Continuing Medical EducationRosacea: II. Therapy☆
Section snippets
Sunscreen
Practicing sun avoidance behaviors is of central importance to rosacea management. In addition, a broad-spectrum sunscreen should be applied daily. The physical blockers titanium dioxide and zinc oxide are well tolerated by most patients. General guidelines for the use of sunscreens by persons with rosacea are provided in Table I. Several rosacea creams contain sunscreen ingredients. A combination sunscreen and 1% metronidazole is now marketed in Canada as Rosasol cream (Stiefel Canada, Inc,
Cosmetics
Cosmetic intolerance and facial skin “sensitivity” are common features of the erythematotelangiectatic and papulopustular subtypes of rosacea. In a series of 32 rosacea patients, 75% experienced stinging after application of 5% lactic acid, compared with 19% of 32 control patients.4 All 7 erythematotelangiectatic patients experienced stinging, as did 17 of 25 papulopustular patients. It is common for many cosmetic formulations to dry and irritate rosacea-prone skin, possibly because of barrier
Topical medications
Three topical medications have been approved by the Food and Drug Administration (FDA) for rosacea. All are indicated for the management of papules, pustules, and erythema. They include 3 varieties of 0.75% metronidazole (Metrocream, Metrogel, and Metrolotion, Galderma Laboratories, Fort Worth, Tex) and 1% metronidazole (Noritate cream, Dermik Laboratories, Berwyn, Pa), several brands of 10% sodium sulfacetamide with 5% sulfur (Sulfacet-R tinted and tint-free lotions, Dermik Laboratories,
Metronidazole
Pye and Burton first reported success with oral metronidazole for rosacea in 1976.9 Nielsen was the first to demonstrate the effectiveness of a topical metronidazole formulation for rosacea during the early 1980s.10., 11., 12. Over the years, debate has surrounded its most effective strength and dosing regimen. The 0.75% formulation was marketed first in the United States, and optimal dosing was determined to be twice daily, based on a half-life of 6 hours for the gel formulation.13 Dahl et al
Sodium sulfacetamide and sulfur
Sodium sulfacetamide 10% and sulfur 5% in combination have undergone a resurgence recently in the treatment of both acne and rosacea. The combination is in pregnancy category C. For more than 50 years, it has provided a safe, well-tolerated, and effective option for the treatment of acne vulgaris, rosacea, perioral dermatitis, and seborrheic dermatitis.24., 25. The use of sodium sulfacetamide and sulfur combinations is contraindicated in patients with sulfonamide hypersensitivity and in
Azelaic acid
The FDA approved azelaic acid 15% gel (Finacea) in December 2002 for the treatment of mild to moderate rosacea. Azelaic acid is a naturally occurring saturated dicarboxylic acid.29 Like metronidazole, azelaic acid is thought to inhibit or reduce the production of reactive oxygen species by neutrophils.30 It is in pregnancy category B.
Two phase III vehicle-controlled, randomized trials have demonstrated the effectiveness and safety of 15% azelaic acid gel in 664 patients with papulopustular
Benzoyl peroxide
Benzoyl peroxide can trigger stinging and erythema in some rosacea patients with barrier dysfunction and “sensitive” skin. In contrast, rapid resolution of erythematous papules and pustules can be achieved in nonsensitive patients (personal observation, M.T.P., W.D.J.), and a recent trial of benzoyl peroxide–clindamycin combination therapy has shown promise in patients with moderate rosacea (data in press, personal communication with James P. Leyden, MD). With few exceptions, patients with
Erythromycin and clindamycin
Mills and Kligman originally described the use of topical erythromycin base for the treatment of rosacea in 1976, when they were prompted by their successful results in acne vulgaris.33 After 4 weeks of twice-daily topical erythromycin (in a vehicle of equal parts water and ethanol), reduction of erythema and suppression of papules and pustules were noted in 13 of 15 patients.33 Side effects included transient stinging and dryness.
Clindamycin lotion is less popular for rosacea but has been
Tacrolimus
Topical tacrolimus has been reported to be an effective treatment for steroid-induced rosacea-like eruptions.35., 36. Tacrolimus 0.1% ointment (Protopic, Fujisawa Healthcare, Inc, Deerfield, IL) is a macrolide nonsteroidal immunomodulatory agent approved in the United States for the treatment of atopic dermatitis. Goldman treated 3 patients with steroid-induced rosacea-like eruption using a 0.075% tacrolimus preparation twice daily for 7 to 10 days.35 None of his patients was given oral
Tretinoin
Dermal inflammation, elastin and collagen degeneration, and alteration of the cutaneous vasculature are the prominent histologic features of rosacea.37., 38., 39. Topical tretinoin promotes connective tissue remodeling in the papillary and reticular dermis and minimizes dermal inflammation with chronic therapy.40., 41., 42. Therefore, it is not surprising that topical retinoids have demonstrated benefit for rosacea, although their clinical response is delayed, often not evident until 2 or more
Tetracyclines
Tetracycline has been a mainstay of rosacea therapeutics for more than 40 years, although it has not been approved by the FDA for treatment of this condition. Sneddon performed a double-blind, placebo-controlled trial of tetracycline for rosacea in 1966 to evaluate its effects on the “erythematous and papular type” and the “pustular form” of rosacea.54 He treated 78 patients with either tetracycline, 250 mg twice daily, or placebo for 4 weeks, followed by a 4-week period during which all
Miscellaneous oral therapies
In 1971 Spirov, Berova, and Vassilev described the benefits of oral contraceptive monotherapy in 30 women with rosacea.78 Before therapy they documented “historical and clinical abnormalities of hormonal origin” in 21 of their 30 patients. Complete resolution of papular lesions and improvement of erythema occurred in 18 patients (60%), with maximal effects requiring 4 months of therapy.78 Mauss treated 3 women with a combination of oral contraceptive plus 10 mg of cyproterone acetate daily
Laser and light therapies for rosacea
Vascular laser therapy for rosacea began in the early 1980s with the argon laser (488-514 nm), initially touted for the treatment of port wine stains and the postrhinoplasty “red nose.”86., 87., 88., 89. Over the past 20 years, laser and light therapy for rosacea has evolved to include an ever-increasing number of devices and therapeutic targets. In addition to telangiectasia, the focus for rosacea laser and light therapies now encompasses a broader approach, including the reorganization and
Rosacea management: a subtype-directed approach
On the basis of their clinical and histologic variations, it is no surprise that erythematotelangiectatic, papulopustular, phymatous, and glandular rosacea respond to different therapies. From a practical standpoint, subtyping can guide choice and structuring of therapy. Certain modalities will be useful in all patients, stemming from overlap among the subtypes; however, the timing of their use may vary. For example, to the extent that all rosacea patients suffer from some degree of central
Future studies
Few questions regarding rosacea pathogenesis have been sufficiently answered, and many more remain uninvestigated. The identification of genetic factors and gene loci that predispose affected persons to a rosacea phenotype is now under way. It is clear that certain populations are more commonly affected by rosacea, and as many as 40% of patients with rosacea have a relative affected with rosacea.42
One area that requires investigation is the histologic and pathologic basis of papules and
References (120)
- et al.
Treatment of rosacea by metronidazole
Lancet
(1976) The relapse rate for rosacea after treatment with either oral tetracycline or metronidazole cream
Br J Dermatol
(1983)- et al.
Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea
J Am Acad Dermatol
(2001) - et al.
The efficacy of metronidazole 1% cream once daily compared with metronidazole 1% cream twice daily and their vehicles in rosacea: a double-blind clinical trial
J Am Acad Dermatol
(1998) A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea
J Am Acad Dermatol
(1999)Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report
J Am Acad Dermatol
(2001)Treatment of photodamage with topical tretinoin: an overview
J Am Acad Dermatol
(1997)Effects of topical tretinoin on non-sunexposed protected skin of the elderly
J Am Acad Dermatol
(1993)- et al.
Topical retinaldehyde on human skin: biologic effects and tolerance
J Invest Dermatol
(1994) - et al.
Regulation of vascular endothelial growth factor expression in human keratinocytes by retinoids
J Biol Chem
(2000)
Action of isotretinoin in acne rosacea and gram-negative folliculitis
J Am Acad Dermatol
Effect of nadolol on flushing reactions in rosacea
J Am Acad Dermatol
Treatment of the red nose with the argon laser
Mayo Clin Proc
The nature and evolution of port wine stains: a computer-assisted study
J Invest Dermatol
A new formulation containing sunscreen (SPF 15) and 1% metronidazole (Rosasol cream) in the treatment of rosacea
Skin Therapy Lett
Silicones in topical dermatologic preparations
Cosmetic Dermatol
Effective sunscreen ingredients and cutaneous irritation in patients with rosacea
Cutis
Stinging and rosacea
Acta Derm Venereol
Recognition of chemically vulnerable and delicate skin
pH measurements during lactic acid stinging test in normal and sensitive skin
Contact Dermatitis
Cosmetics in acne and rosacea
Semin Cutan Med Surg
Use of topical products for maintaining remission in rosacea
Arch Dermatol
A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea
Br J Dermatol
Treatment of rosacea with 1% metronidazole cream. A double-blind study
Br J Dermatol
Topical metronidazole therapy for rosacea
Arch Dermatol
Evaluation of topical metronidazole gel in acne rosacea
Drug Intell Clin Pharm
Metronidazole 1% cream versus placebo cream in the treatment of rosacea
Clin Trials J
A double-blind randomized study of metronidazole 1% cream in the treatment of acne rosacea: a placebo controlled study
Drug Invest
[Double-blind study versus excipient of 0.75% metronidazole gel in the treatment of rosacea] (French)
Ann Dermatol Venereol
A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea
Cutis
Topical metronidazole for severe and recalcitrant rosacea: a prospective open trial
Cutis
A status report on the medical management of rosacea: focus on topical therapies
Cutis
Topical metronidazole maintains remissions of rosacea
Arch Dermatol
Old drug—in a new system—revisited
Cutis
Topical treatment with sulfur 10 per cent for rosacea
Acta Derm Venereol
The treatment of rosacea: the safety and efficacy of sodium sulfacetamide 10% and sulfur 5% lotion (Novacet) is demonstrated in a double-blind study
J Dermatol Treat
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
Manual of dermatologic therapeutics
Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders
Drugs
Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases
Arch Dermatol Res
Topical azelaic acid in the treatment of rosacea
J Dermatol Treat
Letter: Topically applied erythromycin in rosacea
Arch Dermatol
Treatment of rosacea: topical clindamycin versus oral tetracycline
Int J Dermatol
Tacrolimus clinical studies for atopic dermatitis and other conditions
Semin Cutan Med Surg
Concepts in the pathogenesis of rosacea
Br J Dermatol
[Rosacea: histopathologic study of 75 cases] (French)
Ann Dermatol Venereol
Histopathology of rosacea
Arch Dermatol
Reversible histologic effects of tretinoin on photodamaged skin
J Geriatr Dermatol
Inhibitory effects of retinoids on vascular endothelial growth factor production by cultured human skin keratinocytes
Dermatology
Topical tretinoin for rosacea
J Dermatol Treat
Cited by (209)
Ointment containing spray freeze-dried metronidazole effective against rosacea
2022, Journal of Drug Delivery Science and TechnologyCitation Excerpt :The skin care compositions and their ingredients depend on the type of rosacea such as phymatous-, ocular-, erythematous- and papulopustular rosacea, furthermore, it is recommended to avoid sunlight and apply special combination sun creams. Medical preparations for papulopustular rosacea contain azelaic acid, ivermectin, doxycycline, isotretinoin or metronidazole as well as Ti-dioxide and Zn-oxide [1,2]. However, out of these drugs metronidazole is the most commonly used and administered as monotherapy or in combination for local treatment of papulopustular rosacea [3].
Prodrugs of sulfacetamide: Synthesis, X-ray structure, Hirshfeld analysis, antibacterial assessment, and docking studies
2022, Journal of Molecular StructureConsensus on the therapeutic management of rosacea – Brazilian Society of Dermatology
2020, Anais Brasileiros de DermatologiaSystemic Antibacterial Agents
2020, Comprehensive Dermatologic Drug Therapy, Fourth EditionLong-term maintenance treatment of rosacea: experts' opinion
2024, International Journal of DermatologyCutaneous neurogenic inflammation mediated by TRPV1–NGF–TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites
2023, Journal of the European Academy of Dermatology and Venereology
- ☆
Funding sources: None.
Conflict of interest: None identified.
Reprints not available from the authors.