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We present nine cases of systemic lupus erythematosus with refractory disease that we treated with the chimeric monoclonal anti-CD20 antibody rituximab. Three patients had renal disease, three neurological involvement with transverse myelitis and vasculitis of the central nervous system, one thrombocytopenia, one skin involvement with generalized erythema and one patient had constitutional, haematological and immunological symptoms. Two patients with renal disease, the patient with immune thrombocytopenia and the three patients with neurological disease, who stayed in remission despite a reduction of immunosuppressive therapy, responded particularly well to the therapy. Five of nine patients showed an improvement in ECLAM of at least two points. During therapy only minor adverse events were observed. One patient died during follow-up which was unrelated to the therapy. The selective depletion of B-lymphocytes in the therapy of systemic lupus erythematosus seems to be an effective and safe treatment option for different manifestations.

According to the NIH scheme, the "evidence based medicine" standard in the treatment of severe proliferative lupus-nephritis is cyclophosphamide in combination with steroids. Undesired effects, therapy resistance, and deficient long-term effects underscore the necessity for the development of alternative therapies for the treatment of organ involvement. Mycophenolate mofetil (MMF) possesses the potential to decisively improve the therapeutic possibilities for systemic lupus erythematosus (SLE). On the basis of the available data, MMF represents an alternative to the current standard therapies for severe lupus-nephritises and shows less toxicity. MMF is also effective in patients with other manifestations refractory to conventional therapy. Questions remain unanswered on the optimal dosage and possible reduction in cases of remission. In addition, the duration of maintenance therapy is unclear. Therefore, large, prospective, randomized clinical studies in the treatment of lupus-nephritis with a sufficiently long follow-up phase are underway.

Systemic connective tissue diseases (CTDs) are disease entities characterized by a systemic and heterogeneous spectrum of clinical symptoms. The treatment of CDTs has improved substantially, but with the developments of new and probably more expensive targeted therapies, there will be a need of rigorous evaluation in patient-oriented research. Proposed domains for outcome measurement of CTDs are activity, damage by disease and/or medications and quality of life. To evaluate the overall disease activity in CTDs, scores are developed that include typical signs and symptoms. For example, in systemic lupus erythematosus (SLE), various activity instruments have been developed and validated. Recently, a definition for significant reduction in activity based on these scores was proposed and has now to be validated in clinical trials. In addition, the American College of Rheumatology has framed recommendations for response criteria of major target organs. Besides, the rarity of CTDs other than SLE and the rare therapeutic options, especially the heterogeneous disease expression, has prevented development of instruments scoring the disease activity. In individual patients, there is need for a more organ-specific evaluation, and non-disease-specific and/or global health instruments may be used in evaluating the response of individual treatment regimen.

Morbidity and co-morbidities in patients with lupus erythematosus (LE) result in an impairment, limiting activities of daily living. We compared the handicap, appraised by the German welfare system in patients with LE and their diagnosis, morbidities and co-morbidities, therapy, functional capacity, psychological status and general health. The data were obtained in an anonymous self-administered questionnaire conducted by the lupus patient association. 892 data sets were available for the trial. The mean age was 46.9y, disease duration was 10.3y. The patients had 3.8 concomitant diseases on average. 39.7% were still working and 35.4% drew a pension. 59.2% made an application for disability, which wasn't assigned in only 2.5% of cases. 82.6% had an average grade of disability of more than 50%. It demonstrated a good correlation to age, disease duration, type of LE and therapy. Predictors for a worse assessment were disease duration, osteoarthritis, cerebral insults and functional capacity. In conclusion the data demonstrate a fair appraisal of disability by the German welfare system in patients with LE. Self-administered questionaires can yield credible results.

Objective: To evaluate a novel specific psychological intervention aimed at improving coping in patients with systemic lupus erythematosus (SLE)., Methods: 34 community living SLE patients were recruited for the study. Intervention was undertaken in groups of up to eight patients and in two blocks over six months each. Eight patients were enrolled as a waiting list group. The 18 group sessions focused on information about the disease and specific problems of SLE patients, combining psychoeducative and psychotherapeutic elements. Psychological and medical evaluations were conducted at baseline and after three, six, and 12 months, using validated instruments., Results: The 34 SLE patients (91% female, mean age 42 years) improved significantly over a six month period on most of the psychological measuring instruments applied, such as depression, anxiety, and overall mental burden. The waiting list group showed no significant changes., Conclusions: Conceptualised psychoeducational support may produce a significant and sustained improvement in coping skills of SLE patients and hence in their quality of life.

Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported during the last few years in patients with systemic lupus erythematosus (SLE). Studies found relative risks of 5 to 7 for myocardial infarction in SLE patients. The traditional risk factors fail to fully account for accelerated atherosclerosis in SLE and APS, in addition prolonged glucocorticoid therapy and long duration of SLE seem to be of importance. The disease SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response, autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), CD40/CD40 ligand interactions, and bacterial or viral infections responsible for an immune response. The determination of classic and new risk factors, together with specific autoantibody titers and the use of Doppler carotid ultrasound, are useful methods to detect early atherosclerosis. Therapeutic strategies, including early risk factor intervention and effective control of inflammation, are essential to reduce morbidity and mortality and should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.

During the last few decades, the prognosis for patients with systemic lupus erythematosus (LE) has changed from high early mortality to a more chronic longterm course. Although the prevalence of LE has been estimated at 20-50/100,000, data concerning the situation of LE patients in Germany are sparse. Since 2001, a documentation within the German Lupus Self-Help Organisation scheduled for a period of 10 years (LULA) has been recording at the patient level the actual status and the long-term course of a large group of LE patients. A questionnaire adapted from the German rheumatological database is updated once a year and sent to all members.In 2001, 1033 members participated in the documentation. Of these, 92.2% were women (mean age 45.8 years) with a mean disease duration of 9.9 years. 37.6% were employed, and 24.5% were on early retirement. 50.2% rated their overall health status as "not so good" or "poor". Most were receiving treatment with [hydroxy-]chloroquine (35.2%) or azathioprine (21.9%), while 67.9% were receiving corticosteroids. The most frequent comorbidities reported were hypertension (33%), scarring skin disease (24.4%), osteoarthritis (25.2%), osteoporosis (24%), psychiatric disorders/depression (22.9%) and chronic renal disease (22%). Thromboembolic events were reported in 18.5%, myocardial infarction in 2.3% and stroke in 4.8% of cases. Concerning their main contact person for health care, 63.6% specified the rheumatologist. In comparison with other cohort studies and in particular with the German rheumatological database, the data provided exclusively by patients are feasible. Concerning the severity of their disease, their treatment and their global assessment of health status, LULA participants are comparable with other LE patients and can be seen as representative of LE patients in Germany. Further assessment especially of long-term data are needed to obtain additional insights into the burden of the disease and the need for special medical care.

Background: The heteropolymer technology was developed to remove pathogens from the circulation., Objectives: To evaluate the safety and tolerability of a single administration and to establish proof of principle for ETI-104 in normal healthy volunteers (NHV) and patients with systemic lupus erythematosus (SLE) METHODS: The drug was given intravenously to 11 NHV and six patients with SLE. Over 28 days, vital signs were noted, a haematological and chemical analysis of blood and urine was carried out, and adverse events were recorded. CR1 receptor numbers, the ability of antigen based heteropolymers to bind to red blood cells (RBCs), and the clearance of high avidity and total anti-dsDNA antibodies were measured by Farr assays and FACS analysis., Results: No safety measure differed significantly from normal in both groups; no drug related serious adverse events occurred. ETI-104 rapidly bound to RBCs in NHV and patients with SLE. Binding of the drug to RBCs of patients with SLE also caused a rapid reduction of circulating anti-dsDNA antibodies in the plasma 15 minutes after administration, with a maximum reduction of 55% (range 43-62). At 28 days statistically significant decreases were maintained in three patients, while in the other three the values had returned to baseline levels., Conclusion: These clinical trials established the safety and the proof of principle of the new immunoconjugate ETI-104. This provides the basis for further development of this technology for numerous indications-for example, therapeutic options for autoimmune diseases or viral and bacterial infections.

Recombinant human granulocyte colony-stimulating factor (rhuG-CSF) is frequently given to patients with leukopenia or neutropenia caused by various underlying diseases. The treatment with rhuG-CSF is apparently safe, although cutaneous vasculitis and flares in patients with autoimmune diseases are described. We describe 2 patients with histologically proven antineutrophil cytoplasmic antibody-associated systemic vasculitis with disease flares after administration of rhuG-CSF, given to improve collection of stem cells prior to autologous stem cell transplantation.

Guidelines for assessments of connective tissue diseases in social jurisdiction and for insurance are not available in Germany. This article is a guideline reflecting published data, modern therapy and actual prognosis. In addition, help for interpretation and examples are given.