Rheumatoid Arthritis: Germany

Märker-Hermann E, Bauer H, Gromnica-Ihle E. · Klinik Innere Medizin IV (Rheumatologie, klinische Immunologie und Nephrologie), HSK Dr. Horst Schmidt Klinik GmbH, Wiesbaden. · Dtsch Med Wochenschr. · Pubmed #18988134 No free full text.

Abstract: Rheumatic diseases can influence the reproduction, the course of pregnancy and the development of the fetus. The inflammatory rheumatic disease itself can be modulated in its activity in terms of amelioration or exacerbation of the rheumatic symptoms. The associations between rheumatic diseases and pregnancy will be illustrated with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus as examples. Antirheumatic drug therapy during pregnancy and the breast feeding period has to be adapted critically.

Kuhn A, Beissert S, Krammer PH. · Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany. · Arch Dermatol Res. · Pubmed #18985367 No free full text.

Abstract: Natural CD4(+)CD25(+) regulatory T cells (T(reg)) show a potent immunosuppressive function and contribute to immunologic self-tolerance by suppressing potentially auto-reactive T cells. Depletion of these cells leads to the induction of severe autoimmune diseases in animal models; more recently, several studies have also reported an impairment of T(reg) number and/or function in various human autoimmune diseases. For example, aberrant numbers of circulating CD4(+)CD25(+) T(reg) have been seen in patients with type I diabetes, mycosis fungoides, graft-versus-host-reaction, and rheumatoid arthritis. Moreover, increased numbers of functionally active CD4(+)CD25(+) T(reg) have been detected in the synovial fluid of patients with rheumatoid arthritis. In systemic lupus erythematosus (SLE), conflicting data on the role of CD4(+)CD25(+) T(reg) in human autoimmune diseases have been presented in the literature. Decreased numbers of peripheral blood T(reg) have been reported by most studies on SLE patients with active disease, but non-impaired or even increased CD4(+)CD25(+) T(reg) numbers have also been described. In addition, both deficient and normal suppressive capacity of isolated T(reg) have been observed in SLE. Analysis of CD4(+)FoxP3(+) T(reg) in skin lesions of patients with a primarily cutaneous manifestation of the disease showed a significant reduction in cell numbers as compared to other inflammatory skin diseases, suggesting the importance of analyzing T(reg) numbers in the affected tissue. In this review, we discuss the role of CD4(+)CD25(+) T(reg) in autoimmunity and recent published data on SLE. Furthermore, we highlight the need for additional studies that address specific gaps of knowledge regarding the pathophysiological mechanisms as well as the identification of future therapeutic strategies for autoimmune diseases.

Melchers I, Ahnert P. · Klinische Forschergruppe für Rheumatologie, Abteilung für Rheumatologie und Klinische Immunologie, Universitätsklinikum Freiburg, Breisacher Str. 66 (ZKF), 79106, Freiburg. · Z Rheumatol. · Pubmed #18956205 No free full text.

Abstract: PTPN22 620W is regarded as the second most important risk factor for type 1 diabetes and rheumatoid arthritis. Here we describe aspects of the molecular biology of the enzyme and its function, the geographical distribution of the 620W variant, as well as its importance in less frequent rheumatic diseases.

Strietholt S, Maurer B, Peters MA, Pap T, Gay S. · Institute of Experimental Musculoskeletal Medicine, University Hospital Munster, Domagkstrasse 3, 48149 Münster, Germany. · Arthritis Res Ther. · Pubmed #18947370 links to  free full text

Abstract: Over the last decades, genetic factors for rheumatoid diseases like the HLA haplotypes have been studied extensively. However, during the past years of research, it has become more and more evident that the influence of epigenetic processes on the development of rheumatic diseases is probably as strong as the genetic background of a patient. Epigenetic processes are heritable changes in gene expression without alteration of the nucleotide sequence. Such modifications include chromatin methylation and post-translational modification of histones or other chromatin-associated proteins. The latter comprise the addition of methyl, acetyl, and phosphoryl groups or even larger moieties such as binding of ubiquitin or small ubiquitin-like modifier. The combinatory nature of these processes forms a complex network of epigenetic modifications that regulate gene expression through activation or silencing of genes. This review provides insight into the role of epigenetic alterations in the pathogenesis of rheumatoid arthritis and points out how a better understanding of such mechanisms may lead to novel therapeutic strategies.

Weigl M, Schwarzkopf SR, Stucki G. · Klinik und Poliklinik für Physikalische Medizin und Rehabilitation, Klinikum der Universität München, Marchioninistr. 15, 81377, München. · Z Rheumatol. · Pubmed #18825392 No free full text.

Abstract: The International Classification of Functioning, Disability, and Health (ICF) created by the World Health Organization provides both a framework and a classification comprehensively covering domains of function and disability in rheumatologic patients. The ICF can be used as a universal language understood by medical doctors, health professionals, researchers, patients, and other groups. It is based on an integrative biopsychosocial model of functioning. For its implementation in rheumatology and medicine in general, practical ICF-based tools such as the ICF Core Sets are necessary. These Sets, which were developed in a standardized scientific process, consist of the ICF categories that are most relevant for a specific group of patients, e.g. chronic patients with rheumatoid arthritis. In rheumatologic rehabilitation, patient problems, medical findings, treatment goals, and treatment concepts can be structured by applying the ICF, ICF Core Sets, and an ICF assessment sheet to patients. In outcomes research, ICF Core Sets can support the selection of relevant outcome domains.

Schett G, Stach C, Zwerina J, Voll R, Manger B. · Department of Internal Medicine III, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. · Arthritis Rheum. · Pubmed #18821703 No free full text.

This publication has no abstract.

Kiekenbeck A, Preis M, Salzmann G. · Aukamm-Klinik, Leibnizstrasse 21, 65191, Wiesbaden. · Z Rheumatol. · Pubmed #18781313 No free full text.

Abstract: Surgical treatment of patients with rheumatoid arthritis of the shoulder should be one part of a concept of conservative and surgical treatment. In addition to disease-modifying agents, local minimally invasive surgery can avoid structural damage to the shoulder and furthermore achieve a restitution of shoulder function. According to Larsen Stage 0-III, an arthroscopic synovectomy and bursectomy can achieve a good prognosis and help to avoid further structural damage to the rheumatoid shoulder. Minimally invasive procedures in the surgery of the rheumatoid shoulder lead to less immobilisation and faster rehabilitation, to the benefit of the joints in the operated limb, much like therapy of the knee. It is also possible to treat associated pathologies with minimally invasive surgery, such as bursitis, small rotator cuff defects, and synovitis of the acromioclavicular joint, as well as synovectomy of the glenohumeral joint Good results can be achieved in these cases using minimally invasive surgery. However, minimally invasive reconstructive procedures are limited in the rheumatoid shoulder.

Schmidt K. · Abteilung für Orthopädie, Unfallchirurgie, Rheumaorthopädie, Katholisches Krankenhaus Dortmund-West, St. Rochus Hospital Castrop-Rauxel, Zollernstr. 40, 44379, Dortmund. · Z Rheumatol. · Pubmed #18777028 No free full text.

Abstract: With the progression of rheumatoid arthritis more than half of the patients develop an affection of the elbow. Rheumatoid arthritis is the most common cause of elbow arthritis. The complexity of the rheumatic disease, which typically affects many joints, demands an individual therapeutic plan that can only be developed and accomplished successfully, when rheumatologists, rheumatoid surgeons and other specialists cooperate. Consistent use of approved and improved pharmaceuticals is abating the rate of rheumatoid cubarthritis. In cases of recurrent cubarthritis despite adequate medication, adverse reactions and other problems should be borne in mind before making a decision to change to more aggressive medication or synovectomy. Minimally invasive local measures, such as synoviorthesis and arthroscopic synovectomy can relieve pain and swelling, however, if lesions of the cartilage already exist, progressive joint destruction cannot be prevented. In early phases of rheumatoid cubarthritis with tight ligaments and thin synovial lining we prefer synoviothesis. In cases with recurrent cubarthritis after synoviorthesis or strong proliferation of the tunica synovialis, arthroscopic synovectomy is advantageous. Arthroscopic synovectomy is most effective in cases when there is ligament laxity in the sense of a late synovectomy, as removal of loose bodies, smoothening of the cartilage, release of the joint capsule and possibly arthroscopy-assisted resection of the radius head can be performed.

Carl HD, Swoboda B. · Orthopädisch-Rheumatologische Abteilung der Friedrich-Alexander-Universität Erlangen-Nürnberg, Im Waldkrankenhaus St. Marien, Rathsberger Str. 57, 91054, Erlangen. · Z Rheumatol. · Pubmed #18777027 No free full text.

Abstract: Arthroscopic synovectomy in rheumatoid arthritis has proven beneficial in terms of pain relief and joint function, both for upper limb joints (shoulder, elbow, wrist) and the knee. The clinical long-term improvement, such as pain reduction and improved joint mobility, seems more distinct in joints with no or mild joint destruction (early synovectomy) compared to advanced joint damage (late synovectomy). Late-stage elbow arthritis, synovitis of the metacarpophalangeal and proximal interphalangeal joints and the rheumatoid ankle can better be addressed by an open approach. Although a real joint-preserving effect has not been demonstrated, pain reduction and improvement in joint function recommend arthroscopic synovectomy as a substantial treatment option in patients with rheumatoid arthritis.

Schett G, Zwerina J, David JP. · Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. · Nat Clin Pract Rheumatol. · Pubmed #18756273 No free full text.

Abstract: Wnt proteins regulate organ development, tumorigenesis and bone homeostasis, among other functions. The binding of Wnt proteins to plasma membrane receptors on mesenchymal cells induces the differentiation of these cells into the osteoblast lineage and thereby supports bone formation. Wnts are also key signaling proteins in joint remodeling processes. Active Wnt signaling contributes to osteophyte formation and might have an essential role in the anabolic pattern of joint remodeling that is observed in ankylosing spondylitis and osteoarthritis. By contrast, blockade of Wnt signaling facilitates bone erosion and contributes to catabolic joint remodeling, a process that is observed in rheumatoid arthritis. This Review summarizes current knowledge of the molecular regulation of joint remodeling associated with chronic arthritis, focusing on the role of the Wnt proteins and their inhibitors. It also addresses the role of Wnt in determining the differences in clinical presentation of inflammatory arthropathies and discusses implications for future therapy.

Mössner R, Schön MP, Reich K. · Department of Dermatology, Georg-August University, von-Siebold-Str. 3, 37075 Göttingen, Germany. · Clin Dermatol. · Pubmed #18755367 No free full text.

Abstract: The identification of new pathophysiological mechanisms in chronic inflammatory diseases and the development of techniques that allow production of antibodies and fusion proteins that antagonize target molecules with high specificity has not only revolutionized the treatment of rheumatoid arthritis and chronic inflammatory bowel disease, but it also has revolutionized the treatment of psoriasis in recent years. Two different classes of so-called biological therapies (biologics) have become available to treat psoriasis: tumor necrosis factor (TNF) antagonists and T-cell modulators. TNF antagonists that have been studied with psoriasis include the antibodies infliximab and adalimumab and the fusion protein etanercept. These treatments differ in their capacity to reduce the skin symptoms of psoriasis and other important characteristics of the drug profile. This article summarizes the important aspects of efficacy, safety, and practicability of TNF antagonists in the treatment of psoriasis. This article may be helpful for the daily routine when selecting the right therapy for a patient and managing the TNF antagonist during maintenance therapy.

Tarner IH, Müller-Ladner U. · Department of Internal Medicine and Rheumatology, Division of Rheumatology and Clinical Immunology, Justus-Liebig-University of Giessen, D-61231 Bad Nauheim, Germany. · Expert Opin Drug Deliv. · Pubmed #18754751 No free full text.

Abstract: Rheumatoid arthritis (RA) is a severe immune-mediated disease characterized by chronically progressive inflammation and destruction of joints and associated structures. Significant advances in our understanding of its pathophysiology and early diagnosis have led to improved therapy and better outcome. Nevertheless, a number of details in the pathogenesis of RA are still unknown and thus the disease cannot be cured at present. Therefore, current therapy aims at accomplishing complete and long-lasting remission. However, this goal is only achieved in a small proportion of patients, and partial remission and frequent relapses are a common problem. A significant number of patients still do not respond at all to available treatments. In addition, all antirheumatic and immune-modulating drugs developed so far carry a considerable risk of adverse effects, some of which can be severe or even life threatening. This is due, at least in part, to a lack of specificity of most drugs for the target tissue, and to a high volume of distribution for systemic application, which, together with rapid clearance of most drugs, requires frequent application of high dosages. Targeted drug delivery and prolongation of bioavailability would alleviate this issue significantly. This article, therefore, reviews a selection of studies that report promising strategies for joint specific delivery of antiarthritic drugs.

Späh F. · HELIOS Klinikum Krefeld, Medizinische Klinik I, Lutherplatz 40, D-47805 Krefeld, Germany. · Br J Dermatol. · Pubmed #18700910 No free full text.

Abstract: Inflammation plays a key role in the pathogenesis of a number of chronic inflammatory systemic diseases (CISDs), including psoriasis, rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the pathogenesis of atherosclerosis. CISDs and cardiovascular diseases, such as atherosclerosis, share common pathogenic features, and cardiovascular disease is an important cause of morbidity and mortality in patients with CISDs. Activated inflammatory cells and pro-inflammatory cytokines contribute to the development of psoriatic lesions and play an important role in the breakdown of atherosclerotic plaques. Psoriasis and atherosclerosis also have similar histological characteristics involving T cells, macrophages and monocytes. In particular, the extravasation of T cells through the epithelium is characteristic of both psoriatic and atherosclerotic plaques. Cardiovascular disease is an important cause of morbidity and mortality in patients with psoriasis, which is associated with an increased cardiovascular risk profile compared with the general population. Patients with psoriasis are at increased risk of arterial hypertension, coronary heart disease, hyperlipidaemia, obesity and type II diabetes, which are more prevalent than in control patients. This increased risk could be due to the effects of chronic inflammatory changes, particularly the infiltration of T cells and subsequent secretion of pro-inflammatory cytokines. Some drugs used in the treatment of cardiovascular disease, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors have anti-inflammatory activity. In addition, systemic treatments for psoriasis may, by decreasing inflammation, reduce the risk of cardiovascular disease. It is suggested, therefore, that an integrated approach to the treatment of the inflammatory processes underlying both psoriasis and atherosclerosis may be beneficial in reducing cardiovascular risk in patients with psoriasis. The newer targeted biological therapies, such as efalizumab and infliximab, which offer the potential for long-term disease control in psoriasis, may be of particular use in this setting.

Pierer M, Baerwald C. · Sektion Rheumatologie/Gerontologie,Medizinische Klinik & Poliklinik II, Universitätsklinikum Leipzig, AöR, Liebigstrasse 22, 04103, Leipzig, Germany. · Internist (Berl). · Pubmed #18587545 No free full text.

Abstract: The analysis of cytokines (i.e. interleukins, interferons and colony-stimulating factors) has only flourished in the last 25 years subsequently revealing new insights into the pathogenesis of rheumatic diseases that revolutionised the management of patients with chronic rheumatic disorders. Tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6) have been found to play a pivotal role in rheumatic inflammation. As early as in 1992 the first proof of concept study with a monoclonal antibody against TNF was able to demonstrate positive effects in rheumatoid arthritis. Since the approval of the first anti-TNF-alpha therapy, further agents against TNF and other proinflammatory cytokines were approved and even more biological drugs are under development aimed at modulating the disturbed immune system in patients with rheumatic diseases. To date the following biologics are approved for therapy of chronic rheumatic diseases: the TNF antagonists Etanercept, Infliximab and Adalimumab; Anakinra as an IL-1 receptor antagonist; the anti-CD20 monoclonal antibody Rituximab and the anti-CD80/86 fusion protein Abatacept. In the present article, we report on biological therapy modalities in rheumatic diseases as well as the recommendations for initiation of these agents.

Holle JU, Schinke S, Gross WL. · Poliklinik für Rheumatologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 24576 Lübeck, Deutschland. · Z Rheumatol. · Pubmed #18528697 No free full text.

Abstract: Tumor necrosis factor (TNF-alpha) plays an essential role in the orchestration of inflammatory processes including autoimmune disorders, host defence and granuloma formation. TNF antagonists are highly effective in the therapy of rheumatoid arthritis, but they compromise host defence mechanisms, especially concerning bacterial infections inducing granuloma formation, such as tuberculosis. Other biologics have been developed and approved for the therapy of rheumatoid arthritis, e.g. an interleukin (IL-1) blocking agent (anakinra), an antibody that depletes CD20 positive B-cells (rituximab) and an inhibitor of T-cell co-stimulation (abatacept). In spite of initial skepticism regarding side effects, such as an increased risk of infections, biologics now play an essential role in the therapy of autoimmune diseases due to the implementation of efficient screening measures concerning side effects (such as reactivation of tuberculosis). This review summarizes the current available data regarding risk of infection and gives and overview on recommended screening, contraindications and events that require withdrawal of therapy.

Nöth U, Steinert AF, Tuan RS. · Division of Tissue Engineering at Orthopedic Center for Musculoskeletal Research, König-Ludwig-Haus, Julius-Maximilians-University, Würzburg, Germany. · Nat Clin Pract Rheumatol. · Pubmed #18477997 No free full text.

Abstract: Despite the high prevalence and morbidity of osteoarthritis (OA), an effective treatment for this disease is currently lacking. Restoration of the diseased articular cartilage in patients with OA is, therefore, a challenge of considerable appeal to researchers and clinicians. Techniques that cause multipotent adult mesenchymal stem cells (MSCs) to differentiate into cells of the chondrogenic lineage have led to a variety of experimental strategies to investigate whether MSCs instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage. MSC-based strategies should provide practical advantages for the patient with OA. These strategies include use of MSCs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of MSCs. Delivery of MSCs might be attained by direct intra-articular injection or by graft of engineered constructs derived from cell-seeded scaffolds; this latter approach could provide a three-dimensional construct with mechanical properties that are congruous with the weight-bearing function of the joint. Promising experimental and clinical data are beginning to emerge in support of the use of MSCs for regenerative applications.

Herman S, Krönke G, Schett G. · Department of Internal Medicine 3, University of Erlangen-Nuremberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany. · Trends Mol Med. · Pubmed #18468489 No free full text.

Abstract: Chronic inflammatory bone diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis and periodontal disease, demonstrate the major impact of chronic inflammation on both bone metabolism and bone architecture. During the past decade, scientists have gained increasing insight into the link between inflammation and bone. As a result of new discoveries about the molecular mechanisms of inflammatory bone loss, several molecules have been identified that are attractive and novel targets for the treatment of inflammatory bone loss. These novel therapeutic approaches include anti-tumor necrosis factor (TNF)-alpha blocking agents, neutralizing antibodies against certain pro-inflammatory cytokines, such as interleukin (IL)-6 and IL-17, and a set of other promising targets that still require extensive research, such as the Wnt signaling network.

Capellino S, Straub RH. · Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany. · Best Pract Res Clin Rheumatol. · Pubmed #18455685 No free full text.

Abstract: The analysis and understanding of the complex effects of endocrine and nervous system alterations on the inflammatory process in human arthritis is far from complete. Such alterations are observed as decreased responsiveness of the hypothalamic-pituitary-adrenal axis, an inadequate production of cortisol in relation to inflammation, and - consequently - elevated sympathetic activity, alterations of sex hormone metabolism (loss of androgens), psychological alterations (with chronic fatigue and symptoms of depression due to elevated circulating cytokines), local reduction of synovial sympathetic innervation, altered metabolism of estrogens in the synovium, and high expression of estrogen receptors in synovial cells. An understanding of these alterations will help to identify the different neuroendocrine immune mechanisms involved in the pathophysiology of rheumatoid arthritis and could trigger research into novel therapeutic targets for the treatment of patients with rheumatoid arthritis.

Dinser R. · Department of Internal Medicine and Rheumatology, Kerckhoff Hospital, Justus-Liebig-University of Giessen, Benekestrasse 2-8, 61231 Bad Nauheim, Germany. <> · Best Pract Res Clin Rheumatol. · Pubmed #18455683 No free full text.

Abstract: Animal models for rheumatic diseases complement human investigations to study in detail pathogenic hypotheses and therapeutic strategies. An overview of animal studies in the last years shows examples for ideas taken from bench to bedside and from bedside to bench. Depending on the disease studied, progress includes a refinement of physiological and pathogenic thinking and a better definition of promising cellular and molecular therapeutic targets.

Niller HH, Wolf H, Minarovits J. · Department of Microbiology and Hygiene, University of Regensburg, Regensburg, Germany. · Autoimmunity. · Pubmed #18432410 No free full text.

Abstract: Epstein-Barr virus (EBV) is a human herpesvirus hiding in a latent form in memory B cells in the majority of the world population. Although, primary EBV infection is asymptomatic or causes a self-limiting disease, infectious mononucleosis, the virus is associated with a wide variety of neoplasms developing in immunosuppressed or immunodeficient individuals, but also in patients with an apparently intact immune system. In memory B cells, tumor cells, and lymphoblastoid cell lines (LCLs, transformed by EBV in vitro) the expression of the viral genes is highly restricted. There is no virus production (lytic viral replication associated with the expression of all viral genes) in tight latency. The expression of latent viral oncogenes and RNAs is under a strict epigenetic control via DNA methylation and histone modifications that results either in a complete silencing of the EBV genome in memory B cells, or in a cell-type dependent usage of latent promoters in tumor cells, germinal center B cells, and LCLs. Both the latent and lytic EBV proteins are potent immunogens and elicit vigorous B- and T-cell responses. In immunosuppressed and immunodeficient patients, or in individuals with a functional defect of EBV-specific T cells, lytic EBV replication is regularly activated and an increased viral load can be detected in the blood. Enhanced lytic replication results in new infection events and EBV-associated transformation events, and seems to be a risk factor both for malignant transformation and the development of autoimmune diseases. One may speculate that an increased load or altered presentation of a limited set of lytic or latent EBV proteins that cross-react with cellular antigens triggers and perpetuates the pathogenic processes that result in multiple sclerosis, systemic lupus erythematosus (SLE), and rheumatoid arthritis. In addition, in SLE patients EBV may cause defects of B-cell tolerance checkpoints because latent membrane protein 1, an EBV-encoded viral oncoprotein can induce BAFF, a B-cell activating factor that rescues self-reactive B cells and induces a lupus-like autoimmune disease in transgenic mice.

Glück T, Müller-Ladner U. · Department of Internal Medicine, District Hospital Trostberg, Germany. · Clin Infect Dis. · Pubmed #18419456 No free full text.

Abstract: Patients who have chronic rheumatic or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, or vasculitides, show a risk of infection that is at least 2-fold greater than that for healthy individuals. This increased risk is not only a result of the aberrant immunologic reaction itself but also can be attributed to the immunosuppressive therapy required to control the activity of the underlying disease and the associated organ complications. Vaccination is an option for a substantial number of these infections. In this context, pneumococcal and influenza vaccines are the best evaluated and are recommended by standard vaccination guidelines. Some studies have found mildly impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy, but postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals. The accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with chronic autoimmune or rheumatic diseases, especially vaccination against influenza and pneumococci. Vaccination protocols for this population should be better implemented in daily clinical practice.

Dörner T, Burmester GR. · Charite Center 14, Charite University Hospital Berlin, Berlin, Germany. · Curr Opin Rheumatol. · Pubmed #18388516 No free full text.

Abstract: PURPOSE OF REVIEW: This study reviews therapeutic approaches of direct and indirect B-cell targeting in autoimmune diseases and their impact on protective immunity. RECENT FINDINGS: Beyond recent clinical experiences with rituximab as B-cell-depleting agent, other biologicals targeting CD20, such as ocrelizumab, ofatumumab, hA20, and TRU-015 mainly deplete B cells and are under clinical investigation in different entities. Moreover, anti-CD22 targeting as another approach that has been studied in clinical trials showed a modest depletion, but inhibition of B-cell activation. More indirect innovative B-cell-affecting therapies comprise blockade of cytokines, such as B-cell-activating factor (BAFF/BLyS), APRIL, and their receptors as well as blockade of costimulation. Although decreases of immunoglobulin levels were seen, so far no major increases in infections were reported. SUMMARY: The value of certain B-cell-depletion therapies as well as other therapies modulating B-cell functions needs to be further delineated, especially in the therapeutic regimen of rheumatoid arthritis, specific collagen vascular diseases and vasculitis. Long-term observations of protective immunity are also needed to further evaluate the rate of infections.

Weigl M, Cieza A, Cantista P, Reinhardt JD, Stucki G. · Department of Physical Medicine and Rehabilitation, Ludwig-Maximilian-University, University Hospital Munich, Marchioninistrasse 15, Munich, Germany. · Eur J Phys Rehabil Med. · Pubmed #18385630 links to  free full text

Abstract: Knowledge of the determinants of disability in musculoskeletal conditions (MSC) is critical for reducing their burden. No epidemiologic studies from a truly comprehensive perspective consider environmental factors (EF) and personal factors (PF) as determinants of disability. However, one can identify candidate EF from the International Classification of Functioning, Disability and Health (ICF) Core Sets for rheumatoid arthritis (RA), osteoporosis (OP), osteoarthritis (OA), low back pain (LBP) and chronic wide spread pain (CWP). The objective of this literature review was to contribute to the validation of the EF from the ICF Core Sets for MSC and the candidate PF from a (ICF) Delphi exercise, as well as from the report of the Bone and Joint Decade (BJD) Health Strategy Project. The results of the literature search focus on reviews published between January 1991 and March 2006 that contained information on EF and PF that determine disability in LBP, RA and OA. Many PF and EF included in the ICF Core Sets were confirmed as potential determinants of disability. However, regarding some contextual factors, in particular EF referring to the physical environment, there is a lack of reviews and clinical studies that have investigated their relevance to disability. The predominant medical model in studies on disability in MSC may explain this lack of evidence. However, the increasing attention given to the integrative model of functioning, disability and health of the World Health Organization (WHO) and the approval of the ICF by the World Health Assembly in 2001 may stimulate future research on the effect of EF and PF on disability.

Chrubasik C, Roufogalis BD, Müller-Ladner U, Chrubasik S. · Department of Forensic Medicine, University of Freiburg, Albertstr. 9, 79104 Freiburg, Germany. · Phytother Res. · Pubmed #18384191 No free full text.

Abstract: Rose hip, rose hip and seed and rose hip seed, all were negatively monographed by the German Commission E due to insufficient evidence of effects and effectiveness. Therefore a comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of Rosa canina L. to reevaluate its usefulness in traditional medicine.For various preparations of rose hip and rose hip and seed, antioxidative and antiinflammatory effects have been demonstrated. Lipophilic constituents are involved in those mechanisms of action. The proprietary rose hip and seed powder Litozin has been employed successfully in a number of exploratory studies in patients suffering from osteoarthritis, rheumatoid arthritis and low back pain. However, the sizes of the clinical effects for the different indications need to be determined to assure clinical significance.There is also a rationale behind the use of Litozin as part of a hypocaloric diet based on the rose hip probiotic, stool regulating and smooth muscle-relaxing actions, as well as the rose hip seed lipid-lowering, antiobese and antiulcerogenic effects. Further research is needed to clarify the importance of the reported promising experimental effects in clinical use and to characterize the optimum rose hip seed oil preparation for topical use in the treatment of skin diseases.

Schett G. · Department of Internal Medicine 3, University of Erlangen-Nurnberg, Erlangen, Germany. · Autoimmunity. · Pubmed #18365836 No free full text.

Abstract: Cytokine expression in the inflamed synovial membrane of patients with rheumatoid arthritis and other forms of chronic inflammatory arthritis and other forms of chronic inflammatory arthritis leads to formation of osteoclasts. These cells are primarily involved in the resorption of mineralized cartilage and bone and thus participate in joint damage in the course of chronic arthritides. Osteoclastogenesis in the synovial membrane is driven by cytokines such as RANKL, MCSF but also classical proinflammatory mediators such as TNF, IL-1 and IL-6. Inhibition of osteoclast formation has proven as an effective approach to inhibit structural damage in experimental arthritis and preliminary data suggest that such approaches are also effective in human RA.