. The skin microbiota as a link between rosacea and its systemic comorbidities. Int J Dermatol. 2020;59(4):513–514.
  • Dursun R, Daye M, Durmaz K. Acne and rosacea: what’s new for treatment? Dermatol Ther. 2019;32(5):e13020.
  • Zhang H, Tang K, Wang Y, et al. Rosacea Treatment: review and Update. Dermatol Ther (Heidelb). 2021;11(1):13–24.
  • Fritsch P, Kolber MR, Korownyk C. Topical treatments for rosacea. Can Family Physician. 2019;65(11):803. College of Family Physicians of Canada.
  • Moustafa FA, Sandoval LF, Feldman SR. Rosacea: new and emerging treatments. Drugs. Springer International Publishing. 2014;74(13):1457–1465.
  • Rivero AL, Whitfeld M. An update on the treatment of rosacea. Aust Prescr. 2018;41(2):41.
  • Dall’Oglio F, Nasca MR, Micali G. Emerging topical drugs for the treatment of rosacea. Expert Opin Emerg Drugs. 2021;26(1):27–38.
  • Sharma A, Kroumpouzos G, Kassir M, et al. Rosacea management: a comprehensive review. J Cosmet Dermatol. 2022;21(5):1895–1904.
  • Abokwidir M, Feldman SR. Rosacea Management. Skin Appendage Disorders. 2016;2(1-2):26–34.
  • Martins AM, Marto JM, Johnson JL, et al. A review of systemic minocycline side effects and topical minocycline as a safer alternative for treating acne and rosacea. Antibiotics. 2021;10(7):757.
  • Gold LS, Del Rosso JQ, Kircik L, et al. 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(5):1166–1173.
  • Mrowietz U, Kedem TH, Keynan R, et al. A Phase II, randomized, double-blind clinical study evaluating the safety, tolerability, and efficacy of a topical minocycline foam, FMX103, for the treatment of facial papulopustular rosacea. Am J Clin Dermatol. 2018;19(3):427–436.
  • Webster G, Draelos ZD, Graber E, et al. A multicentre, randomized, double-masked, parallel group, vehicle-controlled phase IIb study to evaluate the safety and efficacy of 1% and 3% topical minocycline gel in patients with papulopustular rosacea. Br J Dermatol. 2020;183(3):471–479.
  • Del Rosso JQ. A status report on the use of subantimicrobial-dose doxycycline: a review of the biologic and antimicrobial effects of the tetracyclines. Cutis. 2004;74(2):118–122 .
  • Valentín S, Morales A, Sánchez JL, et al. Safety and efficacy of doxycycline in the treatment of rosacea. Clin Cosmet Investig Dermatol. 2009;2:129–140.
  • Santmyire-Rosenberger BR, Nigra TP. Pulse-therapy with azithromycin in acne rosacea and perioral dermatitis: an open study. J Am Acad Dermatol. 2005;53(1):52.
  • Korting HC, Schöllmann C. Tetracycline actions relevant to rosacea treatment. Skin Pharmacol Physiol. 2009;22(6):287–294.
  • Alikhan A, Kurek L, Feldman SR. The role of tetracyclines in rosacea. Am J Clin Dermatol. 2010;11(2):79–87.
  • Stone DU, Chodosh J. Oral tetracyclines for ocular rosacea: an evidence-based review of the literature. Cornea. 2004;23(1):106–109.
  • Wladis EJ, Adam AP, Singhal D. Immune signaling in rosacea. Ocul Surf. 2021;24:22.
  • Woo YR, Lim JH, Cho DH, et al. Rosacea: molecular mechanisms and management of a chronic cutaneous inflammatory condition. Int J Mol Sci. 2016;17(9):1562.
  • Steinhoff M, Schauber J, Leyden JJ. New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013;69(6 Suppl 1):S15–26.
  • Holmes AD, Steinhoff M. Integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics. Exp Dermatol. 2017;26(8):659–667.
  • Messoud, A. Efficacy and Tolerability of Erenumab in the Management of Persistent Redness and Flushing in Rosacea (STOP Ros) .ClinicalTrials.gov.2022 cited: 24 Sep, 2022.
  • Schaller M, Kemény L, Havlickova B, et al. A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea. J Am Acad Dermatol. 2020;82(2):336–343.
  • Del Rosso J. Combined doxycycline 40 mg modified release capsules plus ivermectin 1% cream therapy for severe papulopustular rosacea. J Am Acad Dermatol. 2019;81(4).
  • Schaller M, Gonser L, Belge K, et al. Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. J Eur Acad Dermatol Venereol. 2017;31 Suppl 4:31.
  • Huang HP, Hsu CK, Lee JYY. Rosacea with persistent facial erythema and high demodex density effectively treated with topical ivermectin alone or combined with oral carvedilol. Dermatol Ther. 2021;34(2):e14899.
  • Gold LS, Kircik L, Fowler J, 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. Journal of Drugs in Dermatology .2014; 13(11):1380–1386.
  • Schaller M, Dirschka T, Kemény L, et al. Superior efficacy with ivermectin 1% cream compared to metronidazole 0.75% cream contributes to a better quality of life in patients with severe papulopustular rosacea: a subanalysis of the randomized, investigator-blinded ATTRACT study. Dermatol Ther (Heidelb). 2016;6(3):427–436.
  • Sobolewska B, Doycheva D, Deuter CM, et al. Efficacy of topical ivermectin for the treatment of cutaneous and ocular rosacea. Ocul Immunol Inflamm. 2021;29(1):29.
  • Cardwell LA, Alinia H, Moradi Tuchayi S, et al. New developments in the treatment of rosacea - role of once-daily ivermectin cream. Clin Cosmet Investig Dermatol. 2016;9:71–77.
  • Sahni DR, Feldman SR, Taylor SL. Ivermectin 1% (CD5024) for the treatment of rosacea. Expert Opin Pharmacother. 2018;19(5):511–516.
  • Rubinchik E, Dugourd D, Algara T, et al. Antimicrobial and antifungal activities of a novel cationic antimicrobial peptide, omiganan, in experimental skin colonisation models. Int J Antimicrob Agents. 2009;34(5):457–61.
  • Ong PY, Ohtake T, Brandt C, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(5):347.
  • Grada A, van Doorn M, Lain E, et al. LB1092 Topical omiganan for severe papulopustular rosacea: a randomized, vehicle-controlled, double-blind, multicenter study. J Invest Dermatol. 2019;139(9):B13.
  • Kisich KO, Carspecken CW, Fiéve S, et al. Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3. J Allergy Clin Immunol. 2008;122(1):62–8.
  • Wang FY, Chi CC. Rosacea, germs, and bowels: a review on gastrointestinal comorbidities and gut–skin axis of rosacea. Adv Ther. 2021;38(3):1415–1424.
  • Parodi A, Paolino S, Greco A, et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008;7(1):6.
  • Weinstock LB, Steinhoff M. Rosacea and small intestinal bacterial overgrowth: prevalence and response to rifaximin. J Am Acad Dermatol. 2013;68(5):875–876.
  • Bageorgou F, Vasalou V, Tzanetakou V, et al. The new therapeutic choice of tranexamic acid solution in treatment of erythematotelangiectatic rosacea. J Cosmet Dermatol. 2019;18(2):563–567.
  • Li Y, Xie H, Deng Z, et al. Tranexamic acid ameliorates rosacea symptoms through regulating immune response and angiogenesis. Int Immunopharmacol. 2019;70:67.
  • Del Rosso JQ, Bruce S, Jarratt M, et al. Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea. Journal of Drugs in Dermatology. 2010;9(6):607–13.
  • Del Rosso JQ, Webster GF, Jackson M, et al. 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;58(1):56.
  • Del Rosso JQ. Systemic therapy for rosacea: focus on oral antibiotic therapy and safety. Cutis; cutaneous medicine for the practitioner. 2000;66(4 Suppl):7–13 .
  • Nagler AR, and Del Rosso J. The use of oral antibiotics in the management of rosacea. J Drugs Dermatol. 2019;18(6):506.
  • Del Rosso JQ, Leyden JJ, Thiboutot D, et al. Antibiotic use in acne vulgaris and rosacea: clinical considerations and resistance issues of significance to dermatologists. Cutis. 2008;82(2 Suppl 2):5–12.
  • Di Nardo A, Holmes AD, Muto Y, et al. Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial. J Am Acad Dermatol. 2016;74(6):1086–92.
  • Gold LS, Del Rosso J, Kircik L, et al. Open-label extension study evaluating the long-term safety, efficacy, and tolerability of FMX103 1.5% topical minocycline foam in the treatment of moderate-to-severe facial papulopustular rosacea. SKIN J Cutaneous Med. 2020;13(11):44–49.
  • Del Rosso JQ, Draelos ZD, Effron C, et al. Oral sarecycline for treatment of papulopustular rosacea: results of a pilot study of effectiveness and safety. Journal of Drugs in Dermatology.2021;20(4):426–431.
  • Lova Navarro M, Sánchez-Pedreño Guillen P, Victoria Martínez AM, et al. Papulopustular rosacea: response to treatment with oral azithromycin. Actas Dermosifiliogr. 2018;109(6):529–535.
  • Akhyani M, Ehsani AH, Ghiasi M, et al. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial. Int J Dermatol. 2008;47(3):284–8.
  • Zimmermann P, Ziesenitz VC, Curtis N, et al. The immunomodulatory effects of macrolides-A systematic review of the underlying mechanisms. Front Immunol. 2018;9:302. DOI: 10.3389/fimmu.2018.00302.
  • Stein Gold L, Baldwin H, Harper JC. Rationale for Use of Combination Therapy in Rosacea. J Drugs Dermatol. 2020;19(10):929–934.
  • Fowler JF. Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, USP monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea. J Drugs Dermatol. 2007;6(6):641–5.
  • Steinhoff M, Vocanson M, Voegel JJ, et al. Topical Ivermectin 10 mg/g and oral doxycycline 40 mg modified-release: current evidence on the complementary use of anti-inflammatory rosacea treatments. Adv Ther. 2016;33(9):1481–1501.
  • Sanchez J, Somolinos AL, Almodóvar PI, et al. A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea. J Am Acad Dermatol. 2005;52(2 Suppl 1):53.
  • Kumar A, Chiou A, Shih Y, et al. LB1106 An exploratory open label phase 1b study of secukinumab in patients with moderate to severe papulopustular rosacea. JInvest Dermatol. 2019;139(9):PB15.
  • Woo YR, Lee SH, Cho SH, et al. Characterization and analysis of the skin microbiota in rosacea: impact of systemic antibiotics. J Clin Med. 2020; 9(1):185.
  • Wladis EJ, Adam AP. Treatment of ocular rosacea. Surv Ophthalmol. 2018;63(3):340–346.
  • Wladis EJ, Bradley EA, Bilyk JR, et al. Oral antibiotics for meibomian gland-related ocular surface disease a report by the American Academy of Ophthalmology. Ophthalmology. 2016;123(3):492–6.
  • Wang Z, Xie H, Gong Y, et al. Relationship between rosacea and sleep. J Dermatol. 2020;47(1):47.
  • Daou H, Paradiso M, Hennessy K, et al. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11(1):1–12.
  • Morgado-Carrasco D, Granger C, Trullas C, et al. Impact of ultraviolet radiation and exposome on rosacea: key role of photoprotection in optimizing treatment. J Cosmet Dermatol. 2021;20(11):3415–3421.
  • Kulkarni NN, Takahashi T, Sanford JA, et al. Innate immune dysfunction in rosacea promotes photosensitivity and vascular adhesion molecule expression. J Invest Dermatol. 2020;140(3):645–655.
  • Wirth PJ, Henderson Berg MH, Real-World SN. Real-World Efficacy of Azelaic Acid 15% Gel for the Reduction of Inflammatory Lesions of Rosacea. Skin Therapy Lett. 2017;22(6):5–7.
  • Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975–80.
  • Kuo S, Huang KE, Davis SA, et al. The rosacea patient journey: a novel approach to conceptualizing patient experiences. Cutis. 2015;95(1):37–43.
  • Gollnick H, Layton A. Azelaic acid 15% gel in the treatment of rosacea. Expert Opin Pharmacother. 2008;9(15):2699–706.
  • Gupta AK, Gover MD. Azelaic acid (15% gel) in the treatment of acne rosacea. Int J Dermatol. 2007;46 Suppl 2:46.
  • Draelos ZD, Elewski BE, Harper JC, et al. A phase 3 randomized, double-blind, vehicle-controlled trial of azelaic acid foam 15% in the treatment of papulopustular rosacea. Cutis. 2015;96(1):54–61.
  • McClellan KJ, Noble S. Topical metronidazole: a review of its use in Rosacea. Am J Clin Dermatol. 2000;1(3):191–199.
  • Hill HE, Pham Q, Jacob SE. Topical metronidazole in the management of rosacea. J Dermatol Nurses Assoc. 2016;8(4):279–282.
  • Elewski BE, Fleischer AB, Pariser DMA. Comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Arch Dermatol. 2003;139(11):1444–50.
  • Gold LS, 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. Journal of Drugs in Dermatology. 2014;13(3):316–23.
  • Ble A. Safety and Efficacy of Rifaximin Delayed Release 400 mg Tablets in Patients With Moderate-to-severe Papulopustular Rosacea and Positive Lactulose Breath Test. A Multicenter Double-blind, Placebo-controlled Randomized Clinical Trial . Clinicaltrials.gov. 2019.
  • van der Linden MMD, van Ratingen AR, van Rappard DC, et al. DOMINO, doxycycline 40 mg vs. minocycline 100 mg in the treatment of rosacea: a randomized, single-blinded, noninferiority trial, comparing efficacy and safety. Br J Dermatol. 2017; 176(6):1465–1474.
  • Thomas K, Yelverton CB, Yentzer BA, et al. The cost-effectiveness of rosacea treatments. J Dermatological Treat. 2009;20(2): 72–75.
  • Taieb A, Gold LS, Feldman SR, et al. Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States. JMCP. 2016;22(6):654–665. DOI: 10.18553/jmcp.2016.15210
  • Tan X, Feldman SR, Chang J, et al. Topical drug delivery systems in dermatology: a review of patient adherence issues. Expert Opin Drug Deliv. 2012;9(10):1263–1271 .
  • Geisler AN, Purvis CG, Dao DPD, et al. Medication therapy management in dermatology: a call to action. J Dermatological Treat. 2021;32(4):373–375.
  • Perche PO, Singh R, Cook MK, et al. Greater rosacea severity correlates with greater adherence and improvement in a clinical study. J Am Acad Dermatol. 2022. DOI:10.1016/j.jaad.2022.04.037.
  • Wolf JE. Medication adherence: a key factor in effective management of rosacea. Adv Ther. 2001;18(6):272–81.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.