Alcohol-induced rosacea flushing blocked by naloxone

We evaluated the roles of endogenous opioid peptides and histamine in the pathophysiology of alcohol-induced facial flushing in rosacea. Non-diabetic patients with rosacea ingested 360 ml of 6% ethanol after receiving either subcutaneous naloxone hydrochloride or oral chloropheniramine maleate. Only pretreatment with naloxone blocked the alcohol-induced rosacea flushing (AIRF), suggesting an active role of endogenous enkephalin and/or endorphin in this vascular reactivity. In this respect, AIRF is similar to chlorpropamide alcohol flushing and menopausal flushing.     

玫瑰痤疮患者阵发性潮红的临床特征分析及对生活质量的影响

【摘要】 目的 探讨玫瑰痤疮患者阵发性潮红的临床特点及对生活质量的影响。方法 采用前瞻性研究，收集2017年8月至2019年8月湘雅医院皮肤科门诊玫瑰痤疮患者728例，采用阵发性潮红国际标准化量表（FSQ）、持久性红斑医生评分量表（CEA）、患者自评量表（PSA）和视觉模拟评分法（VAS）收集资料，分析阵发性潮红的发作特点、严重程度、对生活的困扰度及其与持久性红斑评分的相关性等。统计分析采用χ2检验和Spearman相关分析。结果 728例患者中，阵发性潮红最常出现的部位为颊部（682例，93.7%）及颧部（617例，84.8%）；持续时间5 min至2 h的患者比例最高（484例，66.5%）；317例（43.6%）受刺激后潮红发作，233例（32.0%）潮红每天发作且1天内多次发作。503例（69.1%）患者潮红的总体评分在中度以上；412例（56.6%）认为潮红可对睡眠造成不同程度的影响，其中59例（8.1%）认为影响可达重度及以上；662例（90.9%）认为潮红对生活有不同程度的影响，其中304例（41.8%）认为影响程度在重度及以上。潮红总体评分和其对生活的困扰评分均与医生评价的持久性红斑严重程度（CEA评分）呈低度正相关（rs = 0.166、0.151，均P＜0.05），与患者自评的红斑严重程度（PSA评分）具有显著相关性（rs = 0.518、0.500，均P＜0.05）。结论 玫瑰痤疮患者的阵发性潮红具有典型的发作部位，发作持续时间较长，频率高，影响患者生活质量，需得到临床医生的重视。     

Remission of rosacea induced by reduction of gut transit time

Rosacea is a chronic disorder characterized by hypersensitivity of the facial vasculature, presenting with intense flushing eventually leading to chronic erythema and telangiectasia. Although the precise aetiology of rosacea is not known, numerous associations with inflammatory gastrointestinal tract disorders have been reported. Furthermore, substance P-immunoreactive neurones occur in considerably greater numbers in tissue surrounding affected blood vessels suggesting involvement of neurogenic inflammation and moreover plasma kallikrein-kinin activation is consistently found in patients. In this report, a patient without digestive tract disease is described, who experienced complete remission of rosacea symptoms following ingestion of a material intended to sweep through the digestive tract and reduce transit time below 30 h. It is possible that intestinal bacteria are capable of plasma kallikrein-kinin activation and that flushing symptoms and the development of other characteristic features of rosacea result from frequent episodes of neurogenic inflammation caused by bradykinin-induced hypersensitization of facial afferent neurones. The possible relevance of this hypothesis to other conditions featuring afferent hypersensitivity, such as fibromyalgia, is considered.     

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.     

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。     

Endothelial and axon reflex vasodilatation to acetylcholine in rosacea-affected skin

Rosacea is a chronic skin disorder, characterized by persistent painful facial flushing and often accompanied by papules and pustules. To investigate the mechanism of facial flushing in rosacea, acetylcholine was administered by iontophoresis to a 10-mm diameter site in the forehead of 31 patients with rosacea and in 29 controls of similar age and sex distribution. During the iontophoresis, current strengths doubled in eight steps from 2.5 to 320 μA. For each step, skin blood flow was monitored during 60 s of iontophoresis and for 2 min afterwards with laser Doppler flow probes at the site of iontophoresis and 5–8 mm away in the region of axon reflex vasodilatation. Vascular responses to acetylcholine were similar in patients and controls, but stinging sensations were greater in patients than in controls at the most intense current strength. In addition, axon reflex vasodilatation was greater in patients with severe than mild rosacea. These findings suggest that activation of nociceptive nerve fibres contributes to skin sensitivity in patients with rosacea, and that axon reflexes augment flushing in patients with the most severe symptoms.     

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.     

421例玫瑰痤疮患者临床特征分析

目的 分析玫瑰痤疮患者的临床表现,提高对玫瑰痤疮临床特征的认识.方法 回顾性分析421例玫瑰痤疮患者,统计分析其性别、年龄、皮损部位、皮损表现及自觉症状得分.结果 421例玫瑰痤疮患者中男58例,女363例,男女比例为1:6.25,男女各年龄段均可发病.玫瑰痤疮患者最常见的皮损表现为阵发性潮红(93.8％,395/421)、持久性红斑(84.3％,355/421)及炎性丘疹(68.9％,290/421),且多同时出现≥2种皮损表现(83.1％),阵发性潮红及持久性红斑最常同时出现.患者最常累及部位为颊部(87.2％,367/421),鼻部(76.5％,322/421)及口周(63.7％,268/421),多同时累及≥3个部位(67.2％),且颊部、鼻部及口周为最常同时累及的部位.自觉症状中最常见的3大症状为灼热感(73.6％,310/421)、干燥感(69.6％,293/421)及瘙痒感(66.0％,278/421).结论 颊部、鼻部或口周部的阵发性潮红及持久性红斑为玫瑰痤疮的主要症状,炎性丘疹、脓疱、鼻赘、毛细血管扩张及灼热、干燥、瘙痒感为玫瑰痤疮的重要临床表现.     

红黄光治疗急性肿胀期玫瑰痤疮疗效观察

 目的: 探讨红黄光治疗急性肿胀期玫瑰痤疮的治疗效果。 方法：回顾分析2018年3月至2019年6月在中南大学湘雅医院皮肤科门诊的30例急性肿胀期玫瑰痤疮患者的治疗效果,所有患者均给予红黄光（1次/d,连续3 d）治疗,评估治疗3 d后的疗效以及不良反应。 结果： 治疗3 d后,患者皮肤潮红（2.37±1.10）及肿胀（1.30±0.75）评分均较治疗前（分别为2.80±0.99、1.93±0.74）明显下降,差异具有统计学意义（t值分别为2.77、4.29,P＜0.05）;治疗有效率达70.00%;治疗者满意率达86.66%;治疗期间未见明显不良反应。 结论： 红黄光治疗对于缓解急性肿胀期玫瑰痤疮患者面部潮红肿胀疗效确切,起效快,不良反应少。     

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.     

玫瑰痤疮面部潮红与红斑新认识

【摘要】 持续型面中部红斑与潮红是玫瑰痤疮最常见的临床表现,但对其病理机制了解甚少,并缺乏高证据等级临床研究支持。本文结合国内外研究进展及临床经验,强调将面部潮红与红斑作为独立的临床表型进行研究探讨的必要性,认为精神压力、焦虑和/或抑郁可能是其发病的使动环节。由精神因素出发,探索玫瑰痤疮面部潮红及红斑相关神经炎症与皮肤免疫及血管的关系具有潜在的临床意义。     

Double-blind, randomized, vehicle-controlled clinical trial of once-daily benzoyl peroxide/clindamycin topical gel in the treatment of patients with moderate to severe rosacea

BACKGROUND: Systemic antibiotics such as tetracycline are well accepted as effective in treating the inflammatory papular/pustular phase of rosacea but may be associated with systemic side-effects. Few controlled data on the use of topical antibiotics in rosacea are available. OBJECTIVE: We evaluated the efficacy and tolerability of a fixed combination of 5% benzoyl peroxide and 1% clindamycin in a topical gel for the treatment of rosacea. Methods This was a 12-week, double-blind, vehicle-controlled, randomized, prospective, parallel-group study in 53 patients with moderate to severe rosacea. RESULTS: The mean percentage reduction in papules and pustules from baseline to the end of treatment was 71.3% in the benzoyl peroxide/clindamycin group (n = 26) and 19.3% in the vehicle group (n = 26; P = 0.0056). A significant (P = 0.0141) difference in favor of benzoyl peroxide/clindamycin was evident by the third week of treatment. Severity scores for erythema, papules/pustules, and flushing/blushing decreased more with benzoyl peroxide/clindamycin than with vehicle. Overall rosacea severity, Physician Global Assessment, and Patient's Global Assessment at the end of treatment were all significantly improved with benzoyl peroxide/clindamycin compared with vehicle (P = 0.0101, 0.0026, and 0.0002, respectively). Application site reactions were reported in four patients (14.8%) in the benzoyl peroxide/clindamycin group. CONCLUSION: A once-daily topical application of a combination of 5% benzoyl peroxide and 1% clindamycin is effective and well tolerated in patients with moderate to severe rosacea.     

Risk factors associated with rosacea

Background Although rosacea is a common disease, the cause of disease is still a mystery –Helicobacter pylori infection, genetic predisposition, climatic factors, and detrimental habits are implicated as triggers of rosacea. Objective The aim of current study is to evaluate several suspected risk factors coincidently. Methods Patients with rosacea from a dermatology clinic and skin‐healthy controls from an randomly selected employees' population enrolled the study. Skin status were evaluated by one and same dermatologist. Participants were queried for age, gender, sun‐reactive skin type, and detrimental habits using a questionnaire; blood samples for detecting Helicobacter pylori serostatus were collected. Results Totally 145 skin‐healthy controls and 172 subjects either with flushing episodes or established rosacea included the study. In multivariate analysis, rosacea patients had significantly higher chance to have photosensitive skin types (OR 1.75; 95% CI 1.01–3.04; P < 0.05), positive family history to rosacea (OR 4.31; 95% CI 2.34–7.92; P < 0.0001) or previous smoking status (OR 2.01; 95% CI 1.07–3.80; P < 0.05) comparing with skin‐healthy controls. There were no statistically significant differences either in gender, Helicobacter pylori serostatus, caffeine intake, alcohol consumption, occupational environment, or education level between rosacea patients and controls. Conclusion Rosacea is foremost associated with familial predisposition. There is no association between Helicobacter pylori infection and rosacea in current study.     

A型肉毒毒素皮内注射治疗玫瑰痤疮持久性红斑及潮红专家共识

A型肉毒毒素是一种神经毒素, 广泛用于皮肤美容。有证据表明, 皮内注射A型肉毒毒素能改善玫瑰痤疮患者面部皮肤潮红及持续性红斑, 但对治疗浓度、剂量、操作方法、疗程、治疗间隔等均存在差异。中华医学会皮肤性病学分会玫瑰痤疮研究中心、中国医师协会皮肤科分会玫瑰痤疮专业组在玫瑰痤疮诊疗指南的基础上, 参考新近文献并结合诸多专家临床应用经验撰写本共识, 为A型肉毒毒素皮内注射治疗玫瑰痤疮提供更科学、规范的参考依据。     

1090例玫瑰痤疮患者临床特征分析及玫瑰痤疮新诊断标准探讨

目的 在分析大样本玫瑰痤疮患者临床特征的基础上提出新的诊断标准.方法 纳入中南大学湘雅医院皮肤科门诊初诊的1 090例玫瑰痤疮患者,收集基本资料、临床症状和自觉症状等,根据描述性分析结果,总结玫瑰痤疮临床特点,探讨新的玫瑰痤疮诊断标准.以1 200例以面部红斑为主要临床特点的门诊病例为对象,验证新标准的灵敏度和特异度.结果 1 090例玫瑰痤疮患者,男131例(12.0％)、女959例(88.0％),年龄10～66(33.5±11.1)岁.初始皮损发生在面颊部715例(65.6％),其中712例(99.6％)首发症状为阵发性潮红,689例(96％)伴有干燥、灼热、瘙痒等皮肤敏感症状;初始皮损发生在口周部208例(19.1％),其中204例(98.1％)首发症状为持久性红斑;皮损首发于鼻部167例(15.3％),其中163例(97.6％)首发症状为持久性红斑;伴有眼部症状311例(28.5％),伴有面部以外(颈部、耳后等)症状24例(2.2％).由此拟定新的玫瑰痤疮诊断标准,必备条件:面颊/口周/鼻部阵发性潮红或持久性红斑;次要条件:①灼热、刺痛、干燥或瘙痒等皮肤敏感症状;②毛细血管扩张;③丘疹或脓疱;④肥大增生改变;⑤眼部症状.符合必备条件和1条及以上的次要条件,即可诊断为玫瑰痤疮.将新的诊断标准在1 200例以面部红斑为主要临床特点的面部皮炎患者中进行验证,其灵敏度为99.3％,特异度为95.8％.结论 提出了一个具有较好敏感性和特异性的玫瑰痤疮诊断标准,值得在临床工作中应用.     

短波理疗仪治疗红斑毛细血管扩张型玫瑰痤疮临床观察

目的:观察短波理疗仪治疗红斑毛细血管扩张型玫瑰痤疮(ETR)的临床疗效。方法:收集70例ETR患者,随机分为2组,其中治疗组40例,对照组30例。2组均每日早晚使用保湿霜,治疗组每隔1周进行1次短波理疗,疗程8周。治疗前、后由皮肤科医生盲态下对患者面部红斑及毛细血管扩张进行评分;患者对阵发性潮红、灼热及干燥症状进行评分。评分标准采用玫瑰痤疮4级评分。皮肤检测仪检测2组治疗前、后皮肤含水量和经皮水流失(TEWL)值。记录疗程中的不良反应。结果:治疗后治疗组患者面部红斑、灼热及干燥程度评分均较治疗前明显改善(P<0.05),治疗组改善优于对照组(P<0.05);对照组患者灼热及干燥程度评分均较治疗前明显改善(P<0.05)。2组毛细血管扩张评分及阵发性潮红评分比较,差异均无统计学意义(P>0.05)。治疗后2组患者皮肤含水量均增加,治疗组增加大于对照组(P<0.05);2组TEWL值均下降,治疗组下降大于对照组(P<0.05)。所有患者均无明显不良反应。结论:短波理疗仪治疗可明显改善ETR患者面部红斑、灼热及干燥症状,且安全性较好。     

Flushing in rosacea: A possible mechanism

Summary Flushing in rosacea has been investigated by means of (a) pharmacological inhibition of some possible chemical mediators and (b) titration of bradykinin as a possible effector directly in the blood. Clonidine-inhibited flushing was seen in all patients (mean 45%), other drugs had poorer results. Bradykinin increased in all patients at the climax of flushing (mean 60%). These findings support the hypothesis that epinephrine promotes a bradykinin release responsible for vasodilation.     

Treatment of early-stage erythematotelangiectatic rosacea with a Q-switched 595-nm Nd:YAG laser

Erythematotelangiectatic rosacea presents as persistent erythema and telangiectasia with frequent flushing and blushing on the facial and extrafacial skin. Additionally, papulopustular rosacea shows acneiform papules, pustules, and nodules with persistent plaque-form edema. Despite garnering only grade-C or -D level recommendations, a 585-nm or 595-nm flashlamp-pumped pulsed-dye laser can be considered as an effective therapeutic modality for the treatment of rosacea in patients who are refractory to topical and/or systemic treatments. In this report, treatment with a Q-switched 595-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with low non-purpuragenic fluence proved to be safe and effective in treating early-stage erythematotelangiectatic rosacea in two female Korean patients. Laser treatment for rosacea was delivered with the settings of pulse energy of 0.4–0.5 J/cm², pulse duration of 5–10 ns, 5-mm spot size, 5 Hz, and 500 shots. Additionally, we found that remarkable therapeutic effects were achieved for both rosacea and melasma by combining Q-switched quick pulse-to-pulse 1,064-nm Nd:YAG and Q-switched 595-nm Nd:YAG laser treatments, which required only the changing of handpieces equipped with solid dye. In conclusion, we suggest that treatment with a Q-switched 595-nm Nd:YAG laser with low fluence may provide an additional therapeutic option for treating early-stage erythematotelangiectatic rosacea.     

Effect of subdepressor clonidine on flushing reactions in rosacea. Change in malar thermal circulation index during provoked flushing reactions

The effects of clonidine hydrochloride, an agent effective in suppressing other types of flushing reactions, were investigated in patients with erythematotelangiectatic rosacea. Clonidine hydrochloride, 0.05 mg, was given orally twice daily for two weeks. Mean arterial BP was not altered during clonidine treatment. Flushing reactions provoked with water at 60 degrees C, red wine, and chocolate were not suppressed during clonidine treatment. Clonidine did lead to malar hypothermia. It may be that any treatment benefit obtained from the reduction in vascular reactivity by clonidine in rosacea is offset by the malar hypothermia.     

Radiofrequency irradiation attenuates angiogenesis and inflammation in UVB-induced rosacea in mouse skin

Rosacea is a skin inflammatory condition accompanied by cutaneous signs such as oedema, flushing, erythema, telangiectasia and pustules. Generally, rosacea is triggered by ultraviolet B (UVB) exposure. When exposed to UVB, skin epidermis thickens and produces elevated levels of pro-inflammatory cytokines, especially keratinocyte-related VEGF, a potent angiogenic factor. The upregulations of VEGF expression and its secretion promote the formation of new blood vessels and exacerbates rosacea. In this study, radiofrequency (RF) irradiation reduced keratinocyte proliferation in the epidermal layer, the expressions of pro-inflammatory cytokines, angiogenesis-related inflammatory factors and VEGF in our UVB-induced model of rosacea in vitro and in vivo. RF irradiation attenuated VEGF-induced angiogenesis-associated processes such as tube formation, cell migration and endothelial cell proliferation. Notably, blood vessel densities in the skins of UVB-treated mice and rosacea patients were significantly decreased by RF irradiation. These results provide experimental and molecular evidence regarding the effectiveness of RF irradiation for the treatment of rosacea.