Diagnosing IBD: Exclude known causes of chronic intestinal disease

Q. Please review IBD in dogs.

A. Dr. Karin Allenspach and colleagues at the 2005 American College of Veterinary Internal Medicine Forum in Baltimore gave a lecture entitled "Practical Therapy for Difficult Cases of Canine IBD: Beyond Steroids". Some relevant points in this lecture are provided in this article.

Idiopathic inflammatory bowel disease (IBD) is characterized by infiltration of the gastric, small intestinal and/or large intestinal wall with inflammatory cells, such as plasmacytes and lymphocytes, eosinophils or neutrophils. The cause(s) of canine IBD remain(s) largely unknown. It is speculated that abnormal responses of the mucosa-associated lymphoid tissue that are possibly associated with abnormal permeability of the gut barrier and interactions with intestinal microflora are involved in the pathogenesis. Canine IBD seems to vary in its clinical presentation, natural course, response to treatment and prognosis. It likely encompasses a wide variety of different yet unidentified disease entities.

Idiopathic IBD is diagnosed by systematic exclusion of all known causes of chronic intestinal disease in dogs. It is difficult to clearly differentiate food reactions (including food allergy) from IBD. The typical diagnostic work-up includes CBC, serum chemistry profile, urinalysis, fecal parasitological and bacteriological examination, abdominal ultrasonography and serum trypsin-like immunoreactivity (TLI) assay.

The traditional approach to the treatment of canine IBD relies on components that can be used individually or most often combined: dietary modifications, antibiotic treatment, and specific anti-inflammatory and immunosuppressive drugs. Although most specialists agree that dietary therapy is a central component, the routine use of antibiotics in the treatment of dogs tentatively diagnosed with IBD is subject to controversy. In many instances, immunosuppressive doses of corticosteroids are administered for various lengths of time.

Many dogs with chronic intestinal disease of more than three-weeks duration respond totally or significantly to a one-week food trial with a commercial elimination diet alone (dry formulation). There is currently a wide variety of commercially available diets to recommend for elimination trials. Hydrolyzed diets are a recent alternative to classical diets offering a novel protein source.

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The existence of primary small intestinal bacterial overgrowth (SIBO) is subject to controversy. The more generic denomination "idiopathic antibiotic-responsive diarrhea" (ARD) is currently preferred. ARD is most commonly recognized in young German Shepherds with chronic intermittent diarrhea. It is diagnosed based on signalment, history and clinical signs, as well as on response to an empiric course of oral anti-biotics (e.g., oxytetracycline 10-20 mg/kg TID, or metronidazole 10-20 mg BID, or tylosin 20 mg/kg BID to TID). Recently, histiocytic ulcerative colitis, a severe form of IBD affecting Boxers (mainly but not exclusively) has been shown to respond well to enrofloxacin at usual doses.

Treatment protocols for management of canine IBD most often involve the use of immunosuppressive doses of corticosteroids for several weeks followed by slow tapering to reduce the intestinal mucosal inflammation and achieve clinical remission. The usual protocols for prednisone or prednisolone usage recommend dosages of 1-2 mg/kg BID for approximately two to four weeks, followed by a slow tapering period over weeks to months. However, a number of dogs treated with immunosuppressive doses of corti-costeroids will show either no response at all to the drug or will relapse after weeks to months of treatment. About 16 percent to 20 percent of cases with IBD will not respond to corticosteroid therapy. At high dosages, corticosteroids have numerous side effects such as PU/PD, which may become unbearable for the owners, especially in large-breed dogs. In difficult cases that require prolonged corticosteroid therapy and are sensitive to its side effects, the more expensive drug budesonide has been used with good anecdotal success — 3.0 mg/m2 or about 0.5-3.0 mg per dog, depending on body weight, once daily or every other day. Budesonide undergoes a first-pass hepatic extraction of approximately 80 percent to 90 percent, therefore, only a fraction of the absorbed compound reaches the systemic circulation, theoretically decreasing side effects. Budesonide will suppress the hypothalamic-pituitary-adrenal axis in dogs with IBD.

Other immunosuppressive agents, such as azathioprine, chlorambucil or cyclophosphamide, at the usual dosages, are used alone or in combination with corticosteroids. When used in combination, they may decrease the required dosage of corticosteroids and the associated side effects or allow the dogs to be weaned off corticosteroids as soon as possible. Moreover, these drugs are also used for cases of steroid-refractory canine IBD. They may have a delayed onset of action (weeks to months until maximal effect).

If the IBD is limited to the large bowel, compound molecules containing mesa-lamine (5-ASA) such as sulfa-salazine (initially 10-25 mg/kg orally TID for six weeks, then taper down) or olsalazine (initially 5-10 mg/kg orally TID, then reduce gradually) have proven beneficial effects on the colonic mucosa. Keratoconjunctivitis sicca is a well-known complication in dogs treated with either of these two drugs.

Cyclosporin A (cyA) (5 mg/kg orally once daily for a total of 10 weeks) may be a valid alternative for canine IBD. The cellular infiltrate in canine chronic idiopathic enteropathies mainly consists of lymphocytes and plasma cells in the lamina propria. The anti-inflammatory effect of cyA in IBD is thought to be due to its action on T-cells that infiltrate the mucosa. CyA binds intracellularly to calmodulin, which reduces the release of calcium from the endoplasmic reticulum, thereby inhibiting further down-stream signaling, and finally inhibiting the expression of IL-2. Because IL-2 is necessary for the survival of T-cells for longer than 24-48 hours, it is hypo-thesized that cyA decreases the number of infiltrating T-cells in the mucosa of the dogs, thereby reducing the amount of pro-inflammatory cytokines, and finally, the clinical signs of the disease. Reported side effects are vomiting, partial anorexia, gingival ulceration and alopecia followed by hypertrichosis.

Probiotics are living non-pathogenic micro-organisms that may exert beneficial effects on the immune system. In an ex-vivo culture system of duodenal biopsies from dogs with IBD, addition of three strains of Lactobacilli enhanced the expression of the regulatory cytokine IL-10. Based on these results, the use of such probiotics in vivo in dogs with IBD may be of benefit to decrease intestinal inflammation.

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Send your pediatric/geriatric related questions to: Pediatric/Geriatric Protocol, DVM Newsmagazine, 7500 Old Oak Blvd., Cleveland, OH 44130. Your questions will be answered by Dr. Hoskins in upcoming columns.