Mesangial glomerulopathy and IgM rheumatoid factor in rheumatoid arthritis

Hematuria and proteinuria in rheumatoid arthritis (RA) are commonly associated with drug therapy but occur independently of drugs, amyloid or urologic disorders. The latter occurrences suggest a primary renal lesion associated with RA. Review of reported renal biopsies identifies mesangial glomerulopathy as a common finding in RA patients without associated drug therapy and that it is frequently associated with hematuria in nonrheumatoid patients. Moreover, immunoglobulins have been shown to concentrate in the mesangium in experimental animals, suggesting that a functional response by the kidney mesangium to remove IgM rheumatoid factor (RF)-IgG complexes could lead to this mesangial lesion. We describe 3 patients with RA who had a mesangiopathy characterized by increased quantities of mesangial matrix and deposition of IgM without other lesions. Together, these observations suggest that: (1) mesangial glomerulopathy is common in RA; (2) removal of circulating RF-IgG complexes is a function of the mesangium and might produce this renal lesion; (3) mesangial glomerulopathy may be responsible for much of the hematuria observed in RA patients and, in many cases, may not be drug related and thus may not require discontinuing beneficial therapy.     

Effect of combination therapy and nonsteroidal antirheumatic agents on acute phase reactants in patients with rheumatoid arthritis

The purpose of the study was the evaluation of the effects of the combined therapy and non steroidal anti-inflammatory drugs on the acute phase reactants and clinical symptoms in patients with rheumatoid arthritis. The acute phase reactants that were observed were sedimentation of erythrocytes, C-reactive protein, haptoglobin and fibrinogen, while the clinical parameters that were observed were the number of swollen joints and the number of joints sensitive to the pressure. All the parameters were evaluated before the therapy initiation, there and six months after the therapy was finished. The treatment involved 80 patients with rheumatoid arthritis separated into three groups depending on the therapy applied: Group A (n = 29) received gold salts, sulphasalazine and tenoxicam, Group B (n = 25) received gold salts, sulphasalazine and indometacin, and Group C (n = 26) received gold salts, chloroquine and piroxicam. The results of our examination showed statistically significant descrease in value of acute phase reactants and of clinical indicators after the therapy carried out in each of the patient groups, while the values between the groups were of no statistical significance.     

Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis

AimTo investigate potential predictors of response to conventional DMARDs in RA.MethodsStudy design – 6-month follow-up prospective study.ParticipantsRA patients with active disease.Intervention and follow-upIntroduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria).AnalysisPotential predictors of response, patients’ demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response.ResultsForty-two patients (mean age = 57 ± 13 years, mean disease duration = 5.4 ± 7.2 years) were included. MTX was given to 30. The response to therapy was predicted by the baseline serum level of TNF-α (mean = 30.2 pg/ml ± 18 in non-responders vs. 11.9 pg/ml ± 11.2 in responders). The threshold, which predicted with the best accuracy the response to treatment, was 20.1 pg/ml (sensitivity, specificity, positive and negative predictive values of 75, 78.9, 83.3, and 69.2%, respectively; AUC = 80.3%, 95% CI = 62.8–97.7%). Similar results were obtained in the subgroups of patients treated with MTX and patients with early RA of less than 3 years duration.ConclusionIn the present work, the serum concentration of TNF-α was related to further response to DMARDs. Other works are needed for confirmation and to assess whether such biomarker could be used to predict the response to DMARDs at the individual level.     

Gold therapy in rheumatoid arthritis.

Forty patients with active rheumatoid arthritis were treated with intramuscular injections of gold salts. A significant response was shown by 67,5% of the patients. Treatment was discontinued owing to side-effects in 35%. Dermatitis and proteinuria from renal damage were the commonest complications of treatment. The method of treatment and its side-effects are discussed.     

Knee arthroplasty in rheumatoid arthritis. Four- to six-year follow-up study

A consecutive series of total condylar knee arthroplasties in patients with rheumatoid or related arthritis, with a 4-6-year follow-up period, was studied. Eighty-seven percent had an excellent or good overall result (score of 70 or more on the HSS knee rating scale). The median total score increased from 45 points before operation to 83 after operation. Sixteen complications, mostly minor, occurred in 14 patients. There were no early infections. Two prostheses were removed for deep infection, after 3 and 5 years. One patient had patellectomy for avascular necrosis. The crude prosthesis survival rate was 97%. Tibial radiolucencies were noted in 76% of cases; in 29% they were significant (2 mm or more in one or more of three zones). Two tibial components (2%) were believed to be mechanically loose, but no revisions for mechanical loosening were done. The presence of radiolucencies did not signify an inferior clinical result.     

Gene therapy for patients with rheumatoid arthritis

Gene therapy seeks either to supply a missing or dysfunctional gene or to ensure continuous long-lasting production of a therapeutic protein. Rheumatoid arthritis is a candidate for gene therapy, as the mechanisms leading to joint inflammation and destruction have been partly elucidated. Nevertheless, several crucial questions need to be addressed. Knowledge of the underlying pathophysiological mechanisms is needed to guide selection of the candidate gene. In the light of current data, TNF and IL-1 antagonists are generating interest. A choice must be made between a viral vector (adenovirus, retrovirus, adeno-associated virus) and a nonviral vector (naked DNA, administered by electrotransfer or in liposomes). Finally, the relative merits of intraarticular and systemic administration need to be considered. Safety is a primary concern. The transgene and/or vector may induce adverse effects. For instance, a transgene inserted within the host genome (when a retroviral vector is used) may induce a mutation. A number of vectors and transgenes induce immune responses. Numerous studies are ongoing to investigate the safety and efficacy of gene therapy strategies in experimental models of rheumatoid arthritis. These studies will have to be completed before further clinical trials of gene therapy in rheumatoid arthritis are considered.     

电话随访对类风湿性关节炎患者疲乏症状的影响

目的探讨电话随访对类风湿性关节炎患者疲乏症状的干预效果。方法将128例类风湿性关节炎患者随机分为观察组和对照组各64例,对照组进行常规护理及出院指导,嘱其不适复诊;观察组在对照组干预基础上,于患者出院后进行为期4个月的电话随访,对患者出院后出现的或可能出现的问题进行护理指导。应用疲乏视觉模拟评分法(VAS)、健康评估问卷(HAQ)测评干预前后两组患者的疲乏症状及功能状态。结果出院后4个月随访时观察组疲乏程度及疲乏评分显著低于对照组(P<0.05,P<0.01);功能状态除进食、触物、活动外,其他条目评分显著优于对照组(P<0.05,P<0.01);晨僵时间显著缩短(P<0.01)。结论电话随访能提高患者的功能状态,明显缓解类风湿性关节炎患者的疲乏症状,有助于提高患者的生活质量。     

Bisphosphonate therapy in rheumatoid arthritis

Focal bone damage and generalized bone loss are features of rheumatoid arthritis (RA). The introduction of TNFalpha antagonists has radically improved the management of RA by providing a means of slowing or preventing the occurrence of focal bone damage. However, some patients with severe RA have contraindications to TNFalpha antagonist therapy and others either fail to respond or fail to tolerate TNFalpha antagonists. In addition, whether TNFalpha antagonists effectively combat generalized bone loss remains unknown. Bisphosphonates can prevent generalized bone loss. Their main target is the osteoclast, which has been identified as the culprit in focal bone damage caused by inflammatory diseases. As a result, the potential effects of bisphosphonates on focal bone damage related to RA are generating strong interest. Although results from the few studies in humans have been disappointing, new insights into the mechanisms of action of amino-bisphosphonates and recent data obtained in animals, most notably with new-generation bisphosphonates, have rekindled the hope that bisphosphonates may be beneficial in RA. We review herein the main studies of the effects of bisphosphonate therapy on focal bone damage and generalized bone loss in patients with RA.     

Gold therapy in rheumatoid arthritis

During the period 1971-1979, 114 patients with rheumatoid arthritis attending the arthritis clinics at Groote Schuur Hospital and Princess Alice Orthopaedic Hospital were treated with gold sodium aurothiomalate (Myocrisin). Data obtained from 104 completed protocols showed that 70 patients (67,3%) benefited from chrysotherapy. Forty of these patients went into complete remission. Therapy was discontinued in 58 patients, side-effects accounting for this in 33 cases (31,8%). Adverse reactions included skin rashes in 41 (39%) and renal complications in 16 (14%); 7 (6%) developed haematological complications, which resulted in death in 2 cases. HLA tissue typing in 37 patients with side-effects showed no increase in the HLA Dw2 or HLA Dw3 antigen. There was, however, a significant increase in the HLA DRw4 antigen in both Whites and Coloureds (P less than or equal to 0,008 and P less than or equal to 0,001 respectively).     

Total condylar knee replacement in patients who have rheumatoid arthritis. A ten-year follow-up study

Eighty knee replacements with a total condylar prosthesis in patients who had rheumatoid arthritis were followed for ten years. At ten years, nineteen knees needed revision and sixty-one prostheses were still functioning. The major reasons for revision were loosening of the tibial component or late bacteremic seeding from another site. Radiolucency at the bone-cement interface adjacent to the tibial component was statistically related to malposition of the tibial component. According to the system of The Hospital for Special Surgery, the mean scores were 64 points preoperatively and 85 points postoperatively. Synovitis recurred in only 3 per cent of the knees. When revision, pain, or radiographic evidence of loosening were considered an indication of failure, the ten-year cumulative survival was 75 per cent.     

Combination therapy in rheumatoid arthritis

Rheumatoid arthritis is progressive systemic disorder with poor outcomes. Better recognizing of the disease patophysiology resulted in changing therapeutic approaches in DMARDs treatment and creating new drugs. Combined therapy is accepted worldwide in the last 10 years. The rationale for combined treatment is that different drugs with different mechanisms of action can affect different disease pathways to achieve better outcomes.     

Kudo total elbow arthroplasty in patients with rheumatoid arthritis: a long-term follow-up study.

BACKGROUND: Improvements in the design of total elbow prostheses over the last two decades have led to better and more consistent results. The type-3 Kudo total elbow prosthesis was developed in 1980. The long-term results of use of this implant have not been reported. Because it is an unlinked prosthesis, it is not known whether preservation of the anterior oblique component of the ulnar collateral ligament at the time of implantation is important. METHODS: A type-3 Kudo total elbow arthroplasty with cement was performed in forty-seven patients (fifty elbows) with rheumatoid arthritis. Revision rates, clinical symptoms, postoperative complications, and radiographic changes were assessed eleven to sixteen years (mean, thirteen years) postoperatively. RESULTS: The overall survival rate of the prosthesis was 90% at sixteen years. The mean Mayo elbow performance scores were all poor (mean overall score, 43 points) initially. The overall score was substantially improved at both the intermediate follow-up examination (four to six years after the operation) and the late follow-up examination (eleven to sixteen years after the operation), to 81 and 77 points, respectively. The overall rate of radiolucency about the humeral component was 45% at the intermediate follow-up examination and 100% at the long-term follow-up examination. The rate of radiolucency about the ulnar component at the intermediate and late follow-up examinations was 4.3% and 8.9%, respectively. No great differences in results were found with preservation of the anterior oblique component of the ulnar collateral ligament. CONCLUSIONS: This long-term follow-up study showed acceptable results of the type-3 Kudo total elbow arthroplasty in patients with rheumatoid arthritis. Preservation of the ulnar collateral ligament does not seem to be necessary when performing this procedure.     

Membranous glomerulonephritis probably related to bucillamine therapy in two patients with rheumatoid arthritis

We describe here two patients with rheumatoid arthritis who developed nephrotic syndrome after administration of bucillamine, a novel antirheumatic drug developed in Japan. The nephrotic syndrome occurred after six months' and five months' treatment of bucillamine, respectively. The renal biopsy showed early phase of membranous glomerulonephritis (stage 1) in both patients. The first patient was a 64-year-old man who had received gold therapy for two years, and penicillamine therapy for eight months before bucillamine therapy. The nephrotic syndrome occurred after one year's cessation of the gold therapy and six months' cessation of the penicillamine therapy. The other patient, 57-year-old woman, had no history of gold or penicillamine therapy. Our experience suggests that membranous glomerulonephritis might occur in relation to bucillamine therapy.