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Many bacteria and viruses can cause arthritis without directly invading the joint space. The diseases that result are highly varied and are the focus of this chapter. These processes include reactive arthritis, which occurs after genitourinary or enteric bacterial infections, post-streptococcal reactive arthritis (PSRA), Lyme disease, and viral and post-viral arthritis (including transient synovitis).

Bacterial infection of the joint, with the recovery of the causative organism from the synovial fluid, is called septic arthritis and is addressed in Chapter 105. Acute rheumatic fever (ARF), which can also cause arthritis, is addressed separately (Chapter 57).



Reactive arthritis is the name given to an aseptic arthritis that follows a gastrointestinal or genitourinary infection. It is associated with certain bacteria; specifically, Chlamydia trachomatis, Shigella, Salmonella, Yersinia, or Campylobacter, but recent reports have also implicated atypical organisms as diverse as Giardia lamblia and Clostridium difficile.1 Although by definition reactive arthritis is a sterile arthritis, modern PCR techniques have identified bacterial DNA in synovial tissue.2 The significance of this finding is unclear.

Reactive arthritis is part of a group of diseases called spondyloarthritides (arthritis that affects primarily the axial skeleton), which includes psoriatic arthritis, enthesitis-related arthritis, and ankylosing spondylitis. They have a strong association to human leukocyte antigen B27 (HLA-B27) and share common extra-articular features including enthesitis, uveitis, and inflammatory bowel disease.

The pathogenesis of reactive arthritis is still not well understood. Newer evidence suggests that the arthritis that results is caused by an abnormal innate immune response to bacterial antigens in the joint space, or to mechanical trauma.3


Post-streptococcal reactive arthritis (PSRA) may be caused by antistreptococcal antibodies that cross-react with proteins expressed in the joint cartilage and synovial lining.4


Lyme disease is the most common vector-borne infection in North America. It is caused by the spirochete Borrelia burgdorferi and transmitted to humans by infected Ixodes scapularis and I. pacificus ticks. The disease is endemic in the northeast and north-central regions of the United States, and its incidence is increasing dramatically.5

Although it cannot be cultured from the synovium of patients with Lyme arthritis, B. burgdorferi DNA is detectable in the synovial fluid via PCR. The spirochete does not secrete any toxins but is thought to cause a strong host inflammatory response that leads to arthritis.6 Phagocytosis of live B. burgdorferi by monocytes appears to induce the release of pro-inflammatory cytokines such as type I interferons that induce joint inflammation.7


Viruses cause arthritis by various mechanisms, including the stimulation of pro-inflammatory cytokines, inducing the formation of antibodies that cross-react with ...

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