OBJECTIVE: To translate the Health Assessment Questionnaire Disability Index (HAQ) into a German version, to validate and to compare its properties with two different versions of the Hannover Functional Ability Questionnaire (HFAQ) in a German speaking population. METHODS: The test-retest reliability was tested by Pearson correlation in 32 outpatients of the Department of Rheumatology of the Medizinische Hochschule Hannover. For retesting, the questionnaire was mailed to them 1 week later. To validate the questionnaire it was administered to 110 inpatients in three different hospitals. All patients fulfilled the American College of Rheumatology 1987 revised criteria of rheumatoid arthritis (RA) or the Rome criteria of definitive inactive RA. The internal consistency was measured by Cronbach's coefficient alpha (CCA). To assess criterion validity we compared the HAQ and the two versions of the HFAQ with Keitel's test (KT) and the modified Steinbrocker classification (mSC). Construct validity was assessed by comparing these instruments with different clinical and laboratory variables. A multivariate analysis was used to identify the most important factors that are influencing the HAQ- and HFAQ-scores. RESULTS: Test-retest reliability of the HAQ was r = 0.94. CCA was 0.91 (HAQ), 0.90 (HFAQ-P) and 0.93 (HFAQ-PR). The KT Pearson correlation coefficients reached r = -0.73 (HAQ), r = +0.74 (HFAQ-P) and r = +0.71 (HFAQ-PR). The mSC correlated r = +0.75 (HAQ), r = -0.72 (HFAQ-P) and r = -0.70 (HFAQ-PR). The correlation coefficients of HAQ/HFAQ-P was r = -0.87 and of HAQ/HFAQ-PR r = -0.88. The correlations between other clinical and laboratory variables reached from r = +/-0.58 (pain/HAQ) to r = +/-0.11 (number of swollen joints/HFAQ-PR). In backward multiple regression analysis 59-64% of the variance of disability measured by the questionnaires was explained predominantly by pain (32-33%) and by range of motion (16-21%). CONCLUSION: The German version of the HAQ presented here and the two versions of the HFAQ are reliable and valid instruments for measuring functional disability in a German-speaking population with RA. The construct measured by the HAQ and both versions of the HFAQ showed a high degree of correspondence.

Activities of Daily Living↗

PubMedDate not supplied

Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX), which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostaglandins. Gastrointestinal injury is a common outcome. We compared the efficacy, safety, and tolerability of long-term therapy with celecoxib, a COX-1 sparing inhibitor of COX-2, with diclofenac, a non-specific COX inhibitor. METHODS: 655 patients with adult-onset rheumatoid arthritis of at least 6 months' duration were randomly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks. Anti-inflammatory and analgesic activity and tolerability were assessed at baseline, every 4 weeks, and at week 24. We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available. Analysis was by intention-to-treat. FINDINGS: 430 patients underwent endoscopy (celecoxib n=212, diclofenac n=218). The two drugs were similar in management of rheumatoid arthritis pain and inflammation. Gastroduodenal ulcers were detected endoscopically in 33 (15%) patients treated with diclofenac and in eight (4%) in the celecoxib group (p<0.001). The rate of withdrawal for any gastrointestinal-related adverse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was nearly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p<0.001). INTERPRETATION: Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac, with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events, and tolerability was better.

Analysis of Variance↗

PubMedDate not supplied

The modulation of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27.

OBJECTIVE: The intracellular persistence of viable Chlamydia trachomatis (CT) within the joint is thought to initiate and maintain the inflammatory process in CT-induced arthritis. CT-induced arthritis is associated with HLA-B27. Recently it was shown that HLA-B27, besides being a T-cell restriction element, can directly influence the invasion and/or replication of enterobacteriae and alters salmonella-induced signal transduction. It was the aim of this study to analyze the effect of HLA-B27 on CT-invasion and replication in human host cells. METHODS: Human Hela cells and Hela cells transfected with either HLA-B27 cDNA or controls (HLA-A1 cDNA; HLA-B27 mutant = HLA-B27 without cytoplasmic tail; B27Q10 = HLA-B27 Exon 1-4 linked to Exon 5 of murine Q10) were infected with CT. By direct immunofluorescence chlamydial invasion was determined 4 hours post infection (p.i.), chlamydial replication 2 days and 4 days p.i. The number of infective CT in the different cell lines was determined by titration of the cell lysates on Hep-2 cells with subsequent immunoperoxidase staining. RESULTS: Invasion was not affected by HLA-B27. However, formation of chlamydial inclusion bodies and replication was suppressed by HLA-B27. Genetically engineered mutants of HLA-B27 (HLA-B27 mutant, B27Q10) lacking the cytoplasmic tail of HLA-B27 did not affect replication. CONCLUSION: The reduction of chlamydial replication by HLA-B27 depends on the cytoplasmic domain of HLA-B27, thus providing a new hypothesis for chlamydial persistence in HLA-B27 positive reactive arthritis.

Chlamydia Infections↗

PubMedDate not supplied

Evaluation of amplicor chlamydia PCR and LCX chlamydia LCR to detect Chlamydia trachomatis in synovial fluid.

OBJECTIVES: PCR has been successfully used in research for the detection of C. trachomatis DNA in synovial samples. However, each research laboratory has developed its own PCR, making inter-laboratory comparisons difficult. To allow for standardization we evaluated two commercially available amplification systems originally designed for the examination of urogenital samples (Roche Amplicor Chlamydia PCR and Abbott LCX Chlamydia LCR), using them to analyse spiked and clinical synovial fluid (SF) samples from reactive arthritis (ReA), undifferentiated arthritis (UA), and rheumatoid arthritis (RA) patients. We compared their sensitivity in assays of clinical SF samples with our in-house developed C. trachomatis specific nested PCR. METHODS: SF was spiked with purified C. trachomatis elementary bodies (EB) and analyzed by the commercial assays. Clinical SF samplesfrom ReA (n=21), UA (n=79) and RA (n=50) patients were examined by the two commercial assays and our in-house PCR. RESULTS: Using SF samples spiked with defined numbers of C. trachomatis EB, the sensitivity of the commercial tests was high and similar to published PCR sensitivity. In clinical SF specimens the commercial assays was also able to detect CT; however, the in-house PCR was more sensitive. Out of 10 PCR-positive SF samples Amplicor tested positive in only 4/10 and LCX in only 3/10. The in-house PCR detected chlamydial DNA in synovialfluidfrom 5/21 ReA (24%), 5/79 UA (6%) and in none of the 50 RA patients. CONCLUSION: Commercial amplification assays allow the detection of C. trachomatis in clinical specimens, although with a lower sensitivity than optimized PCR. Potential explanations are discussed.

Adult↗

PubMedDate not supplied

The genetically-engineered secretory B27/Q10 chimeric molecule inhibits HLA-B27 restricted alloreactive T-lymphocytes.

OBJECTIVES: Intracellularly persisting bacterial infections and high association with HLA-B27 are the hallmarks of reactive arthritis. Soluble HLA-B27 molecules are induced by bacterial infection; however their biological role in arthritis is unknown. It was the aim of this study to generate soluble HLA-B27 molecule and to analyze its effect on cytotoxic HLA-B27 alloreactive CD8+ T-lymphocytes in order to better understand potential functional links between persistent infection and HLA-B27 association. METHODS: Using PCR Exons 1 through 4 of HLA-B*2705 were fused to Exon 5 of the soluble murine MHC class I variant Q10 and stably transfected into Hela-cells. Transfectants were analyzed using specific PCR, RT-PCR and intracellular and extracellular staining with anti-HLA-B27 monoclonal antibody ME1. Secretion of B27Q10 in the supernatant was examined by isoelectric focusing (IEF). The effect of B27Q10 on T-cells was analyzed using either HLA-B27- or HLA-A2-restricted alloreactive T-cells in a standard 51Cr-release assay. RESULTS: PCR and RT-PCR demonstrated the DNA and mRNA of B27Q10 in the transfectants. By intracellular and extracellular staining with ME1 B27Q10-molecule was detected intracellularly but was not expressed in the cell membrane. Using IEF soluble B27Q10-molecules were found in supernatants of transfectants in a concentration of up to 1.342 microg/ml. Soluble B27QJO-molecule inhibited specifically the cytotoxicity of HLA-B27-restricted alloreactive T-cells by about 30%. CONCLUSION: The secretory non-membrane-expressed molecule B27Q10 inhibits HLA-B27 specific T-cells. The inhibition of cytotoxic T-cells by bacteria induced soluble HLA-B27 may thus enable bacterial persistence.

Animals↗

PubMedDate not supplied

Anti-tumour necrosis factor (TNF)-alpha therapy in undifferentiated spondyloarthropathy.

The cytokine tumour necrosis factor (TNF)-alpha plays a major role in the spinal inflammatory process of spondyloarthropathy. In contrast to rheumatoid arthritis, disease modifying antirheumatic drugs have not been proved effective against inflammation and progressive ankylosis. Initial studies on TNFalpha inhibitors in ankylosing spondylitis are promising and raise the question as to whether early stages of the disease, mostly classified as "undifferentiated spondyloarthropathy" (uSpA), should also be treated with TNFalpha inhibitors. This article summarises the preliminary results of 11 uSpA patients in 4 different trials treated with TNFalpha inhibitors.

Antibodies, Monoclonal↗

PubMedDate not supplied

Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is a vasculitis predominantly affecting medium- and large-sized arteries. Recent data show the co-localization of dendritic cells and Chlamydia pneumoniae in vascular biopsies from GCA patients. Here we define the topographical relation of dendritic cells and these activated T-cells to determine the antigen presenting cell in GCA, and to examine several auxiliary biochemical and genetic aspects relating to the role of bacteria such as C. pneumoniae in eliciting GCA. METHODS: 18 paraffin-embedded temporal artery biopsy specimens from 14 patients with GCA that were PCR-positive for C. pneumoniae were examined by two-color immunohistochemistry for the topographical relationship between dendritic cells and activated T-cells. In addition the presence of GTP-binding proteins. Tumor necrosis factor alpha (TNF alpha), and Toll-like receptor 4 (TLR4) was investigated. 15 temporal artery specimens from 10 patients without GCA served as controls. RESULTS: In all GCA specimens, dendritic cells co-localized in the immediate vicinity of activated CD4+ Talin-expressing T cells, and these were predominantly found in granulomatous infiltrates. Confocal microscopy confirmed the cell-cell contact of dendritic cells with activated T cells. Results further showed that RhoA and Rac1 were predominantly present in the region of granulomatous infiltrates. TNF alpha production and expression was found in dendritic cells and macrophages, predominantly in granulomatous infiltrates and in endothelial cells of the vasa vasorum dispersed in the adventitial and medial layers of the temporal artery. No control specimens showed TNF alpha expression. More than 95% of dendritic cells were positive for TLR4; macrophages and endothelial cells localized in the adventitia showed TLR4 production. CONCLUSIONS: The immediate co-localization of dendritic cells and activated T cells indicate a high probability that the former represent the antigen presenting cells in GCA. In addition, because of the presence of Rho A and Rac1 in the granulomatous infiltrates, we speculate that they provide the right environment for cell-cell contact and adhesion, and that they may promote the internalization of bacteria. TNF alpha is expressed at high levels in the granulomatous infiltrates of temporal artery specimens from patients with GCA. Since TLR4 is produced in the same cell types, and predominantly in the adventitial layer of the temporal artery, we suggest that these receptors are coupled to signal transduction pathways that control TNF alpha expression.

Aged↗

PubMedDate not supplied

Chlamydial rRNA in the joints of patients with Chlamydia-induced arthritis and undifferentiated arthritis.

Synovial fluid and synovial membrane specimens of 11 patients with Chlamydia-induced arthritis (CIA), 24 patients with undifferentiated arthritis (UndA), 4 patients with post-enteritic reactive arthritis, 3 patients with Lyme arthritis and 9 patients with rheumatoid arthritis were investigated for the presence of Chlamydia trachomatis (C. trachomatis). A single stranded DNA-probe was used for nucleic acid hybridization with ribosomal RNA (rRNA) from C. trachomatis. In 4 patients (CIA = 1, UndA = 3) chlamydial rRNA was found in the synovial fluid. In one additional patient (CIA) the specimen of a synovial membrane biopsy was positive for chlamydial rRNA. The detection of intra-articular chlamydial rRNA is discussed as an indicator for the presence of viable Chlamydiae in inflamed joints.

Arthritis, Infectious↗

PubMedDate not supplied

Early arthritis and rheumatoid arthritis in Germany.

Early arthritis is challenging because the clinical picture often does not allow a distinction between rheumatoid arthritis (RA), self-limiting disease, and other forms of inflammatory arthritis. In Germany the first early synovitis clinic and several inception cohorts of patients with early RA were initiated and evaluated during the 1980s and 1990s to learn more about diagnostic classification, psycho-social problems and socio-economical status including sick-leave, work loss, and indirect costs of patients with early arthritis and early RA. Unclassified arthritis was described as the most frequent diagnosis and the term "undifferentiated arthritis" was chosen to underline the heterogeneity of theses arthritides and the preliminary state of this classification as a working diagnosis. A large National Databank of the German Regional Collaborative Arthritis Centres has been established over the last 10 years. In total, there are some 170,000 cases in the database. Moreover, a prospective multicentre inception cohort of early RA of less than 1 year's disease duration has been started recently to evaluate parameters of potential relevance for the pathogenesis of RA and eventually for the prediction of erosive disease. Studies are in progress to test the diagnostic performance of specific antibodies and antibody patterns for RA. Another topic of research addresses the identification of bacterial DNA in synovial fluid and synovial tissues to improve the differentiation of patients with reactive arthritis from those with early RA and to narrow the working diagnosis of undifferentiated arthritis.

Adolescent↗

PubMedDate not supplied

Evaluation of early diagnostic criteria for ankylosing spondylitis in a 10 year follow-up.

A set of early diagnostic (ED) criteria comprising clinical data, ESR, radiological spinal signs, and the risk factor HLA B27 was evaluated after 5 and 10 years in a follow-up of 54 patients with an initial diagnosis of possible ankylosing spondylitis (AS). After 10 years 32 patients (59%) had developed definite AS according to the New York criteria, 10 individuals (19%) had possible or undifferentiated spondylarthropathy (SA), whereas in 12 patients (22%) other diagnoses were stated. ED criteria had a high discriminatory significance for the development of AS after 5 and 10 years (P less than 0.005, P less than 0.001 respectively). In this respect they were more valuable than B27 determination alone (P less than 0.01) or the ED criteria without HLA B27 (P less than 0.05). Furthermore, patients with still possible or undifferentiated SA had a higher mean score at the first examination than individuals with other final diagnosis (P less than 0.05). Thus, the ED criteria were useful for the identification of patients developing definite AS and of individuals in the AS related group of possible or undifferentiated SA.

Back Pain↗

PubMedDate not supplied

[Preventive and therapeutic effect of estrogen administration in adjuvant arthritis].

Using adjuvant arthritis as a model for human rheumatoid arthritis, we examined prophylactic and therapeutic effects for different doses of estrogen (0.5-5.0 mg estradiol 3x/week) in 40 male Long Evans rats compared to 16 control animals. More than 2.5 mg estradiol resulted in significantly reduced inflammatory activity, both in animals treated before or after induction of arthritis (Mann Whitney U-test, p less than 0.05).

Animals↗

PubMedDate not supplied

Specific serum IgA-antibodies in chlamydial-induced arthritis.

A cohort analytic study was performed to investigate serum IgA-class antibodies against Chlamydia in 24 patients with chlamydial-induced arthritis (CIA). IgA-class antibodies against chlamydial antigens were positive (titre greater than or equal to 1:16) in 23 of the 24 IgG-positive CIA-patients (96%) in contrast to 16 of 40 patients (40%) with other rheumatic diseases (ankylosing spondylitis n = 6; undifferentiated arthritis n = 11; rheumatoid arthritis n = 12; degenerative joint disease n = 11), also positive for IgG-class chlamydial antibodies. Both the presence of specific IgA-antibodies and their geometric mean titre (1:28 vs. 1:4) differed significantly (p less than 0.001) between the two groups.

Adult↗

PubMedDate not supplied

[Clinical studies with salazopyrine--consequences and perspectives].

The efficiency of sulphasalazine (SASP) as a long-acting antirheumatic drug for rheumatoid arthritis is now well established by placebo-controlled studies and comparative trials with injectable gold and D-penicillamin. Early treatment effect and better tolerance suggest the use of SASP especially for early treatment of rheumatoid arthritis. Severe and advanced disease, in which gold and/or D-penicillamin were not effective or toxic, may also be treated with SASP. Open questions are the effect on the radiological progression and the differential indication to antimalarials, oral gold and methotrexat. Positive results of two placebo-controlled studies in ankylosing spondylitis for the first time open the perspective of a long-acting antiphlogistic therapy in this disease. Further open trials observed promising treatment effects of SASP in reactive and juvenile rheumatoid arthritis. Therefore, future clinical studies have to establish indication, benefit-risk-relation and treatment modalities also in these rheumatic disorders.

Arthritis, Rheumatoid↗