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.

Effect of antimicrobial treatment on chronic reactive arthritis.

In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.

Pathogenesis of Yersinia-triggered reactive arthritis: immunological, microbiological and clinical aspects.

When a patient develops reactive arthritis after Yersinia enteritis, the following conditions are often fulfilled: the patient is HLA-B27-positive; however, some B27-negative individuals develop severe arthritis and some positives do not, in the initial phase, the diarrhea is milder, the anti-Yersinia antibody response of IgG class is more vigorous and persists longer, the anti-Yersinia antibody response of IgA class is more vigorous and persists much longer, the anti-Yersinia antibodies of IgA1 and IgA2 subclass, those with J-chain and, especially, those with secretory piece are produced more vigorously, indicating local immunostimulation close to the intestinal epithelium, in the early phase, Yersinia-IgM immune complexes are found in the circulation, and the lymphocyte transformation response against not only Yersinia but also against other gram-negative enteric bacteria is weaker. When all these aspects are considered together a strong suspicion arises that the patients who are destined to develop reactive arthritis fail in their first line of defense against the invading organism when contracting a Yersinia enteritis. This may lead to persistence of the microorganism within the body, e.g., in the intestinal epithelium or in the mesenteric lymphoid tissues, maintaining a stimulus for a prolonged--apparently futile and perhaps harmful--antibody production. Finally, the initiating and decisive factor should not be forgotten: the Yersinia. Why and how it triggers the process is at present one of the enigmas of the pathogenesis of reactive arthritis.