Rheumatoid Arthritis: Köller M

Weidekamm C, Köller M, Weber M, Kainberger F. · Department of Diagnostic Osteology, Universitaetsklinik fuer Radiodiagnostik, Allgemeines Krankenhaus Wien, Waehringer Guertel 18-20, A-1090, Vienna, Austria. · Arthritis Rheum. · Pubmed #12571840 links to  free full text

Abstract: OBJECTIVE: High-resolution sonography enables a detailed assessment of intraarticular and extraarticular soft tissue abnormalities of joints affected by rheumatoid arthritis (RA). This study was undertaken to evaluate the diagnostic value of B-mode sonography and power Doppler compared with that of clinical examinations and conventional radiography. METHODS: The study group comprised 47 patients (14 men, 33 women) with different grades of RA; 31 patients were rheumatoid factor (RF) positive, and 16 were RF negative. The wrists, first through fifth metacarpophalangeal joints, and second through fifth proximal interphalangeal joints of these patients were scored with ultrasound in B-mode and power Doppler application, using a standardized technique. Involvement and severity of inflammation, as well as vascularization, were scored according to a new 3-point scale. The results were correlated with benchmarks of the clinical and radiologic investigations. Clinical status and conventional radiologic status were determined according to the Disease Activity Score and the Larsen score. RESULTS: After preliminary studies in 15 patients, 39% of 704 joints were found to be abnormal by clinical investigation. Erosions were detected by radiography and sonography in 23% and 43% of joints, respectively. Hypervascularization was observed in 34% of 704 joints by power Doppler application. There was a significant correlation (P < 0.001) between the different methods for the detection of the severity of lesions. Use of a modern, state-of-the-art power Doppler program was necessary for semiquantification, and a standardized investigation technique and scoring system provided sufficient quality measures. CONCLUSION: Sonography detects 20% more abnormalities than does radiography, and sonography has the potential to provide simple grading of disease activity. The rate of detection of abnormalities was slightly higher with clinical examination compared with sonography.

Köller M, Nöbauer-Huhmann I. · Klinische Abteilung für Rheumatologie, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Austria. · Wien Med Wochenschr. · Pubmed #19247592 No free full text.

Abstract: Rheumatoid Arthritis (RA) is the most prevalent inflammatory joint disease in adults and shows a destructive course in most cases. The outcome of the disease - functional decline and invalidity - necessitates an early therapy. Recent studies demonstrate that the initiation of the treatment with a disease modifying antirheumatic drug (DMARD) treatment within the first three months after the onset of symptoms is crucial for sustained improvement of prognosis as well as therapeutic success and outcome. In the early stage of the disease, the criteria for the classification of Rheumatoid Arthritis (RA) are frequently not met. Up to over 50% of the patients show an arthritis, which cannot be classified and therefore is seen as undifferentiated arthritis (UA). Early therapeutic intervention appears to prevent the chronification of the disease; thus an early and appropriate disease modifying therapy is mandatory. Age, gender, involvement of the hands, positive rheumatoid factor, as well as the detection of anti cyclic-citrullinated peptide antibodies (anti-CCP Ab) are predictors of the development of RA. Beside conventional X-rays, there are other imaging methods such as magnetic resonance tomography imaging, Power-Doppler or contrast medium enhanced sonography, which may enable the detection not only of synovitis but also of erosive lesions at very early stages. Those patients suffering from UA carry a high risk for the development of a destructive arthritis as seen in RA, and therefore should be treated with an adequate DMARD. In these cases methotrexate is still the drug of first choice.

Pfeiffer M, Köller M, Wanivenhaus A, Trieb K. · Universitätsklinik für Orthopädie, Medizinische Universität, Währinger Gürtel 18-20, 1090, Wien, Osterreich. · Z Rheumatol. · Pubmed #16924455 No free full text.

Abstract: Tumor necrosis factor (TNF) blocking agents, such as adalimumab, are well tolerated and provide improvement in the symptoms and signs of rheumatoid arthritis (RA). Due to its immunosuppressive effect, an increased risk of infection has been suggested, but so far no differences between adalimumab and placebo groups have been found in pivotal trials. Patients with RA succumb to postoperative complications because they have a systemic disease and use medication with immunosuppressive effects. We report on a patient with longstanding, active RA who had received adalimumab 40 mg every other week with prolonged infection, wound dehiscence and pseudoarthrosis following reconstructive forefoot surgery due to deformities secondary to RA. The postoperative infection occurred although adalimumab therapy had been stopped 8 days before surgery. The half-life of adalimumab is 10.0-13.6 days following a single intravenous dose. Whether patients under therapy with adalimumab are at an increased risk of developing postoperative complications is unclear, a retrospective analysis of the pivotal studies would be helpful in estimating the risk of perioperative (wound) infections in patients receiving anti-TNF. Moreover, it is not clear when therapy should be stopped prior to surgical intervention. Obviously prospective clinical trials would be more convincing.

Cauza E, Hanusch-Enserer U, Etemad M, Köller M, Kostner K, Georg P, Dunky A, Ferenci P. · Department of Internal Medicine V, Department of Rheumatology, Wilhelminenspital, Vienna, Austria. · Clin Exp Rheumatol. · Pubmed #15789881 No free full text.

Abstract: OBJECTIVE: Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Among Northern Europeans the carrier frequency is estimated to be 1 in 10, while up to 1 in 200 is affected by the disease. Arthropathy is one early clinical manifestation of this disease, but the articular features are often misdiagnosed. In this study the two frequent mutations of the HLA-linked hemochromatosis gene (HFE) were investigated in a rheumatology clinic population. METHODS: Two hundred and six consecutive patients (mean age 57.7 years; 38 male/168 female) attending a rheumatology clinic over a period of 14 months were screened for HFE mutations (C282Y and H63D). All standard diagnostic procedures were used to identify the aetiology of the arthropathy. Mutations were evaluated by separation on PAGE of digested PCR amplificates of DNA (by SnapI and Bcl-I, for C282Y and H63D, respectively) obtained from PBMCs. RESULTS: The C282Y and H63D allele frequencies were 4.5 and 12.8 in patients with rheumatic diseases. Five patients were homozygote for H63D (2.4%), and one for C282Y (0.5%). Five patients were compound heterozygous (2.4%). The observed C282Y allele frequency in rheumatic patients with undifferentiated arthritis was 12.9 and exceeded that of healthy subjects (p = 0.01). CONCLUSIONS: Determination of the HFE genotype is clinically useful in patients with arthritis of unknown origin, to allow early diagnosis of hemochromatosis.

Aringer M, Stummvoll GH, Steiner G, Köller M, Steiner CW, Höfler E, Hiesberger H, Smolen JS, Graninger WB. · Department of Rheumatology, Internal Medicine III, University of Vienna, Austria. · Rheumatology (Oxford). · Pubmed #11511756 links to  free full text

Abstract: OBJECTIVE: To investigate if interleukin-15 (IL-15) (rather than IL-2) is increased in systemic lupus erythematosus (SLE) and might be responsible for immunological abnormalities of SLE such as the increased lymphocytic expression of Bcl-2 and CD25. METHODS: Serum IL-15, IL-2 and tumour necrosis factor (TNF) levels of 65 SLE patients, 20 healthy persons and 10 rheumatoid arthritis (RA) patients were measured by enzyme-linked immunosorbent assay (ELISA). For 25 SLE patients, the percentage of CD25 + lymphocytes and the lymphocytic Bcl-2 levels were simultaneously determined by fluorocytometry. Peripheral blood mononuclear cells (PBMC) of 15 SLE patients were incubated with or without recombinant IL-15 and the influence on Bcl-2 and CD25 was determined. RESULTS: IL-15 was found to be elevated in 25 SLE sera (38%), but in none of the 20 healthy sera (P = 0.0005) and none of the 10 RA sera. Both lymphocyte CD25 and Bcl-2 expression significantly correlated with serum IL-15 and were increased by recombinant IL-15. CONCLUSION: Serum IL-15 may in part be responsible for the immunological abnormalities seen in active SLE.

Köller M, Aringer M, Kiener H, Erlacher L, Machold K, Eberl G, Studnicka-Benke A, Graninger W, Smolen J. · Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. · Ann Rheum Dis. · Pubmed #10531076 links to  free full text

Abstract: OBJECTIVE: To determine the presence of adhesion molecules on monocytes/macrophages (Mphi) from peripheral blood (PB) and synovial fluid (SF) in patients with osteoarthritis (OA) and inflammatory joint diseases (rheumatoid (RA) and reactive arthritis (ReA)) in order to improve our understanding of the possible mechanisms underlying the inflammatory process. METHODS: Whole blood and SF cells were stained with monoclonal antibodies against CD11a (LFA-1), CD15 s (sialyl-Lewis X), CD44, CD54, VLA-4, and HLA-DR counterstained with anti-CD14 antibodies as a Mphi marker for dual fluorescence analysis by flowcytometry. RESULTS: On PB-Mphi, CD15s was markedly increased in both RA as well as ReA compared with OA. Furthermore, in the PB LFA-1, CD44, and HLA-DR showed a higher surface density on Mphi in ReA than in OA. Comparison between SF and PB showed significantly higher CD44 and CD54 expression on SF-Mphi. These molecules play an important part in lymphocyte-Mphi interaction. CONCLUSION: In PB from patients with inflammatory joint diseases, Mphi are activated, allowing recruitment into the synovial compartment. These disorders, in contrast with OA seem to be "systemic" in nature. Within the SF, different adhesion molecules are expressed on CD14(+) Mphi as compared with PB.