David C. Twedt, DVM, DACVIM
Diarrhea is a common complaint in the cat, and the potential etiologies are extensive. The first step in evaluating the diarrhea case is to determine if it is a primary gastrointestinal disorder or if it may be secondary to systemic or metabolic disease. If the presence of metabolic or systemic disease is ruled out, then the intestine is investigated. A complete diarrhea history will determine if the diarrhea is primarily of large or small bowel in origin. Cats with large bowel disease usually have increased urgency, tenesmus with frequent small stools. Stools may have mucus or fresh blood. Cats may defecate outside the litter box. Weight loss is uncommon and some cats may also have vomiting associated with colitis.
Parasites, dietary intolerances, bacterial causes, and inflammatory bowel disease are but a few etiologies of chronic colitis in the cat. Before beginning extensive diagnostics or obtaining an intestinal biopsy there are important diagnostic tests or trial therapies to consider. Obviously the course of action is predicated in part on a good clinical evaluation and based on the severity of the clinical disease.
Every patient with chronic GI signs should have a thorough history, physical examination, complete blood count, biochemical profile, urinalysis, and fecal examination. In many cases, this initial evaluation will determine the etiology of the diarrhea. If the initial workup fails to provide a clue to the etiology, then a specific GI evaluation is undertaken. The fecal examination should include standard fecal flotation, wet mount preparation, and stained cytology for motile trophozoites or bacteria (i.e., Campylobacter). A Diff-Quik-stained fecal cytology may reveal such things as neutrophils, eosinophils, fungal organisms, or clostridial spores and could provide clues to the etiology of diarrhea. Fecal PCR analysis for pathogens may also be performed at this time.
Next, the patient should be classified based on the severity of disease: either having minimal signs and no debilitation that should first be treated symptomatically or cases having severe disease obviously requiring an in-depth GI workup. For the animal with relatively mild diarrhea I prefer to use trial therapy involving anthelmintic therapy, dietary food trials, and lastly antibiotic therapy. If the patient fails to improve with such therapy, then further GI evaluation is indicated. Additional diagnostic testing may include imaging studies (ultrasonography is preferred as barium studies are rarely helpful), serology or PCR testing (folate, cobalamin), and endoscopy or surgery for intestinal biopsies.
Always Rule Out Parasites
Parasites must always be considered in any patient experiencing chronic GI signs. I will empirically treat with anthelmintics such as fenbendazole or pyrantel. Giardia are usually diagnosed using proper fecal examination techniques. The trophozoites can sometimes be seen as falling leaves on wet mount prep cytology in about 20% of the cases. It is also sometimes difficult to find Giardia cysts on flotation (65% diagnostic rate), hence a more accurate way to diagnose Giardia is through fecal ELISA or a fecal IFA for cysts (both about 95% accuracy). In cats, Giardia lives in the lower small intestine (dogs in upper intestine) and signs can often be associated with colitis-like large bowel signs. The treatment of choice for years has been metronidazole. Currently, metronidazole at a dose of 15–25 mg/kg orally once or twice daily for seven days is recommended. Neurologic signs with metronidazole toxicity occur at higher doses (> 30 mg/kg/day) so appropriate dosing is critical.
Other suggested Giardia therapies include fenbendazole or febantel for five days. With treatment failure, one should make sure that Giardia is truly the cause or that subsequent recontamination following therapy is not occurring. Infection with Giardia does not confer immunity. In resistant cases, combined fenbendazole and metronidazole therapy has been suggested. In cats ronidazole (20–30 mg/kg BID for 5 days see below) has been used in difficult-to-treat cases. High-fiber diets, probiotics, silybin (milk thistle substrate) and intestinal antibiotics may help lessen reinfection when given during the therapy. It is controversial whether to treat healthy cats that test positive for Giardia because Giardia is generally not considered a significant human health risk. I recommend treating the asymptomatic, positive cat and, if on recheck evaluation, the patient is still positive but subclinical, I will repeat therapy using a different agent. If the animal remains positive after two therapies, I simply recheck the patient again at the next yearly health evaluation. Some animals are chronic asymptomatic carriers and are very difficult to clear.
The trophozoite Tritrichomonas foetus (TTF) has been identified as a cause of chronic diarrhea in young cats. Most of the affected cats are under 1 year of age and are reported to have a watery to sometimes mucoid diarrhea. It is most often observed in cats coming from humane shelters or catteries, but Abyssinians and Bengal cats appear to be overrepresented or to have a more resistant disease. The incidence of TTF may be higher than previously thought. In one study, approximately 14% of cats evaluated at national cat show were found positive for TTF. There are several ways to diagnose TTF. In some cases, a diagnosis is made by performing a wet mount fecal prep and identifying the organism. A small amount of very fresh stool is thinned with warm saline solution, a coverslip applied, and the feces examined at 40x. Tritrichomonas foetus is identified by its progressive forward motion due to its undulating membrane (In contrast, Giardia has a falling leaf motion). Feces can also be cultured in house by using the bovine TTF culture technique employing an In Pouch TFTM culture method. With these pouches, a very small amount of stool is placed in the broth and cultured at room temperature. The bag is then examined under a microscope 24 to 72 hours later for evidence of motile organisms. Fecal PCR for TTF is offered by many commercial labs and is considered the test of choice for confirming the infection.
Ronidazole is the only antiprotozoal shown to have efficacy in treating TTF infection. Ronidazole is given at 30 mg/kg q 24 h PO for up to 14 days. Ronidazole has a very narrow therapeutic range; higher doses or a longer duration can result in neurotoxicity. Ronidazole is not approved for use in the United States and must be obtained through a reliable compounding pharmacy. It is very bitter and therefore should be given via capsule; liquid solutions are not recommended. Treatment failures can occur, and a fecal PCR should be performed if a cat fails to respond to therapy because a negative PCR result means TTF is a less likely cause of the diarrhea. When left untreated, many cats eventually do become normal, especially young cats under 1 year of age. In one study, 88% cats with TTF infection were reported to undergo spontaneous resolution of diarrhea within two years of a diagnosis; however, most remained infected (57%) based on PCR results when retested as long as two to five years after the initial diagnosis. The role of these asymptomatic carriers in disease transmission remains unclear.
GI signs may resolve by simply changing a patient's diet. It is my impression, which is supported by a number of clinical studies, that possibly up to 50% of dogs and cats with nonspecific GI disease may respond to diet alone. Food-responsive diarrhea includes both true dietary allergies and dietary intolerances. Allergies result from a reaction with a protein antigen, whereas intolerances occur in response to some substance in the diet, such as a preservative or food coloring. A feline study of 55 cats with GI signs found 49% responded to diet alone. Most cats in that study had large bowel signs with mucus, blood, increased urgency, and 38% were reported to also have flatulence. Clues in the laboratory testing include hypoproteinemia or eosinophilia. Antigen testing did not identify food-responsive cases. Most cats responded within one week of dietary change and beef, wheat and corn were most common proteins incriminated. There is no ideal diet that will consistently resolve diarrhea. The main options include diets that optimize nutrient assimilation or diets that favor antigenic modification (e.g., a novel protein source or a protein hydrolysate). My personal favorite is the use of a hydrolyzed diet. Hydrolyzed diets are single-protein sources (usually soy, rice, or potato-based) and have undergone digestion, producing low-molecular-weight protein derivatives that are thought to be highly digestible with low antigenic potential. Their benefit might actually be because they are very pure and contain little else that might contribute to a dietary intolerance. Feeding novel-protein diets with a single protein antigen would be an alternative approach. If using the novel-antigen diets, one should prescribe only veterinary diets because many over-the-counter novel-protein diets are not all that novel and have been shown to contain many other antigens not listed on the label. Diets containing highly fermentable fibers such as those containing fructooligosaccharides (also referred to as prebiotics diets) are often useful for colonic disease because fermentation products are shown to benefit mucosal function and modify enteric microbiota, promoting "good" bacteria and inhibiting certain pathogenic bacteria. Diets can also be supplemented with soluble fiber for colonic disease such as psyllium.
Antibiotics for Diarrhea
If a diet trial is unsuccessful, the next step is to institute an antibiotic trial. There are many cats with chronic large-bowel disease that have an antibiotic-responsive diarrhea (ARD). An old term for ARD is small intestinal bacterial overgrowth (SIBO). More recently, the term gastrointestinal dysbiosis has been given to conditions associated with an abnormal GI bacterial ecosystem. In simple terms, GI dysbiosis refers to an imbalance in GI bacteria with the loss of the "good bacteria" coupled with an increase in the so-called "bad bacteria." Some cats with gastrointestinal dysbiosis also have decreased serum cobalamin (vitamin B12) concentrations.
Metronidazole is frequently used in GI cases, but long-term administration and potential side effects make it less desirable than other options. Metronidazole has been shown to cause DNA damage in vitro to feline lymphocytes. A suggested GI dosage for metronidazole in cats is 7.5 to 10 mg/kg given orally twice daily. A commonly used alternative, and my first choice, is tylosin. Tylosin is a macrolide, bacteriostatic antibiotic that works by transiently changing the GI enteric bacterial population, probably by promoting the growth of beneficial commensal bacteria while suppressing deleterious bacteria. The initial dose recommendation for tylosin is 15 mg/kg orally twice a day. For cases that respond, the long-term dose can be reduced to as low as 5 mg/kg/day in some.
Probiotics are live microorganisms that, when given in adequate amounts, confer a health benefit to the host. The microorganisms most frequently used are lactic acid bacteria (i.e., Lactobacillus, Enterococcus, Streptococcus, and Bifidobacterium species). They are believed to impart a beneficial effect, but the mechanism remains poorly understood. Some probiotic strains have been shown to modulate the immune system. Others help to restore or normalize the function of the mucosal barrier or protect the normal microbiota from pathogenic bacteria through the production of antimicrobial substances or from competitive exclusion of pathogens. To date, there have been very few controlled clinical studies evaluating probiotic success. However, a large double-blinded placebo control study of shelter cats developing diarrhea found significantly fewer cats that received Enterococcus faecium (2.1 x 109 cfu/day) developed diarrhea for greater than a two-day duration. Probiotics exert their effects as long as they are being given, but, once stopped, the GI flora generally returns to the pretreatment state. It may seem counterintuitive to give antibiotics with probiotics, but clinical improvement is often seen when they are given in combination. Probiotics are considered a safe adjunctive therapy and are commonly used for both acute and chronic diarrhea in cats as well as for the prevention of stress-induced diarrhea.
When Is It Colitis (IBD)?
Inflammatory changes in the colon are usually lymphocytic-plasmacytic, but other forms include eosinophilic, neutrophilic, and granulomatous enteritis. The inflammation can be confined to the colon or also involve the small intestine and then is often termed as inflammatory bowel disease (IBD). Although the etiology is unknown, it is widely accepted that the pathogenesis involves a complex interplay among host genetics, the intestinal mucosal immune system, the environment, and the intestinal microbiota.
Clinically, cats having only the colon involved fail to lose weight. Because of colonic inflammation, many cats also may have vomiting as part of their presenting clinical complaint. Cats having significant colitis signs or those that have failed conservative therapy will require a complete laboratory evaluation including a complete blood count (CBC), biochemical profile, urinalysis, fecal cytology, fecal wet mount prep, and parasite evaluation. It is also important to test the thyroid, FeLV and FIV status. An eosinophilia or hypoproteinemia (rare with only colon involvement) may provide clues to IBD. Abdominal radiographs or ultrasonography may also be helpful. However, ultrasound images showing increased wall thickness are neither specific nor sensitive for the diagnosis of IBD. Specific testing may include measurement of serum folate and cobalamin concentrations. Cobalamin deficiency is a common complication of feline GI disorders suggesting significant ileal disease or bacterial dysbiosis. When cobalamin-deficient, complete improvement in GI function is not possible until the cobalamin deficiency is corrected. Colonoscopy and colon biopsies are required for a definitive diagnosis. We rarely, if ever, perform surgical colonic biopsies. Because of frequent ileal and cecal involvement with lymphoma, it is important during colonoscopy to collect ileal mucosal biopsies.
Treatment of Inflammatory Colitis
Most cats that fail to respond to a diet or antibiotic trials are usually administered glucocorticoids and many will respond. Generally, oral prednisolone is given once daily at a starting dose of 1 to 2 mg/kg, and then the dose is tapered over an eight-week period. Treatment dose and duration is dictated on clinical response. Budesonide is a novel glucocorticoid that is reported to have high first-pass hepatic metabolism and exerts a "local effect" on the intestine with reported minimal systemic effects at least in humans. An enteric-coated formulation is used for people with IBD, but a non-enteric-coated formulation made by a compounding pharmacy should be used. Despite apparent efficacy of budesonide, the systemic steroid effects are present and consequently, its use may have no benefit over traditional corticosteroid therapy in most cases. The recommended dose for budesonide is 1 mg once daily in cats.
If there is poor response to glucocorticoids after the first three to four weeks or if the side effects are severe, then I recommend concurrent immunosuppressive therapy. Considerations include oral cyclosporine 5–7 mg/kg once daily (AtopicaTM liquid). In cats, the use of chlorambucil (2 to 6 mg/m2, q 24 h, PO, or 2 mg/cat three times a week) with prednisolone is used for GI small cell lymphoma and is a protocol I use for severe IBD as well. Azathioprine frequently used in dogs has many side effects in cats and is not recommended.
Other novel or adjunctive therapies could include omega 3 fatty acids for anti-inflammatory effects and various antioxidants. Probiotics may also be beneficial for treating inflammatory colitis due to the multiple mechanisms described above.
1. Tangtrongsup S, Scorza V. Update on the diagnosis and management of Giardia spp. infections in dogs and cats. Top Companion Anim Med. 2010;25(3):155–162.
2. Gookin JL, Breitschwerdt EB, Levy MG, et al. Diarrhea associated with trichomonosis in cats. J Am Vet Med Assoc. 1999;215(10):1450–1454..
3. Guilford WG, Jones BR, Markwell PJ, Arthur DG, Collett MG, Harte JG. Food sensitivity in cats with chronic idiopathic gastrointestinal problems. J Vet Intern Med. 2001;15(1):7–13.
4. Gaschen FP, Merchant SR. Adverse food reactions in dogs and cats. Vet Clin North Am Small Anim Pract. 2011;41(2):361–379.
5. Hall E. Antibiotic-responsive diarrhea in small animals. Vet Clin North Am Small Anim Pract. 2011;41:273–286.