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ID PMID Title PublicationDate abstract
11409664 The effectiveness and toxicity of cyclosporin A in rheumatoid arthritis: longitudinal anal 2001 Jun OBJECTIVE: To determine factors associated with response or toxicity to cyclosporin A (CSA) in a population-based inception cohort with rheumatoid arthritis (RA). METHODS: Prospectively collected longitudinal measures including tender joint count (JC), duration of morning stiffness (MS), systolic and diastolic blood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using generalized estimating equations. Survival methods were used to estimate CSA continuation time and its determinants. RESULTS: Of 133 patients (75% female, median RA duration 13 years), 37 discontinued CSA because of ineffectiveness (19) or because of toxicity (18) including increased SCr in 10, hypertension in 4, infections in 3, and gingival hyperplasia in 1. Patients remained on CSA a median of 75 months (95% confidence interval [CI] 38-112). Those receiving concomitant methotrexate (MTX) were more than 4 times as likely to continue on CSA therapy (hazard ratio 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) and concomitant MTX therapy (RR 0.79, 95% CI 0.63-0.99); decreased MS was predicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% CI 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 micromole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 mm Hg, 95% CI 3.0-6.4). CONCLUSIONS: Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.
9566667 Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. 1998 Mar We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.
11710708 The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor 2001 Nov OBJECTIVE: To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment. RESULTS: Forty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation. CONCLUSION: The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.
10609066 Long-term efficacy and toxicity of cyclosporin A + fluocortolone + methotrexate in the tre 1999 Nov OBJECTIVE: The therapeutic efficacy and tolerability of the combination of cyclosporin A, methotrexate and fluocortolone was evaluated after 96 months of treatment in 140 patients with rheumatoid arthritis. METHODS: The initial dose of CyA was 5 mg/kg per day and was subsequently modified on the basis of the individual clinical response. Fluocortolone was initially administered at a dose that was sufficient to control disease activity (80-130 mg/week) and then was gradually tapered down to a maintenance dose of 15-20 mg/week. MTX was given intravenously at a dose of 15 mg once weekly for 4 consecutive weeks and then, after a 2-week interval, every 2 weeks or every month depending on the evolution of the disease. RESULTS: At the end of the study a statistically significant improvement was observed in both clinical (VAS, grip-strength, duration of morning stiffness, number of swollen joints, number of painful joints, Ritchie's index and Lee's functional index) and laboratory parameters: ESR (p = 0.000); alpha 2 globulins (p = 0.000); hemoglobin (p = 0.000); CRP (p < 0.001); and rheumatoid factor (p = 0.000). Radiological evaluation revealed little progression in anatomic lesions (Larsen score p = 0.699; number of erosions p = 0.344), thus suggesting that our protocol may be capable of showing down both bone resorption and cartilage loss. Renal toxicity, defined as an increase in plasma creatinine concentrations of more than 50% of the baseline value, was observed in 12 patients (8.5%), but the drug was discontinued in only one, who simultaneously presented high blood pressure. CONCLUSION: The positive results so far achieved in our study must be interpreted as being due to the combined action of the individual drugs, which made it possible for them to be used at relatively low dosages that minimised the onset of their side effects while maintaining the efficacy of their suppressive action.
9133932 Histologic liver abnormalities in an autopsy series of patients with rheumatoid arthritis. 1997 Feb A retrospective review was performed on 188 autopsied cases of rheumatoid arthritis at our institutions during 1958-1985, prior to the widespread use of methotrexate. Hepatic histology was reported in 182 cases. All available microscopic liver slides from cases in which the autopsy report described portal tract inflammation, fibrosis, cirrhosis, tumour, amyloid, vasculitis, or infections involving the liver were examined and graded by a hepatic pathologist blinded to the original diagnosis, along with a representative sample of cases with reports describing fatty change or no hepatic pathologic abnormalities. Ninety normal and abnormal cases were reviewed from the 182 for which hepatic histology was available. Fifteen cases of diffuse fibrosis were identified upon blinded review. Two cases were graded as severe fibrosis (grades 3 or 4 on a scale of 0-4) without an identifiable pathologic cause, in both of which the liver disease was suspected premortem (alcohol abuse and viral hepatitis). Although the incidence of fibrosis in this series is slightly higher than that previously described, serious fibrotic liver disease was rare. These results support the current practice of limiting pre-treatment liver biopsies prior to methotrexate therapy to patients with suspected liver disease.
11317015 Methotrexate osteopathy demonstrated by Technetium-99m HDP bone scintigraphy. 2001 May The authors report a case of methotrexate osteopathy as revealed by Tc-99m HDP bone scintigraphy in a patient with rheumatoid arthritis. Methotrexate is used widely in high doses as a chemotherapeutic agent. Lower doses are given in rheumatoid and psoriatric arthritis. Methotrexate affects bone metabolism, resulting in methotrexate osteopathy, characterized by osteoporosis, osseus pain, and even spontaneous (micro)fractures. Radiographic visualization of microfractures is difficult. Tc-99m HDP bone scans have been shown to be very sensitive in the visualization of changes in bone metabolism as a result of methotrexate osteopathy.
11294089 Impaired cutaneous cell-mediated immunity in newly diagnosed rheumatoid arthritis. 2000 Dec BACKGROUND: Rheumatoid arthritis is characterized by an impaired immune response and a defective cutaneous cell-mediated immunity has been reported. This study was realised in order to determine the characteristics of cutaneous cell-mediated immunity in patients affected by recent-onset and untreated rheumatoid arthritis. METHODS: Forty-eight patients affected by newly diagnosed rheumatoid arthritis were studied by skin testing with seven common recall antigens. The skin tests were performed before the administration of disease modifying anti-rheumatic drugs (methotrexate, cyclosporine-A, hydroxychloroquine) and were repeated after four months of therapy. RESULTS: 43.75% of the RA patients (21 out of 48) were defined as anergic compared with 2% of the normal control subjects and the rate of depression of cutaneous cell-mediated immunity was not related either with the markers of disease activity or with the clinical assessment. The impaired cutaneous cell-mediated immunity shows a slight improvement after methotrexate therapy, while cyclosporine-A and hydroxychloroquine were not able to achieve the same result. CONCLUSIONS: Rheumatoid arthritis shows a defective cutaneous cell-mediated immunity when the patients are studied in the early phase of the disease and before a second-line of therapy with disease modifying anti-rheumatic drugs. The anergy does not correlate either with the disease activity or with the short-term response to treatment. The prognostic significance of these data remains uncertain.
11187430 [Anesthesiological considerations in rheumatic diseases]. 2000 Anaesthesia in patients with rheumatic diseases is a special challenge because chronical inflammatory activity leads to multiple pathological alterations. Airway management is of special importance in the perioperative period. If regional anaesthesia techniques are not practicable, intubation of the trachea by direct laryngoscopy may be found difficult or impossible. Possible reasons are the decreased range of motion of the cervical spine and the mandibular joint leading to a reduced opening of the mouth and reduced dorsal extension of the cervical spine. Furthermore, there is the problem of compression of the myelon in patients with subaxial instability of the cervical spine during laryngoscopy. To avoid these complications, fibre-optic intubation should be performed. Visceral manifestations of the underlying disease need particular attention, especially when related to the cardiac (diseases of the endo-, myo- or pericard), the pulmonary (pleural effusion, fibrosis, restriction) or the haematological (anaemia, chronic infection, thrombocytosis) system. Side-effects of medical treatment include adrenal insufficiency because of long-term corticosteroid therapy, coagulation disorders, gastric ulcer or impaired liver or kidney function following non-steroidal antiinflammatoric drugs (NSAID) or methotrexate therapy. Elective major surgery requires a concept for optimal gaining and using of autologous blood resources (preoperative blood donation, blood salvage) to avoid homologous blood transfusion. Even patients with chronic anaemia should not be excluded from preoperative blood donation because they are adapted to low haemoglobin levels. In pain therapy, besides NSAID, corticosteroids, immunosuppressive drugs and disease modifying antirheumatic drugs (DMARD) can be combined with non-opioid or opioid analgetics. Moderate additional opioid therapy can be remarkably successful.
9780474 [Efficacy and tolerability of methotrexate in the treatment of rheumatoid arthritis]. 1998 Mar OBJECTIVE: To verify, in an open study, the efficacy and safety of long-term administration of low weekly doses (5 mg) of methotrexate (MTX) i.m. in different stage rheumatoid arthritis patients. PATIENTS AND METHODS: The study has been performed for 24 months in 42 patients (37 females and 5 males), fulfilling the ARA criteria for rheumatoid arthritis. Main functional parameters, main serological data and some immunology indexes were periodically monitored (after 1, 3, 6, 12 and 24 months of therapy); moreover, some instrumental exams (X-ray of involved joints, liver ultrasound, respiratory function tests) have been performed. RESULTS: Thirty of 42 enrolled patients completed the whole 24 month therapy, and 22 are still using methotrexate. Results were as follows: therapeutic remission in one patient, marked improvement in 12 cases, moderate improvement in 16 and worsening in 1. Among the 12 remaining patients, 2 refused further treatment; 6 and 4 patients were withdrawn from the study because of inefficacy and toxicity, respectively. A significant improvement was observed in all of the main efficacy parameters taken into consideration. Moderate and reversible side effects were registered in 23 patients. CONCLUSIONS: Our results confirm the value of MTX in the treatment of rheumatoid arthritis. In our opinion this drug is very effective even in a relatively early stage of the disease, mainly in patients whose genetic and clinical markers may predict a more aggressive and severe outcome.
11469449 MTX affects inflammation and tissue destruction differently in the rat AA model. 2001 Jul OBJECTIVE: To investigate the dose response relationships of methotrexate (MTX) therapy in rat adjuvant arthritis (AA), an animal model of rheumatoid arthritis (RA). METHODS: Female Lewis rats were fed a defined diet and were treated with 0, 0.3, 1, 2, 3, 5, and 10 mg MTX per week beginning 3 days after adjuvant injection and lasting 6 weeks. The presence or absence of arthritis, and its degree were measured by hindpaw edema scores, ankle widths, and radiographic and histopathologic scores. RESULTS: The 2, 3, 5, and 10 mg MTX per week doses resulted in deaths before the end of the protocol and suppressed normal body weight gain. Tissue destruction, measured by radiographic and histopathologic scores, was reduced in a dose dependent manner with increasing MTX dose. Suppression of inflammation, measured by ankle widths and radiographic and histopathologic scores, reached a maximum at the 1 mg MTX dose and declined at higher doses. CONCLUSIONS: Suppression of tissue destruction and inflammation in rat AA does not occur in a concerted fashion as the dose of MTX increases. The implications of these findings to human disease remain to be determined.
9208075 The safety of weekly low dose oral methotrexate in an Oriental population with rheumatoid 1997 Mar A retrospective review of 50 oriental patients with rheumatoid arthritis treated with weekly oral methotrexate showed adverse events in 15 (30%) patients with 19 occurrences (38%) of leucopaenia (4%), pancytopaenia (2%), gastrointestinal symptoms (18%), hepatic transaminase elevation (6%), rash (2%) and infections (6%). The median duration of treatment with methotrexate was 11 months (range 1 to 105 months). Pancytopaenia occurred in 1 patient with renal failure. All adverse events resolved with cessation of therapy and on several occasions, despite continued therapy. Methotrexate was discontinued permanently in 2 and temporarily in 7 patients as a result of adverse events. No recurrence of adverse events was noted on restarting methotrexate therapy in patients with non life-threatening adverse events. No increase in adverse events was noted in 14 patients treated with a combination of methotrexate and anti-malarial therapy. We conclude that methotrexate was well tolerated by the Oriental patients with rheumatoid arthritis in our study and could be safely restarted in those patients with non life-threatening adverse events.
9217554 Emerging treatments for rheumatoid arthritis. 1997 Jan 27 Rheumatoid arthritis was considered for centuries to be a nuisance condition, limiting in its effects on an individual's range of motion and the source of considerable distress, but not a life-threatening disease. Recently, however, it has become apparent that patients with severe rheumatoid arthritis may have a decreased life span. Current pharmacologic therapies for patients with rheumatoid arthritis, which include nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, methotrexate, and corticosteroids, have been moderately successful in alleviating the discomforts associated with swollen, painful joints. Many practitioners have sought to improve use of these agents and slow joint destruction by challenging traditional treatment paradigms, altering the sequence in which drugs are given. Nevertheless, most standard medical approaches to treatment have had little or no impact on the course of rheumatoid disease. Innovative strategies, particularly those based on new concepts in the immunobiology of rheumatoid arthritis, are being developed to target cellular inflammatory mechanisms and actually prevent disease progression. Some agents, such as inhibitors of 5-lipoxygenase-omega-3 fatty acid and zileuton-may be most useful in treatment of milder disease manifestations such as moderate synovitis. Other agents, such as oral type II collagen, minocycline, subcutaneous interleukin-1ra, and anti-CD4 monoclonal antibodies, have produced such inconsistent results that substantial additional research will be required before any conclusions may be drawn about their value. Among the most promising agents, and the most extensively studied, are tumor necrosis factor-alpha monoclonal antibodies, immunosuppressive drugs such as cyclosporine and mycophenolate mofetil, and the novel compound tenidap, which has both cytokine-modulating and anti-inflammatory properties.
10527958 Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthrit 1999 Oct 15 We investigated 43 patients with seropositive rheumatoid arthritis (RA) under a therapy with methotrexate (MTX) or azathioprine (AZA). All patients fulfilled the American Rheumatism Association criteria. It has been a retrospective study over 2.6 years (MTX: 26 patients, average age 54 +/- 14.6 years, female/male 19:7, AZA: 17 patients, average age 59.4 +/- 12.5 years, female/male 12:5). The mean duration of disease was 8 years (+/- 5.3) in the MTX-group and 7 years (+/- 7.3) in the AZA-group. The mean dose of MTX was 13. 3mg/week and of azathioprine 142.6mg/ daily. The drugs were administered orally. - Radiographs of hands, wrists and feet obtained at enrollment and at review were scored by a rheumatologist according to a modified Larsen score. Radiographic damages were counted in 25 joints of each hand and in 25 joints of each foot. The change in radiological score was calculated by subtracting the joint damage scores at follow up with first damage score at inclusion. The rate of radiological progression (YP) was calculated by dividing the change in radiological score by the number of years during the period of study. - Only 3 patients with MTX showed no radiologic progression. All other patients of both groups showed progressive radiological changes. - The study demonstrated no significant difference in the rate of radiologic progression between the different treatment-groups. However, there was a trend that MTX treated patients (YP 5 +/- 4.4) had a slower radiographic progression compared with those treated with AZA (YP 8.5 +/- 7.7). MTX may be more effective in patients at an earlier stage of rheumatoid arthritis. - When we started a therapy with AZA or MTX in a later period of disease we revealed a better influence of radiologic progression under AZA and a trend towards an increase of the radiologic progression under MTX. - Probably there is a decreasing effect of MTX in later periods of the disease. - The corticoid dose reduction was higher under AZA (AZA: Reduction about 58.6%, MTX: 25%) over the study duration. - Our investigation demonstrated a trend towards reduced radiological progression in MTX treated patients compared to AZA, however statistic analysis showed no significant difference in the rate of radiologic progression. At an earlier stage of the disease there is a better influence of MTX in radiologic progression, at the later stage we showed a slowing of radiological deterioration in AZA treated group.
9266139 Rescue of DMARD failures by means of monoclonal antibodies or biological agents. 1997 May Over the past decade different monoclonal antibodies or other biological agents have been developed to complete the available therapeutic repertoire for treating RA patients. Thus, monoclonal antibodies to block the TNF-alpha or TNF-alpha receptor fusion proteins, respectively, have been successfully applied in the treatment of RA patients refractory to other treatment principles. In addition, using the IL-1 receptor antagonist, similar promising data have been obtained in placebo-controlled, double-blind trials. Initial attempts are presently being conducted to test combination therapies, using monoclonal antibodies directed against the proinflammatory cytokines and cell surface molecules, and long-acting rheumatic drugs such as methotrexate. Hopefully within the next few years newly developed biological agents will be available for use in daily clinical practice.
9779842 Development, recurrence, and severity of infections in Mexican patients with rheumatoid ar 1998 Oct OBJECTIVE: To determine factors associated with development, recurrence, and severity of infections in patients with rheumatoid arthritis (RA). METHODS: A hospital based nested case-control study in a referral center. The same evaluator reviewed clinical charts of 195 consecutive patients with RA seen in our clinic during 1993. Patients who had had at least one infection were classified as "cases" and the others as "controls." We examined 24 demographic, clinical, therapeutic, and infection related variables. A severity index was developed according to scores provided by 12 independent multidisciplinary evaluators. Recurrent infection was defined as > 2 different infections in the same patient during followup. Descriptive statistics were employed, with comparison between cases and controls by univariate analysis and multiple logistic regression. RESULTS: Two hundred eleven infections were detected in 1274 patient-years (incidence of 0.17 new infections per patient-year). We studied 174 women and 21 men, mean 41 years of age, with a mean duration of symptoms of RA of 5 years. Ninety-five were cases and 100 controls. Cases had longer disease duration before admission and followup (p < 0.05). Infections most commonly seen were upper respiratory tract (n = 74), skin (41), urinary tract (27), and herpes zoster (15). Steroids and/or methotrexate (MTX) were associated in 95% of infections. Infection was associated with duration of RA before admission and followup, comorbidity, extraarticular disease, mean cumulative dose of MTX, time taking steroids, and mean daily dose of D-penicillamine, by univariate analysis. Severity of infection was related to the same variables and years of formal education, and recurrence of infection was related to time of followup and mean dose of MTX and steroids. Multiple logistic regression showed that variables associated with infection were cumulative MTX dose, time taking steroids, and mean daily dose of D-penicillamine. CONCLUSION: Infections were frequent in our RA population. The risk factors associated with infections were the cumulative dose of MTX, duration taking steroids, and mean daily dose of D-penicillamine.
11123029 Therapy of rheumatoid arthritis: new developments and trends. 1999 Dec The medical therapy of rheumatoid arthritis (RA) has been influenced strongly during the past decade by the recognition that many patients develop joint damage within the first year of disease. This observation has motivated rheumatologists to initiate disease-modifying antirheumatic drugs (DMARDs) early in the disease course. This trend has been matched by the increased use of combination DMARD therapy, with the aim to maximize control of the signs and symptoms of RA and limit the development of joint damage. The results from controlled clinical trials generally have supported the concept that early, aggressive treatment with DMARDs is superior to less intensive strategies. In addition, certain DMARD combinations are more effective than the individual components of these regimens, but the evidence is strong for only a few DMARD combinations such as methotrexate and cyclosporine A. Three new drugs have been recently approved for the treatment of RA. Celecoxib, a selective cyclooxygenase-2 inhibitor, has similar clinical efficacy as conventional nonsteroidal anti-inflammatory drugs, and in short-term studies causes no more gastric and duodenal ulcers and erosions than patients treated with placebo. Treatment with leflunomide, an inhibitor of pyrimidine synthesis, has been shown in controlled clinical trials to produce significant clinical improvement in 50% to 60% of patients with RA and delay radiologic progression of disease. The era of biologic therapy has dawned with the apparent success of tumor necrosis factor (TNF)-alpha blockade using etanercept, a recombinant TNF receptor:Fc fusion protein, and infliximab, a chimeric anti-TNF monoclonal antibody. These new agents expand our treatment options in RA and should lead to innovative and more effective treatment approaches.
11083260 Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations. 2000 Nov OBJECTIVE: To compare the efficacy of combination therapy with disease-modifying antirheumatic drugs (DMARDs) versus single therapy with DMARDs in the prevention of early cervical spine changes in patients with rheumatoid arthritis (RA). METHODS: One hundred ninety-five patients with recent-onset RA (mean disease duration 8 months) were randomly assigned to receive a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single DMARD with or without prednisolone. After 2 years of followup, cervical spine radiographs were taken of 176 of these patients (85 in the combination-therapy group and 91 in the single-therapy group). These radiographs were evaluated, and the findings were correlated with the therapy strategies as well as with peripheral joint destruction and clinical and laboratory variables describing the disease activity. RESULTS: Anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI; i.e., vertical subluxation), and subaxial subluxation (SAS) were found in only 6 (3.4%), 2 (1.1%), and 5 (2.8%) of the patients, respectively. Interestingly, none of the patients in the combination-therapy group had aAAS or AAI. The incidences of aAAS and AAI in the single-therapy group were 6.6% and 2.2%, respectively. SAS was present in 2 patients (2.2%) in the single-therapy group and in 3 patients (3.5%) in the combination-therapy group. The difference in the incidence of aAAS between the treatment groups was statistically significant (P = 0.029). None of the patients with cervical spine changes achieved remission of RA during the study. CONCLUSION: In the present study, the incidence of cervical spine subluxations in patients treated with single-drug therapy was in accord with findings of previous studies. However, none of the patients in the combination-therapy group had aAAS or AAI. These findings suggest that early, aggressive combination-DMARD therapy with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone can prevent or retard the development of rheumatoid atlantoaxial disorders.
10217559 Primary juxtaarticular soft tissue lymphoma arising in the vicinity of inflamed joints in 1999 Mar AIMS: Primary soft tissue lymphoma is uncommon and little is known regarding its aetiology and pathogenesis. In a review of 37 soft tissue lymphomas we uncovered three cases associated with rheumatoid arthritis which we report herein. METHODS AND RESULTS: The clinical records and pathology of the cases are described together with the results of in situ hybridization studies with oligonucleotide probes to Epstein-Barr virus (EBV) encoded RNA (EBER). All three patients were females with a long-standing history of rheumatoid arthritis ranging from 9 to 17 years. Each presented with a soft tissue mass in the vicinity of a joint affected by rheumatoid disease. All had received prior treatment with nonsteroidal anti-inflammatory drugs and one also received gold, penicillamine and intra-articular steroids to affected joints. None had received methotrexate. Histologically, the juxtaarticular soft tissue masses were all B-cell lymphomas. None were associated with EBV as determined by in situ hybridization. CONCLUSIONS: These cases document an association between rheumatoid arthritis and soft tissue lymphoma of B-cell type, arising in the vicinity of an affected joint. Chronic local immune stimulation may have played a significant role in the genesis of these lymphomas, unlike the frequently reversible and EBV-positive lymphomas that occur in rheumatoid patients on immunosuppressive therapy.
10381063 Successful treatment of methotrexate induced nodulosis with D-penicillamine. 1999 Jun Accelerated nodulosis is a recognized complication of methotrexate (MTX) therapy in rheumatoid arthritis (RA). We describe 3 patients with accelerated nodulosis treated with D-penicillamine (D-Pen) while continuing MTX. The combination of D-Pen with MTX therapy resulted in regression of subcutaneous nodules in all patients, disappearance of pulmonary nodules in one patient, and resolution of vasculitic lesions in 2 patients. Clinical response was observed within the first few weeks of therapy and usually required moderate doses (500 mg/day). Our observations suggest that addition of D-Pen to MTX therapy can be an alternative therapeutic option for accelerated nodulosis in patients with RA.
9779839 Intention-to-treat analysis of 200 patients with rheumatoid arthritis 12 years after rando 1998 Oct OBJECTIVE: To assess existing disease modifying antirheumatic drugs (DMARD) using a strategy aiming for sustained suppression of inflammation. METHODS: We conducted intention-to-treat analysis of open randomized study [sulfasalazine (SASP) or penicillamine (PEN)], followup 12 years, conducted at specialist rheumatology clinics in Glasgow, Scotland. Subjects were 200 patients with rheumatoid arthritis (RA) with established disease. In this "true to life" approach, comorbidity was not an exclusion criterion unless it prejudiced assessment of drug toxicity. The main outcome measure was the Health Assessment Questionnaire (HAQ) functional score. RESULTS: Over 12 year followup 95 (47.5%) patients died; this was the commonest reason for study groups being unfulfilled. There was one drug related death (methotrexate). Patients who were socially disadvantaged were more likely to die prematurely. HAQ did not deteriorate significantly in those who continued taking their original DMARD, or in the SASP intention-to-treat group over 12 years. Sustained suppression of disease activity was possible in the entire group available for followup at 12 years. Most toxicity occurred early and no unexpected side effects were observed. CONCLUSION: High premature mortality in RA was confirmed and an association between mortality and deprivation was demonstrated. Sustained reduction in acute phase response was possible using sequential single DMARD. This study provides useful baseline and longterm information against which to evaluate combination therapy or new agents.
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