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.     

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.     

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.     

A study on the epidemiology of rosacea in the U.K

Background Rosacea is a chronic facial skin disease of unclear origin. Epidemiological data are scarce and controversial, with reported prevalences ranging from 0·09% to 22%. To our knowledge, incidence rates have not been quantified before. Objectives In this observational study we quantified incidence rates of diagnosed rosacea in the U.K. and described demographic characteristics and the prevalence of ocular symptoms in patients with rosacea. We compared lifestyle factors such as smoking and alcohol consumption between patients with rosacea and controls. Methods Using the U.K.‐based General Practice Research Database, we identified patients with an incident diagnosis of rosacea between 1995 and 2009 and matched them (1 : 1) to rosacea‐free control patients. We assessed person‐time of all patients at risk and assessed incidence rates of rosacea, stratified by age, sex, year of diagnosis and region. Results We identified 60 042 rosacea cases and 60 042 controls (61·5% women). The overall incidence rate for diagnosed rosacea in the U.K. was 1·65 per 1000 person‐years. Rosacea was diagnosed in some 80% of cases after the age of 30 years. Ocular symptoms were recorded in 20·8% of cases at the index date. We observed a significantly reduced relative risk of developing rosacea among current smokers (odds ratio 0·64, 95% confidence interval 0·62–0·67). Alcohol consumption was associated with a marginal risk increase. Conclusions We quantified incidence rates and characteristics of patients with rosacea diagnosed in clinical practice in a large epidemiological study using primary care data from the U.K. Smoking was associated with a substantially reduced risk of developing rosacea.     

Childhood ocular rosacea: Considerations for diagnosis and treatment

Rosacea in children is not as well described as it is in adults. Ocular signs may be a dominant feature and some children with what has previously been called periorificial dermatitis may in fact have rosacea. We report three cases of paediatric ocular rosacea responding to prolonged treatment with oral erythromycin. Our cases demonstrate the close association of periorificial dermatitis with childhood rosacea, and highlight the importance of eye signs in its diagnostic criteria.     

Rosacea and Use of Continuous Positive Airway Pressure Mask for Obstructive Sleep Apnea Syndrome: Report of Five Cases

Rosacea is a chronic inflammatory skin disease of unknown etiology. We noticed a series of patients who were diagnosed with rosacea as well as obstructive sleep apnea syndrome (OSAS), for which they used a continuous positive airway pressure (CPAP) mask. This case series aims to give insight in the possible relationship between rosacea and the use of a CPAP mask for OSAS. We present five patients with OSAS who developed or worsened rosacea symptoms after use of a CPAP mask covering nose and mouth. Two patients showed centrofacial symptoms consistent with the shape of the CPAP mask; three patients had nasal cutaneous symptoms. It is postulated that the occlusive effect of the CPAP mask, increasing skin humidity and temperature, can induce primary symptoms in patients with an underlying sensibility for rosacea. This could have implications for choice of CPAP mask type and topical therapeutic options for rosacea.     

The effect of azithromycin on reactive oxygen species in rosacea

BACKGROUND: Recent evidence suggests that inflammation in rosacea is associated with generation of reactive oxygen species (ROS) that are released by inflammatory cells. The efficacy of current therapeutic agents for rosacea such as tetracyclines and metronidazole has also been attributed to their antioxidant properties. Recently, a macrolide antibiotic, azithromycin, has been found to be an effective alternative in the treatment of rosacea. AIM: We planned a study to evaluate the antioxidant effects of azithromycin on ROS in rosacea. We compared basal ROS concentrations measured in the facial skin of patients with rosacea with the post-treatment levels and with those of healthy controls. METHODS: Facial skin biopsies of 17 papulopustular patients with rosacea and 25 healthy controls were taken. Rosacea patients were assigned to receive oral azithromycin 500 mg on three consecutive days each week for 4 weeks. The total number of inflammatory lesions (the sum of papules and pustules) on the face of each patient with rosacea was counted at each visit. The luminol- and lucigenin-enhanced chemiluminescence (CL) levels of patients with rosacea were measured before and after 4 weeks of treatment and compared with those of healthy controls. RESULTS: Rosacea patients had higher ROS levels than healthy controls (P < 0.001). A statistically significant decrease of both luminol- and lucigenin-enhanced CL levels were observed in patients with rosacea after treatment with azithromycin (t = 4.602, P < 0.001; vs. t = 4.634, P < 0.001, respectively). CONCLUSION: Rosacea patients have higher ROS levels than healthy controls. The results of our study support the antioxidant properties of azithromycin in rosacea.     

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.     

Erythematotelangiectatic rosacea may be associated with a subclinical stage of demodicosis: a case–control study

Demodex mites are small parasites that live in the skin pores of all adult humans, mainly on the face, and feed on human cells. Demodicosis is a facial skin condition that occurs when the mites proliferate (multiply) abnormally. Demodicosis shows as scales on the skin surface and, when the mites cause inflammation, by redness and/or red or weeping spots. Rosacea is another frequent skin condition affecting more than 10% of the population and characterised by facial redness. Sometimes spots develop and the condition is then called papulopustular rosacea (PPR). The cause of rosacea is still controversial, but it has been suggested that Demodex mites may be involved, because patients with PPR have a high density of mites on the facial skin, similar to patients with demodicosis. In this study, from Belgium, the density of Demodex mites was measured by two successive skin biopsies in patients in the early stage of a condition called erythematotelangiectatic rosacea (ETR), where patients have only redness without spots. The mean densities were lower than the densities in patients with PPR and patients with demodicosis but higher than in patients with healthy skin and patients with other skin conditions. The authors suggest that ETR may favour Demodex proliferation and may represent an early phase of demodicosis, with mites beginning to proliferate but not yet clinically visible. As such, dermatologists should look for Demodex mites in patients with ETR, so that appropriate treatment can be offered if densities are high.     

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.     

Effects of Helicobacter pylori treatment on rosacea: A single‐arm clinical trial study

Rosacea is a chronic dermatological disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, we attempted to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single‐arm clinical trial, patients ascertained to have H. pylori infection based on serological studies were assessed to examine existence of rosacea. Patients with concurrent rosacea and H. pylori infection were included in the study and underwent standard H. pylori eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score at the beginning, 2 months later and at the end of the trial (day 180). Of 872 patients positive for H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (P < 0.001) and with a female sex predominance (P = 0.03) when compared with rosacea‐free patients. Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day 0, 60 and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the existence of peripheral involvement (P = 0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea.     

Rosacea in the pediatric population

Rosacea is a condition of vasomotor instability characterized by facial erythema most notable in the central convex areas of the face, including the forehead, cheek, nose, and perioral and periocular skin. Rosacea tends to begin in childhood as common facial flushing, often in response to stress. A diagnosis beyond this initial stage of rosacea is unusual in the pediatric population. If a child is identified with the intermediate stage of rosacea, consisting of papules and pustules, an eye examination should be performed to rule out ocular manifestations. It may be beneficial to recognize children in the early stage of rosacea; however, it is uncertain if prophylactic treatment is necessary.     

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.     

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.     

Inhibition of mast cell infiltration in an LL‐37‐induced rosacea mouse model using topical brimonidine tartrate 0.33% gel

Brimonidine is a highly selective α2‐adrenergic receptor agonist approved by the FDA for the treatment of rosacea. Rosacea is a major clinical disease with vasodilatation and rash on the centre of the face, and that brimonidine as a vasoconstrictor can act as a remedy for rosacea. However, there is no study of how brimonidine has an effect on rosacea‐related immune cells or mechanisms in the skin to improve rosacea. In this study, we observed that clinical features of rosacea induced by LL‐37 in Balb/c mice were improved after the application of brimonidine gel, and we also showed a marked decrease in the number of inflammatory cells, especially mast cells (MCs) histologically. Furthermore, we confirmed that mRNA levels of MC enzymes increased by LL‐37 were reduced by brimonidine gel. To our knowledge, we first found that brimonidine has a mechanism of treating rosacea by reducing the number and mRNA levels of MC‐specific enzymes, an important immune cell in the pathogenesis of rosacea.     

Clinical presentations and classification of rosacea

Rosacea is a chronic skin disease affecting up to 10% of the population in some European countries. Rosacea manifests as various combinations of characteristic signs and symptoms in a centrofacial distribution. At present, there is no consensus about the definition or classification of the clinical patterns of rosacea. Initially, four stages were differentiated (pre-rosacea then stages I through III), with several variants (e.g., persistent erythema and edema, rosacea conglobata, and rosacea fulminans). The National Rosacea Society (NRS) in the USA has classified rosacea into four subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (lupoid or granulomatous rosacea). This classification scheme does not mention progression from one type to another and makes no reference to pathophysiological considerations. It uses major and minor diagnostic criteria based on the physical findings and symptoms. The NRS has also developed criteria for grading disease severity. The classification of rosacea into stages or subtypes, without considering the possibility of progression from one to another, will probably remain controversial until additional knowledge on the pathophysiology of rosacea is obtained.     

Rosacea: current thoughts on origin

Rosacea is a clinical pattern beginning and evolving in the genetically susceptible individual in response to a host of exposures. It produces a variety of clinical presentations, which vary over time and with age. Recently, many specific mediators of rosacea development have been described. A primary genetic cause for rosacea is suggested as single genes often control such mediators: enzymes, neuroendocrine transmitters, and cytokines are found in pathways to rosacea signs and symptoms. Currently, neither a specific cause nor a laboratory indicator of rosacea has been suggested. However, broadening interest in rosacea portends future increase in knowledge.     

Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey--Outpatient Department data collected by the U.S. National Center for Health Statistics from 1995 to 2002

BACKGROUND: Psychogenic factors have been considered to be important in the exacerbation and possibly the onset of rosacea. However, there are very few studies that have reported conclusive findings. OBJECTIVES: To examine the association between rosacea and major depressive disease, a common and usually treatable psychiatric disorder. METHODS: Data from 1995 to 2002, collected by the National Ambulatory Medical Care Survey and the outpatient component of the National Hospital Ambulatory Care Survey, which are both nationally representative surveys of healthcare visits in the U.S.A., were studied. The basic sampling unit in both surveys is the patient visit or encounter. A "Rosacea" variable was created by grouping all rosacea (ICD-9-CM code 695.3) visits and a "Depression" variable was created by grouping the patient visits related to major depressive disorder (ICD-9-CM codes 296.2, 296.3 and 311). As alcohol abuse has been implicated in rosacea, and alcohol can confound symptoms of depression, an "Alcohol" variable was created by grouping all ICD-9-CM codes related to alcohol dependence and abuse (codes 303, 303.0, 303.9 and 305.0). All analyses were conducted using the Complex Samples module of SPSS version 13, to account for the multistage probability sampling design used to collect the data. RESULTS: The weighted data were representative of over 608 million dermatology visits between 1995 and 2002. Logistic regression analysis using "Rosacea" as the dependent variable and age, sex, "Alcohol" and "Depression" as independent variables revealed that the odds ratio for depressive disease in the rosacea group was 4.81 (95% confidence interval 1.39-16.62). The association between "Alcohol" and "Rosacea" was not significant. CONCLUSIONS: The comorbidity between major depressive disease and rosacea may have important clinical implications. Alcohol abuse does not appear to play a significant role in this association.     

Is rosacea a systemic disease?

Rosacea is a chronic inflammatory facial disease occurring world-wide. The incidence of rosacea is increasing with age, with the clinical course being characterized by relapses. The pathogenesis of rosacea is not completely understood, but neurovascular and immunologic mechanisms are involved. Rosacea has a number of known extrinsic triggers that should be avoided, such as sun exposure, heat and cold, alcoholic beverages, and spicy food. Of greater importance is the observation that rosacea may develop as a manifestation of systemic diseases with a significant morbidity and even mortality. Obesity, Helicobacter pylori infection, smoking, and inflammatory bowel disease bear a significant risk for the development of rosacea. Metabolic, psychiatric, and neurologic disorders and certain types of cancer show a significant association with rosacea. The possible link to cardiovascular events is debatable. There are extrafacial and extracutaneous manifestations of rosacea, such as the red scalp syndrome, ocular rosacea, and migraine. Rosacea should be considered a systemic disease.