Topical metronidazole therapy for rosacea

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.     

A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial

OBJECTIVE: 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. DESIGN: Multicenter, double-blind, randomized, parallel-group study. SETTING: Thirteen US centers. PATIENTS: A total of 251 patients with papulopustular rosacea with persistent erythema and telangiectasia. INTERVENTIONS: Patients were randomized to receive azelaic acid gel or metronidazole gel twice daily for 15 weeks. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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).     

Rosacea and its management: an overview

BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the population. The prevalence of rosacea is highest among fair-skinned individuals, particularly those of Celtic and northern European descent. Since a cure for rosacea does not yet exist, management and treatment regimens are designed to suppress the inflammatory lesions, erythema, and to a lesser extent, the telangiectasia involved with rosacea. OBJECTIVES: This review outlines the treatment options that are available to patients with rosacea. METHODS: Published literature involving the treatment or management of rosacea was examined and summarized. RESULTS: Patients who find that they blush and flush frequently, or have a family history of rosacea are advised to avoid the physiological and environmental stimuli that can cause increased facial redness. Topical agents such as metronidazole, azelaic acid cream or sulfur preparations are effective in managing rosacea. Patients who have progressed to erythematotelangiectatic and papulopustular rosacea may benefit from the use of an oral antibiotic, such as tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the rosacea flare-up under control. Treatment with a topical agent, such as metronidazole, may help maintain remission. Patients with ocular involvement may benefit from a long-term course of an antibiotic and the use of metronidazole gel. A surgical alternative, laser therapy, is recommended for the treatment of telangiectasias and rhinophyma. Patients with distraught feelings due to their rosacea may consider cosmetic camouflage to cover the signs of rosacea. CONCLUSIONS: With the wide variety of oral and topical agents available for the effective management of rosacea, patients no longer need to feel self-conscious because of their disorder.     

Efficiency of benzoyl peroxide-erythromycin gel in comparison with metronidazole gel in the treatment of acne rosacea

Oral wide-spectrum antibiotics are the linchpin of rosacea treatment. Oral and topical metronidazole, topical tretinoin, and topical benzoyl peroxide may also be used in the treatment of rosacea. We aimed to show that benzoyl peroxide-erythromycin gel is efficient in the treatment of acne rosacea. Fifty-six patients with acne rosacea were enrolled in our study. We administered benzoyl peroxide-erythromycin gel to 27 patients and metronidazole gel to 29 patients. In all the patients, the intensities of erythema, telangiectasia, papules/pustules, and nodules were evaluated before, during and after the treatment. The positivity of Demodex folliculorum from skin scratches was compared between the two groups at each visit. At the end of the therapy on the third examination, in the benzoyl peroxide-erythromycin group, 91.7% of the patients showed marked clinical improvement, and 8.3% of them showed complete remission. In the metronidazole group, 73.3% showed marked clinical improvement, and 26.7% of them showed complete remission. Clinical improvement in the papular component was 65.2% for the benzoyl peroxide-erythromycin group, and 81.5% for metronidazole group. In the first examination, the clinical results of the agents were similar. Although both of the drugs were found to be effective in the second and third examinations, metronidazole gel was more effective than benzoyl peroxide-erythromycin. Both of the drugs were found to be significantly effective especially in treating the papular component of rosacea. Demodex folliculorum was found to be positive in 74.1% of the benzoyl peroxide-erythromycin group and in 62.1% of the metronidazole group at the beginning. In the benzoyl peroxide-erythromycin group, 40.7% of Demodex folliculorum positive patients, became negative by the first examination. This was 17.2% for the metronidazole group. In the benzoyl peroxide-erythromycin group, among the patients who were positive for Demodex folliculorum in the first examination, 37.5% of them became negative. This was 36.7% for the metronidazole group. Benzoyl peroxide-erythromycin gel was superior to metronidazole gel in decreasing Demodex folliculorum by the first examination, but the effect of the two drugs on Demodex folliculorum was similar by the second examination. As a result, topically applied combined benzoyl peroxide-erythromycin gel may be an alternative choice of treatment for acne rosacea.     

Acne and rosacea. New and emerging therapies

The goal of this article is to highlight recent developments in the treatment of acne and rosacea. An update on the use of isotretinoin, minocycline, topical retinoids, and hormones in the treatment of acne are presented. Highlights of research findings that may lead to future acne therapies are discussed. New in the management of rosacea are studies demonstrating the efficacy of 1% topical metronidazole in the treatment of rosacea, reports on the successful maintenance of remissions of rosacea with 0.75% metronidazole gel, and data regarding the controversial association of rosacea with Helicobacter pylori infection.     

The management of rosacea

Rosacea is a multiphasic disease which is associated with flushing, erythrosis, papulopustular rosacea and phymas; each phase is likely to have its own treatment. Flushing is better prevented rather than treated, and its etiology investigated. Beta-blockers, atenolol in particular, are worthy of prophylactic trials examining their efficacy in treating the flushing associated with rosacea. Currently, clonidine is the only drug available for the treatment of flushing. Treatment for erythrosis includes topical and systemic therapies. Metronidazole 1% cream and azelaic acid 20% cream have been reported to reduce the severity score of erythema. The systemic treatment of erythrosis is based on the association of Helicobacter pylori with rosacea. However, this role is still being debated. Eradication of H. pylori can be achieved using a triple therapy regimen lasting 1 to 2 weeks [omeprazole and a combination of two antibacterials (a choice from clarithromycin, metronidazole or amoxicillin)]. Both the flashlamp-pumped long-pulse dye laser and the potassium-titanyl-phosphate laser may be used in the treatment of facial telangiectases. Both systemic and topical remedies may be used to treat the papulopustules of rosacea. Systemic treatment includes metronidazole, doxycycline, minocycline, clarithromycin and isotretinoin, while topical treatment is based on metronidazole cream and gel. The presence of Demodex folliculorum is important in the inflammatory reaction, whether it is pathogenetic or not. Crotamiton 10% cream or permethrin 5% cream may be useful medications for papulopustular rosacea, although they are rarely successful in eradicating D. folliculorum. Oral or topical ivermectin may also be useful in such cases. Ocular involvement is common in patients with cutaneous rosacea and can be treated with orally administered or topical antibacterials. Once rhinophyma starts to be evident, the only way to correct it is by aggressive dermatosurgical procedures. Decortication and various types of lasers can also be used. Associated conditions, such as seborrheic dermatitis and possible contact sensitizations, deserve attention.     

Randomized placebo-controlled trial of metronidazole 1% cream with sunscreen SPF 15 in treatment of rosacea

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.     

Use of permethrin in the treatment of rosacea fulminans during pregnancy: One case report

Rosacea fulminans (RF) is a rare dermatological condition which occurs exclusively in women and it is characterized by a sudden onset of painful papules, pustules, cysts, and nodules on the face. A 28‐year‐old woman was referred to our clinic due to a painful facial eruption within the 13th week of her second pregnancy. After physical examination, the diagnosis of RF during pregnancy was established. Several treatments were used: mupirocin ointment, topical zinc oxide, topical erythromycin, oral erythromycin, metronidazole gel, oral metronidazole, oral amoxiciline, and oral prednisone. Finally, the patient was started on 5% permethrin cream with complete clearing of the lesions. Nowadays, a wide range of treatments for rosacea is available: topical metronidazole, oral metronidazole, topical ivermectin, oral tetracyclines, oral isotretinoin, systemic steroids, photodynamic therapy, or pulsed dye laser. However, in pregnant patients, the treatment alternatives are limited. We consider that 5% permethrin cream could be an effective, cheap, and safe treatment not only in regular patients with rosacea but also in pregnant women, representing an important alternative in the context of pregnancy when therapeutic options are limited. To our knowledge, this is the first case of rosacea treated with 5% permethrin cream in monotherapy during pregnancy.     

A study into minocycline as a treatment for papulopustular rosacea

Papulopustular rosacea is a disease that causes redness and inflammtory lesions (patches) on the face. It is thought to affect about 16 million Americans and 34 million people worldwide. Rosacea may impact patients in different ways, such as itching, stinging, or embarrasment and self-consciousness, or it may impact leisure or social activites. Minocycline, as a pill, has been shown to be an effective treatment for the inflammatory lesions of rosacea. However, there may be side effects to using minocycline pills. This study evaluated the clearing of inflammatory lesions on the face of patients with rosacea after using a topical minocycline gel. The study was done at 26 clinics in the U.S.A. 270 people applied either 1% minocycline gel, or 3% minocycline gel, or just the vehicle gel (no medicine) to the face at bedtime for 12 weeks. Dermatologists were asked to count the number of inflammatory lesions on the face and the severity of disease before starting the study, and then throughout the 12 weeks of treatment. The authors found that the gels were generally safe and well tolerated. They also found that there was a greater reduction of inflammatory lesions in both the 1% and 3% minocycline groups compared to the vehicle gel group, and a higher percentage of people achieved clear or almost clear skin after 12 weeks of treatment for the 3% minocycline group. This indicates that a topical minocycline gel may be a safe and effective treatment for the inflamamtory lesions of papulopustular rosacea. Linked Article:   Webster et al. Br J Dermatol 2020; 183 :471–479 .     

Adapalene vs. metronidazole gel for the treatment of rosacea

BACKGROUND: Rosacea is a common, chronic dermatosis that requires long-term therapy. Oral isotretinoin and topical and/or oral antibiotics are effective, but their usage may be limited due to side-effects. OBJECTIVE: The goal of the study was to compare the efficacy of topical adapalene gel (0.1%) and topical metronidazole gel (0.75%) in the treatment of patients with papulopustular rosacea. METHODS: This study included 55 patients with papulopustular rosacea. Diagnostic efforts were focused on clinical and histological features. Patients were randomly assigned to the adapalene (n = 30) and metronidazole (n = 25) groups. Sunlight protection factor 20 cream was used to protect all patients from sunlight. The characteristics and numbers of inflammatory papules, pustules, erythema and telangiectasia were scored at baseline and after 2, 4, 8 and 12 weeks. Side-effects were recorded at each visit. RESULTS: Fifty patients, 27 in the adapalene group and 25 in the metronidzaole group, completed the study. Significant reductions in the total number of inflammatory lesions were found in the adapalene group compared with the metronidazole group. There was no significant difference in the scores of erythema and telangiectasia in the adapalene group. However, a significant reduction in erythema was seen in the metronidazole group. CONCLUSIONS: Adapalene gel is well tolerated and can be used as an alternative for topical treatment of papulopustular rosacea.     

Comparison of tazarotene and minocycline maintenance therapies in acne vulgaris: a multicenter, double-blind, randomized, parallel-group study

OBJECTIVE: To evaluate the efficacy of 3 maintenance regimens (topical tazarotene, oral minocycline hydrochloride, or both) in sustaining improvement in acne. DESIGN: Multicenter, open-label treatment phase followed by double-blind, randomized, parallel-group maintenance phase. SETTING: Ambulatory patients in research or referral centers. PATIENTS: Volunteer sample of 189 patients with moderately severe to severe acne vulgaris (110 entered maintenance phase, 90 completed, and 2 discontinued because of adverse events). INTERVENTIONS: All patients were treated with 0.1% tazarotene gel (each evening) and a 100-mg capsule (twice daily) of minocycline hydrochloride for up to 12 weeks. Patients with 75% or greater global improvement at week 12 were randomly assigned to 12 weeks of maintenance therapy with tazarotene gel plus placebo capsules, vehicle gel plus minocycline capsules, or tazarotene gel plus minocycline capsules. MAIN OUTCOME MEASURES: Overall disease severity, global improvement, and lesion counts. RESULTS: All regimens were effective in sustaining improvements in acne. After 12 weeks of maintenance therapy, the mean reductions from baseline in noninflammatory and inflammatory lesion count, respectively, were 60% and 54% with tazarotene, 52% and 66% with minocycline, and 64% and 66% with tazarotene plus minocycline. At week 24, more than 80% of patients in each group had maintained a 50% or greater global improvement from baseline, and more than 50% had maintained a 75% or greater global improvement. CONCLUSIONS: A high percentage of patients with moderately severe to severe acne can maintain improvement in their condition with topical retinoid monotherapy. Maintenance with combination tazarotene and minocycline therapy showed a trend for greater efficacy but no statistical significance vs tazarotene alone. Topical retinoid monotherapy should be considered for maintenance to help minimize antibiotic exposure.     

Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials

OBJECTIVE: To evaluate the clinical efficacy of topical 20% azelaic acid cream and 15% azelaic acid gel compared with their respective vehicles and metronidazole gel in the treatment of papulopustular rosacea. DATA SOURCES: Electronic searches of MEDLINE, EMBASE, BIOSIS, and SciSearch through July or August 2004 and the Cochrane Central Register of Controlled Trials through 2004 (issue 3). We performed hand searches of reference lists, conference proceedings, and clinical trial databases. Experts in rosacea and azelaic acid were contacted. STUDY SELECTION: Randomized controlled trials involving topical azelaic acid (cream or gel) for the treatment of rosacea compared with placebo or other topical treatments. Two authors independently examined the studies identified by the searches. Ten studies were identified, of which 5 were included (873 patients). DATA EXTRACTION: Two authors independently extracted data from the included studies, then jointly assessed methodological quality using a quality assessment scale. DATA SYNTHESIS: Because standard deviation data were not available for 4 of the 5 studies, a meta-analysis could not be conducted. Four of the 5 studies demonstrated significant decreases in mean inflammatory lesion count and erythema severity after treatment with azelaic acid compared with vehicle. None of the studies showed any significant decrease in telangiectasia severity. CONCLUSIONS: Azelaic acid in 20% cream and 15% gel formulations appears to be effective in the treatment of papulopustular rosacea, particularly in regard to decreases in mean inflammatory lesion count and erythema severity. Compared with metronidazole, azelaic acid appears to be an equally effective, if not better, treatment option.     

Comparative study of some treatment modalities of rosacea

Background   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.
Patients and methods   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.
Results   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.
Conclusion   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.     

A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: Azelaic acid 20% cream provides an effective and safe alternative to metro-nidazole 0.75% cream with the added benefit of increased patient satisfaction. (J Am Acad Dermatol 1999;40:961-5.)     

Azelaic Acid 15% Gel

Azelaic acid is a naturally occurring, straight-chain dicarboxylic acid which is effective in the treatment of rosacea, presumably on account of its anti-inflammatory properties. In randomized, double-blind, multicenter studies involving patients with moderate papulopustular facial rosacea, twice-daily topical application of azelaic acid 15% gel to the face was significantly more effective than twice-daily administration of either its vehicle (two studies) or metronidazole 0.75% gel (one study) in reducing inflammatory lesion counts and erythema severity. However, neither active treatment had a clinically discernable effect on telangiectasia. In all three studies, azelaic acid 15% gel recipients experienced continuous decreases in lesion counts and erythema throughout the 12- to 15-week treatment periods. However, the effects of metronidazole 0.75% gel plateauxed after 8 weeks. In other efficacy assessments in these studies, azelaic acid 15% gel was superior to its vehicle and metronidazole 0.75% gel in both the investigators' global assessment of rosacea and the investigators' end-of-study evaluation of overall improvement, and superior to its vehicle in the patients' end-of-study evaluation of overall improvement. The most frequent treatment-related cutaneous adverse events during administration of azelaic acid 15% gel include burning/stinging/tingling and pruritus (itching); however, these events are predominantly transient in nature and mild-to-moderate in intensity.     

Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review

Rosacea is a common chronic skin disease affecting the face. There are numerous treatment options, but it is unclear which are the most effective. The aim of this review was to assess the evidence for the efficacy and safety of treatments for rosacea. Searches included the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and Ongoing Trials Registers (updated February 2011). Randomized controlled trials in people with moderate to severe rosacea were included. Fifty-eight trials, including 27 from the original review, comprising 6633 participants were included in this updated review. Interventions included topical metronidazole, oral antibiotics, topical azelaic cream or gel, topical benzoyl peroxide and/or combined with topical antibiotics, sulphacetamide/sulphur, and others. There was some evidence that topical metronidazole and azelaic acid were more effective than placebo. Two trials indicated that doxycycline 40mg was more effective than placebo. There was no statistically significant difference in effectiveness between doxycycline 40mg and 100mg but there were fewer adverse effects. One study reported that ciclosporin ophthalmic emulsion was significantly more effective than artificial tears for treating ocular rosacea. 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 (40mg) in the treatment of moderate to severe rosacea, and ciclosporin 0·05% ophthalmic emulsion for ocular rosacea. Further well-designed, adequately powered randomized controlled trials are required.     

Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Perioral dermatitis

Perioral dermatitis is a relatively common inflammatory disorder of facial skin, often appearing in patients with rosacea, but with less inflammation. A typical perioral dermatitis presentation occurs with the eruption of papules and pustules confined to the nasolabial folds and the skin of the chin. Clinically, small pink papules and pustules may recur over weeks to months, sometimes with fine scales. The differential diagnosis includes seborrheic dermatitis, systemic lupus erythematosus, acne vulgaris, lupus miliaris disseminatus faciei, steroid-induced rosacea, and even basal cell carcinoma. The histopathology is similar to that found in rosacea. With advancement of the process, a perivascular and perifollicular lymphohistiocytic infiltrate develops. Sebaceous hyperplasia may be prominent in some patients. The most severe forms of disease show perifollicular noncaseating epithelioid granulomas. Treatment may include topical metronidazole as for rosacea (once or twice daily), azelaic acid cream, benzyl peroxide preparations, and to a lesser degree, topical erythromycin, clindamycin, or tetracycline. Oral tetracycline, doxycycline, or minocycline may also be helpful in presentations that are more resistant.     

Treatment of rosacea

A range of treatment options are available in rosacea, which include several topical (mainly metronidazole, azelaic acid, other antibiotics, sulfur, retinoids) and oral drugs (mainly tetracyclines, metronidazole, macrolides). In some cases, the first choice is a systemic therapy because patients may have sensitive skin and topical medications can be irritant. Isotretinoin can be used in resistant cases of rosacea. Unfortunately, the majority of studies on rosacea treatments are at high or unclear risk of bias. A recent Cochrane review found that only topical metronidazole, azelaic acid, and oral doxycycline (40 mg) had some evidence to support their effectiveness in moderate to severe rosacea and concluded that further well-designed, adequately-powered randomised controlled trials are required. In our practice, we evaluate our patients for the presence of two possible triggers, Helicobacter pylori infection and small intestinal bacterial overgrowth. When they are present we use adapted antibiotic protocols. If not, we use oral metronidazole or oral tetracycline to treat papulopustolar rosacea. We also look for Demodex folliculorum infestation. When Demodex concentration is higher than 5/cm(2) we use topical crotamiton 10% or metronidazole.     

The CLEAR trial: results of a large community-based study of metronidazole gel in rosacea

A phase 4, open-label, multicenter, community-based study was conducted in subjects with mild to moderately severe papulopustular rosacea of various etiologies and locations to identify subgroups particularly responsive to twice-daily application of metronidazole topical gel 0.75% to the affected areas of the face. A total of 582 subjects were randomized. Evaluations were conducted at baseline and at weeks 4, 8, and 12. At each evaluation, investigator global assessment (IGA) scores, mean papule and pustule counts, erythema scores, and telangiectasia scores improved significantly (P < .0001), with consistent results across sex and age subgroups. The mean erythema severity score decreased significantly (P < .0001) from baseline by week 4 and continued to decline at all study visits, with a nearly 50% reduction by week 12. At study end, subjects indicated a 25% improvement in itching, pain, soreness, or stinging; a 53% improvement in embarrassment or self-consciousness; and a 31% improvement in rosacea's effect on social or leisure activities. Metronidazole topical gel 0.75% was associated with a very low incidence of side effects in this trial, similar to previous clinical trials. The most common treatment-related adverse event (AE) reported in this study was mild application-site discomfort. The gel formulation was well-tolerated and effective in all subject subgroups and in a variety of climates. The findings of this study expand the collected data on the efficacy and safety of metronidazole topical gel 0.75% beyond that demonstrated in controlled clinical trials and confirm the utility of this therapy in the community setting.