Rheumatoid Arthritis: Kötter I

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.

Kötter I, Wacker A, Koch S, Henes J, Richter C, Engel A, Günaydin I, Kanz L. · University Hospital, Department of Internal Medicine II, Tübingen, Germany. · Semin Arthritis Rheum. · Pubmed #17583775 No free full text.

Abstract: OBJECTIVE: To determine the efficacy of the interleukin (IL)-1-receptor antagonist (IL-1RA) anakinra in patients with adult-onset Still's disease (AOSD) refractory to standard treatments such as glucocorticosteroids (GC), immunosuppressive drugs, and tumor necrosis factor (TNF)-antagonists; to verify disease remission objectively by serial cytokine measurements; and to review the current literature on anakinra for this indication. METHODS: Four patients with AOSD--2 with acute flares of the chronic form of the disease and 2 with intermittent disease--were treated with prednisolone and methotrexate. One was also treated with several other immunosuppressive drugs including etanercept and infliximab. One patient had life-threatening symptoms (toxic megacolon, pneumonitis, disseminated intravascular coagulation) despite high-dose prednisolone. Treatment with anakinra 100 mg/d subcutaneously was initiated. White blood cells (WBC), C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), liver enzymes, ferritin levels, and serum cytokines were analyzed. The current literature on the efficacy of anakinra for AOSD is reviewed. RESULTS: Patients with chronic AOSD quickly responded to anakinra treatment (1 day to 3 days). GC could be tapered. ESR, CRP, WBC, ferritin, and liver enzymes returned to normal. Serum cytokine measurements revealed moderately elevated IL-1beta levels and highly elevated IL-18 levels in active disease, which normalized with anakinra. TNF-alpha and IL-6 were moderately elevated only in the 2 patients with chronic AOSD. In the literature, 17 similar cases have been reported to date. CONCLUSIONS: Anakinra is effective in treatment-resistant and in life-threatening AOSD. IL-18 serum levels, in addition to CRP, ESR, liver enzymes, ferritin, and WBC, may be helpful in assessing disease activity and response to treatment.

Kötter I, Deuter C, Günaydin I, Zierhut M. · University Hospital, Department of Internal Medicine II, Tübingen, Germany. · Clin Exp Rheumatol. · Pubmed #17067439 No free full text.

Abstract: INTRODUCTION: In 1985, Firestein et al. described 5 patients with relapsing polychondritis and Behçet's disease (BD) and proposed the term "MAGIC" syndrome as an acronym for "Mouth and Genital ulcers with Inflamed Cartilage". We report on an additional case of this syndrome and critically review the literature. RESULTS: From 1985 to 2004 eleven cases of MAGIC syndrome were described. All patients had chondritis and oral aphthous ulcers, as well as ocular inflammation (mainly anterior uveitis or scleritis/episcleritis). Most patients also presented with genital ulcers and arthritis. In one case, aortic aneurysm, in another aortic insufficiency was described, one had meningoencephalitis, one had antiphospholipid syndrome and one was HIV positive. Before 1985, we could find 4 additional probable cases. Our own patient presented with oral and genital ulcers, auricular chondritis and episcleritis. HLA-typing was performed and revealed HLA-B*51, B*15, DRB1*04x and DRB1*11x. Only in one Japanese patient from the literature, HLA-typing was available and revealed HLA-B*56, B*62, DRB1*0406 and DRB1*0901. CONCLUSIONS: Relapsing polychondritis is associated with HLA-DRB1*04 suballeles, but not necessarily only with those being associated with RA (DRB1*0401 and 0404). In 2 MAGIC patients these suballeles were found. All patients described in the literature had typical polychondritis, but not all did fulfil the classification criteria for BD. Many features of both diseases overlap and are not specific. As polychondritis is associated with other inflammatory rheumatic conditions such as SLE, spondyloarthropathy, rheumatoid arthritis and systemic vasculitides in 30% of all cases, we suggest that MAGIC syndrome is not a disease entity, but merely the association of BD with polychondritis.

Kötter I, Müller CA, Einsele H, Mohren M, Kanz L. · Medizinische Universitätsklinik, Otfried-Müller-Str. 10 D-72076, Tübingen. · Z Rheumatol. · Pubmed #10502017 No free full text.

Abstract: We describe a patient with chronic myelogenous leukemia (CML) and a patient with hairy cell leukemia being effectively treated with alpha-interferon who developed a seropositive chronic polyarthritis formally fulfilling the ACR criteria for rheumatoid arthritis. Because of its efficacy, interferon was not discontinued, and the arthritis treated with low-dose prednisolone or NSAIDS. These are the 19th and 20th case of symmetrical polyarthritis during alpha-interferon therapy fulfilling the criteria for RA. The possible mechanisms of the relatively frequent appearance of autoimmune diseases during interferon therapy are discussed.

Biegert C, Wagner I, Lüdtke R, Kötter I, Lohmüller C, Günaydin I, Taxis K, Heide L. · Pharmaceutical Institute, Eberhard Karls-Universität, Tübingen, Germany. · J Rheumatol. · Pubmed #15517622 No free full text.

Abstract: OBJECTIVE: To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient's assessment of pain rated on a 100 mm visual analog scale (VAS). RESULTS: OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 mm (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 mm (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA). CONCLUSION: The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA.

Kötter I. · Abt. Innere Medizin II (Hämatologie, Onkologie, Immunologie, Rheumatologie, Pulmologie), Medizinische Universitätsklinik, Otfried-Müller-Str. 10, 72076 Tübingen. · Z Rheumatol. · Pubmed #17334735 No free full text.

This publication has no abstract.

Lenk S, Fischer S, Kötter I, Claussen CD, Schlemmer HP. · Abteilung für Diagnostische Radiologie, Klinikum der Eberhardt-Karls-Universität Tübingen. · Radiologe. · Pubmed #15349730 No free full text.

Abstract: This contribution outlines possibilities and limitations of whole-body MRI for investigating musculoskeletal diseases. Benefits and drawbacks of the novel whole-body MRI technology are discussed and a possible whole-body MRI sequence protocol for musculoskeletal examinations is proposed. Muscle, joint and bone diseases are discussed in which the application of whole-body MRI may be of advantage. Particularly, polymyositis, muscledystrophy, rheumatoid arthritis, spondylitis ancylosans, multiple trauma, skeletal metastases, multiple myeloma and malignant lymphoma are mentioned. Whole-body MRI opens new advantages for the examination of multifocal musculoskeletal diseases. The clinical benefit of this method for particular diseases has to be evaluated in further studies, however.

Schepp CP, Dannecker L, Haug M, Kümmerle-Deschner J, Beck H, Kötter I, Holzer U, Dannecker GE. · University Children's Hospital, Eberhard Karls University, Tuebingen, Germany. · J Rheumatol. · Pubmed #15290745 No free full text.

Abstract: OBJECTIVE: Antibodies recognizing the ubiquitous cytosolic enzyme glucose-6-phosphate isomerase (GPI) cause arthritis in the K/BxN mouse model. Studies have shown that these antibodies are not specific for rheumatoid arthritis (RA) in humans. We evaluated GPI as a target of autoantibodies in juvenile idiopathic arthritis (JIA). METHODS: We studied 324 serum and 48 synovial fluid (SF) samples from 103 patients with JIA, 36 with RA, and 8 with arthralgia and 11 controls. Anti-GPI antibodies were assessed by densitometrically evaluating immunoblots and ELISA using native and recombinant GPI. We determined the GPI activity of the soluble antigen in serum and SF. RESULTS: Although several samples contained anti-GPI-IgG antibodies, this was not specific for JIA or its subgroups, or for RA. Other proteins in the GPI preparation were also frequently recognized by antibodies. Additionally, we observed increased GPI activity in patients with the systemic manifestation of JIA, but not in other patients. Neither anti-GPI concentrations nor GPI activity were associated with disease activity. CONCLUSION: In addition to the findings in RA, our results indicate that GPI is not a general target of autoantibodies in JIA.

Treusch M, Vonthein R, Baur M, Günaydin I, Koch S, Stübiger N, Eckstein AK, Peter HH, Ness T, Zierhut M, Kötter I. · Department of Internal Medicine II (Hematology/Oncology/Immunology/Rheumatology), University Hospital, Otfried-Müller Strasse 10, D-72076 Tübingen, Germany. · Rheumatology (Oxford). · Pubmed #15252211 links to  free full text

Abstract: OBJECTIVE: In Behçet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-alpha2a (IFN-alpha2a) (response rate 92%), although this is counterintuitive because IFN-alpha is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-alpha might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-alpha2a treatment. METHODS: Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-alpha treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry. RESULTS: Compared with the controls there is a significant elevation of monocytes (CD14(+)), CD8(+)/gammadelta T cells, CD3(+)/gammadelta T cells, natural killer (NK) cells (CD56(+)/CD16(+)) and activated/regulatory T cells (CD4(+)/CD25(+) and CD8(+)/CD25(+)) in patients with active BD before treatment with IFN-alpha2a. Numbers of naïve T cells (CD8(+)/CD45(+)RA(+)/RO(-), CD4(+)/CD45(+)RA(+)/RO(-)) were significantly lower. Under therapy, NK cells, CD8(+)/gammadelta T cells and CD3(+)/gammadelta T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients. CONCLUSION: These results implicate the participation of NK cells and gammadelta T cells, especially CD8(+)/gammadelta T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-alpha2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-alpha2a. The reduced expression of HLA class I on monocytes in HLA-B*51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B*51.

Kötter I, Stübiger N. · No affiliation provided · J Rheumatol. · Pubmed #14994421 links to  free full text

This publication has no abstract.