Problem

A 5-year-old spayed female German Shorthair Pointer weighing 20.2 kg (44.4 lb) was referred for evaluation of a 6-month history of weight loss and polyphagia. Initially, clinical signs included infrequent vomiting and diarrhea of large bowel origin, which progressed to diarrhea indicative of small and large bowel involvement.

Diagnostic testing performed by the referring veterinarian included 2 fecal evaluations for parasites, 2 Giardia ELISAs, serum biochemical analysis, urinalysis, a CBC, and measurement of serum total thyroxine concentration, serum cobalamin and folate concentrations, and trypsin-like immunoreactivity. Test results were unremarkable, as were results of thoracic and abdominal radiography. Empirical treatment had been initiated, including an antiemetic (maropitant citrate), antimicrobials (metronidazole and amoxicillin), and an antiulcer medication (sucralfate). After the dog failed to respond, therapeutic nutritional intervention was initiated. The dog's regular diet of generic dry dog food was slowly changed to a low-fat, highly digestible therapeutic food.^a However, despite resolution of the vomiting and diarrhea, weight loss continued.

Physical examination findings at the time of referral were unremarkable except for a body condition score of 2 (thin) on a scale from 1 to 5. Despite the dog's ravenous appetite and consumption of approximately 1.5 times the calculated daily energy requirements, its weight had decreased by 14% over a 6-month period. Results of abdominal ultrasonography were consistent with subtle thickening and mild increased opacity of the mucosal layer of the duodenum. Gross endoscopic findings included moderate pyloric erosions and increased granularity of the duodenum. Histologic evaluation of duodenal tissue specimens revealed mild changes consistent with lymphoplasmacytic, eosinophilic gastroenteritis. These changes supported a diagnosis of inflammatory bowel disease (IBD).

Formulation of Clinical Question

The desired outcome for this dog was resolution of polyphagia, a return to normal body condition, and prevention of recurrence of clinical signs. Treatment options included dietary modification, antimicrobial medication, and immunosuppressive treatment.

Clinical Question

For dogs with mild lymphoplasmacytic, eosinophilic gastroenteritis, which treatment strategies have been shown to effectively resolve clinical signs of vomiting, diarrhea, and weight loss?

Evidentiary Search Strategy

The PubMed database was searched for scientific reports published between 1997 and 2009 on therapeutic options for dogs with IBD. The following key terms were used: canine OR dog AND IBD AND treatment.

Review of the Evidence

Abstracts identified through the keyword search were reviewed and evaluated for their relevance to the clinical question. A total of 27 abstracts were identified; however, abstracts containing information not concerned with the clinical aspects of treatment or involving another species (ie, rat) were excluded. Once relevant abstracts were identified, the articles were reviewed to evaluate the quality of evidence provided by each through use of a published grading system for studies in veterinary clinical nutrition,¹ with I representing the highest grade (ie, a properly designed randomized, controlled clinical trial involving the target species) and IV representing the lowest (ie, opinion based on clinical experience). Factors such as study design, results obtained, and relevance to the canine species were also evaluated.

Two studies^2,3 were identified in which the use of tylosin for treatment of chronic diarrhea in dogs was evaluated. The first study² was a prospective case series involving 7 colony Beagles with chronic diarrhea. Those with persistent diarrhea (of at least 1 month's duration) and fecal consistency scores of 3.5 to 4.5 (median, 4.0), based on a 5-point scale with 1 being hard, dry, and crumbly feces and 5 being very watery diarrhea, were treated with tylosin and had firmer feces 2 to 3 days afterward, with a median consistency score of 2.75, which was significantly (P < 0.05) lower than the score prior to treatment. Improvement was also evident with dietary change from a highly digestible, moist food designed for dogs with gastrointestinal upset^b to an adult maintenance diet based on turkey and rice,^c resulting in a significant (P < 0.05) decrease in median consistency score to 2.5. The limitations of this study include the small sample size and the combination of dietary change with administration of tylosin to obtain maximal effect.

The second study³ was a nonrandomized clinical trial involving 14 client-owned dogs with chronic or intermittent diarrhea (duration > 1 year) successfully treated with tylosin at a dosage of 6 to 16 mg/kg (2.7 to 7.3 mg/lb; mean, 11.7 mg/kg [5.32 mg/lb]), PO, every 24 hours for a minimum of 6 months. Tylosin administration was continued for 2 weeks following the start of the study, then discontinued. Dogs that had a recurrence of diarrhea (12/14) were moved to the next phase of the study, during which they were given another 2 week course of tylosin (9/12), followed by probiotic administration (9/9) and prednisone administration (9/9). When diarrhea failed to resolve with other treatments in the remaining dogs (9/9), tylosin administration was reinitiated. The typical age at onset of diarrhea was 3 to 4 years (range, 1 to 6 years), indicating tylosin may be appropriate in this age group. An important limitation of this study was the small sample size. However, dietary change was not a factor because the dogs received their original diet throughout the study period. Inclusion criteria for the study dogs included previous successful treatment with tylosin, so the sample was biased to reflect tylosin-responsive patients. After tylosin administration, prednisone and probiotics were also administered to evaluate whether these tylosin-responsive dogs would also respond to these treatments. Consequently, this study design provides less information about the ability of individual dogs to respond to tylosin treatment alone.³

A prospective cohort study⁴ involving 70 dogs ranging in age from 6 months to 13 years (mean ± SD age, 5.3 ± 2.9 years) with chronic gastrointestinal disease resulted in a 56% (39/70) response rate (ie, resolution of clinical signs) when a 10-day elimination diet comprised of novel protein was fed. These dogs did not require additional treatment for chronic enteropathy during the 3-year follow-up period and were younger than the dogs that did not respond (3.53 ± 2.36 years). Dogs with diarrhea not responsive to the elimination diet were treated with immunosuppressive doses of corticosteroids, and 48% (10/21) responded and had no relapses in the 3-year follow-up period. Of the remaining 11 patients, 3 were euthanized for lack of response to prednisone and 2 improved after initiation of cyclosporine treatment. Certain variables were also evaluated as prognostic indicators. An endoscopy score of 3 of 4 (severe inflammation) in the duodenum, hypoalbuminemia (< 20 g/L), and hypocobalaminemia (< 200 ng/L) were each associated with a negative outcome (P = 0.01, P < 0.01, and P < 0.01, respectively). The advantages of this study include the large sample size, prospective nature, and inclusion of dogs naturally affected by chronic enteropathy evaluated at a referral institution (which were similar to the dog in the present scenario).

In a retrospective cohort study⁵ of 80 dogs with IBD that were evaluated at a referral institution from 1995 to 2002, change to a prescription diet (variable between patients) in 53% (38/72) was not significantly (P = 0.64) associated with outcome. The median age of dogs in this study was 4.3 years (range, 6 months to 14 years). Outcome was categorically classified as in remission from IBD, intermittent signs, uncontrolled IBD, and euthanasia owing to IBD. This study also has the advantage of a large sample size; however, a disadvantage is the retrospective nature of this study resulting in differences between individuals. This can make it more difficult to determine the effects of a particular treatment because all aspects of the case management are not consistent between all subjects in the study. The study design and lack of comparison of age in dogs responding to dietary treatment with other dogs may explain the inconsistent results with regard to the previous study.⁴ The retrospective study⁵ also identified hypoalbuminemia as being significantly (P < 0.001) associated with a negative outcome.

Given the aforementioned evidence, what decision would you make?

Decision and Outcome

The dietary history indicated the dog of this report did not respond to a low-fiber, highly digestible diet. Because most of the identified studies provided evidence that both tylosin administration and a novel protein diet may be effective, and because the patient lacked other factors associated with a negative outcome, the decision was made to feed the dog a novel protein diet^d and begin treatment with tylosin (10 mg/kg [4.5 mg/lb], PO, q 8 h). The dog's owners were advised to avoid feeding it treats or foods other than the recommended novel protein diet. Treatment was continued for 2 months, at which time physical examination findings included a normal body condition score (3/5) and a return to the dog's previous healthy weight of 24.5 kg (54 lb). During the 2-month treatment period, the dog had reportedly done well at home with no recurrent vomiting or diarrhea. Tylosin administration was discontinued, but the owners were instructed to continue feeding the novel protein diet because some dogs with food-responsive disease have a relapse of clinical signs after returning to their original diet.⁴

Discussion

Bacteria may play a major role in stimulation of the gastrointestinal immune system, and limiting bacterial numbers and types is often beneficial in management of IBD. The disease is believed to be secondary to chronic inflammation resulting from disruption of the mucosal barrier, dysregulation of the mucosal immune response, and alteration in the bacterial flora. In dogs with IBD, tylosin may have direct or indirect immunologic properties and may reduce antigenic stimulation, which may be a possible mechanism for recovery in those responding to tylosin.³ Considering the role of altered antigens in chronic IBD, favorable clinical experiences, minimal adverse effects, and low cost of the drug, tylosin remains an option for treatment of canine IBD.

Dietary treatment is generally considered an important aspect of the management of IBD. Studies specifically designed to evaluate the use of novel protein diets are limited; however, findings do suggest dogs with IBD have an improvement in clinical signs.⁴ The evidence also supports initiating a trial period of feeding a novel protein diet prior to beginning corticosteroid treatment in dogs with chronic diarrhea, particularly in young dogs because they appear more likely to be responsive to food than are older dogs.⁴

Immunosuppressive medication is another potential treatment option should other treatments fail. Expert opinion suggests that avoiding use of immunosuppressants as a first-line treatment unless the patient is unstable and waiting to allow for other treatment approaches to take effect is not appropriate. Although the dog of this report was approaching middle age for her breed and older patients may be less likely to be responsive to food,⁴ corticosteroid treatment was not started because it is not recommended for use as a first-line strategy.

In 1 study,³ treatment with prednisone was not as effective as treatment with tylosin in resolving diarrheal signs, possibly emphasizing the importance of using adjunct treatments whenever possible. Another study⁴ showed that dogs that are middle aged or older with more severe disease than other dogs with IBD and a predominance of small intestinal diarrhea are more likely to require corticosteroid treatment to improve.⁴ Such dogs may also be more likely to have a poor outcome than dogs classified as food responsive.⁴ Dogs with characteristics associated with a negative outcome (ie, hypocobalaminemia, severe duodenal inflammation, or hypoalbuminemia) may be candidates for more aggressive diagnostic testing or treatment strategies earlier in the course of the disease.

Irritable bowel disease can be a rewarding and challenging disease to treat. Various treatment options are available. In selecting a treatment strategy, patient characteristics and history should be considered. Even when IBD is confirmed through histologic evaluation of gastrointestinal biopsy specimens, milder forms of the condition do not always require immunosuppression and can often be managed with a combination of diet change, antimicrobials, and time.