Hypothesis 3
Immune-Mediated Inflammatory Arthropathy

Inflammatory arthropathies are characterized by a marked 
synovitis, although cartilage and bone destruction can occur.  
Although the etiology of rheumatoid arthritis is unknown, it is 
considered to be immune-mediated due to the identification of 
antibody (rheumatoid factor) reactive against IgG in many cases of 
the disease.   The basic underlying immunopathologic process 
appears to involve the creation of immune complexes, generated 
either locally within the joint, and/or systemically within the 
circulation followed by deposition in the joints.  The immune 
complexes stimulate inflammation via a type 3 hypersensitivity 
reaction, and the immune complexes fix complement in the 
synovial membrane and synovial fluid, after which a complement 
cascade results.  The complement cascade causes local tissue 
damage and releases products that are chemotactic for 
polymorphonuclear phagocytes, which migrate to the joint and 
phagocytize immune complexes and release enzymes that cause 
inflammation.  Affected joints are often swollen and painful on 
manipulation, and in advanced cases, gross deformity with 
abnormal motion and crepitus is apparent.  Stretching and rupture 
of ligaments and joint capsule secondary to the inflammatory 
process is common and can lead to joint collapse, instability, and 
osteoarthritic changes.  Any limb joint can be affected. 

While the underlying etiology is unknown, it is most likely 
multifactorial and probably involves microbial or viral infections, 
either within the joint itself or elsewhere in the body (stimulating 
the formation of circulating immune complexes).   The disease can 
affect any breed of dog, and animals are usually adult; an average 
onset age of 5-6 years has been reported.  

Clinical signs of rheumatoid arthritis include morning stiffness, 
stiff-legged gait, pain on manipulation of one or more joints, 
reluctance to exercise, and swelling of the affected joints.  The 
peripheral joints are most commonly affected, and the extent of 
joint involvement may be so severe that the animal may not be able 
to walk.   Many of these clinical signs correlate with BonnieÕs 
history and physical exam, which revealed effusion of the left stifle 
joint with a distention of the joint capsule on either side of the 
straight patella ligament, and pain on manipulation of the stifle.