Tips to treat persistent cases of chronic diarrhea in pets (Sponsored by Nestle Purina)

Gastrointestinal disorders are frequently either unrecognized or misdiagnosed. The appropriate recognition of a specific condition and subsequent therapy may resolve the disorder. The purpose of this presentation is to provide important practice tips for diagnosing and managing various gastrointestinal disorders associated with diarrhea.

Chronic diarrhea is a common complaint, and the potential etiologies are extensive. Parasites, dietary intolerances, metabolic disease, pancreatic disease, bacterial causes, and inflammatory bowel disease are but a few etiologies of chronic diarrhea. Inflammatory bowel disease (IBD) is a common condition diagnosed in dogs and cats; however, it is not a specific disease but rather a term that describes animals having gastrointestinal (GI) signs with histologic evidence of inflammation within the intestine. IBD does not, however, describe the etiology, nor does the extent of inflammatory cells parallel the severity of clinical signs. Before beginning extensive diagnostic tests or obtaining an intestinal biopsy specimen from a patient with chronic diarrhea, there are a few diagnostic tests or trial therapies to consider (Figure 1). Obviously the course of action is predicated, in part, on a good clinical evaluation and based on the severity of the clinical disease.

Figure 1. A basic approach in the work-up and clinical management of a chronic diarrhea case.

Every patient with chronic GI signs should have a thorough history, physical examination, complete blood count, serum chemistry profile, urinalysis, and fecal examination performed. In many cases, this initial evaluation will determine if the etiology of the diarrhea is primary GI disease or secondary to other systemic or metabolic disease, or if the diarrhea is predominantly of small bowel or large bowel origin. For example, Addison's disease, liver disease, and renal disease can all be associated with secondary GI involvement. If the initial work-up fails to provide a clue as to the etiology, then begin a specific GI evaluation. The fecal examination should include standard fecal flotation, wet-mount preparation, and stained cytology. A Diff-Quik-stained cytologic slide may reveal such things as neutrophils, eosinophils, fungal organisms, or clostridial spores and may provide clues about the etiology (Figures 2A-2D). This is also the time to classify the patient based on the severity of disease: minimal signs and debilitation or those cases having severe disease obviously requiring an in-depth GI work-up.

Figures 2A-2D. Fecal cytology showing: (A) a Diff-Quik-stained thin fecal smear, (B) normal feces with amorphous debris and mixed bacterial flora, (C) abundant clostridial spores, and (D) many neutrophils.

For the animal with relatively mild diarrhea without weight loss or debilitation, I prefer to use trial therapy as part of the clinical evaluation. Trial therapy involves antiparasitic therapy, dietary food trials, and antibiotic therapy. If these trial therapies fail to resolve the diarrhea, further GI evaluation is indicated. Additional diagnostic testing may include imaging studies (ultrasonography is preferred, as barium studies are rarely helpful), serology (trypsin-like immunoreactivity, folate, cobalamin), and endoscopy or surgery for intestinal biopsies.

Always rule out parasites

Parasites must always be considered in any dog experiencing chronic GI signs.1 Giardia species and common nematodes are usually diagnosed using proper fecal examination techniques. Often it is difficult to find Giardia cysts on flotation, hence a more accurate way to diagnose Giardia infection is through fecal ELISA, which is highly sensitive and specific. It is important to know that Giardia species also have antimicrobial sensitivity patterns like bacteria. Thus, it is impossible to predict which anti-Giardia drug will be effective in an individual dog or cat. The treatment of choice for years has been metronidazole. Metronidazole at a dose of 25 mg/kg orally, twice daily, for seven days is preferred; however, there are many different doses and durations of therapy reported (Table 1). Neurologic signs associated with toxicosis occur at higher doses.

Table 1. Drugs for the treatment of Giardia infection

Other suggested Giardia therapies include febendazole or febantel for five days.1 High-fiber diets may help lessen reinfection when given during the therapy. With treatment failure, one should make sure that Giardia infection is truly the problem and also that subsequent recontamination is not occurring. Infection with Giardia species does not confer immunity. In resistant cases, combined febendazole and metronidazole therapy has been suggested. In difficult cases, bathing the animal before therapy and decontaminating the environment using quaternary ammonium compounds is also recommended.

It is controversial whether to treat healthy dogs and cats that test positive for Giardia species because Giardia is generally not considered a significant health risk for people. I recommend treating the asymptomatic positive dog 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 difficult to clear. It is a more significant concern when infected dogs live with immunocompromised individuals or young children.

Young cats with diarrhea

The organism Tritrichomonas foetus (TTF) has been identified as a cause of chronic diarrhea in young cats.2 This organism appears to be genetically similar to that associated with bovine venereal disease. 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 from humane shelters or catteries, and Abyssinians and Bengal cats appear to be over-represented or to have a more resistant disease.

There are several ways to diagnose TTF. In some cases, a diagnosis can be made by performing a wet-mount fecal prep and identifying the organism. A small amount of stool is thinned with warm saline solution, a coverslip applied, and the feces examined at 40X. It is important that the stool is fresh for examination. A colonic flush of saline can also be used to obtain fecal material for cytology and culture. TTF is identified by its progressive forward motion. (In contrast, Giardia has a falling leaf motion.) Feces can also be cultured in your practice using the bovine TTF culture technique, employing an In Pouch TF™ culture method (Biomed Diagnostic Labs) (Figure 3). 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 laboratories and is considered the test of choice for confirming the infection.

Figure 3. An In Pouch TF can be used to culture feline feces for Tritrichomonas foetus.

Ronidazole is the only antimicrobial shown to have efficacy in treating TTF infection.3 Ronidazole is given at 30 mg/kg orally once a day, for up to 14 days. Ronidazole has a narrow therapeutic range; higher doses or a longer duration can result in neurotoxicosis. Ronidazole is not approved for use in the United States and must be obtained through a reliable compounding pharmacy. It is bitter and, thus, should be given in a capsule; liquid solutions are not recommended. Treatment failure can occur, and a fecal PCR should be performed if a cat fails to respond to therapy. A negative PCR result means TTF is a less likely cause of the diarrhea. When left untreated many cats eventually 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 based on PCR results when retested as long as two to five years after the initial diagnosis.4 The role of these asymptomatic carriers in disease transmission remains unclear.

When the diet works

Over the years, I have become more and more impressed to see GI signs resolve simply by changing a patient's diet. It is my impression, which is supported by a number of clinical studies, that possibly 30% to 50% of dogs and cats with nonspecific GI disease may respond to diet alone.5-7 Dogs with food-responsive diarrhea tended to be younger, and more have large bowel signs and higher serum albumin concentrations. However, I have recently observed a debilitated and hypoproteinemic patient respond to a diet change only. Consequently, a dietary trial should be the first step in evaluating a patient that has chronic diarrhea after systemic, metabolic, and GI parasitic disease are eliminated as potential causes. Severely debilitated or anorectic patients with GI disease would obviously require more specific and aggressive evaluation. For the remainder of patients with chronic diarrhea, a dietary trial is justified.

Diarrhea that responds positively to a diet trial is referred to as food-responsive diarrhea (FRD). FRDs include diarrhea caused by 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. Dietary trials using a test diet generally require two weeks or less to appreciate a response; the GI signs seem to respond much faster than dermatologic signs, which that may take eight weeks or more to improve.

There is no ideal diet that will consistently resolve diarrhea. The main options include diets that optimize nutrient assimilation (e.g. highly digestible, fat-restricted, or low-fiber food) or diets that favor antigenic modification (e.g. a novel protein source or a protein hydrosylate). My personal favorite is the use of a hydrolyzed diet, such as Purina HA®.

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 pure and contain little else that might contribute to a dietary intolerance. These diets have now become the ideal initial trial diet. If a positive response is observed, then the patient's GI signs can be controlled with a diet. The patient can either continue on the test diet or you can attempt to find another long-term diet that works well for both the client and patient. Some clinicians recommend that if there is a diet response the patient be fed that diet exclusively for at least three months, at which time the diet can be changed or even the original diet reintroduced. Only a small percentage of dogs with GI signs (~8%) relapse on challenge and are, thus, truly food allergic.7

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.8 Highly digestible GI diets such as Purina EN® may improve assimilation, promote GI health, and modify the microbiota. 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.9 If a diet trial is unsuccessful, with no improvement in clinical signs after 10 to 14 days, the next step is to institute an antibiotic trial.

GI drugs and bugs

There are many dogs with chronic large or small bowel disease that have antibiotic-responsive diarrhea (ARD). An old term for ARD is small intestinal bacterial overgrowth (SIBO). However, SIBO is a poorly defined syndrome in dogs, and we have no way to adequately and convincingly diagnose bacterial overgrowth or to know in which cases antibiotics would be beneficial, short of a therapeutic trial. More recently the term GI dysbiosis has been given to conditions associated with an abnormal GI bacterial ecosystem.10 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." For chronic diarrhea cases that do respond to antibiotic therapy, it is likely the antibiotics are not eliminating a specific pathogen but rather changing the overall bacterial ecosystem, promoting a more normal bacterial makeup. Some cats and dogs with GI dysbiosis have decreased serum cobalamin (vitamin B12) concentrations.11 The cobalamin deficiency can be due to lack of intrinsic factor production, abnormal increased intestinal bacterial utilization, or ileal disease causing inadequate cobalamin absorption. Serum folate concentrations are usually variable in patients with dysbiosis.

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 to feline lymphocytes in vitro. There is also evidence in laboratory animals that it has some carcinogenic potential.12 A suggested GI dosage for metronidazole in cats and dogs is 7.5 to 10 mg/kg, given orally, twice daily.

A commonly used alternative, and my first choice, is tylosin. Tylosin was first reported to be useful for treating chronic diarrhea in the early 1970s, and there has been a recent resurgence in interest and use of the antibiotic. Tylosin is a macrolide, bacteriostatic antibiotic that is marketed over-the-counter for the treatment of respiratory disease in chickens. Tylosin has activity against most gram-positive and gram-negative cocci, gram-positive rods, and Mycoplasma species; however, the gram-negative bacteria Escherichia coli and Salmonella species are intrinsically tylosin-resistant.13

Tylosin works by transiently changing the GI enteric bacterial population, probably by promoting the growth of beneficial commensal bacteria while suppressing deleterious bacteria. Once tylosin is discontinued, the original bacterial population often returns to its pretreatment state. There is also a suggestion that tylosin may have anti-inflammatory properties.13 Tylosin appears to have almost no systemic or toxic side effects. The initial dose recommendation for tylosin in both dogs and cats is 15 mg/kg orally, twice a day, mixed with food (has a bitter taste) or given in a gelatin capsule. (Note: it comes as a powder and a #3 gelatin capsule holds 130 mg, a #1 capsule holds 240 mg, a #0 capsule holds 345 mg, and a #00 capsule holds 430 mg.) For cases that respond, the long-term dose can be reduced to as low as 5 mg/kg/day.13 Tylosin is effective for treating most Clostridium perfringes and is considered by many to be the treatment of choice for suspected clostridial diarrhea.14

Probiotics

In a review of referral histories at a teaching hospital in Liverpool, England, during an eight-year period, up to 26% of dogs treated for diarrhea received alternative therapies usually including probiotics.15 By definition, 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 (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 few controlled clinical studies evaluating probiotic success. However, a large double-blinded placebo control study of shelter dogs and cats developing diarrhea found significantly fewer cats that received Enterococcus faecium (FortiFlora®, 2.1 x 109 cfu/day) developed diarrhea for more than a two-day duration.16

Probiotics exert their effects as long as they are being given; 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 treating both acute and chronic diarrhea in dogs and cats, as well as for the prevention of stress-induced diarrhea.15-17

Recommendations for the ideal probiotic, containing an adequate type and number of viable organisms for specific GI disorders, are difficult to make. Some over-the-counter preparations have been found not to contain the label claims.18 My recommendation is to use a product produced by a reputable veterinary company that has done research on it product.

German shepherds with chronic diarrhea

A clinical syndrome frequently encountered in German shepherd dogs is chronic GI signs and weight loss. Exocrine pancreatic insufficiency is common in the breed, requiring pancreatic enzyme supplementation. Thus, it must first be ruled out. The diagnosis is made by documenting a subnormal trypsin-like immunoreactivity (TLI) concentration followed by improvement with pancreatic enzyme replacement.

A second group of German shepherd dogs with similar clinical signs have normal TLI concentrations (Figure 4). Many of these dogs turn out to have ARD due to GI dysbiosis. Testing should include measurement of folate and cobalamin (serum B12) concentrations. Low cobalamin and high folate concentrations are characteristic of both exocrine pancreatic insufficiency and GI dysbiosis. Dogs with subnormal cobalamin concentrations will require parenteral supplementation (initially, about 500 μcg, subcutaneously, weekly) as part of their therapy. The cause of GI dysbiosis in German shepherds is unknown. Researchers have investigated IgA concentrations, suggesting the possibility of an inherent deficiency leading to altered GI immunity. More recently researchers have measured toll-like receptors (TLR) in the GI tract of these dogs with a documented abnormal expression of the receptors. Using candidate gene analysis, polymorphisms in TLR4 and TLR5 were recently shown to be significantly associated with IBD in German shepherds.19 Furthermore, the same polymorphisms in TLR5 were also associated with IBD in a heterogeneous population of dogs consisting of 38 different breeds.19

Figure 4. A 2-year-old neutered male German shepherd dog with chronic diarrhea and failure to gain weight. The dog responded to tylosin therapy, which is typical of antibiotic-responsive diarrhea.

These mutations could well play an important role in the pathogenesis of IBD in dogs, A mutated receptor will lead to misrepresentation of commensal bacteria as pathogens, thus signaling "danger" to the host and initiating the characteristic inflammatory response seen in this disease.

Management of affected German shepherds involves diet, antibiotics, and cobalamin supplementation. Prebiotics and probiotics are also often given as additional adjunctive therapy. This condition tends to require lifelong management.

When is it inflammatory bowel disease?

I generally consider IBD as the probable diagnosis when GI parasites have been ruled out and when the patient fails to respond to appropriate dietary and antibiotic trials or if the clinical severity is such that trial therapies should be precluded. The classification of IBD is generally based on the region of the GI tract affected and on the predominant cell type in the inflammatory infiltrate. Lymphocytic-plasmacytic enteritis is the most common type of IBD observed in dogs and cats. Other forms include eosinophilic, neutrophilic, and granulomatous enteritis. There are also breed-specific forms of IBD, best recognized in soft-coated Wheaten terriers with a protein-losing enteropathy (PLE), in Basenjis with an immunoproliferative enteropathy, in Norwegian Lundehunds with IBD and PLE, and in Boxers with histiocytic ulcerative colitis.

Although the exact etiology of IBD 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. Studies using both histochemical and immunohistochemical techniques to describe immune cell populations and cytokine expression in the intestinal mucosa have had variable results, preventing the compilation of a general description of abnormalities in IBD. Histopathology confirms IBD or, more appropriately, inflammatory changes in the intestine (Figure 5). However, architectural changes (such as villous atrophy) seem to be more important than solely identifying the inflammatory infiltrates present. Also, the lesions can be variable throughout the GI tract, so multiple biopsy samples from different areas are suggested.

Figure 5. Endoscopic biopsy showing mixed inflammatory lymphocytic-plasmacytic infiltrates with villous blunting. This patient failed to respond to prednisolone therapy but responded to cyclosporine therapy.

A diagnosis of IBD requires a complete laboratory evaluation to rule out other diseases. A complete blood count, serum chemistry profile, urinalysis, fecal cytology, and parasite evaluation are required in all cases. An eosinophilia or hypoproteinemia may provide clues to IBD. Abdominal radiography or ultrasonography may be helpful. However, ultrasound images showing increased wall thickness are neither specific nor sensitive for the diagnosis of IBD.20

Specific testing may include measurement of fecal 1-proteinase inhibitor concentrations for documenting GI protein loss and measurement of serum folate and cobalamin concentrations. Cobalamin deficiency is a common complication of feline GI disorders, and complete improvement in GI function is not possible until cobalamin deficiency is corrected.11

An overall impression is that most cases of IBD can be managed; however, unless the underlying etiology can be identified and removed, it can become a long-term proposition. A retrospective study demonstrated that only 26% of canine IBD cases progressed to complete remission, with intermittent clinical signs remaining in about half of the cases, 4% being completely uncontrolled, and 13% resulting in euthanasia because of poor response to treatment.21 Another study found 18% of the dogs were euthanized because of their disease.6 Poor prognostic indicators are hypoalbuminemia and hypocobalaminemia.6

Treatment of IBD

Patients that do not respond to a diet or an antibiotic trial are usually administered glucocorticoids. It is estimated that about 30% of the dogs that fail to respond to a change of diet and antibiotics will respond to corticosteroids. Generally oral prednisolone is given to dogs and cats once daily at a starting dose of 1 to 2 mg/kg, and then the dose is tapered over an eight-week period. However, the side effects of glucocorticoids can be marked, and I try never to exceed a total of 40 mg per day in large-breed dogs.

Budesonide is a novel glucocorticoid that is reported to have high first-pass hepatic metabolism and exerts a "local effect" on the intestine with minimal systemic effects. An enteric-coated formulation is given to people with IBD but a nonenteric coated formulation made by a compounding pharmacy should be given. Despite apparent efficacy of budesonide in dogs and cats, the systemic steroid effects are present, and consequently, its use may have no benefit over traditional corticosteroid therapy in most cases. The recommended dose is 1 mg, once daily, in cats and toy breeds and up to 2 mg, once daily, for large-breed dogs.

If there is poor response to glucocorticoids in dogs after the first three or four weeks or if the side effects are severe, then I recommend oral cyclosporine at 5 to 10 mg/kg, once daily, for at least two months. Many dogs with IBD that are steroid-refractive are reported to respond to cyclosporine.22

In cats, the use of chlorambucil (2 to 6 mg/m2, orally, once a day, or 2 mg/cat three times a week) with prednisolone is preferable if there is inadequate response to glucocorticoid treatment alone. If chlorambucil is used, hematologic parameters should be monitored regularly. Cyclosporine blood concentrations do not need to be monitored regularly unless side effects induced by the cyclosporine treatment are suspected or an inadequate response to treatment is observed. If measuring cyclosporine serum concentrations, it is recommended to take blood samples one or two hours after giving the medication to ensure that peak concentrations are measured. If the cyclosporine serum concentration is above 700 ng/ml at peak level, then halving the dosage for the first two weeks can reduce the side effects.22 If the patient responds to cyclosporine, then the medication can either be tapered slowly or stopped after 10 weeks.

Sulfasalazine (20 to 50 mg/kg orally, three times daily, for three to six weeks) and related drugs are often administered to dogs when IBD is limited to the large intestine. Side effects include keratoconjunctivitis sicca, so tear production should be monitored regularly when giving these drugs. I rarely prescribe sulfasalazine for large bowel disease because, in my experience, most patients get better with a diet change and antibiotic administration.

Other novel or adjunctive therapies could include omega 3 fatty acids for anti-inflammatory effects and various have also been suggested to be beneficial for treating IBD because of the multiple mechanisms described above.

Is it feline IBD or lymphoma?

When a cat fails to respond to traditional therapy for IBD, one must consider GI lymphoma. Lymphoma is the most common neoplasia in cats, and most feline lymphomas involve the GI tract.23 GI lymphoma has been classified histologically as B-cell or T-cell in origin. The most common is the low-grade T-cell lymphoma that is characterized by the mucosal and submucosal infiltration of small well-defined lymphocytes (Figures 6A-6C.) Cats with these lymphomas are usually FeLV-negative. The low-grade lymphocytic form usually responds well to chemotherapy. The infiltration in the bowel by the tumor generally results in malabsorption. In contrast, lymphoblastic (generally B-cell origin) lymphomas usually present with a mass-like lesion (most often in the stomach and colon) and generally have a poor prognosis.

Figures 6A-6C. (A) A 12-year-old neutered male domestic shorthaired cat that presented for weight loss, vomiting, and lethargy. (B) Endoscopic view of the proximal duodenum appeared normal. Biopsy showed lymphocytic-plasmacytic enteritis. There was little improvement with diet and prednisolone therapy, which prompted full-thickness small bowel biopsies. (C) There is marked lymphocytic infiltrates in the mucosa and deeper layers, typical of small cell lymphocytic lymphoma.

Most cats with GI lymphoma (small cell) are middle-aged or older domestic shorthaired cats. Weight loss, vomiting, chronic small bowel diarrhea, and progressive inappetence are common features of GI lymphoma. Some cats may present only with weight loss as the chief complaint. On physical examination, the bowel may be normal or feel diffusely thickened. Mesenteric lymphadenopathy may also be identified. Less commonly organomegaly may occur.

Routine laboratory testing is often unremarkable or may reveal hypoalbuminemia. Anemia may also be present. Most cats with GI lymphoma have significantly subnormal serum concentrations of cobalamin. Serum folate concentrations may also be reduced. Some cats may also have concurrent pancreatitis with increases in pancreatic lipase or cholangitis with increased liver enzymes.

Ultrasonography is useful for evaluating intestinal thickness or loss of normal layering and detecting mesenteric lymphadenopathy. The diagnosis can occasionally be made by demonstrating neoplastic lymphocytes in aspirates from enlarged intestinal or peripheral lymph nodes. Frequently though, lymph nodes show only reactive changes. Endoscopic visualization and biopsy can enable the accurate diagnosis of many cases of GI lymphoma. Endoscopy biopsies can, however, miss submucosal and serosal lesions or yield a diagnosis of lymphoplasmacytic enteritis (IBD) because of inadequate tissue. One report suggests that GI lymphoma is more common in the ileum than in the duodenum, so ileal biopsies are indicated in suspected cases.24 Because of concurrent liver and pancreatic disease and the possible location of tumor in the ileum, exploratory surgery may be indicated in some cases.25

In a study of 41 cats with low-grade lymphoma, the lymphoma was confined to the GI tract in 68% of cats.26 Eighty-nine percent of the lymphomas were determined to be of T-cell origin through immunohistochemistry, while 8% (three of 36) were of B-cell origin. Fifty-five percent of cats achieved a complete response to therapy, and 37% achieved a partial response.

In another study of 67 cases, most cats (76%) received prednisolone at a dose of 5 to 10 mg, orally once or twice a day, and most (85%) received chlorambucil at a dose of 2 mg, orally, every other day.27 Overall median remission duration was 948 days. Partial response to therapy was associated with shorter remission duration. Overall median survival time was 704 days. No factors were significantly associated with survival time. Eight percent of the cats experienced no response.27

Hypocobalaminemia was found in 78% of cats tested, and supplemental cobalamin (250 μg given subcutaneously once a week) should be given as required. Intravenous pulse chlorambucil or other chemotherapy may be also tried; however, in most cases, every-other-day oral therapy is easier for the client.

Differentiating between IBD and lymphoma histologically can sometimes be difficult, and IBD may progress to lymphoma over time. Using the PCR for antigen receptor rearrangement, or PARR assay, for clonality (neoplastic cells have one basic clone type) may help and is thought to be about 90% accurate for detecting lymphoma. Fresh tissue from a biopsy or an unstained histology slide is needed for this test. PARR is available at Colorado State University (http://www.cvmbs.colostate.edu/ns/departments/mip/cilab/faq_parr.aspx). More recently, a blood test measuring thymidine kinase activity used to distinguish feline IBD from GI lymphoma has become commercially available. Increased thymidine kinase activity results with proliferative neoplastic disease. As yet there is limited information on this test.

Summary

Chronic diarrhea is a common and often frustrating clinical problem. Work-up of a case generally requires a systematic approach. Trial therapies involving parasite control, dietary manipulation, and antibiotic therapy are often used in noncritical cases. With a failure to respond to simple trial therapies or in critical cases, in-depth diagnostic testing and specific therapy protocols are necessary.

David C. Twedt, DVM, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado.

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