Continuing Medical Education
Rosacea: II. Therapy

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Abstract

Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtypes of rosacea include erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. These phenotypic expressions are probably caused by divergent pathogenic factors and consequently respond to different therapeutic regimens. A subtype-directed approach to therapy is discussed in part II of this review. We provide an overview of the available topical, oral, laser, and light therapies in the context of these cutaneous subtypes, review the evidence that supports their use, and outline their therapeutic approach. Suggestions for future areas of study also are provided.

Learning objective

At the completion of this learning activity, participants should be familiar with the subtype-directed approach to therapy for rosacea including available topical, oral, laser, and light therapies.

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

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