离子通道与玫瑰痤疮发病机制的研究进展

外界理化因素和情绪改变等会诱发玫瑰痤疮患者出现面部阵发性潮红, 并伴有灼热、刺痛和瘙痒感。大量研究提示, 离子通道激活后释放神经肽诱导的神经血管失调和神经源性炎症与玫瑰痤疮发病相关。本文综述近年来离子通道与玫瑰痤疮发病机制的研究进展, 为以离子通道作为玫瑰痤疮的治疗靶点提供依据。     

瞬时受体电位离子通道与玫瑰痤疮

玫瑰痤疮发病机制尚未完全明确,神经源性炎症和神经血管功能失调均参与其中。瞬时受体电位(TRP)离子通道蛋白在初级感觉神经元和非神经细胞中广泛表达,近年研究表明TRP家族中瞬时受体电位香草酸亚型(TRPV)1～4、瞬时受体电位锚蛋白(TRPA)1和M型瞬时受体电位(TRPM)8可能与玫瑰痤疮发病相关。该文主要对上述离子通道与玫瑰痤疮病理生理过程的关系作一综述。     

A型肉毒毒素微滴注射治疗玫瑰痤疮的研究进展

A型肉毒毒素是一种神经毒素,临床上广泛应用于皮肤美容.近年来研究证实其治疗玫瑰痤疮相关的面部红斑及毛细血管扩张安全、有效.本文对肉毒毒素治疗玫瑰痤疮的机制、临床应用、疗效及安全性等进行评价.     

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。     

玫瑰痤疮发病机制的研究进展

玫瑰痤疮是一组主要累及面中部的皮肤慢性炎症性疾病,其确切发病机制尚不明确,目前认为具有遗传背景的个体,在外界刺激因素下,神经血管功能失调、先天免疫及获得性免疫紊乱共同参与导致。该文就玫瑰痤疮发病机制研究进展作一综述。     

肥大细胞及其稳定剂在玫瑰痤疮发病机制及治疗研究进展

肥大细胞是人体天然免疫细胞，广泛参与人体多种炎症性疾病，现有研究提示其在玫瑰痤疮发病过程中具有重要作用，且肥大细胞稳定剂能抑制肥大细胞脱颗粒和炎症介质的释放，已被证实可用于治疗玫瑰痤疮。本文将肥大细胞在玫瑰痤疮发病机制中的作用以及肥大细胞稳定剂治疗玫瑰痤疮的基础和临床研究进展进行综述，以期为进一步阐明玫瑰痤疮发病机制以及探索更多临床治疗方案基础研究提供依据。     

肉毒毒素医学美容注射应用

A型肉毒毒素进行面部美容是目前常用的美容方法,其安全性也受到美容医师和患者的关注。肉毒毒素可通过抑制突触前膜乙酰胆碱释放,阻断神经肌肉传导,导致肌肉松弛性麻痹,达到治疗目的。文中通过采编国内外肉毒毒素治疗数据,分析A型肉毒毒素用于面颈部祛皱塑形、身体外形塑造、多汗症和腋臭的治疗适应症以及肉毒毒素的毒副作用、注意事项等方面资料,提示美容医师需要遵守神经毒药物的使用技术标准以及熟悉局部药理作用,以尽量减轻患者的不良反应。     

玫瑰痤疮发病的免疫机制研究进展

与玫瑰痤疮发生发展有关的因素包括免疫反应、微生物的增多以及神经血管功能失调等。免疫学发病机制涉及固有免疫反应异常,包括皮损处LL-37、KLK5、TLR2表达的增多、炎性体的活化以及肥大细胞的参与等,适应性免疫机制也参与其致病过程,本文对玫瑰痤疮发病的免疫机制研究进展进行综述。     

微生物在玫瑰痤疮中致病机制的研究进展

玫瑰痤疮是一种好发于面中部的慢性炎症性皮肤病,以面部阵发性潮红、持久性红斑、丘疹脓疱等为主要表现,其病因及发病机制尚不清楚.关于微生物在玫瑰痤疮中的致病作用存在争议.微生物一般通过破坏皮肤屏障、诱发炎症反应、分泌生物活性因子及毒素等方式介导玫瑰痤疮的发生.本文总结国内外近年关于微生物与玫瑰痤疮发病的相关研究,进一步揭示...     

玫瑰痤疮与皮肤屏障

玫瑰痤疮是一种病因复杂的慢性炎症性疾病,主要与血管舒缩功能、神经血管调节功能、免疫功能等有关。近年来,越来越多的研究表明,玫瑰痤疮的发生、发展与皮肤屏障功能的受损有密切的联系,而修复皮肤屏障的治疗同时可明显缓解玫瑰痤疮患者干燥、瘙痒、刺痛、阵发性潮红等临床症状。这个特点使得皮肤屏障功能的研究在玫瑰痤疮的研究中越来越受到重视,皮肤屏障功能的研究也为玫瑰痤疮的发病机制及治疗提供了新的思路。     

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.     

A Pilot Study to Evaluate the Efficacy and Safety of Treatment with Botulinum Toxin in Patients with Recalcitrant and Persistent Erythematotelangiectatic Rosacea

BackgroundThere are few pharmacologic options to reduce erythema and flushing in patients with recalcitrant erythematotelangiectatic rosacea (ETR). We previously reported two cases of refractory flushing and erythema of rosacea that were successfully treated with intradermal botulinum toxin injection, and additional research is needed to prove the efficacy and safety of this treatment.ObjectiveTo report the efficacy and safety of botulinum toxin injection as an aid in persistent erythema of rosacea patients.MethodsA total of 20 Korean patients with recalcitrant ETR were enrolled to receive treatment by injection of botulinum toxin. Patients received one treatment of intradermal botulinum toxin injection and were assessed 1, 2, 4, and 8 weeks after treatment. The severity of erythema and telangiectasia was investigated by a non-treating physician, and the Erythema Index (EI) was assessed by mexameter at each visit. Patient satisfaction and any adverse events were also assessed at each visit.Results17 patients completed all follow-up visits and were included in the analysis. Intradermal injection of botulinum toxin significantly reduced erythema severity and EI in ETR patients. Patients reported a satisfaction score of 2.94±0.56 at 8 weeks after treatment. Except for three patients who discontinued the study early due to inconvenience of facial muscle paralysis, 17 patients participating in the final analysis did not report side effects except injection pain at the time of the procedure.ConclusionIntradermal injection of botulinum toxin can be used as an effective and relatively safe adjuvant agent for recalcitrant and persistent erythema of ETR patients.     

Rosacea: Treatment targets based on new physiopathology data

Over the past 15 years, numerous clinical, epidemiological and physiopathological articles have been published on rosacea. There is now increasing evidence that rosacea is an inflammatory disease characterised by abnormal innate immune response, major vascular changes, and increased colonisation by Demodex mites, along with a genetic predisposition and multiple external aggravating factors. It is thus possible to define treatment targets and possible treatments: 1) permanent vascular changes (medical and instrumental treatments); 2) flushing (betablockers, botulinum toxin); 3) innate immunity (antibiotics, nonspecific antioxidants and anti-inflammatory molecules); 4) a neurovascular component (analgesics, antidepressants); 5) Demodex (antiparasitic drugs); 6) microbiome; 7) skin barrier impairment (cosmetics and certain systemic drugs); 8) sebaceous glands (isotretinoin, surgery); 9) environmental factors (alcohol, coffee, UV exposure). Treatment recommendations are now available in many countries and benefit from the new phenotypic approach to rosacea, in which every sign or symptom is considered separately rather than having to deal with overlapping subtypes. Since the 2000s, many good quality clinical trials have been published in the field of rosacea and many others are still ongoing. Rosacea is a complex disease involving many different mechanisms and with numerous possible treatments, but there are still some important unmet needs with regard to optimal care.     

Relationship between rosacea and sleep

Rosacea is a chronic facial skin disease involved in neurovascular dysregulation and neurogenic inflammation. Behavioral factors such as stress, anxiety, depression and sleep were identified to be associated with other inflammatory skin diseases. Few studies have reported sleep status in rosacea. Aiming to investigate the relationship between rosacea and sleep, a case–control survey was conducted, enrolling 608 rosacea patients and 608 sex- and age-matched healthy controls. Sleep quality was assessed through the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Diagnosis and severity grading of rosacea were evaluated under the standard guidelines of the National Rosacea Society. More rosacea patients (52.3%, n = 318) suffered poor sleep quality (PSQI, >5) than the healthy controls (24.0%, n = 146), displaying a much higher PSQI score (rosacea vs control, 6.20 vs 3.95). There was a strong association between sleep quality and rosacea (odds ratio [OR], 3.525; 95% confidence interval [CI], 2.759–4.519). Moreover, the severity of rosacea was also associated with sleep quality (OR, 1.847; 95% CI, 1.332–2.570). Single nucleotide polymorphisms in hydroxytryptamine receptor 2A and adrenoceptor-β1 genes, which are associated with sleep behaviour, were detected and revealed to be associated with rosacea. Furthermore, the LL-37-induced rosacea-like phenotype and sleep-deprivation mice models were applied, revealing that sleep deprivation aggravated the rosacea-like phenotype in mice, with higher expression of matrix metallopeptidase 9, Toll-like receptor 2, cathelicidin antimicrobial peptide and vascular endothelial growth factor. In conclusion, rosacea patients presented poorer sleep quality, as well as a higher propability of genetic background with sleep disturbance. In addition, poor sleep might aggravate rosacea through regulating inflammatory factors, contributing to a vicious cycle in the progression of disease.     

Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea

Rosacea is a frequent chronic inflammatory skin disease of unknown etiology. Because early rosacea reveals all characteristics of neurogenic inflammation, a central role of sensory nerves in its pathophysiology has been discussed. Neuroinflammatory mediators and their receptors involved in rosacea are poorly defined. Good candidates may be transient receptor potential (TRP) ion channels of vanilloid type (TRPV), which can be activated by many trigger factors of rosacea. Interestingly, TRPV2, TRPV3, and TRPV4 are expressed by both neuronal and non-neuronal cells. Here, we analyzed the expression and distribution of TRPV receptors in the various subtypes of rosacea on non-neuronal cells using immunohistochemistry, morphometry, double immunoflourescence, and quantitative real-time PCR (qRT-PCR) as compared with healthy skin and lupus erythematosus. Our results show that dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4, and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased. Thus, dysregulation of TRPV channels also expressed by non-neuronal cells may be critically involved in the initiation and/or development of rosacea. TRP ion channels may be targets for the treatment of rosacea.     

玫瑰痤疮难治性红斑治疗进展

玫瑰痤疮伴发的难治性红斑给患者带来了极大的困扰。目前治疗方法有α-肾上腺素能受体激动剂、β 肾上腺素能受体阻滞剂、肉毒素、激光和光子等。本文就玫瑰痤疮难治性红斑治疗进展进行综述。     

Integrative concepts of rosacea pathophysiology,clinical presentation and new therapeutics

Rosacea is a chronic relapsing inflammatory skin disease with high prevalence worldwide. Recent research suggests that dysregulation of innate and adaptive immune pathways as well as neurovascular changes is present, with different degrees of importance in the various subtypes. Neither the aetiology, genetics nor pathophysiological basis of the vascular, inflammatory or fibrotic changes is well understood. The clinical spectrum comprises a huge variability from erythema (vasodilation) to papules/pustules (inflammatory infiltrate) to phymata (fibrosis, glandular hyperplasia) making it a valuable human disease model to understand the interplay between the neurovascular and immune systems as well as the progression from chronic inflammation to fibrosis in skin. The lack of appropriate animal models emphasizes the importance of further translational research validating observed molecular pathways under disease conditions. A wide spectrum of physical (UV, temperature), biological (microbiota, food) and endogenous (genetic, stress) stimuli has been discussed as “trigger factors” of rosacea. Novel findings implicate keratinocytes, smooth muscle cells, endothelial cells, macrophages, mast cells, fibroblasts, Th1/Th17 cells, antibody‐producing B cells and neurons in the pathobiology of rosacea. So far, pattern recognition receptors like TLR2, transient receptor potential ion channels, cytokines, chemokines and proteases have been implicated as critical receptors/mediators. However, our understanding of the interactive networks on the molecular level is very limited. Identification of critical molecular components of the inflammatory cascade including antimicrobial peptides, the IL‐1β inflammasome, TNF, IFN‐γ, proteases and neuropeptides may provide the basis for novel pathomechanism‐based therapeutic approaches for this frequent and bothersome skin disease.     

How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review.