Effect of treatment of Helicobacter pylori infection on rosacea.

OBJECTIVE: To evaluate the clearing and intensity of symptoms of rosacea 60 days after the treatment of Helicobacter pylori infection. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: The dermatology section of a large multispecialty clinic in the North Central United States. PARTICIPANTS: Men and women older than 25 years with active signs of rosacea who tested positive for H pylori with both the rapid whole blood test and the urea breath test. INTERVENTION: Treatment of H pylori infection with 14-day therapy using clarithromycin. 500 mg orally 3 times a day, and omeprazole, 40 mg orally once a day. MAIN OUTCOME VARIABLES: The extent and intensity of rosacea as measured by the number of papules and pustules and the extent and intensity of erythema and telangiectasia. RESULTS: Three hundred twenty patients presented with rosacea. For 50 patients, the results of a urea breath test were positive for H pylori, and 44 patients were enrolled in the study. Rosacea abated in almost all patients, but none were cured. Notably, lessening of rosacea for patients treated for H pylori was not significantly better than for the control cohort. CONCLUSIONS: Rosacea abated in most participants in this study, whether they were in the treatment or the control cohort. There was no statistical difference when the results of active treatment were compared with those of placebo. Treating H pylori infection has no short-term beneficial effect on the symptoms of rosacea to support the suggested causal association between H pylori infection and 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.     

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.     

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.     

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.     

The potential role of microorganisms in the development of rosacea

Rosacea is a chronic cutaneous disorder characterized by centrofacial persisting erythema, telangiectases, papules, pustules, edema, phymas and ocular involvement. Despite being one of the most common skin disorders, its pathogenesis remains unclear and controversial. Although the disease triggering factors are well recognized, the underlying causes of rosacea have not yet been identified. Several different postulates about its pathogenesis can be found in the medical literature. Abnormalities of the pilosebaceous unit, as well as genetic, vascular, inflammatory, environmental and microbial factors have been described. The microorganisms that have been associated include Helicobacter pylori, Demodex folliculorum, Staphylococcus epidermidis, and Chlamydia pneumonia; all the studies have been inconclusive. We review currently available scientific data on the potential pathogenetic role of microorganisms in the development of rosacea.     

Helicobacter pylori eradication treatment reduces the severity of rosacea

BACKGROUND: A higher prevalence of Helicobacter pylori infection in rosacea patients than in healthy controls has been reported. OBJECTIVE: The aim of this study was to investigate the effect of H. pylori eradication therapy in patients with rosacea. METHODS: Twenty-five rosacea patients and 87 age- and sex-matched healthy controls were included in this study. We detected IgG and IgA antibodies against H. pylori in both groups. An upper gastrointestinal endoscopy and a rapid urease test were performed on the 13 patients with rosacea who accepted this procedure. Amoxicillin 500 mg 3 times daily, metronidazole 500 mg 3 times daily, and bismuth subcitrate 300 mg 4 times daily were administered to patients positive for H. pylori. The severity of rosacea was scored before and after treatment. RESULTS: There was no statistical difference in seropositivity in either group. In H. pylori-positive rosacea patients there was a significant decrease in the severity of rosacea at the end of the treatment as compared with the initial scores. CONCLUSION: Our findings suggest that H. pylori may be involved in rosacea and that eradication treatment may be beneficial.     

幽门螺杆菌和酒渣鼻关系的研究进展

酒渣鼻是发生在中年人鼻部及面部的一种慢性炎症,许多因素参与了其发病机制,一些学者认为幽门螺杆菌在酒渣鼻的发病机制中扮演了重要角色,其伴随产生的细胞毒素和细胞因子在酒渣鼻的发生和发展中起着重要作用,本文综述了幽门螺杆菌和酒渣鼻的关系以及幽门螺杆菌的检查方法和治疗。     

酒渣鼻发病机制中微生物的作用

酒渣鼻是一种常见的面部慢性炎症性皮肤病,其发病机制尚不明确,其中微生物起重要作用。蠕形螨虫与酒渣鼻发病有密切相关,可能通过Ⅳ型免疫反应致病。在对蠕形螨虫所携带的细菌的研究中,人们发现奥列伦芽胞杆菌、表皮葡萄球菌可能由蠕形螨虫携带,并与之共同致病;幽门螺杆菌、小肠细菌过度生长等可能在合并消化道症状的酒渣鼻发病中起作用,但其相关性和致病机制并不确切。目前尚未发现痤疮丙酸杆菌、沃尔巴克体与酒渣鼻发病有关。     

Rosacea: a cutaneous marker of Helicobacter pylori infection? Results of a pilot study

Given the long purported anecdotal association between rosacea and gastrointestinal disease, the discovery that Helicobacter pylori causes gastritis and duodenal ulcer disease has led to a hypothesized role for this organism in the aetiology of rosacea. We conducted a case-series study of 49 patients to assess the potential association between severity of rosacea and direct and serological evidence of H. pylori infection. Patients were classified by severity into non-inflammatory erythematotelangiectatic or inflammatory/papulopustular rosacea and were tested for current H. pylori infection and evidence of previous exposure. Positive 13C-urea breath test and ELISA tests were more likely to be observed in patients with inflammatory rosacea, although not statistically significantly so (OR = 3.0, p = 0.15 and OR = 2.9, p = 0.16, respectively). However, the proportion of patients who tested positive in both assays (versus negative in at least one) was even higher in the inflammatory rosacea group and neared statistical significance (OR = 4.5, p = 0.06). This pilot study provides sufficient evidence suggestive of a positive association between the severity of rosacea and the presence of H. pylori to warrant further research.     

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.     

幽门螺杆菌感染与酒渣鼻的相关性

为了研究幽门螺杆菌(HP)感染与酒渣鼻的相关性 ,研究了42例酒渣鼻患者的血清HP IgG浓度、消化道症状及抗HP治疗的疗效 ,并以33例寻常痤疮作对照。发现酒渣鼻患者的血清抗体及消化道症状阳性率及抗HP治疗的疗效明显高于对照组 ,且6例接受胃镜及组织学检查的酒渣鼻患者的检查结果均显示有异常。结果提示 ,HP感染与酒渣鼻可能存在一定的相关性。     

幽门螺杆菌细胞毒素相关蛋白A与酒渣鼻的相关性

目的探讨幽门螺杆菌(HP)细胞毒素相关蛋白A(CagA)与酒渣鼻发生的关系。方法使用酶联免疫法测定76例酒渣鼻患者及31例健康对照者的血清CagA-Hp抗体,并检测CagA-Hp阳性及阴性情况下IL-8,TNF-α,VEGF水平。结果酒渣鼻组血清CagA-Hp阳性率为71.05%,对照组为22.58%,两组差异有显著性(P<0.05)。CagA-Hp阳性的酒渣鼻患者血清IL-8,TNF-α水平高于CagA-Hp阴性者(P<0.05)。CagA-Hp抗体水平与酒渣鼻病情轻重呈正相关。抗HP治疗可促进酒渣鼻的恢复。结论CagA-Hp阳性菌株感染与酒渣鼻的发生有关,是其发病的危险因素。     

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.     

The seroprevalence of Helicobacter pylori and nitric oxide in acne rosacea

BACKGROUND: Acne rosacea is a dermatosis with unknown etiology. Some studies have reported a high prevalence of Helicobacter pylori infection in acne rosacea. Other studies have reported a decrease in the severity of the lesions of acne rosacea after eradication of H. pylori. H. pylori is a Gram-negative bacterium which colonizes the gastric mucosa and increases the synthesis of oxygen radicals, such as superoxide and proinflammatory cytokines. These cytokines have been demonstrated to stimulate the synthesis of the inflammatory species nitric oxide (NO). In this study, we examined the role of NO in the possible effect of H. pylori in acne rosacea. METHODS: Thirty-three acne rosacea patients were included in the study and the control group comprised 20 healthy individuals. The levels of immunoglobulin G antibodies against H. pylori in the serum samples were measured using the enzyme-linked immunoabsorbent assay method. Measurement of nitrate was performed using chemiluminescence in accordance with the method described by Braman and Hendrix (Braman RS, Hendrix SA. Nanogram nitrite and nitrate determination in environmental and biological materials by vanadium(iii) reduction with chemiluminescence detection. Anal Chem 1989; 61: 2715-2718). For statistical analysis, the t-test was used. RESULTS: The seropositivity of H. pylori in acne rosacea patients was found to be high; however, the serum nitrate levels were found to be normal. CONCLUSIONS: The results of the study indicate that the inflammatory species NO, which has been hypothesized to be associated with H. pylori, has no role in the inflammatory mechanism of acne 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.     

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.     

The link between Helicobacter pylori infection and rosacea

BACKGROUND: Rosacea is a common condition of unknown aetiology that is usually accompanied by gastrointestinal symptoms and responds favourably to treatment with antibiotics. AIMS/METHODS: This study was designed to examine the prevalence of gastric Helicobacter pylori (Hp) infection verified by 13C-UBT, CLO-test, Hp culture and serology (IgG and IgA) and the presence of Hp in the oral cavity evidenced by CLO-test, Hp culture and saliva anti-Hp antibodies (IgG and IgA). During gastroduodenoscopy antral and fundic biopsy samples were taken for histological evaluation (the Sydney system). This study was performed on 60 subjects 30-70 years old with visible cutaneous rosacea symptoms and 60 age- and gender-matched controls without skin diseases but with dyspeptic symptoms similar to those of rosacea and without endoscopic changes in gastroduodenal mucosa (non-ulcer dyspepsia--NUD). RESULTS: The Hp prevalence in rosacea patients was about 88%, compared to 65% in the NUD controls. A noticeable number of rosacea patients showed chronic active gastritis predominantly in antrum but also in the corpus while those with NUD showed only mild gastritis confined to the antrum only. Following the initial examination, a typical 1 week systemic anti-Hp therapy, induding omeprazole (2 x 30 mg), clarithromycin (2 x 500 mg) and metronidazole (2 x 500 mg), plus gargling and application of metronidazole paste in the case of Hp oral cavity infection. After the application of the systemic and local therapy in the oral cavity, Hp was eradicated from the stomach in 97% and from the oral cavity in 73% of treated patients. Within 2-4 weeks, the symptoms of rosacea disappeared or decreased markedly in 51 subjects. SUMMARY: We conclude that: (1) rosacea is a disorder with various gastrointestinal symptoms closely related to gastritis, especially involving the antrum mucosa; (2) the eradication of Hp leads to improvement of symptoms of rosacea and reduction in related gastrointestinal symptoms; (3) the lack of improvement of cutaneous symptoms in rosacea after eradication of Hp from the gastric mucosa could depend on bacteria in the oral cavity; and (4) rosacea could be considered as one of the extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins and cytokines.     

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.     

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.