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TOPICAL METRONIDAZOLE AND AZELAIC ACID are equally effective for the papulopustular lesions of acne rosacea, although metronidazole is better tolerated. Oral doxycycline, tetracycline, and metronidazole are also effective, but not enough evidence exists to determine whether one is more effective than another or more effective than topical therapy (strength of recommendation [SOR]: A, systematic review and individual randomized controlled trials [RCTs]).
Some evidence supports a benefit for topical sodium sulfacetamide with sulfur, and benzoyl peroxide (SOR: B, small single RCTs).
Pulsed-light and laser therapy may improve the erythema and telangiectasias associated with acne rosacea (SOR: C, case series).
All patients with acne rosacea should use sunscreen and emollients, and avoid skin irritants (SOR: C, expert opinion).
Evidence summary
A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).1
Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).2
TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials1,2
| Primary intervention | Number of trials | Number of patients | Physician assessment of improvement vs placebo |
|---|---|---|---|
| Topical metronidazole | 9 | 488 | OR=7.01 (95% CI, 2.5-20) |
| Topical azelaic acid | 4 | 778 | OR=2.23 (95% CI, 1.66-3.00) |
| Topical benzoyl peroxide | 1 | 58 | OR=3.17 (95% CI, 1.08-9.31) |
| Topical sodium sulfacetamide with sulfur | 1 | 94 | 90%-98% vs 58%-68% improved (P<.01) |
| Oral doxycycline | 2 | 577 | 9.5 and 11.8 fewer lesions with doxycycline vs 4.3 and 5.9 fewer lesions with placebo (P<.001 for both RCTs) |
| Oral tetracycline | 3 | 152 | OR=6.06 (95% CI, 2.96-12.4) |
| Oral metronidazole | 1 | 27 | OR=13.75 (95% CI, 2.05-92.04) |
| CI, confidence interval; OR, odds ratio; RCTs, randomized controlled trials. | |||
Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.1 A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.3,4
Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)1
Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.3,5
Other comparisons that found no significant difference in effectiveness included:
- 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid1,2
- 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid6
- 1 RCT (N=43) that compared topical metronidazole with topical permethrin1
- 1 RCT (N=40) that compared oral metronidazole with oral tetracycline1
- 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily4
- 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.7
Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).1 Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).4
Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).2 Another case series with 17 patients reported improvements with photodynamic therapy with red ight.8
General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.9 Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.1,2
Recommendations
The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.
The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.10
1. van Zuuren EJ, Graber MA, Hollis S, et al. Interventions for rosacea. Cochrane Database Syst Rev. 2005;(3):CD003262.-
2. Pelle MT, Crawford GH, James WD. Rosacea: II. Therapy. J Am Acad Dermatol. 2004;51:499-512.
3. Conde JF, Yelverton CB, Balkrishnan R, et al. Managing rosacea: a review of the use of metronidazole alone and in combination with oral antibiotics. J Drugs Dermatol. 2007;6:495-498.
4. Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatol. 2008;7:573-574.
5. Fowler JF, Jr. 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;6:641-645.
6. Thiboutot DM, Fleischer AB, Jr, Del Rosso JQ, et al. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol. 2008;7:541-546.
7. Akhyani M, Ehsani AH, Ghiasi M, et al. Comparison of efficacy of azithromycin versus doxycycline in the treatment of rosacea: a randomized open clinical trial. Int J Dermatol. 2008;47:284-288.
8. Bryld LE, Jemec GB. Photodynamic therapy in a series of rosacea patients. J Eur Acad Dermatol Venereol. 2007;21:1199-1202.
9. Laquieze S, Czernielewski J, Baltas E. Beneficial use of Cetaphil moisturizing cream as part of a daily skin care regimen for individuals with rosacea. J Dermatolog Treat. 2007;18:158-162.
10. Del Rosso JQ, Baldwin H, Webster G. American Acne and Rosacea Society. American Acne and Rosacea Society rosacea medical management guidelines. J Drugs Dermatol. 2008;7:531-533.
TOPICAL METRONIDAZOLE AND AZELAIC ACID are equally effective for the papulopustular lesions of acne rosacea, although metronidazole is better tolerated. Oral doxycycline, tetracycline, and metronidazole are also effective, but not enough evidence exists to determine whether one is more effective than another or more effective than topical therapy (strength of recommendation [SOR]: A, systematic review and individual randomized controlled trials [RCTs]).
Some evidence supports a benefit for topical sodium sulfacetamide with sulfur, and benzoyl peroxide (SOR: B, small single RCTs).
Pulsed-light and laser therapy may improve the erythema and telangiectasias associated with acne rosacea (SOR: C, case series).
All patients with acne rosacea should use sunscreen and emollients, and avoid skin irritants (SOR: C, expert opinion).
Evidence summary
A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).1
Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).2
TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials1,2
| Primary intervention | Number of trials | Number of patients | Physician assessment of improvement vs placebo |
|---|---|---|---|
| Topical metronidazole | 9 | 488 | OR=7.01 (95% CI, 2.5-20) |
| Topical azelaic acid | 4 | 778 | OR=2.23 (95% CI, 1.66-3.00) |
| Topical benzoyl peroxide | 1 | 58 | OR=3.17 (95% CI, 1.08-9.31) |
| Topical sodium sulfacetamide with sulfur | 1 | 94 | 90%-98% vs 58%-68% improved (P<.01) |
| Oral doxycycline | 2 | 577 | 9.5 and 11.8 fewer lesions with doxycycline vs 4.3 and 5.9 fewer lesions with placebo (P<.001 for both RCTs) |
| Oral tetracycline | 3 | 152 | OR=6.06 (95% CI, 2.96-12.4) |
| Oral metronidazole | 1 | 27 | OR=13.75 (95% CI, 2.05-92.04) |
| CI, confidence interval; OR, odds ratio; RCTs, randomized controlled trials. | |||
Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.1 A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.3,4
Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)1
Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.3,5
Other comparisons that found no significant difference in effectiveness included:
- 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid1,2
- 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid6
- 1 RCT (N=43) that compared topical metronidazole with topical permethrin1
- 1 RCT (N=40) that compared oral metronidazole with oral tetracycline1
- 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily4
- 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.7
Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).1 Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).4
Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).2 Another case series with 17 patients reported improvements with photodynamic therapy with red ight.8
General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.9 Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.1,2
Recommendations
The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.
The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.10
TOPICAL METRONIDAZOLE AND AZELAIC ACID are equally effective for the papulopustular lesions of acne rosacea, although metronidazole is better tolerated. Oral doxycycline, tetracycline, and metronidazole are also effective, but not enough evidence exists to determine whether one is more effective than another or more effective than topical therapy (strength of recommendation [SOR]: A, systematic review and individual randomized controlled trials [RCTs]).
Some evidence supports a benefit for topical sodium sulfacetamide with sulfur, and benzoyl peroxide (SOR: B, small single RCTs).
Pulsed-light and laser therapy may improve the erythema and telangiectasias associated with acne rosacea (SOR: C, case series).
All patients with acne rosacea should use sunscreen and emollients, and avoid skin irritants (SOR: C, expert opinion).
Evidence summary
A Cochrane systematic review found that topical metronidazole and azelaic acid are both more effective than placebo for patients with papulopustular lesions of acne rosacea (TABLE). The authors noted that the studies were generally weak because of poor methodology and reporting, small sample sizes, and lack of quality-of-life measures (only 2 RCTs evaluated patient assessment of treatment effectiveness).1
Another systematic review reported small case series suggesting possible effectiveness with topical tretinoin (43 cases), oral clindamycin (43 cases), oral erythromycin (13 cases), and topical tacrolimus (3 cases).2
TABLE
Papulopustular acne rosacea: Doctors assess treatment efficacy in placebo-controlled trials1,2
| Primary intervention | Number of trials | Number of patients | Physician assessment of improvement vs placebo |
|---|---|---|---|
| Topical metronidazole | 9 | 488 | OR=7.01 (95% CI, 2.5-20) |
| Topical azelaic acid | 4 | 778 | OR=2.23 (95% CI, 1.66-3.00) |
| Topical benzoyl peroxide | 1 | 58 | OR=3.17 (95% CI, 1.08-9.31) |
| Topical sodium sulfacetamide with sulfur | 1 | 94 | 90%-98% vs 58%-68% improved (P<.01) |
| Oral doxycycline | 2 | 577 | 9.5 and 11.8 fewer lesions with doxycycline vs 4.3 and 5.9 fewer lesions with placebo (P<.001 for both RCTs) |
| Oral tetracycline | 3 | 152 | OR=6.06 (95% CI, 2.96-12.4) |
| Oral metronidazole | 1 | 27 | OR=13.75 (95% CI, 2.05-92.04) |
| CI, confidence interval; OR, odds ratio; RCTs, randomized controlled trials. | |||
Oral metronidazole and tetracycline also work
The Cochrane systematic review also found that oral metronidazole and tetracycline were more effective than placebo for papulopustular lesions.1 A subsequent systematic review found that anti-inflammatory doses of oral doxycycline (20-40 mg daily) were effective.3,4
Evidence for other oral drugs is limited or inconclusive
Limited supporting evidence exists for oral macrolides, isotretinoin, and spironolactone.1,2 Three small placebo-controlled RCTs found insignificant or inconclusive benefits for ampicillin, oral clarithromycin plus omeprazole, and oral rilmenidine (a centrally acting, sympatholytic antihypertensive.)1
Many studies, little difference in drug effects
A large number of studies have compared the effectiveness of one treatment against another, but only one comparison demonstrated a statistically significant benefit. Two RCTs enrolling 104 patients found that oral doxycycline (40 mg daily) in combination with topical metronidazole reduced the number of lesions more than topical metronidazole alone (4 and 7 fewer lesions; P<.01 for both studies). It is unclear whether the reduction is clinically significant.3,5
Other comparisons that found no significant difference in effectiveness included:
- 3 RCTs (N=491) that compared topical metronidazole with topical azelaic acid1,2
- 1 RCT (N=72) that compared once-daily with twice-daily topical azelaic acid6
- 1 RCT (N=43) that compared topical metronidazole with topical permethrin1
- 1 RCT (N=40) that compared oral metronidazole with oral tetracycline1
- 1 RCT (N=91) that compared oral doxycycline 100 mg daily with 40 mg daily4
- 1 open trial (N=67) that compared oral doxycycline with oral azithromycin.7
Not all therapies were equally well-tolerated, however. Topical metronidazole produced fewer adverse events than topical azelaic acid (odds ratio=4.56; 95% confidence interval, 2.07-10.03).1 Doxycycline dosed at 40 mg daily produced fewer gastrointestinal adverse effects than 100 mg daily (5% vs 26%; P value not given).4
Therapy for erythema and telangiectasia
A systematic review described multiple small case series that reported improvements in erythema and telangiectasias with pulsed-light therapy (188 cases) and laser therapy (82 cases).2 Another case series with 17 patients reported improvements with photodynamic therapy with red ight.8
General skin care measures
A case series reported improved symptom scores among 20 patients using twice-daily metronidazole gel when they added moisturizing lotion to one side of their face.9 Expert opinion recommends using sunscreen and protective emollients and avoiding triggers that cause flushing, such as certain foods, beverages, and cosmetics.1,2
Recommendations
The American Acne and Rosacea Society guidelines state that good evidence supports 3 topical treatments—metronidazole, azelaic acid, and sulfacetamide/sulfur—as well as anti-inflammatory doses of oral doxycycline.
The guidelines also list other topical and oral antibiotic treatments, but cite low-quality evidence for their efficacy and concerns about the emergence of antibiotic resistance. They advise appropriate skin care, including gentle cleansers, moisturizers, and sun protection.10
1. van Zuuren EJ, Graber MA, Hollis S, et al. Interventions for rosacea. Cochrane Database Syst Rev. 2005;(3):CD003262.-
2. Pelle MT, Crawford GH, James WD. Rosacea: II. Therapy. J Am Acad Dermatol. 2004;51:499-512.
3. Conde JF, Yelverton CB, Balkrishnan R, et al. Managing rosacea: a review of the use of metronidazole alone and in combination with oral antibiotics. J Drugs Dermatol. 2007;6:495-498.
4. Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatol. 2008;7:573-574.
5. Fowler JF, Jr. 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;6:641-645.
6. Thiboutot DM, Fleischer AB, Jr, Del Rosso JQ, et al. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol. 2008;7:541-546.
7. Akhyani M, Ehsani AH, Ghiasi M, et al. Comparison of efficacy of azithromycin versus doxycycline in the treatment of rosacea: a randomized open clinical trial. Int J Dermatol. 2008;47:284-288.
8. Bryld LE, Jemec GB. Photodynamic therapy in a series of rosacea patients. J Eur Acad Dermatol Venereol. 2007;21:1199-1202.
9. Laquieze S, Czernielewski J, Baltas E. Beneficial use of Cetaphil moisturizing cream as part of a daily skin care regimen for individuals with rosacea. J Dermatolog Treat. 2007;18:158-162.
10. Del Rosso JQ, Baldwin H, Webster G. American Acne and Rosacea Society. American Acne and Rosacea Society rosacea medical management guidelines. J Drugs Dermatol. 2008;7:531-533.
1. van Zuuren EJ, Graber MA, Hollis S, et al. Interventions for rosacea. Cochrane Database Syst Rev. 2005;(3):CD003262.-
2. Pelle MT, Crawford GH, James WD. Rosacea: II. Therapy. J Am Acad Dermatol. 2004;51:499-512.
3. Conde JF, Yelverton CB, Balkrishnan R, et al. Managing rosacea: a review of the use of metronidazole alone and in combination with oral antibiotics. J Drugs Dermatol. 2007;6:495-498.
4. Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatol. 2008;7:573-574.
5. Fowler JF, Jr. 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;6:641-645.
6. Thiboutot DM, Fleischer AB, Jr, Del Rosso JQ, et al. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol. 2008;7:541-546.
7. Akhyani M, Ehsani AH, Ghiasi M, et al. Comparison of efficacy of azithromycin versus doxycycline in the treatment of rosacea: a randomized open clinical trial. Int J Dermatol. 2008;47:284-288.
8. Bryld LE, Jemec GB. Photodynamic therapy in a series of rosacea patients. J Eur Acad Dermatol Venereol. 2007;21:1199-1202.
9. Laquieze S, Czernielewski J, Baltas E. Beneficial use of Cetaphil moisturizing cream as part of a daily skin care regimen for individuals with rosacea. J Dermatolog Treat. 2007;18:158-162.
10. Del Rosso JQ, Baldwin H, Webster G. American Acne and Rosacea Society. American Acne and Rosacea Society rosacea medical management guidelines. J Drugs Dermatol. 2008;7:531-533.
Evidence-based answers from the Family Physicians Inquiries Network