Search

Objective: To identify the most important and relevant concepts of daily functioning from the perspective of patients with systemic lupus erythematosus (SLE)., Methods: We conducted a consensus-building, 3-round, electronic mail survey with SLE patients using the Delphi technique. The Delphi technique is a structured communication process with 4 key characteristics: anonymity, iteration with controlled feedback, statistical group response, and informed input. The concepts contained in the answers of the patients were extracted and linked to the International Classification of Functioning, Disability and Health (ICF)., Results: Of the total 225 participants, 194 (86.2%) completed the questionnaires from all 3 Delphi rounds. In total, after the third Delphi round, 307 concepts were identified. Ninety concepts (55 in the domain body functions and structures, 16 in activities and participation, and 19 in environmental factors) were considered relevant by at least 50% of the participants in the third round and linked to the ICF. Twelve concepts were considered important by at least 75% of the participants., Conclusion: The high number of concepts resulting from this large-scale patient Delphi approach underlines the great variety of SLE patients' problems in daily functioning. The results of this patient Delphi project supplement the findings of our focus-group study in establishing a comprehensive overview of the patient perspective in SLE.

Objective: To evaluate the ability to teach scleroderma experts and young rheumatologists to perform the modified Rodnan skin score test., Methods: Three international "teaching courses for teachers" were conducted with 6-9 experts who performed 3-9 skin score tests each. In addition, an international course for 90 young rheumatologists, in which 18 patients with systemic sclerosis (SSc) participated, was also organised. Finally, a local repeated training course for 5-9 rheumatologists was performed, in which 6-7 patients with SSc participated., Results: When 6-9 scleroderma specialists investigated the patients, the intraclass correlation coefficient (ICC) showed "good" to "excellent" values (0.865 and 0.710, respectively). When 90 young rheumatologists were involved in one teaching course, the coefficient of variation (CV) was relatively satisfactory (35%) owing to the high number of investigators, and with a considerable within-patient SD value of 5.4. Repeated teaching of 5-9 young rheumatologists in local courses clearly improved the consistency. The ICC increased from 0.496 to a "good" level of 0.722. The within-patient SD values for intraobserver variability ranged between 2.5 and 2.9. The intraobserver CV was about 20%., Conclusions: This study strongly supports the need for standardisation among different centres when using skin scoring for clinical trials. The intraobserver variability and within-patient SD values can be significantly reduced by repeated teaching. For inexperienced rheumatologists, at least one repeated teaching course is needed.

Objective: To analyze changes in autoantibodies occurring in patients with systemic lupus erythematosus (SLE) treated with 4 infusions of the chimeric anti-tumor necrosis factor alpha (TNFalpha) antibody infliximab., Methods: In an open-label safety study, 7 patients with SLE were treated with infliximab at weeks 0, 2, 6, and 10 in combination with azathioprine or methotrexate. Antibodies to double-stranded DNA (dsDNA) were determined by radioimmunoassay and the Crithidia luciliae indirect immunofluorescence assay; anticardiolipin antibodies (aCL) and antibodies to histone and chromatin were measured by enzyme-linked immunosorbent assay. Antihistone antibodies were also analyzed by immunoblotting. Peripheral blood mononuclear cells from healthy individuals and SLE patients were incubated for 2 weeks with or without TNFalpha. TNFalpha was removed by washing and by the addition of infliximab. Apoptotic cells were stained with annexin V and analyzed by flow cytometry., Results: Autoantibodies to dsDNA increased in 5 of 7 patients. Histone, chromatin, and IgM aCL levels were increased in 4 of 7, 6 of 7, and 4 of 7 patients, respectively, peaking 4-10 weeks after the last infliximab infusion, but falling to baseline levels or lower thereafter. In the in vitro experiments, TNF withdrawal after long-term incubation with recombinant human TNF led to increased percentages of apoptotic cells., Conclusion: While TNF blockade was clinically effective, the majority of SLE patients treated with infliximab showed an increase in autoantibodies to nuclear antigens and phospholipids. These increases were transient and were not associated with disease flares. Increased availability of apoptotic antigens after TNF blockade may play a role in the autoantibody formation induced by TNF blockade.

Objective: To investigate the safety of therapeutic tumor necrosis factor alpha (TNFalpha) blockade in patients with systemic lupus erythematosus (SLE), in whom this proinflammatory cytokine is significantly increased and may be involved in the disease pathogenesis., Methods: In an open-label study, 6 patients with moderately active SLE (4 with nephritis and 3 with arthritis refractory to other therapies) were given 4 300-mg doses of infliximab, a chimeric anti-TNFalpha antibody, in addition to immunosuppression with azathioprine or methotrexate., Results: The only significant adverse events observed were urinary tract infection in 3 patients, 1 of which was accompanied by Escherichia coli bacteremia, and a prolonged febrile episode of putatively viral origin in 1 of them. These patients had similar infectious conditions in the past. In none of the patients was it necessary to terminate the treatment prematurely. Levels of antibodies to double-stranded DNA and cardiolipin increased in 4 patients each, but this was not associated with a decrease in serum complement levels, with vascular events, or with flares. In contrast, disease activity declined during therapy. All 3 patients with joint involvement experienced remission of arthritis, which relapsed 8-11 weeks after the last infliximab infusion. In the 4 patients with lupus nephritis, proteinuria decreased significantly within 1 week after initiation of therapy and was diminished by > or = 60% within 8 weeks, remaining at low levels until the end of the observation period (at least several months)., Conclusion: Infliximab did not lead to adverse events related to an increase in SLE activity, although autoantibodies to double-stranded DNA and cardiolipin increased, as expected. This finding, coupled with the clinical improvement in the inflammatory manifestations of the disease, indicates that further study in larger controlled trials is warranted., (Copyright 2004 American College of Rheumatology)

Because of Cyclooxygenase-2 selective non steroidal anti-inflammatory drugs (NSAIDs), the therapy of articular pain has become safer and more convenient. Currently, two highly Cyclooxygenase-2 selective drugs, celecoxib and rofecoxib, are available. Both are effective for patients with osteoarthritis (at daily dosages of 200 mg and 12.5 mg, respectively) and rheumatoid arthritis (RA) (at twice the above dosages). At higher daily dosages of 800 mg and 50 mg these substances still appear safe with regard to life-threatening gastrointestinal complications (perforation, obstruction, bleeding), if not given with concomitant aspirin. However, Cyclooxygenase-2 selective non steroidal anti-inflammatory drugs do not confer protection against platelet aggregation and aspirin must be given where required for cardiovascular prophylaxis. Most patients will then routinely need gastroprotective agents such as proton pump inhibitors or misoprostol; it is unclear whether coxibs confer any benefit under such circumstances. Although not a coxib, Meloxicam does not appear to cause serious gastrointestinal complications if the low daily dosage of 7.5 mg is sufficient for the control of less pronounced pain and thus not exceeded. The gastrointestinal safety of nimesulide can not be sufficiently evaluated based on the available clinical data.