Diarrhea is generally regarded as the most consistent clinical sign of intestinal disease in the cat, and one of the most frustrating maladies for many veterinarians to diagnose and manage. Incomplete resolution of the problem can result in frustration and dissatisfaction for the owner and potential suffering for the animal. Antibiotics are commonly administered injudiciously to diarrheic animals, with resolution of clinical signs often wrongly equated with eradication of a "putative" infectious pathogen. Chronic diarrhea is characterized by persistent or relapsing diarrhea of 3–4 weeks duration or longer. In contrast to acute diarrhea that is often a self-limiting problem and does not typically require a comprehensive work-up of the animal, chronic diarrhea cases warrant a step-by-step approach to obtain a diagnosis and formulate an optimal therapeutic plan. The history and physical examination are paramount for determining whether the diarrhea is due to primary disease of the gastrointestinal tract or secondary to extraintestinal diseases, such as hyperthyroidism (Table 1).

Diagnostic Approach

History

The history can indicate the location, severity, and probable cause of the disease process. The categorization of diarrhea into "small bowel" or "large bowel" in origin is helpful for prioritizing certain differentials (Table 1) and for determining which segment of bowel to biopsy if warranted. Caution should be heeded in the oversimplistic anatomical differentiation of the affected segment of bowel, because animals manifesting clinical signs of colitis often have concurrent disease in the small bowel and vice versa. In addition, most veterinary gastroenterologists prefer to biopsy the small and large intestine, whenever feasible, to maximize the diagnostic yield of the procedure. A careful history should also indicate the presence of extraintestinal disease as the underlying cause of diarrhea and may identify important predisposing factors, such as diet, environmental influences, exposure to parasites, infectious agents, drugs or toxins. The failure to consider the role of the diet or dietary supplements in precipitating or alleviating the gastrointestinal disorder can result in delayed diagnosis or improper dietary recommendations for the animal. The history should also focus on the duration of the diarrhea, the appearance of the feces (color, volume, mucus, presence of fresh blood), worming and vaccination history, defecation frequency, aggravating or alleviating factors, and defecation urgency.

Table 1. Common differential diagnoses for chronic diarrhea in the cat

Primary gastrointestinal disorders

 Inflammatory bowel disease (SI, LI)

 Infiltrative neoplasia (SI, LI), (lymphoma, mast cell tumor)

 Endoparasites (SI, LI) (helminths, Giardia, Tritrichomonas foetus, Isospora, Cryptosporidium)

 Food-responsive enteropathy (SI, LI)

 Bacterial, viral, and fungal enteropathogens (SI, LI) (Campylobacter spp., Salmonella, Histoplasma, FeLV or FIV-associated enteritis)

 Intestinal obstruction secondary to strictures, intussusception (SI, LI)

 Ileus (SI)

Extra-gastrointestinal disorders

 Hyperthyroidism (SI)

 Pancreatitis (SI, LI)

 Exocrine pancreatic insufficiency (SI)

 Pancreatic neoplasia (SI)

 Liver failure (SI) (uncommon cause of diarrhea)

 Uremia (SI)

Key: SI = small intestine; LI = large intestine

Physical Examination

The physical examination should emphasize the detection of fever, cachexia, dehydration, weakness or lethargy, pallor (blood loss anemia) and effusions or edema (hypoalbuminemia). Careful palpation of the cervical region for a thyroid slip is warranted, particularly in cats > 5 years old. Intestinal loops should be carefully palpated for masses [large cell lymphoma, mast cell tumors, gastrointestinal stromal tumors (GIST), leiomyosarcomas, FIP, foreign bodies, etc.], diffuse intestinal thickening (IBD or small cell lymphoma), distension, pain, or associated lymphadenomegaly. The liver should be carefully palpated, as hepatomegaly could reflect hepatic lipidosis, lymphoma, mast cell tumor, or another neoplastic process. A rectal examination is not typically performed in awake cats, but can be done using one's little finger if the cat is sedated or anesthetized.

Table 2. Diagnostic approach to cats with chronic enteropathies

Detailed and accurate history, including comprehensive dietary history
Physical examination

Minimum data base

 CBC

 Chemistry panel

 Urinalysis

 T4 (cats > 5 years)

 Fecal centrifugation flotation and direct wet-prep

Additional fecal tests that may be warranted

 Fecal Giardia ELISA or IFA test for Giardia and Cryptosporidium
(Fecal ELISA testing for Giardia should only be used as a screening test to diagnose infection prior to anthelminthic therapy)

 Fecal InPouch culture or PCR for Tritrichomonas foetus (cats with colitis)

 Fecal enteric panel (culture and toxin assays) or Fecal PCR panel
Reserved for cats developing diarrhea after boarding or show attendance, cats with an acute onset of bloody diarrhea in association with evidence of sepsis, diarrhea outbreaks occurring in more than one pet in a household, and for zoonotic concerns (Campylobacter spp., Salmonella spp.) in diarrheic pets exposed to immunocompromised people)

Empirical deworming with a broad-spectrum anthelminthic
Tests of assimilation

 Serum cobalamin and folate (assessment of absorption in the ileum and jejunum, respectively)

 Trypsin-like immunoreactivity (fTLI) for diagnosis of exocrine pancreatic insufficiency

Imaging

 Abdominal ultrasound (evaluation of the pancreas, intestinal wall thickening, layering of the wall, echogenicity of the layers, mesenteric lymph nodes, liver, spleen, kidneys, evaluation for peritoneal fluid)

 Abdominal radiographs (relatively low-yield procedure in animals with chronic diarrhea, but is indicated in animals suspected of having partial obstructions due to foreign bodies, intussusceptions, or masses, or gas distention/torsion of the gastrointestinal tract)

Diet trial

Elimination diet or hydrolyzed diet for gastric and intestinal disease is selected based on the animal's dietary history and is recommended before procuring intestinal biopsies in stable animals with chronic enteropathies (no evidence of hypoalbuminemia, hypocobalaminemia, fever). Higher fiber diets can be tried in animals with colitis if there is a lack of response to a dietary trial using an elimination diet. The trial should last for 2–3 weeks.

Antibiotic trial

Antibiotic-responsive diarrhea (ARD) is a canine phenomenon, and has not been well described in cats to date. The antimicrobials listed below are typically advocated for use in dogs with suspected ARD, although the antimicrobials can be used for a defined period (2 weeks) in diarrheic cats with chronic enteropathies and no evidence of severe disease (hypoalbuminemia, hypocobalaminemia, etc.) following a diet trial and prior to procurement of intestinal biopsies.

 Tylosin (10 mg/kg q 24 hrs)

 Metronidazole (8–10 mg/kg q 12 hrs)

Miscellaneous tests or procedures

 FeLV/FIV serology

 Spec fPL (pancreatitis)

 Rectal scraping (pythiosis, histoplasmosis, protothecosis, and eosinophilic colitis or proctitis)

GI biopsies

 Endoscopy (recommended to procure ileal biopsies whenever feasible)

 Full-thickness biopsies (laparotomy vs. laparoscopy)

Fecal Examination

The diagnosis of gastrointestinal parasites in dogs and cats is an integral component of small animal practice and the guidelines below should be followed to maximize the diagnostic yield of fecal examinations.

1. Examine fresh fecal specimens

Fecal flotations should be performed on fresh fecal specimens (< 2 hours old), whenever possible, to ensure that eggs, oocysts, and larvae do not develop beyond their diagnostic stages.¹ Fresh fecal specimens can be refrigerated for up to 96 hours to facilitate preservation of eggs, oocysts, and cysts if immediate examination cannot be performed. Fecal specimens can be placed in 10% buffered formalin if more than one hour will elapse before analysis or refrigeration. Specimens fixed in formalin are suitable for concentration techniques, acid-fast stains, and immunoassays.

2. Perform centrifugation fecal flotations

Fecal flotations are excellent for recovering common nematode ova, oocysts of coccidia (including Cryptosporidium spp.), and Giardia cysts. The most important considerations for fecal flotations include: 1) choice of flotation solution and its specific gravity; 2) selection of standing versus centrifugal flotation; and 3) transfer of the meniscus. Three solutions in common use are zinc sulfate (s.g. 1.18 to 1.2); Sheather's sugar (s.g. 1.27); and sodium nitrate (s.g. 1.2). Sodium chloride is an unacceptable flotation medium, even when used with centrifugation, as it will not float Trichuris ova. Aqueous zinc sulfate (ZnSO₄) with a specific gravity of 1.18 to 1.2 has been widely recommended, because it will float cysts, oocysts, and most helminth eggs with a minimum of distortion and fecal debris. Flotation with centrifugation is considerably more efficient than standing (gravitational) flotations (e.g., Ovassay®, Fecalyzer®, Ovatector®), which may not detect parasite stages shed in low numbers. Quantitative comparisons have shown that egg counts achieved using flotation with centrifugation was 2.4 to 6.0 times higher compared to standing flotation.² Once the flotation procedure is complete, the meniscus containing the parasite stages should be transferred by coverglass to a clean glass slide after approximately 10 minutes. The meniscus should be transferred by lifting the coverslip directly off the fluid surface and placing it on a slide. Meniscus transfer using a loop or glass rod is the poorest method of meniscus transfer and reduces the sensitivity of any flotation technique, because only a small portion of the parasites recovered is actually transferred to the slide for examination.

3. Understand benefits and limitations of immunoassays

Giardia infections in adult dogs and cats are often subclinical³ or associated with a transient softening of the stool early in the infection; however, acute diarrhea tends to occur in puppies and kittens shortly after infection. The diagnosis of Giardia infection traditionally has depended on microscopic identification of trophozoites or cysts in feces from affected animals. However, microscopic diagnosis of Giardia infection can be difficult, because cysts may be shed intermittently and because cysts are so delicate.¹ Many artifacts (grass pollen, yeast, etc.) mimic to varying degrees the morphology of Giardia cysts, and care must be exercised in differentiating these from Giardia. A recent survey evaluating the sensitivity of fecal flotation for detection of Giardia in dogs confirmed the poor performance of current in-house microscopy testing for Giardia compared to ELISA.⁴ Microscopy following fecal flotation only identified half of infected dogs, and falsely diagnosed up to 25% of uninfected patients.

Direct immunofluorescence (DIF) is often the standard against which other tests for Giardia are measured.⁵ The Merifluor® Cryptosporidium/Giardia assay (Meridian Diagnostics, Inc., Cincinnati, OH) uses a fluorescein isothiocyanate (FITC)-labeled monoclonal antibody directed against cell wall antigen of Giardia cysts (not trophozoites) in the feces. A positive result is indicated by apple green fluorescence of the cyst. Morphologic identification is necessary for this technique. The test has been shown to have excellent specificity and sensitivity in humans, although it requires a fluorescent microscope that is typically available in large reference laboratories or universities. Specimens sent to commercial laboratories for DIF should be fixed in 10% buffered formalin. Meridian's DIF combines the Giardia-specific and Cryptosporidium parvum-specific antibodies in one reagent, so specimens can be examined for both parasites with a single test.

Enzyme immunoassays (EIA): Many veterinarians and reference laboratories have resorted to using ELISA tests that rely upon detection of Giardia cyst wall protein I (GCWP 1). The ELISA tests are advantageous because they are generally easy to perform and results are easy to interpret. In addition, the test does not rely upon morphological identification of cysts or oocysts via microscopy, thus saving technician time and potentially avoiding false negative interpretations. The EIA tests can also detect GCWP 1 in the absence of detectable cysts. The SNAP® Giardia Test (IDEXX Laboratories, Inc., Westbrook, ME) is a rapid in-house enzyme immunoassay that can be performed on fresh feces, previously frozen feces, or feces stored at 2–7°C for up to 7 days. This test represents the first commercially available EIA designed specifically for dogs and cats, and has the added advantages of simplicity, rapid availability of results (8 minutes following mixing of the conjugate solution with feces), and low cost. Despite the impressive performance characteristics of this rapid assay, it should not be used as a test to assess response to therapy in animals that have completed a recent course of anthelminthic therapy for their infection, because animals can remain positive for Giardia on the SNAP ELISA for several weeks following successful eradication of the parasite.

4. Recognize limitations and benefits of fecal PCR

Commercial reference labs can perform PCR testing for Giardia and Cryptosporidium, although the author recommends fecal flotation and DIF testing for the diagnosis of both organisms routinely. An exception is the use of PCR for determination of Giardia "assemblages," which vary in their infectivity for animals and humans. Dogs have mainly Assemblages C and D. Cats have Assemblages A1 and F. Humans are infected with Assemblages A2 and B. The assemblages can be determined via PCR⁶ to determine the likelihood of zoonotic transmission from animals to people, although the risk of transmission of Giardia to people is generally very low.

Fecal Enteric Panel

Proper collection and preservation of feces frequently are neglected but important requirements for the isolation of putative bacterial enteropathogens. Approximately 2–3 grams of fresh feces should be collected into a clean, sealed and leak-proof cup or sterile container and transported to the laboratory, as soon as possible, to maximize survival of Salmonella and Campylobacter spp. Specimens should be processed within 2 hours after collection. If the laboratory is on site, no transport medium is required. Transport medium, such as Cary-Blair or Amies gel, should be used for specimens that cannot be cultured within 2 hours of collection.⁷ Rectal swabs are suboptimal for bacterial isolation given the limited volume of feces obtained. If rectal swabs are used, the specimen should be collected with a sterile swab, placed in Amies transport medium, and transported to the laboratory as soon as possible. Specimens should be kept cool at 4–10°C, but not frozen. Fecal specimens submitted for ELISA testing should not be placed in transport media.

Fecal culture and toxin assays are typically a low-yield diagnostic procedure in animals with diarrhea, because the clinical documentation of enteropathogenic bacteria causing diarrhea is clouded by the presence of these organisms in apparently healthy animals. If bacterial enteritis or enterocolitis is suspected, the feces should be cultured or PCR should be performed for specific enteropathogens, such as Salmonella or Campylobacter jejuni. Fecal enteric panels should be reserved for animals developing diarrhea after boarding or show attendance, in animals with an acute onset of bloody diarrhea in association with evidence of sepsis, or in diarrhea outbreaks occurring in more than one pet in a household. Lastly, Campylobacter spp. and Salmonella spp. are potentially zoonotic organisms, and can cause disease in immunocompromised people. A recent study in 219 diarrheic cats and 54 nondiarrheic cats showed that Campylobacter was isolated from significantly fewer diarrheic (21/219 or 9.6%) versus nondiarrheic cats (15/54 or 27.8%, P = 0.001), and was detected in 74 of 131 cats (56.5%) via PCR.⁸ Campylobacter jejuni, C. helveticus, and C. upsaliensis were detected in 6.8, 100, and 44.6% of the 74 cats. Multiple Campylobacter spp. were identified in 47.3% of these cats. All cats were negative on fecal culture for Salmonella and for Clostridium difficile TcdA via ELISA. Clostridium perfringens enterotoxin was detected via ELISA in 9/219 diarrheic (4.1%) and in 1/54 nondiarrheic cats (1.9%, P = 0.69). This study underscored the limited diagnostic value of routine fecal cultures and toxin immunoassays for detection of enteropathogenic bacteria in diarrheic cats. Molecular-based testing was superior to fecal cultures for detection and identification of Campylobacter spp., but positive test results did not correlate to the presence of disease.⁸

Fecal Cytology on Stained Fecal Smears

Stained fecal smears are commonly evaluated by veterinarians and veterinary technicians in an effort to identify the underlying cause of the diarrhea by looking for the presence of spiral-shaped bacteria (Campylobacter-like organisms), white blood cells, and fecal endospores associated with Clostridium perfringens. Unfortunately, the diagnostic yield of stained fecal smears is extremely low, and the author does not recommend their routine use in practice for several important reasons:

1.  Fecal endospores are of no diagnostic value, and the lack of association between the presence of endospores and the presence or absence of diarrhea, and between the endospore count and enterotoxin results has been well documented.^9,10

2.  Spiral-shaped bacteria are commonly found in fecal smears from healthy and diarrheic dogs and cats, and the spiral-shaped bacteria can be representative of a Campylobacter-like organism, including Helicobacter and Arcobacter spp. The problem is that there are over 18 different species of Campylobacter, many of which are non-pathogenic. The mere presence of spiral-shaped organisms among other bacterial forms is of no clinical relevance, and is not sufficient for a diagnosis of Campylobacter.

Veterinarians should be cognizant of the fact that most bacterial enteropathogens are associated with self-limiting diarrhea, and the injudicious administration of antimicrobials could be more harmful than beneficial. Supportive therapy and appropriate hygiene control should be considered in all cats with suspected or confirmed bacteria-associated diarrhea, and antimicrobials should only be administered to animals manifesting systemic signs of illness.⁷

Tests of Intestinal Function

Low serum B12 or cobalamin has often been regarded solely in the context of its diagnostic utility in identifying dogs with small intestinal bacterial overgrowth. However, low serum B12 has been described in cats in association with a wide variety of gastrointestinal disease including IBD.¹¹ It is plausible that mucosal repair is impeded in the initial management of IBD when B12 is deficient and its absorption impaired. Measurement of serum B12 in the initial evaluation of dogs and cats with chronic intestinal disease, followed by parenteral administration if low serum cobalamin is identified, is pivotal for successful management of the patient. Dogs and cats are typically supplemented with B12 at a dose of 250–1,500 µg per dose (depending on the weight of the animal), subcutaneously, for 6 weeks on a weekly basis, with supplementation continued on an as-needed basis.

Interpretation of Hematology and Biochemistry Panels

The complete blood count may reveal a peripheral eosinophilia secondary to endoparasitism, eosinophilic IBD, abdominal mast cell neoplasia, or lymphoma (paraneoplastic phenomenon).¹² Anemia may result from enteric blood loss or from depressed erythropoiesis caused by systemic disease or chronic inflammation. The serum biochemistry panel can provide additional information pertaining to the likely cause of diarrhea and help rule out extra-GI causes of diarrhea (renal disease, hepatic insufficiency). Protein-losing enteropathies represent a syndrome of intestinal disorders (severe IBD, lymphoma, intestinal ulceration) that typically manifest with abnormal loss of serum proteins across an inflamed or abnormally permeable intestinal mucosal barrier. Hypocholesterolemia can be seen secondary to malabsorption. A discordant BUN:creatinine ratio can be seen secondary to dehydration (pre-renal azotemia), gastrointestinal bleeding, a high protein meal, and cachexia. Elevated liver enzymes should be interpreted cautiously in cats and dogs with intestinal disease or pancreatitis, because drainage of bacteria or endotoxin via the portal circulation can precipitate a "reactive hepatopathy" secondary to extrahepatic disease.

Abdominal Imaging

Survey abdominal radiographs are a relatively low yield procedure in most cats and dogs with chronic diarrhea, but are indicated in animals suspected of having partial obstructions due to foreign bodies, intussusceptions, or masses, or in animals with gas distention or displacement of the stomach or bowel. Abdominal ultrasound is complimentary to survey abdominal radiographs and is more sensitive for the detection of abdominal masses, intestinal mural thickening, intussusceptions, and mesenteric lymphadenopathy.¹³ In addition; ultrasound-guided percutaneous biopsy or aspiration of masses is an effective diagnostic procedure. Contrast radiography and fluoroscopy are occasionally indicated for identification of partial obstructions and intestinal motility disorders, respectively.

Endoscopy and Biopsy - Pitfalls and Recommendations

Endoscopy is a valuable procedure for the diagnosis of intestinal mucosal disorders that are associated with morphologic changes. Endoscopy, however, does not differentiate intestinal motility disorders, secretory diarrheas, or brush border enzyme defects, and is likely to miss lesions in the intestinal submucosa and muscularis propria layers of the bowel. In addition, endoscopy is limited by the working length of the scope, precluding endoscopic examination of the jejunum. Regardless of the method used to procure intestinal biopsies, the interobserver variation among histopathologic evaluations of intestinal tissues from dogs and cats is unacceptably high, and an intestinal biopsy sent to four different pathologists may result in four different biopsy reports.¹⁴ With the support of the WSAVA, the Gastrointestinal Standardization Group has proposed a standardized histologic evaluation system that can be applied to all companion animal gastroenterologic disorders. Standardization should yield several obvious benefits including uniform diagnosis of disease, staging of disease, and the subsequent development of controlled clinical trials for the treatment of canine and feline gastrointestinal disorders.

Common Chronic Enteropathies In Cats

1. Parasitic Infection

Tritrichomonas foetus is an important and common protozoal pathogen that causes colitis primarily in young pedigree cats living in confined areas such as catteries and shelters worldwide.¹⁵ Clinical signs associated with T. foetus infection in cats generally consist of a chronic or recurrent large intestinal diarrhea characterized by increased mucus, tenesmus, and increased frequency.¹⁶ Eradication of the infection can be frustrating for veterinarians and breeders alike, as 57% of cats diagnosed with T. foetus-associated diarrhea persist in shedding the organism for up to 5 years following treatment.¹⁶ A variety of antimicrobials have been attempted to eradicate T. foetus infection with limited success. More recent therapeutic approaches have involved the use of ronidazole (30 mg/kg q 24 hrs for 14 days), a 5-nitroimidazole with similar properties to metronidazole; however, clinical resistance to metronidazole, low efficacy of tinidazole, and documentation of in vivo and in vitro resistance to ronidazole in some cats are consistent with a high level of cross resistance of feline T. foetus to conventional 5-nitroimidazole drugs.¹⁷ The diagnosis of T. foetus infection in cats is best done via PCR testing on feces or utilization of a proprietary InPouch culture medium (BioMed Diagnostics Inc., White City, OR), and both methods are vastly superior to the wet-prep technique.

2. Food-Responsive Enteropathy

Elimination diets containing novel, single sources of protein have proved to be effective in dogs and cats with a variety of chronic enteropathies, including small and large intestinal lymphocytic-plasmacytic, eosinophilic, and mixed cellular infiltrates or forms of IBD.^18-21 In one study, Guilford et al. found that in 16 feline cases of elimination-challenge proven dietary hypersensitivity with chronic gastrointestinal signs, all 16 had mild to severe inflammatory infiltrates in at least one region of the bowel.¹⁸ The infiltrates were lymphocytic, lymphocytic-plasmacytic (most cases), or eosinophilic (2 cases). All cases responded completely to the elimination diet alone and offending foods were identified in all cases. In a report of 13 dogs with lymphocytic-plasmacytic colitis, clinical signs resolved in all 13 with the introduction of an elimination diet, and of 11 dogs re-challenged with their original diet, 9 relapsed.²¹ In a further report of 6 cats with lymphocytic-plasmacytic colitis, all 6 responded completely to an elimination diet.²⁰

The theoretical basis for the use of protein hydrolysate diets is that a reduction in immunogenic epitopes being presented to the mucosal immune system whilst dysregulation is present will increase the potential for resolution. Thus, the argument for the use of a hydrolysate diet is independent of whether a dietary specific immunological response is suspected to be present or not. Experience with protein hydrolysate diets is increasing, and anecdotally they appear to be very effective adjuncts to pharmacological therapy, even as sole therapy. Clinical resolution with histological improvement has been reported in 4 of 6 dogs with refractory IBD when treated with a hydrolyzed soy-protein diet alone.²² In addition, the administration of a hydrolyzed diet to 18 dogs with chronic enteropathy was shown to be superior to the administration of a highly digestible control diet for the long-term management of the chronic small bowel enteropathy.²³ However, it is possible that nutritional factors other than protein hydrolysis were responsible for the improvement. These could include dietary digestibility, correction of vitamin or mineral deficiencies, a lowered n-6:n-3 fatty acid ratio, and the potential for an immunomodulatory effect of soy isoflavones within the hydrolyzed diets.

3. Inflammatory Bowel Disease

The diagnosis of IBD is based on the presence of compatible clinical signs (chronic diarrhea, vomiting, weight loss, with or without borborygmus and flatulence), and the exclusion of metabolic, infectious, neoplastic, and obstructive disorders of the gut. Gastrointestinal biopsies must show histological evidence of a moderate to marked infiltration of the gastrointestinal mucosa by inflammatory cells (predominantly lymphocytes and plasma cells) and changes in mucosal architecture for a diagnosis of IBD to be rendered.

The association between the mucosal bacteria and intestinal inflammation has been provocatively demonstrated by Janeczko et al., in 17 cats undergoing a comprehensive workup for clinical signs of gastrointestinal disease and 10 healthy age-matched controls.²⁴ The number of mucosa-associated Enterobacteriaceae, E. coli, and Clostridium spp. was higher in cats with signs of gastrointestinal disease than healthy cats, and total numbers of mucosal bacteria were strongly associated with changes in mucosal architecture and the density of mucosal infiltrates, particularly macrophages. In addition, the numbers of mucosa-associated bacteria were associated with upregulation of cytokine mRNA (particularly IL-1, -8, and -12).²⁴ Management of feline IBD includes the use of elimination or hypoallergenic diets, administration of antimicrobials (tylosin, metronidazole) and/or immunomodulatory drugs (prednisolone, budesonide, chlorambucil), and supplementation with cyanocobalamin. Treatment failures are usually due to an incorrect diagnosis, suboptimal medical or dietary therapy, poor client compliance, and/or the presence of concurrent disease such as pancreatitis or hepatobiliary disease.

4. Intestinal Lymphoma

There are several classifications of alimentary lymphoma in the cat. Small-cell (well differentiated lymphoma or low-grade lymphoma) is the most prevalent, and represents 75% of the alimentary lymphoma cases diagnosed in cats.²⁵ Recent studies have indicated that low-grade lymphoma is more likely to be T-cell in origin, and high-grade alimentary lymphoma is more likely to be B-cell lymphoma. Large-cell lymphoma (high-grade lymphoma, lymphoblastic lymphoma) tends to have a more rapid onset and progression resulting in acute and often severe clinical signs. Lastly, large, granular cell lymphoma often starts in the alimentary system of the cat before rapidly spreading to other organ systems. This is an aggressive form of lymphoma that responds poorly to chemotherapy administration. These cells contain cytoplasmic granules that can be demonstrated on Giemsa stains, which explains their name, and are thought to be of the T-cell/natural killer cell immunophenotype.

Immunohistochemistry and clonality are becoming more established for confirming gastrointestinal lymphoma and helping to differentiate lymphoma from inflammatory bowel disease (IBD.25 Utilizing these markers in cats with small cell T-cell gastrointestinal lymphoma, an ultrasonographic pattern of diffuse thickening of the muscularis propria of the small intestine has been recognized.²⁶ This pattern has also been described in cats with IBD and smooth muscular hypertrophy.²⁶

5. "Triaditis"

The term "triaditis" is a lay-term and refers to the syndrome of concurrent cholangitis, pancreatitis, and inflammatory bowel disease (IBD) in cats. The association of these entities may reflect a common underlying disease mechanism. It is felt that the predominant signs of triaditis are attributable to hepatobiliary disease, with pancreatitis and IBD occurring as secondary complications. Despite the relatively high prevalence of triaditis in cats, the temporal nature of the relationship as well as the specific cause(s) of cholangitis, pancreatitis, and feline IBD have not been well elucidated to date. Ascending passage of bacteria or bacterial products from the intestine is a plausible factor in the development of pancreatitis, and it is plausible that the retrograde ejection of bile up the pancreatic and common bile ducts during vomiting increases the risk for pancreatic inflammation and cholangitis. Interestingly, a recent study by Warren et al. comparing histopathologic features, immunophenotyping, clonality, and fluorescence in situ hybridization (FISH) in 51 cats with lymphocytic cholangitis failed to document strong evidence implicating in situ bacterial colonization as an etiopathogenesis of lymphocytic cholangitis.²⁷ A similar study critically evaluating the role of bacterial colonization in cats with neutrophilic cholangitis is warranted. Weiss et al. reported an association between inflammatory liver disease and IBD, pancreatitis, and interstitial nephritis in 78 cats at necropsy.²⁸ Although the temporal relationship between disease entities could not be established, all cats with cholangitis should be evaluated for concurrent IBD and pancreatitis. It is plausible that altered mucosal integrity secondary to IBD could precipitate inflammatory mediators, endotoxins, and microbial components access to the portal circulation with consequent deposition of immune complexes in the liver, activation of the complement system, and hepatocellular necrosis. Measurement of serum cobalamin concentrations is warranted in all anorexic cats, particularly those with IBD, pancreatitis, or hepatobiliary disease, given the high incidence of subnormal cobalamin concentrations in these cats.

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