Frequency of triggering bacteria in patients with reactive arthritis and undifferentiated oligoarthritis and the relative importance of the tests used for diagnosis.

OBJECTIVE: Reactive arthritis (ReA) triggered by Chlamydia trachomatis or enteric bacteria such as yersinia, salmonella, Campylobacter jejuni, or shigella is an important differential diagnosis in patients presenting with the clinical picture of an undifferentiated oligoarthritis (UOA). This study was undertaken to evaluate the best diagnostic approach. PATIENTS AND METHODS: 52 patients with ReA, defined by arthritis and a symptomatic preceding infection of the gut or the urogenital tract, and 74 patients with possible ReA, defined by oligoarthritis without a preceding symptomatic infection and after exclusion of other diagnoses (UOA), were studied. The following diagnostic tests were applied for the identification of the triggering bacterium: for yersinia induced ReA-stool culture, enzyme immunoassay (EIA), and Widal's agglutination test for detection of antibodies to yersinia; for salmonella or campylobacter induced ReA-stool culture, EIA for the detection of antibodies to salmonella and Campylobacter jejuni; for infections with shigella-stool culture; for infections with Chlamydia trachomatis-culture of the urogenital tract, microimmunofluorescence and immunoperoxidase assay for the detection of antibodies to Chlamydia trachomatis. RESULTS: A causative pathogen was identified in 29/52 (56%) of all patients with ReA. In 17 (52%) of the patients with enteric ReA one of the enteric bacteria was identified: salmonella in 11/33 (33%) and yersinia in 6/33 (18%). Chlamydia trachomatis was the causative pathogen in 12/19 (63%) of the patients with urogenic ReA. In patients with the clinical picture of UOA a specific triggering bacterium was also identified in 35/74 (47%) patients: yersinia in 14/74 (19%), salmonella in 9/74 (12%), and Chlamydia trachomatis in 12/74 (16%). CONCLUSIONS: Chlamydia trachomatis, yersinia, and salmonella can be identified as the causative pathogen in about 50% of patients with probable or possible ReA if the appropriate tests are used.

[Hypertrophic osteoarthropathy and thrombocytopenia in bronchial carcinoma]. / Hypertrophische Osteoarthropathie und Thrombozytopenie bei Bronchialkarzinom.

SYMPTOMS: A 40-year-old woman presented with an arthritis of the knees and ankles, digital clubbing and thrombocytopenia. EXAMINATIONS: Blood tests proved an inflammatory reaction. Clinical findings were the above mentioned oligoarthritis and a periostitis of the long extremity bones. Chest X-ray showed a lung tumor. THERAPY: After surgical treatment of the lung cancer both arthritis and thrombocytopenia normalized. CONCLUSION: Hypertrophic osteoarthropathy is characterized by the combination of clubbing, arthropathy and periostitis. This paraneoplasia may be the presenting manifestation of occult malignancy. The diagnosis of hypertrophic osteoarthropathy should cause an intensive search of cancer. Further associated diseases are discussed.

No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

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.

Bacteria-specific lymphocyte proliferation in peripheral blood in reactive arthritis and related diseases.

The cellular immune response seems to be important for the pathogenesis of reactive arthritis (ReA) and a bacteria-specific lymphocyte proliferation (LP) is often found in synovial fluid (SF) of ReA patients. However, the role of the bacteria-specific LP in peripheral blood (PB) is less well defined. In this study, we investigated 215 paired samples of SF and PB from patients with ReA (n = 65), undifferentiated oligoarthritis (n = 133) and undifferentiated spondylarthropathy (n = 17) to analyse the LP in PB and SF in relation to time. In 24 out of 87 patients (27.6%) with a bacteria-specific LP in synovial fluid, a positive LP to the same bacterium was also found in PB. While a positive LP in SF was found most frequently in the first week of the arthritis, a positive LP in PB was detected in 45% of patients when investigated between weeks 2 and 4 after the onset of arthritis, but was rarely found very early and late in the course of the arthritis. The time point seems to be crucial for the investigation of an LP in PB in patients with ReA.

Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multiple bacterial species in inflammatory joint diseases. I. Screening of synovial fluid samples of patients with spondyloarthropathies and other arthritides.

OBJECTIVE: Bacteria play a crucial pathogenetic role in Lyme arthritis (LA), reactive arthritis (ReA), other forms of spondyloarthropathy (SpA), and possibly in undifferentiated oligoarthritis (uOligo). Polymerase chain reaction (PCR) technology has been applied to detect bacterial DNA of individual microbes in synovial fluid (SF) of patients with arthritides. We screened for DNA sequences of 8 bacterial species simultaneously in SF of patients with inflammatory joint disease. METHODS: We examined 104 SF samples of 96 patients with ReA (n = 13), undifferentiated SpA (uSpA, n = 10), uOligo (n = 50), juvenile chronic arthritis (JCA, n = 13), and rheumatoid arthritis (RA, n = 10). A nested PCR approach was developed to detect DNA sequences of 8 bacteria: Chlamydia trachomatis, C. pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi. The detection limit was determined at 10 bacterial/sample. Serology and lymphocyte proliferation assay were done in parallel in most patients. RESULTS: In 12 cases bacterial DNA of B. burgdorferi (n = 7), C. trachomatis (n = 2), C. jejuni (n = 2), and C. pneumoniae (n = 1) was detected in patients with uOligo (n = 9) and JCA (n = 3), while no evidence of bacterial DNA was found in patients with ReA, uSpA, and RA. Shigella flexneri DNA was detected in 4 cases, but the significance of this finding remains uncertain due to the high sequence homology of this species with Escherichia coli. DNA of Y. enterocolitica, S. enteritidis, or K. pneumoniae was not found. A positive serologic response was found in 7/9 PCR positive patients. In 11/96 cases antibodies to 2 or more bacteria were found in parallel (11.5%). Antigen specific lymphocyte proliferation was observed in 5/9 PCR positive patients. CONCLUSION: Bacterial DNA was detected in peripheral joint of patients with uOligo and JCA, but not in ReA, uSpA, or RA in this study. The detection of bacterial DNA in synovial material by PCR technology gives useful diagnostic information, especially when antibodies against several microbes are present or antibodies are not detectable. Failure to detect bacterial DNA in patients with ReA and uSpA with longstanding disease suggests that in later stages autoimmune mechanisms may operate.

Chlamydia pneumoniae--a new causative agent of reactive arthritis and undifferentiated oligoarthritis.

OBJECTIVE: To examine whether reactive arthritis (ReA) known to occur after a urogenital infection with Chlamydia trachomatis can also follow an infection with Chlamydia pneumoniae, a recently described species of Chlamydiae that is a common cause of respiratory tract infections. METHODS: Specific antibodies (microimmunofluorescence test) and lymphocyte proliferation to C trachomatis and C pneumoniae in paired samples of peripheral blood and synovial fluid were investigated in 70 patients with either reactive arthritis (ReA) or undifferentiated oligoarthritis (UOA). RESULTS: Five patients with acute ReA after an infection with C pneumoniae are reported. Three had a symptomatic preceding upper respiratory tract infection and two had no such symptoms. In all patients a C pneumoniae-specific lymphocyte proliferation in synovial fluid and a high specific antibody titre suggesting an acute infection was found. CONCLUSION: C pneumoniae needs to be considered a new important cause of reactive arthritis.

The possible role of Shigella in sporadic enteric reactive arthritis.

Reactive arthritis (ReA) occurs after a urogenital infection usually with Chlamydia trachomatis or an enteritis due to Yersinia, Salmonella, Campylobacter or Shigella, Shigella, except during epidemics, is not considered to be a frequent cause of enteric reactive arthritis. However this might be due to the lack of a reliable antibody test, which makes diagnosis difficult. We compared synovial and peripheral blood lymphocyte proliferation to various bacterial antigens in 19 consecutive patients with ReA or undifferentiated oligoarthritis. In five patients Shigella was identified as the causative microbe by a specific synovial lymphocyte proliferation. All five patients had a history of symptomatic diarrhoea and had negative stool cultures by the time arthritis developed. Four of the five were HLA B27 positive. We conclude that Shigella may be underestimated as a cause of non-epidemic ReA.

[Reactive arthritis associated bacteria as the etiology of undifferentiated oligoarthritis]. / Reaktive Arthritis-assoziierte Bakterien als auslösende Ursache der undifferenzierten Oligoarthritis.

Undifferentiated oligoarthritis (UOA) resembles clinically reactive arthritis (ReA), but does not fulfill the diagnostic criteria. In 46 patients with UOA, in 16 with ReA, and in 15 with rheumatoid arthritis (RA) the humoral and cellular immune response to the ReA-associated bacteria Chlamydia trachomatis, Yersinia enterocolitica, Shigella flexneri, Salmonella enteritidis, Campylobacter jejuni and Borrelia burgdorferi was investigated in paired samples of synovial fluid and peripheral blood. An antigen-specific lymphocyte proliferation in SF was found in 75% of the ReA and in 39% of UOA patients, but in none with RA. Shigella and Chlamydia in ReA and Yersinia and Chlamydia in UOA were the most frequent stimulating antigens. There was a poor correlation between antigen specific lymphocyte proliferation and specific antibodies. We conclude that these bacteria might have a pathogenetic role, not only in ReA, but also in UOA.

Pathogenetic role of Chlamydia, Yersinia and Borrelia in undifferentiated oligoarthritis.

We studied the cellular and humoral immune response to Chlamydia trachomatis, Yersinia enterocolitica and Borrelia burgdorferi in paired samples of peripheral blood and synovial fluid (SF) in undifferentiated oligoarthritis, reactive arthritis (ReA) and rheumatoid arthritis. Antigen specific lymphocyte proliferation was found in SF of 43% of patients with ReA and 34% of patients with undifferentiated oligoarthritis. C. trachomatis was the most frequent single agent. HLA-B27 was positive in 83% of patients with ReA and in 62% of patients with undifferentiated oligoarthritis with antigen specific lymphocyte proliferation. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. Only chlamydial antigen was detected in SF cells using monoclonal antibodies. We conclude that some patients with undifferentiated oligoarthritis may have a forme fruste of ReA. This finding is important in view of recent evidence supporting the efficacy of antibiotic therapy in ReA.