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 cipro-floxacin 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.

Conclusions-Chlamydiatrachomatis, 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. (Ann Rheum Dis 2001;60:337-343) Reactive arthritis (ReA) is a well known complication of enteric infections caused by yersinia, salmonella, shigella, and campylobacter, or of urogenital tract infections caused by Chlamydia trachomatis.

Yersinia enterocolitica serotype O:3 and O:8 urease-negative mutants unable to express the 19-kDa ␤ subunit of urease were constructed and tested for virulence and arthritogenicity. Our results indicate that urease is needed for full virulence in oral infections and that it is not an arthritogenic factor in the rat model.

Objective. To study the effect of antibiotic prophylaxis and treatment of reactive arthritis (ReA), using an experimental model.Methods. Yersinia enterocolitica 0:8, when injected intravenously into Lewis rats, causes a sterile arthritis closely resembling human ReA in 70% of the animals. Arthritis develops in 1-2 weeks; in some of the animals it remains chronic, and exacerbations occur. This model was applied to study the effect of a 7-day treatment with ciprofloxacin, using 2 different dosages (20 or 100 mg/kg/day) and 4 different schedules for initiation of treatment. The effects were evaluated by determining the daily arthritis score, the number of rats developing arthritis, and fecal excretion of Yersiniu. In addition, weight gain was monitored. At autopsy (35 or 60 days after inoculation with bacteria), samples were obtained for determination of Yersiniu-specific antibodies in the serum. At the same time, samples were collected from mesenteric lymph nodes, lung, spleen, and liver for bacterial cultures, and from the ankle joints for histologic evaluation. In a separate experiment, ciprofloxacin concentrations in samples from serum and mesenteric lymph nodes were analyzed by high performance liquid chromatography.Results. A 7-day course with 100 mg/kg/day of ciprofloxacin, started on day 3 after bacterial inocula-

Outer membrane protein YadA, the Yersinia adhesin, is one of the plasmid-encoded virulence factors of yersiniae. To evaluate the role of YadA in the pathogenesis of reactive arthritis experimentally, we used YadAstrain YeO8-116, a kanamycin GenBlock insertion mutant derived from Yersinia enterocolitica 0:8 wild-type strain 8081. As control strains, a plasmid-cured derivative (8081-c) of 8081 and a YopHmutant (8081-yoph) were used. In addition, YeO8-116, with theyad4 mutation transcomplemented with plasmid pMW10, was used.