Is it IBD? (Proceedings)

Diagnostics for chronic gastrointestinal problems include a complete blood count (including manual differential), biochemical profile, urinalysis, fecal flotation (+/- direct examination, fecal cytology, sedimentation, acid-fast staining, occult blood, PCR testing for parasites), thoracic and abdominal radiographs and abdominal ultrasound. Trypsin-like immunoreactivity may be indicated.

In the stable patient with a prolonged history of vomiting and/or diarrhea I delay biopsies until empirical trials have been performed. A 5-day course of metronidazole (10 mg/kg/day once daily), 3-day course of fenbendazole and 4-10 week hypoallergenic feeding trial are prescribed. In the "sick" patient (severe clinical signs, weight loss, panhypoproteinemia) I proceed directly to gastrointestinal biopsy. I chose endoscopy for its lack of morbidity but prefer full thickness biopsies for patients suspected of having intestinal neoplasia.

The diagnosis of gastrointestinal problems is made by pattern recognition, diagnostic testing, therapeutic trials, and gastrointestinal biopsy. Unfortunately, biopsy of the intestinal tract often reveals nonspecific inflammatory change the cause of which remains to be determined.

Clostridium perfringens-associated diarrhea (perhaps more accurately termed Antibiotic-Responsive Diarrhea?).

This is a common cause of diarrhea in the dog but rare in cats. Clostridium perfringens may cause acute, intermittent or chronic signs. In the ACUTE form dogs show signs of large bowel diarrhea (blood, mucus and/or straining) but act well and eat normally. Occasional vomiting may occur, but loss of appetite or severe listlessness excludes this diagnosis. Signs may develop after boarding, grooming, or hospital visit and is commonly described as "stress colitis." The INTERMITTENT form presents as large bowel diarrhea that resolves and recurs at weekly to monthly intervals. The patient remains healthy and eats well during these episodes. The CHRONIC form presents as large bowel diarrhea that responds to antibiotics but relapses whenever antibiotics are stopped. All forms are more common in dogs eating low fiber diets.

The diagnosis should be suspected in patients with large bowel diarrhea, clostridial spores on fecal cytology, and an immediate response to antimicrobial therapy.

For fecal cytology a fresh stool sample is rolled onto a glass slide using a cotton-tipped applicator, air-dried, and stained with Diff-Quik®. Examination at 1000x reveals the overgrowth of large rods and presence of vegetative spores. Spores do not take up stain and appear clear or light green. The presence of more than five spores per 1000x field is considered abnormal.

Fecal culture for C. perfringens is not useful because most dogs carry this bacterium as part of their normal flora. The diagnostic value of testing for C. perfringens enterotoxin is uncertain.

Antimicrobial therapy is helpful for diagnosis as well as treatment of the disease. Beta-lactam antibiotics, metronidazole and tylosin are all effective. Either oral or parenteral therapy stops diarrhea within 12 hours and lower than normal doses of antibiotics are effective. If diarrhea persists for longer than 24 hours after antimicrobials have been started, the diagnosis is excluded. Doses higher than 10 mg/kg/d of metronidazole are not more effective.

The ACUTE form responds to a 5-day course of therapy. Additional dietary fiber is recommended for patients with the INTERMITTENT or CHRONIC forms together with 2-4 weeks of antibiotics. The use of grocery store "senior" diets may be adequate or fiber may be added through the addition of Metamucil®, coarse bran or canned pumpkin. Some patients require high fiber diets (such as Hills W/d or R/d®) or rarely intermittent or continuous antimicrobial therapy.

Pancreatic insufficiency.

Chronic diarrhea, voluminous stool, and ravenous appetite in a young dog is classic for pancreatic insufficiency. However the early stages may demonstrate intermittent diarrhea with antibiotic or dietary responsiveness. In these cases the disease progresses over a 3-6 month period to persistent diarrhea with weight loss. Pancreatic insufficiency is rare in the cat, but usually seen in mature to elderly cats. The test of choice is the trypsin-like immunoreactivity (TLI) assay which is diagnostic even in the early stages of the disease.

Treatment for pancreatic insufficiency is frequently successful but unfortunately, expensive. I recommend Viokase® 1 tsp/20 lb/meal and two daily meals of reduced-fat food. If diarrhea resolves and the dog regains body weight, the dose of Viokase is tapered to the minimum necessary dose. Once that is determined, the diet is changed to a commercial diet. Avoid high fiber diets initially, but some patients do better on one diet than another and experimentation is necessary.

If diarrhea fails to resolve on Viokase and low fat diet, consider antibiotic-responsive disease, Vitamin B deficiency, and/or concurrent inflammatory bowel disease. Note: oral bleeding has been associated with pancreatic enzyme replacement therapy.

Tritrichomoniasis

Cats may develop large-bowel diarrhea associated with the presence of trichomonads in the feces. The disease appears more commonly in young, purebred cats obtained from a cattery or shelter. Patients act and eat well, but have intermittent to persistent diarrhea. The diagnosis may be confirmed by direct fecal examination. Fresh stool is mixed with 0.9% saline and examined at both 100 and 400x. Use of tap water will rapidly destroy the trichomonads. Tritrichomonads can be differentiated from Giardia trophozoites by their rapid forward motility. Negative fecal examination does not exclude the diagnosis; PCR testing is more sensitive and specific than pouch culture.

The best treatment for trichomoniasis is unclear. Response to metronidazole (30 mg/kg/d) is common, but so is relapse. Paromomycin has been associated with renal failure and should not be used. Ronidazole is currently the treatment of choice at 30 mg/kg q 12-24 hours (stop at first sign of neurologic toxicity). High fiber diets (Hills W/d or R/d®) may be helpful. The disease may self-resolve with age.

Tritrichomonas may be associated with diarrhea in dogs, but information is still scarce.

Food intolerance

Food intolerance may cause small and/or large intestinal disease and signs may be constant or intermittent. Concurrent dermatologic signs may be present. Cases may be subdivided into diet-induced disease (clinical signs resolve when the diet is changed, and return when the original diet is again fed) and diet-responsive disease (signs resolve when the diet is changed but do not relapse when rechallenged with the original diet).

     A summary of veterinary food intolerance studies:

           1. Inflammatory bowel disease should not be considered idiopathic until a thorough attempt has been made to exclude food intolerance.

           2. No commercially prepared diet should be expected to be "non-allergenic" to all patients. Intolerance has been documented to all commercially prepared diets.

           3. An elimination diet should be chosen based upon dietary history, the owner's enthusiasm to prepare food, and their willingness to accept a false result.

           4. Home-cooked diets are preferred for elimination trials. Novel ingredients should be chosen for both the protein and carbohydrate sources. Hydrolyzed diets show similar efficacy to novel protein-source foods (50-80% efficacy when food intolerant patients are challenged).

           5. The optimum duration of the feeding trial is unknown. Currently 4-6 weeks are recommended for dermatologic trials. Response in gastrointestinal cases may occur in a shorter period of time.

Idiopathic inflammatory bowel disease (IBD)

Inflammatory bowel disease may cause waxing and waning or constant signs of disease. Vomiting, diarrhea and/or poor appetite are most common, although belching, excessive licking, pica, and borborygmus may be the presenting complaint.

The diagnosis of inflammatory bowel disease is one of exclusion. The presence of inflammation on intestinal biopsies does not guarantee the patient has primary (idiopathic) inflammatory disease.

Treatment involves an easily digested or novel protein diet and prednisone 1-2 mg/kg/day orally. Metronidazole 10 mg/kg/d once daily is added if diarrhea is present. Azathioprine 2 mg/kg once daily orally or cyclosporine (5 mg/kg q 12-24 h) is added if hypoproteinemia is present. Once response is seen the dose of all drugs is tapered over a 6-month period. In some cases medications may be stopped and in others life-long therapy is necessary.

Lack of response to prednisone, metronidazole and dietary change suggests a need for reevaluation. Azathioprine, cyclosporine, or chlorambucil may be used to provide additional immunosuppression. Other considerations include: Is the diagnosis appropriate? Has food intolerance been excluded? Has concurrent C. perfringens-associated enteritis occurred? Has the patient developed salmonellosis, giardiasis, toxoplamosis or cryptosporidiosis? Could the patient have lymphoma? The diagnosis and exclusion of gastrointestinal lymphoma is particularly challenging and full-thickness biopsies may be needed.

Gastrointestinal lymphosarcoma

Controversy exists whether IBD may progress over time to gastrointestinal lymphosarcoma (GI LSA); in most cases initial misdiagnosis is more common. Reasons for misdiagnosis include the method of acquiring the biopsy (endoscopic biopsies will not detect all cases) as well as variation between pathologists in sample interpretation.

GI LSA may present with diffuse infiltration or focal masses in any part of the gastrointestinal tract. Diagnostic testing may reveal peripheral lymphadenopathy, intestinal thickening, abdominal masses, circulating lymphoblasts, hypercalcemia, or an anterior mediastinal mass. Ultrasound may reveal changes in the gastrointestinal tract or lymph nodes and allow percutaneous sampling. In some patients no abnormalities are found and GI LSA is diagnosed only after intestinal biopsy. I prefer full thickness biopsies when GI LSA is considered likely. If endoscopic biopsies reveal only inflammatory changes the presence of GI LSA cannot be excluded.

All forms of GI LSA are treated with chemotherapy. Focal lymphosarcoma of the feline stomach may undergo dramatic remission and sometimes cure. Rarely, focal lymphosarcoma of the feline intestine may do the same. "Small cell lymphoma" of the feline intestine (diffuse lymphocytic rather than lymphoblastic infiltration) responds well to prednisolone and chlorambucil with long-term (1-3 year) remission. Unfortunately most forms of canine GI LSA carry a poor long-term prognosis.