Attenuation of axon reflexes to compound 48/80 after repeated iontophoresis of compound 48/80 in skin of the human forearm

The aim of this study was to determine whether the iontophoretic administration of the mast cell degranulator compound 48/80 influences axon reflex vasodilatation in the skin of the human forearm. In stage 1, compound 48/80 was administered by iontophoresis to a circular site in the forearm of 9 healthy men and 8 healthy women on four occasions spread over 24 h. Two control sites were also prepared by passing the iontophoretic current through 0.9% saline. Large wheals initially developed at the compound 48/80 site in 8 of the males and in 2 of the females, but wheals were minimal in all subjects by the fourth administration. In stage 2, compound 48/80 iontophoresis provoked substantial flaring at the first control site, whereas saline iontophoresis induced only minor flaring at the second control site, indicating that compound 48/80 induced axon reflex vasodilatation. However, prior treatment with compound 48/80 inhibited flaring to compound 48/80 in subjects who initially developed wheals, consistent with mast cell degranulation. In stage 3, flaring after iontophoresis of histamine was investigated at the site of compound 48/80 pretreatment and at the second control site in 12 subjects. Flaring was impaired only slightly in 6 subjects who initially developed wheals to compound 48/80. The persistence of flaring indicates that repeated administrations of compound 48/80 did not abolish neurogenic inflammation. Transcutaneous iontophoresis of compound 48/80 may be an attractive alternative to intradermal injection in studies that aim at clarifying the function of mast cells in healthy and diseased skin.     

Impaired sweating function in adult atopic dermatitis: results of the quantitative sudomotor axon reflex test

Summary Background Impaired sweating is thought to be a cause of barrier dysfunction in atopic dermatitis (AD). Objectives To examine the sweating function in AD in a quantitative manner. Methods We investigated the sweating response of lesional and non‐lesional skin of adult patients with AD by a quantitative sudomotor axon reflex test in which the axon reflex is stimulated by acetylcholine iontophoresis. Sweat volume on the volar aspect of the forearm was measured in 18 adult patients with AD and in 40 non‐atopic controls; five patients with Sjögren's syndrome were also studied as disease comparators. We also evaluated the sweating function in four AD patients after topical corticosteroid therapy. Latency time, direct (DIR) sweat volume and axon reflex‐mediated indirect (AXR) sweat volume were the variables studied. Results The latency time in AD patients was significantly prolonged and AXR sweat volume significantly reduced compared with those in non‐atopic control subjects. The latency time and AXR sweat volume of lesional AD skin were significantly more prolonged and reduced, respectively, than those of non‐lesional skin. In contrast, the DIR sweat volume of lesional or non‐lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced when compared with that in non‐atopic controls. Latency time and sweat volumes of lesional and non‐lesional AD skin improved after topical corticosteroid therapy. Conclusions These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is reversed by topical corticosteroid administration.     

Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age‐matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross‐sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age‐ and sex‐matched healthy volunteers. Non‐invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age‐matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro‐inflammatory cytokines (Il‐8, Il‐1b, TNF‐a) and inflammasome‐related genes (NALP‐3 and CASP‐1) in rosacea, especially PPR. Overexpression of LL‐37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.     

Sweating patterns in atopic dermatitis patients

Summary Postganglionic sweat output in ten patients with atopic dermatitis was determined by a quantitative sudomotor axon reflex test in which the output results from axon reflex stimulation by acetylcholine iontophoresis. All measurements were obtained from normal skin on the volar aspect of the left wrist and dorsal aspect of the left foot of the atopic patients. Latency, sweat volume, and dynamic sweat pattern were variables included in the study. An abnormal value or configuration was found in nine of the ten patients studied. Seven of the ten patients had abnormal sweat output values. Atopic patients have abnormal sweating patterns, which may be inherently responsible for or related to their disorder.     

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.     

Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy

Summary Background In many Demodex‐associated skin diseases Demodex mites are present in abundance and seem to be at least partially pathogenic. So far all diagnostic approaches such as scraping or standardized superficial skin biopsy are (semi‐)invasive and may cause discomfort to the patient. Objectives To see whether confocal laser scanning microscopy (CLSM) – a noninvasive method for the visualization of superficial skin layers – is able to detect and quantify D. folliculorum in facial skin of patients with rosacea. Methods Twenty‐five patients (34–72 years of age) with facial rosacea and 25 age‐ and sex‐matched normal controls were examined by CLSM. Mosaics of 8 × 8 mm and 5 × 5 mm were created by scanning horizontal layers of lesional skin and quantification of mites per follicle and per area as well as follicles per area was performed. Results In all patients D. folliculorum could be detected by CLSM and presented as roundish or lengthy cone‐shaped structures. CLSM allowed the quantification of Demodex mites and revealed significant differences (P < 0·0001): the mean number of mites was 165·4 per 8 × 8 mm area and 94·2 per 5 × 5 mm area in the patients compared with 34·7 and 22·4, respectively, in the controls. The corresponding mean number of mites per follicle was 0·7 and 0·8, respectively, in the patients and 0·1 and 0·2, respectively, in the controls. Conclusions With the help of CLSM it is possible to detect, image and quantify Demodex mites noninvasively in facial skin of patients with rosacea.     

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。     

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.     

Positive correlation between serum immunoreactivity to Demodex‐associated Bacillus proteins and erythematotelangiectatic rosacea

Background Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. Objectives To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. Methods Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography‐mass spectrometry (LC‐MS) analysis. Results Eighty per cent (21/26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62‐ and 83‐kDa proteins of B. oleronius, compared with 40% (9/22) of controls (P = 0·004). The 62‐kDa protein was characterized by LC‐MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83‐kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. Conclusions The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium.     

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。     

IFAG and Childhood Rosacea: A Possible Link?

Idiopathic facial aseptic granuloma (IFAG) is a disorder that usually occurs during early childhood. Its pathogenesis remains poorly understood. The objective of this study was to investigate possible relationships between IFAG and childhood rosacea. This was a retrospective multicenter study of patients attending four French dermatologic centers diagnosed with IFAG between October 2000 and July 2007. Patients and their parents were asked to come for a follow‐up visit or to make an appointment for a telephone interview. Clinical symptoms of childhood rosacea were recorded: flushing, permanent or recurrent erythema; facial telangiectasia; papules and pustules on the face without comedones or microcysts; preferential location of the lesions on the convexity of the face; and ophthalmologic involvement of rosacea (recurrent chalazions, conjunctival hyperemia, keratitis). Thirty‐eight patients, 20 girls and 18 boys, were included in the study. The median age at the time of diagnosis of IFAG was 43 months, with a median follow‐up of 3.9 years. Sixteen patients (42.1%) had at least two criteria of childhood rosacea, 11 of 32 (34.4%) with a single lesion and 5 of 6 (83.3%) with multiple lesions. Children with IFAG are at risk for childhood rosacea, and follow‐up is advised, including periodic ophthalmologic assessment.     

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.     

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.     

Demodex folliculorum infestations in common facial dermatoses: acne vulgaris,rosacea, seborrheic dermatitis

BackgroundDemodex mites are found on the skin of many healthy individuals. Demodex mites in high densities are considered to play a pathogenic role.ObjectiveTo investigate the association between Demodex infestation and the three most common facial dermatoses: acne vulgaris, rosacea and seborrheic dermatitis.MethodsThis prospective, observational case-control study included 127 patients (43 with acne vulgaris, 43 with rosacea and 41 with seborrheic dermatitis) and 77 healthy controls. The presence of demodicosis was evaluated by standardized skin surface biopsy in both the patient and control groups.ResultsIn terms of gender and age, no significant difference was found between the patients and controls (p > 0.05). Demodex infestation rates were significantly higher in patients than in controls (p = 0.001). Demodex infestation rates were significantly higher in the rosacea group than acne vulgaris and seborrheic dermatitis groups and controls (p = 0.001; p = 0.024; p = 0.001, respectively). Demodex infestation was found to be significantly higher in the acne vulgaris and seborrheic dermatitis groups than in controls (p = 0.001 and p = 0.001, respectively). No difference was observed between the acne vulgaris and seborrheic dermatitis groups in terms of demodicosis (p = 0.294).Study limitationsSmall sample size is a limitation of the study. The lack of an objective scoring system in the diagnosis of Demodex infestation is another limitation.ConclusionThe findings of the present study emphasize that acne vulgaris, rosacea and seborrheic dermatitis are significantly associated with Demodex infestation. Standardized skin surface biopsy is a practical tool in the determination of Demodex infestation.     

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.     

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.     

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.     

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。     

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...     

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.