A discussion of the general diagnostic approach to cats with GI symptoms, along with some of the specialized tests available at reference laboratories.

Gastrointestinal (GI) disease is common in cats but can often be accompanied by nonspecific clinical signs. Cats tend to hide discomfort well and can present with a different spectrum of clinical signs than dogs or humans. Recognizing feline GI disease thus poses a diagnostic challenge. In this article, we will discuss the general approach to cats with GI signs and review some current specialized tests available at reference laboratories.

What test should I use for a feline patient with GI signs?

The chronicity and severity of clinical signs often dictate which specific laboratory tests should be considered. The diagnostic plan can be complemented by a general guideline in order to approach each patient systematically. For example, in cats with acute diarrhea, the clinician can consider parasitic and enteropathogen testing or empirical anthelmintic therapy. In cases with chronic GI signs (more than three weeks), a broader diagnostic approach may be needed, including evaluation for systemic (minimum database and serum total thyroxine, with added free thyroxine and cTSH for older cats with occult hyperthyroidism) and gastrointestinal causes of the signs as outlined below and in the sidebars.

Testing for enteropathogens and parasites

PCR-based testing is available as a panel to screen for multiple bacterial and protozoal organisms. Indications for performing the panel include:

1. Diarrhea that is severe (especially in young or immunocompromised animals)
2. Cases when multiple animals are affected
3. Screening donors prior to collection for fecal microbiota transplantation.

In general, PCR testing has a high sensitivity, so it is important to remember that several of the bacterial organisms and toxins tested are frequently found in healthy animals without diarrhea. Therefore, PCR testing might be useful when initial diagnostics (e.g. fecal exam, ELISA, cytology, or culture) are inconclusive. However, a positive result does not prove causation. The management of uncomplicated cases of diarrhea is nonspecific and supportive. Only animals that are systemically ill (e.g. with evidence of sepsis) should receive antimicrobial therapy.

When diarrhea is suspected to be associated with protozoa, direct fecal or wet mount smears can be performed to detect motile protozoa, such as Giardia and Tritrichomonas foetus. The protozoa trophozoites can be differentiated by their characteristic motion and morphology. Giardia cysts can be detected by fecal flotation with centrifugation techniques. Since false negatives are common, feces from multiple time points should be evaluated. If cytology is inconclusive, further testing such as fecal culture and/or PCR assay for T. foetus, fecal antigen ELISA assays, immunofluorescence assays (IFA), and PCR assays for Giardia spp. are recommended.

For cases in which T. foetus is strongly suspected based on cytology or clinical signs, fecal culture of T. foetus can be performed using a commercially available culture system, InPouch TF (BioMed Diagnostics, White City, OR).^1,2 This test has an approximately 50% sensitivity, whereas PCR, the gold standard for diagnosis of T. foetus, has a sensitivity of approximately 90%.³

For symptomatic animals suspected of having Giardia spp. infection, it is recommended to perform a fecal antigen ELISA assay in combination with fecal flotation. IFA is recognized as the gold standard for diagnosing Giardia spp. infection, and allows for the concurrent detection of Cryptosporidium spp.^4,5 PCR assays for Giardia spp. and Cryptosporidium spp. are generally not indicated unless the animal is known to be positive and the genotype of the organisms is of interest.

Further information regarding diagnosis and treatment of parasites can be found on the Companion Animal Parasite Council website.

Measuring serum fTLI, fPLI, cobalamin, and folate concentrations

For cats with chronic GI signs, especially those for which a systemic cause cannot be identified or initial therapies (e.g. diet, anthelmintic therapy) have not resulted in improvement, consider the measurement of serum fTLI, fPLI, cobalamin, and folate concentrations.

• Feline trypsin-like immunoreactivity (fTLI)

Cats with exocrine pancreatic insufficiency (EPI) often do not display the classic clinical signs described for dogs (polyphagia, weight loss, and unformed feces).⁶ Indeed, weight loss can be a lone clinical sign in cats with EPI. It is therefore suggested that in cats with unexplained weight loss or chronic diarrhea, serum fTLI should be measured to evaluate for EPI. Although fTLI is highly sensitive and specific for the diagnosis of EPI, it might be increased in cats with renal failure. Also, serum fTLI concentrations can be slightly increased after feeding. Therefore, at least eight hours of fasting is recommended before collecting a blood sample. Both the canine and the feline TLI assays are species-specific, and thus are not affected by pancreatic enzyme supplementation.

Serum fTLI concentrations increase in approximately 30% of cats with pancreatitis.^7-9 Therefore, in cases of suspected pancreatitis, serum fPLI measurements are needed. If a high fTLI concentration with a normal Spec fPLI is obtained, intestinal disease should be suspected, as pancreatitis is unlikely.

• Feline pancreatic lipase immunoreactivity (fPLI)

Serum fPLI is the current diagnostic test of choice for pancreatitis. In clinical settings, when pancreatitis is suspected, it is recommended to first screen with SNAP fPL (IDEXX Laboratories, Westbrook, ME), for convenience. SNAP fPL is a semi-quantitative test. A negative result helps rule out pancreatitis; a positive result correlates with the serum fPLI >3.5 µg/L, and further confirmation is needed. This can be done by performing an abdominal ultrasound or ideally by measuring Spec fPL.¹⁰ The latter can serve for evaluating therapeutic efficacy and future monitoring. An increase or decrease by two to three times the previous value may indicate a more significant change in disease state; an increased serum fPLI concentration in a clinically normal cat may suggest subclinical pancreatic acinar cell damage.

The influence of renal disease on serum fPLI concentrations is controversial. Serum fPLI concentration was not found to be significantly increased in cats with experimentally induced chronic kidney disease.¹¹ In contrast, another study found that renal insufficiency, but not prerenal azotemia, can result in an increase of Spec fPL.¹² However, this study did not report how many cats had other evidence compatible with pancreatitis (e.g. clinical signs, ultrasonography). Therefore, Spec fPL concentration is still considered specific and can be used to diagnose pancreatitis in cats with renal failure.

Questions have been raised as to whether feline pancreatitis has been overdiagnosed.¹³ To avoid over-diagnosis, one should also evaluate other concurrent diseases and diagnose pancreatitis only with a combination of history, physical examination, ultrasonography (where available), and laboratory tests.

• Cobalamin and folate

Dietary insufficiency is unlikely to contribute to hypocobalaminemia or hypofolatemia since commercial diets are replete in these water-soluble vitamins. However, animals that are fed exclusively a non-fortified vegetarian diet for prolonged periods without proper supplementation might develop cobalamin deficiency.

Measurement of serum cobalamin and folate concentrations can help identify the presence of GI disease associated with malabsorption, since their uptake occurs at specific sites and depends on several factors. When inflammatory disorders (e.g. IBD, lymphoma, fungal disease) are severe and chronic, intestinal receptor damage can occur. Depending on the affected location, the damage can result in subnormal concentrations of these vitamins.¹⁴ A low serum folate concentration suggests proximal intestinal (duodenal, jejunal) disease, while a low serum cobalamin concentration suggests ileal disease; decreased concentrations of both vitamins indicate a diffuse and potentially severe process.

Serum cobalamin and folate concentrations are often abnormal in cats with EPI, as the exocrine pancreas appears to be the exclusive source of intrinsic factor in cats.¹⁵ Serum cobalamin must bind to intrinsic factor in order to be absorbed in the distal ileum. Therefore, cats with EPI almost always have subnormal serum cobalamin concentrations. Also, whereas dogs with EPI often have increased serum folate concentrations due to decreased pancreatic secretion, cats with EPI often have concurrent intestinal disease that may damage folate receptors and thus often have decreased serum folate concentrations. When fTLI is normal, serum cobalamin and folate abnormalities are highly suggestive of intestinal disease.

Folate is absorbed as folate monoglutamate in the proximal small intestine after dietary folate polyglutamate is deconjugated by brush border enzymes located in the jejunum. If folate-producing bacteria proliferate in the proximal small intestine, the bacteria can increase serum folate concentrations by producing folate available for host absorption and/or decrease serum cobalamin concentrations by consuming luminal cobalamin. The finding of hyperfolatemia should be considered in conjunction with other clinical data and should not necessarily prompt any therapeutic intervention (e.g., antibiotic administration). However, it is important to note that a normal serum cobalamin and folate concentration does not rule out the presence of intestinal dysbiosis.

Historically, hyperthyroidism has been associated with low serum cobalamin, low serum folate, or both. However, in one study of cats with hyperthyroidism, hypocobalaminemia was uncommon.¹⁶ Low serum folate concentration might occur with hyperthyroidism in cats but concentrations tend to normalize following establishment of euthyroidism.¹⁶ Therefore, if small intestinal disease is suspected in a cat with hyperthyroidism, cobalamin and folate concentrations should be measured, when possible, once the cat is euthyroid.

Conclusion

In this article, we have reviewed some routinely available specialized assays for use in cats with GI signs. Many other tests, for example for intestinal permeability and inflammation markers, are being studied. Although most are currently of limited availability and for research use only, more tools are expected to become available to help us evaluate and manage feline patients with GI disease.

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¹Gookin JL, Foster DM, Poore MF, Stebbins ME, Levy MG. “Use of a commercially available culture system for diagnosis of Tritrichomonas foetus infection in cats”. J Am Vet Med Assoc. 2003;222(10):1376-1379.

²Ceplecha V, Svoboda M, Cepička I, Husník R, Horáčková K, Svobodová V. “InPouch™ TF-Feline medium is not specific for Tritrichomonas foetus”. Vet Parasitol. 2013;196(3-4):503-505.

³Gookin JL, Stebbins ME, Hunt E, et al. “Prevalence of and risk factors for feline Tritrichomonas foetus and Giardia infection”. J Clin Microbiol. 2004;42(6):2707-2710.

⁴Rishniw M, Liotta J, Bellosa M, Bowman D, Simpson KW. “Comparison of 4 Giardia diagnostic tests in diagnosis of naturally acquired canine chronic subclinical giardiasis”. J Vet Intern Med. 2010;24(2):293-297.

⁵Vasilopulos RJ, Rickard LG, Mackin AJ, Pharr GT, Huston CL. “Genotypic analysis of Giardia duodenalis in domestic cats”. J Vet Intern Med. 2007;21(2):352-355.

⁶Xenoulis PG, Zoran DL, Fosgate GT, Suchodolski JS, Steiner JM. “Feline exocrine pancreatic insufficiency: a retrospective study of 150 cases”. J Vet Intern Med. 2016;30(6):1790-1797.

⁷Swift NC, Marks SL, MacLachlan NJ, Norris CR. “Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of pancreatitis in cats”. J Am Vet Med Assoc. 2000;217(1):37-42.

⁸Gerhardt A, Steiner JM, Williams DA, et al. “Comparison of the sensitivity of different diagnostic tests for pancreatitis in cats”. J Vet Intern Med. 2001;15(4):329-333.

⁹Steiner JM, Williams DA. “Disagrees with criteria for diagnosing pancreatitis in cats”. J Am Vet Med Assoc. 2000;217(6):816-818.

¹⁰Schnauß F, Hanisch F, Burgener IA. “Diagnosis of feline pancreatitis with SNAP fPL and Spec fPL”. J Feline Med Surg. 2019;21(8):700-707.

¹¹Xenoulis PG, Finco DR, Suchodolski JS, Steiner JM. “Serum fPLI and Spec fPL concentrations in cats with experimentally induced chronic renal failure [JVIM abstract 250]”. J Vet Intern Med. 2009;23(3):758.

¹²Jensch S. “The effect of naturally occurring renal insufficiency on serum pancreatic-specific lipase in cats”. Comp Clin Path. 2013;22(5):801-803.

¹³Bazelle J, Watson P. “Is it being overdiagnosed? feline pancreatitis”. Vet Clin North Am Small Anim Pract. 2020.

¹⁴Simpson KW, Fyfe J, Cornetta A, et al. “Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease”. J Vet Intern Med. 2001;15(1):26-32.4

¹⁵Fyfe J. “Feline intrinsic factor (IF) is pancreatic in origin and mediates ileal cobalamin (CBL) absorption”. J Vet Intern Med. 1993;7:133.

¹⁶Geesaman BM, Whitehouse WH, Viviano KR. “Serum cobalamin and methylmalonic acid concentrations in hyperthyroid cats before and after radioiodine treatment”. J Vet Intern Med. 2016;30(2):560-565.

¹⁷Ruaux CG, Steiner JM, Williams DA. “Relationships between low serum cobalamin concentrations and methylmalonic acidemia in cats”. J Vet Intern Med. 2009;23(3):472-475.