Inflammatory Bowel Disease - The Merck Veterinary Manual

Inflammatory Bowel Disease

Idiopathic inflammatory bowel disease (IBD) constitutes a group of GI diseases characterized by persistent clinical signs and by histologic evidence of inflammatory cell infiltrate of unknown etiology. The various forms of IBD are classified by anatomic location and the predominant cell type involved. Included in this group are lymphocytic-plasmacytic enteritis of cats (the most common form of IBD in cats), chronic lymphocytic-plasmacytic colitis of dogs, eosinophilic gastroenteritis and colitis, granulomas, histiocytic colitis, granulomatous enteritis (rare) and colitis, transmural granulomatous enterocolitis, suppurative colitis, and the diarrheal syndromes of the Basenji and Lundehund. German Shepherds may be predisposed to lymphocytic-plasmacytic enteritis.

Etiology and Pathophysiology:

The etiology of IBD is unknown. Suspected factors include defective immunoregulation of gut-associated lymphoid tissue (GALT); permeability defects; genetic, ischemic, biochemical, and psychosomatic disorders; infectious and parasitic agents; dietary allergens; and adverse drug reactions. Defective immunoregulation of GALT results in exposure and adverse reaction to antigens that normally would not evoke such a response. Although dietary allergy is an unlikely cause of IBD (except in eosinophilic gastroenteritis), it may contribute to increased mucosal permeability and food sensitivity.

Current evidence supports the likely involvement of hypersensitivity reactions to antigens (eg, food, bacteria, mucus, epithelial cells) in the intestinal lumen or mucosa. More than one type of hypersensitivity reaction is involved in IBD. For example, type I hypersensitivity is involved in eosinophilic gastroenteritis, whereas type IV hypersensitivity is likely involved in granulomatous enteritis. The hypersensitivity reaction incites the involvement of inflammatory cells that results in mucosal inflammation. Inflammation impairs the mucosal barrier, facilitating increased intestinal permeability to additional antigens. Persistent inflammation results in fibrosis.

Clinical Findings:

There is no apparent age, sex, or breed predisposition associated with IBD. However, it may be more common in German Shepherds, Yorkshire Terriers, Cocker Spaniels, and purebred cats. The mean age reported for the development of clinical disease is 6.3 yr in dogs and 6.9 yr in cats, but IBD has been documented in dogs <2 yr old. Clinical signs are often chronic and sometimes cyclic or intermittent. Vomiting, diarrhea, changes in appetite, and weight loss may be seen. In a retrospective study of cats with lymphocytic-plasmacytic enterocolitis, weight loss, intermittent vomiting progressing to more frequent vomiting on a daily basis, diarrhea, and anorexia were seen most often. Vomiting, melena, and cranial abdominal pain are often seen with gastroduodenal ulceration and erosion. When erosion or ulceration does occur, it is seen most often in the areas that do not produce acid (ie, the fundus, antrum, and pylorus). The duodenum has also been implicated as a frequent site for this problem. Clinical signs of large-intestinal diarrhea, including anorexia and watery diarrhea, are not uncommon.

An association between gastric dilatation-volvulus ( Gastric Dilatation-volvulus) and IBD in dogs has also been postulated. In this case, inflammation of the bowel may cause alterations in gastric motility and emptying and in GI transit time, thus predisposing to dilatation-volvulus.

An association between inflammatory hepatic disease, pancreatitis, and IBD has been reported in cats, although an etiology for this triad of diseases has not been established. However, cats with cholangiohepatitis should also be evaluated for IBD and pancreatitis. Although as yet unproved, it has been suggested that severe IBD in cats may progress to lymphosarcoma.

Diagnosis:

Thickened intestinal loops may be palpated in >50% of cats with lymphocytic-plasmacytic enterocolitis; 50% of affected cats are thin or cachectic in appearance. Diagnosis requires intestinal mucosal biopsy.

There are no consistent abnormalities on CBC, biochemical evaluations, or radiographs. Erythrocytosis associated with fluid loss from vomiting and diarrhea and a stress leukogram may be seen. Thrombocytopenia has been observed in dogs with IBD. It may resolve in some dogs with successful management of the disease. The degree of thrombocytopenia does not correlate with the severity of the intestinal lesions, nor does it lead to clinical evidence of bleeding. Histologic infiltrates with eosinophils may be found in some dogs and cats with absolute eosinophilia. Nonresponsive anemia, if present, likely reflects anemia of chronic or inflammatory disease.

Hypoproteinemia due to reduced dietary intake and malabsorption or increased loss via the GI tract, may be seen. Increases in serum amylase as a consequence of inflammation of the bowel is also reported. Hypokalemia secondary to anorexia, potassium loss from vomiting and diarrhea, and low serum levels of folate and cobalamin are also documented. Additionally, mild increases in serum levels of liver enzymes can be expected. Hypocholesterolemia was reported to be the most common biochemical abnormality noted in one study of cats with the disease and was attributed to malabsorption.

Radiographic changes may include gas or fluid distention of the stomach and increased total diameter of small-intestinal loops. Contrast films may show diffuse or focal mucosal irregularities suggestive of infiltrative disease. Abdominal ultrasound may reveal thickened intestinal walls.

Gross mucosal lesions seen endoscopically may be evident in ~50% of cases and may include erythema, friability, enhanced granularity, erosion, and ulceration. In one report, 28% of cats had endoscopic evidence of disease of the stomach and 50% of the duodenum. In many cases, the endoscopic appearance is normal. Even in the absence of gross changes, biopsy samples should always be taken. Small populations of lymphocytes, plasma cells, macrophages, eosinophils, and neutrophils are normal components of intestinal mucosal tissue. Increased numbers of plasma cells, lymphocytes, eosinophils, and neutrophils in the lamina propria are seen in IBD. However, these morphologic features may also be seen with other causes of GI disease (eg, Giardia , Campylobacter , Salmonella , lymphangiectasia, and lymphosarcoma). The interpretation of histologic specimens of intestinal tissues from dogs and cats appears to vary substantially among pathologists. A histologic diagnosis of intestinal pathology may be made in a clinically normal dog, normal intestinal mucosa may be reported from dogs dying of intestinal disease, and tissue samples from clinically normal dogs have been described as having neoplastic infiltrates. Biopsy must always be considered in relation to clinical signs, and the animal treated accordingly.

Treatment and Control:

The goals of therapy are to reduce diarrhea, promote weight gain, and decrease intestinal inflammation. If a cause can be identified (eg, dietary, parasitic, bacterial overgrowth, drug reaction, etc), it should be eliminated. Dietary manipulation by itself may be effective in some cases (eg, in chronic colitis); in other cases, it can enhance the efficacy of concurrent medical therapy allowing for the drug dosage to be reduced or for drug therapy to be discontinued once clinical signs are in remission. Corticosteroids, azathioprine, sulfasalazine, tylosin, and metronidazole are among the drugs most often used in the management of IBD.

Dietary modification generally involves feeding a hypoallergenic or elimination diet, ie, feeding a source of protein that the animal has not been previously exposed to such as homemade diets of lamb and rice or venison and rice or commercial diets. This diet should be the sole source of food for a minimum of 4-6 wk, and no treats of any kind should be fed. Novel protein diets alone are effective in controlling clinical signs in cats with IBD, but not in cats with food sensitivity or food allergy. Dogs with large-intestinal diarrhea may benefit from diets high in insoluble fiber content. Supplementation of dietary fiber alone is rarely effective in cases with severe inflammatory cell infiltrate.

Corticosteroids may be useful for small- as well as large-intestinal disease. Initial dosages recommended are 2.2 mg/kg/day for prednisone or prednisolone and 0.22 mg/kg/day for dexamethasone. Budesonide (dogs: 2 mg/dog/day, PO; cats: 1 mg/cat/day, PO) has a high topical glucocorticoid activity and a substantial first-pass elimination. The drug is rapidly inactivated in the liver, resulting in lower systemic bioavailablility and reduced effects on the hypothalamic-pituitary-adrenal axis, making iatrogenic hyperadrenocorticism less common. In cats with mild to moderate IBD or relapse of clinical signs, and in those in which administration of oral medication is difficult, methylprednisolone at a dose of 20 mg, SC or IM, every 2 wk for 2-3 doses, then every 2-4 wk, may be effective as the sole treatment or as an adjunct to prednisone and metronidazole. Dosages should be gradually reduced every 7-10 days to the lowest possible dose required to control clinical signs and, if possible, discontinued altogether. Animals in which this is not possible should be closely monitored for adverse effects associated with longterm or high-dose corticosteroid therapy. Prednisone alone or in combination with another drug is effective in controlling clinical signs in most cats with lymphocytic-plasmacytic enterocolitis. When combination therapy is indicated in cats, prednisone is often combined with metronidazole.

Azathioprine is commonly used in the management of IBD in dogs and cats. However, because of the potential adverse effects (eg, hepatotoxicity, myelosuppression, pancreatitis), it should be used only in cases refractory to dietary manipulation and corticosteroid therapy. Recommended dosages of azathioprine are 2.2 mg/kg, PO, sid, for dogs, and 0.3 mg/kg, every other day, PO, for cats. Cats are especially prone to bone marrow toxicity, and the dosage is decreased accordingly. Clinical signs typically improve in 3-5 wk. A CBC should be completed at 2-wk intervals to monitor for evidence of myelosuppression.

Sulfasalazine is used in the management of colitis in dogs. In the colon, this drug is split to release 5-aminosalicylic acid, which exerts its anti-inflammatory activity in the mucosa. The principal adverse effects noted in dogs are keratoconjunctivitis sicca and vasculitis. A dosage of 3-4.5 mg/kg, bid-tid for 7-10 days, is recommended in cats. Other newer aminosalicylic drugs without some of the adverse effects of sulfasalazine are available, eg, olsalazine (10-20 mg/kg, PO, tid in dogs) and mesalamine (10 mg/kg, PO, tid in dogs).

Metronidazole (10-20 mg/kg, PO, bid-tid) is also commonly used for the treatment of IBD in dogs and cats. Management for gastric ulcer or erosion may include misoprostol, omeprazole, cimetidine or ranitidine, or sucralfate. Cyclosporine has been recommended in people with severe, unresponsive IBD.

Ursodeoxycholic acid (10-15 mg/kg/day, PO), an agent used to treat chronic inflammatory cholestatic liver disease, primary biliary cirrhosis, chronic persistent hepatitis, cirrhosis, and biliary atresia, promotes biliary flow, has anti-inflammatory properties and may also have a role in reducing inflammation associated with IBD in cats.

The prognosis for feline IBD is good for adequate control but poor for cure. It has been reported that 79% of cats with IBD treated with a combination of diet and prednisone had a positive clinical response. A more guarded prognosis is reported in cases with severe histologic lesions, mucosal fibrosis, eosinophilic enteritis, or hypereosinophilic syndrome. Relapses occur and are most often precipitated by dietary indiscretion.