Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea. Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies. Randomized placebo-controlled trial of a flavonoid-rich plant extract-based cream in the treatment of rosacea. Comparative effectiveness of tetracycline and ampicillin in rosacea. A controlled trial. Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. Combination sodium sulfacetamide 10% and sulfur 5% cream with sunscreens versus metronidazole 0.75% cream for rosacea. Comparative efficacy of nonpurpuragenic pulsed dye laser and intense pulsed light for erythematotelangiectatic rosacea. A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open-label clinical trial. Permethrin 5% cream versus metronidazole 0.75% gel for the treatment of papulopustular rosacea. A randomized double-blind placebo-controlled study. Treatment of rosacea by metronidazole. Efficacy of 1% 4-ethoxybenzaldehyde in reducing facial erythema. Topical metronidazole therapy for rosacea. Treatment of rosacea with i% metronidazole cream. A double-blind study. A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Double-blind comparison of azelaic acid 20% cream and its vehicle in treatment of papulo-pustular rosacea. Topical metronidazole in the treatment of rosacea. Treatment of rosacea: topical clindamycin versus oral tetracycline. 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. Pimecrolimus cream 1% for papulopustular rosacea: a randomized vehicle-controlled double-blind trial. Effect of treatment of Helicobacter pylori infection on rosacea. 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. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. 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. The efficacy of topical metronidazole in the treatment of ocular rosacea. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Topical metronidazole maintains remissions of rosacea. Oral zinc sulfate in the treatment of rosacea: a double-blind, placebo-controlled study. Topical treatment of acne rosacea with benzoyl peroxide acetone gel. A double-blind study of I% metronidazole cream versus systemic oxytetracycline therapy for rosacea. Treatment of facial telangiectasia using a dual-wavelength laser system (595 and 1,064 nm): a randomized controlled trial with blinded response evaluation. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. 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. 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. Efficacy of topical cyclosporine for the treatment of ocular rosacea. Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea. A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea. [Rilmenidine in rosacea: a double-blind study versus placebo]. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Effect of nadolol on flushing reactions in rosacea. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial. An evaluation of a polyhydroxy acid skin care regimen in combination with azelaic acid 15% gel in rosacea patients. Comparative study of some treatment modalities of rosacea.
The papules and pustules of rosacea can be effectively treated with topical metronidazole. The optimal concentrations of metronidazole and optimum frequencies of application are uncertain. Traditionally, twice-daily applications have been advised, based on the pharmacokinetic profile of metronidazole. Once-daily applications may be safer and less expensive, and they may enhance patient compliance.
                We compared the efficacy and safety of 2 commercially available topical metronidazole formulations (0.75% metronidazole cream formulation and 1.0% metronidazole cream formulation) when both were used in a once-daily regimen.
                A multicenter, randomized, investigator-blind, parallel group trial was conducted at 3 separate clinical sites located in 3 US cities. The study enrolled 72 rosacea patients with at least 8 to 50 inflammatory facial lesions (pustules and papules) and moderately severe facial erythema. Patients were randomly assigned to receive either 0.75% metronidazole cream or 1.0% metronidazole cream and instructed to apply the medication once daily for 12 weeks. Patients' lesions were evaluated at baseline and at weeks 3, 6, 9, and 12.
                There were no significant differences between treatment groups for any of the efficacy parameters evaluated. The overall median percentage change in lesion count at end point for patients in the 0.75% metronidazole cream treatment group was -62% compared with -60% for the 1.0% metronidazole cream treatment group. The overall percentage change in erythema scores at endpoint for patients in the 0.75% metronidazole cream treatment group was -26% compared with -30% for patients in the 1.0% metronidazole cream treatment group. Regarding physician assessment of global severity, 57% of subjects (20/35) in the 0.75% metronidazole cream group compared with 37% of subjects (13/35) in the 1.0% metronidazole cream group were rated as having a clear to mild condition at end point. Both drugs were well tolerated; there was no significant difference in the number of drug-related adverse events between the two agents.
                This controlled trial demonstrates that both 0.75% metronidazole cream and 1.0% metronidazole cream, when used once daily, provide well-tolerated efficacy for moderate to severe rosacea. Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed.
                The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea.
                Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points. Overall, 329 patients were enrolled in study 1 and 335 patients in study 2.
                Both studies consistently demonstrated the superiority of AzA gel over vehicle in the topical treatment of moderate, papulopustular rosacea. AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1 (P =.0001); 51% versus 39%, study 2 (P =.0208). Significantly higher proportions of patients treated with AzA gel experienced improvement in erythema compared with vehicle gel: 44% versus 29%, study 1 (P =.0017); 46% versus 28%, study 2 (P =.0005). Using the investigator's global assessment, therapeutic success in terms of a clear, minimal, or mild final result was achieved in 61% and 62% of patients treated with AzA gel in studies 1 and 2, respectively, which was significantly superior to the result achieved with vehicle (40% and 48%, respectively) (P <.0001, study 1; P =.0127, study 2). No serious, treatment-related adverse events were reported.
                The results of these 2 controlled studies demonstrate that AzA gel, used twice daily, is an efficacious, safe, and well-tolerated topical treatment for moderate, papulopustular rosacea. Biological research suggests that vascular changes may play a major role in rosacea pathogenesis. Chrysanthellum indicum is a plant-based extract containing a unique combination of phenylpropenoic acids, flavonoids and saponosids, and has a well-documented effect on vascular wall permeability and increase of the mechanical resistance of capillaries.
                To determine the efficacy and safety of a cream containing 1%C. indicum extract with vitamin P properties in the treatment of rosacea.
                This study included 246 patients diagnosed clinically as having moderate rosacea. Patients were randomly allocated to C. indicum extract-based cream (n = 125) and placebo (n = 121) groups. Patients were advised to apply the products on their face twice a day for a 12-week period. The patients were examined at the end of each 4-week period. Severity of erythema (graded by reference to six photographs), surface of erythema and rosacea overall severity scores were recorded at each visit on days 0, 28, 56 and 84. Investigators carried out a final efficacy assessment at the end of week 12. Volunteers' final overall efficacy assessment was recorded in a self-administered questionnaire. Adverse events were identified through examination, interview and collection of comments in patients' questionnaires.
                Treatment with the C. indicum extract-based cream resulted in significant improvement (P < 0.05) in severity of erythema, overall rosacea severity compared to baseline and placebo, and investigator and patient overall efficacy assessment scores (P = 0.046 and P = 0.001, respectively) compared with placebo scores. Adverse reactions were mild, and did not differ between the C. indicum extract-based cream and the placebo groups.
                Chrysanthellum indicum extract-based cream is an effective and well-tolerated topical agent for the treatment of moderate rosacea. The mode of action of the active ingredient suggests that additional efficacy might be expected from combination with other topical treatments. nan Rosacea is an inflammatory dermatologic disorder characterized by the presence of facial erythema, visible blood vessels, papules, and pustules. The National Rosacea Society has established a classification system that identifies 4 distinct rosacea subtypes based on clinical presentation: erythematotelangiectatic, papulopustular, phymatous, and ocular. The goal of topical therapy for rosacea is to reduce inflammatory lesion counts; decrease intensity of erythema; and reduce symptoms such as stinging, burning, and pruritus. Metronidazole and azelaic acid are thought to reduce the inflammation associated with rosacea by inhibiting the production of reactive oxygen species produced by neutrophils. Both metronidazole 1% gel and azelaic acid 15% gel recently have been approved for the treatment of rosacea. The current study was conducted to compare the once-daily application of metronidazole 1% gel with twice-daily applications of azelaic acid 15% gel for the treatment of patients with moderate rosacea (N=160). Both treatments showed similar reductions in inflammatory lesion counts (77% for metronidazole 1% gel and 80% for azelaic acid 15% gel) and high success rates in both global severity (53.7% vs 56.4% for metronidazole 1% gel and azelaic acid 15% gel, respectively) and erythema (42.7% vs 42.3% for metronidazole 1% gel and azelaic acid 15% gel, respectively). On average, the efficacy (including reduction in erythema) of the once-daily application of metronidazole 1% gel and twice-daily applications of azelaic acid 15% gel were similar. Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea.
                To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea.
                In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count.
                The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%).
                In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea.
                Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea. Topical metronidazole and combination sodium sulfacetamide and sulfur commonly are used to treat rosacea. Recently, the relative efficacy and safety of sodium sulfacetamide 10% and sulfur 5% cream with sunscreens (Rosac Cream) (n = 75) and metronidazole 0.75% cream (Metrocream) (n = 77) were compared in an investigator-blinded, randomized, parallel-group study at 6 sites. After 12 weeks of treatment with sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, there was a significantly greater percentage reduction (80%) in inflammatory lesions compared with metronidazole 0.75% cream (72%)(P = .04), as well as a significantly greater percentage of subjects with improved erythema (69% vs 45%, respectively; P = .0007). In addition, the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group had a significantly greater proportion of subjects with success in global improvement at week 12 compared with the metronidazole 0.75% cream group (79% vs 59%, respectively; P = .01). There was no significant difference between treatment groups in the percentage of subjects with improvement in investigator global severity. Overall tolerance was good or excellent in 85% of subjects in the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group and in 97% of subjects in the metronidazole 0.75% cream group. Seven subjects had poor tolerance to the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, possibly caused by a sulfa drug allergy. Erythematotelangiectatic (ET) rosacea is commonly treated with a variety of laser and light-based systems. Although many have been used successfully, there are a limited number of comparative efficacy studies.
                To compare nonpurpuragenic pulsed dye laser (PDL) with intense pulsed light (IPL) treatment in the ability to reduce erythema, telangiectasia, and symptoms in patients with moderate facial ET rosacea.
                Twenty-nine patients were enrolled in a randomized, controlled, single-blind, split-face trial with nonpurpuragenic treatment with PDL and IPL and untreated control. Three monthly treatment sessions were performed with initial PDL settings of 10-mm spot size, 7 J/cm(2), 6-ms pulse duration and cryogen cooling, and initial IPL settings of 560-nm filter, a pulse train of 2.4 and 6.0 ms in duration separated by a 15-ms delay, and a starting fluence of 25 J/cm(2). Evaluation measures included spectrophotometric erythema scores, blinded investigator grading, and patient assessment of severity and associated symptoms.
                PDL and IPL resulted in significant reduction in cutaneous erythema, telangiectasia, and patient-reported associated symptoms. No significant difference was noted between PDL and IPL treatment.
                A series of nonpurpuragenic PDL and IPL treatments in ET rosacea was performed with similar efficacy and safety, and both modalities seem to be reasonable choices for the treatment of ET rosacea. There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some reports have indicated beneficial effects of topical pimecrolimus.
                To compare the efficacy and safety of pimecrolimus 1% cream and metronidazole 1% cream in the treatment of patients with papulopustular rosacea (PR).
                A group of 49 patients with PR was investigated in this single-centre, randomized, open-label study. Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Response was evaluated by the inflammatory lesion count, the severity of facial erythema and telangiectasia, Physician's Global Assessment (PGA), and safety and tolerability at baseline and at weeks 3, 6, 9 and 12.
                In total, 48 patients completed the study. Both treatments were very effective in the treatment of PR. There were no significant differences between the treatments in inflammatory lesion counts, overall erythema severity scores and PGA evaluated from baseline to week 12 (P > 0.05). Neither treatment produced any clinically relevant improvement in telangiectasia.
                Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR. Permethrin 5% cream used against human ectoparasites suggests that it may be effective in papulopustular rosacea.
                This study included 63 patients diagnosed as having papulopustular rosacea based on the clinical and histological findings. Patients were randomly assigned into permethrin (n = 23), metronidazole (n = 20) and placebo (n = 20) groups. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and Demodex folliculorum were determined. Twenty-three patients were given permethrin 5% cream (Zalvor 5% skin cream, 20 patients metronidazole 0.75% gel (Roza gel and 20 patients placebo cream (Basis cream, in packages looking identical to those of metronidazole and permethrin creams, and were recommended to apply them to their faces twice a day. All patients were also given SPF 20 cream for protection against sunlight. Two months of treatment were planned, and the patients were invited to the clinic for fortnightly controls. Scores of erythema, telangiectasia, edema and rhinophyma and the numbers of papules, pustules, inflammatory nodules and D. folliculorum were recorded at each visit. The mean scores of erythema and the mean numbers of papules, pustules and D. folliculorum were determined at baseline and on days 15, 30, 45 and 60. Side effects were also detected.
                The effect of permethrin 5% cream on D. folliculorum was superior to that of metronidazole 0.75% gel. The effect of permethrin 5% cream on erythema and papules was found to be more effective than placebo and as effective as metronidazole 0.75% gel. However, it had no effect on telangiectasia, rhinophyma and pustules.
                It can be concluded that the application of permethrin 5% cream twice daily for 2 months can be as effective and reliable as metronidazole in the treatment of rosacea and a greater benefit can be gained when it is combined with other systemic and/or topical treatments.
                Copyright 2002 S. Karger AG, Basel A double-blind trial in twenty-nine patients with rosacea showed that, after 6 weeks' treatment, metronidazole was therapeutically superior to a placebo (P less than 0-02). It was particularly effective against papules and pustules. The mode of action of metronidazole and other antibiotics in rosacea is not known. Facial erythema is a common postsurgical and dermatologic problem. It is commonly the result of dermal inflammation arising from either a facial surgical procedure, such as laser resurfacing, dermabrasion, or a face peel, or from an underlying dermatologic condition, such as rosacea. Facial erythema is difficult for the dermatologist to treat in both settings because topical corticosteroids cannot be used long term on the thin facial skin and anti-inflammatory oral or topical antibiotics have associated side effects.
                The goal of this pilot study was to evaluate the anti-inflammatory effect of 1% 4-ethoxybenzaldehyde in a rosacea model of facial erythema.
                Thirty subjects with mild to moderate stable rosacea were enrolled in this 4-week, double-blind, vehicle-controlled study. Photographs, investigator assessment, and subject assessment were the efficacy criteria.
                There was a statistically significant reduction in facial erythema (p<.01) in those subjects who used the active for 4 weeks, as well as a statistically significant improvement in uneven skin tone (p<.01) and the overall severity of the disease (p<.01). There was no statistically significant difference in any of these three indices in the vehicle-treated group.
                The results suggest that benzaldehyde-derived anti-inflammatory agents may be useful in reducing facial erythema in a rosacea model. Forty patients with rosacea were treated topically with 0.75% metronidazole gel in a randomized split-face double-blind paired-comparison trial. With twice-daily applications, 36.7, 48.5, and 65.1 mean percent reductions in total papules and pustules were noted over baseline at 3, 6, and 9 weeks, respectively, on the side of the face receiving metronidazole therapy. Therapy with vehicle alone produced a maximum mean percent reduction of 14.9 at nine weeks. Erythema also responded but was less improved by the end of nine weeks of therapy. A mild increase in telangiectasia was noted on both actively treated and placebo-treated sides. The gel was locally well tolerated. Only two of 40 patients failed to complete the trial, both because of flares of rosacea (one at two days, and one at five weeks). No systemic symptoms were noted, and no consistent abnormalities were found in the results of laboratory studies (hematology, chemistry, and urinalysis). Topical metronidazole gel therapy appears to be a safe and efficacious therapy in the treatment of moderate to severe rosacea. Eighty-one patients with rosacea were treated with either I% metronidazole cream or the cream base as a placebo for two months. The trial was performed double-blind, and the patients were assessed once each month. The variates studied were: (I) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, and (5) patient's opinion. Four patients dropped out of the trial (one treated with metronidazole, three with placebo). In all the variates, I% metronidazole cream proved to be significantly more effective than placebo. Forty patients with papulo-pustular rosacea were treated for 12 weeks on a random double-blind basis either with oxytetracycline 250 mg twice daily or with metronidazole 200 mg twice daily. Both drugs produced an improvement which was greater after 12 weeks than after 6 weeks, but there was no significant difference between them. Metronidazole appears to be a safe and effective drug for the treatment of rosacea. Previous investigations have indicated that topical azelaic acid has beneficial effects in rosacea. This 3-month randomized, double-blind, multicentre study compared the efficacy and safety of azelaic acid 20% cream with its vehicle, in the treatment of papulo-pustular rosacea. A total of 116 patients were enrolled in the study and medication was applied twice daily. Azelaic acid cream produced significantly greater mean reductions in total inflammatory lesions than did vehicle (azelaic acid: 73.4%; vehicle: 50.6%; (p = 0.011), and erythema severity score (azelaic acid: 47.9%; vehicle: 37.9%; (p = 0.031). Azelaic acid cream treatment also resulted in significantly more favourable overall improvements than vehicle in both physician (p = 0.020) and patient ratings (p = 0.042). Neither azelaic acid cream nor vehicle produced any clinically relevant improvement in telangiectasia. Local adverse events were transient and mainly mild or moderate, and rates were similar for azelaic acid cream (39.5%) and vehicle (38.5%). Burning was the symptom most frequently reported. More than 90% of patients rated the overall local tolerability of their treatment as good or acceptable. In conclusion, azelaic acid 20% cream is effective and well tolerated in the treatment of papulo-pustular rosacea. One percent metronidazole in an emollient cream base was compared with 250 mg oral tetracycline taken twice daily for the treatment of seventy-five patients with rosacea. After eight weeks of treatment there was no statistically significant difference between the results of the two treatments. Tetracycline did have a more rapid onset of effect on papules and pustules. Both treatments were well tolerated. A new topical antibiotic preparation, clindamycin in a lotion base, was compared with oral tetracycline in the treatment of rosacea. Forty-three patients clinically diagnosed as having rosacea were examined in an investigator-blinded study.
                Patients used topical clindamycin lotion applied twice daily or the usual oral dose of tetracycline hydrochloride (250 mg four times a day for 3 weeks, then 250 mg twice a day for the remaining 9 weeks). Patients' lesions were examined clinically at 3-week intervals over a period of 12 weeks.
                Topical clindamycin treatment produced similar clinical results to oral tetracycline and was superior in the eradication of pustules.
                These results show topical clindamycin in a lotion base to be a safe and effective alternative to oral tetracycline therapy in the treatment of rosacea. Systemic antibiotics such as tetracycline are well accepted as effective in treating the inflammatory papular/pustular phase of rosacea but may be associated with systemic side-effects. Few controlled data on the use of topical antibiotics in rosacea are available.
                We evaluated the efficacy and tolerability of a fixed combination of 5% benzoyl peroxide and 1% clindamycin in a topical gel for the treatment of rosacea. Methods This was a 12-week, double-blind, vehicle-controlled, randomized, prospective, parallel-group study in 53 patients with moderate to severe rosacea.
                The mean percentage reduction in papules and pustules from baseline to the end of treatment was 71.3% in the benzoyl peroxide/clindamycin group (n = 26) and 19.3% in the vehicle group (n = 26; P = 0.0056). A significant (P = 0.0141) difference in favor of benzoyl peroxide/clindamycin was evident by the third week of treatment. Severity scores for erythema, papules/pustules, and flushing/blushing decreased more with benzoyl peroxide/clindamycin than with vehicle. Overall rosacea severity, Physician Global Assessment, and Patient's Global Assessment at the end of treatment were all significantly improved with benzoyl peroxide/clindamycin compared with vehicle (P = 0.0101, 0.0026, and 0.0002, respectively). Application site reactions were reported in four patients (14.8%) in the benzoyl peroxide/clindamycin group.
                A once-daily topical application of a combination of 5% benzoyl peroxide and 1% clindamycin is effective and well tolerated in patients with moderate to severe rosacea. Rosacea remains difficult to treat, despite many therapeutic options.
                To investigate the effect of pimecrolimus cream 1% (Elidel; Novartis Pharma, Nuremberg, Germany) in the treatment of papulopustular rosacea.
                Forty patients with rosacea (25 men and 15 women, mean age 58 years) were enrolled in a randomized, vehicle-controlled, double-blind study. For 4-8 weeks, patients applied pimecrolimus cream or vehicle twice daily to the involved areas on the face. Rosacea severity score, subjective severity assessment and quality of life assessment were obtained, along with photographic documentation.
                Both treatment groups of 20 patients showed an improvement after 4 weeks. The differences were not significant (P > 0 x 05) with regard to mean absolute values, mean percentage changes from baseline, or mean absolute values as differences from baseline for the total score or scores of the different clinical signs (erythema, papulation, scaling and pustules). In the subjective severity score and the quality of life assessment, there was also no significant difference between pimecrolimus and the vehicle (P > 0 x 05).
                Treatment of rosacea for 4-8 weeks with the topical calcineurin inhibitor pimecrolimus cream 1% was not more efficacious than treatment with the vehicle cream. To evaluate the clearing and intensity of symptoms of rosacea 60 days after the treatment of Helicobacter pylori infection.
                Randomized, double-blind, placebo-controlled clinical trial.
                The dermatology section of a large multispecialty clinic in the North Central United States.
                Men and women older than 25 years with active signs of rosacea who tested positive for H pylori with both the rapid whole blood test and the urea breath test.
                Treatment of H pylori infection with 14-day therapy using clarithromycin. 500 mg orally 3 times a day, and omeprazole, 40 mg orally once a day.
                The extent and intensity of rosacea as measured by the number of papules and pustules and the extent and intensity of erythema and telangiectasia.
                Three hundred twenty patients presented with rosacea. For 50 patients, the results of a urea breath test were positive for H pylori, and 44 patients were enrolled in the study. Rosacea abated in almost all patients, but none were cured. Notably, lessening of rosacea for patients treated for H pylori was not significantly better than for the control cohort.
                Rosacea abated in most participants in this study, whether they were in the treatment or the control cohort. There was no statistical difference when the results of active treatment were compared with those of placebo. Treating H pylori infection has no short-term beneficial effect on the symptoms of rosacea to support the suggested causal association between H pylori infection and rosacea. This two-phase, multicenter study was undertaken to examine the safety and efficacy of combination therapy with oral doxycycline and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172) received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for < or = 12 weeks. In the second, double-blind study phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved > or = 75% inflammatory lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24 weeks. Assessments of efficacy were obtained at four-week intervals throughout both phases of the study and included change in inflammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement, with the participant rating cosmetic acceptability and the investigator rating treatment as "success" or "failure" based on IGA score. During the second phase of the trial, the rate of relapse -- defined as either a 50% deterioration in the lesion count improvement from phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the subject -- was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events (AEs) and a rating of cutaneous tolerability by the subject. By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in inflammatory lesion count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month duration of the maintenance phase. Additionally AzA 15% gel showed a statistically significantly lower deterioration in absolute inflammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs were encountered in the study, and 98.5% of subjects were satisfied with the local tolerability of both AzA gel and vehicle. Twice-daily azelaic acid (AzA) is the conventional regimen for papulopustular rosacea, but once-daily AzA may be equally effective, with greater convenience and dosing flexibility. In order to test this hypothesis, an exploratory study was conducted.
                The evaluable efficacy population of this 12-week double-blind, parallel-group study included 72 patients and the population that was used to report safety results included 92 patients. Baseline characteristics were comparable between the once-daily and twice-daily study groups. Evaluations were performed at baseline and at weeks 4, 8, and 12.
                No significant difference was found between the once-daily and twice-daily groups at the end of study therapy in mean investigator global assessment (IGA) scores, treatment success, or treatment response. The mean number of inflammatory lesions, the intensity of erythema intensity, and the intensity of telangiectasia at treatment end were likewise not significantly different (P>.205 for all). More than 90% of subjects in each group rated cosmetic acceptability of this AzA gel as satisfactory or better.
                Based on these findings and those of prior studies, once-daily AzA 15% gel can therefore be utilized as a safe, effective, and economical dosing option for the treatment of mild-to-moderate papulopustular rosacea. Once-daily dosing of AzA 15% gel was well accepted by patients and can offer considerable dosing flexibility and convenience for the patient as well as for the dermatologist. Research into the pathophysiology of rosacea suggests a central role for inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). Effective treatments for rosacea, including topical metronidazole and systemic antibiotics, have anti-inflammatory activity, which may be more important than their antimicrobial activity in this setting. Phase III studies have substantiated the efficacy of anti-inflammatory dose doxycycline (40-mg doxycycline monohydrate controlled-release capsules) administered once daily for the treatment of inflammatory lesions of rosacea. Results of a 16-week, randomized, double-blind, placebo-controlled study of anti-inflammatory dose doxycycline plus topical metronidazole gel 1% for mild to moderate rosacea are presented here. At week 12, metronidazole was discontinued and patients continued on either placebo or doxycycline. Combination therapy significantly reduced inflammatory lesion counts as early as week 4 and through week 12 compared to topical metronidazole 1% gel monotherapy. The combined therapy appeared effective and well-tolerated. The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea.
                Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface.
                Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study.
                Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis. Although it is important for physicians to have sufficient clinical data on which to base treatment decisions, little comparative data exist regarding newer treatment modalities for rosacea.
                The goal of the study was to compare the efficacy and safety of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. Parameters of patient satisfaction to treatment were also assessed.
                Forty patients with the clinical manifestation of symmetric facial rosacea were investigated in this single-center, double-blind, randomized, contralateral split-face comparison clinical trial.
                After 15 weeks of treatment, both azelaic acid and metronidazole induced significant, albeit equal reductions in the number of inflammatory lesions (pustules and papules). A significantly higher physician rating of global improvement was achieved with azelaic acid. Changes in the rosacea signs and symptoms of dryness, burning, telangiectasia, and itching were equal between treatments. A reduction in erythema tended toward significance with azelaic acid at week 15. A trace amount of stinging on application was noted with azelaic acid; however, such discomfort did not appear to concern patients because their overall impression of azelaic acid was superior to that of metronidazole.
                Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream with the added benefit of increased patient satisfaction. Rosacea is a chronic skin disease that requires long-term therapy. Oral antibiotics and topical metronidazole successfully treat rosacea. Because long-term use of systemic antibiotics carries risks for systemic complications and adverse reactions, topical treatments are preferred.
                To determine if the use of topical metronidazole gel (Metrogel) could prevent relapse of moderate to severe rosacea.
                A combination of oral tetracycline and topical metronidazole gel was used to treat 113 subjects with rosacea (open portion of the study). Successfully treated subjects (n = 88) entered a randomized, double-blind, placebo-controlled study applying either 0.75% topical metronidazole gel (active agent) or topical metronidazole vehicle gel (placebo) twice daily (blinded portion of the study).
                Subjects were enrolled at 6 separate sites in large cities at sites associated with major medical centers.
                One hundred thirteen subjects with at least 6 inflammatory papules and pustules, moderate to severe facial erythema and telangiectasia entered the open phase of the study. Eighty-eight subjects responded to treatment with systemic tetracycline and topical metronidazole gel as measured by at least a 70% reduction in the number of inflammatory lesions. These subjects were randomized to receive 1 of 2 treatments: either 0.75% metronidazole gel or placebo gel.
                Subjects were evaluated monthly for up to 6 months to determine relapse rates.
                Inflammatory papules and pustules were counted at each visit. Relapse was determined by the appearance of a clinically significant increase in the number of papules and pustules. Prominence of telangiectases and dryness (roughness and scaling) were also observed.
                In the open phase, treatment with tetracycline and metronidazole gel eliminated all papules and pustules in 67 subjects (59%). The faces of 104 subjects (92%) displayed fewer papules and pustules after treatment, and 82 subjects (73%) exhibited less erythema. In the randomized double-blind phase, the use of topical metronidazole significantly prolonged the disease-free interval and minimized recurrence compared with subjects treated with the vehicle. Eighteen (42%) of 43 subjects applying the vehicle experienced relapse, compared with 9 (23%) of 39 subjects applying metronidazole gel (P<.05). The metronidazole group had fewer papules and/or pustules after 6 months of treatment (P<.01). Relapse of erythema also occurred less often in subjects treated with metronidazole (74% vs 55%).
                In a majority of subjects studied, continued treatment with metronidazole gel alone maintains remission of moderate to severe rosacea induced by treatment with oral tetracycline and topical metronidazole gel. Rosacea is a skin problem not uncommonly encountered world-wide. There is a need for an effective and well-tolerated treatment for this disease.
                To evaluate the efficacy and side-effects of zinc sulfate in rosacea in a randomized, controlled, double-blind trial.
                Patients with rosacea who attended the outpatient Clinic of Dermatology and Venereology in Baghdad Teaching Hospital were recruited into this study between October 2002 and August 2004. A disease severity score was calculated for each patient. The patients were randomly allocated to receive either zinc sulfate 100 mg or identical placebo capsules three times per day. Zinc sulfate and placebo capsules were given in a double-blind manner. Following 3 months of starting the treatment, the patients crossed over, i.e. patients on placebo crossed over to zinc sulfate and those on zinc sulfate crossed over to placebo.
                Twenty-five patients with rosacea were included in this study: 16 (64%) females and nine (36%) males. Nineteen patients completed the study: 11 (58%) females and eight (42%) males. Patient age ranged from 21 to 64 years with a mean +/- SD of 48.2 +/- 9.3 years. Duration of the disease ranged from 1 to 14 years with a mean +/- SD of 4.4 +/- 3.2 years. In the group started on zinc sulfate, the score before therapy ranged from 5 to 11 with a mean +/- SD of 8 +/- 2.0. The mean started to decrease directly after the first month of therapy with zinc sulfate to a significantly lower level. After shifting to placebo treatment, the mean started to rise gradually in the fifth month but remained significantly lower than the levels before therapy. In the group started on placebo, the score before therapy ranged from 5 to 9 with a mean +/- SD of 7 +/- 1.3. The mean remained high in the first 3 months of therapy while the patients were on placebo. After shifting to zinc sulfate, the mean started to decrease after the fourth month to significantly low levels. No important side-effects were reported apart from mild gastric upset in three (12%) patients on zinc sulfate.
                Zinc sulfate was found to be a good option in the treatment of rosacea, as it was safe, effective and lacking important side-effects. A group of patients with acne rosacea was treated with 5 percent benzoyl peroxide acetone gel for four weeks and then with 10 percent benzoyl peroxide acetone gel for an additional four weeks. A parallel group of patients was treated with a matching placebo (acetone gel vehicle). At the end of the first four weeks of treatment the dropout rate due to lack of improvement was 23 and 63 percent for benzoyl peroxide acetone gel and placebo, respectively. Benzoyl peroxide acetone gel was superior to placebo with respect to improvement in the overall severity of the lesions when judged by photographs, and by reduction of erythema, papules, and pustules. Results after treatment with benzoyl peroxide acetone gel were better during weeks five to eight than during weeks one to four for all lesions except telangiectasia. Benzoyl peroxide acetone gel was superior to placebo when the overall responses were compared. In addition, the benzoyl peroxide acetone gel-treated group, but not the placebo-treated group, showed a significantly better response during weeks five to eight compared to weeks one to four. In a randomized double-blind trial fifty-one patients with rosacea were treated for 2 months with either I% metronidazole cream and placebo tablets or with 250 mg oxytetracycline tablets taken twice daily, and placebo cream (the cream base). The patients were assessed before and at the end of the trial, using the following criteria: (1) overall clinical assessment, (2) lesion counts, (3) degree of erythema, (4) independent photographic evaluation, (5) patients' opinion. An improvement was shown in 90% of the patients of both groups, and there was no significant difference between the two treatments. Pulsed dye (PDL) 595- and 1,064-nm Nd:YAG lasers are used for the treatment of vascular lesions. PDL-heated blood exhibits increased absorption of radiation at 1,064 nm, suggesting that the use of combined sequential dual wavelengths may offer benefits over single-wavelength treatments. This study compares the treatment efficacy of combined sequential dual-wavelength versus single delivery of 595-nm PDL or 1,064-nm Nd:YAG wavelengths in facial telangiectasia in a split face study design using subpurpuric parameters.
                Twenty patients were studied using the sequential delivery of PDL and Nd:YAG wavelengths on one side of the nose. The other side received either PDL or Nd:YAG treatment. Vessels (<0.6 mm in diameter) were treated with a 7-mm spot size at 10 J/cm(2), 10 ms with the PDL, followed by the Nd:YAG at 70 J/cm(2), 15 ms with a multiplex interpulse delay of 100 ms. Subjects received a single treatment, and results were evaluated after 4-week follow-up. Improvement was determined by blinded assessment of photographs taken before and after final evaluation.
                The efficacy of the dual-wavelength laser treatment when compared to Nd:YAG or PDL laser alone was significantly more evident than either single-wavelength treatment (p<.05). There was no statistically significant difference in efficacy between the single-wavelength treatment groups.
                The sequential delivery of 595- and 1,064-nm-wavelength radiation with an interpulse delay suggests that the synergistic approach to laser therapy for facial telangiectasia is a superior method compared to standard single wavelength therapy. nan nan Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy.
                The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea.
                Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16.
                Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy.
                Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy. This study was designed to compare the efficacy of cyclosporine ophthalmic emulsion 0.05% with an artificial tear solution for the treatment of rosacea-associated eyelid and corneal pathology.
                Double-masked, randomized, 3-month clinical trial of 37 patients with rosacea-associated eyelid and corneal changes (defined as lid margin telangiectasia, meibomian gland inspissation, and/or fullness of the lid margin). All findings were standardized and compared to photographs for grading.
                There was a statistically significant increase in Schirmer (with anesthesia) scores of 2.7+/-2.2 mm after 3 months of treatment in the topical cyclosporine group (P<0.001), compared with a mean decrease of -1.4+/-4.6 mm (P=0.271) in the artificial tears group. The mean tear break-up time score significantly improved in the topical cyclosporine group (mean increase of 3.56+/-1.5 seconds, P<0.001), but worsened in the control group, although this change was not significantly significant (mean decrease of -0.04+/-1.6 seconds, P=0.929). The topical cyclosporine group exhibited a significantly greater mean reduction in corneal staining scores (-1.3+/-0.53) compared with the control group (-0.2+/-0.83; between groups P<0.001). The topical cyclosporine group had a greater improvement in Ocular Surface Disease Index scores than those using artificial tears (P=0.022). Limitations of the study included an older, predominantly Caucasian patient population and short trial length.
                Topical cyclosporine 0.05% is more effective than artificial tears for the treatment of rosacea-associated lid and corneal changes. Rosacea is a photoaggravated dermatosis responsive to treatment with topical and oral antibiotics. A formulation combining metronidazole 1% cream with sunscreen SPF 15 was developed for the treatment of rosacea.
                The objective of this study was to determine the safety and efficacy of a formulation combining metronidazole 1% cream with sunscreen SPF 15 in the treatment of moderate to severe rosacea.
                One hundred and twenty patients with moderate to severe rosacea were enrolled for a randomized, placebo-controlled (vehicle containing sunscreen with SPF 15), double-blind study. Study cream was applied twice daily to the entire face over a 12-week period.
                Treatment with metronidazole 1% cream with sunscreen SPF 15 resulted in significant improvement (p <0.05) in inflammatory lesion count, erythema and telangiectasiae scores, and investigator and patient global assessment scores compared with baseline and placebo. Adverse reactions related to study medication were typically mild, occurred at the site of application, and were reversible. There was no difference between the safety profiles of metronidazole 1% cream with sunscreen SPF 15 and placebo.
                The combined topical formulation of metronidazole 1% cream with sunscreen SPF 15 was an effective, well-tolerated topical agent for the treatment of moderate to severe rosacea. The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low. The usual treatments of rosacea (cyclines and metronidazole) are mainly effective on reducing the number of papules and pustules. Clonidine only was employed in order to treat flushes observed in rosacea. Rilmenidine is a central hypotensive drug which acts more specifically than clonidine on imidazoline receptors and which has no sedative side effects. The purpose of this study was to evaluate the efficacy of rilmenidine 1 mg/d in the treatment of rosacea.
                A total of 41 patients suffering from typical rosacea were selected in this randomised double blind study rilmenidine versus placebo. The study comprised an 1-month observation period without treatment followed by 3 months of treatment. The major assessment criteria was the proportion of responders at the end of the treatment period. Responders were defined as patients showing a decrease of more than 50 p. 100 in the count of papules and pustules. Minor criterias were the variation of the number of flushes, self-evaluated by the patient and the variation of the redness of the face, noted by the investigator on a scale from 0 to 5.
                Fifteen patients treated by rilmenidine (R) and 19 patients receiving the placebo (P) were evaluated. The proportion of responders was 69.2 p. 100 in group R and 57.1 p. 100 in group P (p = 0.69). The variations of the number of papules and pustules and of the redness of the face were not significantly different in the two groups. The decrease in the number of flushes was higher in group R (around -13) than in group P (around -5), but the difference was not really significant (p = 0.076). Arterial pressure decreased in 3 patients in group R and in 2 patients in group P. Minor side effects were noted in a similar proportion of patients in the two groups.
                Rilmenidine is not efficient in reducing the number of papules and pustules but could decrease the number of flushes. Nevertheless, many patients were lost for follow-up and because of a major placebo effect, the conclusions of this study are not strong enough. Another study including more patients and using evaluation criteria based on the vascular components of rosacea could perhaps confirm this hypothesis. To compare the efficacy and safety of a novel formulation of 15% azelaic acid gel (Finacea; Berlex Laboratories, Inc, Montville, NJ) with 0.75% metronidazole gel (MetroGel; Galderma Laboratories LP, Fort Worth, Tex) as topical therapy for moderate, papulopustular facial rosacea.
                Multicenter, double-blind, randomized, parallel-group study.
                Thirteen US centers.
                A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia.
                Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks.
                Nominal and percent change in inflammatory lesion count, change in erythema and telangiectasia severity ratings, investigator's global assessment of rosacea, and investigator's and patient's overall improvement ratings.
                Azelaic acid gel was superior to metronidazole gel in reduction of mean nominal lesion count (-12.9 vs -10.7, respectively) (P =.003) and mean percent decrease in inflammatory lesions (-72.7% vs -55.8%, respectively) (P<.001). With respect to erythema severity, 56% of azelaic acid gel-treated patients were rated improved vs 42% of metronidazole gel-treated patients (P =.02). The effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15. Neither treatment had a clinically appreciable effect on telangiectasia. Both the investigator's global assessment (P =.02) and overall assessment of improvement (P =.005) showed a significant therapeutic advantage for azelaic acid gel. Azelaic acid gel also scored higher on the patient's overall assessment of efficacy. Both treatments were rated as having high cosmetic acceptability. No serious or systemic treatment-related adverse events were reported in either group.
                Use of 15% azelaic acid gel twice daily for 15 weeks demonstrated significant superiority over using 0.75% metronidazole gel in improving principal signs of rosacea (inflammatory lesions and erythema). The effect of nadolol versus placebo on both flushing provoked in a laboratory setting and spontaneous flushing was studied in 15 patients with erythematous telangiectatic rosacea. The intensity of the flushing reactions was assessed in the laboratory by the cutaneous perfusion index method with laser-Doppler velocimetry. No effect of nadolol on the flushing reactions provoked in the laboratory was detected. Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne.
                For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty-seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness.
                Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline.
                This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea. nan Rosacea is a disease of complex pathogenesis and variable response to various therapeutic methods. Aim of the work To evaluate and compare the efficacy, safety and side effects of some topical lines of treatment of rosacea.
                The study included 24 patients (23 females and 1 male) with rosacea on the face. They were classified into three groups--each including eight patients (16 face sides)--and treated with one of three topical agents (azelaic acid 20% cream, metronidazole 0.75% cream or permethrin 5% cream) on one side of the face and another one on the other side twice daily for 15 weeks.
                There was a significant improvement of lesions after 15 weeks of topical treatment with the three agents. Azelaic acid cream was significantly more effective on inflammatory lesions but not erythema than the other two creams. Side effects--mostly transient--were observed with topical creams with no significant difference. They included itching, burning sensation, oedema and scales. Patients who used azelaic acid 20% cream were more satisfied than with other modalities.
                Azelaic acid 20% cream provides an effective and safe alternative to metronidazole 0.75% cream or permethrin 5% cream with the added benefit of increased patient satisfaction.
Although the majority of included studies were assessed as being at high or unclear risk of bias there was some evidence to support the effectiveness of topical metronidazole, azelaic acid, and doxycycline (40 mg) in the treatment of moderate to severe rosacea, and cyclosporine 0.05% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately-powered randomised controlled trials are required.