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ID PMID Title PublicationDate abstract
12009565 The role of innate mediators in inflammatory response. 2002 May Cytokines produced by innate immune response can profoundly influence the subsequent adaptive immunity. IL-15 and -18 are two of several mediators produced by macrophages that perform such a function. Here we present recent data mainly from our own laboratory illustrating the important role of IL-15 and -18 in the induction and perpetuation of chronic inflammation during experimental and clinical rheumatoid synovitis.
14648087 [Patient education in practice-a workshop in a small group]. 2003 The aim of the workshop was to work out concrete plans and steps for implementing patient education courses in an outpatient setting by the collaborative arthritis centers in Germany. Primarily the patient education model of Lower Saxony was illustrated as an example of successful implementation of patient education programs in practice. In this state patient education courses are run in cooperation between the Arthritis Center of Hannover and the League against Rheumatism in Lower Saxony. Both institutions are in discussion with the health insurance companies for paying the costs for the patient education courses. Then the group discussed several important aspects which have to be considered when establishing patient education courses such as recruiting and motivating the trainers, recruiting the participants, choosing adequate rooms, fund raising and responsibilities. The participants considered the patient education model of Lower Saxony as a transferable model for every collaborative arthritis center in Germany and recommended to follow that path.
12357690 [Dorsal instability of the ulnar stump following distal resection: hemi extensor-carpi-uln 2002 Jul Dorsal instability of the ulnar stump may be a complication of Darrach and Sauve-Kapandji procedures. Stabilizing procedures are numerous using flexor carpi ulnaris, extensor carpi ulnaris tendons or a combination of both tendons, the palmaris longus, and even synthetic or free grafts. The authors report nine cases of ulnar stump instability, five times post-traumatic and four as a result of rheumatoid arthritis. A tenodesis using a strip half of the extensor carpi ulnaris was performed in all these patients. Post-operatively eight patients were pain-free with in one case occasional pain after heavy work. All stumps were clinically stable. Forearm rotation and grip strength were maintained. Radiological dorsal ulnar subluxation was always reduced. Treatment of these instabilities should be preventive. When dorsal instability of the ulnar stump occurs, the half strip extensor carpi ulnaris tenodesis provides consistent satisfactory results in both arthritic and post-traumatic-related instability.
12942694 Different monocyte reaction patterns in newly diagnosed, untreated rheumatoid arthritis an 2003 Jul OBJECTIVES: To investigate the different capacities of monocytes to produce cytokines in newly diagnosed, untreated patients with rheumatoid arthritis (RA) or systemic lupus and to examine the possible correlation among serum C-reactive protein (CRP), cytokines, swollen joint counts, and erythrocyte sedimentation rates (ESR) in untreated RA patients. METHODS: Monocytes from untreated RA or lupus patients were cultured in vitro with lipopolysaccharide (LPS, as bacterial infection) or immune complexes (as endogenous immune deviation) and supernatants were collected for cytokine determination. Sera from RA patients were assayed for interleukin-6 (IL-6), IL-1 beta, IL-10, tumor necrosis factor-alpha (TNF-alpha) and IL-1 receptor antagonist (IL-1ra). These cytokines were related to serum CRP, swollen joint counts, and ESR. RESULTS: RA monocytes uniformly produced IL-6, IL-1 beta, TNF-alpha, or IL-10 in vitro. In contrast, lupus monocytes could be divided into two subsets: (i) monocytes which produce cytokines on LPS stimulation but not on challenging with immune complexes; and (ii) monocytes which, interestingly, generate cytokines on stimulation by immune complexes but not LPS. These cytokines in turn stimulate the liver to synthesize CRP differently in the SLE subsets and RA patients. Moreover, serum IL-1ra levels correlated significantly with serum IL-6, IL-1 beta, and TNF-alpha concentrations (p = 0.005, 0.008, or 0.040, respectively), but not with IL-10 (p = 0.582) in RA patients. CONCLUSIONS: Two lupus subsets exist that react either to LPS or immune complexes to produce CRP-inducing cytokines, in contrast to homogeneous RA monocytes. This is the first report that different reaction patterns of CRP-inducing cytokine production in RA and lupus monocytes probably underlie the high CRP levels in RA versus low heterogeneity in lupus. The correlation of serum IL-1ra levels with serum IL-6, IL-1 beta, or TNF-alpha concentrations, and the borderline correlation of the former with CRP levels, demonstrate that IL-1ra is an acute phase reactant in RA as well as in SLE patients.
15510715 Difficult diagnosis of infliximab-related miliary tuberculosis. 2004 Apr The use of Infliximab in the treatment of patients with rheumatoid diseases unresponsive to conventional therapies has been reported to be complicated by opportunistic infections. We report the case of a 56-yr old female rheumatoid arthritis patient complaining of fever and respiratory symptoms 9 months after commencing Infliximab, who received no ethiologic diagnosis for the six months before admission. Tuberculosis was suspected upon chest radiographic pictures and empirical treatment for miliary tuberculosis instated in the wake of microbiological confirmation. The case typifies the difficulties of diagnosing miliary tuberculosis in the immunocompromised as well as in the immunocompetent patient.
12972474 Detection of cases of inflammatory rheumatic disorders: performance of a telephone questio 2003 Oct OBJECTIVE: To assess the performance in the detection of cases of rheumatoid arthritis (RA) and the spondyloarthropathies (SpA) of a questionnaire suitable for use in telephone surveys conducted by patient interviewers. METHODS: A questionnaire was designed with reference to the signs, symptoms, and epidemiological criteria for RA (ACR 1987) and SpA (ESSG 1991). Three groups of respondents were recruited from the rheumatology outpatient clinics of 10 university hospitals: 235 with RA, 175 with SpA, and 195 controls with other rheumatological disorders. All diagnoses were confirmed by a rheumatologist. Patient from self help groups and social organisations were trained by a polling company professional to conduct a standard telephone interview using the new questionnaire. RESULTS: In an RA-control comparison, logistic regression showed that a set of five items, predominantly ACR criteria, were the most informative. Self reported diagnosis performed best (sensitivity 0.99, specificity 0.87). In an SpA-control comparison, a set of three items from the ESSG criteria were the most informative, with self reported diagnosis again performing best (sensitivity 0.85, specificity 0.96). Overall agreements with clinical diagnoses were 97.7% for RA and 94.4% SpA, dropping to 90.4% and 79.1%, respectively, when self reported diagnosis was excluded. Without self reported diagnosis, questions about peripheral joint and spinal pain made significant contributions to diagnostic performance. CONCLUSION: A questionnaire in plain language was developed for use in detecting cases of RA and SpA. It performed satisfactorily when administered by patient interviewers and is now available for epidemiological surveys of the general population.
12379516 Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases. 2002 Nov OBJECTIVE: To review publications relating to the blocking of interleukin 1 (IL1) as a strategy for treating human disease, ranging from rheumatoid arthritis (RA) to Alzheimer's disease. METHODS: The National Library of Medicine's PubMed database was searched for articles about pharmaceutical agents that reduce the biological actions of IL1. RESULTS: Fish oils and corticosteroids were identified as non-selective pharmacological interventions that reduce the activity of IL1, whereas a recombinant human IL1 receptor antagonist (anakinra) and a soluble recombinant type I IL1 receptor act selectively. To date, anakinra is the only selective intervention that has been shown in controlled clinical trials to be effective and well tolerated in the treatment of a specific human disorder, RA. In controlled clinical trials, anakinra provided significant clinical improvement and slowed radiographic disease progression in patients with active RA. Moreover, addition of anakinra to existing methotrexate treatment significantly reduced signs and symptoms of active disease. CONCLUSIONS: The clinical use of anakinra has been demonstrated in the management of RA, but blocking of IL1 in other human disorders, as well as the safety of the use of these blocking agents in chronic diseases, still needs to be defined by controlled clinical investigations.
12137705 Rofecoxib for the treatment of rheumatoid arthritis. 2002 BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following electronic databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institute for Clinical Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inhibitors for arthritis. SELECTION CRITERIA: We included randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1996) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating rofecoxib for the treatment of RA were identified and met the inclusion criteria. One compared rofecoxib to placebo and was designed to assess the safety and efficacy of several doses of rofecoxib. The second trial compared rofecoxib to naproxen and was primarily designed to assess the safety of rofecoxib so did not include all the recommended RA efficacy measures. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Compared to patients taking naproxen, patients taking rofecoxib had a greater risk of having any cardiovascular event (45/4047 = 1.1% vs 19/4029 =0.47%) (RR 2.36 CI 1.38 to 4.02) and had greater risk of having a non-fatal myocardial infarction (MI) (18/4047 =0.44% and 4/4029 =0.1%) (RR 4.48, 95% CI, 1.52 to 13.23). REVIEWER'S CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.
15334454 Regional variation and differential response to therapy for knee synovitis adjacent to the 2004 Aug OBJECTIVE: To use magnetic resonance imaging (MRI) to investigate the importance of knee joint synovitis at the cartilage-pannus junction (CPJ) in rheumatoid arthritis (RA) as compared with synovitis at a distant site in the suprapatellar pouch (SPP) and as compared with CPJ synovitis in the spondylarthropathies (SpA), and to assess the relative response of knee joint synovitis to therapy at the CPJ and SPP sites. METHODS: Dynamic contrast-enhanced MRI (DEMRI) of actively involved knee joints in 24 patients (13 with RA and 11 with SpA) was undertaken. The area of synovitis was calculated at the CPJ and SPP regions of interest in patients with RA and in patients with SpA. Differences in CPJ and SPP synovitis were determined using calculated DEMRI parameters which included the initial rate of contrast enhancement (IRE) and the maximal enhancement (ME). Changes in the synovial area at the CPJ and SPP were also measured in 10 patients with early RA, following treatment with disease-modifying antirheumatic drugs (DMARDs) (either methotrexate or leflunomide). RESULTS: In patients with RA or SpA, the area of synovitis was significantly larger immediately adjacent to the CPJ compared with a distant site at the SPP (in RA, mean synovitis area 162 mm2 at the CPJ versus 114 mm2 at the SPP [P = 0.010]; in SpA, mean synovitis area 214 mm2 at the CPJ versus 143 mm2 at the SPP [P = 0.002]), but the differences in the areas of synovitis at these sites were not significant between the RA and SpA patients. The IRE and ME values were also higher at the CPJ compared with the SPP, both in the RA patients (IRE P = 0.054, ME P = 0.018) and in the SpA patients (IRE P = 0.002, ME P = 0.001). A larger reduction in the area of synovitis was seen at the SPP compared with the CPJ following DMARD therapy in the RA patients (mean reduction 35% at the SPP [P = 0.023] and 12% at the CPJ [P not significant]). CONCLUSION: The non-disease-specific variations in synovitis and the differential responses to therapy in RA patients have implications for improving our understanding of CPJ synovitis. The results suggest that the pathophysiologic events at the CPJ reflect common anatomic, immune system, or biomechanical factors that play a role in modulating the severity of arthritis, and these events are not specific to RA since the same process was observed in other arthritides.
12794793 A comparison of self-reports of distress and affective disorder diagnoses in rheumatoid ar 2003 Jun 15 OBJECTIVE: To compare 3 commonly used psychiatric symptom checklists (the Center for Epidemiological Studies Depression Scale [CES-D], the Positive and Negative Affect Schedule, and the Endler Multidimensional Anxiety Scales [EMAS]) to determine their sensitivity, specificity, and ability to discriminate between a disorder (Major Depression [MD], Generalized Anxiety Disorder [GAD]), and no disorder. To compare the checklists for their ability to discriminate between type of disorder (MD and GAD). To evaluate the discriminant ability of the subscales, particularly positive affect; whether the somatic items in the CES-D artificially inflate affective scores; and the optimal cut off score for the CES-D. METHODS: We compared the 3 scales to diagnostic criterion of MD, GAD, and comorbid disorder using receiver operator characteristic (ROC) and logistic regression analyses. The sample consisted of a national panel of 415 individuals with rheumatoid arthritis (RA). RESULTS: Each of the scales had high sensitivity and specificity (areas under the curve: CES-D = 0.92, negative affect = 0.88, positive affect and EMAS = 0.82). The CES-D, however, demonstrated better sensitivity and specificity than the positive affect and the EMAS, but not the negative affect scale. CONCLUSION: All 3 self-reports have high combined sensitivity and specificity as measures of affective disorders among RA patients.
11954893 Rheumatoid syndrome associated with lung interstitial disorder in a dental technician expo 2002 Feb Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.
12176805 Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and vascular endothelial growt 2002 Sep BACKGROUND: Cell adhesion molecules and endothelial growth factors have an important role in the infiltrating of rheumatoid synovium with mononuclear cells, leading to the initiation and progression of the disease. OBJECTIVE: To investigate whether the serum profile of soluble adhesion molecules and of vascular endothelial growth factor (VEGF) is associated with the histological appearance of rheumatoid arthritis (RA). METHODS: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were assessed by enzyme linked immunosorbent assay (ELISA) in 40 patients with RA and 32 patients with osteoarthritis (OA). RESULTS: Histological analysis of synovium specimens distinguished two types of rheumatoid synovitis. Twenty four RA samples presented diffuse infiltrates of mononuclear cells without any further microanatomical organisation, whereas in the remaining 16 samples lymphocytic follicles with germinal centre-like structures were identified. In comparison with patients with OA, constituting a control group, higher serum concentrations of sICAM-1 (p<0.001), sVCAM-1 (p<0.001), sE-selectin (p<0.01), and VEGF (p<0.001) were detected in patients with RA. Raised concentrations of sICAM-1, sVCAM-1, and VEGF dominated in the serum of patients with RA with follicular synovitis compared with those with diffuse synovitis (p<0.01 for all comparisons). The serum concentrations of sICAM-1, sVCAM-1, and VEGF correlated with markers of disease activity such as the erythrocyte sedimentation rate and C reactive protein levels. Furthermore, the clinical data analysed in our study indicated that patients with RA with follicular synovitis tend to have more severe disease. CONCLUSIONS: The distinct histological appearances of rheumatoid synovitis associated with different serum profiles of sICAM-1, sVCAM-1, and VEGF reflect varied clinical activity of the disease and confirm RA heterogeneity. Patients with different histological forms of synovitis may respond differently to the treatment regimens.
14705230 Fat suppression magnetic resonance imaging in shoulders of patients with polymyalgia rheum 2004 Jan OBJECTIVE: To evaluate the sites of inflammatory process in the shoulders of patients with polymyalgia rheumatica (PMR) using fat suppressed magnetic resonance imaging (MRI). METHODS: Six consecutive, untreated new patients with PMR were investigated. Five patients with early rheumatoid arthritis (RA) and 4 patients with early psoriatic arthritis (PsA) with bilateral shoulder symptoms served as a control group. Bilateral shoulder fat-suppressed MRI sequences were performed in all patients and controls. We evaluated the presence of joint synovitis, bursitis, tenosynovitis, and bone and soft tissue edema. RESULTS: Bilateral subacromial/subdeltoid bursitis was found in all patients with PMR, in 1/5 (20%) patients with RA (p < 0.05), and in none with PsA (p < 0.02). Glenohumeral synovitis was present in all case and controls. Biceps tenosynovitis was observed in 4/6 (67%) patients with PMR, in 4/5 (80%) with RA (not significant, NS), and in all 4 patients with PsA (NS). No evidence of bone edema adjacent to the joint capsule and entheseal insertions or in the soft tissues was present in either cases or controls. CONCLUSION: The absence of extracapsular abnormalities in the early shoulder disease of PMR does not confirm the hypothesis of a capsular-based disorder.
15361388 Detection of small joint synovitis by ultrasonography: the learning curve of rheumatologis 2004 Oct BACKGROUND: Ultrasonography allows assessment of soft tissue structures and has become a valued tool for diagnosing synovitis. OBJECTIVE: To assess the learning curve for ultrasonography in evaluating synovitis of the small joints in rheumatoid arthritis. METHODS: Metacarpophalangeal (MCP), metatarsophalangeal (MTP), and proximal interphalangeal (PIP) joints were evaluated using ultrasonography (Esaote AU 5 Epi, linear probe 10-13 MHz) by four rheumatologists, the first being experienced (senior), the others having no (fellows 1 and 2) or little (fellow 3) experience in ultrasonography. For each fellow, the learning curve was divided into blocks. In each block the fellow examined five consecutive patients with the senior; then, blinded to the senior's results, two further patients alone (seven patients examined per block). For each evaluation, the MCP, PIP, and MTP joints were individually tagged as having synovitis or not. The ultrasonography results were compared between fellow and senior for the two last patients of each block, using proportions of agreement and kappa statistics. RESULTS: 70 patients were evaluated (seven practice patients, followed by nine blocks). For fellows 1 and 2, the proportions of agreement were respectively 42% and 47% (kappa = 0 and 0) at the first evaluation, and rose progressively to 82% and 82% (kappa = 0.63 and 0.62) at the ninth evaluation. For fellow 3, initially good results were followed by decreased accuracy. CONCLUSIONS: Detecting synovitis of the MCP, PIP, and MTP joints using ultrasonography can be done accurately by rheumatologists initially not experienced in this technique. At least 70 examinations were necessary to develop competence.
11974948 [Maintenance and improvement of quality of life among elderly patients using a pet-type ro 2002 Mar There have been reports of cases in which quality of life and loneliness of elderly people have been affected by interaction with the pet-type robot AIBO. In the present comparison between first and 20th sessions of activity with the pet-type robot, statistically significant improvements were observed in speech, emotional words and satisfaction index. The AKO loneliness scale value was 3.33 at the first session, and was 1.00 at the 20th session (statistically significant decrease). In a comparison of health-related QOL before and after interaction with AIBO, using the SF-36 survey, role function (RP) was statistically higher at the 20th session than at the first session. Evaluation by CgA, a mental stress index, showed a statistically significant decrease as the number of AIBO sessions increased. Case 1: The patient was a 68-year-old woman with chronic rheumatoid arthritis. Her AKO loneliness scale value was 4 on the first session and 1 on the 20th session. She said, "I do not think about anything while playing with the pet-type robot. It heals my mind." Case 2: The patient was a 74-year-old woman with cervical osteochondrosis. Her AKO loneliness scale value was 5 on the first session and 2 on the 20th session. She said, "The first time, I didn't like playing with the robot because I was depressed. After I had played with the robot several times, I felt good." Case 3: The patient was an 84-year-old man with cerebral apoplexy sequelae. His AKO loneliness scale value was 6 on the first session and 1 on the 20th session. He sang with the robot occasionally. The amount of conversation between him and his children greatly increased. Unlike animals, a pet robot does not carry the risk of bacterial infection. The present results suggest the possibility of using robots as a substitute for animal-assisted therapy and other psychosocial therapy in aseptic rooms, ICUs, children's wards, and special care wards for patients with dementia.
12635469 Intravenous anti TNF-alpha antibody therapy leads to elevated triglyceride and reduced HDL 2002 Dec 30 BACKGROUND & AIMS: We investigated the effect of Infliximab, an anti TNF-alpha antibody, on plasma lipids and lipoproteins in patients with rheumatoid arthritis and psoriatic arthritis. METHODS: Five male and 10 female patients with a mean age of 56.7 years were included in this study. Seven of the patients were diagnosed with rheumatoid arthritis and 8 patients with psoriatic arthritis. All patients received infusions of 3 mg/kg Infliximab (at week 0, 2 and 6). Lipids, lipoproteins and standard clinical parameters were assessed at baseline (0 week), after 2 weeks, and in 4 patients after 6 weeks. RESULTS: There was a significant increase in triglyceride levels during treatment with Infliximab (112 +/- 48 versus 133 +/- 53 mg/dl, p < 0.01). In contrast, HDL-cholesterol levels were significantly lowered (56 +/- 12 versus 50 +/- 13 mg/dl, p < 0.006) by the treatment. There was no significant difference in total cholesterol (209 +/- 25 versus 205 +/- 36 mg/dl) or in LDL-cholesterol (131 +/- 24 versus 118 +/- 43 mg/dl) before and after treatment. Similarly, lipoprotein(a) levels did not alter during treatment (median: 1.1 versus 1.4 mg/dl). CONCLUSION: This study shows that intravenous Inflixmab therapy leads to changes in plasma lipid and lipoprotein levels in patients with rheumatoid and psoriatic arthritis and may result in a more atherogenic lipid and lipoprotein profile. Although larger patient numbers need to be studied to confirm our findings, these results suggest that lipid levels should be checked and monitored in patients receiving infliximab therapy, particularly in patients with vascular disease.
12874646 [Plasma procalcitonin in rheumatic diseases]. 2003 Data on the origin and biological function of procalcitonin, the pro-hormone of calcitonin, are scarce. Since this peptide can be induced in bacterial invasive infections, serum procalcitonin levels may be useful in differential diagnosis of systemic inflammatory response syndrome. This review will focus on the clinical significance of changes in serum procalcitonin levels in patients with connective tissue diseases and other rheumatic disorders.
14994391 Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report 2004 Mar OBJECTIVE: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis. METHODS: The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire. RESULTS: Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer. CONCLUSION: Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.
14740460 Growth reconstitution in juvenile idiopathic arthritis treated with etanercept. 2003 Nov OBJECTIVE: Growth failure is a leading problem in uncontrolled juvenile idiopathic arthritis. It also affects 10% of patients who are not treated with corticosteroids. The influence of proinflammatory cytokines like interleukin-1 beta, interleukin-6 and tumour necrosis factor on the neuroendocrine axis as well as on the production of insulin-like growth factors (IGFs) has been postulated. The objective of the current study was to evaluate effects of highly active antirheumatic treatment with tumour necrosis factor antagonist on growth retardation. Seven out of 18 patients with refractory juvenile idiopathic arthritis treated with etanercept demonstrated growth retardation leading to short stature. METHODS: Antropometric measurements and disease activity parameters--including the number of swollen and tender joints, morning stiffness, ESR and CRP levels--were monitored monthly during the first year of treatment and every 3 months thereafter. Serum levels of IGF-1 and IFG-BP were measured as well. RESULTS: Upon treatment with etanercept, growth velocity increased from 3.7 +/- 1.2 cm before the beginning of the therapy to 7.6 +/- 1.2 cm in the first year of treatment (p < 0.001). The average length-standard-deviation-score (SDS) increased from -2.4 +/- 1.0 to -1.9 +/- 0.9 after one year and to -1.1 +/- 0.9 after two years (p = 0.05) indicating catch-up growth. Prior to the therapy, serum levels of insulin-like growth factor-1 and of insulin-like growth factor binding protein-3 were within the normal range but increased significantly upon treatment (p < 0.001). An inverse correlation of the IGF-1 serum level to CRP was found. CONCLUSIONS: An intensified anti-inflammatory treatment using etanercept has a beneficial effect on growth in children with a so far uncontrolled inflammatory disease. This effect might be related to the cessation of the inhibitory effect of proinflammatory cytokines on the synthesis of IGF-1 and IGF-BP-3 in the liver. Growth failure should be included in the evaluation of antirheumatic treatment.
12066349 Advances in the medical management of rheumatoid arthritis. 2002 May New treatments, such as leflunomide and biologic therapy, are making an important impact on the management of rheumatoid arthritis. This article reviews the efficacy of these agents, the use of combination therapy, and the importance of early treatment with a disease-modifying antirheumatic drug.