The inflammatory bowel diseases (IBDs) are the most common causes of chronic vomiting and diarrhoea in dogs and cats, and refer to a group of poorly understood enteropathies characterised by the infiltration of the gastrointestinal mucosa by inflammatory cells. The cellular infiltrate is composed of variable populations of lymphocytes, or combinations of these cells. Changes in the mucosal architecture characterised by villous atrophy, fusion, fibrosis and lacteal dilation frequently accompany the cellular infiltrates.

Aetiology of IBD

Although the aetiology of canine and feline IBD is poorly understood, there is provocative evidence from clinical observations and animal models to incriminate normal luminal bacteria or bacterial products in the initiation and perpetuation of canine and feline IBD. Evidence of the role of enteric microflora in the pathogenesis of IBD in people is supported by clinical responses to faecal stream diversion treatment in patients with Crohn's disease (CD) and antimicrobial therapy in CD and ulcerative colitis (UC) patients. Additionally, there are increases in circulating and intraluminal humoral and T-cell responses to the enteric microflora in human IBD patients. Furthermore, genetic mutations in NOD2/CARD15 and TLR-4 in IBD patients make them less able to detect bacterial components, resulting in defective responses to enteric microflora. Studying the composition of the intestinal microflora has been a challenge to researchers; however, recent work has focused closely on the bacteria associated with the mucosal lining. A study of adherent mucosal bacteria in IBD patients concluded that Bacteroides fragilis comprised >60% of the biofilm mass in patients with IBD. Dietary factors also appear to play a role in the aetiopathogenesis of IBD in dogs and cats based on the clinical response to 'hypoallergenic' diets in many of these animals.

Diagnosis of IBD

The diagnosis of IBD is based on the exclusion of known causes of diarrhoea, vomiting and weight loss, followed by histological confirmation of infiltration of the gastrointestinal mucosa by inflammatory cells and changes in mucosal architecture. The standard work-up for a dog or cat suspected of IBD should include a detailed and accurate history and comprehensive physical examination, followed by a minimum database consisting of a centrifugation faecal flotation and direct wet preparation, complete blood count (CBC), chemistry panel and urinalysis. Abdominal ultrasonography is a valuable diagnostic tool for evaluating the gastric and intestinal wall for alterations in thickness, alterations in the layering pattern (particularly the mucosa and muscularis layers), assessing changes in mesenteric lymph node size and echo texture, and assessing the ultrasonographic appearance of the liver, pancreas and adrenal glands. Measurement of serum trypsin-like immunoreactivity (TLI) is warranted in animals suspected of exocrine pancreatic insufficiency. Measurement of serum B12 (cobalamin) and folate is commonly performed by veterinary surgeons to evaluate the absorptive capacity of the ileum and jejunum, respectively, and to detect abnormal changes in the intestinal microflora. The limited diagnostic utility of measurement of serum folate and cobalamin concentrations for diagnosing small intestinal bacterial overgrowth (SIBO) has been documented by German et al. Additional diagnostic tests that should be performed on a case-based nature include the measurement of serum thyroxin concentration; feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) serology; faecal culture for Tritrichomonas foetus; faecal direct fluorescent antibody test or enzyme-linked immunosorbent assay (ELISA) for Giardia and/or Cryptosporidium spp., and a faecal enteric panel for enteropathogenic bacteria.

Endoscopy is a valuable procedure for the diagnosis of intestinal mucosal disorders such as IBD that are associated with morphological changes; however, endoscopy is limited by the working length of the scope, precluding endoscopic examination of the jejunum. Regardless of the method used to procure intestinal biopsy specimens (endoscopy, laparotomy, laparoscopy), the interobserver variation among histopathological evaluations of intestinal tissues from dogs and cats is unacceptably high. With the support of the WSAVA, the Gastrointestinal Standardization Group has proposed to develop a standardised histological evaluation system that will be applied to all companion animal gastroenterological disorders.

Management of IBD

Nutritional Management

 Elimination/novel protein diets. Antigenic determinants on proteins are incriminated in many cases of IBD, implying that the feeding of select protein diets containing a single, highly digestible, novel protein source might be beneficial for managing dogs and cats with IBD.

 Hypoallergenic diets. The ability to induce an antibody-mediated hypersensitivity response appears to be dependent upon the size and structure of the protein. The allergens in soybean protein, for example, are between 20 and 78 kilodaltons, suggesting that soybean proteins with a molecular weight below this threshold would be less likely to illicit an immune-mediated response. Hypoallergenic diets are particularly beneficial as elimination diets for the diagnosis and management of food hypersensitivity, when a patient appears to be allergic to multiple allergens, when a complicated dietary history makes it difficult to identify a 'novel' protein, or when a patient has severe IBD.

 Dietary fibre. The gelling and binding properties of fatty acids and deconjugated bile acids in soluble fibres may be beneficial in certain gastrointestinal diseases. The use of soluble (fermentable) fibre in preference to insoluble (non-fermentable) fibre is generally advocated because most soluble fibres generate butyrate, the principle source of energy for the colonocyte, and other short-chain fatty acids. Short-chain fatty acids may lower the colonic luminal pH, impeding the growth of pathogens. The health benefits derived from dietary supplementation of prebiotics have been documented in humans and feeding oligofructose to dogs decreased the concentrations of faecal ammonia and amines and increased the numbers of bifidobacteria in dog faeces.

 Polyunsaturated fatty acids. Fish oil has been reported to be beneficial in ulcerative colitis and Crohn's disease patients, but the results are controversial. Only a few studies found significant decreases in rectal leukotriene B4 concentrations; the others simply reported clinical improvement. There are no published studies in the veterinary literature to date demonstrating the efficacy of omega-3 fatty acid supplementation in managing canine or feline patients with IBD.

 Fat. Avoiding excessive fat can be instrumental in the management of various gastrointestinal diseases because fat delays gastric emptying in dogs and high-fat foods may contribute to osmotic diarrhoea. Malabsorbed fatty acids are hydroxylated by intestinal bacteria and stimulate colonic water secretion, exacerbating diarrhoea as well as gastrointestinal protein and fluid losses.

 Vitamins and minerals. Water-soluble vitamins are often depleted by the fluid losses associated with diarrhoea and fat-soluble vitamin loss can be significant in animals with steatorrhoea. Magnesium deficiency has been well documented in Yorkshire Terriers with severe inflammatory bowel disease and lymphangiectasia. Cats with severe IBD frequently have subnormal serum cobalamin concentrations.

Pharmacological Management

Most dogs and cats with moderate to severe IBD will require adjuvant pharmacological therapy in combination with dietary management. It is important to understand that the therapy of IBD must be tailored according to each patient's response.

 Oral corticosteroids. Corticosteroids remain the cornerstone of medical therapy for IBD, despite the lack of published controlled clinical trials documenting their benefit in dogs and cats with IBD. The value of corticosteroids relates to their antiinflammatory and immunosuppressive properties, although they also increase intestinal sodium and water absorption in the small and large bowel, and regulate basal colonic electrolyte transport. The dosage and duration of therapy is based on the severity and duration of clinical signs, the severity and type of inflammation, the clinical response and tolerance to the drug. The initial dosage of prednisone for therapy of IBD in dogs is 1-2 mg/kg q12h. Most cats are started at a dose of 5 mg per cat q12h. The drug is gradually tapered over a 6-10-week period once clinical remission is attained. Combination therapy with dietary therapy, azathioprine or metronidazole is undertaken with the goal of reducing the dose of prednisone. Parenteral corticosteroid therapy is reserved for vomiting patients, or animals with severe non-responsive disease. Budesonide, an orally administered corticosteroid structurally related to 16-hydroxyprednisolone, has high topical antiinflammatory activity and low systemic activity because of its high affinity to the steroid receptor and rapid hepatic conversion to metabolites with minimal or no steroid activity. The drug is dosed at 1 mg once daily for cats and toy-breed dogs, up to a maximum dose of 3 mg q12h for a large or giant-breed dog.

 Azathioprine. This is an antimetabolite that is converted to 6-mercaptopurine in the liver and then to thioinosinic acid. The latter compound impairs purine biosynthesis and this biochemical reaction inhibits cellular proliferation and reduces natural killer cell cytotoxicity. The onset of these immunological effects is slow, and can require several months for maximal effectiveness. The drug is most useful in dogs as adjunctive therapy in severe or refractory IBD. Azathioprine can also be used for its steroid-sparing effects when the adverse effects of prednisone are unacceptably high. The dose for dogs is 50 mg/m2 or 1-2 mg/kg once daily for 2 weeks, followed by alternate-day administration, whereas cats should receive 0.3 mg/kg q48h. The most significant side effect of azathioprine is bone marrow suppression, particularly in cats. Other side effects include anorexia, pancreatitis and hepatic dysfunction.

 Chlorambucil. The alkylating agent chlorambucil is beneficial for managing refractory cases of IBD, particularly in cats. Haematological monitoring is warranted every 3-4 weeks to assess for neutropenia. Chlorambucil can be administered at 15 mg/m2 orally once per day for 4 consecutive days, and repeated every 3 weeks (in combination with prednisone) or administered at 2 mg per cat every 4 days indefinitely. In dogs chlorambucil is administered at 1.5 mg/m2 every other day.

 Ciclosporin. This has been demonstrated to be effective in dogs with IBD that were refractory to immunosuppressive doses of prednisone. The dose of ciclosporin used was 5 mg/kg q24h and the drug was well tolerated.

 Sulfasalazine. The drug consists of sulfapyridine linked to mesalamine (previously called 5-aminosalicylic acid) by an azo bond that is cleaved by colonic bacteria with subsequent release of the active moiety of the drug, mesalamine. Sulfapyridine is almost completely absorbed in the colon, metabolised in the liver and excreted in the urine. The mesalamine moiety is locally absorbed and inhibits the formation and degradation of inflammatory mediators, including leukotrienes, prostaglandins, thromboxane and platelet-activating factor, histamine and a number of cytokines. Sulfasalazine is of no value in managing small bowel inflammation because colonic bacterial metabolism is needed to release the active moiety. The usual initial dose in dogs is 20-40 mg/kg q8h for 3 weeks, followed by 20-40 mg/kg q12h for 3 weeks, and 10-20 mg/kg q12h for 3 weeks. The drug should be used with caution and at a lower dose (10-20 mg/kg q24h) in cats because of the salicylate portion of the drug. The most common side effects of sulfasalazine include anorexia, vomiting, cholestatic jaundice, allergic dermatitis and keratoconjunctivitis sicca (KCS).

 Antimicrobials:

 Metronidazole, an inhibitor of cell-mediated immunity, has been frequently used as an adjunctive agent for the management of IBD. The dose of metronidazole is 10-15 mg/kg q8-12h. Metronidazole tablets have a sharp, unpleasant, metallic taste when scored that can cause severe salivation. Side effects are rare, although metronidazole has been associated with a peripheral neuropathy in humans and animals. Less common side effects include inappetence, nausea, vomiting, seizures and reversible neutropenia.

 Tylosin is a macrolide antibiotic that has been reported to be effective and safe in managing canine IBD and antibiotic-responsive diarrhoea (ARD). Although the drug's mechanism of action is unknown, it appears to be effective in some dogs refractory to other forms of therapy. The dose range is 20-40 mg/kg q12h.

References

1.  Allenspach K, Rüfenacht S, et al. Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroid-refractory inflammatory bowel disease. Journal of Veterinary Internal Medicine 2006; 20(2): 239-244.

2.  German AJ, Day MJ, et al. Comparison of direct and indirect tests for small intestinal bacterial overgrowth and antibiotic-responsive diarrhoea in dogs. Journal of Veterinary Internal Medicine 2003; 17(1): 33-43.

3.  Guilford WG, Jones BR, et al. Food sensitivity in cats with chronic idiopathic gastrointestinal problems. Journal of Veterinary Internal Medicine 2001; 15: 7-13.

4.  Westermarck E, Skrzypczak T, et al. Tylosin-responsive chronic diarrhea in dogs. Journal of Veterinary Internal Medicine 2005; 19(2): 177-186.