TNF-α与关节病型银屑病

临床中通过阻断TNF-α治疗关节型银屑病有效,因此TNF-α可能在PsA的发病中起重要作用,本文对TNF-α在关节病型银屑病中的作用机制做一综述。     

依那西普治疗银屑病的疗效和安全性

依那西普为肿瘤坏死因子α的拮抗剂，可用于治疗斑块状银屑病和银屑病关节炎。近期完成的Ⅱ、Ⅲ期临床试验证明，短期25mg或50mg皮下注射，每周2次连续12周，或者更长期的依那西普治疗．可以明显改善患者的症状和生活质量，不良反应较少且轻微，与对照组之间差异无统计学意义，在治疗儿童重度银屑病方面也有很好前景。依那西普可作为中重度斑块状银屑病和银屑病关节炎患者的治疗选择，但仍需进一步的大规模临床试验以充分明确其各方面特性。     

银屑病性关节炎患者血清中抗麦胶蛋白抗体检测

银屑病性关节炎(psoriatic arthritis,PsA)是一种与银屑病相关的关节疾病,因其临床表现与其他类风湿因子阴性的脊柱关节病相似,且与人类白细胞抗原(HLA)B27有一定相关性而被归类为血清阴性脊柱关节病.PsA除关节表现外,还有炎性肠病、脊椎炎性心脏病、眼病等关节外损害.已经发现,同时患有关节炎的乳糜泻患者,在给予无麦胶饮食治疗后,关节症状也明显改善,而乳糜泻与血清抗麦胶蛋白抗体(AGA IgA或IgG)有明确相关性[1].我们采用ELISA法检测PsA患者及寻常性银屑病患者血清中的AGA IgA抗体浓度,以研究PsA患者血清中AGA IgA抗体的表达及其意义.     

关节病型银屑病治疗进展——国际国内最新治疗建议与诊疗共识解读

关节病型银屑病(psoriatic arthritis, PsA)是一种与银屑病相关的慢性炎症性骨骼肌肉疾病,是银屑病的一种特殊类型。2021年国际银屑病和PsA研究评价组(Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, GRAPPA)更新了关节病型银屑病治疗建议,我国也发表了《中国关节病型银屑病诊疗共识(2020)》。本文将2021年GRAPPA新版诊疗共识与2015年版以及我国2020年新版诊疗共识进行比较,重点解读两个新版共识在关节病型银屑病治疗上的更新内容,以及国内外关节病型银屑病在药物治疗上的差异,以此梳理该病的最新诊疗思路。     

指间关节病性银屑病14例临床分析

关节病性银屑病(PsA)又称银屑病性关节炎,远端指间关节受累、不对称性关节炎、附着点炎及指(趾)炎是PsA的经典表现[1].Moll-Wright分类标准将本病分为5种类型:①远端指(趾)间关节炎型(DIP);②非对称性少关节炎型(AO);③对称性多关节炎型(SP);④残毁性关节炎型(AM);⑤脊椎关节病型(SPON)[2].为探讨特定类型PsA的临床特点,本文对首发类型为DIP型PsA患者的临床资料进行归纳总结.     

MTX对关节病型银屑病患者血清TNF-α影响的研究

目的：研究肿瘤坏死因子α（TNF-α）在关节病型银屑病发病中的作用及MTX对其调节作用，探讨MTX治疗关节病型银屑病的机制。方法：应用双抗体夹心酶联免疫吸附法（ELISA），检测15例关节病型银屑病患者经MTX治疗前后外周血清中TNF-α的水平。结果：MTX治疗前血清中。的水平显著高于治疗后及正常人对照组（P〈0．001）。结论：TNF—α在关节病型银屑病致病中可能起重要作用。MTX治疗关节病型银屑病的机制可能是通过抑制TNF-α的分泌而达到治疗作用。     

英夫利西单抗治疗关节病性银屑病进展

关节病性银屑病（PsA）可累及四肢、脊柱等单个或多个关节,是一种慢性炎症过程。70% ~ 85%患者在关节症状出现前有过皮损。约25% ~ 34%银屑病患者并发关节症状［1］。PsA具有较大侵蚀性,严重时可使关节畸形,甚至使患者丧失基本活动能力,具有难治性特点［2-3］。在银屑病的进程中,肿瘤坏死因子α（TNF-α）是占主导作用的炎症细胞因子,可刺激巨噬细胞和T细胞分泌炎症因子如白介素1（IL-1）、IL-6、IL-8,从而导致T细胞活化及增殖;TNFα也促进了破骨细胞的分化和成熟,并刺激成纤维细胞、破骨细胞和软骨细胞释放酶蛋白,从而破坏关节软骨和骨组织［4］。英夫利西单抗是抗TNFα单克隆抗体,系鼠源性抗原结合可变区与人源性免疫球蛋白G 1恒定区组成的生物嵌合体,与体液中或细胞膜表面的TNF-α具有高亲和力,干扰其与受体结合,从而阻断TNF-α的作用［5］……     

关节病型银屑病易感基因研究进展

关节病型银屑病(PsA )是一种伴有炎症性关节病变的严重类型银屑病.遗传流行病学研究显示与寻常型银屑病相比,PsA 具有更强的遗传易感性.近期全基因组关联研究发现了IL-12B 、IL-23R、TNF AIP3、TNIP1、IL-13、LCE等多个易感基因位点,揭示了Th17 细胞通路、NFκB通路、Th2 细胞通路、表皮分化通路等在银屑病和PsA发病机制中的作用.     

银屑病关节炎的药物治疗现状

银屑病关节炎(psoriatic arthritis,PsA)是一种与银屑病相关的炎性关节病,多为隐匿发病,病程迁延,易复发,晚期可有关节破坏强直,导致残疾。目前临床医师对于该病治疗的关键是在对其皮损治疗的基础上,缓解关节肿痛,保护功能,防止畸形发生。及时、合理地治疗可减少畸残,缓解皮损,提高生活质量,减轻患者的社会、心理压力。本文就银屑病关节炎的临床药物,如:非甾体类、激素类、抗风湿类及生物制剂等作一综述。     

银屑病关节炎发病的风险因素及其分子细胞机制研究进展

银屑病关节炎(psoriatic arthritis,PsA)是一种与银屑病相关的慢性炎症性关节病,主要表现为外周关节炎、附着点炎、指(趾)炎和脊柱关节炎,其临床表现和治疗反应具有较高的异质性,表现形式多样、复杂,且有一定的致残率,严重影响患者的身心健康、生活质量和工作能力。早期诊断和干预其病程可显著改善PsA临床前阶段的临床指标和影像学结果,因此,早期识别、治疗PsA对于改善患者长期预后非常重要。本文将就PsA的发病风险因素、早期预防策略及单纯皮肤受累的银屑病(cutaneous psoriasis,PsC)向PsA转变的分子细胞学机制进行综述。     

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白联合甲氨蝶呤治疗银屑病及其对白细胞介素17A和肿瘤坏死因子α的影响

目的 探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc,商品名益赛普)联合甲氨蝶呤对中重度斑块型银屑病患者血清和单个核细胞中白细胞介素(IL) 17A和肿瘤坏死因子(TNF-α)的影响.方法 2014年8月至2016年2月同济大学附属第十人民医院皮肤科门诊收治的30例中重度斑块型银屑病患者,分为益赛普组(15例)和益赛普+甲氨蝶呤组(15例),疗程24周.采用酶联免疫吸附法(ELISA)和实时定量PCR法检测两组患者治疗前后血清和外周血单个核细胞的IL-17A和TNF-α的浓度和mRNA表达水平.结果 治疗前益赛普+甲氨蝶呤组和益赛普组患者,血清IL-17A,TNF-α水平以及外周血PBMC中IL-17A,TNF-α mRNA的表达均显著高于健康对照组(P＜0.05);治疗后,益赛普+甲氨蝶呤组血清IL-17A、TNF-α浓度(142.67±14.82,70.07±25.02)及外周血PBMC中IL-17A、TNF-α mRNA表达(1.12±0.33,2.50±1.04)与益赛普组血清IL-17A、TNF-oα浓度(163.54±23.18,91.98±14.62)及外周血PBMC中IL-17A、TNF-α mRNA的表达(1.56±0.77,3.61±2.14)比较显著下降(P＜0.05).结论 益赛普联合甲氨喋呤治疗银屑病疗效优于单用益赛普治疗,联合治疗可以缩短治疗时间,提高疗效,其作用机制可能与下调IL-17A、TNF-α的表达量有关.     

中国关节病型银屑病诊疗共识（2020）

【摘要】 关节病型银屑病（又称银屑病关节炎）是银屑病的一种特殊类型，表现为外周、中轴关节不同程度受累，严重影响患者的生活质量。近年来其诊疗手段有了快速的发展，特别是生物制剂的出现明显提高了其治疗效果。本共识在国内外最新共识及指南的基础上，结合我国的诊疗现状，重点阐述关节病型银屑病的临床表现及分型、影像学及实验室检查、诊断标准和治疗等，为临床医生的诊疗工作提供参考依据。     

Efficacy and safety of etanercept in the treatment of recalcitrant psoriasis: An open-label,retrospective, observational study in Taiwan

BackgroundPsoriasis is a chronic inflammatory disease affecting the quality of life of patients. Traditional treatments are limited by adverse side effects. Etanercept is a biological agent used as an alternative treatment for psoriasis.MethodsThis open-label, observational study conducted in Taiwan involved 22 patients with recalcitrant psoriasis who received a 24-week treatment with etanercept—50 mg twice weekly (BIW) during the first 12 weeks and 25 mg BIW in the next 12 weeks. Psoriasis Area and Severity Index (PASI) score at Weeks 0, 12, and 24 were recorded. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), and tumor necrosis factor-alpha (TNF-α) at baseline, Week 12, and Week 24 were obtained. Adverse events and blood tests were recorded as safety assessment.ResultsAt Week 12, 54.5% and 13.6% patients achieved ≥50% improvement from baseline in PASI score (PASI 50 and PASI 75, respectively); at Week 24, 66.7% and 23.8% patients achieved PASI 50 and PASI 75, respectively. The mean improvement in PASI was 49.8% at Week 12 and 59.8% at Week 24, while 100% and 62.5% patients had reduced ESR and CRP levels, respectively. There were no deaths or serious adverse events. Four patients developed positive ANA, one of whom had poor psoriasis control. Most patients (93.8%) had higher serum TNF-α levels compared to baseline.ConclusionsEtanercept is effective and safe in treating recalcitrant psoriasis, reduces ESR and CRP levels, and occasionally induces positive ANA titer associated with poor psoriasis control. Serum TNF-α level may increase after treatment, but this does not seem to affect PASI improvement.     

英夫利西单抗长疗程治疗关节病型银屑病的临床疗效分析

目的：评价长疗程应用英夫利西单抗治疗关节病型银屑病的临床疗效。方法：随访分析2016年11月至2018年11月就诊于中国人民解放军总医院皮肤科接受英夫利西单抗治疗的关节病型银屑病患者。观察第2周、6周以及此后每间隔8周用药后的关节症状及皮损改善情况以及肿瘤坏死因子-α(TNF-α)等指标的变化。结果：8例患者用药疗程满30周,纳入数据分析, 其中5例满46周。LSD法显示,治疗后患者肿胀关节数（0周VS 30周：t=6.939,P<0.001;0周VS 46周：t=3.822,P=0.019)、压痛关节数（0周VS 30周：t=5.353,P=0.001;0周VS 46周：t=3.132,P=0.035)明显减少,PASI值在第30周时下降最明显（0周VS 30周：t=3.742,P=0.007）, TNF-α水平在第22周最高（0周VS 22周：t=3.569,P=0.009）,超过22周后逐渐降低（30周VS 46周：t=4.104,P=0.009）。 结论：英夫利西单抗能够显著改善关节病型银屑病患者的关节症状和皮损,但长疗程应用时疗效呈降低趋势。     

450例银屑病患者的口腔表现调查结果

为了探讨银屑病在口腔粘膜的临床表现及与皮损间的关系 ,对450例有皮肤病损的银屑病患者进行了口腔常规检查 ,并排除某些与银屑病可疑口腔病损有相似症状、体征的疾病。发现11例银屑病患者口腔粘膜发生病损 ,主要在红皮病型、掌跖脓疱型及关节病型中表现出来 ,有地图舌样损害、沟纹舌、粘膜糜烂、牛肉色变及口角炎 ,与皮损间有消长一致的关系。提示口腔粘膜可发生银屑病 ,其临床表现呈多样性 ,损害的发生与皮损的类型及严重程度有关。     

关节病型银屑病患者外周血中血管内皮生长因子(VEGF)水平的动态观测

目的：检测关节型银屑病患者外外周血中VEGF水平的改变，探讨其与PASI评分、治疗前后的关系。方法：采用双抗体夹心酶联免疫技术（ELISA）检测23例关节病型银屑病患者治疗前、中、治疗后血清中VEGF水平。另检测了23例正常人血清中的VEGF水平作为对照组。结果：关节病型银屑病患者血清中VEGF水平较正常对照组显著增高（P〈0．001），治疗前后患者血清中VEGF水平有显著差异（P〈0．05）。结论：VEGF在关节病型银屑病发病机制中起重要作用。     

Granulocyte pyruvate kinase in psoriasis vulgaris and psoriasis arthropathica

The activity of granulocyte pyruvate kinase in 46 patients with psoriasis vulgaris and eight patients with psoriasis arthropathica was investigated. It was found that in both groups of patients the activity of pyruvate kinase was significantly higher than in healthy individuals. This suggests that the rate of glycolysis in granulocytes of patients with psoriasis is markedly increased. The activity of granulocyte pyruvate kinase in 11 psoriatic patients with actively spreading lesions was compared with the activity of this enzyme when the patients were in remission. The activity of the enzyme was significantly increased during the active stage of the disease and returned to normal during remission.     

沙利度胺治疗关节病型银屑病疗效评价及对血浆VEGF水平的影响

目的：评价沙利度胺治疗关节病型银屑病的临床疗效以及对患者外周血中VEGF水平的影响。方法：30例关节病型银屑病患者口服沙利度胺治疗,150mg,每日1 次,疗程 12周;采用PASI评分标准及关节症状评分评价疗效。采用酶联免疫吸附试验（ELISA）测定患者治疗前后血清VEGF水平。结果：患者治疗后皮损和关节炎均较治疗前得到明显改善;血清中VEGF水平治疗后为(578.38±169.05) pg/L较治疗前（1045.56±289.28pg/L）明显下降。结论：沙利度胺治疗关节病型银屑病安全有效,其作用机制可能与抑制患者血浆VEGF有关。     

Subpopulations of T lymphocytes in psoriasis patients and their changes during immunotherapy

The content of T-lymphocytes and their basic subpopulations T-helpers and T-suppressors have been studied by means of monoclonal antibodies in the peripheral blood of 104 patients with different forms of psoriasis (56 patients with psoriasis vulgaris, 25 with exudative psoriasis, 10 with psoriasis arthropathica, and 13 with erythrodermic psoriasis). In all forms of psoriasis with a slight alteration in T-lymphocyte content a significant dysbalance of T-helpers and T-suppressors was found that brought about a decrease in the correlation ratio T-helpers/T-suppressors (T-helpers/T-suppressors in patients suffering from psoriasis vulgaris, 1.55 +/- 0.12; in those with exudative psoriasis, 1.24 +/- 0.16; with psoriasis arthropathica, 1.33 +/- 0.16; with erythrodermic psoriasis, 1.33 +/- 0.18; the control showed 1.82 +/- 0.08). The decrease in T-helpers/T-suppressors to 1.2 and lower that corresponded to a more severe clinical course of the disease was revealed in 27 patients having psoriasis vulgaris, in 13 with exudative psoriasis, in 7 with psoriasis arthropathica, and in 9 with erythrodermic psoriasis. The dysbalance in T-helpers/T-suppressors was due to a decrease in T-helpers and an increase in T-suppressors. To normalize T-helpers/T-suppressors, 27 psoriatics (20 with psoriasis vulgaris, 6 with exudative psoriasis, 1 with erythrodermic psoriasis) received immunomodulators Thymalinum and Natrii nucleinas in addition to antipsoriatic therapy, which resulted in an increase in T-helper/T-suppressor ratio, on the average up to 1.74 +/- 0.16 (prior to treatment T-helper/T-suppressor ratio in these patients was 1.0 +/- 0.14) and was followed by a favorable clinical course (shorter periods of skin rash regression, prolonged remissions).(ABSTRACT TRUNCATED AT 250 WORDS)     

TNF-α downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-α antagonists to improve skin barrier

Filaggrin (FLG), loricrin (LOR), and involucrin are important epidermal barrier proteins. As psoriasis is characterized by overexpression of tumor necrosis factor-α (TNF-α) and impaired skin barrier, we investigated the expression of skin barrier proteins in psoriasis patients and whether their expression was modulated by TNF-α. The expression of FLG and LOR was found to be decreased in lesional and non-lesional skin of psoriasis patients. A correlation was found between the expression of TNF-α and epidermal barrier proteins in psoriasis. TNF-α was found to modulate the expression of FLG and LOR via a c-Jun N-terminal kinase-dependent pathway. Importantly, we report that clinical treatment of psoriasis patients with a TNF-α antagonist results in significant enhancement of epidermal barrier protein expression. Our current study suggests that TNF inhibits barrier protein expression, and TNF-α antagonists may contribute to clinical improvement in patients with psoriasis by improving barrier protein expression.