How to manage feline chronic diarrhea, Part I: Diagnosis - Veterinary Medicine
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How to manage feline chronic diarrhea, Part I: Diagnosis
A combination of patient history, fecal analysis, and additional diagnostic tests will help you discover the cause of this all-too-common clinical sign.


VETERINARY MEDICINE


Illustration by Laurie O'Keefe
An increase in the frequency and liquidity of bowel movements is an important sign of gastrointestinal (GI) disease in cats. Veterinarians are often consulted when diarrhea is associated with systemic illness or when it becomes persistent. When diarrhea occurs either intermittently or continuously for three weeks or more, it is considered a chronic condition. Chronic diarrhea in cats can be a diagnostic and therapeutic challenge, so we'll help you approach these cases logically and thoroughly. First we'll discuss which diagnostic tests are most helpful in cats with chronic diarrhea, and in the article that follows we'll cover drug and dietary treatments.

HISTORY

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.


Table 1: Clinical Signs Associated with Diarrhea
Ask additional questions that focus on the diarrhea and elucidate the onset, duration, specific characteristics, and associated clinical signs. A description of the feces (color, volume, presence of blood or mucus), the frequency and urgency of defecation, and associated clinical signs (anorexia, weight loss, vomiting, tenesmus, dyschezia) may localize the problem to a specific region of the GI tract (Table 1). Also ask about response to any treatments or dietary changes to help identify aggravating or alleviating factors.

PHYSICAL EXAMINATION

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.

FECAL DIAGNOSTICS

Gross appearance

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


Figure 1. A fecal smear showing several Campylobacter species organisms. Note the characteristic gull-wing shape of the organisms (Gram stain; 1,000X). (Photo courtesy of Michael D. Willard, DVM, DACVIM.)
Perform fecal flotation and saline smear evaluations multiple times since some GI parasites may be missed on a single examination. To perform a saline smear, mix fresh feces with a small amount of saline solution to form a thin slurry. Place a drop of the mixture on a slide, and top it with a coverslip. Routine fecal cytology with Gram staining may reveal the gull-wing-shaped rods of Campylobacter species (Figure 1). Examine the slide microscopically at low and high magnification to identify trophozoites and cysts. A fresh fecal sample (less than 30 minutes old) is necessary to ensure optimal diagnostic sensitivity. Trophozoite motility decreases quickly after removal from the host, so saline smears should be performed as promptly as possible. Direct smears may be preferable to flotation to identify heavy eggs, delicate larvae, and trophozoites.1 Tritrichomonas and Giardia species trophozoites appear grossly similar and may be mistaken for each other on cursory examination. However, distinct differences between the two organisms will help correct identification. Tritrichomonads have a long, undulating membrane along their entire bodies, and their movement is jerky and axial (Figure 2). Giardia species trophozoites demonstrate a more rolling motion commonly compared to falling leaves. They are pear-shaped and contain a characteristic concave ventral disk (Figure 3).


Figure 2. A fecal smear showing five trichomonads. Note the anterior flagella (Giemsa stain; 1,000X). (Photo courtesy of Thomas M. Craig, DVM, PhD.)
When performing fecal flotation, centrifugal flotation methods substantially improve the sensitivity of the process.2 Mix 2 to 3 g (about ½ tsp) of fresh feces with 5 to 10 ml of flotation solution. If the sample is very soft or watery, use 5 g (1 tsp) of feces to account for the dilution effect. Sheather's flotation method using sugar solution allows good parasite recovery in most cases, but a zinc sulfate flotation test should be used if infection with Giardia species is suspected since this solution is less likely to shrink and distort protozoan cysts.1


Figure 3. A zinc sulfate flotation sample showing several Giardia species cysts and one trophozoite. Note the characteristic pear shape and bilateral symmetry (1,000X). (Photo courtesy of Thomas M. Craig, DVM, PhD.)
Strain the fecal mixture through cheesecloth into a container suitable for pouring. Pour the contents of the container into a centrifuge tube. If a swinging bucket centrifuge is used, fill the tube with enough solution to create a meniscus, and place a coverslip on top. Centrifuge for 10 minutes at 1,500 rpm. If a fixed-angle centrifuge is used, do not fill the centrifuge tube to the top. Create a meniscus by adding flotation solution after centrifugation, and then place the coverslip on top. Let the sample stand for three or four minutes, and then transfer the coverslip to a slide. Examine the sample at low magnification to identify pathogenic ova, cysts, and oocysts. If time is limited, samples for flotation can be refrigerated and examined later in the day.

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 .


Figure 4. A fecal smear showing numerous endospores of Clostridium perfringens (modified Wright's stain; 1,000X). (Photo courtesy of Debra Zoran, DVM, DACVIM.)
Clostridium perfringens enterotoxicosis (CPE) is a less common cause of diarrhea in cats. Keep in mind that C. perfringens may be isolated from the feces of clinically normal cats.6 A trigger, such as antibiotic administration, diet change, or intestinal pathogen coinfection, causes the vegetative form of the organism to sporulate and release enterotoxins. CPE cannot be presumptively diagnosed based on findings of fecal cytologic examination alone (Figure 4) because large numbers of endospores have been reported in the feces of healthy cats.7 Immunodetection of fecal enterotoxin is available as a reverse passive latex agglutination assay (PET-RPLA Toxin Detection Kit—Oxoid) or ELISA (C. perfringens Enterotoxin Test—TechLab). PCR testing on feces has been used to identify the gene that encodes for enterotoxin production (cpe). Using a combination of immunodetection and PCR appears to offer optimal diagnostic sensitivity.8 The Gastrointestinal Laboratory at Texas A&M University offers the PCR test for the cpe gene, and information regarding sample handling and submission is provided at http://www.cvm.tamu.edu/gilab/assays/C.%20perfringens%20enterotoxin%20gene.shtml|~http://www.cvm.tamu.edu/gilab/assays/C.%20perfringens%20enterotoxin%20gene.shtml .

SYSTEMIC EVALUATION

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 IMAGING

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.

ENDOSCOPY

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.

EXPLORATORY LAPAROTOMY

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.

CONCLUSION

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
Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM-CA
Department of Small Animal Clinical Sciences
College of Veterinary Medicine
Texas A&M University College Station, TX 77843-4474

REFERENCES

1. Bowman DD. Georgis' parasitology for veterinarians. 9th ed. St. Louis, Mo.: Saunders Elsevier, 2009;295-371.

2. Gates MC, Nolan TJ. Comparison of passive fecal flotation run by veterinary students to zinc-sulfate centrifugation flotation run in a diagnostic parasitology laboratory. J Parasitol 2009;95(5):1213-1214.

3. Mekaru SR, Marks SL, Felley AJ, et al. Comparison of direct immunofluorescence, immunoassays, and fecal flotation for detection of Cryptosporidium spp. and Giardia spp. in naturally exposed cats in 4 Northern California animal shelters. J Vet Intern Med 2007;21(5):959-965.

4. Rossi M, Hänninen ML, Revez J, et al. Occurrence and species level diagnostics of Campylobacter spp., enteric Helicobacter spp. and Anaerobiospirillum spp. in healthy and diarrheic dogs and cats. Vet Microbiol 2008;129(3-4):304-314.

5. Gookin JL, Stebbins ME, Hunt E, et al. Prevalence of and risk factors for Tritrichomonas foetus and Giardia infection. J Clin Microbiol 2004;42(6):2707-2710.

6. Lubbs DC, Vester BM, Fastinger ND, et al. Dietary protein concentration affects intestinal microbiota of adult cats: a study using DGGE and qPCR to evaluate differences in microbial populations in the feline gastrointestinal tract. J Anim Physiol Anim Nutr (Berl) 2009;93(1):113-121.

7. Marks SL, Melli A, Kass PH, et al. Evaluation of methods to diagnose Clostridium perfringens-associated diarrhea in dogs. J Am Vet Med Assoc 1999;214(3):357-360.

8. Marks SL, Kather EJ. Clostridium perfringens-associated diarrhea. In: Greene CE, ed. Infectious diseases of the dog and cat. 3rd ed. St. Louis, Mo.: Saunders Elsevier, 2006;364-366.

9. Gabor LJ, Canfield PJ, Malik R. Haematological and biochemical findings in cats in Australia with lymphosarcoma. Aust Vet J 2000;78(7):456-461.

10. Suchodolski JS, Steiner JM. Laboratory assessment of gastrointestinal function. Clin Tech Small Anim Pract 2003;18(4):203-210.

11. Steiner JM, Williams DA. Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency. J Vet Intern Med 2000;14(6):627-629.

12. Forman MA, Marks SL, De Cock HEV, et al. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Intern Med 2004;18(6):807-815.

13. Baez JL, Hendrick MJ, Walker LM, et al. Radiographic, ultrasonographic, and endoscopic findings in cats with inflammatory bowel disease of the stomach and small intestine: 33 cases (1990-1997). J Am Vet Med Assoc 1999;215 (3):349-354.

14. Willard MD, Mansell J, Fosgate GT, et al. Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats. J Vet Intern Med 2008;22(5):1084-1089.

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