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PubMed1992

Yersinia-triggered reactive arthritis. Use of polymerase chain reaction and immunocytochemical staining in the detection of bacterial components from synovial specimens.

OBJECTIVE: To investigate whether microbial DNA is present in synovial specimens from patients with Yersinia-triggered reactive arthritis. METHODS: Synovial specimens from 13 patients with Yersinia enterocolitica O:3-triggered reactive arthritis and from 16 control patients were studied using polymerase chain reaction and immunocytochemical staining techniques. RESULTS: Yersinia chromosomal DNA was not found in any of the synovial specimens from Yersinia-triggered arthritis patients or controls, whereas with immunocytochemical techniques, Yersinia antigens were observed in synovial specimens from all of the patients with Yersinia-triggered reactive arthritis. CONCLUSION: Only stable bacterial degradation products, not whole bacteria, are present at the site of inflammation in Yersinia-triggered reactive arthritis.

Adult↗
PubMed1991

[The comparative effectiveness of serological and microbiological studies in the etiological diagnosis of reactive arthritis].

The information content of serological and microbiological studies was studied and compared in 72 patients suffering from enterogenous reactive arthritis. A high level of antibodies to intestinal Yersinia was detected in 11.1% of the patients, positive coproculture in 8.3%. Only one patient demonstrated at a time a high level of antibodies and isolation of intestinal Yersinia coproculture. The causative agent could usually be isolated in patients with the symptoms of enterocolitis. It is assumed that among patients suffering from reactive arthritis there are at least two different groups: with positive coproculture and a low level of antibodies and with a high level of antibodies and negative coproculture. The indicated conditions can be regarded as different phases of the disease in the same patients and reflect the pathogenetic heterogeneity of the patients' group with reactive arthritis. Serological and microbiological tests are viewed as equivalent in etiological diagnosis of reactive arthritis. Emphasis is laid on the fact that microbiological tests are more successful in patients with the symptoms of concomitant enterocolitis.

Antibodies, Bacterial↗
PubMed2004

Different cytokine profiles in patients with chronic and acute reactive arthritis.

OBJECTIVE: Analysis of cytokine production in patients with acute and chronic reactive arthritis (AcReA/ChrReA) in order to search for new treatment possibilities. METHODS: Cytokine production by peripheral blood and synovial fluid mononuclear cells (PBMCs/SFMCs) of 28 patients with AcReA, 27 patients with ChrReA, 26 patients with rheumatoid arthritis (RA) and 31 healthy controls was analysed by enzyme-linked immunosorbent assay (ELISA) and flow-cytometry. Production of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-10 was measured by ELISA, while the percentages of TNF-alpha-, IFN-gamma- and IL-4-positive CD3+ cells were determined in the same groups of patients and healthy subjects using flow cytometry. RESULTS: Spontaneous TNF-alpha production observed in PBMCs of ChrReA, but not of AcReA, patients was significantly higher (P<0.001) than in healthy controls. The percentages of TNF-alpha-positive CD3+ blood cells in ChrReA exceeded that of RA patients and healthy controls (P<0.05 and P<0.001, respectively). Also, the percentages of IFN-gamma-positive CD3+ cells were significantly higher in peripheral blood and synovial fluid of ChrReA patients (P<0.05 and P<0.05, respectively) as compared with AcReA. In ChrReA spontaneous IL-10 production in PBMCs was similar to that observed in healthy controls, while in RA and AcReA the production of IL-10 was significantly increased (P<0.05 and P<0.05, respectively). IL-4 production was low in all study groups with no significant differences detected. CONCLUSIONS: High production of TNF-alpha and IFN-gamma detected in ChrReA supports the possible use of anti-TNF-alpha treatment in ChrReA.

Acute Disease↗
PubMed1995

Fast food arthritis--a clinico-pathologic study of post-Salmonella reactive arthritis.

OBJECTIVE: To study the clinical presentation, immunogenetics, and serum immune response to lipopolysaccharide (LPS) in a cohort of patients with post-Salmonella reactive arthritis (ReA). METHODS: A validate ReA screening questionnaire (Quest 2) was mailed to 919 individuals reporting symptoms of gastroenteritis to the health department after eating at a single restaurant. Three hundred twenty-one persons returned questionnaires; 170 reported symptoms outside the gastrointestinal tract; 23 of those 170 reporting persistent joint symptoms were seen 4 to 16 weeks after the outbreak and 5 of the 23 were seen in followup 12 to 20 weeks later. Clinical features, HLA Class I typing, serum soluble CD8 levels, and serum antibodies to gram negative LPS by ELISA were determined. RESULTS: Joint complaints were reported more frequently by individuals with a longer duration of diarrhea. Upper extremity joints were frequently involved, and 66% reported one or more extraarticular symptoms of Reiter's syndrome. Three of 5 typed individuals were HLA-B27 positive, including 3 of the 4 most severely involved. Serum soluble CD8 levels correlated poorly with disease activity measured either clinically or by C-reactive protein. Antibodies to Klebsiella and Shigella LPS rose over time, while antibodies to Salmonella LPS fell. CONCLUSION: The clinical picture of post-Salmonella ReA is less stereotyped than often assumed, although severity correlated with HLA-B27 status. The association of joint symptoms with duration of diarrhea and the kinetics of the anti-LPS antibody response support the hypothesis that abnormal gut permeability plays a role in the pathogenesis of post-Salmonella ReA.

Antibodies, Bacterial↗
PubMed2002

Reactive arthritis after BCG immunotherapy: T cell analysis in peripheral blood and synovial fluid.

OBJECTIVE: To investigate the pathogenic mechanism of reactive arthritis after instillation of Calmette-Guérin bacillus (BCG). Although the clinical features of reactive arthritis after BCG therapy are well described, only a few reports have studied the possible pathogenic mechanisms. METHODS: We analysed by flow cytometry the phenotype and T-cell receptor (TCR) expression of peripheral blood (PB) and synovial fluid (SF) T cells in a patient who developed reactive arthritis (ReA) following intravesical BCG immunotherapy for bladder cancer. The proliferative response of short-term T-cell lines (TCL) from PB of this patient to mycobacterial antigens was tested by bromodeoxyuridine incorporation. RESULTS: CD4(+) and CD8(+) SF T cells with activated and memory phenotype were observed at the onset of arthritis. We were able to detect BV-restricted expansion of CD8(+) T cells in PB (BV17) and in SF (BV5S1 and BV12). The percentage of PB and SF CD8(+) T cells that expanded diminished when the symptoms remitted. The strongest response of CD4(+) TCL from the patient in vitro was obtained for human hsp-60 in an inversely dose-dependent manner. Very important was the finding that CD8(+) TCL from the patient demonstrated no proliferative response to any antigenic challenge that was reversed after the addition of exogenous interleukin 2. CONCLUSION: Although the identity of the stimulating antigen that led to the expansions observed in this patient is not clarified by the present data, both CD4(+) and CD8(+) T cells might play a role in the development of ReA following intravesical administration of BCG.

Arthritis, Reactive↗
PubMed2005

Successful treatment of postvenereal reactive arthritis with synovectomy and 3 months' azithromycin.

BACKGROUND: The effects of antibiotic therapy on the course of postvenereal reactive arthritis have not yet been elucidated. OBJECTIVE: The objective of this study was to observe the clinical course and outcome of synovectomy and 3 months of azithromycin therapy in patients with reactive arthritis and previously diagnosed triggering bacteria. METHODS: We performed an open, prospective study on 20 (14 male/6 female) patients with postvenereal reactive knee arthritis, aged 36.7 +/- 14.8 years, and with 16.5 +/- 20.4 months' duration of the disease. Detection of bacteria triggers was done by polymerase chain reaction, isolation and identification, and electron microscopy. Synovectomy was performed in all patients at entry into the study. Azithromycin was given at a dose of 500 mg per day for 5 days, and then 500 mg twice a week, during a 3-month period. Patients without remission were treated with combined antibiotic therapy using a macrolide, quinolone, and tetracycline for the next 4 months. Outcome evaluations of therapeutic efficacy and azithromycin safety were done after 1 and 3 months and 2 years of follow up. RESULTS: Remission, defined by the absence of joint swelling and tenderness, and extraarticular signs, was reached after 3 months in 15 of 20 (75.0%) patients (P = 0.025). Of 5 patients with persistent knee arthritis, remission was achieved with combined antibiotic therapy in 4. Visual analog scale scores (P < 0.01), the number of patients (P = 0.002), and the number of samples (P = 0.01) with a positive finding of bacteria or their DNA were significantly lower after 3 months of therapy. During the azithromycin therapy, there were no significant adverse effects. CONCLUSIONS: These patients with reactive arthritis did extremely well on the regimen described. In our study group, the number of patients and the number of samples with positive findings of bacteria or their DNA were lower after the antibiotic treatment combined with surgery, although not all bacteria were eradicated. Adverse effects of prolonged azithromycin administration were insignificant. This open treatment approach is recommended but does need a study with controls.

Adolescent↗
PubMed1984

Reactive arthritis.

Although sometimes used to refer to any sterile arthritis occurring in association with infection, the term 'reactive arthritis' is better reserved for arthritis following sexually acquired nonspecific urethritis or enteric infections with organisms such as Shigella, Salmonella, Yersinia and Campylobacter, because these arthropathies are unified by a number of shared clinical characteristics and an association with HLA B27. This review suggests that these arthropathies may also share a common pathogenic pathway, triggered by an ' arthritogenic factor' common to the diverse microbes which cause the disease and modified by genetic factors other than HLA B27. Although uncommon, reactive arthritis is important because it could provide the key to understanding the other seronegative arthropathies and mechanisms basic to chronic inflammatory synovitis.

Arthritis, Infectious↗
PubMed1997

Limited effect of sulphasalazine treatment in reactive arthritis. A randomised double blind placebo controlled trial.

OBJECTIVE: To assess the efficacy and safety of sulphasalazine in reactive arthritis. METHODS: Double blind placebo controlled trial of six months duration comparing sulphasalazine 2-3 g per day (n = 37) with matching placebo (n = 42) in adults with active reactive arthritis (age 19-57 years, median 34). Treatment response was evaluated once a month by changes in erythrocyte sedimentation rate (ESR), pain, peripheral arthritis, tender iliosacral joints, entesopathy, extra-articular manifestations, and working ability. RESULTS: 15 patients in the sulphasalazine group and eight in the placebo group withdrew from the study prematurely. Adverse events, primarily gastrointestinal, were the main reason for withdrawal in the actively treated group. Intention-to-treat analyses showed significant improvements over time in both groups in ESR, pain, and number of swollen joints (P < 0.01). Number of days on sick leave decreased significantly in the sulphasalazine group only (P < 0.01). No significant differences between the two groups were present after six months. Among the patients completing the trial according to protocol, persistent complete remission had occurred within two months in five (23%) of the actively treated, but in no placebo treated patients (P = 0.013). CONCLUSIONS: Sulphasalazine seemed to improve only the very short term outcome of reactive arthritis. The possible beneficial effect of the drug should also be weighed against the risk of adverse events. Although these were mainly mild, almost 25% of the patients in the actively treated group gave up treatment for this reason.

Adult↗
PubMed2004

[Poststreptococcal reactive arthritis].

Arthritis, following infection caused by group A beta-hemolytic streptococcus, is classically attributed to acute rheumatic fever. However, a new clinical syndrome, called poststreptococcal reactive arthritis, as a distinct entity from acute rheumatic fever, was described recently. The purpose of this paper is to provide a summary of published information on poststreptococcal reactive arthritis. The paper outlines its clinical description and proposed diagnostic criteria. Similarities and differences between poststreptococcal reactive arthritis and acute rheumatic fever are discussed. Information regarding long-term risk of carditis following poststreptococcal reactive arthritis is provided, and therapeutic recommendations are outlined.

Acute Disease↗
PubMed1995

Pathogen antigen- and superantigen-reactive synovial fluid T cells in reactive arthritis.

Analysis of pathogen-reactive T cell clones (CD3+4+8-TCR alpha beta +), isolated from the synovial fluid of 2 HLA-B27-positive patients with Yersinia enterocolitica-triggered reactive arthritis, has provided important information about the cellular immune response to this disease-inciting pathogen. This study demonstrates that the proteins secreted by Y. enterocolitica, including a protein with tyrosine phosphatase activity (YopH), are potent immunogens stimulating CD4+ cells within the inflamed joint. The pathogen-reactive T cell clones preferentially utilized a limited set of T cell receptor variable region gene segments. A purified Yersinia superantigen triggered a proliferative response in most of the antigen-reactive T cell clones tested. These results suggest that the activity of this pathogen's superantigen influences the cellular immune response to its antigens.

Adult↗
PubMed1994

Epidemiologic aspects, clinical features, and management of ankylosing spondylitis and reactive arthritis.

The generally reported prevalence of 0.1% to 0.2% for ankylosing spondylitis in the white population is probably too low, because it is based almost entirely on hospital records. The incidence and clinical presentation of ankylosing spondylitis have not changed during the past few decades. For reactive arthritis, the list of microbes recognized as triggering agents is continuously increasing. Reactive arthritis is divided into urogenic, enterogenic, respiratory tract-associated, and idiopathic arthritides. In addition, several microbial diseases may be accompanied by reactive arthritis, even though the identity of the causative agent is not always known. In the diagnosis of the spondyloarthropathies, definite progress has been made in developing classification criteria. Intensive research is going on to evaluate new therapies, with special attention to the use of antimicrobial agents for the treatment of reactive arthritis.

Arthritis, Reactive↗
PubMed1992

Does reduced erythrocyte C3b receptor (CR1) activity contribute to the pathogenesis of yersinia triggered reactive arthritis?

Erythrocyte C3b receptor (CR1) activity was measured in 27 patients with yersinia triggered reactive arthritis and in 151 control subjects, including 36 patients with uncomplicated yersiniosis and 115 healthy subjects. CR1 was measured by the immune adherence haemagglutination method. Patients with yersinia triggered reactive arthritis had reduced levels of CR1 compared with the controls. This difference was mainly due to the finding that five out of six HLA B27 negative patients with arthritis had decreased CR1 activity. Such a quantitative difference may contribute to the pathogenesis of reactive arthritis by affecting the clearance of immune complexes.

Adult↗
PubMed2005

Pathogenesis of ankylosing spondylitis and reactive arthritis.

PURPOSE OF REVIEW: The hallmark of ankylosing spondylitis is acute and chronic spinal inflammation initiating in the sacroiliac joints, often coupled with enthesitis, presenting as chronic inflammation at the sites of ligamentous and tendinous insertions into bone. Peripheral joint synovitis can be a prominent feature as well. Reactive arthritis is a sterile synovitis arising after an extra-articular infection of enteric or urogenital tracts. HLA-B27 has been known for about the past 30 years to be associated with ankylosing spondylitis and reactive arthritis, but the pathogenesis of ankylosing spondylitis and reactive arthritis is still not well defined. Although the clinical manifestations of ankylosing spondylitis and reactive arthritis may differ, this update discusses the two diseases together and focuses on recent evidence in both. RECENT FINDINGS: With respect to HLA-B27 several recent studies address arthritogenic peptides, molecular mimicry, and aberrant forms of B27. Several candidate genes in addition to B27 have been implicated in recent genetic studies. With respect to bacterial infection, recent findings in bacterial antigenicity, host response through interactions of antigen-presenting cells, T cells, and cytokines are providing new understanding of host-pathogen interactions and the pathogenesis of arthritis. Endogenous host factors such as proteoglycans may play a role as autoantigens and contribute to chronic inflammation on that basis. SUMMARY: Recent advances provide additional new insights into distinct pathogenetic mechanisms in AS and ReA that arise from a complex interplay between genetic factors including HLA-B27 and environmental factors.

Arthritis, Reactive↗
PubMedDate not supplied

A longitudinal study of calprotectin as an inflammatory marker in patients with reactive arthritis.

OBJECTIVE: To examine the value of calprotectin, a major granulocyte protein with bactericide properties, as an inflammatory marker in patients with reactive arthritis. METHODS: Twenty-five patients with Chlamydia-induced and 27 patients with enterobacteria-induced reactive arthritis were analysed. At the first visit and after 3, 12, 24, 52 and 104 weeks, calprotectin concentrations were measured in plasma and when possible, in synovial fluid. C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were analysed and clinical assessments of disease activity were performed. RESULTS: Of the inflammatory markers, the plasma calprotectin concentrations were the first to normalize during recovery. Calprotectin concentrations in the plasma were highly correlated with CRP and ESR, and calprotectin was found to have high correlation coefficients with the clinical assessments of disease activity. High calprotectin concentrations were found in the synovial fluid. CONCLUSION: The high correlations between calprotectin in plasma and clinical and laboratory markers of inflammation, as well as the rapid normalization following clinical improvement, demonstrate that calprotectin may be used as an inflammatory marker in patients with reactive arthritis.

Adolescent↗
PubMed1998

Longitudinal investigation of bacterium-specific synovial lymphocyte proliferation in reactive arthritis and lyme arthritis.

BACKGROUND: Antigen-specific lymphocyte proliferation of synovial fluid mononuclear cells (SF MNC) has been reported repeatedly in reactive arthritis and Lyme arthritis; however, less information is available on serial investigations of SF MNC in the same patients. METHODS: In this study, the synovial lymphocyte proliferation to Yersinia, Chlamydia, Shigella and Borrelia burgdorferi was investigated sequentially at different time points in 28 patients with reactive arthritis, undifferentiated oligoarthritis or Lyme arthritis responding to one of these bacteria. RESULTS: The same bacterium was always recognized in arthritis triggered by Chlamydia, Shigella or Borrelia, with much variation in the proliferative response. Only the Yersinia-specific responses changed specificity, suggesting that the proliferative response to Yersinia is non-specific in some patients. CONCLUSIONS: Our data support the concept of a local antigen-specific T-cell response in reactive arthritis or Lyme arthritis but not the concept suggested by others that a switch to an autoimmune response takes place in long-standing disease.

Antigens, Bacterial↗
PubMed2000

Characterisation of autoantibodies to neutrophil granule constituents among patients with reactive arthritis, rheumatoid arthritis, and ulcerative colitis.

OBJECTIVE: To study the frequency and distribution of antineutrophil cytoplasmic autoantibodies (ANCA) among patients with reactive arthritis (ReA), rheumatoid arthritis (RA), and ulcerative colitis (UC) using different immunological methods. METHODS: Fifty serum samples from patients with reactive arthritis (26 with acute disease and 24 with chronic disease-that is disease of more than one year) were analysed for ANCA with indirect immunofluorescence, enzyme linked immunosorbent assay (ELISA) with six different neutrophil granule proteins as antigens, and immunoblotting on whole neutrophil extract and extracts of azurophil and specific granules. Thirty serum samples from patients with RA and UC served as controls in ELISA and indirect immunofluorescence. RESULTS: Sixteen per cent of patients with ReA were positive in immunofluorescence compared with 30% of patients with RA, and 70% of patients with UC. Thirty two per cent of patients with ReA were positive in ELISA. Antibodies directed against lactoferrin occurred in 20%, antibodies against bactericidal permeability increasing protein (BPI), elastase, cathepsin G, myeloperoxidase, and proteinase 3 were found in 8%, 2%, 2%, 8%, and 6%, respectively. Overall, 50% of RA sera and 53% of UC sera were positive in one or more ELISA assays, the corresponding figures for antibodies against individual antigens were for RA 7%, 3%, 0%, 13%, 47%, 17% and for UC 13%, 20%, 0%, 23%, 10%, and 17%. In immunoblotting, bands corresponding to lactoferrin and BPI were recognised in 44% and 22% of ReA sera. CONCLUSION: Antibodies against neutrophil granule antigens are often found in patients with ReA, primarily among those with chronic disease. The different methods detect various subsets of antibodies, with immunoblotting being the most and immunofluorescence the least sensitive.

Acute Disease↗
PubMed1988

Reactive arthritis associated with Shigella sonnei infection.

Several studies have failed to show an association between Shigella sonnei dysentery and reactive arthritis. We describe 3 patients who had reactive arthritis and a recent or concurrent S sonnei infection. To our knowledge, this is only the second study to suggest this association. We propose that S sonnei should be considered as a triggering agent for reactive arthritis.

Adult↗