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.  


Another possible etiology for immune mediated arthropathy is an 
infectious arthritis caused by a tick borne agent.  Because Bonnie 
is frequently taken for walks in the woods, it is hypothesized that 
she may be suffering from a tick born disease.  Lyme disease is 
caused by the spirochete Borrelia burgdorferi. B. burgdorferi is 
transmitted primarily through the bite of an infected Ixodid tick.  
Infection may result in fever, mono-or polyarticular arthritis, 
and/or arthralgia (pain in joint).  The animal may present with 
acute lameness, usually with no history of trauma. Single or 
multiple joints may be involved.  An acute transient mono- or 
polyarticular arthritis occurs for 50 to 90 days after infection, 
almost exclusively in the limb closest to the tick bite.

Arthritis due to B. burgdorferi is caused by indirect injury that is 
medicated through immune complex formation deposited in the 
joint(s). Intra-articular enzymes originating form inflammatory 
cells, granulation tissue, synoviocytes, and cartilage beginning to 
break down the cartilaginous matrix.  Destruction of the cartilage 
matrix exposes collagen fiber and mechanically weakens the 
cartilage, making it very susceptible to damage by physical forces 
such as those that occur with weight bearing.  Pannus formation 
(granulation tissue forming over the cartilage surface) adds to 
cartilage destruction through additional enzymatic degradation of 
matrix and by physically isolating the covered cartilage from 
needed nutrients. Joint motion is reduced and fibrous ankylosis 
with or without persistent pain may be the final out come if the 
infectious arthritis in uncontrolled.

A rickettsial disease is another rule out for Bonnie's case. Rocky 
Mountain Spotted Fever( Rickettsia rickettsii) and Canine 
Ehrlichiosis(Ehrlicia canis) which are both transmitted by ticks.  R. 
Rickettsii infection of dogs is often subclinical. However, in severe 
cases a systemic vasculitis may occur.  Polyarthritis is a prominent 
feature of this vasculitis.  Even though Bonnie appears to only 
have a monoarthritis and does not have additional clinical signs 
indicative of Rocky Mountain Spotted Fever, it should not be 
completely ruled out.  Erlichia canis infection can present as acute, 
chronic(subclinical) or severe as a prominent or secondary feature.  
Other clinical signs include fever, depression, lymphadenopathy, 
and various hematologic abnormalities (thrombocytopenia).  While 
Bonnie does not appear to have these clinical sign, a titer test for 
Ehrlichia may be appropriate.