甲氨蝶呤对关节病性银屑病患者血清金属蛋白酶-2、-9的影响

银屑病性关节炎（psoriasis arthritis,PA）又称为关节病性银屑病。近年来大量的实验研究揭示,在关节病性银屑病滑膜血管翳的形成与降解胶原和蛋白聚糖等细胞外基质的一组金属蛋白酶（matrix metalloproteinases,MMPs）有关,MMPs家族的某些成员可能是促进滑膜血管翳形成的重要因素。笔者对关节病性银屑病患者在甲氨蝶呤（MTX）治疗前、后进行血清MMP-2和MMP-9检测．以期阐明它们在关节病性银屑病发病中的作用,及进一步探讨MTX治疗关节病性银屑病的机制。[第一段]     

甲氨蝶呤治疗银屑病的再评价

甲氨蝶呤是一个有效的抗银屑病药物,自1960年以来已广泛地用于治疗严重的、急性泛发性脓疱型、红皮病型、关节病型以及外用药无效的泛发性慢性斑块状银屑病。目前尚无与其它治疗严重银屑病的系统疗法如:环孢素、维A酸或PUVA等光化学疗法的比较资料,但甲氨蝶呤比较便宜,正确使用还是安全的。其重要的不良反应为急性骨髓抑制,特别是老年患者、有肾脏损害和(或)叶酸缺乏者容易发生,也可能是用药过量或药物相互作用等原因造成的。长期用甲氨蝶呤的危险是肝纤维化,其与甲氨蝶呤的累积量相关。     

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。     

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。     

红皮病型、脓疱型、关节病型银屑病并发11例临床分析

目的:分析重症银屑病的临床特征。方法:对2011-2013年11例红皮病型银屑病、脓疱型银屑病及关节病型银屑病同时并发的患者进行回顾性分析。结果:重症银屑病经治疗,大部分患者皮损缓解较快,而关节炎缓解较慢。结论:关节病型银屑病是治疗难点,以传统抗风湿病药物治疗为主,可同时应用生物制剂以改善病情。     

银屑病住院患者251例回顾性分析

目的总结北京某三甲医院近十年银屑病住院患者的诊治经验。方法回顾总结2007年6月-2018年4月间所有住院银屑病患者病历。结果共有251例患者住院492次,男性占68.13%。13.55%的患者合并代谢综合征,其中10.36%为住院后首次发现。住院时长中位数9 d(1 d,19 d),住院费用中位数6 802.97元(4 329.92元,13 820.26元),自2015年生物制剂开始使用后,住院时长明显缩短,但住院费用明显增加。10.16%例次出现发热。IgE升高达47.63%例次,IgE水平与血沉和C反应蛋白显著相关;红皮病型银屑病IgE水平显著高于非红皮病型银屑病;关节病型银屑病IgE水平显著高于非关节病型银屑病。最常用的非生物制剂治疗是苦参素葡萄糖注射液(58.19%例次)和丹参注射液(33.10%例次);阿维A、甲氨蝶呤和环孢素的应用例次分别为33.10%、4.18%和2.09%;生物制剂中应用最多的是英夫利昔单抗(38.82%例次)。结论生物制剂显著改变了银屑病患者的治疗模式;银屑病与代谢综合征的关系需要进一步重视;IgE在银屑病尤其是红皮病型和关节病型银屑病的发病中具有一定意义。     

误用大剂量甲氨蝶呤致大疱性表皮松解性药疹

患者女,22岁。因关节病性银屑病在外院给予甲氨蝶呤100mg每日1次静脉滴注,连用5d后全身皮肤出现弥漫性红斑、肿胀、水疱、糜烂伴疼痛,并累及口、眼、鼻等腔口部位,伴血液系统及肝脏损害。诊断:(1)大疱性表皮松解性药疹(甲氨蝶呤所致);(2)继发性粒细胞缺乏(甲氨蝶呤所致);(3)关节病性银屑病。治疗:予以亚叶酸钙,水化,碱化尿液,甲泼尼龙,丙种球蛋白,重组人粒细胞刺激因子,防治感染及对症支持治疗,2周后缓解出院。随访1年,病情稳定。     

重症关节病型银屑病误诊与治疗分析

我科于2005年7月～2006年9月收治2例重症关节病型银屑病,应用维A酸治疗取得满意疗效,现报道如下.     

IL-17A单抗治疗儿童泛发性脓疱型银屑病一例并文献复习

传统药物如甲氨蝶呤,阿维A和环孢菌素A等治疗儿童泛发性脓疱型银屑病（GPP）受到限制,目前没有针对青少年GPP的标准化诊疗指南,本文报道IL-17A单抗成功治疗儿童脓疱型银屑病一例并进行文献复习。     

阿维A治疗重症银屑病的临床评价

于2004年7月～2006年6月应用阿维A治疗重症银屑病33例,取得满意疗效,现报道如下. 临床资料 重症银屑病患者33例,女14例,男19例,其中红皮病型为24例,脓疱型4例,关节病型5例.     

Therapeutic depletion of myeloid lineage leukocytes by adsorptive apheresis for psoriatic arthritis: Efficacy of a non‐drug intervention for patients refractory to pharmacologics

Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease‐modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn^®. The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in seven of 10 (70%) and five of 10 (50%) patients at the follow‐up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA.     

复方甘草酸苷递减疗法联合依巴斯汀治疗慢性荨麻疹疗效观察

目的观察复方甘草酸苷递减疗法联合依巴斯汀治疗慢性荨麻疹的疗效。方法 90例慢性荨麻疹患者随机分为治疗组和对照组,各45例。治疗组口服依巴斯汀片10mg,1次/d,同时口服复方甘草酸苷,第1～4周递减疗法依次为50mg3次/d,50mg2次/d,25mg3次/d,25mg2次/d,第5～6周25mg1次/d。对照组口服依巴斯汀片10mg,1次/d,复方甘草酸苷50mg,3次/d。均连用6周后计算疗效指数并判定疗效。结果两组有效率(88.10%,68.29%)和复发率(16.22%,46.43%)比较差异均有统计学意义(P<0.05)。结论复方甘草酸苷递减疗法联合依巴斯汀治疗慢性荨麻疹疗效肯定,复发率较低。     

The morbidity of psoriatic disease

There is a considerable area of intersection between the negative consequences of psoriatic skin inflammation and the negative consequences of psoriatic joint inflammation. However, available evidence indicates that PsA also has a unique set of possible undesirable outcomes, such as severe disability and increased mortality, that are particularly serious. In light of this evidence, it has become increasingly clear that PsA is not the relatively mild condition it was once believed to be, but rather a disease that can have a dramatic negative impact on affected patients.     

Efalizumab for the treatment of psoriatic arthritis

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. Efalizumab, a T cell-targeted, recombinant human monoclonal antibody, is approved for the treatment of adult patients with chronic moderate to severe plaque psoriasis. The effect of efalizumab therapy on PsA has not previously been investigated. OBJECTIVE: This phase II randomized, double-blind, placebo-controlled multicenter study evaluated the efficacy and safety of efalizumab for the treatment of PsA. METHODS: Patients were required to be on at least one of the following concomitant systemic therapies for PsA: nonsteroidal anti-inflammatory drugs, corticosteroids, and/or sulfasalazine or methotrexate. One hundred fifteen patients with active PsA were enrolled and randomized in the study. Of these, 107 were treated weekly with efalizumab 1 mg/kg or placebo for 12 weeks, followed by 12 additional weeks of open-label efalizumab. RESULTS: At week 12, 28% of efalizumab-treated patients achieved ACR-20 response (a 20% reduction from the baseline in the American College of Rheumatology response criteria), the primary end point, compared with 19% of placebo patients (p = .27). The safety profile was comparable between efalizumab- and placebo-treated patient groups, regardless of methotrexate background therapy, and no worsening of joint disease occurred with efalizumab therapy. CONCLUSIONS: Efalizumab was not effective in treating PsA; efalizumab therapy did not worsen PsA. The efalizumab safety profile does not appear to be altered with the concomitant use of methotrexate therapy.     

Adalimumab markedly improves enthesitis in patients with psoriatic arthritis: Evaluation with a magnetic resonance imaging scoring system

Psoriatic arthritis (PsA), a seronegative arthropathy, may often result in progressive joint damage without treatment, leading to disability and impaired quality of life. Early therapeutic intervention of PsA is therefore crucial before the development of irreversible joint damage. Because psoriatic skin lesions generally precede the onset of PsA, dermatologists occupy an important position in treating patients with early PsA. This study aimed to evaluate the efficacy of adalimumab in treating joint disease in patients with PsA, using the PsA magnetic resonance imaging scoring system (PsAMRIS). Five adult Japanese male patients with active PsA were treated with adalimumab. Magnetic resonance imaging was obtained at baseline and 8–32 weeks with 2–3 time points following adalimumab treatment and assessed using PsAMRIS. Adalimumab treatment markedly improved clinical symptoms and disease activities of joint disease, which was confirmed by the reduction of PsAMRIS scores in all patients. Bone marrow edema and periarticular inflammation, reflecting the presence of enthesitis, were dramatically improved at week 8, while improvement of synovitis and flexor tenosynovitis was observed later, at week 24 or 32. However, bone erosion was not improved by adalimumab treatment during the follow‐up period. These results indicate that adalimumab treatment is associated with dramatic improvement of enthesitis in patients with PsA, whereas bone erosion may be resistant to such treatment. PsAMRIS appears to be useful for the evaluation of treatment efficacy in PsA.     

Doxycycline 40 mg Capsules (30 mg Immediate-Release/10 mg Delayed-Release Beads)

Anti-inflammatory dose doxycycline 40 mg capsules (30 mg immediate-release and 10 mg delayed-release beads) provide a sub-antimicrobial dose that reduces the inflammatory response in patients with rosacea without producing drug concentrations required to treat bacterial diseases. The efficacy of oral, anti-inflammatory dose doxycycline 40 mg capsules once daily in the treatment of adults with rosacea was demonstrated in two pivotal large, randomized, double-blind, placebo-controlled, multicenter trials. After 16 weeks’ therapy, anti-inflammatory dose doxycycline 40 mg was significantly more effective in improving rosacea than placebo, providing a greater reduction in the total inflammatory lesion count (primary endpoint) than placebo. Anti-inflammatory dose doxycycline 40 mg was associated with a rapid onset of action, achieving a significantly greater decrease in total inflammatory lesion count than placebo by the first follow-up visit at week 3 in both studies. Maximum anti-inflammatory efficacy appears to be achieved with doxycycline 40 mg capsules once daily, as no additional improvement in rosacea symptoms was achieved with oral doxycycline 100 mg once daily (usual antibacterial dosage) in a small, randomized, double-blind trial. Anti-inflammatory dose doxycycline 40 mg was generally well tolerated in clinical trials, with most adverse events being of mild to moderate intensity.     

How does the joint dermatology–rheumatology clinic benefit both patients and dermatologists?

Psoriasis (Pso) and psoriatic arthritis (PsA) are chronic and debilitating diseases which often develop in the same patient and are linked to a wide range of comorbid conditions. Dermatologists and rheumatologists need to cooperate in combined clinics, especially when they deal with severe, recalcitrant disease, and multiple comorbidities. The clinical and research benefits of this collaboration have been previously described to contribute to a better and more sustainable health care system. To apply a more holistic approach of patients with Pso and PsA, we established the first dual care clinic in Greece, for Pso and PsA patients, based at Attikon General University Hospital. Hereby, we describe the infrastructure and operation of a combined Pso and PsA clinic (PPAC), in the national health care system of Greece, and its impact on the management of Pso and PsA. The PPAC is a single‐day joint clinic, held once a week, which consists of three dermatologists and three rheumatologists. We present the results of 185 newly diagnosed patients between December 2018 and January 2019. Mean age of onset of Pso was 34 ± 16 years old and 47 ± 12 years old for PsA. Most patients suffered from severe plaque Pso (144/185, 78%) and asymmetric oligoarticular arthritis (59/185, 32%), for which they were receiving treatment with biologic agents (105/185, 57%). Many required monitoring for hypertension (74/185, 40%), dyslipidemia (69/185, 37%), diabetes (17/185, 9%), and depression (20/185, 11%). Patients reported high levels of care satisfaction (visual analogue scale: 86 ± 11.5), using the PPAC facility, compared to different referrals between specialties. This is the first joint dermatology–rheumatology clinic in Greece, providing comprehensive care in patients with Pso and PsA. Our results support the concept of combined clinics delivering better integrated care for such patients.     

司库奇尤单抗治疗红皮病型银屑病一例并文献复习

报道一例司库奇尤单抗治疗红皮病型银屑病治疗效果并复习相关文献。41岁红皮病型银屑病男性患者，在排除肝炎、结核的基础上，经知情同意后，给予司库奇尤单抗标准方案：0~4周每周皮下注射300 mg，随后每4周注射300 mg。在第4周达到PASI 75，第8周达到PASI 100。随访32周未见明显复发及不良反应。     

钙泊三醇搽剂联合丙酸倍氯米松霜治疗头皮银屑病疗效观察

目的评价钙泊三醇搽剂联合丙酸倍氯米松霜治疗头皮银屑病的疗效与安全性。方法将55例患者随机分为治疗组和对照组,治疗组每早1次使用钙泊三醇头皮搽剂,每周用量不超过15mL;每晚1次使用丙酸倍氯米松霜,每周用量不超过15mg。对照组:每日早晚各1次使用丙酸倍氯米松霜,每周用量不超过30mg,疗程均为6周。结果治疗组和对照组有效率分别为85.30%和52.38%,差异有显著性意义(X2=9.361,P<0.05)。结论钙泊三醇搽剂联合丙酸倍氯米松霜治疗头皮银屑病安全、有效。     

司库奇尤单抗300 mg和150 mg治疗银屑病性关节炎长期疗效比较meta分析

目的：比较司库奇尤单抗300 mg和150 mg治疗银屑病性关节炎(PsA)长期疗效的差异。方法：在Pubmed、Cochrane Library、 MEDLINE、EMBASE、中国知网、万方数据库和维普数据库中检索司库奇尤单抗300 mg和150 mg治疗PsA的随机对照试验（RCTs），提取相关数据，用RevMan5.3软件进行meta分析。结果：根据纳入标准共纳入5篇文献进行分析，包括3项RCTs。52周时，司库奇尤单抗300 mg治疗后美国风湿病学会疗效标准改善20%、50%及70%（ACR 20/50/70）的应答率、起止点炎缓解率、指趾炎缓解率与150 mg相比无显著差异，而300 mg治疗的PASI提高75%、90%（PASI 75/90）应答率均高于150 mg（P=0.002，0.01）。52周时，接受过肿瘤坏死因子抑制剂治疗(TNFi-exposed)的患者司库奇尤单抗300 mg治疗后ACR 20和PASI 75应答率均高于150 mg（P=0.006，0.04），而在未接受过肿瘤坏死因子抑制剂治疗(TNFi-naive)患者中300 mg和150 mg治疗后ACR 20和PASI 75应答率无显著差异(P=0.85，0.59)。结论：在长期疗效方面，司库奇尤单抗300 mg对PsA患者关节损害及功能的改善与150 mg无显著差异，而对皮损的改善有优势；对TNFi-exposed的PsA患者，司库奇尤单抗300 mg比150 mg有更好的疗效。