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A report of three cases of Yersinia reactive arthritis.

Three cases of reactive arthritis associated with Yersinia enterocolitica bowel infection are reported. In one case Y. enterocolitica was cultured from stools while all three exhibited a significant increase in serum antibody titres to Y. enterocolitica. These are believed to be the first reports of Yersinia reactive arthritis in Australia. Synovial membrane biopsy in one case revealed a mixed inflammatory cell infiltrate the appearance of which was quite dissimilar to that of rheumatoid arthritis (RA). Mononuclear cells of the peripheral blood, but not the synovial fluid from another patient had reduced functional activity compared to RA patients as determined by response to phytohemagglutinin stimulation and allogeneic responses. Large numbers of HLA-DR and acid phosphatase positive macrophages were also found in the synovial fluid of this patient. The reason for joint involvement in Y. enterocolitica reactive arthritis is unknown and further work is necessary.

Adolescent↗

Are antibiotics of any use in reactive arthritis?

In the pathogenesis of reactive arthritis, infection through the mucosal route and genetic susceptibility (HLA-B27) are the most important contributing factors. With regard to non-specific urethritis, most probably caused by Chlamydia trachomatis infection, the use of early antimicrobial therapy has been shown to be effective in preventing arthritic recurrences. When the arthritis has been initiated, short-term conventional antimicrobial therapy seems unable to modify the course of the ongoing disease. In patients with acute reactive arthritis, a prolonged (3-month) treatment with tetracycline shortens the duration of arthritis when triggered by Chlamydia trachomatis, while such treatment has not proved effective in enteroarthritis. In patients with chronic reactive enteroarthritis, a prolonged course of quinolones, such as ciprofloxacin, might be of benefit. Sulfasalazine, which has an effect in the acute exacerbations of ankylosing spondylitis, is probably also effective in chronic reactive arthritis. An antimicrobial effect can be one of the mechanisms by which sulfasalazine exerts its therapeutic effect. Follow-up studies are necessary to assess the influence of antibiotic therapy on the late prognosis of patients with reactive arthritis.

Anti-Bacterial Agents↗

Cationic Yersinia antigen-induced chronic allergic arthritis in rats. A model for reactive arthritis in humans.

Cationic antigens are known to have considerable arthritogenic potential in experimental systems. During a systematic search for suitable, naturally occurring candidates an intracellular protein was isolated from the ribosomal pellet of Yersinia enterocolitica 0:3, a bacterial strain associated with reactive arthritis in humans. The protein is highly cationic, contains two 19-kD polypeptide chains linked by a disulfide bond, and reveals a strong tendency for spontaneous aggregation. It is suggested to be a nucleic acid binding protein. We tested this antigen for its ability to induce arthritis after intra-articular challenge in preimmunized rats. An acute inflammatory phase followed by transition to chronicity was observed both by technetium-99m scintigraphy and from histology. Massive polymorphonuclear leucocyte infiltration of the synovium was seen early on and fibrosis and thickening of the joint capsule occurred in later stages. Control groups showed no evidence of inflammation. Western blot and ELISA analysis of unselected sera from Yersinia enterocolitica 0:3-infected patients revealed antibodies to the antigen in the majority of cases, whereas healthy individuals rarely reacted. This is the first report of a naturally occurring cationic antigen capable of inducing immunologic tissue injury; it justifies the speculation that cationic antigens from prokaryotic cells could trigger reactive arthritis in humans.

Animals↗

IgA-anti-yersinia antibodies in yersinia triggered reactive arthritis.

Patients who develop reactive arthritis after yersinia enteritis are characterised by high and persisting IgA-anti-yersinia antibodies. We have further analysed the humoral immune response to yersinia in this condition. Total concentrations of IgM, IgG, IgA, and secretory IgA in the serum and specific anti-yersinia antibodies belonging to IgA1, IgA2, or secretory IgA were compared in patients with or without reactive arthritis. In the former group the serum concentration of secretory IgA and of yersinia specific antibodies in all categories studied was raised compared with the level in patients without joint symptoms; the difference was most significant for the IgA-anti-yersinia antibodies with secretory piece or with J chain. The findings suggest that the strong antibody response in the patients developing reactive arthritis is due to a chronic stimulation of the intestinal lymphoid tissue.

Antibodies, Bacterial↗

Identification of a 2-Md plasmid from Shigella flexneri associated with reactive arthritis.

The development of reactive arthritis, a sterile inflammatory polyarthropathy that primarily affects HLA-B27 positive individuals, has been associated with previous enteric infections caused by various gram-negative bacteria. The possibility that a common bacterial epitope triggers the disease was investigated by screening a panel of documented arthritogenic Shigella strains as well as 2 epidemic-associated nonarthritogenic Shigella controls. A 2-Md plasmid specific to the arthritogenic strains was identified and sequenced. The plasmid encodes a number of small peptides that could be related to the development of reactive arthritis. Within 1 of these is a stretch of 5 consecutive amino acids, inferred from the DNA sequence and contained within an open reading frame, that is homologous to amino acid residues 71-75 of the polymorphic region of the alpha 1 domain of HLA-B27. The data indicate that there is a bacterial plasmid common to arthritogenic Shigella strains that may play a role in triggering reactive arthritis. The finding that this plasmid encodes an epitope shared with HLA-B27 suggests that molecular mimicry may play a role in the induction of this disease.

Amino Acid Sequence↗

Gastrointestinal accumulation of indium-111 labelled granulocytes in reactive arthritis.

Six patients with reactive arthritis (ReA) were examined for gastrointestinal accumulation of Indium-111 labelled granulocytes. Abnormal scintigrams were found in three of six patients all of which showed early (less than 4 h) accumulation of indium-111 labelled granulocytes which may represent small intestinal inflammation. Our findings may indicate that the small intestine is involved in ReA, and that indium-111 granulocyte scintigraphy is a useful method for demonstrating inflammatory changes in the small intestine in reactive arthritis (ReA).

Adult↗

Solute carrier family 11 member A1 gene polymorphisms in reactive arthritis.

To investigate the role of SLC 11A1 polymorphisms in the development of reactive arthritis, 91 patients with reactive arthritis and 163 healthy controls were enrolled in this study. The SLC 11A1 polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. The genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were significantly different between the patients with reactive arthritis and controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the SLC 11A1 274C/T showed a significant association with reactive arthritis. The patients with reactive arthritis have a significantly higher frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was resistant to the development of reactive arthritis. The allele frequencies of SLC 11A1 274T and 823C were significantly increased in the patients with reactive arthritis in comparison with those of the controls, independent of HLA-B27. On the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly decreased in the patients with reactive arthritis. The estimated haplotype frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are associated with susceptibility to reactive arthritis independently of HLA-B27 in Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1 274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.

Arthritis, Reactive↗

Unusual causes of reactive arthritis: Leptospira and Coxiella burnetii.

Reactive arthritis is a well-defined clinical syndrome occurring after various infections, although most cases are usually associated with Chlamydiae and gastrointestinal pathogens. Its immunologic background has been extensively studied, as has its relationship with HLA-B27. We describe two cases of reactive arthritis arising after infections with two pathogens not so far related to the occurrence of reactive arthritis: one patient exhibited migratory oligoarthritis shortly after the course of acute Q fever, and another patient developed monoarthritis during recovery from leptospirosis. Arthritis was transient and did not exhibit a chronic course in either patient. We further discuss the context of pathophysiology of the arthritis in these patients, with an emphasis on the immunomodulatory properties of these two pathogens.

Adult↗

Expression of interferon beta in synovial tissue from patients with rheumatoid arthritis: comparison with patients with osteoarthritis and reactive arthritis.

BACKGROUND: IFNbeta may have immunomodulatory effects in rheumatoid arthritis (RA) and its increased production in RA synovium may be a reactive attempt to inhibit inflammation. OBJECTIVE: To determine the expression of IFNbeta in the synovial tissue of patients with RA, osteoarthritis, and reactive arthritis. METHODS: Synovial biopsy specimens were obtained by arthroscopy from patients with RA and disease controls for immunohistological analysis using a monoclonal antibody specific for IFNbeta. Bound antibody was detected by an immunoperoxidase method. Stained sections were evaluated by computer assisted image analysis. Double stainings were performed with antibodies to detect CD55 positive fibroblast-like synoviocytes (FLS), CD68 positive macrophages, and CD83 positive dendritic cells (DCs) co-expressing IFNbeta. RESULTS: IFNbeta protein was abundantly expressed in the synovium of patients with RA. Digital image analysis showed a significant increase in the mean integrated optical density for IFNbeta expression in RA synovial tissue compared with disease controls. Specific up regulation of IFNbeta expression was also seen when the results were controlled for cell numbers. Phenotypic analysis showed that FLS, especially, but also macrophages and DCs may express IFNbeta in RA synovial tissue. CONCLUSIONS: The increased expression of IFNbeta in RA synovium suggests activation of an immunomodulatory mechanism that could inhibit synovial inflammation.

Adult↗

Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis.

BACKGROUND: Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA. OBJECTIVE: To evaluate the effect of a three month course of ciprofloxacin on ReA. METHODS: In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery. RESULTS: Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study. CONCLUSION: Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

Adult↗

[Reactive arthritis].

In most cases, reactive arthritis occurs after urogenital and gastrointestinal infections. Anamnesis, clinical picture, antigen HLA-B27 determination and serologic antibody ascertainment are of essential importance to the diagnosis. The therapeutic value of antibiotics is questionable, owing above all to the fact that in chlamydia-induced arthritis the causative agent was found in the intraarticular biopsy specimen. The prognosis of the disease is favourable although relapses are frequent. Especially Reiter's disease may have a chronic course.

Arthritis, Reactive↗

[The reactive arthritis syndrome. Rheumatological limits].

The term reactive arthritis (RA) refers to an inflammatory joint disease in the absence of bacteria in the joint, but which is caused by a distant extra-articular infection. They occur as a result of a variety of infections, which are essentially genital or gastro-intestinal in subjects with a particular genetic predisposition characterized by the presence of the HLA-B27 antigen or one of the CREG group of antigens (B7 - B27 - BW22 - BW42). The most complete clinical expression of reactive arthritis is the Fiessinger-Leroy-Reiter syndrome. Apart from the reactive arthritis with a generally accepted aetiology such as those following infections of the genital tract (Chlamydia trachomatis, Ureaplasma urealyticum or of the gastrointestinal tract: Yersinia enterocolitica and pseudotuberculosis, Shigella flexneri, Salmonella minor, Campylobacter jejuni), the authors discuss the possibility of including, in a broader definition of RA, post-streptococcal arthritis and cases of arthritis following gonococcal, meningococcal and Brucella infections. RA does not always have a favourable clinical course. It is not exceptional to see a picture of recurrences with progression towards chronic inflammatory rheumatism.

Arthritis↗

[A 2-year evaluation of antibacterial serology adapted to the diagnosis of reactive arthritis (168 cases)].

The diagnosis of reactive arthritis requires the identification of a trigger infection. Since 1984 we have carried out a series of serological tests that we have called "serology of reactive arthritis": they aim at detecting antibodies against the most common infectious agents in this particular pathology. This serology is essentially based on the complement-fixation test. Here we report the results obtained over a period of two years, comparing them with clinical and biological data: 168 cases have been studied. They include to two groups of patients: group A reassembling seronegative spondylarthropathies and including reactive arthritis (N = 104), and group B with patients suffering from a typical rheumatic affection usually having no relation to spondylarthropathies (N = 64). We propose for each antigen a level of positivity from which the presence of antibodies can be taken into consideration as part of the diagnosis. With reference to these levels we have obtained a significant relationship to recent antecedents (genito-urinary and intestinal), to the presence of IgM circulating immune complexes and to the precocity of the serological tests. The contribution of this type of serology to the recognition of reactive arthritis has been studied together with the other diagnosis factors of the diseases. We have been able to show significant rates of antibodies in more than 50% of the cases. The negative results and limits of this serodiagnosis are discussed.

Adolescent↗

Reactive arthritis induced by Strongyloides stercoralis.

Reactive arthritis induced by Strongyloides is exceedingly rare. A case in a 53-year-old man from the Guadeloupe (French Antilles) is reported. The outcome was rapidly favorable under thiabendazole therapy. The cycle of Strongyloides is reviewed, and the contribution of parasites to reactive arthritis in patients with genetic risk factors is discussed. Establishing the correct diagnosis is sometimes difficult but is essential in order to avoid inappropriate administration of corticosteroids that can lead to fatal, multivisceral dissemination of the parasite, particularly in patients with strongyloidiasis.

Animals↗