Feline inflammatory bowel disease (Proceedings)

Gastrointestinal disorders include some of the most common reasons why cats are presented for veterinary care. Diseases both within and outside of the gastrointestinal tract (GIT) affect the function of the GIT and can result in similar clinical signs. The term inflammatory bowel disease (IBD) does not indicate one specific, unique disease, but rather encompasses a variety of conditions that cause chronic inflammation within the gastrointestinal tract.

Etiology and pathogenesis

Inflammatory bowel disease is by definition an idiopathic disorder. Most likely, IBD encompasses a group of diseases which have similar clinical signs. IBD is classified by the region of the gastrointestinal tract (GIT) affected and by the predominant inflammatory cell type. Lymphocytic-plasmacytic inflammation is most commonly found, followed by eosinophilic inflammation. IBD is believed to be immune-mediated in origin. The normal intestinal mucosa is supposed to serve as a barrier and control exposure of antigens to the GI lymphoid tissue (GALT). The function of GALT is to generate appropriate, protective immune responses against pathogens while remaining tolerant of harmless antigens such as commensal bacteria and food. IBD develops when there is a break-down in this process and inappropriate immune responses occur.

Clinical presentation

The clinical signs for cats with IBD reflect the portion of the GIT that is involved. Gastric involvement may accompany small intestinal disease in IBD but does not occur as a sole site of disease. Patients with small intestinal disease often present for inappetance, weight loss, vomiting, and diarrhea. Because cats are so good at conserving water, it may be difficult for owners to notice small bowel diarrhea. Small bowel diarrhea is characterized by large volumes with only a minimal increase in frequency of defecation. In contrast, large bowel diarrhea is characterized by frequent defecations of small amounts. Large bowel diarrhea often contains mucous and frank blood. Some patients will have involvement of both the small and large intestine with clinical signs referable to both components of the GIT. Typically in those cats, large bowel diarrhea will predominant in terms of fecal quality but the cat will also lose weight and vomit. Regardless of whether it is small or large intestine involvement, there are not any clinical signs which are pathognomonic for inflammatory bowel disease.

No gender predispositions have been documented for inflammatory bowel disease in cats. It is typically diagnosed in middle-aged cats but can be seen in any age. Siamese cats may be predisposed to develop lymphocytic-plasmacytic enteritis.

Physical examination findings are more likely to be abnormal in cats with small intestinal involvement. Affected cats may be thin or have an appreciable loss of muscle mass. Thickened, "ropey" bowel loops are often appreciated during abdominal palpation. This finding is both non-specific and subjective.

Diagnosis

Minimum database Perhaps the most important step in diagnosing inflammatory bowel disease is ruling out other causes of diarrhea, weight loss and vomiting. Retroviral testing should be performed on all cats for whom viral status is not known. A minimum database consisting of a CBC, chemistry profile, T4 and urinalysis will be very helpful in ruling out other causes of gastrointestinal signs such diabetes mellitus, hyperthyroidism, liver disease, etc. CBC findings are usually non-specific in IBD. A mature neutrophilia may be present. Eosinophilia is rarely found but may accompany eosinophilic disorders (eosinophilic IBD, hypereosinophilic disease) and parasitism. Hypoalbuminemia is consistent with small intestinal disease but may be seen with liver disease and renal losses. A concurrent hypoglobulinemia is suggestive of GI disease. Increased liver enzymes are less likely to accompany feline IBD than canine given the shorter half-life in the cat. However, some cats may have a reactive hepatopathy and have mild increases in liver enzymes. If increased liver enzymes are documented in a cat with IBD, this is suggestive of "triaditis" wherein there is concurrent IBD, hepatitis and pancreatitis.

Fecal examination Fecal examination should be performed to rule out parasitism. Fecal floatation using zinc sulphate is recommended to rule out Giardia. Alternatively, ELISA testing can be performed to rule out Giardia. A fecal smear should be examined for coccidia and tritrichomonas foetus. Protozoal culture and PCR can also be performed to look for t. foetus. Indoor only adult cats that have not been exposed to other animals rarely suffer from parasites.

Cobalamin and Folate Additional diagnostic testing may include cobalamin and folate levels. Cobalamin is a water-soluble vitamin that acts as a co-factor for many different enzymatic reactions. Cobalamin actually refers to a group of substances containing a cobalt atom, all of which are exclusively derived from bacterial sources. Because it is absorbed in the small intestine, cobalamin deficiency can be seen with a variety of different gastrointestinal disorders. Cobalamin supplementation aids in optimal treatment of IBD in cases where deficiency has been documented. Folate is also absorbed in the proximal small intestine. Values below the reference range are seen with diseases affecting the proximal small intestine whereas values above the reference range are found with small intestinal bacterial overgrowth (SIBO).

Diagnostic Imaging Diagnostic imaging is usually performed in the work-up of a cat with IBD. Plain radiographs yield little information regarding IBD. Intestinal thickness cannot adequately be determined on radiographs. Ultrasound is much more useful in the workup of IBD. The intestines can be examined for segmental versus diffuse disease which is important in determining how to best obtain biopsies. If segmental and/or only distal small intestinal disease is found, surgical exploratory may be the preferred route for obtaining biopsies. Additional information obtained from ultrasound includes overall wall thickness and whether normal wall layering is present. Excessively thickened walls and/or the loss of normal layering is more suggestive of lymphoma. Mesenteric lymphadenopathy may also be noted on abdominal ultrasound. Mild lymphadenopathy can be seen as a reactive change with IBD; more severe lymphadenopathy is suggestive of lymphoma. If lymphadenopathy is present, fine needle aspirates should be obtained for cytological examination. Cytology can confirm the presence of lymphoma but it cannot definitively rule out lymphoma.

Histopathology In order to definitively diagnose IBD, a biopsy sample is required. In most cases, endoscopy is the preferred route for obtaining biopsies. Endoscopy allows visualization of the mucosa and is minimally invasive. Changes that may be seen upon endoscopic examination of the cat with IBD include a "cobble-stone" appearance, mucosal irregularity and friable tissue. Changes are not pathognomonic for IBD and the severity of the changes seen upon endoscopic examination do not correlate with histopathologic diagnosis (IBD can often look worse than lymphoma!). The quality of samples obtained via endoscopy varies tremendously and greatly influences the pathologist's ability to render an accurate diagnosis. It is crucial to obtain adequate biopsies, both in terms of tissue obtained and number. A minimum of 6-7 biopsies should be obtained from each site examined. Additionally, crush artifact needs to be avoided. Full thickness biopsies, as obtained by either laparoscopy or exploratory may be optimal. Discordant reults have been documented between partial and full-thickness biopsies. A 2010 ACVIM abstract reported 2/11 cats had lymphoma diagnosed via full-thickness biopsy that was called IBD based on an endoscopic biopsy obtained at the same time (the other 9 cases had the same diagnosis reached).

Treatment

Treatment for IBD is multi-factorial and components of treatment are typically instituted prior to a diagnosis of IBD being made. Empiric deworming with fenbendazole 50 mg/kg PO q24h x days and/or antibacterial therapy with metronidazole 10 mg/kg PO q12h is often instituted based upon the clinical sign of diarrhea, prior to obtaining biopsy samples. Metronidazole is preferred as an antibiotic for suspected IBD because it is suspected to possess immunomodulatory properties.

Diet

While dietary therapy is an important aspect of treating IBD, there are a variety of different ways in which the diet may be modified, consistent with the notion that IBD actually encompasses a group of disorders. Dietary therapy for feline IBD may focus on 1. Digestibility 2. Fiber content or 3. Novel antigen/exclusion diets. Highly digestible diets minimize the amount of substrate available to intestinal bacteria and minimize the amount of undigested protein reaching the colon. Large amounts of undigested protein results in an increase in the biomass of GI bacteria and more water being secreted into the feces, the combination of which results in poor quality feces and diarrhea. Highly digestible diets are typically low in soluble fiber. Some examples include Purina EN, Royal Canin Intestinal HE, Science diet I/D.

For some cats with colitis, increasing the amount of insoluble fiber in the diet is beneficial. Insoluble fiber may be helpful because it increases the bulk of the feces. The increase bulk creates a stretch response in the colon which may stimulate motility. Purina OM, Science diet W/D, Royal Canin Calorie Control CC High Fiber are examples of high fiber diets. If owners do not wish to purchase prescription pet foods, typically diets formulated for weight loss and geriatric cats are higher in fiber.

Many cats with either presumed or diagnosed IBD respond very well to novel antigen/hydrolyzed protein diets. It is difficult to ascertain the true prevalence of food allergy but studies suggest that approximately one-quarter of cats with IBD suffer from a food allergy. For suspected food allergy, dietary therapy centers on either a novel protein source (ie a protein source the pet has not consumed before) or a hydrolyzed protein. Hydrolyzed proteins are low-molecular weight proteins. They are created from either soy or chicken protein which then undergoes a chemical or enzymatic treatment, rendering the protein less antigenic. Both novel proteins and hydrolyzed proteins tend to be highly digestible. As commercial food manufacturers incorporate more "exotic" proteins into over-the-counter diets, it may become harder to find novel protein sources.

Regardless of the aspect of the diet that is modified, the most crucial aspect of a diet for a cat is that the cat eats it! Owners should be instructed to not to try to starve their cat into eating a diet that he/she does not find palatable. The new diet should be slowly introduced, over the period of a week. Food trials may take 8-12 weeks to show a beneficial response. It is crucial that the cat eats only the prescribed diet during the food trial.

Immunosuppressive therapy

For cats who do not respond to dietary therapy, immunosuppressive therapy is necessary. It is strongly preferred to have obtained biopsies of the GIT prior to instituting immunosuppressive therapy because such treatment will potentially alter future biopsy results. Prior treatment with steroids may not only create inaccurate histopathologic results which can then limit treatment choices, but it can also lead to multi-drug resistance. The mainstay of immunosuppressive therapy in the cat for IBD is prednis(ol)one 1 mg/kg PO bid. For diabetics and other cats who have difficulties with systemic corticosteroids, budesonide may be a reasonable option. Budesonide is a glucocorticoid with high first-pass metabolism. Budesonide is enterically coated which prevents dissolution until it reaches the duodenum. Budesonide exerts topical anti-inflammatory effects in the small intestine and has minimal systemic effects.

In cats with an inadequate response to corticosteroids, additional medications can be added. Chlorambucil (Leukeran) is a nitrogen mustard derivative that is often used in conjunction with steroids. For cats weighing over 4 kg, chlorambucil is initiated at a dose of 2 mg/cat PO every other day; in cats weighing < 4 kg, the dose is 2 mg every third day. Chlorambucil can cause myelosuppression so frequent monitoring of the CBC is recommended.

Cyclosporine has also gained popularity in the treatment of feline IBD. While evidence supporting its use is primarily anecdotal, cyclosporine appears to have a place in the treatment of feline IBD. The appearance of a product formulated for veterinary use has made cyclosporine easier to administer to cats because there are less concerns over achieving appropriate serum levels and which formulation to use. The typical dose is 5 mg/kg PO bid.

Lymphoma

One of the greatest challenges in diagnosing and treating IBD in cats is in distinguishing it from small cell lymphoma. Small cell lymphoma (LSA), also known as low-grade LSA, is the most common form of GI LSA in the cat and comprises 75% of the cases of feline GI LSA. Differentiating between the two conditions can be challenging for pathologists. The clinical signs for cats with small cell LSA are the same as for IBD. Usual history involves chronic weight loss and diarrhea. Physical examination often reveals ropey intestines. Cats with small cell LSA typically test negative for FeLV. While usually confined to the GIT, small cell LSA in cats can be diffuse or focal. Rarely, cats may present for obstruction secondary to a focal mass lesion. Imaging findings are similar to IBD although lymphadenopathy may be more pronounced. It is very difficult, if not impossible, for pathologists to diagnose small cell LSA on cytology. Small cell LSA by definition is an infiltration with mature, well-differentiated lymphocytes; the lymphocytes do not appear malignant. Histopathology is necessary to differentiate between IBD and small-cell LSA and may not always be able to discriminate between the two entities. Unlike their canine counterparts, cats with GI LSA have a very good prognosis. Chemotherapy is the treatment of choice for diffuse disease. Treatment with prednisone and chlorambucil has been shown to be very effective and has the advantage of being oral, thus owners can administer it at home. A median survival time of 18-24 months has been found using these prednisone in combination with chlorambucil. Cats who achieve a complete remission with therapy have a better prognosis than those who achieve only a partial remission. Response is not necessarily immediate however and may require a few administrations of chemotherapy to be fully noted.