小剂量强力霉素联合甲硝唑凝胶治疗酒渣鼻疗效观察

目的观察小剂量强力霉素联合甲硝唑凝胶治疗酒渣鼻的临床疗效和安全性。方法将入选的90例酒渣鼻患者随机分成3组,各30例,治疗组口服强力霉素20mg,同时外搽0.75%甲硝唑凝胶,均2次/d;对照1组仅口服强力霉素,对照2组仅外用0.75%甲硝唑凝胶,用法同治疗组,均4周为1个疗程,共治疗3个疗程。每个疗程结束后分别观察疗效。结果治疗组有效率(96.55%)明显优于对照1组(75.00%)和对照2组(76.67%),差异均有统计学意义(P均<0.05),而对照1组有效率和对照2组比较差异无统计学意义(P>0.05)。治疗组不良反应发生率为10.34%、对照2组为13.33%,该两组均表现为用药局部皮肤轻度干燥,对照1组未见不良反应。结论小剂量强力霉素联合甲硝唑凝胶外搽治疗酒渣鼻疗效肯定,安全性好。     

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 Role of Tetracyclines in Rosacea

There is a great deal of evidence to support the use of tetracycline and doxycycline in the treatment of papulopustular rosacea. Nevertheless, these agents have shared and unique adverse effects and relative contraindications. Recently, subantimicrobial-dose doxycycline was demonstrated to be an effective treatment for rosacea, due to its inherent anti-inflammatory properties. Furthermore, subantimicrobial-dose doxycycline has a more preferable tolerability profile and a lower occurrence of bacterial resistance than traditional-dose doxycycline. To further elucidate the role of tetracycline agents in rosacea, clinical trials that compare these agents with each other as well as with other effective rosacea treatments are called for. Adherence studies comparing oral tetracycline treatment with topical metronidazole treatment may also enhance clinical decision making.     

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.     

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.     

Doxycycline 40 mg Capsules (30 mg Immediate-Release/10 mg Delayed-Release Beads)

Anti-inflammatory dose doxycycline 40 mg capsules (30 mg immediate-release and 10 mg delayed-release beads) provide a sub-antimicrobial dose that reduces the inflammatory response in patients with rosacea without producing drug concentrations required to treat bacterial diseases. The efficacy of oral, anti-inflammatory dose doxycycline 40 mg capsules once daily in the treatment of adults with rosacea was demonstrated in two pivotal large, randomized, double-blind, placebo-controlled, multicenter trials. After 16 weeks’ therapy, anti-inflammatory dose doxycycline 40 mg was significantly more effective in improving rosacea than placebo, providing a greater reduction in the total inflammatory lesion count (primary endpoint) than placebo. Anti-inflammatory dose doxycycline 40 mg was associated with a rapid onset of action, achieving a significantly greater decrease in total inflammatory lesion count than placebo by the first follow-up visit at week 3 in both studies. Maximum anti-inflammatory efficacy appears to be achieved with doxycycline 40 mg capsules once daily, as no additional improvement in rosacea symptoms was achieved with oral doxycycline 100 mg once daily (usual antibacterial dosage) in a small, randomized, double-blind trial. Anti-inflammatory dose doxycycline 40 mg was generally well tolerated in clinical trials, with most adverse events being of mild to moderate intensity.     

Interventions for rosacea: abridged updated Cochrane systematic review including GRADE assessments

Rosacea is a common chronic facial dermatosis. This update of our Cochrane review on interventions for rosacea summarizes the evidence, including Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group assessments, of the effects of the currently available treatments. Searches included the following: Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, EMBASE, LILACS and the Science Citation Index, and ongoing trials registries (July 2014). We included 106 randomized controlled trials (RCTs) with 13 631 participants, a more than 80% increase since the last update in 2011. Pooling of data was feasible for a few outcomes, for topical metronidazole and azelaic acid and both appeared to be more effective than placebo (moderate and high‐quality evidence, respectively). Topical ivermectin was more effective than placebo based on two studies (high‐quality evidence), and slightly more effective than metronidazole in one study. Brimonidine was more effective than vehicle in reducing erythema in rosacea (high‐quality evidence). Ciclosporin ophthalmic emulsion was effective for ocular rosacea (low‐quality evidence). For oral treatments there was moderate‐quality evidence for the effectiveness of tetracycline based on two old studies, and high‐quality evidence for doxycycline 40 mg compared with placebo according to physician assessments. One study at high risk of bias demonstrated equivalent effectiveness for azithromycin and doxycycline 100 mg. Minocycline 45 mg may be effective for papulopustular rosacea (low‐quality evidence). Low‐dose isotretinoin appeared to be slightly more effective than doxycycline 50–100 mg (high‐quality evidence). Laser and light‐based therapies for erythema in rosacea were effective (low‐quality evidence). Further RCTs are required for ocular rosacea.     

Pathogenese,Klinik und aktuelle Therapie der Rosazea

Rosacea is a common chronic inflammatory disease, especially in patients with fair skin and positive family history. Typical locations are forehead, nose, cheeks and chin; the periorbital region is usually not involved. Clinical features can be very heterogeneous. Besides different subtypes (erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea), which often overlap, various special forms of rosacea exist. Up to 60?% of patients with cutaneous rosacea suffer from ocular rosacea. In Germany, brimonidine, metronidazol, azelaic acid, and ivermectin are approved for topical therapy of rosacea; for systemic therapy, doxycycline at a subantimicrobial dose (40 mg/day) is the only approved substance. In case of resistance to this therapy, contraindications or side effects, various alternative therapies are available, however off-label.     

Interventions for rosacea based on the phenotype approach: an updated systematic review including GRADE assessments

Rosacea is a common, chronic skin condition causing flushing, redness, red pimples and pus-filled spots (pustules) on the face. It affects about 1-20% of people worldwide. Rosacea can also cause inflammation of the eyes/eyelids (ocular rosacea) and thickening of the skin, especially the nose (rhinophyma). Although the cause of rosacea is unclear, treatments are available for this distressing disease. This review from the Netherlands, U.K. and Canada aimed to find out which treatments are effective for rosacea. The authors included data from 152 studies. For reducing redness, brimonidine and oxymetazoline worked from three up to 12 hours after being applied. For reducing pimples and pustules with topical (applied to the skin) treatments, azelaic acid, ivermectin and metronidazole were effective and safe. Ivermectin was slightly more effective than metronidazole. Minocycline foam also showed a large reduction in pimples and pustules. With oral (taken by mouth) antibiotics, tetracycline, doxycycline 40 mg or minocycline 45 mg reduced the number of pimples and pustules. Doxycycline 40 mg was likely as effective as 100 mg, with fewer side effects like diarrhoea and nausea. Oral minocycline 100 mg was as effective as doxycycline 40 mg. Azithromycin may be as effective as 100 mg doxycycline. Isotretinoin 0.25 mg/kg decreased pimples and pustules by 90%, and increased quality of life and patients’ satisfaction. Isotretinoin 0.3 mg/kg appeared to be slightly more effective than 50-100 mg doxycycline. However, isotretinoin is known to cause serious birth defects, so pregnancy must be avoided when using it. For treating dilated blood vessels, laser therapy and intense pulsed light therapy were both effective, but these studies had limited data. In ocular rosacea, ciclosporin 0.05% ophthalmic emulsion increased quality of life and improved the amount/quality of tears, and was slightly more effective than oral doxycycline. Omega-3 fatty acids likely improve dry eyes and tear gland function.     

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.     

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.     

Systemische Therapie der Rosazea

The only medication which is authorized for therapy of rosacea is doxycycline. It is usually administered at a dose of 40–100 mg daily for 3–6 months. In case of a lack of efficacy or in case of contraindications (e.g. pregnancy, children below 8 years), azithromycin or metronidazole are alternative systemic therapies. Those forms of rosacea which involve hyperplasia of sebaceous glands respond well to retinoids such as isotretinoin. Dapsone has been successfully used for the treatment of granulomatous rosacea and rosacea fulminans. Erythema can be reduced by use of beta blockers. If patients do not respond to various therapies or if they are immunocompromised, the differential diagnosis of demodicosis should be considered; here the treatment is oral ivermectin. Some forms of rosacea (rosacea fulminans and granulomatous rosacea) may be treated initially with oral corticosteroids. Ophthalmic rosacea is treated topically as well as with tetracyclines or macrolides.     

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.     

Rosazea 2009

Rosacea is one of the most common dermatoses of adults. In recent years many studies have contributed to a better understanding of the pathophysiology of rosacea. They suggest that an altered innate immune response is involved in the vascular and inflammatory manifestations seen in rosacea. A good understanding of the disease and its special features is necessary for the differential diagnosis of the many clinical subtypes and for a stage- and phase-specific treatment approach. Topical treatments that are widely accepted are metronidazole and azelaic acid; agents under investigation that show promise include permethrin, calcineurin inhibitors and sulfur compounds. For systemic therapy antibiotics (tetracyclines, macrolides) and recently doxycycline in anti-inflammatory rather than anti-microbial dosages are used, as well as isotretinoin in severe cases. Findings such as rhinophyma and telangiectases can be treated using different laser systems or dermabrasion. This article gives an overview regarding rosacea, a challenging condition with multiple therapeutic options.     

TREATMENT OF ROSACEA: TOPICAL CLINDAMYCIN VERSUS ORAL TETRACYCLINE

Background. 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. Methods. 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. Results. Topical clindamycin treatment produced similar clinical results to oral tetracycline and was superior in the eradication of pustules. Conclusions. 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.     

Topical metronidazole for severe and recalcitrant rosacea: a prospective open trial

Nineteen patients with severe or recalcitrant rosacea were treated twice daily with 0.75 percent metronidazole topical gel in an open label study. Sixteen of the patients (84 percent) showed 50 percent or greater reduction in inflammatory lesions, while fifteen (79 percent) demonstrated a reduction in erythema severity and an improvement when evaluated by the investigator global assessment. No positive response was recorded for any patient prior to topical medication, whereas six of nine patients previously treated with tetracycline/minocycline demonstrated improvement. Seven of these nine patients responded to topical metronidazole treatment. One additional patient who did not respond to minocycline or desonide treatment showed a good response to topical metronidazole. Only one patient reported local irritation after using metronidazole. These results demonstrate that topical metronidazole gel is safe and effective for the treatment of severe or recalcitrant rosacea.     

Topical Metronidazole

Conclusions

Topical metronidazole formulations are significantly more effective than placebo when used in the initial treatment of patients with moderate to severe rosacea. Furthermore, limited evidence suggests that the use of topical metronidazole alone may be as effective as oral tetracyclines against the disorder’s inflammatory component. Therefore, for those patients with a preference for topical rather than oral therapy, the use of a topical metronidazole formulation must be a consideration.     

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.     

Topische Therapie der Rosazea

Metronidazole and azelaic acid are the only topical medications approved for rosacea. All other topical treatments for rosacea and its special forms are used off-label. Topical steroids are not indicated in rosacea, because of their side effects (induction of steroid rosacea, high risk of facial skin atrophy, and high risk of rebound after cessation of therapy). Topical as well as systemic steroids are allowed only as initial and short term therapy for acute forms of rosacea (e.g. rosacea fulminans). Papular and pustular rosacea is the major indication for topical therapy. Sebaceous gland and connective tissue hyperplasia in glandular-hypertrophic rosacea as well as erythema in erythematous rosacea do not respond well to topical measures. A new active substance, the alpha-2-adrenoreceptor agonist brimonidine, will be approved soon for the topical treatment of erythema in rosacea. All severe forms of rosacea should initially be treated with a combination of topical and systemic agents. After improvement of the clinical symptoms, topical treatment alone is usually adequate to maintain the control.     

Topical metronidazole does not abate UVB-induced erythema

BACKGROUND: The capacity of topical metronidazole to reduce erythema severity scores in rosacea has been attributed to its anti-inflammatory activity. METHODS: Nine healthy subjects were irradiated on three 1-cm(2) areas on their volar forearm with 2 MEDs of UVB. Twenty-four hours later, one of the irradiated areas was treated daily with metronidazole 1% vanishing cream, one with the vehicle only and the third was left untreated (control). The intensity of erythema was measured, at 24, 48, 72 and 96 h after irradiation, by a Chromameter CR200 (Minolta, Japan) and expressed in the L*a*b* system. The a* parameter was taken as the measure of redness. RESULTS: Overall, redness diminished over time in a linear way, but treatments did not influence it significantly. CONCLUSION: In our vehicle, metronidazole 1% cream failed to abate the UVB-induced erythema. An activity other than the anti-inflammatory one should be suggested to explain the topical metronidazole efficacy in rosacea.