Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 18/03/2015
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John Berth-Jones
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Rosacea is a common inflammatory skin disease, generally confined to the face, principally the cheeks, forehead, nose, and chin. In some cases lesions may extend on to the scalp, and occasionally also onto the neck and the upper part of the body. A common early feature is flushing, often accompanied by a burning sensation. Inflammatory lesions (papulation and pustulation) are characteristic and may become florid. Vascular changes (telangiectasia and erythema) are also frequently observed. These are initially mild, but may later become very conspicuous. Other later features are the development of lymphedema, thickening, and induration. On the nose and, less often the ears, forehead or chin, hypertrophy and lymphedema of subcutaneous tissue may develop into distinct swellings known as phymas, of which rhinophyma is most familiar. Ocular involvement is frequent and manifests as a sensation of grittiness, which may be accompanied by conjunctivitis, blepharitis, episcleritis, chalazion, hordeolum, iritis, and occasionally severe keratitis. The etiology and pathogenesis of rosacea remain poorly understood. Hopefully, improvements in our understanding of the etiology will one day facilitate a more rational approach to treatment, which has so far developed rather empirically.
Patients may find it beneficial to avoid alcohol, spicy food, hot drinks, etc. which may induce flushing and promote the development of telangiectasia. Exposure to irritants should be avoided, and emollients can be helpful. Cosmetic camouflage of the erythema and telangiectasia can be helpful. Facial massage may promote lymphatic drainage and reduce the development of lymphedema. Papulation, pustulation, and erythema can be effectively suppressed using a variety of topical and systemic antibiotics, retinoids, and other agents described below. Unfortunately, these modalities are usually not very effective for suppressing flushing and have little effect on established telangiectasia. Telangiectasia and erythema can be effectively treated by physical measures to ablate the vessels, such as intense pulsed light or vascular lasers. Flushing is usually the most difficult feature to treat, but sometimes improves during treatment of telangiectasia. Ocular rosacea is often treated symptomatically with a range of ‘artificial tears’ (the ophthalmic equivalent of emollients). Systemic tetracyclines, used as for cutaneous rosacea, and topical ophthalmic formulations of fusidic acid are also helpful. The use of retinoids for rosacea requires special care in patients with eye involvement and may be poorly tolerated. Treatments are discussed below in sections focused on inflammatory rosacea, erythematotelangiectatic rosacea, flushing, lymphedema, ocular rosacea, and rosacea fulminans. Treatments for rhinophyma and perioral dermatitis are described in separate chapters.
In selected cases
Urinary 5-HIAA to exclude carcinoid syndrome
Serology to exclude lupus
Treatment of rosacea with 1% metronidazole cream.
A double-blind study. Nielson PG. Br J Dermatol 1983; 108: 327–32.
Eighty-one patients were treated with 1% metronidazole cream or vehicle for 2 months. Metronidazole cream was significantly more effective than placebo in suppression of inflammatory lesions and erythema.
The efficacy of metronidazole 1% cream once daily compared with metronidazole cream twice daily and their vehicles in rosacea: a double-blind clinical trial.
Jorizzo JL, Lebwohl M, Tobey RE. J Am Acad Dermatol 1998; 39: 502–4.
This study also demonstrated improvements in numbers of inflammatory lesions and in erythema relative to placebo. However, there was no apparent difference between once-daily and twice-daily application.
Topical metronidazole maintains remissions of rosacea.
Dahl MV, Katz HI, Krueger GG, Millikan LE, Odom RB, Parker F, et al. Arch Dermatol 1998; 134: 679–83.
Eighty-eight subjects who had responded to treatment with systemic tetracycline and topical metronidazole were randomized to receive 0.75% metronidazole gel or placebo gel for 6 months. In those applying the metronidazole, 23% developed a relapse of papulopustular lesions, and 55% a worsening of erythema, compared to 42% and 74% of subjects, respectively, in the placebo gel group.
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.
Sanchez J, Somolinos AL, Almodovar PI, Webster G, Bradshaw M, Powala C. J Am Acad Dermatol 2005; 53: 791–7.
Combinations of topical and systemic treatment are often used and seem likely to be more effective than either used alone. In this study the addition of low-dose (20 mg) doxycycline improved the response to topical metronidazole.
Topical azelaic acid in the treatment of rosacea.
Carmichael AJ, Marks R, Graupe KA, Zaumseil RP. J Dermatol Treat 1993; 4: 19–22.
Topical azelaic acid 20% cream was shown to be more effective than the base alone in a double-blind, controlled, split-face study with 33 patients. Treatment was given for 9 weeks and improvement was seen in papules, pustules, and erythema, but not telangiectasia.
Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea.
Bjerke R, Fyrand O, Graupe K. Acta Derm Venereol 1999; 79: 456–9.
A 3-month randomized, double-blind study compared the efficacy and safety of azelaic acid 20% cream, applied twice daily, with its vehicle in 116 patients. Azelaic acid cream produced significantly greater mean reductions in total inflammatory lesions than did vehicle: 73.4% vs 50.6%, respectively. Erythema also responded.
A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea.
Elewski BE, Fleischer AB, Pariser DM. Arch Dermatol 2003; 139: 1444–50.
A double-blind study on 251 patients with papulopustular rosacea. In these formulations, azelaic acid proved superior to metronidazole for reducing inflammatory lesions and erythema. Metronidazole was somewhat better tolerated.
A clinical trial of tetracycline in rosacea.
Sneddon IB. Br J Dermatol 1966; 78: 649–52.
A double-blind trial with 78 evaluable subjects comparing tetracycline 250 mg twice daily with placebo after 4 weeks of treatment. There was a significantly superior response to active treatment, even though a pronounced placebo effect was observed. During subsequent follow-up it was found that some patients could be completely controlled using only 100 mg daily.
Safety of long-term tetracycline therapy for acne.
Sauer GC. Arch Dermatol 1976; 112: 1603–5.
A study of 325 patients treated with oral tetracycline for 3 years or more showed the drug was generally well tolerated. However, elevated bilirubin and alkaline phosphatase levels were found in approximately 5% of cases (the majority being minimally so, or returning to normal on repeat testing), suggesting that liver function should be monitored in patients on long-term therapy. One patient developed mild jaundice while taking 500 mg of tetracycline daily.
Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea.
Del Rosso JQ, Webster GF, Jackson M, Rendon M, Rich P, Torok H, et al. J Am Acad Dermatol 2007; 56: 791–802.
Doxycycline appears to be effective even at low dose.
A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea.
Nielsen PG. Br J Dermatol 1983; 109: 63–5.
A randomized, double-blind trial in which 51 patients were treated for 2 months with 1% metronidazole cream and placebo tablets, or with oxytetracycline 250 mg twice daily and placebo cream. Improvement occurred in 90% of the patients. There was no significant difference between the treatments.
Steroid rosacea in prepubertal children.
Weston WL, Morelli JG. Arch Pediatr Adolesc Med 2000; 154: 62–4.
A retrospective evaluation of 106 children younger than 13 years with steroid rosacea. Abrupt cessation of topical corticosteroid use and initiation of treatment with oral erythromycin stearate for 4 weeks produced complete clearing in 86% of children within 4 weeks and in 100% by 8 weeks.
The efficacy of oral tetracyclines seems to be well established, although most of the trials on the use of these antibiotics have been against active comparators rather than placebo. Both tetracycline and oxytetracycline are generally used at the dose of 250–500 mg twice daily in rosacea. Other systemic tetracyclines, such as minocycline 100 mg daily, doxycycline 40 mg or 100 mg daily, and lymecycline 408 mg daily, are also often prescribed. These offer the advantage of once-daily administration and their absorption is less influenced by dietary calcium, so they can be taken with food. Erythromycin 250–500 mg twice daily is also often prescribed and widely held to be effective, and can be useful when rosacea occurs in children, for whom tetracyclines are contraindicated.
Beneficial use of Cetaphil moisturizing cream as part of a daily skin care regimen for individuals with rosacea.
Laquieze S, Czernielewski J, Baltas E. J Dermatol Treat 2007; 18: 158–62.
Twice-daily application of a moisturizer appeared beneficial in this open study on 20 patients.
Topically applied erythromycin in rosacea.
Mills OH, Kligman AM. Arch Dermatol 1976; 112: 553–4.
A 2% solution applied twice daily to 15 patients produced a 50–100% improvement in 87% of cases, and treatment was effective by 4 weeks. Once-daily application was sufficient once the disease was controlled.
Treatment of rosacea: topical clindamycin versus oral tetracycline.
Wilkin JK, DeWitt S. Int J Dermatol 1993; 32: 65–7.
A randomized, blinded trial comparing topical clindamycin lotion twice daily with oral tetracycline in 43 patients evaluated over 12 weeks. Similar improvements were found in both groups, although clindamycin was superior in eradication of pustules.
Double-blind, randomized, vehicle-controlled clinical trial of once-daily benzoyl peroxide/clindamycin topical gel in the treatment of patients with moderate to severe rosacea.
Breneman D, Savin R, VandePol C, Vamvakias G, Levy S, Leyden J. Int J Dermatol 2004; 43: 381–7.
This combination of 5% benzoyl peroxide and 1% clindamycin was effective and well tolerated.
Treatment of rosacea by metronidazole.
Pye RJ, Burton JL. Lancet 1976; 1: 1211–2.
A double-blind, placebo-controlled, parallel-group trial demonstrating the efficacy of oral metronidazole 200 mg twice daily after 6 weeks of treatment. Ten out of 14 patients treated with metronidazole showed a good response.
A double-blinded trial of metronidazole versus oxytetracycline therapy for rosacea.
Saihan EM, Burton JL. Br J Dermatol 1980; 102: 443–5.
Forty patients were treated for 12 weeks with oxytetracycline 250 mg twice daily or metronidazole 200 mg twice daily. On both drugs the degree of improvement was greater after 12 weeks than after 6 weeks. There was no significant difference between them.
Although metronidazole is generally well tolerated and it has been used long term, there is a risk of peripheral neuropathy if it is used for longer than 3 months.
Topical treatment of acne rosacea with benzoyl peroxide acetone gel.
Montes LF, Cordero AA, Kriner J. Cutis 1983; 32: 185–90.
Benzoyl peroxide gel (5% increasing to 10%) was significantly superior to vehicle, although it was poorly tolerated and there was a high drop-out rate.
Comparative effectiveness of tetracycline and ampicillin in rosacea. A controlled trial.
Marks R, Ellis J. Lancet 1971; 2: 1049–52.
A double-blind, placebo-controlled trial lasting 6 weeks and completed by 56 patients. Both antibiotics were significantly more effective than placebo. Tetracycline was apparently (but not significantly) more effective than ampicillin.
A novel treatment for acne vulgaris and rosacea.
Elewski BE. J Eur Acad Dermatol Venereol 2000; 14: 423–4.
Ten patients were treated in an open study of azithromycin, 500 mg on day 1, followed by 250 mg/day for 4 consecutive days beginning on the first and 15th days of each month for 3 months. All patients improved, and nine were clear by 3 months.
Therapeutic potential of azithromycin in rosacea.
Bakar O, Demircay Z, Gurbuz O. Int J Dermatol 2004; 43: 151–4.
In a 12-week open study on 18 patients, azithromycin was used at a dose of 500 mg/day for 3 consecutive days each week for the first 4 weeks, 250 mg/day on 3 days for the next 4 weeks, and 500 mg once weekly for the last 4 weeks. Both inflammatory lesions and erythema improved markedly in the 14 evaluable subjects.
Oral use of azithromycin for the treatment of acne rosacea.
Fernandez-Obregon A. Arch Dermatol 2004; 140: 489–90.
Ten patients responded well to azithromycin 250 mg/day for 3 days each week (Monday, Wednesday, and Friday), within 4 weeks. Ocular symptoms also improved.
Azithromycin has a relatively long half-life and is therefore suited to this sort of regimen.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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