Rosacea: an update

Rosacea is a common chronic cutaneous disorder of unknown etiology which occurs most commonly in middle-aged individuals. Cutaneous manifestations include transient or persistent facial erythema, telangiectasia, edema, papules and pustules that are usually confined to the central portion of the face. The National Rosacea Society's Expert Committee on the Classification and Staging of Rosacea identified four subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous and ocular. Recently, a standard grading system for assessing gradations of the severity of rosacea has been reported. Little is known about the cause of rosacea. Genetic, environmental, vascular, inflammatory factors and microorganisms such as Demodex folliculorum and Helicobacter pylori have been considered. Topical metronidazole and azelaic acid have been demonstrated to be effective treatments for rosacea. Severer or persistent cases may be treated with oral metronidazole, tetracyclines or isotretinoin.     

Systemic isotretinoin in the treatment of rosacea – doxycycline‐ and placebo‐controlled,randomized clinical study

Background: Systemic isotretinoin has been known for decades to be effective in the treatment of severe forms of rosacea, but it must be used off‐label because of the lack of evidence‐based data. Patients and Methods: 573 patients with rosacea subtype II and III received one of three different dosages of isotretinoin (0.1 mg, 0.3 mg, or 0.5 mg per kg body weight), doxycycline (100 mg daily for 14 days, then 50 mg daily) or placebo in a double‐blinded, randomized way for 12 weeks in 35 German centers. Results: Isotretinoin 0.3 mg/kg proved to be the most effective dose with significant superiority versus placebo. Isotretinoin 0.3 mg/kg showed also significant non‐inferiority versus doxycycline with reduction of lesions of 90 % compared to 83 % with doxycycline. Investigators diagnosed complete remission in 24 % and marked improvement in further 57 % of patients with isotretinoin treatment, in contrast to remission in 14 % and marked improvement in 55 % of patients treated with doxycycline. Isotretinoin 0.3 mg/kg revealed a similar safety profile as for the treatment of acne. Isotretinoin 0.5 mg/kg showed more dermatitis facialis as compared to 0.3 mg/kg. Conclusions: Isotretinoin 0.3 mg/kg is an effective and well‐tolerated therapy option for the treatment of rosacea subtype II and III and can therefore be used successfully as an alternative to therapy with oral antibiotics.     

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.     

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.     

Clinical evaluation of 30 patients with localized nasal rosacea

The clinical features of localized nasal rosacea have not been described in detail. This study was designed to analyze the subtypes and severity of localized nasal rosacea. Our present study included 30 patients with localized nasal rosacea. The erythematotelangiectatic subtype (13/30, 43.3%) was the most common type, followed by the phymatous subtype (9/30, 30%). The duration of rosacea was shorter and the severity of localized nasal rosacea was lower in the erythematotelangiectatic subtype cases compared with the patients with mixed or phymatous subtypes. Almost all of the papulopustular eruptions or phymatous lesions were associated with erythematotelangiectatic lesions. These findings suggest that the erythematotelangiectatic subtype may be considered the initial phase of localized nasal rosacea.     

Lupoide Rosazea als Sonderform der Rosazea

Lupoid or granulomatous rosacea is classified as a special form of rosacea which along with the typical rosacea symptoms features monomorphic yellow-brown and red papules and nodules on the cheeks and periorificial areas. Histology shows noncaseating epithelioid cell granulomas with surrounding mononuclear cell infiltrates. It is difficult to treat. Currently, the only officially approved systemic treatment is tetracycline. However, there is a broad experience with off-label use of isotretinoin (10-20 mg daily). We describe a patient with an excellent response to 20 mg isotretinoin daily.     

Roaccutan in acne and rosacea

Isotretinoin (Accutane) is a lately developed synthetic oral retinoid for treatment of severe forms of cystic acne resistant to therapy. Its pharmacological effect principally consists in decreased size of the sebaceous glands, reduced sebum production, as well as alteration of the bacterial micropopulation. At a dosage of 0.5 mg up to 1.0 mg/kg body weight daily, isotretinoin led to significant reduction of the inflammatory skin eruptions and long-lasting remission after discontinuation of the drug. With regard to 18 patients suffering from rosacea, the application of Accutane brought about satisfactory results, as well. Mucocutaneous side-effects were almost compulsory, but did never lead to discontinuation of the treatment. Because of its teratogenity, isotretinoin must not be applied in case of gravidity. Accutane offers new modes of therapy with respect to patients suffering from nodulocystic acne or severe rosacea which did not respond to common forms of treatment.     

Rosacea and rhinophyma

Rosacea is a common and chronic inflammatory cutaneous disease with unknown etiology. The pathophysiology of rosacea is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been detected yet. Recent molecular studies propose that an altered innate immune response is involved in the pathogenesis of the rosacea disease. Signs of rosacea are indicated by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. A wide range of drug options is available for the treatment of rosacea, including several topical ones (metronidazole, antibiotics, azelaic acid, benzoyl peroxide, sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines, metronidazole, macrolides, isotretinoin). This review highlights the recent clinical and pathophysiological developments concerning rosacea.     

Non-Acne Dermatologic Indications for Systemic Isotretinoin

Systemic isotretinoin has been used to treat severe acne vulgaris for 20 years. However, isotretinoin also represents a potentially useful choice of drugs in many dermatologic diseases other than acne vulgaris. Diseases such as psoriasis, pityriasis rubra pilaris, condylomata acuminata, skin cancers, rosacea, hidradenitis suppurativa, granuloma annulare, lupus erythematosus and lichen planus have been shown to respond to the immunomodulatory, anti-inflammatory and antitumor activities of the drug. Isotretinoin also helps prevent skin cancers such as basal cell carcinoma or squamous cell carcinoma. A combination of systemic isotretinoin and interferon-alpha-2a may provide a more potent effect than isotretinoin alone in the prevention and treatment of skin cancers.Systemic isotretinoin may be considered as an alternative drug in some dermatologic diseases unresponsive to conventional treatment modalities. However, randomized clinical trials aimed at determining the role of systemic isotretinoin therapy in dermatologic diseases other than acne vulgaris are required.     

中国玫瑰痤疮临床特征分析和诊断标准再探讨

【摘要】 目的 在分析玫瑰痤疮临床特征的基础上,提出中国玫瑰痤疮诊断标准并验证其敏感性和特异性。方法 纳入2017年12月至2018年7月于中南大学湘雅医院皮肤科门诊初诊的3 350例玫瑰痤疮患者,分析患者表型及临床特征,提出改良版中国玫瑰痤疮诊断标准。全国28个中心对该标准进行临床验证,纳入2 269例玫瑰痤疮和2 408例其他面部皮肤病患者,与2017版美国国家玫瑰痤疮专家委员会（NRSEC）制订的国际诊断标准比较,评估其敏感性和特异性。结果 3 350例玫瑰痤疮患者均存在面中部持续性红斑（100%）。在1 861例主要表现为面颊部红斑的患者中,1 850例（99.4%）在红斑之前或同时出现阵发性潮红;在1 489例主要表现为鼻或口周部红斑的患者中,仅52例（3.5%）发生阵发性潮红; 342例有肥大增生的患者均在肥大增生改变之前发生持续性红斑。基于以上临床特征提出,面颊部可周期性加重的伴有阵发性潮红的持续性红斑,可诊断为玫瑰痤疮;对于表现为鼻、口周部持续性红斑的患者,需合并至少1项选择性表型（阵发性潮红、毛细血管扩张、丘疹脓疱、肥大增生改变或眼部症状）才可诊断为玫瑰痤疮。全国多中心临床验证结果显示,改良版中国玫瑰痤疮诊断标准敏感性为99.6%,接近国际标准100%,特异性为91.9%,而国际标准为73.3%。结论 改良版中国玫瑰痤疮诊断标准具有良好的敏感性和特异性,也更有利于增生肥大型玫瑰痤疮的早期诊断。     

The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

Background Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4‐oxo‐isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half‐life. Objectives To determine if isotretinoin (13‐cis‐RA), its main metabolite 4‐oxo‐isotretinoin (4‐oxo‐13‐cis‐RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4‐oxo metabolite were determined. Patients/methods Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self‐administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4‐oxo‐isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse‐phase high‐performance liquid chromatography. Results Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4‐oxo metabolite or the all‐trans compounds was chromatographically detectable in any of the patients’ plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies. Conclusions The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long‐term isotretinoin treatment. After ceasing long‐term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.     

Aktuelles Verständnis der Pathophysiologie der Rosazea

Rosacea is a chronic inflammatory skin disease mainly affecting the face. Four major clinical subtypes of rosacea can be identified: erythemato-telangiectatic, papulopustular, phymatous and ocular rosacea. Still, it is currently unclear whether these subtypes develop consecutively or if any subtypes may occur individually as part of a syndrome. Rosacea is characterized by facial flushing, erythema, chronic inflammation, edema and fibrosis. Several trigger factors can worsen the disease or cause recurring episodes of inflammation. Although some aspects in the pathophysiology of rosacea have been characterized in more detail during the past years, the precise interplay of the various dysregulated systems is still poorly understood. In early disease manifestations and milder stages, dysfunction of neurovascular regulation and the innate immune system seem to be driving forces in rosacea pathophysiology. A disturbed chemokine and cytokine network further contributes to disease progression. This current review highlights some of the recent findings in rosacea pathophysiology and points out novel targets for therapeutic intervention.     

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.     

Swiss S1 guideline for the treatment of rosacea

Rosacea (in German sometimes called ‘Kupferfinne’, in French ‘Couperose’ and in Italian ‘Copparosa’) is a chronic and frequently relapsing inflammatory skin disease primarily affecting the central areas of the face. Its geographic prevalence varies from 1% to 22%. The differential diagnosis is wide, and the treatment is sometimes difficult and varies by stage of rosacea. For erythematous lesions and telangiectasia, intense pulsed light (IPL) therapy and lasers are popular treatment option. In addition, a vasoconstrictor agent, brimonidine, has recently been developed. For papulopustular rosacea, topical antibiotics, topical and systemic retinoids, as well as systemic antibiotics are used. A topical acaricidal agent, ivermectin, has undergone clinical development and is now on the market. In the later stages, hyperplasia of the sebaceous glands develops, resulting in phymatous growths such as the frequently observed bulbous nose or rhinophyma. Ablative laser treatments have largely replaced classical abrasive tools. Here, we reviewed the current evidence on the treatment of rosacea, provide a guideline (S1 level) and discuss the differential diagnosis of rosacea.     

Treatment of Rosacea with Isotretinoin

A multicenter trial of isotretinoin in severe papulopustular rosacea in adult patients was undertaken to evaluate the efficacy and safety of this treatment. A 20-week course of therapy was instituted in 92 patients from 11 dermatology departments. At the end of the study period, isotretinoin was found to be highly effective in the clearing of refractory rosacea lesions.     

Current topical and systemic approaches to treatment of rosacea

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline. Conventionally, 100–200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

Conflicts of interest

None declared.     

Isotretinoin treatment of rosacea

Twenty patients with severe rosacea were treated with isotretinoin for 3-6 months. Six patients initially received 1.0 mg/kg and 14 patients 0.5 mg/kg of isotretinoin. The response was good or excellent in all patients and the papulopustular lesions in particular cleared promptly. Patients receiving 1.0 mg/kg of isotretinoin experienced more side-effects and the dose had to be lowered in five of the six patients. Seventeen of the 20 patients had no relapses during a follow-up of one year showing that isotretinoin has a long-lasting favourable effect in rosacea.     

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.     

强脉冲光治疗酒渣鼻疗效评价

目的:评价强脉冲光治疗酒渣鼻的疗效。方法:治疗组采用强脉冲光照射,每3周1次,4次为1疗程;对照组口服异维A酸10 mg,日2次,连续12周。结果:治疗组总有效率为89.74%,对照组为71.05%,差异有统计学意义(P0.05)。结论:强脉冲光治疗酒渣鼻疗效优于异维A酸。     

Rosacea. Clinical features, pathogenesis and therapy

Rosacea is a common facial dermatosis, which may have detrimental effects on the patient's psychological and social interactions. It is a disease of the middle aged, skin types I and II are more often affected than darker skin types. Clinically, pre-rosacea, and rosacea grade I-III may be distinguished. Pre-rosacea is characterized by flushing and blushing, grade I to III by erythemato-teleangiectasies, papulopustules, and inflammatory nodules. Especially severe subtypes include rosacea conglobata and rosacea fulminans. Hyperglandular subtypes lead to different forms of phyma, of which Rhinophyma is the most frequent. Pathogenetically destruction of the dermal vessels and connective tissue seems to be decisive for the development of a chronic inflammation, which leads to the phenotype of the various forms of rosacea. Mild forms can be treated exclusively by topical medication. Antibiotics (erythromycin, clindamycin, tetracyclin), metronidazol, azelaic acid, and the retinoid adapalene have been shown to be effective in well controlled randomized studies. The best evaluated topical medication is metronidazol. In severe forms systemic therapy must be applied. Systemic antibiotics are effective and especially isotretinoin has shown a very good response even in low dose regimens. Rhinophyma must be treated surgically.