IMPA (immune-mediated polyarthritis) in dogs (Proceedings)
Idiopathic, non-infectious, non-erosive immune-mediated polyarthritis (IMPA) is the most common immune-mediated arthritic condition in the dog, resulting in effusion, pain, and decreased range of motion in multiple joints. Although considered a Type III hypersensitivity disorder, an underlying etiology is not often found. Treatment of IMPA requires both treatment of the underlying immunologic trigger, if identified, and treatment of joint inflammation. Failure to achieve this goal may result in persistence or recurrence of clinical signs. Glucocorticoids are the most widely used treatment for IMPA in dogs. Although initial response rate to glucocorticoids has been reported as high as 81%, side effects ranging from polyuria, polydipsia, and polyphagia to diabetes mellitus, urinary tract infections, pyoderma, and breakdown of collagen in tendons and ligaments are prevalent. As a result, alternative or combination therapy is often sought, either to avoid complications associated with glucocorticoid therapy or for treatment of unresponsive disease.
Immune-mediated polyarthritis (IMPA) can cause either erosive or non-erosive change of articular cartilage. Classifications of polyarthritis consist of both infectious and non-infectious (inflammatory); non-infectious, inflammatory polyarthritis can be further broken down into sub-categories of non-erosive and erosive. Types of erosive polyarthritis can include: rheumatoid arthritis, polyarthritis of Greyhounds or Felty's syndrome (rheumatoid arthritis, splenomegaly, neutropenia). Non-erosive polyarthritis includes: idiopathic (type I -no underlying disease, type II - reactive, type III – enteropathic, IV – neoplasia related), systemic lupus erythematosus (SLE), vaccine-associated, drug-induced (secondary to sulfa drugs), polyarthritis/polymyositis, polyarthritis/meningitis, polyarthritis nodosa, Sjogren syndrome (arthritis, keratoconjuctivitis sicca, xerostomia), arthritis of adolescent Akita Inus, Shar Pei fever syndrome (amyloidosis, hock joint involvement), or lymphocytic-plasmacytic gonitis.Mechanisms/causes
Due to an immunologic trigger in the body, immune complexes are created and deposited within the basement membrane of the synovium. Through activation of the complement cascade, inflammatory cells, including neutrophils and macrophages, are recruited to the site of inflammation. The end result, after phagocytosis of the immune complexes, is the release of nitric oxide, free radicals, and proteases which cause tissue destruction. The cause is unknown but most likely results from immunologic mechanisms.
When the conditions occur that a primary or underlying disease can not be identified it is deemed idiopathic. This type of diagnosis can be made only after ruling out the other possible causes of arthritis. It is most commonly seen in large and small breed dogs but is uncommon in cats. German shepherds, Doberman pinschers, retriever breeds as well as spaniels, pointers, Toy Poodles, Lhaso Apsos, Yorkshire terriers and Chihuahuas are over represented. The mean age and range is typically from young to middle aged dogs; incidence peaks at 2.5-4.5 years of age however any age can be affected. Males and females are equally represented.
Clinical features of IMPA include stiffness and lameness most commonly, as well as pyrexia, lymphadenopathy, inappetence, lumbar spinal pain, depression, exercise intolerance, and lethargy. Decreased range-of-motion, effusion, heat, and pain upon manipulation of affected joints may be appreciated. Bilaterally symmetrical joint involvement is common with IMPA. Diarthrodial joints most often affected (in descending order) are the carpi, tarsi, stifles, and elbows-all may be affected. At times these signs are cyclic in nature. Many patients are seen because of decreased appetite or because of a fever of unknown origin. This can also be present with no palpable joint effusion or localized pain.
Diagnosis of IMPA is based on a significant increase in the synovial fluid cell count within affected joints; however a complete diagnostic work-up is recommended including a complete blood cell count (CBC), serum biochemical testing, urinalysis, thoracic radiographs, abdominal ultrasound, joint radiographs, arthrocentesis (including cytology and culture), and serologic testing for infectious agents. Testing for antinuclear and rheumatoid factor autoantibodies (ANA and RF) is commonly performed. However, unlike in human beings, these tests are not sensitive or specific for IMPA. A positive ANA or RF titer in the canine patient may result from any chronic inflammatory disease that leads to persistent antigen exposure and production of immune complexes. ANA titers are more sensitive when the test is reserved for dogs in which systemic lupus erythematosus (SLE) is suspected. An underlying immunologic trigger for IMPA is rarely found.
Results from the CBC commonly show neutrophilia although neutropenia is occasionally noted and some dogs show completely normal CBC's. Radiographs are often times normal or limited to joint or periarticular swelling with no boney or cartilage abnormalities. Synovial fluid is often times thin and may be turbid. The mucin clot test results are usually normal or show a slight decrease. Nucleated cell counts are increased (4,000 to 370,000 cells/µl) and nondegenerate neutrophils dominate (usually <80%). Patients that present with less severe cases or that have begun being treated (particularly with corticosteroids) may have a lower WBC and a lower percentage of neutrophils (30-80%). Blood, urine and synovial fluid are typically negative for bacteria and Mycoplasma.