Polyarthritis: Clinical approach to medical joint disease (Proceedings)

Nontraumatic inflammatory joint disease is a relatively common, but under-recognized, cause of fever and morbidity in dogs. In one review of 66 dogs referred for fever of unknown origin to a veterinary teaching hospital, approximately 8% were diagnosed with immune-mediated polyarthritis. In addition to immune-mediated polyarthritis (i.e. inflammatory joint disease in the absence of an underlying genetic, infectious, or other secondary cause) there are a number of additional syndromes that have been recognized in dogs and cats. This lecture will review the general approach to non-traumatic joint disease in small animal patients, the differential diagnoses encountered in dogs and cats, and then review the clinical features and treatment of immune-mediated polyarthritis in detail.

Definition and Differential Diagnosis

Polyarthritis is defined as inflammation in two or more joints. Although any joint may be affected, including the inter-vertebral joints, large proximal limb joints and small distal limb joints, it is the stifle, carpal, and tarsal joints which are usually most severely affected. In addition, swelling due to effusion is easiest to appreciate in these three sets of joints. Primary immune mediated polyarthritis is a type III hypersensitivity disorder—circulating immune complexes are deposited in the synovial membrane and initiate inflammation, recruitment of inflammatory cells, release of cytokines and proteolytic enzymes including metalloproteinases, with resultant pain, excess joint fluid production, and eventual cartilage degeneration. In secondary polyarthritis, immune complex deposition in the joints may occur secondary to any concurrent inflammatory/infectious or neoplastic disease. Some of the best recognized causes of secondary immune-mediated polyarthritis are the chronic tick-borne infectious agents, including Anaplasma spp, Ehrlichia spp, and Borrelia burgdorferi, in dogs, and a post-calicivirus vaccine transient polyarthritis that may occasionally be seen in cats.

The forms of immune-mediated polyarthritis described in dogs and cats include:

Non-erosive polyarthritides

• Idiopathic, immune-mediated polyarthritis (large breed dogs)

• Secondary immune-mediated polyarthritis (no breed predisposition)

• Breed-specific idiopathic non-erosive polyarthritis (described in young Akitas, Weimeraners, Newfoundlands)

• Shar-Pei polyarthritis (oftentimes associated with renal/systemic amyloidosis, also known as 'Shar-Pei fever')

• Lymphoplasmacytic synovitis (Rottweilers, Labrador Retreivers, Newfoundlands, Staffordshire Terriers)

• Systemic lupus erythematosus

Erosive polyarthritides

• Rheumatoid arthritis (small/toy breeds)

• Erosive polyarthritis of greyhounds (Greyhounds, usually young at onset of clinical signs)

• Feline chronic, progressive polyarthritis (high association with FeLV, young male cats)

Immune-Mediated Polyarthritis

      Epidemiology and Clinical Signs

Idiopathic, immune-mediated polyarthritis is most commonly diagnosed in young-to-middle aged large breed dogs. The median age of onset is approximately 5 years, but has been reported in dogs from 6 months to 12 years. The most common clinical signs reported by owners include unwillingness to rise, cervical pain, a 'saw horse,' or 'walking on eggshells' gait, and anorexia and lethargy. Abnormal physical examination findings oftentimes include shifting-leg lameness, joint swelling and pain, and fever. In one retrospective review of dogs with primary immune-mediated polyarthritis, approximately 55% of affected dogs had body temperatures greater than 103 F at the time of diagnosis. Cervical pain may be due to involvement of the intra-vertebral joints in the disease process, or because sterile meningitis-arteritis may occur concurrently in up to 50% of dogs with immune-mediated polyarthritis and neck pain. It is important to remember this association because dogs with polyarthritis are oftentimes misdiagnosed as having probably neurologic disease due to the obvious neck involvement; however, dogs with polyarthritis, even with concurrent meningitis-arteritis, have normal neurologic examinations. Patients with chronic untreated disease or with the less common but more rapidly progressive erosive forms of disease may have distorted or collapsed joints and resultant severe gait abnormalities that are unfortunately irreversible.

      Diagnosis

Diagnosis of immune-mediated polyarthritis is made by cytologic observation of inflammation within the synovial fluid. Because not all joints may be affected, and because the diagnosis of polyarthritis requires that inflammation be documented in multiple joints, fluid for cytologic evaluation and culture should ideally be collected from at least three joints. For the reasons mentioned above, synovial fluid should be collected from the more distal joints (carpus, tarsus, stifle) since these are the most commonly affected, and because they are the easiest to sample. Normal joint fluid should be translucent, clear to very slightly yellow-tinged, and highly viscous. In dogs with polyarthritis larger-than-normal amounts of fluid may be obtained (normal joints should only have a few drops of fluid collectable by arthrocentesis), may be discolored or turbid, and viscosity may be decreased.

Cytologic evaluation of joint fluids from dogs with polyarthritis should reveal neutrophilic inflammation with no evidence of sepsis, as opposed to the normal low number of mononuclear cells present in healthy joints without associated neutrophils. Neutrophils may be degenerate with signs of toxicity. Fluid should also be collected for culture and sensitivity to rule out low-grade septic arthritis, particularly if one joint is affected much more severely than others, or if the patient is more likely to suffer from hematogenous polyarthritis (i.e. very young animals).

Once polyarthritis has been diagnosed, the type should be determined based on exclusion of secondary causes (any current infectious or inflammatory disease, including rickettsial infections and neoplasms), whether the polyarthritis is erosive or non-erosive, and whether the polyarthritis is due to a systemic immune-mediated syndrome or is an isolated immune-mediated polyarthritis. The most common diagnostic tests to perform following diagnosis of polyarthritis include a CBC, biochemistry profile, urinalysis, urine culture, thoracic radiographs, abdominal ultrasound, and infectious disease titers testing(E. canis, A. phagocytophilum, B. burgdoferi). In dogs with erosive arthritis, rheumatoid factor should be assayed, whereas dogs and cats with evidence of multiple organ involvement should have ANA titer measured.

      Treatment

Treatment of secondary cases of immune-mediated polyarthritis requires the identification of and management or resolution of the underlying cause. Polyarthritis usually resolves with appropriate treatment, and use of anti-inflammatory doses of glucocorticoids or non-steroidal anti-inflammatory drugs are often only required for short periods of times. In dogs with primary (autoimmune) polyarthritis, immunosuppressive dosages of glucocorticoids are the initial treatment of choice (2-4 mg/kg/day), although some orthopedic surgeons have begun advocating NSAIDs as a primary treatment modality; this has not been systematically evaluated as of yet. Adjunctive immunosuppressive treatment is necessary in dogs that fail to respond to corticosteroids alone or that relapse following glucocorticoid withdrawal. The most commonly used adjunctive immunosuppressive drug is azathioprine, although cyclophosphamide and cyclosporine have also occasionally been used. Rarer treatments that have been anecdotally suggested as being effective in dogs that fail more traditional therapies include gold sodium thiomalate (Myochrysine), tetracycline and niacinamide

Response to treatment should be monitored by owner perception of clinical signs, orthopedic examination and palpation for recurrence of pain and/or effusion, and most importantly, recurrence of inflammation within joint fluid. Joint fluid should be cytologically unremarkable prior to decreasing immunosuppressive therapy. Failure to establish cytologic remission in addition to absence of clinical signs may result in disease relapse and subsequent greater difficulty in achieving remission, or progressive injury to the joints that ultimately results in severe degenerative joint disease and in many cases, joint collapse. Approximately 80% of dogs with idiopathic non-erosive polyarthritis treated with prednisone alone respond well to initial treatment, and as many as 50% of these dogs only require therapy for a maximum of 6 months. The prognosis for idiopathic non-erosive polyarthritis is good with a mortality/euthanasia rate of less than 20%. Despite this low mortality rate, relapses are common, and some dogs require life-long therapy. Unfortunately, the prognosis for other forms of immune-mediated polyarthritis varies with the different forms of the disease but in general is poorer than primary, non-erosive autoimmune polyarthritis.