Long-Term Prospective Study of Methotrexate in the Treatment of Rheumatoid Arthritis

Objective. To determine the long-term efficacy and safety of low-dose methotrexate (MTX) in rheumatoid arthritis (RA). Methods. Eighty-four—month open prospective trial at a single academic rheumatology center. Results. Twenty-six patients were enrolled in a prospective study of the long-term efficacy of MTX in RA; a significant improvement had been demonstrated after 36 months of therapy. Twelve patients remained in the study at the 84-month visit; the mean weekly dosage of MTX was 10.2 mg. A significant improvement was still noted at 84 months in the number of painful joints, number of swollen joints, joint pain index, joint swelling index, and physician and patient global assessments. A 50% improvement in the joint pain index and joint swelling index was observed in more than 80% of the 12 patients still enrolled. A significant reduction in prednisone dosage was achieved; of 14 patients taking prednisone at entry, 7 had discontinued prednisone completely. Fourteen patients withdrew from the study: 10 between 0 and 36 months, and 4 between 36 and 84 months. Toxicity in 3 patients and visit noncompliance in 1 patient were the reasons for withdrawal between 36 and 84 months. At 84 months, 46% of the patients remained in the study; 11.5% had discontinued due to MTX toxicity. Conclusion. The effectiveness of MTX in the treatment of RA continues to be demonstrated in this prospective study, after 84 months of treatment.     

Reactive Arthritis: Developments and Challenges in Diagnosis and Treatment

Reactive arthritis (ReA) has traditionally been described as a nonseptic arthritis occurring in the joint following an extra-articular bacterial infection. This concept became clinically associated with antecedent infections of either the gastrointestinal or genitourinary tract. Yet this operational definition of ReA has led to diagnostic uncertainty in different clinical settings. There are several scenarios in which the ReA has been complex. One is in the SAPHO syndrome, which shares many features with ReA. Another is the development of arthritis after infection with atypical organisms such as Clostridium difficile and Giardia lamblia. Treatment of ReA remains an area of ongoing investigation. There has been a randomized controlled trial of combination antibiotics in Chlamydia-induced ReA, which reported a positive result. There are several uncontrolled reports of anti-TNF agents being used successfully in refractory ReA. These studies in treatment modalities require validation on larger samples but do provide some encouraging preliminary findings from which to develop new therapeutic approaches.     

Long-Term Prospective Study of the Use of Methotrexate in the Treatment of Rheumatoid Arthritis

Objective. To determine and describe the clinical, radiographic, and toxicity profile in a cohort of rheumatoid arthritis patients receiving weekly oral methotrexate (MTX) over a mean period of 90 months, and to compare and contrast these data with our previous data on this cohort, reported after 53 months. Methods. Prospective, open observational study over a mean treatment period of 90 months (range 79—107 months). Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, 1 month, 3 months, and every 3 months thereafter. Results. A significant improvement from baseline was maintained in all clinical parameters but the number of tender joints. Toxic reactions were as common in months 54—90 as during the first 53 months. The mean dosage of MTX decreased from 14.6 mg/week at the time of the last report to 11.7 mg/week, while the mean prednisone dosage increased from 1.9 mg/day to 2.1 mg/day. Radiographic scores for erosive disease became statistically significantly different from baseline at year 8, and scores for joint space narrowing differed significantly from baseline at years 5 and 8. Since study entry, 2 patients (6.9%) have experienced MTX pneumonitis. Conclusion. We conclude that a majority of rheumatoid arthritis patients are able to continue MTX treatment with generally sustained efficacy, for intervals that meaningfully exceed those reported previously.     

Report on the Fourth International Workshop on Reactive Arthritis

There are large differences in the antigenicity and biology of the ReA-associated bacteria. For induction of arthritis, the relevance seems to be only that antigenic material reaches the joint, alive or dead. If there is a common antigen, it has to be a highly conserved one. Bacterial hsp60 seems to be an immunodominant T cell antigen in ReA, but there must be other relevant antigens shared by these different bacteria. An ineffective immune response (for example, low production of TNFalpha) seems to contribute to the manifestations and course of ReA. Although arthritis can also occur in its absence, HLA-B27 plays an important role in the pathogenesis of ReA and the other SpA. Current data suggest that B27 probably acts as an antigen-presenting molecule for a still-unknown arthritogenic molecule. Comparison of ReA with IBD-associated arthritis suggests that there might indeed be a common antigen shared by ReA-associated bacteria and bacteria of the gut flora. CD8+ T cells seem to be important in ReA and other SpA. In some parts of the world, such as in Mexico, ReA could be a major predisposing cause of the development of AS. Antibiotic treatment is not effective, probably because the triggering bacteria are already dead or in a partly latent state at the time arthritis occurs. Based on this knowledge and on new technologies, it should be possible in future years to derive answers to the questions about ReA and the other SpA and, as a consequence, to find a cure.     

The Story Behind the Use of Glucocorticoids in the Treatment of Rheumatoid Arthritis

Cortisone was introduced in the treatment of rheumatoid arthritis (RA) in 1948 by Hench and colleagues at the Mayo Clinic which resulted in dramatic improvement of inflammation, function and sense of well-being. It became obvious early on that side effects could develop depending on the dose and duration of use.When cortisone became available in 1950 the practicing physician developed practice patterns without guidance from government agencies, professional organizations or the pharmaceutic industry. The physician did not have guidance about what dose to use or the duration of use, as is available today. In the last 25 years, controlled studies have shown the benefits and safety of low dose prednisone in early RA. The diurnal effect of endogeneous glucocorticoids provides a clue to the timing of a glucocorticoid dose and the duration of the dose is established. The guidelines by the American College of Rheumatology (ACR) particularly but also the European League Against Rheumatism (EULAR) have emphasized side effects and stressed limited use of glucocorticoids in RA. Biologics have been developed and promoted that are used to replace and taper off low dose prednisone. Yet, glucocorticoids used appropriately can be the cornerstone of effective, safe, and inexpensive treatment of early active rheumatoid arthritis.     

自主神经对心室晚电位各参数的昼夜影响

采用数字化Holter监测仪对 30例健康人进行连续监测 ,计算其心室晚电位 (VLP)及心率变异性 (HRV)指标的动态变化 ,以评价出两者之间的关系。所有健康受试者 ,均按立体正交导联方式佩戴 2 4h动态心电图 ,分别记录午夜 2时及下午 14时左右这两个时间点的VLP及HRV数值 :夜间LF 4 93.5 7± 15 6 .6 2ms2 ,HF 6 89.73± 172 .19ms2 ,LF/HF 0 .74 3± 0 .118,T QRS 10 0 .1± 12 .79ms ;白天LF 4 14 .75± 176 .6 1ms2 ,HF 318.5 1± 116 .6 1ms2 ,LF/HF 1.399± 0 .2 81,T QRS 90 .0 3± 9.70ms(P <0 .0 5 ) ,结果显示VLP与HRV均存在昼夜的明显变化 ,T QRS与HF在夜间均增高 ,白天均降低 ,且表现出明显的正相关 ;TQRS与LF/HF比值则表现出明显的负相关。结论 :VLP存在与自主神经相关的昼夜规律性变化。     

Treatment Strategies in Early Rheumatoid Arthritis and Prevention of Rheumatoid Arthritis

Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA-ideally, less than 3-6?months after symptom onset-improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease.     

类风湿关节炎的诊治进展

近十余年来类风湿关节炎(rheumatoid arthri-tis,RA)从遗传基因、发病机制到临床诊断治疗方面都取得了飞跃的发展,极大的改善了,患者的顶后,被称为类风湿关节炎跨越的十年.但在国内发展尚不平衡.刘栩等报道[1]:RA患者在风湿免疫专科首次就诊比例低,就诊及确诊均存在时间延误,从患者出现症状到确诊RA的中位时间为6个月;约半数以上的患者未接受正规的DMARDs治疗,在非专科RA的非正规化诊治现象仍很常见等.