Recognizing and treating immune-mediated polyarthritis in dogs - Veterinary Medicine
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Recognizing and treating immune-mediated polyarthritis in dogs
This inflammatory joint condition presents in many forms, often causing systemic illness and sometimes causing cartilage and bone destruction. Learn to distinguish these forms and what treatments induce remission and alleviate pain.


VETERINARY MEDICINE


TREATMENT


Table 3
Treatment of erosive and nonerosive IMPA involves treating joint inflammation and any identified, underlying immunologic trigger. Numerous treatment regimens have been proposed that involve single or multiple agents, including immunosuppressive drugs, immunomodulating drugs, or newer disease-modifying agents (defined by their ability to slow disease progression) (Table 3). A standard treatment of IMPA is difficult to identify, as controlled prospective clinical trials are unavailable.

Regardless of the treatment regimen chosen, the goal is remission. If remission is not attained, the goals of treatment are to achieve the lowest possible level of joint inflammation, minimize joint damage, and enhance physical function and quality of life while minimizing drug toxicity. Monitor the patient regularly to ensure that these goals are being met and, if not, determine if an alternative course of therapy is necessary.

Nonerosive

Treatment of idiopathic types II through IV IMPA, drug-induced IMPA, and vaccine-associated IMPA relies on identifying and treating underlying causes. Failure to identify triggers will result in persistent or recurrent joint inflammation.1,2,4 Once the cause is addressed, most cases resolve on their own. Some may require additional treatment as discussed below. Other treatments may be indicated for SLE and Shar-Pei fever, as previously discussed.

Other forms of IMPA, including idiopathic type I IMPA, SLE polyarthritis, polyarthritis-meningitis syndrome, polyarthritis-myositis syndrome, and polyarthritis in Akitas, require treatment with immunosuppressive, immunomodulating, and disease-modifying drugs.

Immunosuppressants. Corticosteroids are often the initial treatment of choice because of the low cost of treatment and rapid rate of action.1,2,4,6,18 About 80% of dogs with idiopathic type I IMPA respond to immunosuppressive doses of prednisone,9,15 but half of these dogs require long-term or combination drug therapy to maintain remission.15,18 Prednisone is initially administered at immunosuppressive doses of 2 to 4 mg/kg/day until remission is achieved (see Monitoring section below). Once remission is achieved, prednisone is then gradually reduced over an extended period, usually two to four months.1,4,6,18

If clinical signs recur upon dose reduction or discontinuation, reinstitute prednisone at the initial dose or add another drug to therapy. If a patient needs to receive prednisone long-term to control clinical signs, use the lowest effective dose, preferably on an every-other-day dosing schedule. Side effects associated with long-term corticosteroid use include iatrogenic hyperadrenocorticism, diabetes mellitus, urinary tract infections, pyoderma, and breakdown of collagen in tendons and ligaments.35

If prednisone montherapy is ineffective, not tolerated, or not preferred, an additional cytotoxic drug is used adjunctively with prednisone. Azathioprine and cyclophosphamide are most commonly used with prednisone and have been shown to induce remission in patients with IMPA.15,18 The superiority of one drug over the other is unknown. Azathioprine is initiated at a dose of 2.2 mg/kg daily for two to four weeks and given concurrently with prednisone at an anti-inflammatory dose of 0.5 to 1 mg/kg every other day.2,6 After induction, azathioprine is then reduced to an every-other-day dose that alternates with prednisone.2,6 Cyclophosphamide is initiated at a dose of 1.5 mg/kg (for dogs > 30 kg), 2 mg/kg (for dogs 15 to 30 kg), or 2.5 mg/kg (for dogs < 15 kg) for the first four consecutive days of each week and given concurrently with prednisone at an anti-inflammatory dose once daily.6 Both treatment regimens are continued for two to four months, after which, if a patient is in remission, the azathioprine or cyclophosphamide is gradually withdrawn.6

Side effects of azathioprine include bone marrow suppression and hepatotoxicosis.35 Side effects of cyclophosphamide include bone marrow suppression and hemorrhagic cystitis.35 Because of the potential for hemorrhagic cystitis, cyclophosphamide should not be used for more than four months,1,6 and azathioprine may have the advantage of being better tolerated for long-term use. If a patient cannot be weaned from cyclophosphamide, chlorambucil may be substituted for maintenance therapy with fewer side effects.6,29 Chlorambucil has not been shown to be effective at inducing IMPA remission.

If a patient remains in remission once the cytotoxic agent is discontinued, a patient can be gradually weaned off prednisone. If remission is not attained with the addition of cyclophosphamide or azathioprine or is not maintained once the drugs are removed, levamisole, leflunomide, or cyclosporine may be added or substituted for the cytotoxic agent (Table 3).

Immunomodulating drugs. Levamisole, an anthelmintic with immunomodulating properties, has been shown to be effective in treating SLE polyarthritis36 and in relapsing cases of IMPA.1,4 In a study population of German shepherds affected with SLE and polyarthritis, levamisole induced remission in 76% of dogs.36 It is administered at a range of dosages but most commonly at 2.2 mg/kg every other day or 0.5 to 2 mg/kg three times weekly.35 To treat SLE, levamisole was administered at a dosage of 2 to 5 mg/kg (maximum of 150 mg/dog) every other day with a concurrent initial dosage of prednisone of 1 to 2 mg/kg/day.36 Side effects may include lethargy, vomiting, diarrhea, agitation, hemolytic anemia, and cutaneous drug eruption; these signs appear to occur most commonly at higher dosages.35

Disease-modifying agents. Leflunomide has been recently evaluated for use in treating canine IMPA.3 The drug was used as monotherapy in dogs not receiving previous medication for polyarthritis and in those that relapsed while receiving prednisone. Ninety-three percent of dogs had a complete or partial response with treatment, and, of those responding, 63% had to continue to receive the drug long-term to maintain remission.3 Leflunomide was used at a dose of 3 to 4 mg/kg in this study and appeared to be safe and well-tolerated. Some authors recommend adjusting the leflunomide dose to a trough level of 20 g/ml.6,35 It has not been investigated for use in combination with corticosteroids. Side effects include mild anemia, decreased appetite, and lethargy.37

Cyclosporine has gained popularity for use in the treatment of a variety of immune-mediated conditions and may prove useful in treating IMPA. When used as a sole agent for treating IMPA, it was ineffective.9 Further investigation may find it efficacious as adjunct therapy. Side effects include gingival hyperplasia, gastrointestinal upset, or recrudescence of infectious disease.35


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Source: VETERINARY MEDICINE,
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