Managing inflammatory bowel disease in cats (Proceedings)

Idiopathic inflammatory bowel disease (IBD) is defined as gastrointestinal signs (vomiting, anorexia, diarrhea) greater than 3 weeks duration, with incomplete response to dietary trials and anthelmintics, biopsy findings of mucosal inflammation, and clinical response to immunomodulatory therapies. IBD is believed to be due to a loss of mucosal tolerance to intestinal antigens such as commensal enteric bacteria or dietary components. Important differential diagnoses for IBD include systemic diseases (hyperthyroidism, diabetes mellitus, liver disease, pancreatitis, renal failure), food sensitivity, gastrointestinal lymphoma, chronic parasitism (giardia, tritrichomonas), and infectious diseases. A therapeutic trial with fenbendazole (Panacur) 50 mg/kg/day for 5 days should be considered for treatment of occult giardia, prior to pursuing more in-depth diagnostics. Diagnosis of IBD requires intestinal biopsies. The cornerstone of treatment for IBD consists of immunomodulatory drug therapy (usually prednisolone), which should ideally not be given without biopsy confirmation of IBD, since infectious intestinal disease can mimic IBD and could become substantially worse on immunosuppressive therapy. Furthermore, a long duration of signs (>1 year) does not eliminate GI lymphoma as a potential differential diagnosis, where chemotherapy would be more appropriate. All of the other therapies described below are often used prior to intestinal biopsy or in conjunction with immunomodulatory therapy after biopsy confirmation.

A dietary trial is often the first step in managing cats with suspected or confirmed IBD. Cats may improve on novel protein (elimination) diets, because these diets avoid exposure to proteins to which the cat's GI system may have previously become sensitized. Commercial "hypoallergenic" diets contain a single protein source, and are usually milk-, corn-, and wheat-free. They are highly digestible with a moderate amount of soluble fiber. A complete dietary history should be taken, so that a diet with a novel protein (for that cat) can be selected. Hydrolyzed protein diets such as Hill's z/d Ultra Allergen Free or Royal Canin Feline Hypoallergenic diet are formulated to avoid the antigenicity of intact dietary proteins. Diarrhea or lack of palatability can be an issue with some cats. The prevalence of food sensitivity in cats with idiopathic chronic GI signs was 16/55 (29%) in one large study. An additional 11/55 (20%) had signs resolve on diet change but did not reoccur on rechallenge. Although a 4-6 week dietary trial has been recommend, in the above study, cats improved within 2-3 days after a diet change. A response to dietary therapy is more likely in cats with concurrent dermatologic signs (military dermatitis, pruritis of the head and neck, alopecia). Response to a dietary trial occurred in cats who did not necessarily have a peripheral or tissue eosinophilia on biopsies. GI signs may also improve after a change in diet, even if the cat does not have a true dietary allergy (immunologic event). Non-immunologic causes of an adverse reaction to food may occur because of disaccharides (such as lactose), food additives (coloring agents), pharmacologically active products (histamine), or food toxins. Many GI diets are highly digestible diets of moderate energy density, which do not contain preservatives or coloring agents, and are given in small frequent feeding (at least 3-4 meals/day). A high-fiber diet has been recommended in cats with colitis

Probiotics are live organisms (usually bacteria but sometimes yeasts) that promote a beneficial microbial balance in the intestinal tract. Examples include Lactobacillus species, Enterococcus faecium, Bifidobacterium species, and Saccharomyces species. Potential benefits of probiotics include inhibition of intestinal colonization by pathogenic bacteria, modulation of gut flora, and inhibition ofbacterial translocation across the intestinal wall. Purina fortiflora (encapsulated E faecium strain SF68) is reported by the manufacturer to decrease fecal concentrations of clostridium perfringens and diarrhea in kittens. Probiotis may be beneficial in the treatment of IBD, but it is important that the probiotic contain viable organisms that have been shown to colonize the intestinal tract of cats.

Low serum cobalamine (B12) is a common finding in cats with GI disease. Cobalamine is required for normal enterocyte function. Low cobalamine levels can be caused by intestinal malabsorption or pancreatic disease with lack of intrinsic factor. Low cobalamine levels are associated with signs of intestinal disease; even if the underlying cause of cobalamine malabsorption is effectively treated, GI signs may not resolve until cobalamine deficiency resolves with B12 supplementation. Serum cobalamine levels should be measured in all cats with chronic small bowel diarrhea and IBD, especially if they have a low body condition score. Low serum cobalamine is treated with 250 ug SC q 7 days for 6 weeks, then q 14 days for 6 weeks, then once monthly, then as needed based on serum cobalamine levels.

Metronidazole has several potential mechanisms of action, including anti-protozoal activity, inhibition of cellular immunity, anaerobic antibacterial activity. It is commonly used, either alone or in combination with corticosteroids, in the treatment of feline IBD. A dose of 10-15 mg/kg/day has been recommended. Daily doses exceeding 60 mg/kg/day can be associated with neurotoxicity. Metronidazole is unpalatable and commonly causes inappetence in cats. Metronidazole benzoate may be better tolerated. Since it is only about 60% metronidazole by weight, a dose of 25 mg/kg/day should be given (to deliver the equivalent drug as with 15 mg/kg/day of metronidazole). Benzoate can be neurotoxic in cats, but should not be a clinical problem when used at the dose described above. It may requires 3 to 5 weeks to see effects. It is usually used in combination with corticosteroids. Sulfasalazine (Azulfidine®) is sulfapyridine plus 5-aminosalicylic acid. It is used only with colonic involvement. The dose is 10-20 mg/kg PO q 12 to 24 h for a maximum of 10 days. It should be used cautiously in cats due to cats' sensitivity to salicylates.

Immunosuppressive therapy with prednisolone is the treatment of choice for feline IBD. Although prednisone can be used, there is recent evidence that absorption or conversion of prednisone to the active form, prednisolone, is poor in cats. A dose of 1-2 mg/kg/day is recommended initially for two to four weeks. Once clinical signs improve, the dose can be tapered by 50% at 2-4 week intervals until a maintenance dose of 0.5-1.0 mg/kg is given every other day. As opposed to dogs given corticosteroids, most cats do not become polydipsic or polyuric. If these clinical signs occur while on corticosteroid therapy, a blood glucose and urine dipstick should be performed to screen for diabetes mellitus, which can be precipitated by glucocorticoid therapy. Other potential complications of corticosteroid therapy in cats include increased susceptibility to infections and precipitation of underlying heart failure due to sodium and water retention. Longterm high dose therapy can be associated with development of "Cushingoid" side effects.

Budesonide is an orally administered glucocorticoid which is believed to be associated with fewer systemic side effects because of extensive hepatic clearance after intestinal absorption. It has been used anecdotally in cats with IBD at a dose of 0.5-0.75 mg/cat/day. It comes as a 3 mg enteric-coated gelcap, which must be reformulated for administration. The degree of systemic absorption has not been determined in cats, and side effects should be monitored as for prednisolone. Other immunomodulating drugs used for refractory IBD include chlorambucil (Leukeran®) and cyclophosphamide. Chlorambucil is an alkylating agent similar to cyclosphosphamide, and is effective for cats with small cell GI lymphoma and refractory IBD. It comes as a 2 mg tablet which should not be broken. It should be kept refrigerated and protected from moisture and light. Several dosing strategies have been empirically been recommended. With pulse-dosing, chlorambucil is given once every 2-3 weeks (0.4 mg/kg PO q 2weeks or 20 mg/M2 PO q 3 weeks; or approximately 2 mg total dose q 2 or 3 weeks). Chlormabucil has also been recommended at 2 mg/cat every 48-72 hours (approximately 0.1-0.2 mg/kg). Chlorambucil appears to be well tolerated but potential side effects may include bone marrow suppression (monitor CBC), vomiting, muscle twitching, and possibly hepatotoxicity (monitor liver enzymes). Cyclosporin is an immunosuppressant that inhibitis T cell function. It has been anecdotally recommended in cats with refractory IBD at a dose of 5 mg/kg once or twice daily. Vomiting and decreased appetite are common side effects but often improve with a 50% dose reduction.

Suggested Reading: Guilford WG et al. JVIM15:7-13, 2001; Trepanier L. J Fel Med and Surg 11:32-38, 2009.