Erosive

The use of many drugs in the treatment of erosive IMPA has been extrapolated from data in human patients, and a variety of different therapeutic protocols and agents have been suggested. Within veterinary medicine, little evidence exists regarding the superiority of one protocol over another, and no treatment has proved consistently effective in halting the progression of erosive IMPA in dogs. For best efficacy, treatment needs to begin early in the disease process, before marked joint damage. Drugs used to treat erosive IMPA include immunosuppressive, disease-modifying, or palliative medications.

Immunosuppressants. Immunosuppressive agents used to treat erosive IMPA in dogs include prednisone, azathioprine, cyclophosphamide, and chlorambucil. Using corticosteroids as monotherapy in dogs with erosive IMPA has a limited effect^6,29 and is not recommended as it may promote cartilage damage.³⁸ Administering prednisone in combination with azathioprine, cyclophosphamide, or chlorambucil has a variable benefit in slowing the progression of disease.^2,6,29 Protocols for these agents are similar to those described above for nonerosive IMPA except that prednisone is initiated at higher immunosuppressive doses for several weeks to allow time for other agents to reach efficacy.² Long-term therapy is generally required, and care must be taken to monitor for adverse effects.

Gold salts, hydroxychloroquine, and penicillamine reportedly have had some therapeutic success in treating erosive IMHA but with variable efficacy. Objective data evaluating these drugs are limited, but the use of gold salts is reported most frequently.

Gold salts include an injectable formulation (sodium aurothiomalate) and an oral formulation (auranofin). They have been used most successfully in combination with anti-inflammatory doses of prednisone. Protocols vary, but sodium aurothiomalate is given at a dosage of 1 mg/kg intramuscularly once weekly for six weeks. Six week cycles are repeated every two to three months as a patient requires. Auranofin is given at a dosage of 0.05 to 0.2 mg/kg orally twice daily. Side effects of gold salts include blood dyscrasias, diarrhea, ulceration of mucous membranes, erythema multiforme, hepatotoxicosis, and renal disease³⁵ and may limit their use in some patients. Thus, close monitoring during therapy is critical.

Leflunomide and methotrexate have proven efficacious in treating a rheumatoid-like syndrome in cats.³⁹ Neither drug has been evaluated for erosive IMPA in dogs, but some authors recommend their use in refra ctory cases.^1,2

Palliative therapy. Erosive IMPA is often diagnosed after severe joint disease has occurred and palliative therapy should be used to improve function and control pain. Palliative therapy includes administering NSAIDs and other pain medications such as opioids or tramadol. Additionally, physical therapy, surgical stabilization of joints, and the supplementation of glucosamine-chondroitin and omega-3 fatty acids may be beneficial.^{2,4,6,16,18,29,34}

MONITORING

Assess a patient's response to therapy through its clinical signs and repeated synovial fluid analysis.^1,2,6,16,18 Reducing or withdrawing drugs prematurely may result in exacerbating the clinical signs and make it more difficult to sustain a long-standing remission. Even in the absence of clinical signs, synovial inflammation may persist. Ideally, arthrocentesis should be performed before each anticipated reduction in drug dose but is especially important before the first drug reduction. Repeated arthrocentesis should be performed on previously documented inflamed joints.⁶ No recommendation exists on the number of joints to reevaluate with synovial fluid analysis. Repeated arthrocentesis in a healthy dog does not appear to alter the type and numbers of cells in synovial fluid significantly.⁴⁰ However, sequential arthrocentesis in a patient receiving immunosuppressive therapy is still a concern, and strict aseptic technique should be used.

C-reactive protein may be useful for monitoring IMPA remission. C-reactive protein is an acute phase protein that rapidly increases in the serum of patients in response to infection, inflammation, and tissue destruction. Several studies have demonstrated a linear relationship between the amount of C-reactive protein in serum and the amount of inflammation in synovial fluid in patients with IMPA.^41,42 Because of these studies and the existence of reference values at major laboratories,⁴³ C-reactive protein values can be used to monitor the induction and maintenance of remission in IMPA patients.

Patients also need to be monitored for potential adverse effects of medications used to treat IMPA. This monitoring may include performing CBCs, serum chemistry profiles, urinalyses, and urine bacterial cultures. Monitoring should begin within one or two weeks after initiating the drug and be continued at appropriate intervals thereafter. If adverse effects are noted, appropriate dose reductions should be made or the drug should be discontinued.

SUMMARY

Canine IMPA can be a challenging disease to diagnose and treat. Nonerosive IMPA predominates, with idiopathic type I accounting for most cases. Keys to diagnosis are recognizing the clinical signs, performing synovial fluid analysis, and ruling out other disease processes. The treatment of both nonerosive and erosive IMPA involves immunosuppressive, immunomodulating, and disease-modifying drugs. In dogs with nonerosive IMPA, the prognosis and response to treatment vary according to cause but is often guarded to good, with many patients responding to single agent or combination drug therapy. In dogs with erosive IMPA, treatment needs to be aggressive and lifelong, and efficacy is limited by the presence of marked joint damage before the initiation of treatment.

Caroline M. Kiss, DVM, DABVP (canine and feline practice)
Gregory C. Troy, DVM, MS, DACVIM
Department of Small Animal Clinical Sciences
Virginia-Maryland Regional College of Veterinary Medicine
Virginia Tech
Blacksburg, VA 24060