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Update on managing inflammatory bowel disease and intestinal lymphoma in cats (Proceedings)

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Oct 01, 2008

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) currently is recognized as a common and important medical problem in cats. Three general types of clinical presentations have been identified in cats with idiopathic IBD: (1) a clinical course characterized primarily by vomiting, (2) a clinical course characterized primarily by diarrhea, and (3) a clinical course that includes both vomiting and diarrhea as primary signs. Associated clinical signs can include change in appetite (anorexia, inappetence, or ravenousness), weight loss, and lethargy. In some cats, the clinical signs are cyclic; they seem to flare up and then abate in a predictable pattern.

Vomiting, one of the most frequent clinical signs of IBD in cats, is most often recognized as an intermittent occurrence for weeks, months, or years. Affected cats are frequently misdiagnosed as having hairballs as the primary problem. As the disorder progresses, an increased frequency of vomiting often leads the owner to seek veterinary attention. In addition to vomiting, diarrhea is a common sign observed in feline IBD and most likely is due to derangement of normal mechanisms of absorption and motility caused by mucosal inflammation. In most cases, diarrhea is intermittent early in the course of the disorder, and there may be a transient response (weeks to several months) to dietary manipulation or any of a variety of medications. Later, the diarrhea becomes persistent and usually responds only to specific treatment, which is determined after a definitive diagnosis is made. Signs of small bowel diarrhea predominate, but signs of large bowel diarrhea may be evident as well if there is generalized intestinal tract involvement.

Appetite changes in cats with idiopathic IBD vary from decreased appetite to complete anorexia to ravenousness. Inappetence seems to occur more commonly in cats that have vomiting as the primary clinical sign and usually occurs during exacerbation of clinical signs, and vomiting or diarrhea is not observed until later or not at all. The three leading differential diagnoses for a cat with a ravenous appetite, diarrhea, and weight loss are IBD, hyperthyroidism, and exocrine pancreatic insufficiency (uncommon).

A definitive diagnosis of IBD can be made based only on intestinal biopsy. Further tests are run to evaluate the overall health status of the patient and to rule out other disorders. Recommended baseline tests include a complete blood count, biochemical profile, urinalysis, fecal exams for parasites, serum thyroxine test, and a feline leukemia virus test. Testing for feline immunodeficiency virus should be considered in cats with chronic wasting disease.

Treatment

It is important that the clinician formulate a treatment protocol based on a correlation of clinical course, laboratory and gross findings, and histologic findings rather than relying on histologic changes alone. Corticosteroids are the cornerstone of treatment for idiopathic inflammatory bowel disorders. Mild to moderate cases often respond to prednisone or prednisolone at a starting dose of 1 to 2.2 mg/kg divided twice daily for two to four weeks followed by a gradual decline in 50% increments at two week intervals. Cats with inflammatory changes graded as mild usually respond quite well to the lower dose and alternate day or every third day treatment can often be achieved by two to three months. Occasionally treatment can be discontinued altogether by three to six months.

If biopsies reveal disease that is moderate to severe a prednisolone dose of 2.2 to 4.4 mg/kg divided twice daily is used for the first 2 to 8 weeks or until clinical signs resolve. I do prefer to use prednisolone over prednisone in cats with inflammatory disorders of a moderate to severe nature, as there may be improved bioavailability in some cats with prednisolone. This dose of corticosteroid is usually well tolerated in cats. In these cases a dose of 1 to 2.2 mg/kg per day may be necessary long term (months to years) to maintain clinical remission. Use of combination drug therapy may also be required at the outset to control clinical signs and prevent progression of the disease. Cats with hypoproteinemia and histologic changes graded as severe often respond quite well when an aggressive therapeutic course is undertaken.

Budesonide is a glucocorticoid that represents a new alternative for management of IBD in dogs and cats, especially in severe cases that have proven to be refractory to prednisolone, metronidazole, azathioprine, and dietary management; or that are intolerant of the corticosteroids discussed above. Budesonide is a new and recently approved corticosteroid for use in humans. It is one of a group of novel corticosteroids that have been in development for use in humans in an attempt to make available alternative preparations that will help limit toxicity associated with corticosteroid use. Others include fluticasone propionate, tixocortol pivalate, and beclomethasone dipropionate.

Budesonide undergoes high first pass metabolism in the liver and 90% is converted into metabolites with low corticosteroid activity. It has minimal systemic availability. The potential for typical corticosteroid side effects is significantly reduced as a result of decreased bioavailability and the resulting limited systemic exposure, which makes this a particularly attractive drug for use in humans and animals that are poorly tolerant of other corticosteroids. Budesonide also has a high receptor-binding affinity in the mucosa. It has been referred to as a "locally acting" corticosteroid.

Therapeutic results with budesonide have been promising in humans with Crohn's disease, collagenous colitis and lymphocytic colitis, ulcerative colitis, either when administered as a retention enema or in oral form, and primary biliary cirrhosis.

Budesonide has been used by some veterinary clinicians in recent years to treat IBD in dogs and cats. Dose recommendations vary. In humans, a range of 6 mg to 9 mg per day has been used during initial therapy. The following general recommendations have been made for dogs and cats. In general, budesonide is administered to cats and small dogs at 1 mg administered once per day. Budesonide is supplied as a 3 mg capsule (Entocort, AstraZenica). Compounding is necessary for accurate dosing for cats and small dogs (to a 1 mg prep).

Budesonide can be used in combination with other drugs. Since cats tolerate corticosteroids very well, there is little indication to use budesonide as initial therapy for IBD. However, this may be a very attractive option for use in diabetic cats that also have IBD, or in patients where conventional therapies have not been sufficiently effective.

Potential adverse effects include PU/PD, when budesonide is used at the high end of the dose range, and GI ulceration. These reactions have been observed in some human patients. These problems would be more likely to occur in dogs than in cats. It appears to be very safe when used at the levels listed above.

When combination therapy is indicated metronidazole (Flagyl) is usually the first choice to be used in conjunction with prednisone. Metronidazole's mechanism of action includes an antiprotozoal effect, inhibition of cell-mediated immune responses, and anaerobic antibacterial activity. A dosage of 10 to 20 mg/kg two times daily is used for IBD. Ideally, at least several months of metronidazole therapy is given once it is started. In some cats with severe disease long term consecutive use or one to two month cycles of treatment may be required. Side effects to metronidazole at this low dose are uncommon in cats. Occasionally nausea or vomiting may be seen.