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Severe MTX Toxicity in Rheumatic Diseases - Analysis of 22 Cases 甲氨蝶呤在风湿病中的严重毒性22例分析
Pub Date : 2019-03-31 DOI: 10.23937/2469-5726/1510070
R. Bergner, D. Wadsack, C. Löffler
Background: Severe MTX (methotrexate) toxicity due to low dose MTX used in rheumatic diseases is rare but linked with a high mortality ranging from 13 to 44%. We analyzed 22 cases with a minimum toxicity of CTC (common toxicity criteria) grade 2, that were admitted to our hospital. Methods: We retrospectively analyzed epidemiological data, the weekly MTX dosage, renal function before and at the beginning of the adverse event, co-medication with influence on MTX toxicity or on renal function and potential other co-factors like infections, as well as the outcome, respectively. Results: 22 patients were involved in the study. Three patients died due to pneumonia, all other patients recovered. The main reason for toxicity was an impaired renal function (82%), either from acute renal failure or from acute on chronic renal failure or chronic renal disease stage 4. In 5 cases a dosing error, mainly with daily instead of weekly MTX intake, was the reason. Only in one case the reason remains unclear. Discussion: An impaired renal function with an estimated glomerular filtration rate (eGFR) of 11-54 ml/min was the main cause for MTX toxicity with dosage errors being the second numerous reasons. Our data are in accordance with previous case series, but the influence of reduced renal function is still higher than in the most reports. One reason might be that most case series took only into account the serum creatinine but not a calculated GFR. Serum creatinine alone underestimates the stage of renal failure in patients with lower muscle mass.
背景:由于用于风湿病的低剂量甲氨蝶呤引起的严重甲氨蝶呤毒性很少见,但与13%至44%的高死亡率相关。我们分析了22例最低毒性为CTC(常见毒性标准)2级的住院患者。方法:回顾性分析流行病学资料、不良事件发生前和开始时甲氨喋呤周剂量、肾功能、联合用药对甲氨喋呤毒性或肾功能的影响以及感染等潜在的其他辅助因素以及结局。结果:22例患者纳入研究。3名患者死于肺炎,其余患者均已康复。毒性的主要原因是肾功能受损(82%),无论是急性肾功能衰竭还是急性或慢性肾功能衰竭或慢性肾脏疾病4期。在5例病例中,剂量错误是主要原因,主要是每天而不是每周服用MTX。只有一个案例的原因尚不清楚。讨论:估计肾小球滤过率(eGFR)为11-54 ml/min的肾功能受损是MTX毒性的主要原因,剂量错误是第二个众多原因。我们的数据与以前的病例系列一致,但肾功能下降的影响仍然高于大多数报道。一个原因可能是大多数病例序列只考虑了血清肌酐而没有计算GFR。血清肌酐单独低估了低肌肉量患者肾功能衰竭的分期。
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引用次数: 1
Muscle Ultrasound in Inflammatory Myopathies: A Critical Review 肌肉超声在炎性肌病中的应用综述
Pub Date : 2019-03-31 DOI: 10.23937/2469-5726/1510069
Leeuwenberg Kristofoor E, Albayda Jemima
Muscle ultrasonography is an upcoming tool in the evaluation of neuromuscular disorders. It is easily applicable in multiple clinical settings, has no contraindications, and provides a cost-effective alternative to other imaging modalities such as MRI. However, a known disadvantage of ultrasound is its dependence on examiner expertise. Furthermore, the assessment of muscle quality is done mainly through an assessment of muscle echo intensity, which is affected by machine/system settings, hampering comparison across centers. Over the years new methods have been developed to make results more objective and comparable for the assessment of myopathies. In this review, we will examine the role of ultrasound in the evaluation of idiopathic inflammatory myopathies (IIM), a heterogeneous group of autoimmune disorders which may be treatment-responsive. Studies have shown that ultrasound can be useful both for diagnosis and follow-up of IIM, particularly for dermatomyositis and inclusion body myositis. The addition of other ultrasound modalities such as Doppler and elastography, as well as the application of machine learning, appear promising for IIM. Further developments of these techniques are expected and will lead to more widespread use of ultrasound in the clinical assessment of IIM.
肌肉超声检查是神经肌肉疾病评估的新工具。它很容易适用于多种临床环境,没有禁忌症,并提供了一种具有成本效益的替代其他成像方式,如MRI。然而,超声波的一个众所周知的缺点是它依赖于审查员的专业知识。此外,肌肉质量的评估主要是通过评估肌肉回声强度来完成的,这受到机器/系统设置的影响,阻碍了跨中心的比较。多年来,新的方法已经发展,使结果更加客观和可比较的评估肌病。在这篇综述中,我们将研究超声在特发性炎症性肌病(IIM)评估中的作用,IIM是一种异质的自身免疫性疾病,可能对治疗有反应。研究表明,超声可用于IIM的诊断和随访,特别是皮肌炎和包涵体肌炎。多普勒和弹性成像等其他超声模式的加入,以及机器学习的应用,对IIM来说似乎很有希望。这些技术的进一步发展有望导致超声在IIM临床评估中的更广泛应用。
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引用次数: 15
Modulation of Histone Deacetylases (HDACs) Expression in Patients with and without Systemic Lupus Erythematosus: Possible Drug Targets for Treatment 组蛋白去乙酰化酶(hdac)在系统性红斑狼疮患者和非系统性红斑狼疮患者中的表达调节:可能的药物治疗靶点
Pub Date : 2018-12-31 DOI: 10.23937/2469-5726/1510060
Wiley Kenneth L, Treadwell Edward, M. Kayihura, Word Beverly, Oates Jarren, Lyn-Cook Beverly D
There is increasing evidence that epigenetic factors may play a role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Both global and gene specific methylation is known to occur in lupus patients, as well as, changes in histone acetylation status. Histone acetylation is associated with active chromatin or activation of genes, whereas histone deacetylase (HDAC) activity is associated with silencing of genes. Therefore, HDACs have been targeted as potential therapeutic targets for a number of diseases, including lupus. The purpose of this study was to determine histone deacetylase (HDAC) expression in patients who are diagnosed with SLE compared to age-matched healthy controls. Quantitative real-time PCR expression levels of HDAC 1, HDAC 2 and HDAC 7 were investigated in peripheral blood mononuclear cells of African American and European American women. Our results showed that HDAC 1 expression is significantly (p < 0.0039) elevated in lupus patients compared to controls. HDAC 2 expression is also increased in lupus patients (p < 0.0427). However, HDAC 7 showed no significant difference (p < 0.4644) in expression in our SLE patients compared to their controls. Those lupus patients with a SLE disease activity index (SLEDAI) of 4 or greater showed lower expression of HDAC 1 (p < 0.0026) compared to those with modest disease and a SLEDAI of less than 4. However, in those lupus patients with a SLEDAI of 4 or greater showed increased expression of HDAC2 (p < 0.053) when compared to those with a SLEDAI of less than 4. This observation was also noted in HDAC7. Increased expression in HDAC 1 and 2 has been associated with induced kidney injury and induction of proinflammatory cytokines.
越来越多的证据表明,表观遗传因素可能在系统性红斑狼疮(SLE)的发病机制中发挥作用。已知狼疮患者会发生整体甲基化和基因特异性甲基化,以及组蛋白乙酰化状态的变化。组蛋白乙酰化与染色质活性或基因激活有关,而组蛋白去乙酰化酶(HDAC)活性与基因沉默有关。因此,hdac已成为包括狼疮在内的许多疾病的潜在治疗靶点。本研究的目的是确定组蛋白去乙酰化酶(HDAC)在SLE患者中的表达,并与年龄匹配的健康对照进行比较。采用实时荧光定量PCR检测非裔美国人和欧裔美国女性外周血单核细胞中HDAC 1、HDAC 2和HDAC 7的表达水平。我们的研究结果显示,与对照组相比,狼疮患者的HDAC 1表达显著(p < 0.0039)升高。HDAC 2在狼疮患者中的表达也有所增加(p < 0.0427)。然而,与对照组相比,HDAC 7在SLE患者中的表达无显著差异(p < 0.4644)。SLE疾病活动性指数(SLEDAI)大于或等于4的狼疮患者与SLE疾病活动性指数小于4的狼疮患者相比,HDAC 1的表达较低(p < 0.0026)。然而,与SLEDAI小于4的狼疮患者相比,SLEDAI大于或等于4的狼疮患者HDAC2表达增加(p < 0.053)。在HDAC7中也注意到了这一点。HDAC 1和2的表达增加与诱导肾损伤和诱导促炎细胞因子有关。
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引用次数: 1
Clinical Pharmacological Management Status of Systemic Lupus Erythematous Population: Situational Analysis 系统性红斑狼疮人群的临床药理学管理现状:情境分析
Pub Date : 2018-12-31 DOI: 10.23937/2469-5726/1510068
Balushi Farida Al, Salmi Issa Al, Metry Abdel Masiah, Yousef Mohammed Abdalla, H. Suad
Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has various manifestations among different populations. This study aims to provide an overview of medical pharmacological management that SLE population received immediately at time of diagnosis. Method: This is a retrospective analysis using patients’ registry medical information system. All patients diagnosed with SLE were reviewed by accessing their medical records including pharmacy prescription and dispersions at the Royal hospital from 2006 to 2014. The following comorbidities were analyzed: diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, lung disease, cardiovascular disease (CVD), cerebrovascular accident (CVA), chronic kidney disease (CKD), end-stage kidney disease (ESKD), infections, thyroid disease, malignancy, and miscarriages. Results: There were 966 patients diagnosed with SLE during the period from 2006 to 2014. The Mean (SD) of age at presentation was 35.5 (11.5) years. Most patients were female (88.7%) with mean age of 27.6 (1.4) years. Unsurprisingly anti-malarial drug, hydroxychloroquine was used in 95% of SLE patients and steroid therapy was used in 93% in which 60.95% received Methylprednisolone pulse. The immunosuppressive agent of choice was Cyclophosphamide in 25.04%. Mycophenolic acid (MPA) medication in 39.85% and azathioprine in 37.06% of patients. Anti CD20 monoclonal antibodies, rituximab, was used in 20.91%. Calcineurin inhibitors were used in total of 11% of patients (cyclosporin a in 6.72% and tacrolimus in 4.35%). Conclusion: The complexity of SLE presentation have led to diverse pharmacotherapeutic strategies based on the organ systems involved. Management is individualized and depends on presenting symptoms and reducing the likelihood of permanent damage to organs and tissues. Strengthen health system at primary level and education of public and health work force is the main challenge to further improve the management. The overall aim of management was to determine the extent of disease and prevent extensive organ involvement and deal with various traditional and non-traditional CVD risk factors. The involvement of clinical pharmacist is very important to further strengthen the pharmacological management of lupus patients.
系统性红斑狼疮(SLE)是一种慢性炎症性疾病,在不同人群中有不同的表现。本研究旨在概述SLE人群在诊断时立即接受的药物管理。方法:采用患者登记医疗信息系统进行回顾性分析。所有被诊断为SLE的患者通过查阅其2006年至2014年在皇家医院的医疗记录进行审查,包括药房处方和分散。分析了以下合并症:糖尿病(DM)、高血压(HTN)、高脂血症、肺病、心血管疾病(CVD)、脑血管意外(CVA)、慢性肾病(CKD)、终末期肾病(ESKD)、感染、甲状腺疾病、恶性肿瘤和流产。结果:2006 - 2014年诊断为SLE患者966例。发病时平均年龄(SD)为35.5(11.5)岁。大多数患者为女性(88.7%),平均年龄27.6(1.4)岁。不出所料,95%的SLE患者使用抗疟疾药物羟氯喹,93%的SLE患者使用类固醇治疗,其中60.95%接受甲基强的松龙脉冲治疗。选择免疫抑制剂为环磷酰胺(25.04%)。服用霉酚酸(MPA)的占39.85%,服用硫唑嘌呤的占37.06%。20.91%的患者使用抗CD20单克隆抗体利妥昔单抗。11%的患者使用钙调磷酸酶抑制剂(环孢素a占6.72%,他克莫司占4.35%)。结论:SLE表现的复杂性导致了基于所涉及器官系统的不同药物治疗策略。治疗是个体化的,取决于表现症状和减少对器官和组织造成永久性损害的可能性。加强基层卫生体系建设和公共卫生队伍教育是进一步提高管理水平的主要挑战。管理的总体目标是确定疾病的程度,防止广泛的器官受累,并处理各种传统和非传统的心血管疾病危险因素。临床药师的参与对进一步加强狼疮患者的药理管理至关重要。
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引用次数: 2
Rheumatologic Diseases as Paraneoplastic Syndromes - A Paradigmatic Case 类风湿疾病作为副肿瘤综合征-一个典型案例
Pub Date : 2018-12-31 DOI: 10.23937/2469-5726/1510067
Figueiredo Inês Rego de, Alves Rita Vieira, Castro Sara Guerreiro, Lourenço Filipa, Antunes Ana Margarida, Gruner Heidi, Panarra António
Rheumatic diseases can be a paraneoplastic syndrome for an occult neoplasia. Some syndromes are more characteristic than others. In this case report, we present a patient with musculoskeletal symptoms suggestive of both carcinomatous arthritis and polymyalgia rheumatica that was shown to have adenocarcinoma of the lung. The musculoskeletal symptoms accompanied the course of the disease, disappearing with the treatment and re-occurring when it relapsed. *Corresponding author: Inês Rego de Figueiredo, Serviço de Medicina 7.2 Hospital Curry Cabral, Centro Hospitalar Lisboa Central (CHLC), Rua da Beneficiência 8, 1050-099 Lisboa, Portugal CASe RePoRt
风湿病可以是隐匿性肿瘤的副肿瘤综合征。有些综合症比其他综合症更具特征性。在这个病例报告中,我们提出了一个患有癌性关节炎和风湿性多肌痛的肌肉骨骼症状的患者,该患者被证明患有肺腺癌。肌肉骨骼症状伴随病程,随治疗消失,复发时再次出现。*通讯作者:Inês Rego de Figueiredo, servialo de Medicina 7.2 Hospital Curry Cabral, Centro Hospital Lisboa Central (CHLC), Rua da Beneficiência 8,1050 -099葡萄牙里斯本病例报告
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引用次数: 3
Monitoring the Time Course of Disability through a Self-Assessment Instrument "Activity Index" (IA) in RA Patients 通过自我评估工具“活动指数”(IA)监测RA患者残疾的时间过程
Pub Date : 2018-09-30 DOI: 10.23937/2469-5726/1510065
Ren L, Zhang X, L. Zg, Tang H, Theiler R
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引用次数: 1
A Case of Hydroxychloroquine Induced Hypoglycaemia in a Non-Diabetic Patient 羟基氯喹致非糖尿病患者低血糖1例
Pub Date : 2018-09-30 DOI: 10.23937/2469-5726/1510066
D. Richard, D. Teresa
Citation: De-Heer R, Doherty T (2018) A Case of Hydroxychloroquine Induced Hypoglycaemia in a Non-Diabetic Patient. J Rheum Dis Treat 4:066. doi.org/10.23937/2469-5726/1510066 Accepted: September 27, 2018: Published: September 29, 2018 Copyright: © 2018 De-Heer R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
引用本文:De-Heer R, Doherty T(2018) 1例羟氯喹诱导的非糖尿病患者低血糖。《风湿病杂志》第4期。doi.org/10.23937/2469-5726/1510066接收日期:2018年9月27日发布日期:2018年9月29日版权所有:©2018 De-Heer R, et al.。这是一篇根据知识共享署名许可协议发布的开放获取文章,该协议允许在任何媒体上不受限制地使用、分发和复制,前提是要注明原作者和来源。
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引用次数: 5
Ten Year Risk of Cardiovascular Events during anti-TNF Alpha in Rheumatoid Arthritis Patients 类风湿关节炎患者抗tnf α期间心血管事件的10年风险
Pub Date : 2018-06-30 DOI: 10.23937/2469-5726/1510061
C. Ilaria, Scire Carlo Alberto, Dallara Francesca, Muiesan Maria Lorenza, Tincani Angela, F. Franco
Objective: To analyze the rate of major CV events in 433 patients with longstanding RA, treated for more than 10 years with anti-TNFα or DMARDs. Methods: All RA patients treated with anti-TNF-α from 2000 and 2002 (n. 86; TNF+ group) and a random sample of 258 patients treated with DMARDs out of 829 followed-up in the same period in the same Unit (TNFgroup) were analyzed. Myocardial infarction, heart failure, stroke, transient cerebral ischemic attack were considered. Exposure (anti-TNF-α vs. DMARDs) and outcome (CV events) were analyzed by the proportional hazard Cox regression, adjusting for RA duration, DAS 28, seropositivity (RF, anti CCP), treatment and Framingham CV risk factors (adjusted according to EULAR recommendations). Results: CV events were detected in 18.9% of cases with an incidence rate of 2.4% patients/year (95%CI: 1.5-3.7) in TNF+ and 1.3% patients/year (95%CI: 0.9-1.7) in TNFgroup. Events occurred after a mean of 8.3 ± 3.6 years of anti-TNF exposure and 13.3 ± 8 years of DMARDs exposure (p: 0.006). Cox analysis, adjusted for sex, age, CV risk factors, DAS28, FR positivity, corticosteroids, anti-inflammatory drugs and methotrexate treatment, showed that only Framingham risk score is slightly associated with CV events (HR: 1.03, 95%CI: 1.01-1.06). In addition, diabetes (p: 0.017) and coronary artery disease (p: 0.015) were associated with myocardial infarction, while higher age at RA onset (p: 0.02) and Framingham risk score (p: 0.0008) were associated with heart failure. Conclusions: CV events occurred in 2.4% patient/year during anti-TNF alpha treatment. A strict cardiovascular monitoring was mandatory in order to prevent major CV events.
目的:分析433例接受抗tnf α或DMARDs治疗超过10年的长期RA患者的主要CV事件发生率。方法:2000年至2002年接受抗tnf -α治疗的所有RA患者(86例;对同一单位(TNF组)同期随访的829例接受dmard治疗的患者中随机抽取258例进行分析。考虑心肌梗死、心力衰竭、中风、短暂性脑缺血发作。暴露(抗tnf -α vs. DMARDs)和结局(CV事件)通过比例风险Cox回归分析,调整RA持续时间、DAS 28、血清阳性(RF、抗CCP)、治疗和Framingham CV危险因素(根据EULAR建议调整)。结果:18.9%的病例检测到CV事件,TNF+组的发生率为2.4% (95%CI: 1.5-3.7), TNF组的发生率为1.3% (95%CI: 0.9-1.7)。事件发生在抗tnf暴露的平均8.3±3.6年和DMARDs暴露的平均13.3±8年之后(p: 0.006)。经性别、年龄、CV危险因素、DAS28、FR阳性、皮质类固醇、抗炎药物和甲氨蝶呤治疗校正后的Cox分析显示,只有Framingham风险评分与CV事件有轻微关联(HR: 1.03, 95%CI: 1.01-1.06)。此外,糖尿病(p: 0.017)和冠状动脉疾病(p: 0.015)与心肌梗死相关,而RA发病年龄较高(p: 0.02)和Framingham风险评分(p: 0.0008)与心力衰竭相关。结论:在抗tnf α治疗期间,每年有2.4%的患者发生CV事件。严格的心血管监测是强制性的,以防止主要的心血管事件。
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引用次数: 0
Autoimmunity and Lymphoma: A Brief Review 自身免疫与淋巴瘤:综述
Pub Date : 2018-06-30 DOI: 10.23937/2469-5726/1510062
Miller Edward B
The relationship between the immune system and both Hodgkin’s (HL) and Non-Hodgkin’s (NHL) lymphomas is a complex bidirectional process which has fascinated researchers and clinicians for many years. Lymphomas of all types are known to be associated with autoimmune paraneoplastic manifestations, and conversely are recognized in increased frequency in patients with pre-existing autoimmune diseases. This review briefly surveys this two-way process whereby lymphomas induce autoimmune dysfunction, and autoimmune system dysfunction induces lymphomagenesis. An emphasis on the clinical manifestations of these disorders is presented along with a brief overview of the pathophysiologic mechanisms involved. *Corresponding author: Edward B. Miller, MD., Head, Division of Rheumatology, Assistant Head, Department of Internal Medicine, Kaplan Medical Center, POB 1, Rehovot, 76100, Israel, Tel: 972-8-9441-991, Fax: 972-8-9440-053, E-mail: edward_m@clalit.org.il REviEw ARticlE
免疫系统与霍奇金淋巴瘤(HL)和非霍奇金淋巴瘤(NHL)之间的关系是一个复杂的双向过程,多年来一直吸引着研究人员和临床医生。已知所有类型的淋巴瘤都与自身免疫性副肿瘤表现相关,相反,在已有自身免疫性疾病的患者中发病率增加。本文综述了淋巴瘤诱导自身免疫功能障碍和自身免疫系统功能障碍诱导淋巴瘤发生的双向过程。强调这些疾病的临床表现,并简要概述所涉及的病理生理机制。*通讯作者:Edward B. Miller,医学博士,风湿科主任,内科助理主任,卡普兰医疗中心,POB 1, Rehovot, 76100,以色列,电话:972-8-9441-991,传真:972-8-9440-053,E-mail: edward_m@clalit.org.il综述文章
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引用次数: 8
Trend of Frequency and Outcome of Reactive Arthritis in Japanese Patients with Bladder Cancer following Intravesical BCG Therapy over the Last 20 Years 过去20年膀胱内卡介苗治疗后日本膀胱癌患者反应性关节炎的发病率和预后趋势
Pub Date : 2018-06-30 DOI: 10.23937/2469-5726/1510064
Taniguchi Yoshinori, Nishikawa Hirofumi, Yoshinaga Yasuhiko, Amano Eri, K. Shigeto, T. Yoshio
{"title":"Trend of Frequency and Outcome of Reactive Arthritis in Japanese Patients with Bladder Cancer following Intravesical BCG Therapy over the Last 20 Years","authors":"Taniguchi Yoshinori, Nishikawa Hirofumi, Yoshinaga Yasuhiko, Amano Eri, K. Shigeto, T. Yoshio","doi":"10.23937/2469-5726/1510064","DOIUrl":"https://doi.org/10.23937/2469-5726/1510064","url":null,"abstract":"","PeriodicalId":73938,"journal":{"name":"Journal of rheumatic diseases and treatment","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75978851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of rheumatic diseases and treatment
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