Rheumatoid Arthritis: Germany

Horneff G. · Universitätsklinik und Poliklinik für Kinder und Jugendmedizin, Halle. · Z Rheumatol. · Pubmed #16372138 No free full text.

Abstract: The group of biologics for the treatment of rheumatic diseases is continuously growing. They have become an important option not only for treatment of so far untreatable chronic inflammatory or rheumatic disease, but also for juvenile idiopathic arthritis. In addition, the velocity and the degree of improvement is better than with to conventional therapies. Furthermore, toxicity and risks seem to be lower with higher safety and compatibility. Although the data are scarce, they are widely used. Therefore, the German Arbeitsgemeinschaft Kinder- und Jugendrheumatologie is updating the current recommendation for the treatment of juvenile idiopathic arthritis using biologics.

Niehues T, Horneff G, Michels H, Höck MS, Schuchmann L, Anonymous00331, Anonymous00332. · Pediatric Immunology and Rheumatology, Department of Pediatric Oncology, Hematology and Immunology, Centre for Child Health, Heinrich-Heine-University, Dusseldorf, Germany. · Rheumatol Int. · Pubmed #15688190 No free full text.

Abstract: Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with non-steroidal anti-inflammatory drugs (NSAID) and physiotherapy. However, in a significant number of cases the disease is resistant to this therapy, and treatment with "second line" disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as "first-choice second-line agent" for the treatment of JIA. To increase drug safety, the Working Groups for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words "Methotrexate" and "juvenile arthritis" limited to age 0-18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin DRFZ), experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded, and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.

Kalden JR, Scott DL, Smolen JS, Schattenkirchner M, Rozman B, Williams BD, Kvien TK, Jones P, Williams RB, Oed C, Rosenburg R, Anonymous00047. · Department of Internal Medicine III, University of Erlangen-Nuremberg, Germany. · J Rheumatol. · Pubmed #11550964 No free full text.

Abstract: OBJECTIVE: We previously reported that the new disease modifying antirheumatic drug leflunomide resulted in significant improvement in functional ability compared with placebo and sulfasalazine in a 6 month double blind, randomized, Phase III trial in rheumatoid arthritis (RA). The current study compared functional disability in cohorts of patients with RA from the initial study who volunteered to continue treatment with leflunomide or sulfasalazine. METHODS: The Health Assessment Questionnaire (HAQ) was used to assess functional ability in patients completing 6 months of therapy who chose to continue in double blinded 12 and 24 month extensions. Patients on active regimens continued taking leflunomide 20 mg/day or sulfasalazine 2 g/day; those taking placebo were switched at Month 6 to sulfasalazine. RESULTS: Leflunomide significantly improved patients' functional ability compared to placebo (p < or = 0.0001) and sulfasalazine (p < or = 0.01) at 6 months. These changes were seen as early as Month 1, and continued improvements were seen in 12 and 24 month cohorts. Mean HAQ scores were significantly improved with leflunomide compared with sulfasalazine at 24 months (-0.65 vs -0.36; p = 0.0149); corresponding changes in HAQ Disability Index (DI) were -0.73 vs -0.56 and were not statistically different. Leflunomide is safe and well tolerated and no unexpected adverse events were noted during the 2 year period; diarrhea, nausea, and alopecia were less frequent with continued treatment. CONCLUSION: These longterm data confirm leflunomide improves functional ability as shown by reductions in HAQ scores. The benefit of leflunomide is reflected in other efficacy criteria, such as global assessments and the American College of Rheumatology response rates, all of which showed significantly more improvement with leflunomide than sulfasalazine at 24 months.

Keitel W, Genth E, Gromnica-Ihle E, Häntzschel H, Kalden JR, Mathies H, Raspe HH, Schneider M, Warnatz H, Zacher J, Abholz HH. · Rheumaklinik und Rheumaforschungsinstitut, Aachen. · Z Rheumatol. · Pubmed #10929443 No free full text.

Abstract: The guideline "Joint Swelling" is addressed to primary care physicians--general practitioners, internists or orthopedists without special experience in rheumatology. It provides a framework for interviewing patients, as well as for physical, laboratory and imaging examinations and for selection of treatment appropriate to the level of primary care. Situations which call for urgent evaluation and criteria for referral to rheumatologists are described. The appendix contains comments on signs and symptoms to differentiate arthralgia from joint swelling and on the diagnostic value of a history of joint swelling without confirmation by the physician. Further recommendations for the evaluation of patient history and physical and technical examinations are given in a tabular form. The significance of laboratory and imaging procedures is discussed.

Schmidt K, Rüther W. · Klinik für Orthopädie und Rheumaorthopädie, Katholisches Krankenhaus Dortmund-West, Zollernstrasse 40, 44379, Dortmund. · Z Rheumatol. · Pubmed #18779969 No free full text.

This publication has no abstract.

Rüther W. · Orthopädische Klinik der Rheumaklinik Bad Bramstedt, Universitätsklinikum Hamburg-Eppendorf. · Z Rheumatol. · Pubmed #17896423 No free full text.

This publication has no abstract.

Märker-Hermann E. · Klinik Innere Medizin IV, Dr. Horst Schmidt Kliniken (HSK) GmbH, HSK Wilhelm Fresenius Klinik, Aukammallee 39, 65191, Wiesbaden, Deutschland. · Z Rheumatol. · Pubmed #17006701 No free full text.

This publication has no abstract.

Martignoni ME, Kunze P, Friess H. · Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110 Germany. · Mol Cancer. · Pubmed #14613583 links to  free full text

Abstract: In recent years many efforts of researchers and clinicians were made to improve our knowledge of cachexia syndrome. Not only cancer, but also many chronic or end-stage diseases such as AIDS, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, tuberculosis and Crohn's disease are associated with cachexia, a condition of abnormally low weight, weakness, and general bodily decline which deteriorates quality of life and reduces the prognosis of the patients who suffer from it. In the present editorial we will focus cachexia related on cancer and provide some insight into this prognosis-limiting syndrome.

Hönscheid A, Rink L, Haase H. · Institute of Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany. · Endocr Metab Immune Disord Drug Targets. · Pubmed #19519463 No free full text.

Abstract: The trace element zinc is a crucial cofactor for many proteins involved in cellular processes like differentiation, proliferation and apoptosis. Zinc homeostasis is tightly regulated and disturbance of this homeostasis due to genetic defects, zinc deficiency, or supplementation influences the development and the progression of various infectious and autoimmune diseases. The immune system is strongly impaired during zinc deficiency, predominantly the cell-mediated response by T-lymphocytes. During zinc deprivation T-lymphocyte development, polarization into effector cells, and function are impaired. This leads to reduced T-cell numbers, a decreased ratio of type 1 to type 2 T-helper cells with reduced production of T-helper type 1 cytokines like interferon-gamma, and compromised T-cell mediated immune defense. Accordingly, disturbed zinc homeostasis increases the risk for infections, and zinc supplementation restores normal immune function. Furthermore, several disorders, like mycobacterial infections, asthma, diabetes, and rheumatoid arthritis are accompanied by decreased zinc levels and in some cases disease progression can be affected by zinc supplementation. On the molecular level, apoptosis of T-cell precursors is influenced by zinc via the Bcl-2/Bax ratio, and zinc ions inhibit caspases-3, -6, -7, and -8. In mature T-cells, zinc interacts with kinases involved in T-cell activation, like protein kinase C and the lymphocyte protein tyrosine kinase (Lck), while higher zinc concentrations are inhibitory, reducing the activities of the interleukin-1 receptor-associated kinase (IRAK) and calcineurin. Taken together, zinc homeostasis influences T-lymphocytes via several molecular targets, leading to a modulation of T-cell-dependent immune responses.

Mankan AK, Lawless MW, Gray SG, Kelleher D, McManus R. · Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College, Dublin, Ireland. · J Cell Mol Med. · Pubmed #19438970 No free full text.

Abstract: Nuclear factor kappaB (NF-kappaB) is an inducible transcription factor that tightly regulates the expression of a large cohort of genes. As a key component of the cellular machinery NF-kappaB is involved in a wide range of biological processes including innate and adaptive immunity, inflammation, cellular stress responses, cell adhesion, apoptosis and proliferation. Appropriate regulation of NF-kappaB is critical for the proper function and survival of the cell. Aberrant NF-kappaB activity has now been implicated in the pathogenesis of several diseases ranging from inflammatory bowel disease to autoimmune conditions such as rheumatoid arthritis. Systems governing NF-kappaB activity are complex and there is an increased understanding of the importance of nuclear events in regulating NF-kappaB's activities as a transcription factor. A number of novel nuclear regulators of NF-kappaB such as IkappaB-zeta and PDZ and LIM domain 2 (PDLIM2) have now been identified, adding another layer to the mechanics of NF-kappaB regulation. Further insight into the functions of these molecules raises the prospect for better understanding and rational design of therapeutics for several important diseases.

Braun J, Rau R. · Rheumazentrum Ruhrgebiet, Landgrafenstr 15, Herne 44652, Germany. · Curr Opin Rheumatol. · Pubmed #19373092 No free full text.

Abstract: PURPOSE OF REVIEW: Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about three decades now. MTX is one of the most effective and commonly used medicines to treat various forms of arthritis and other rheumatic conditions. MTX was shown to improve signs and symptoms of RA, disease activity and function, to a similar degree as the tumor necrosis factor blockers, and it inhibits radiographic progression to a smaller degree than the antitumor necrosis factor agents. MTX is considered as the anchor drug among the disease-modifying antirheumatic agents, and it is internationally accepted as the first choice in the management of RA. This review was performed on the basis of a PubMed literature search looking at all publications on MTX and arthritis in 2008. RECENT FINDINGS: MTX seems to even prolong the life span of patients who tolerate the drug and have clinical benefit from this therapy; this may partly be explained by beneficial effects on cardiovascular mortality. The reason for this may well be the suppression of inflammation, but direct atheroprotective effects of MTX may also play a role. MTX is used as monotherapy and in combination with other disease-modifying antirheumatic agents or biologic agents such as the antitumor necrosis factor agents. The 'early' use of MTX within 5 years after disease onset is clearly associated with improved outcomes. The management of RA should include an early strong suppression of inflammation and continuously a tight control strategy. The pharmacodynamics and kinetics of MTX are still incompletely understood. SUMMARY: In this review, we especially cover the following themes: new clinical studies on the use of MTX in RA, the use of MTX in other rheumatic conditions, prediction of response to MTX, optimal dosage, MTX use in the elderly, the mechanism of action, the pharmacokinetics and the pharmacogenetics of MTX, the prevention of side effects, and the overall long-term safety.

Ziegenhagen DJ. · Abteilung Medizinische Beratung, Köln. · Versicherungsmedizin. · Pubmed #19370838 No free full text.

Abstract: Biologics include a wide range of medications that are produced by means of biological processes involving recombinant DNA technology. Approximately one in four of the recently approved new therapeuticals belongs to this group. Biologics have added major therapeutic options for the treatment of many diseases with an especially profound impact on rheumatoid arthritis, chronic inflammatory bowel disease, psoriasis, multiple sclerosis and a great array of malignancies. Many more targets are already screened in clinical research. Despite their clinical promises, monoclonal antibodies are raising concern about the potential adverse effects of long-term use. Costs are dramatically higher than for conventional medications, raising severe pharmacoeconomic concerns.

Rubbert-Roth A, Finckh A. · Department of Internal Medicine, University of Cologne, Josef-Stelzmann-Strasse, 50924 Cologne, Germany. · Arthritis Res Ther. · Pubmed #19368701 links to  free full text

Abstract: Conventional disease-modifying antirheumatic drugs such as methotrexate are the mainstay of treatment for rheumatoid arthritis. More recently, biologic agents such as etanercept, infliximab and adalimumab, which act by inhibiting tumour necrosis factor (TNF), have become available. TNF inhibitors have proved to be very effective in patients not responding to conventional disease-modifying antirheumatic drugs. However, about 20% to 40% of patients treated with a TNF inhibitor fail to achieve a 20% improvement in American College of Rheumatology criteria, and more lose response over time (secondary failure or acquired therapeutic resistance) or experience adverse events following treatment with a TNF inhibitor. In this group of patients, therapeutic options were limited until recently and an established treatment approach was to switch from one TNF inhibitor to another. In recent years, therapeutic options in these patients have increased with the introduction of biologic agents with novel mechanisms of action, such as rituximab and abatacept. This review outlines the current evidence in support of the available treatment strategies in patients with an inadequate response or intolerance to an initial TNF inhibitor.

Pechlivanis I, Scholz M, Harders A, Schmieder K. · Klinik für Neurochirurgie, Ruhr-Universität Bochum. · Z Orthop Unfall. · Pubmed #19358082 No free full text.

Abstract: Lumbar synovial cysts represent a rare condition, they are believed to arise from defects of the joint capsule due to degeneration, trauma, rheumatoid arthritis or spondylosis. The symptom spectrum ranges from neural claudication to neurological deficits. We report the case of a contralateral asynchronous facet joint cyst after surgical resection and review the literature.

Daridon C, Burmester GR, Dörner T. · Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin and Deutsches, Rheumaforschungszentrum, Berlin 10098, Germany. · Curr Opin Rheumatol. · Pubmed #19346949 No free full text.

Abstract: PURPOSE OF REVIEW: To evaluate the impact of particular anticytokine therapies able to indirectly target B cells with emphasis on the tumor necrosis factor (TNF) family members, B cell activating factor/B lymphocyte stimulator (BAFF/BLyS) and a proliferation-inducing ligand (APRIL). RECENT FINDINGS: Although blockade of TNF/lymphotoxin by etanercept has been shown to have an impact on memory B cells, recent studies of inhibiting the TNF family members BAFF/BlyS or simultaneously blocking BAFF/BlyS and APRIL in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) clearly demonstrated biologic activity, including reductions of immunoglobulin levels. However, clear evidence of clinical activity by any of the compounds interfering with BAFF/BLys or APRIL has not yet been shown. SUMMARY: Although anticytokine therapies mainly blocking signaling pathways of innate immunity, that is TNF-alpha, have shown efficacy in the treatment of arthritides and have partial effects on memory B cells, current studies evaluate effects on adaptive immunity by blocking BAFF/BlyS and/or APRIL which indirectly act on B and plasma cells.

Schett G. · Department of Internal Medicine 3, University of Erlangen-Nuremberg, Krankenhausstrasse 12, Erlangen, Germany. · Ann N Y Acad Sci. · Pubmed #19250229 No free full text.

Abstract: A bone marrow edema pattern on MRI has a similar signal quality as an inflamed synovium and may, in fact, reflect true inflammatory infiltrates rather than a pure accumulation of extracellular fluid. Bone lesions near sites of rheumatoid arthritis-related inflammation are heavily vascularized, contributing to the high water content and enhanced visibility on MRI. However, even without erosive change, periarticular bone marrow lesions may be seen. This chapter describes the nature of bone marrow lesions detected by MRI in patients with inflammatory arthritis.

Simon S, Schwarz-Eywill M, Bausewein C. · Institute of Palliative Care, Oldenburg, Germany. · J Palliat Care. · Pubmed #19227019 No free full text.

Abstract: Currently, the main goal in rheumatic research is to achieve remission, even in highly active stages of the disease. However, there is a lack of understanding of how to manage patients when some rheumatic diseases such as vasculitis, connective tissue disease, or rheumatoid arthritis develop fulminant, progressive, and complicated courses. There is a clear role for palliative care to enhance patients' quality of life, but hardly any data exist regarding the prevalence and management of symptoms, and the special needs of these patients and their relatives. Rheumatologists, and palliative and primary care physicians should become more aware of this patient group so as to offer them the care they need. Further research is necessary in this field.

Korb A, Pavenstädt H, Pap T. · Department of Internal Medicine, University Hospital Muenster, Munster, Germany. · Apoptosis. · Pubmed #19199037 No free full text.

Abstract: Apoptosis plays a pivotal role in tissue homoeostasis both under physiological and pathological conditions and several studies have shown that some characteristic changes in the composition and structure of the inflamed synovial membrane in rheumatoid arthritis (RA) are linked to an altered apoptotic response of synovial cells. As a result, a hyperplastic synovial tissue is generated that mediates the progressive destruction of articular cartilage and bone. In addition to inflammatory cells, these changes most prominently affect resident fibroblast-like cells that have been demonstrated to be of utmost importance for joint destruction. Once activated, these cells pass through prominent molecular changes resulting in an aggressive, invasive behaviour. Research of the past years has identified different mechanisms that prevent synovial cells in RA from apoptosis. They include changes in the mitochondrial pathway as well as altered expression of downstream modulators of death receptors and transcriptional regulators such as NFkappaB. This review summarises our recent progress in understanding aberrant apoptosis in the RA synovial membrane and points to possibilities of intervening specifically with this aspect of the pathogenesis of RA.

Nagel A, Hertl M, Eming R. · Department of Dermatology and Allergology, Philipps University, Marburg, Germany. · J Invest Dermatol. · Pubmed #19148218 No free full text.

Abstract: The basic understanding of inflammatory dermatoses and autoimmune-mediated skin disorders has greatly advanced and broadened our understanding of underlying immune mechanisms that shape the complex network of chronic inflammation and autoimmunity. The new treatment options for psoriasis exemplify how new insights into (auto)immune responses, especially the role and function of various immune cells and proinflammatory cytokines, may lead to new therapeutic strategies. The concept of targeting B cells in autoimmune-mediated disorders is closely related to the discovery of autoantibodies and their cellular origin. However, the appreciation of B cells in autoimmunity has significantly changed and is not limited to their role as progenitors of autoantibody secreting plasma cells. Recent investigations of various inflammatory skin diseases, that is, autoimmune blistering disorders, collagen vascular diseases, and atopic dermatitis, actually support the concept that B cells might be as important as T cells in the etiopathogenesis of these disorders. The striking clinical improvement seen in patients with rheumatoid arthritis following B-cell depletion with the anti-CD20 mAb rituximab has tremendously catalyzed the interest in B-cell-targeted therapies in different autoimmune diseases. Future translational and clinical investigations are mandatory to precisely define the role and the contribution of impaired B-cell function in (auto)immune-mediated skin diseases.

Heinzl S. · Arzneimittelinformation, Aulberstr 8, 72764 Reutlingen. · Med Monatsschr Pharm. · Pubmed #19133593 No free full text.

This publication has no abstract.

Larbi A, Fülöp T, Pawelec G. · Center for Medical Research (ZMF), Tübingen Aging and Tumour Immunology Group, Section for Transplantation Immunology and Immunohematology, University of Tübingen, Waldhörnlestrasse 22, D-72072 Tübingen, Germany. · Adv Exp Med Biol. · Pubmed #19065799 No free full text.

Abstract: Aging is associated with a myriad of changes including alterations in glucose metabolism, brain function, hormonal regulation, muscle homeostasis and the immune system. Aged dividuals, generally still defined as over 65 years old, differ from middle-aged or young donors in many features of the immune system. The major observation is that the elderly population is not able to cope with infections as well as younger adults and recovery generally takes longer. Moreover, some diseases first appear with advancing age and are likely associated with dysfunction of the immune system. Thus, Alzheimer's disease, atherosclerosis, type II diabetes and some autoimmune disorders are linked to changes in immune function. One major immune cell population implicated as being responsible for the initiation and chronicity of immune dysfunction leading to diseases or immunosuppression is the T-cell. Although many changes in B-cell and innate immune function in aging are associated with the appearance of disease, they are not as well studied and clearly demarcated as changes in the T-cell compartment. The adaptive immune system is coordinated by T-cells, the activation of which is required for the initiation, maintenance and termination of responses against pathogens. Changes in the expression and functions of the T-cell receptor (TCR) for antigen and its co-receptors are closely associated with immunosenescence. Certain similar changes have also been found in some other disease states, e.g., rheumatoid arthritis, systemic lupus erythematosus and cancer. In this chapter, we will summarize our knowledge about multichain immune recognition receptor signaling, mainly the TCR, in aging and autoimmune diseases.

Tomiak C, Dörner T. · Reha-Zentrum Bad Aibling, Deutsche Rentenversicherung Bund, Rheumazentrum - AHB, Bad Aibling. · Hautarzt. · Pubmed #19037678 No free full text.

This publication has no abstract.

Siegel L, Pierer M, Stein C, Baerwald C. · Klinik für Anästhesiologie und operative Intensivmedizin , Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Hindenburgdamm 30, 12200, Berlin, Deutschland. · Z Rheumatol. · Pubmed #19011881 No free full text.

Abstract: Opioids are the most potent analgesics available and are well established for the treatment of severe acute, surgical and cancer pain. Due to their high effectiveness, their use in chronic non-cancer pain (CNCP) is being propagated. However, the use of opioids is still controversial due to their side effects, such as tolerance, addiction or withdrawal, and administrative difficulties associated with their prescription. Chronic rheumatic diseases, in particular low back pain and arthritis, are the leading causes of CNCP. The present article provides a brief overview of the role of opioids in chronic rheumatic diseases, pointing out that a national guideline for opioid use in CNCP is expected at the end of 2008. Furthermore, the peripheral effects of opioids on pain and inflammation in rheumatic diseases will be outlined.

Kötter I, Schmalzing M, Henes J, Vogel W, Kanz L. · Abteilung Innere Medizin II, Medizinische Universitätsklinik Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland. · Z Rheumatol. · Pubmed #19011875 No free full text.

Abstract: Transplantations of autologous or allogeneic stem cells from bone marrow or peripheral blood are preformed for the treatment of resistant autoimmune diseases. Data have been systematically collected since 1996. We describe the historical development of this procedure for autoimmune diseases, the possible mechanisms of action, the options for stem cell collection, purging and conditioning (high-dose chemotherapy, combination with monoclonal anti-T- or B-cell antibodies, total body irradiation), as well as the reported outcomes in the literature.

Lange U, Müller-Ladner U. · Klinische Immunologie, Kerckhoff-Klinik, Justus-Liebig-Universität Giessen, Benekestr. 2-8, 61231, Bad Nauheim, Deutschland. · Z Rheumatol. · Pubmed #19002473 No free full text.

Abstract: Inflammatory rheumatic disorders usually progress towards morphologic and functional deficits and thus cause substantial impairment of physical health. Amongst the therapeutic options physiotherapeutic strategies are essential and are often required to maintain the individual's quality of life. Because of the large variety of physiotherapeutical approaches, differentiated clinical examination is needed in order to implement physiotherapeutics in a treatment plan that is based on pathophysiologic and regeneration-specific aspects. The article presents a current overview of evidence-based physiotherapeutic strategies for musculoskeletal pain reduction in daily practice.