Research Article| Volume 35, ISSUE 2, P207-212, March 2017

Pharmacologic treatments for rosacea


      Rosacea represents a common and chronic inflammatory skin disorder. Clinical features include transient and permanent erythema, inflammatory papules and pustules, phymatous changes, and ocular signs and symptoms. Rosacea is generally classified into four subtypes and one variant. Subtype 1, erythematotelangiectatic rosacea, includes clinical features of flushing and persistent central facial erythema with or without telangiectasia. Subtype 2, papulopustular rosacea, is characterized by persistent central facial erythema with transient papules or pustules or both on the central face. Subtype 3, phymatous rosacea, includes thickening of the skin with irregular surface nodularities and enlargement. Subtype 4, ocular rosacea, includes inflammation of different parts of the eye and eyelid. A variant, granulomatous rosacea, is noninflammatory and is characterized by hard, brown, yellow, or red cutaneous papules or nodules of uniform size. Patients may present with more than one subtype, and each individual characteristic may fluctuate. There is debate whether rosacea progresses from one subtype over time or subtypes represent discreet entities. Defining clinical presentation and improved understanding of pathophysiology has resulted in identification of novel treatment approaches. This contribution outlines a rationale for treatment, highlights an evidence-based approach with approved treatments, and considers novel developments and off-license therapy available.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinics in Dermatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Del Rosso J.Q.
        • Thiboutot D.
        • Gallo R.
        • et al.
        Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 2: A status report on topical agents.
        Cutis. 2013; 92: 277-284
        • Elewski B.E.
        • Draelos Z.
        • Dréno B.
        • Jansen T.
        • Layton A.
        • Picardo M.
        Rosacea-global diversity and optimized outcome: Proposed international consensus from the Rosacea International Expert Group.
        J Eur Acad Dermatol Venereol. 2011; 25: 188-200
        • Culp B.
        • Scheinfeld N.
        Rosacea: A review.
        P T. 2009; 34: 38-45
        • Korting H.C.
        • Schöllmann C.
        Current topical and systemic approaches to treatment of rosacea.
        J Eur Acad Dermatol Venereol. 2009; 23: 876-882
        • Bhatia N.
        • Del Rosso J.
        Optimal Management of papulopustular rosacea: Rationale for combination therapy.
        J Drug Dermatol. 2012; 11: 838-844
        • Dahl M.V.
        • Katz H.I.
        • Krueger G.G.
        • et al.
        Topical metronidazole maintains remissions of rosacea.
        J Drug Dermatol. 1998; 134: 679-683
        • Thiboutot D.M.
        • Fletscher A.B..
        • Del Rosso J.Q.
        • Rich P.
        A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy.
        J Drug Dermatol. 2009; 8: 639-648
        • Forstinger C.
        • Kittler H.
        • Binder M.
        Treatment of rosacea-like demodicidosis with oral invermectin and topical permethrin cream.
        J Am Acad Dermatol. 1999; 41: 775-777
        • Bikowski J.B.
        The pharmacological therapy of rosacea; a paradigm shift in progress.
        Cutis. 2005; 75: 27-32
        • Clyti E.
        • Sayavong K.
        • Chanthavisouk K.
        Demodecie chez un malade infecte par le VIH: Guerison pas ivermectine.
        Ann Dermatol Venereol. 2005; 132: 459-461
        • Clyti E.
        • Nacher M.
        • Sainte-Marie D.
        • Pradinaud R.
        • Couppie P.
        Ivermectin treatment of three cases of demodecidosis during human immunodeficiency virus infection.
        Int J Dermatol. 2006; 45: 1066-1068
        • Ci X.
        • Li H.
        • Yu Q.
        • et al.
        Avermectin exerts anti-inflammatory effect by down regulating the nuclear transcription factor kappa-B and mitogen activated protein kinase activation pathway.
        Fundam Clin Pharmacol. 2009; 23: 449-455
        • Stein-Gold L.
        • Kicik 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 Drug Dermatol. 2014; 13: 316-323
        • Taieb A.
        • Ortonne J.P.
        • Ruzicka T.
        • et al.
        Ivermectin Phase III study group. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: A randomised, investigator-blinded trial.
        Br J Dermatol. 2015; 172: 1103-1110
        • Del Rosso J.Q.
        Management of facial erythema of rosacea: What is the role of topical α-adrenergic receptor agonist therapy?.
        J Am Acad Dermatol. 2013; 69: S44-S56
        • Fowler J.
        • Jarratt M.
        • Moore A.
        • et al.
        Brimonidine Phase II Study Group. 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: 633-641
        • Fowler Jr., J.
        • 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: 650-656
        • Rahman M.Q.
        • Ramaesh K.
        • Montgomery D.N.I.
        Brimonidine for glaucoma.
        Expert Opin Drug Saf. 2010; 9: 483-491
        • Del Rosso J.
        Advances in understanding and managing rosacea: Part 2.
        J Clin Aesthet Dermatol. 2012; 5: 26-36
        • Kawana S.
        • Ochiai H.
        • Tachihara R.
        Objective evaluation of the effect of intense pulsed light on rosacea and solar lentigines by spectrophotometric analysis of skin color.
        Dermatol Surg. 2007; 33: 449-454
        • Tanghetti E.
        • Del Rosso J.Q.
        • Thiboutot D.
        • et al.
        Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: A status report on physical modalities and devices.
        Cutis. 2014; 93: 71-76
        • Tanghetti E.A.
        • Jackson M.
        • Belasco K.T.
        • et al.
        Optimising use of topical brimonidine in rosacea management: Panel recommendations.
        J Drugs Dermatol. 2015; 14: 33-39
        • Altinyazar H.C.
        • Koca R.
        • Tekin N.S.
        • et al.
        Adapalene vs metronidazole gel for the treatment of rosacea.
        Int J Dermatol. 2005; 44: 252-255
        • Leyden J.J.
        Efficacy of a novel rosacea treatment system: An investigator-blind, randomized, parallel-group study.
        J Drugs Dermatol. 2011; 10: 1179-1185
        • Bribeche M.R.
        • Fedotov V.P.
        • Gladichev V.V.
        • Pukhalskaya D.M.
        • Kolitcheva N.L.
        Clinical and experimental assessment of the effects of a new topical treatment with praziquantel in the management of rosacea.
        Int J Dermatol. 2015; 54: 481-487
        • Two A.M.
        • Hata T.R.
        • Nakatsuji T.
        • et al.
        Reduction in serine protease activity correlates with improved rosacea severity in a small, randomized pilot study of a topical serine protease inhibitor.
        J Invest Dermatol. 2015; 134: 1143-1145
        • Leyden J.J.
        Randomized, phase 2, dose-ranging study in the treatment of rosacea with encapsulated benzoyl peroxide gel.
        J Drugs Dermatol. 2014; 13: 685-688
        • Lebwohl M.G.
        • Medansky R.
        • Russo C.
        • Plott R.
        The comparative efficacy of sodium sulfacetamide 10%/sulfur 5% (Sulfacet-R) lotion and metronidazole 0.75% (Metrogel) in the treatment of rosacea.
        J Geriatr Dermatol. 1995; 3: 183-185
        • Chang A.L.
        • Alora-Palli M.
        • Lima X.T.
        • et al.
        A randomized, double-blind, placebo-controlled, pilot study to assess the efficacy and safety of clindamycin 1.2% and tretinoin 0.025% combination gel for the treatment of acne rosacea over 12 weeks.
        J Drugs Dermatol. 2012; 11: 333-339
      1. Novartis. 2014;
        • Luger T.
        • Peukert N.
        • Rother M.
        A multicentre, randomized, placebo-controlled trial establishing the treatment effect of TDT 068, a topical formulation containing drug-free ultra-deformable phospholipid vesicles, on the primary features of erythematotelangiectatic rosacea.
        J Eur Acad Dermatol Venereol. 2015; 29: 283-290
        • Weissenbacher S.
        • Merkl J.
        • Hildebrandt B.
        • et al.
        Pimecrolimus cream 1% for papulopustular rosacea: A randomized vehicle-controlled double-blind trial.
        Br J Dermatol. 2007; 156: 728-732
        • van Zuuren E.J.
        • Fedorowicz Z.
        • Carter B.
        • van der Linden M.M.D.
        • Charland L.
        Interventions for Rosacea.
        Cochrane Database Syst Rev. 2015; 4
        • Alikhan A.
        • Kurek L.
        • Feldman S.R.
        The role of tetracyclines in rosacea.
        Am J Clin Dermatol. 2010; 11: 79-87
        • Bakar O.
        • Demircay Z.
        • Toker E.
        • Cakir S.
        Ocular signs, symptoms and tear function tests of papulopustular rosacea patients receiving azithromycin.
        J Eur Acad Dermatol Venereol. 2009; 23: 544-549
        • Bikowski J.B.
        Sub-antimicrobial dose doxycycline for acne and rosacea.
        Skinmed. 2003; 2: 234-245
        • Sloan B.
        • Scheinfeld N.
        The use and safety of doxycycline hyclate and other second-generation tetracyclines.
        Expert Opin Drug Saf. 2008; 7: 571-577
        • Wilkin J.K.
        Rosacea pathophysiology and treatment.
        J Drug Dermatol. 1994; 130: 359-362
        • Thiboutot D.
        • Gollnick H.
        • Bettoli V.
        • et al.
        New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne group.
        J Am Acad Dermatol. 2009; 60: S1-S50
        • Israel H.A.
        • Ramamurthy N.S.
        • Greenwald R.
        • Golub L.
        The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint.
        Adv Dent Res. 1998; 12: 51-55
        • Del Rosso J.Q.
        • Webster G.F.
        • 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; 56: 791-802
        • Cazalis J.
        • Bodet C.
        • Gagnon G.
        • Grenier D.
        Doxycycline reduces lipopolysaccharide-induced inflammatory mediator secretion in macrophage and ex vivo human whole blood models.
        J Periodontol. 2008; 79: 1762-1768
        • Ueyama Y.
        • Misaki M.
        • Ishihara Y.
        • Matsumura T.
        Effects of antibiotics on human polymorphonuclear leukocyte chemotaxis in vitro.
        Br J Oral Maxillofac Surg. 1994; 32: 96-99
        • Pruzanski W.
        • Stefanski E.
        • Vadas P.
        • McNamara T.F.
        • Ramamurthy N.
        • Golub L.M.
        Chemically modified non-antimicrobial tetracyclines inhibit activity of phospholipases A2.
        J Rheumatol. 1998; 25: 1807-1812
        • Hoyt J.C.
        • Ballering J.
        • Numanami H.
        • Hayden J.M.
        • Robbins R.A.
        Doxycycline modulates nitric oxide production in murine lung epithelial cells.
        J Immunol. 2006; 176: 567-572
        • Akamatsu H.
        • Asada M.
        • Komura J.
        • Asada Y.
        • Niwa Y.
        Effect of doxycycline on the generation of reactive oxygen species: A possible mechanism of action of acne therapy with doxycycline.
        Acta Derm Venereol. 1992; 72: 178-179
        • Dan L.
        • Shi-long Y.
        • Miao-li L.
        • et al.
        Inhibitory effect of oral doxycycline on neovascularization in a rat corneal alkali burn model of angiogenesis.
        Curr Eye Res. 2008; 33: 653-660
        • Kanada K.N.
        • Nakatsuji T.
        • Gallo R.L.
        Doxycycline indirectly inhibits proteolytic activation of tryptic kallikrein-related peptidases and activation of cathelicidin.
        J Invest Dermatol. 2012; 132: 1435-1442
        • Del Rosso J.Q.
        • Schlessinger J.
        • Werschler P.
        Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea.
        J Drugs Dermatol. 2008; 7: 573-576
        • Webster G.F.
        An open label, community based, 12 week assessment of the effectiveness and safety of monotherapy with doxycycline 40 mg (30 mg immediate release and 10 mg delayed release beads).
        Cutis. 2010; 86: 7-15
        • Gollnick H.
        • Blume-Peytavi U.
        • Szabó E.L.
        • et al.
        Systemic isotretinoin in the treatment of rosacea-doxycycline- and placebo-controlled, randomized clinical study.
        J Dtsch Dermatol Ges. 2010; 8: 505-515
        • Nickle S.B.
        • Peterson N.
        • Peterson M.
        Updated physician's guide to the off-label uses of oral isotretinoin.
        J Clin Aesthet Dermatol. 2014; 7: 22-34
        • Daly T.J.
        • Weston W.L.
        Retinoid effects on fibroblast proliferation and collagen synthesis in vitro and on fibrotic cells in vivo.
        J Am Acad Dermatol. 1986; 15: 900-902
        • Madan V.
        • Ferguson J.E.
        • August P.J.
        Carbon dioxide laser treatment of rhinophyma: A review of 124 patients.
        Br J Dermatol. 2009; 161: 814-818
        • Craige H.
        • Cohen J.B.
        Symptomatic treatment of idiopathic and rosacea-associated cutaneous flushing with propranolol.
        J Am Acad Dermatol. 2005; 53: 881-884
        • Hsu C.C.
        • Lee J.Y.
        Pronounced facial flushing and persistent erythema of rosacea effectively treated by carvedilol, a nonselective beta-adrenergic blocker.
        J Am Acad Dermatol. 2012; 67: 491-493
        • Hsu C.C.
        • Lee J.Y.
        Carvedilol for the treatment of refractory facial flushing and persistent erythema of rosacea.
        Arch Dermatol. 2011; 147: 1258-1260
        • Allen K.J.
        • Davis C.L.
        • Billings S.D.
        • Mousdicas N.
        Recalcitrant papulopustular rosacea in an immunocompetent patient responding to combination therapy with oral ivermectin and topical permethrin.
        Cutis. 2007; 80: 149-151
        • Aquilina C.
        • Viraben R.
        • Sire S.
        Ivermectin-responsive Demodex infestation during human immunodeficiency virus infection. A case report and literature review.
        Dermatology. 2002; 205: 394-397
        • Jackson J.M.
        • Kircik L.H.
        • Lorenz D.J.
        Efficacy of extended-release 45 mg oral minocycline and extended-release 45 mg oral minocycline plus 15% azelaic acid in the treatment of acne rosacea.
        J Drugs Dermatol. 2013; 12: 292-298
        • Bamford J.T.
        • Gessert C.E.
        • Haller I.V.
        • Kruger K.
        • Johnson B.P.
        Randomized, double-blind trial of 220 mg zinc sulfate twice daily in the treatment of rosacea.
        Int J Dermatol. 2012; 51: 659-662