How to manage feline chronic diarrhea, Part I: Diagnosis
In evaluating cats with chronic diarrhea, first obtain a careful and complete history that includes signalment, vaccination and deworming history, and information about the cat's environment, recent travel, past medical problems or surgeries, current diet regimen plus recent changes, and current prescription medications and nutraceuticals. A thorough history may suggest extraintestinal disease or exposure to parasites, infectious agents, drugs, or toxins.
Thoroughly evaluate all body systems before focusing on the GI tract. You may identify a fever or detect evidence of weight loss, cachexia, dehydration, or other signs of systemic disease. Palpate the thyroid glands and perform an ophthalmic examination including fundic evaluation. Consider a rectal examination if the history suggests large bowel diarrhea or rectal or anal disease.
Abdominal palpation in cats is usually straightforward because most patients are small, and abdominal contents are often readily palpable. The best assessment is obtained by using the flats of your hands and fingers against the abdomen as opposed to your fingertips. Using intermittent pressure and release minimizes patient discomfort. Elevating the cat's front end helps position the cranial abdominal organs within reach. Abdominal palpation should be systematic and include the small and large bowel as well as the abdominal lymph nodes. Take note of intestinal location, size, pain, masses, thickening, and fluid or gas distention. The presence and severity of abnormalities determines how aggressive or conservative the next diagnostic steps should be.
Macroscopically examine the feces in all cases. Note the fecal color, and look for mucus, undigested food, and blood. This information, along with the history, should be enough to classify the diarrhea as large bowel, small bowel, or both (Table 1).
Fecal smear and flotation
Antigen detection, cultures, and PCR and enterotoxin tests
Fecal antigen tests may be a useful addition to routine flotation methods.3 ELISA kits are available for Giardia species antigen detection (e.g. SNAP Giardia Test—Idexx Laboratories; ProSpecT Giardia—Remel).
Fecal bacterial and trichomonad cultures for Campylobacter jejuni and Tritrichomonas foetus, respectively, are usually low-yield but are appropriate in cases in which signalment and clinical signs suggest the possibility of infection.
Infection with C. jejuni is most often diagnosed in cats less than 6 months of age and is associated with mucoid diarrhea with fresh blood. Bacterial culture of fresh feces remains the most reliable way to establish a diagnosis. The organism is microaerophilic, so use anaerobic swabs for transport. Inform the laboratory ahead of time if Campylobacter species infection is suspected since special culturing methods are required. Campylobacter jejuni has been identified in both asymptomatic cats and in cats with diarrhea, so interpret positive culture results with caution.4
Tritrichomonas foetus usually affects young cats and kittens kept in crowded environments.5 Clinical signs consist of waxing and waning chronic large bowel diarrhea with blood, mucus, flatulence, profound anal irritation, and involuntary passing of feces. Tritrichomonas foetus can be cultured by using a commercially available culture system (InPouch TF-Feline—BioMed Diagnostics). A small fecal sample is needed to inoculate the medium inside the pouch, which is then held at room temperature for up to one week. It should be examined under the microscope every day for evidence of the motile trophozoites.
The most sensitive method for confirming tritrichomoniasis is a fecal polymerase chain reaction (PCR) test. This test is performed at Texas A&M University, College of Veterinary Medicine Gastrointestinal Laboratory and at North Carolina State University, College of Veterinary Medicine Intestinal Pathogens Research Laboratory. Information regarding sample handling and submission is provided at http://www.cvm.tamu.edu/gilab/assays/Tritrichomonas.shtml|~http://www.cvm.tamu.edu/gilab/assays/Tritrichomonas.shtml and http://www.cvm.ncsu.edu/docs/personnel/gookin_jody.html|~http://www.cvm.ncsu.edu/docs/personnel/gookin_jody.html .
Additional diagnostic tests for any cat with chronic diarrhea should include a serum chemistry profile, a complete blood count including white blood cell differential, an electrolyte panel, a urinalysis, and feline leukemia virus antigen and feline immunodeficiency virus antibody tests. Thyroxine concentrations should be measured in any cat over 7 years of age or with clinical signs suggestive of hyperthyroidism.
This laboratory data helps determine the severity of systemic disease and may identify potential extragastrointestinal causes of chronic diarrhea. Hypoalbuminemia is suggestive of serious GI disease and can be noted with alimentary lymphoma or fungal enteritis.9 Markedly increased hepatic enzyme activity (e.g. alanine transferase, alkaline phosphatase) or bilirubin concentration may indicate concurrent or secondary hepatopathies. The peripheral eosinophil count is often elevated in cats with parasitic, fungal, or eosinophilic enteritis. Anemia along with decreased total protein and increased blood urea nitrogen concentrations may suggest GI blood loss.
ADDITIONAL LABORATORY TESTING
Other specific laboratory tests may provide additional information about the nature and location of intestinal disease. In some cases, a definitive diagnosis may be provided. Some of these tests are referred to as GI function tests. It is important to point out, however, that many of the essential functions of the GI tract, such as secretion, motility, and immunologic surveillance and protection, are not readily evaluated.
Folate (vitamin B9) is a water-soluble B-group vitamin. Serum folate concentrations are influenced by dietary intake, small intestinal brush border enzyme activity, and the number and function of specific folate carriers in the proximal small intestine. Dietary deficiency of folate is extremely uncommon, and low serum folate concentrations strongly suggest proximal small intestinal mucosal disease.10 Proper sample handling is important since hemolysis causes the release of folate from red blood cells, resulting in spuriously high concentrations.
Cobalamin (vitamin B12) is also a water-soluble B-group vitamin. Only bacteria are capable of cobalamin synthesis, and cats are dependent on dietary sources for their cobalamin needs. After ingestion, cobalamin is bound to salivary and gastric proteins and then transferred to intrinsic factor in the duodenum. In cats, the exocrine pancreas is the only source of intrinsic factor. The cobalamin-intrinsic factor complex then attaches to specific receptors in the ileum. As a result, subnormal serum cobalamin concentrations suggest mucosal disease in the distal small intestine or exocrine pancreatic insufficiency (EPI).10
The trypsin-like immunoreactivity assay (TLI) determines serum trypsinogen and trypsin concentrations. Small amounts of these enzymes can be found in the bloodstream after synthesis by the pancreatic acinar cells. Subnormal TLI concentrations are a sensitive and specific marker for EPI.11 Administration of oral pancreatic extracts does not affect serum TLI concentrations. However, cats should be fasted for 12 hours before serum collection because patients with borderline exocrine pancreatic function may have results within the normal range.
Additional testing for pancreatitis may be warranted in any cat with chronic signs of GI disease, especially if triaditis complex—concurrent inflammation of the pancreas, hepatobiliary system, and GI tract—is suspected. The feline pancreatic lipase immunoreactivity (fPLI) test has higher sensitivity and specificity when compared with abdominal ultrasonography for identifying pancreatic inflammation, although the two tests may provide complementary information.12 Measuring serum amylase and lipase activities is no longer considered useful, and TLI concentrations are of limited value for diagnosing feline pancreatitis.
Abdominal radiography in cats with chronic diarrhea is usually unrewarding but may indicate a foreign body, an obstruction, an intussusception, a traumatic or congenital hernia, megacolon, or a mass lesion. An upper GI barium series may help to detect motility disorders, bowel thickening, partial obstruction, bowel torsion or displacement, strictures, or masses. A barium enema may be helpful to assess the large intestinal mucosa.
Abdominal ultrasonography is a more sensitive tool than radiography for detecting abdominal masses, intussusceptions, lymphadenopathy, and intestinal wall thickening or loss of normal intestinal layering.13 Abnormal organ parenchyma, masses, and lymph nodes can be aspirated or biopsied with ultrasonographic guidance. Cytologic examination of mesenteric lymph nodes cannot distinguish small cell lymphoma from normal lymph nodes. However, fungal disease, mast cell disease, and large cell lymphoma can be reliably identified with cytologic evaluation of intestinal or lymph node aspirates.
Depending on the results of the initial diagnostic tests, an endoscopic examination of the GI tract may be considered. This test is relatively noninvasive but does have substantial limitations. Most important, not all of the intestine can be evaluated since much of the small bowel is out of reach. An upper endoscopic examination permits visualization of the esophagus, stomach, and proximal duodenum. The distal ileum may be reached via the colon during a lower endoscopic examination, but the jejunum is inaccessible. In addition, only mucosal lesions can be identified, and focal thickening or submucosal changes will not be appreciated. Thus, endoscopy is most appropriate in patients in which diffuse inflammatory or infiltrative mucosal disease is suspected.
This diagnostic procedure requires specialized equipment and expertise. An inexperienced practitioner may have difficulty entering the duodenum or ileum, and biopsy quality may be suboptimal.14 Multiple (six to 10) mucosal biopsy samples should be collected from the stomach, duodenum, ileum, and colon for histologic examination, even if the tissue is grossly normal. Handle the samples carefully, and fix them quickly to avoid manipulation artifact or drying.
A few cases of chronic diarrhea may warrant an exploratory laparotomy, such as cats with mass lesions or those in which jejunal disease or submucosal pathology is suspected. When compared with an endoscopic examination, a surgical approach provides some advantages, including therapeutic mass removal, collection of full-thickness biopsy samples, and examination of the liver, pancreas, and abdominal lymph nodes. However, patient discomfort and recovery time are increased with surgery, and the risk-benefit ratio of surgery vs. endoscopy should be carefully evaluated in each patient. If surgery is performed, it is essential to evaluate the entire abdominal cavity. Even if focal disease is identified, it is often worthwhile to take full-thickness biopsy samples from each area of the GI tract, even if it looks and feels grossly normal.
Accurate and thorough diagnostic testing is often crucial in determining the underlying cause of chronic diarrhea. Even with the most sensitive tests, the disease process leading to chronic diarrhea can be painstakingly elusive. Ultimately, test results partnered with response to therapy may be the only way to definitively diagnose the cause of chronic diarrhea in many of our feline patients. See the second part of this article for details on treatment.
Sally Purcell, DVM
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