Involucrin in the differential diagnosis between linear psoriasis and inflammatory linear verrucous epidermal nevus: a report of one case

Inflammatory linear verrucous epidermal nevus is a variant of verrucous epidermalnevus, characterized by recurrent inflammatory phenomena. Despite well-establishedclinical manifestations, the differential diagnosis between inflammatory linearverrucous epidermal nevus and linear psoriasis remains difficult. Clinical history,physical examination and histopathology analysis may not be sufficient to confirm thediagnosis. We report the case of a 4-year-old girl in which the involucrinimmunostaining was helpful in the diagnosis of inflammatory linear verrucousepidermal nevus. Our findings confirm that involucrin immunohistochemistry is auseful tool in such cases.     

皮肤屏障与银屑病研究进展

皮肤作为人体的第一道防线,对抵御外界有害因素的损伤以及维持人体内环境的稳态有着至关重要的作用。皮肤屏障的结构和功能与一些皮肤病的发生发展有着重要的联系。研究发现皮肤屏障功能受损可能是银屑病发生的重要诱因,然而皮肤屏障缺陷与银屑病发生的确切机制仍不清楚。该文主要对近年来皮肤屏障与银屑病的研究进展作一综述。     

寻常型银屑病与血脂代谢异常相关性分析

目的通过分析相关临床资料,探讨寻常型银屑病患者伴血脂代谢异常之间的相关性。方法收集2017年12月至2018年5月在我院门诊及住院治疗的143例寻常型银屑病患者作为观察组,选取同期健康体检的人员143例作为对照组。收集两组人员的一般资料,检测血脂指标、炎性指数。结果观察组体重指数(BMI)、中性粒细胞与淋巴细胞比值(NLR)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)高于对照组,高密度脂蛋白胆固醇(HDL-C)水平低于对照组(P <0.05)。结论 NLR水平可反映寻常型银屑病的炎症程度,患者肥胖、脂代谢紊乱、炎症程度与寻常型银屑病密切相关。     

计算机图像分析在轻度皮肤刺激反应评判中的运用研究

作者借助Ｐｈｏｌｔｏｓｈｏｐ来分析评判轻度皮肤刺激反应。每个受试区用皮肤分光光度测量仪检测,并在试验前后在设定的条件下摄取图像,临床评估则按照ＩＧＤＲＧ标准。所有图像用图像分析表在ＧｒｅｙｓｃａｌｅＲＧＢ,ＣＭＹＫ和Ｌａｂ模式颗各个光亮度或灰度值同皮肤反应程度呈 线性相关。同样皮肤分光光度测量仪所测Ｌ和值与各种模式的光亮度和ＲＧＢ模式和Ｒ和Ｌａｂ的ａ值也是呈很好的线性相关。作者认为用Ｐｈｏｔｏｓｈ     

Pan-selectin antagonism improves psoriasis manifestation in mice and man

The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant (P=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases.Markus Friedrich and Daniel Bock equally contributed to the study     

The importance of disease associations and concomitant therapy for the long-term management of psoriasis patients

It is well established that several inflammatory-type conditions, such as arthritis, diabetes, cardiovascular disease, and irritable bowel disease exist comorbidly and at an increased incidence in patients with psoriasis. Psoriasis and other associated diseases are thought to share common inflammatory pathways. Conditions such as these, with similar pathogenic mechanisms involving cytokine dysregulation, are referred to as immune-mediated inflammatory diseases (IMIDs). Considerable evidence for the genetic basis of cormobidities in psoriasis exists. The WHO has reported that the occurrence of chronic diseases, including IMIDs, are a rising global burden. In addition, conditions linked with psoriasis have been associated with increasing rates of considerable morbidity and mortality. The presence of comorbid conditions in psoriasis patients has important implications for clinical management. QoL, direct health care expenditures and pharmacokinetics of concomitant therapies are impacted by the presence of comorbid conditions. For example, methotrexate is contraindicated in hepatic impairment, while patients on ciclosporin should be monitored for kidney function. In addition, some agents, such as beta blockers, lithium, synthetic antimalarial drugs, NSAIDs and tetracycline antibiotics, have been implicated in the initiation or exacerbation of psoriasis. Consequently, collaboration between physicians in different specialties is essential to ensuring that psoriasis treatment benefits the patient without exacerbating associated conditions.The authors are consultants to Schering-Plough Pharmaceuticals and have received an honorarium for their participation in this programme.     

The expression of interleukin-8 receptor in untreated and treated psoriasis

The expression of IL-8 in psoriasis has been clearly shown with the use of immunocytochemical, RT-PCR and in situ hybridization methods. The presence of its ligand, the IL-8 receptor, has been demonstrated by the RT-PCR technique. We report here a study of the expression of both IL-8 type A and B receptors by immunohistochemical techniques, using one polyclonal and four monoclonal antibodies. By this technique, we found that the neutrophilic granulocytes express the IL-8 type A receptor, whereas the IL-8 type B receptor was present on the keratinocytes. The type B receptor on the keratinocytes was localized in the suprabasal layers of the epidermis. Following therapy, the expression of the IL-8 type B receptor on the keratinocytes was reduced. This could suggest that IL-8 in psoriasis is involved in the disturbed differentiation rather than in proliferation, probably via an autocrine loop. Received: 18 October 1996     

斑秃毛囊退行性变及局部炎症细胞浸润的研究进展

斑秃是一种非瘢痕性的炎症性脱发性疾病,病情多能自限,但容易复发。斑秃发病机制不明,组织病理上表现为生长期毛囊周围炎症浸润及毛囊退行性变两个部分。目前研究认为,内外源因素作用于遗传易感人群引起生长期毛囊深层周围炎症细胞浸润,浸润的炎症细胞及细胞因子、神经肽等形成恶性循环,循环结局为毛囊上皮细胞凋亡,大批毛囊同时陕速进入退行期,导致斑秃发生。     

Autoradiographic and planimetric analyses of the inflammatory infiltrate in psoriatic lesions under PUVA-therapy

Summary The effects of oral 8-methoxypsoralen-photochemotherapy (PUVA-therapy) on the inflammatory infiltrate in 14 psoriatic skinlesions and on normal skin of 7 controls were investigated by means of autoradiography and planimetry. Under PUVA-therapy, one finds a significant decrease in dermal cells per millimeter lesion in psoriasis. Percentage of ³H-TdR-labeled dermal cells in the lesions and total number of dermal cells in the control group do not change significantly. The relative decrease of dermal cells per millimeter lesion in psoriasis is far less significant than the reduction of ³H-TdR-labeled epidermal cells under PUVA-therapy.Lecture held at VII^th Annual Meeting of the Arbeitsgemeinschaft Dermatologische Forschung (ADF), Innsbruck, Austria, November 16–18, 1979     

microRNA在炎症性皮肤病中作用的研究进展

【摘要】 microRNA（miRNA）是一类转录后调控基因表达的非编码RNA分子,参与皮肤各种病理生理过程。近年来,miRNA表达谱的变化已被报道与部分炎症性皮肤病相关,例如miR-203、miR-146a、miR-21在银屑病皮损中表达上调;miR-155、miR-146a在特应性皮炎皮损中表达上调;miR-21、miR-223、miR-142-3p、miR142-5p在过敏性接触性皮炎皮损表达上调;而miR-146a、miR-155在系统性红斑狼疮患者外周血表达下调;miR-223在皮肌炎皮损中表达下调等。本文综述miRNA与部分炎症性皮肤病发生、发展之间的联系。     

Biomarkers of psoriasis severity and therapy monitoring

Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluated using tools like Psoriasis Area and Severity Index that present some limitations and subjectivity. Clinicians select the therapy according to psoriasis severity, aiming that patients achieve longer remission periods and improve their quality of life. Biological markers for diagnosis and prognosis of psoriasis help to establish its severity and to monitor the therapeutic response; moreover, biomarkers of psoriasis assist clinicians in their therapeutic decision to treat psoriasis and to choose earlier and more adequate therapeutic strategies, avoiding or minimising worsening of psoriasis. With these markers, they would be able to monitor therapeutics, avoiding unnecessary therapeutic surcharge or changes to a more aggressive therapy. As any attempt to identify these biomarkers should be encouraged, in this review, we will debate published data concerning the proposal of biomarkers to evaluate severity and response to treatment of psoriasis vulgaris.     

A multicentre evaluation of the guidelines for the use of cyclosporin A in severe psoriasis

Background Controversy still exists as lo whether a dosage scheme for the treatment of severe psoriasis with cyclosporin A (CsA) should start with low dosages (3 mg/kg/day) or rather with high dosages (5 mg/kg/day). Aims In this open prospective multi-centre trial guidelines for the use of CsA in psoriasis beginning with low dosages were evaluated. A secondary aim of the study was to elucidate factors predicting efficacy of CsA treatment. Methods Efficacy and tolerability of CsA were evaluated monthly during 16 weeks in 86 patients (56 males, 30 females, mean age 43,0 ± 14,9 years) suffering from chronic severe plaque-type psoriasis, not responding to topical therapy (mean PASI 18.0 ± 8.1). All patients started with 3 mg/kg/day. Patients were defined as responders with a PASI reduction > 25% at month 1, ≥ 25% at month 1, ≥ 60% at month 3 and ≥ 70% at month 4. When a patient was a failure, the dose was increased by 1 mg/kg/day lo a maximum of 5 mg/kg/day. Results A gradual mean PASI reduction of 38%. 59%, 72% to 76% was reached with a mean CsA dose of 3.0, 3.2, 3.5, and 3.6 mg/kg/day at weeks 4, 8, 12 and 16. respectively. At the end of the study period, 39 patients were still on 3, 24 patients were on 4 and 15 patients were on 5 mg/kg/day. Due to subjective side-effects 6 patients dropped out on 3 mg/kg/day and 2 on 4 mg/kg/day. Diastolic and systolic blood pressure and creatinine levels were stable. Overall, CsA was relatively well tolerated. Absence of previous therapies, low baseline PASI and failure at week 4 were predictive for higher drop-out and failure rate and lower PASI at the end of study. Conclusions This study shows that a significant proportion of severe psoriasis patients can be treated with 3 mg/kg/day CsA with good tolerability and excellent clinical results. It is concluded that a treatment scheme with an optimal risk-benefit ratio should start with low dosages of CsA (3 mg/kg/day).     

寻常性银屑病患者并发代谢综合征影响因素的Logistic回归分析

目的探讨寻常性银屑病患者发生代谢综合征的相关影响因素。方法对202例确诊为寻常性银屑病的门诊患者进行问卷调查、体格及实验室检查,对寻常性银屑病患者发生代谢综合征的相关因素进行Logistic回归分析。结果年龄大、A型性格、不吃早餐、饮酒是寻常性银屑病患者并发代谢综合征的独立危险因素。结论积极调整患者心态,减轻精神压力,改善生活方式,可望降低和预防寻常性银屑病患者代谢综合征的发生。     

Alefacept therapy reduces the effector T-cell population in lesional psoriatic epidermis

Alefacept, a LFA-3/IgG1 fusion protein, interferes with the activation and proliferation of T cells by binding to the CD2 receptor on their surfaces. The clinical efficacy of this drug has been demonstrated in chronic plaque psoriasis. We performed a single-center, open-label study to investigate the immunohistochemical effects in psoriatic lesional skin. A group of 11 patients with plaque psoriasis all received 12 weekly doses of 7.5 mg alefacept intravenously. Skin biopsies were obtained at baseline and on days 8, 43 and 92, and were evaluated by digital image analysis after immunohistochemical staining. After completion of treatment, 8 out of the 11 patients experienced a reduction in PASI of 50% or more compared to baseline. Immunohistochemical analysis displayed a gradual decrease in the number of cutaneous T cells during therapy, with a significant reduction in epidermal CD8⁺ cells and dermal CD4⁺ cells on day 92. Patients with a reduction in PASI of 50% or more after therapy had a clearance of effector/memory T cells from the epidermis, in contrast to patients with a reduction in PASI of less than 50%. These findings support the hypothesis that effector/memory T cells play a prominent role in the pathogenesis of psoriasis, and that alefacept is capable of reducing these cells in lesional psoriatic skin.     

DNA repair elicited by UVB during PUVA therapy for psoriasis

Summary The skin of patients receiving psoralen and UVA (PUVA) therapy for psoriasis is exposed to trace amounts of UVB radiation emitted by PUVA irradiators in addition to UVA. DNA repair activity was measured using autoradiography in the uninvolved skin of PUVA-treated patients in order to determine whether 8-methoxypsoralen (8-MOP) plus UVA elicits repair, inhibits the skin repair response to UVB, or protects epidermal-cell DNA from UVB damage by promoting a tan. Epidermal-DNA repair activity was observed in 27 out of 37 patients following the first PUVA treatment. Phototesting with multiples of the initial UV dose elicited a linear increase in repair activity. Glass-filtered radiation failed to stimulate repair, indicating that the reaction was due to UVB, not to 8-MOP plus UVA. The same amount of repair activity was observed in the skin of patients irradiated either before or after 8-MOP ingestion, demonstrating that the drug did not interfere with the response of the skin to UVB. At clearing, however, the repair activity was never greater than that elicited at the initial treatment and was often undetectable despite a tenfold increase in UV exposure. It is proposed that DNA damage should be measured to determine whether epidermal cells are entirely protected from UVB radiation at the completion of therapy.     

Ex vivo culture of lesional psoriasis skin for pharmacological testing

BackgroundPsoriasis is a chronic, inflammatory skin disorder resulting from a complex interplay between immune and skin cells via release of soluble mediators. While a lot is known about the molecular mechanisms behind psoriasis pathogenesis, there is still a need for preclinical research models that accuratelyreplicate the disease.ObjectiveThis study aimed to develop and characterize ex vivo culture of psoriasis skin as a model for pharmacological testing, where the immunological events of psoriasis can be followed.MethodsFull thickness punch biopsies of lesional psoriasis skin were cultured in submerged conditions up to 144 h followingin situ T cell stimulation with rhIL-23 and anti-CD3 and anti-CD28 antibodies. The T cell mediated skin inflammation was assessed by gene and protein l analysis for a panel of inflammatory mediators. Tissue integrity and morphology were evaluated by histological analysis.ResultsT cell stimulation resulted in functional and psoriasis specificin situ activation of T cells. The expression levels of most of the proinflammatory mediators related to both immune and skin cells were comparable to these in freshly isolated tissue at 48 and 96 h of culture. Tissue integrity and morphology were sustained up to 96 h. Treatment with a corticosteroid reduced the expression of several pro-inflammatory cytokines and chemokines, whereas anti-IL-17A antibody treatment reduced the expression of the IL-17A downstream markers IL-8 and DEFB4.ConclusionBy preserving keyimmunopathological mechanisms of psoriasis, ex vivo culture of psoriasis skin can be used for the investigation of inflammatory processes of psoriasis and for preclinical drug discovery research.     

Optimal use of topical corticosteroids in inflammatory skin diseases

The optimal use of topical corticosteroids (TC) in the treatment of inflammatory disorders of the skin is related to a number of factors concerning the drug on the one hand (potency, pharmacological properties, formulation), and the patient on the other hand (type and phase of the disease, characteristics of the lesion, site to be treated, age and general conditions). The careful balance between drug and disease/patient allows the establishment of a simple series of gold standard guidelines for TC treatment.     

白细胞介素8在银屑病发病机理中的作用

用酶免疫组化法１３例银屑病皮撷 、９例非皮损皮肤和１０例正常皮肤组织中ＩＬ－８的表达与分布，并研究ＩＬ－８对表皮细胞增殖的影响。结果表明９例皮损组织 表层层显著显示ＩＬ－８阳性反应，而患者非皮损皮肤及正常人皮肤表皮层均呈阴性反应。体外实验证实，ＩＬ－８能明显促进原代培养的人表皮细胞增国殖，并呈一定的剂量依赖性。     

膜联蛋白A2在银屑病中的表达及意义

目的探讨银屑病患者外周血单个核细胞(PBMC)及皮损处膜联蛋白A2(annexin A2)的表达及其在银屑病发病中的意义。方法流式细胞术检测annexin A2在21例寻常型、5例脓疱型、5例关节病型、12例红皮病型银屑病患者及10例正常人PBMC上的表达;免疫荧光染色检测annexin A2在7例寻常型银屑病患者皮损和4例正常人皮肤处表达。结果 annexin A2在寻常型银屑病患者PBMC及皮损部位中表达均较正常对照增高(P<0.05),关节病型银屑病患者PBMC中annexin A2表达也增高(P<0.05),而红皮病型银屑病患者PBMC中annexinA2表达低于正常对照(P<0.01)。结论 annexin A2在寻常型银屑病患者PBMC和皮损处高表达,在关节病型银屑病PBMC中也高表达,而在红皮病型银屑病患者PBMC中低表达。     

早发型与晚发型银屑病的临床特点及遗传学研究

寻常性银屑病可根据年龄分为早发型与晚发型,许多学者就其遗传学和临床特点两方面进行了大量研究.最近的研究发现,早发型银屑病发病与等位基因rs10852936(17q12/IKZF3)突变等有关,晚发型银屑病发病则与白细胞介素1受体1等位基因中单核苷酸多态性rs887998、人白细胞抗原A中单核苷酸多态性rs2256919及等位基因人白细胞抗原C*12:02等有关.同时,地域间早发型与晚发型银屑病的临床特点也存在差异.早发型银屑病更易复发,易合并心理障碍;青春期发病患者发生点滴状皮损的概率高,且多与链球菌感染有关.晚发型银屑病易发生掌跖脓疱病、红皮病性银屑病,易合并糖耐量异常及肥胖症;老年发病患者家族史阳性率低,皮损较轻.