Treatment of severe rheumatoid arthritis

The basis for the application of remittive agents in rheumatoid arthritis is still hypothetical and empirical. Immunoreactions may be of pathogenetic significance in rheumatoid arthritis but definite evidence is lacking. Similarly the rheumatoid inflammation may be 'non-specific' or immune mediated. Therefore at present there is no basis for 'guidelines' for immunotherapy. Controlled trials have provided little or no information on the mechanism of action of the remittive agents. Furthermore classical controlled trials have severe limitations and require great resources. Therefore we need a new strategy for controlled trials. The emphasis should be on elucidation of the mechanism of actions of remittive agents with already established clinical efficacy. It is now possible in controlled trials to analyse immunological factors of possible pathogenetic significance, factors in the processes of inflammation and the interaction between the immune system, inflammation and connective tissue. Thereby a proper evaluation of the mechanism of action of remittive agents as well as of pathogenetic factors in rheumatoid arthritis seems possible.     

Lyme arthritis

Infection with B. burgdorferi can cause a large joint inflammatory arthritis in patients who have not been treated for early Lyme disease; the knee is the most common joint affected. The diagnosis depends on a history of known exposure to the spirochete, characteristic clinical features, and serologic studies (ELISA and Western blot) confirming exposure to the spirochete. In most patients, antibiotic therapy is curative, but in a smaller percentage of patients, the presence of the HLA-DR beta 1*0401 haplotype can trigger treatment-resistant arthritis, in which antibiotic therapy is ineffective; in these instances, remittive agents, such as hydroxychloroquine and methotrexate, are indicated. Arthroscopic synovectomy may be considered when antibiotic therapy is not curative. Fibromyalgia can follow infection with B. burgdorferi but is unresponsive to antibiotic therapy; it is treated with tricyclic antidepressants and an exercise program. Lyme arthritis is the only chronic inflammatory arthritis in which the specific cause is known and can be cured. As such, it serves as an excellent model with which to study the pathogenesis of more common inflammatory arthritides, such as rheumatoid arthritis.     

Fever without localizing signs in children

Because rheumatoid arthritis varies in presentation and in course, trials of therapeutic drugs are hard to perform and remission is hard to assess. Corticosteroids have been shown to have some value in treating this disease, but because of their side effects and impact on the immune system when given over a long period, they must be administered with caution. Dr Iannuzzi reviews clinical trials that have been done using a low dose of corticosteroid to slow progression of the disease, describes patients who may benefit from these agents, and provides guidelines on prescribing and withdrawing them.     

Treatment of rheumatoid arthritis. New thoughts on the classic pyramid approach.

Treatment of rheumatoid arthritis can be quite challenging. Toxicity profiles of the various anti-inflammatory agents are often unacceptable, mainly because of gastrointestinal intolerance or bleeding. In addition, epidemiologic data suggest that rheumatoid arthritis is a disease with substantial morbidity and increased mortality. Consequently, newer trends in therapy involve earlier use of remittive agents as well as use of low-dose steroids. These modifications of the classic pyramid approach and the investigation of other methods may significantly influence the future of rheumatoid arthritis therapy and improve quality of life in those with the disease.     

Penicillamine and other remittive agents in rheumatoid arthritis: comparisons and interaction

Penicillamine treatment of rheumatoid arthritis was compared with gold and other remittive agents by reviewing the literature and studying the patients in our penicillamine clinic with respect to their previous responses to chrysotherapy. Penicillamine compares well with other remittive agents with respect to efficacy and toxicity. Prior chrysotherapy does not determine or predict the subsequent efficacy of penicillamine . Patients who reacted adversely to gold tended to react adversely to penicillamine; proteinuria and rash tended to recur.     

Plasmapheresis versus lymphoplasmapheresis in rheumatoid arthritis: immunologic comparisons and literature review

Eight patients with Functional Class III, seropositive, erosive rheumatoid arthritis unresponsive to remittive drugs each underwent nine aphereses over 3 weeks. Four had a 40-ml/kg plasma exchange and four others had a 40-ml/kg plasma exchange plus a mean 5.67 X 10(9) lymphocyte depletion. Both groups appeared to improve clinically. T and B cell counts and OK T4 and OK T8 ratios decreased in the lymphoplasmapheresis group. Phytohemagglutinin stimulation decreased in lymphoplasmapheresis and increased in plasmapheresis patients with significant comparisons (p = 0.02). These findings confirm and extend previous work. Plasmapheresis and lymphoplasmapheresis appear to have fundamentally different actions on lymphocyte function.     

The influence of prednisone on the muscle morphology and muscle enzymes in patients with rheumatoid arthritis

Thirty-five female patients, mean age 63 years, suffering from rheumatoid arthritis participated the study. Twenty patients had been on long-term low-dose corticosteroid treatment. Fifteen patients had never received corticosteroids. A control group of 15 age- and sex-matched healthy subjects was also studied. Examination of muscle biopsies from the (right) vastus lateralis and measurements of isokinetic and isometric knee-extension muscle strength were performed in all subjects. Rheumatoid arthritis patients treated with corticosteroid showed a low percentage of type I fibres, mean 35.7 (range 17-66) % compared with patients who did not receive corticosteroid (P less than 0.005). The latter group did not differ from the controls. The muscle fibre areas also were affected in the corticosteroid treated rheumatoid patients. Type I and type II mean fibre areas were reduced by 32% and 50%, respectively, when compared with non-prednisone treated patients. The latter group did not differ from the controls in this respect. A correlation was found between the isokinetic muscle strength of the knee extensors and the mean areas of type I and type II in patients treated with prednisone (r = 0.48, P less than 0.05 and r = 0.58, P less than 0.02 respectively). No such correlation was found when using isometric measurements of the knee extensors. A positive correlation was found in both groups of rheumatoid arthritis patients between the areas of the type I and type II fibres (r = 0.66 - 0.68, P less than 0.05 - 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

78例类风湿关节炎胸腔积液临床特点分析

目的 探讨类风湿关节炎胸腔积液的特点,提高对该病的认识。方法 回顾分析类风湿关节炎胸腔积液的特点。结果 类风湿关节炎缓解状态下无胸腔积液出现,胸腔积液发生在疾病活动期,且集中在疾病中度、高度活动期,两组低、中、高度患者构成比差异具有统计学意义(P＜0.05)。有胸腔积液组平均血沉(erthrocyte sedimentation rate,ESR)、C反应蛋白(C-reactive protein,CRP)较无胸腔积液组高,类风湿因子(rheumatoid factor,RF)、抗环瓜氨酸肽抗体(anti-cyclic citrullinated peptide antibaody,抗CCP抗体)阳性率较无胸腔积液组高(P＜0.05)。有胸腔积液组平均压痛关节数、平均肿胀关节数较无胸腔积液组多,平均晨僵时间较无胸腔积液组长(P＜0.05)。有胸腔积液组病情缓解数较无胸腔积液组少,有新增关节变形个数较无胸腔积液组多(P＜0.05)。结论 类风湿关节炎患者出现胸腔积液是病情活动的标志,与免疫指标,临床症状呈正相关,临床应进行强有力的治疗。     

Study of pirprofen (rengasil) combined with maintenance doses of corticosteroids in rheumatoid arthritis in a double-blind multicenter trial

A study of pirprofen (rengasil) combined with small doses of corticosteroids in 93 patients with rheumatoid arthritis during a double blind multicentre testing showed good and satisfactory therapeutic results in 60%. A decrease in morning rigidity, pains in the joints especially at night, the joint index and in the number of inflammed joints was noted. Rengasil tolerance was good, side effects were few. The new nonsteroid antiinflammatory drug rengasil combined with maintenance doses of corticosteroids can be recommended for a prolonged treatment of patients with rheumatoid arthritis.     

25-羟维生素D水平与早期类风湿性关节炎的相关性研究

目的探讨25-羟维生素D浓度与早期类风湿性关节炎的相关性。方法收集东阳市人民医院2009年1～7月类风湿性关节炎患者126例,记录肿胀关节数、压痛关节数、骨侵蚀度等临床指标,并测定25-羟维生素D浓度,分析维生素D水平与患者临床指标的变化,并测定健康对照组40例25-羟维生素D浓度。结果类风湿性关节炎患者25-羟维生素D浓度为(21.3±4.8)ng/mL,健康对照者25-羟维生素D浓度为(37.2±8.6)ng/mL,类风湿性关节炎患者25-羟维生素D浓度低于健康对照者,差异有统计学意义(P0.05),25-羟维生素D浓度与类风湿性关节炎疾病严重程度密切相关,差异有统计学意义(P0.05)。结论外周血25-羟维生素D水平与类风湿性关节炎密切相关,但其作用机制有待深入研究。     

Evaluation of therapeutic potential of ivermectin against complete Freund's adjuvant-induced arthritis in rats: Involvement of inflammatory mediators

Rheumatoid arthritis is a chronic systemic inflammatory disease with genetic manifestations. According to recently published case reports, patients taking corticosteroid medication for the management of rheumatoid arthritis develop strongloidiasis and are at high risk of developing associated infections. This study explored the antiarthritic role of ivermectin, a drug used in the treatment of strongyloides and to compare its results with dexamethasone. Thirty-two male Wistar rats were randomly divided into four groups: control, diseased, dexamethasone, and ivermectin groups. Rheumatoid arthritis in all rats except the control group was induced by using complete Freund's adjuvant. After 7 days of rheumatoid arthritis induction, animals were treated with dexamethasone 5 mg/kg and ivermectin 6 mg/kg. Body weight, visual arthritic score, total leukocyte count, differential leukocyte count, proinflammatory genes, and histopathological findings were used to assess the effects of ivermectin on rheumatoid arthritis. Treatment with ivermectin showed a significant reduction in inflammatory cells levels, body weight, and visual arthritic score, indicating an improvement in the degree of inflammation as compared with the diseased group. Treatment with ivermectin and dexamethasone significantly reduced the augmentation in the mRNA expression levels of IL-17, TLR-2, TNF, and NF-κB as a result of arthritic development. Ivermectin treatment also showed a significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to dexamethasone, a corticosteroid used for the treatment of rheumatoid arthritis. Ivermectin has significant antiarthritic properties and can be a novel treatment agent for the management of rheumatoid arthritis patients suffering from strongyloidiasis.     

Rituximab after methotrexate failure in rheumatoid arthritis: evaluation of the SERENE trial

B cell targeted therapy using rituximab, a genetically engineered chimeric mouse/human monoclonal antibody, is recommended for patients with active rheumatoid arthritis who have failed to respond to both conventional disease-modifying drugs and TNF inhibitors. The value of ritixumab in patients with earlier disease, who have only failed methotrexate, was evaluated in a large multicentre randomised, placebo-controlled trial. The Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE) trial enrolled 511 patients with active rheumatoid arthritis. They received one of two doses of rituximab (500 mg × 2 or 1000 mg × 2) or placebo in addition to methotrexate therapy. By 6 months significantly more patients receiving active treatment with rituximab achieved American College of Rheumatology 20 and 50% responses and had low disease activity or remission. These benefits extended to 12 months. There was not an excess of adverse reactions with rituximab. There was some evidence, albeit incomplete, that patients who were seronegative for rheumatoid factor were less likely to respond to rituximab. There is some evidence rituximab might be suitable as first choice biologic treatment, although head-to-head trials are needed against TNF inhibitors before such an approach can be justified. Its value is likely to be restricted to seropositive patients.     

Tumour necrosis factor as a therapeutic target in rheumatoid arthritis and other chronic inflammatory diseases: the clinical experience with infliximab (REMICADE)

Therapeutic strategies that aim to neutralise the important pro-inflammatory cytokine tumour necrosis factor alpha (TNF alpha) have gained considerable prominence in the therapy of chronic inflammatory diseases, notably rheumatoid arthritis and Crohn's disease. This drug focus review will concentrate on the antitumour necrosis factor antibody infliximab (Remicade), which has been approved for the treatment of rheumatoid arthritis and Crohn's disease in both the US and Europe. In addition, infliximab is under investigation for several other indications, mainly inflammatory rheumatic diseases. Clinical trials have been persuasive that infliximab is both safe and effective, and it has been proven to be far superior to the conventional drug therapy in both rheumatoid arthritis and Crohn's disease. Remarkably, infliximab in combination with methotrexate controls both the inflammatory joint symptoms and the progression of joint damage, which renders it a very attractive therapeutic option in moderate to severe, therapy-resistant rheumatoid arthritis.     

Rituximab after methotrexate failure in rheumatoid arthritis: evaluation of the SERENE trial

B cell targeted therapy using rituximab, a genetically engineered chimeric mouse/human monoclonal antibody, is recommended for patients with active rheumatoid arthritis who have failed to respond to both conventional disease-modifying drugs and TNF inhibitors. The value of ritixumab in patients with earlier disease, who have only failed methotrexate, was evaluated in a large multicentre randomised, placebo-controlled trial. The Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE) trial enrolled 511 patients with active rheumatoid arthritis. They received one of two doses of rituximab (500 mg × 2 or 1000 mg × 2) or placebo in addition to methotrexate therapy. By 6 months significantly more patients receiving active treatment with rituximab achieved American College of Rheumatology 20 and 50% responses and had low disease activity or remission. These benefits extended to 12 months. There was not an excess of adverse reactions with rituximab. There was some evidence, albeit incomplete, that patients who were seronegative for rheumatoid factor were less likely to respond to rituximab. There is some evidence rituximab might be suitable as first choice biologic treatment, although head-to-head trials are needed against TNF inhibitors before such an approach can be justified. Its value is likely to be restricted to seropositive patients.     

横络解结法治疗活动期类风湿关节炎的临床疗效评价

目的客观评价横络解结法治疗活动期类风湿关节炎的临床疗效。方法将类风湿关节炎患者80例随机分为常规药物治疗组(对照组)与横络解结法治疗组(治疗组),均予药物常规处理,治疗组加用横络解结法治疗。结果经治疗12周后,治疗组与对照组总有效率相近,但其晨僵时间、平均握力、关节疼痛程度、关节疼痛、肿胀个数、红细胞沉降率、C-反应蛋白及类风湿因子的改善程度明显优于对照组。结论横络解结法可有效抑制活动期类风湿关节炎患者关节炎症,改善病变关节功能。     

Piroxicam in the treatment of rheumatoid arthritis

Open and double blind trials in 80 patients with proved and definite rheumatoid arthritis have shown that piroxicam possesses marked analgesic and antiinflammatory action, is well tolerated producing a therapeutic effect only at high doses exceeding the mean ones recommended in the literature.     

关节镜下诊断和治疗早期类风湿关节炎

目的：探讨早期类风湿关节炎的诊断与治疗。方法：分析研究25例早期不典型类风湿关节炎患者，结合关节镜下的形态学特征、关节液检查、病理诊断等方法完成对单关节类风湿的诊断，关节镜下滑膜切除术治疗早期类风湿关节炎。结果：17例患者在随访过程中出现典型的类风湿关节炎症状，进行滑膜切除术的关节症状较术前明显减轻。结论：关节镜下关节滑膜和血管翳的形态学特征有助于早期不典型类风湿关节炎的诊断，关节镜下滑膜切除对早期类风湿关节炎是一种有效的治疗方法。     

Adalimumab for rheumatoid arthritis

In the last few years significant advances have been made in our understanding of the molecular mechanisms underlying rheumatoid arthritis pathogenesis. Pro-inflammatory cytokines, such as TNF-alpha, play a pivotal role in its pathogenesis. Anti-TNF-alpha biological agents are considered a major advance in the treatment of rheumatoid arthritis. Adalimumab is a fully human monoclonal antibody that binds specifically to TNF-alpha, thereby neutralising its activity. It had significant efficacy in well-designed, placebo-controlled trials in patients suffering from rheumatoid arthritis, both as monotherapy and in combination with various disease-modifying antirheumatic drugs, including methotrexate. Adalimumab was generally well tolerated during both concomitant therapy with methotrexate or standard antirheumatic therapy and monotherapy. In addition, the radiographic progression of structural joint damage was significantly inhibited by adalimumab and improved quality of life. This review summarises the recent available data.     

蜂针疗法治疗类风湿性关节炎的疗效观察

目的观察蜂针疗法对类风湿关节炎患者的临床疗效。方法将75例符合类风湿性关节炎诊断标准的患者随机分为蜂针组、药物组和蜂针+药物组。比较3组的疗效。结果治疗结束后以及治疗结束后3个月随访,3组患者关节疼痛度、关节肿胀度、关节压痛度、晨僵时间(h)、关节疼痛数变化、HAQ、ESR、RF、CRP均有显著差异(P0.05)。结论蜂针疗法能有效缓解类风湿关节炎患者的临床症状。     

Increased renal tubular cell excretion by patients receiving chronic therapy with gold and with nonsteroidal anti-inflammatory drugs

Using rheumatoid arthritis patients who were receiving gold as models, we evaluated the renal effects of the chronic administration of very low doses of a nephrotoxic drug. The heavy metal gold has been shown to increase urinary enzyme excretion when it is given in usual doses for the treatment of rheumatoid arthritis. It is not clear whether the increased urine enzyme excretion caused by long-term drug therapy represents injury to the kidney or whether it is merely an effect of the drug. Urinary N-acetyl-beta-glucosaminidase and renal tubular cell excretion rates were measured in 19 patients who were receiving chronic treatment with gold and with nonsteroidal anti-inflammatory drugs for rheumatoid arthritis, in 10 patients who were receiving nonsteroidal anti-inflammatory drugs, and in 8 healthy control subjects. No subjects showed evidence of kidney disease. Both renal tubular cell and enzyme excretion rates were elevated in the gold-treated group. This showed that there was increased renal tubular cell turnover in this group, which suggests low level renal tubular injury and not merely an effect of the usual dose of gold.