Reactive arthritis (ReA), an acute nonpurulent form of arthritis, is a complication of many infectious diseases that affect parts of the body distinct from those involved in the acute illness (Yu and Kuipers 2003). The disease chiefly follows urogenital or diarrheal infections by multiple etiologic agents, including Campylobacter. ReA that occurs after an episode of campylobacteriosis usually is manifested within several weeks of the acute gastrointestinal illness (Blaser 2000).
The clinical manifestations ReA range from isolated transient monoarthritis to severe multisystem disease. Although it can be highly inflammatory and severe, ReA usually is moderate in intensity. Patients often manifest such constitutional symptoms as fatigue, malaise, fever, and weight loss. The arthritis typically is asymmetric and additive, with new joints becoming involved over days or weeks. Joints of the lower extremities suffer most. Tendinitis is common, as are urogenital, ocular, and mucocutaneous lesions. Rarely, ReA is associated with aortic insufficiency and cardiac conduction abnormalities. Reiter’s syndrome—the triad of arthritis, urethritis, and conjunctivitis—makes up just one portion of the ReA spectrum and is more closely associated with Shigella and Chlamydia trachomatis infections than with Campylobacter.
ReA following infections by various agents occurs most often, although not exclusively, in people who have the gene that encodes a histocompatibility antigen called HLA-B27. Between 30% and 85% of ReA patients have the HLA-B27 gene. However, only 8% of healthy people have the HLA-B27 gene, and only about 20% of them will develop ReA if they contract the triggering infections (NIH 2002). People who are 18-40 years old are at greatest risk for ReA. Men and women are equally likely to contract ReA from enterically-acquired infections; in contrast, ReA from sexually-acquired infections predominantly affects men.
Long-term followup studies of patients who have ReA suggest that some joint symptoms persist for months in 10-60% of cases and that acute symptoms commonly recur (Hannu et al. 2004a; Hannu et al. 2002; Rees et al. 2004). Up to 25% of affected people must change or curtail their work because of joint symptoms. The symptoms of ReA usually last 1-21 weeks and occasionally up to a year (Skirrow and Blaser 2002). Symptoms that persist beyond a year tend to be mild and nondeforming.
ReA is a clinical diagnosis, but the finding of HLA-B27 positivity is helpful. Treatment is symptomatic and uses primarily anti-inflammatory agents, including nonsteriodal anti-inflammatory agents, especially indomethacin.
Population-based studies have provided the most convincing evidence of an association between Campylobacter infection and ReA. Two such studies found that 7% and 1.8% of patients with laboratory-confirmed Campylobacter infection later developed ReA (Hannu et al. 2002; Rees et al. 2004). They validated the results of three independently conducted rheumatologic surveys administered after distinct outbreaks of Campylobacter infection (Bremell et al. 1991; Eastmond et al. 1983; Hannu et al. 2004a). The surveys found that 0.7-2.6% of adults infected with Campylobacter later developed ReA. The scientific literature also contains reports of at least 40 sporadic cases of ReA associated with Campylobacter infection (Hannu et al. 2002). The disparate geographic locations of the studies—including Finland and California—indicate that the association of Campylobacter with ReA is a general, not local, phenomenon.
The pathogenesis of bacteria-induced ReA is poorly understood. Campylobacter organisms invade such host cells as monocytes and dendritic cells, which transport the bacteria