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.     

酒渣鼻的激光和光动力疗法

酒渣鼻是一种常见的慢性炎症性皮肤疾病,其临床特点为面部红斑伴丘疹脓疱或毛细血管扩张,病情发展晚期可有鼻赘形成.酒渣鼻分为4种亚型,针对不同亚型临床特点可采用相应的激光和光化学疗法,主要包括脉冲染料激光、强脉冲光疗法、光动力疗法及二氧化碳激光磨削.概述上述疗法在酒渣鼻治疗中的机制,疗效和不良反应发生.

Abstract：

Rosacea is a common chronic inflammatory disease of the skin.It is characterized by erythematous changes of the facial skin accompanied by papules,pustules or telangiectasias,and eventually,it may progress into rhinophyma.Rosacea can be categorized into four subtypes.To get a satisfactory outcome,appropriate lasers and photochemotherapies should be selected from pulsed dye laser,intense pulsed laser,photodynamic therapy and carbon dioxide laser according to the subtype of rosacea.This review states the mechanisms,efficacy,side effects as well as targeting subtypes of these phototherapies for rosacea.     

Rosacea: I. Etiology, pathogenesis, and subtype classification

Rosacea is one of the most common conditions dermatologists treat. Rosacea is most often characterized by transient or persistent central facial erythema, visible blood vessels, and often papules and pustules. Based on patterns of physical findings, rosacea can be classified into 4 broad subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. The cause of rosacea remains somewhat of a mystery. Several hypotheses have been documented in the literature and include potential roles for vascular abnormalities, dermal matrix degeneration, environmental factors, and microorganisms such as Demodex folliculorum and Helicobacter pylori. This article reviews the current literature on rosacea with emphasis placed on the new classification system and the main pathogenic theories. Learning objective At the conclusion of this learning activity, participants should be acquainted with rosacea's defining characteristics, the new subtype classification system, and the main theories on pathogenesis.     

Clinical, cellular, and molecular aspects in the pathophysiology of rosacea

Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a "developmental march" of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating "human disease model" for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology.     

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.     

玫瑰痤疮药物治疗进展

玫瑰痤疮是一种常见的慢性炎症性皮肤病,根据临床表现不同可分为红斑毛细血管扩张型、丘疹脓疱型、肥大型和眼型.美国国家玫瑰痤疮协会的诊疗指南认为,玫瑰痤疮应按照不同亚型给予相应的治疗.治疗方法包括一般护理、药物、激光、手术等.目前针对红斑毛细血管扩张型的α肾上腺素能受体激动剂、β受体阻滞剂、肉毒素A及针对丘疹脓疱型的亚抗生素剂量多西环素、伊维菌素等的出现,为治疗玫瑰痤疮提供了可能.由于酒石酸溴莫尼定、亚抗生素剂量多西环素、伊维菌素的使用时间较短,其安全性及功效性尚需更多的临床研究证据.     

Rosacea,not just skin deep: Understanding thesystemic disease burden

Rosacea is a common inflammatory skin condition with four main clinical subtypes: erythematotelangiectatic, papulopustular, rhinophymatous, and ocular. Although several genetic and environmental factors have been linked with triggering rosacea, the pathogenesis still remains poorly understood. There is an increasing evidence in the literature to support that rosacea is a harbinger of several systemic comorbidities and may represent a chronic, systemic, inflammatory state. We have provided the most up-to-date evidence on the association between rosacea and several systemic diseases, discussing that rosacea is not just a skin disorder but a systemic disease process.     

Prognosis of 234 rosacea patients according to clinical subtype: The significance of central facial erythema in the prognosis of rosacea

Rosacea has a wide spectrum of clinical features, which include persistent facial redness, flushing, telangiectasia, inflammatory papules/pustules, hypertrophy and/or ocular features. The prognosis of rosacea according to clinical subtype has not been evaluated. We analyzed the prognosis of rosacea in 234 patients, which included 120 patients with mixed subtype, 75 with the erythematotelangiectatic rosacea subtype and 39 with the papulopustular rosacea (PPR) subtype. The prognosis of rosacea was classified as: (i) no improvement; (ii) partial remission; and (iii) complete remission. The frequencies of complete remission, time to complete remission and 1‐year complete remission rate were compared between subtypes. Follow‐up periods ranged 2–72 months (median follow‐up, 17.5). Aggravation of the disease was found in 50.4% of patients during follow up. Partial or complete remission was noted in 61.5% and 20.9% of patients, respectively. The median time to complete remission was 56.0 months. The prognosis of disease was more favorable for patients with the PPR subtype than for patients with other subtypes with respect to the frequency of complete remission, median time to complete remission and the 2‐year complete remission rate. In conclusion, papulopustular rosacea without remarkable centrofacial erythema showed a more favorable prognosis than other subtypes. Erythematotelangiectatic lesions in rosacea patients present a challenge for the treatment of rosacea.     

Rosacea under the microscope: characteristic histological findings

Rosacea is a common facial dermatosis that is seldom biopsied; thus, histological aspects have not been well described. Biopsies are generally performed in the presence of atypical symptoms (e.g. granulomas). Differential diagnosis with sarcoidosis, lupus miliaris or lupus erythematosus is another indication for biopsy. There are few published studies addressing the microscopic aspects of rosacea and describing the histological and immunohistochemical features of this disease. While some textbooks consider the microscopic signs of rosacea to be non‐diagnostic, experienced dermatopathologists are generally able to make the diagnosis via histology. This article discusses the specific combinations of histological features that are highly suggestive of rosacea.     

Ocular rosacea and treatment of symptomatic Helicobacter pylori infection: a case series

Rosacea is a chronic inflammatory skin disease characterized by recurrent episodes of facial flushing, erythema, papules, pustules, and telangiectasia. More than half of all rosacea patients may have ocular symptoms. Rosacea is associated with certain digestive diseases, such as gastritis, hypochlorhydria, or a number of jejunal mucosal abnormalities, and many patients have Helicobacter pylori infection. The role of Helicobacter pylori has often been a subject of investigation; these studies show conflicting results. Here we present results of the effects of treatment given for H. pylori eradication in seven patients with ocular rosacea that, at the same time, had clinical and serological evidence of H. pylori infection. Six weeks after completion of the treatment, all patients experienced improvement of their rosacea symptoms. Ocular disease responded better than cutaneous rosacea.     

Etiopathogenesis, classification, and current trends in treatment of rosacea

Rosacea is a common chronic dermatosis characterized by varying degrees of flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and phymas. Etiology and pathogenesis of rosacea are still unknown. Many possible causes have been described as inducing the disease or contributing to its manifestation, such as genetic predisposition, abnormal vascular reactivity, changes in vascular mediating mechanisms, Helicobacter pylori infection, Demodex folliculorum infestation, seborrhea, sunlight, hypertension, and psychogenic factors. However, none of these factors has been proved. Rosacea shows a wide spectrum of clinical presentations, which vary over time and with age. Successful management of rosacea requires careful patient evaluation and individualized therapy with appropriate variations and modifications, as the severity of the disorder fluctuates. In mild cases of rosacea, patients are instructed to avoid sun, to apply sun-protective creams, and to avoid facial irritants and other triggers that provoke symptoms. At later stage, drug therapy is often necessary. The disease commonly requires long-term treatment with topical or oral medicaments. Surgical correction may be required for rhinophyma and telangiectasia. We reviewed the current literature on the aspects of the pathogenesis, diagnostic criteria, and treatment options for rosacea.     

Neurovascular and neuroimmune aspects in the pathophysiology of rosacea

Rosacea is a common skin disease with a high impact on quality of life. Characterized by erythema, edema, burning pain, immune infiltration, and facial skin fibrosis, rosacea has all the characteristics of neurogenic inflammation, a condition induced by sensory nerves via antidromically released neuromediators. To investigate the hypothesis of a central role of neural interactions in the pathophysiology, we analyzed molecular and morphological characteristics in the different subtypes of rosacea by immunohistochemistry, double immunofluorescence, morphometry, real-time PCR, and gene array analysis, and compared the findings with those for lupus erythematosus or healthy skin. Our results showed significantly dilated blood and lymphatic vessels. Signs of angiogenesis were only evident in phymatous rosacea. The number of mast cells and fibroblasts was increased in rosacea, already in subtypes in which fibrosis is not clinically apparent, indicating early activation. Sensory nerves were closely associated with blood vessels and mast cells, and were increased in erythematous rosacea. Gene array studies and qRT-PCR confirmed upregulation of genes involved in vasoregulation and neurogenic inflammation. Thus, dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea. Drugs that function on neurovascular and/or neuroimmune communication may be beneficial for the treatment of rosacea.     

Rosacea and rhinophyma in the elderly

Rosacea is a chronic inflammatory disease with a predominance of facial manifestations. The prevalence is increasing with age, peaking in the group aged older than 65 years. In 1997, one in eight Americans was aged 65 years and older. By 2030, more than 70 million individuals will be in this age group. This contribution reviews the current understanding of pathogenesis, aggravating factors, classification, comorbidities, and treatment options. Rosacea is a manageable disease that negatively affects quality of life. Rosacea increases the risk of depression and shows a significant proportion of extracutaneous manifestations, in particular ocular rosacea.     

Klinik und Klassifikation der Rosazea

Rosacea is a frequent chronic dermatological disorder mainly affecting the face. Since it affects the appearance, it can be very distressing for the patient leading to psychosocial disturbances. Rosacea occurs in adults, peaking between 40 and 50 years of age. The course of rosacea is quite variable and the disease may stop at any stage. Generally, three main stages are differentiated: erythemato-teleangiectatic rosacea (rosacea stage I), papulopustular rosacea (rosacea stage II), hyperglandular-hypertrophic rosacea (rosacea stage III). Besides these main manifestations numerous special forms exist, which often lead to difficulties in the differential diagnoses and require specific therapeutic strategies. These include rosacea conglobata, rosacea fulminans, granulomatous rosacea, persisting edema, (Morbihan disease), gram negative rosacea, ocular rosacea, and steroid rosacea. Recently increasing numbers of patients have been observed, whose rosacea was were induced by inhibitors of epidermal growth factors (cetuximab, geftinib) used as chemotherapy in patients with different malignancies. These side effects have been described as acneiform eruptions but at least some of the described patients have a rosacea-like appearance; therefore, this form can be classified as a subset of drug induced 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.     

Critical review of the manner in which the efficacy of therapies for rosacea are evaluated

BACKGROUND: Rosacea is a relatively common disorder that may affect individuals of all races, particularly those of northern European decent. Its onset generally occurs in individuals between the ages of 20 and 50 years. Rosacea may be classified into four subtypes and one variant. Although individuals with rosacea may not pass through all of the stages, the primary features of the disorder include frequent flushing and blushing, nontransient erythema, the presence of papules and pustules, and telangiectasia. Many agents have been used to treat rosacea stigmata, especially because none of these is uniformly effective. AIM: To identify the parameters that are used to evaluate the response to therapy when different agents are used to treat rosacea. For a given parameter, to determine whether the different trials are consistent in the manner in which this variable is measured. METHODS: The reports on the efficacy and safety of the different drug therapies used to treat rosacea were identified. We searched MEDLINE (1966 to June 2002) for studies where rosacea was treated. The parameters used to evaluate the efficacy of therapy were determined. For each parameter, the ways in which it has been measured were identified. RESULTS: Efficacy of treatment is generally judged by evaluating the effect of the intervention on papules and pustules, erythema, and telangiectasia. Manual lesional counts of papules and pustules are usually performed. There is, however, substantial variation in the methodology chosen for comparison of erythema and telangiectasias. Color scales are popular for erythema and telangiectasia, while grading scales are most commonly used for physician and patient evaluations. CONCLUSIONS: For each of the parameters that are commonly used to measure the efficacy of treatments for rosacea, the different approaches by which it has been measured in the various trials have been highlighted; these dissimilarities can make it problematic to compare between clinical trials. A greater degree of uniformity in the manner in which the various parameters are evaluated would enable a more objective comparison between the studies.     

Photodynamic therapy in a series of rosacea patients

BACKGROUND: Rosacea is a common disease that often has a chronic intermittent course despite current treatment; therefore, additional treatment options are desirable. The pathogenesis of the disease is unknown. OBJECTIVES: We have previously suggested that photodynamic therapy (MAL-PDT) may be of benefit as rosacea therapy. The purpose of this study was to further assess the possible benefit of this treatment of rosacea. METHODS: An exploratory review of case notes from rosacea patients treated with PDT was performed. Patients referred to our department with rosacea were offered PDT if requesting an alternative to previously tried conventional therapy. Routine MAL-PDT with methylaminolevulate and red light was given one to four times; results were evaluated 1-2 months after PTD was initiated and subsequently followed up. RESULTS: Good results were seen in 10 out of 17 patients, and fair results in another 4 patients. The majority of patients treated could stop or significantly reduce other rosacea therapy for a period lasting from about 3 months and up to 2 years. The study is limited by strong selection bias, and the clinical evaluation was obtained from case notes and photos. CONCLUSIONS: An apparent effect of MAL-PDT on rosacea could be observed. This is in accordance with our previous experience, and observations made by other researchers. A future randomized controlled trial therefore seems justifiable.     

Epidemiology of rosacea: updated data

The epidemiological data on rosacea remain fragmentary and the methodological quality debatable. Rosacea affects mainly adults around the age of 30 years and classically predominates in females. Recent Estonian and Irish studies suggest that the female predominance may not be as high as previously believed. However, prevalence does increase with age. The prevalence statistics published in Europe and the United States are highly variable, ranging from less than 1% to more than 20% of the adult population; actually, the methods used and the populations studied vary greatly from one study to another; consequently, they cannot be compared. A family history of the disease is a risk factor, as is the very light skin phototype (Celtic skin type). Alcohol and coffee, classically blamed, are not risk factors; however, tobacco may have a protective effect. New studies are undoubtedly necessary: they should use the diagnostic and severity criteria established in 2002 and 2004. Rosacea has a strong impact on quality of life and can be associated with depressive symptoms. A specific quality-of-life scale, the RosaQol, has been established and validated in the United States, by the same group that elaborated the Skindex scale. Translations of this scale into French, Italian, German, and Spanish have been validated, which may allow future intercultural comparisons.     

Epidemiological and clinical features of rosacea in Korea: A multicenter cross‐sectional study

Rosacea is a common chronic inflammatory skin condition. Although several epidemiological and etiologic studies with large sample sizes have been conducted on Caucasians, such data regarding Asian populations are lacking. A total of 580 patients diagnosed with rosacea were enrolled from October 2014 to February 2015 at 14 general hospitals. Questionnaires, including the standard classification and grading system, were used for evaluation. The average age of the patients was 47.9 years. While 83.8% of patients revealed a single subtype, 16.2% of patients revealed mixed subtypes showing two or more subtypes simultaneously. Erythematotelangiectatic rosacea (ETR) was the most prevalent subtype. ETR combined with papulopustular rosacea showed the highest proportion in the mixed subtype group. Mild severity was revealed in 71.9% of patients. The most common aggravating factor was emotional changes (51.7%), followed by stress (48.4%). Approximately half of the patients (47.4%) showed relatively low awareness of rosacea. By identifying the epidemiological and etiologic features in Korea, we can suggest valuable clinical avenues for research, education and awareness among rosacea patients.     

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.