Inflammatory Bowel Disease in Dogs

Inflammatory bowel disease is a collective term that describes a disorder of the small or large intestines characterized by persistent or recurrent gastrointestinal signs and histologic evidence of intestinal inflammation characterized on a biopsy sample. The cause of idiopathic inflammatory bowel disease is, by definition, unknown. Variations in the histologic appearance of the inflammation suggest that idiopathic inflammatory bowel disease is not a single disease entity and the nomenclature merely reflects the predominant cell type present. Lymphocytic-plasmacytic enteritis (LPE) is the most common form reported; eosinophilic gastroenteritis (EGE) is less common; and granulomatous enteritis is rare. Neutrophilic infiltration is a feature of human IBD but is sometimes seen in feline and rarely in canine idiopathic IBD.

BACKGROUND

Idiopathic IBD is a common cause of chronic vomiting and diarrhea in dogs and cats, but its true incidence is unknown. In reality it is often over-diagnosed because of difficulties in interpretation of histopathologic specimens and failure to eliminate other causes of mucosal inflammation. No apparent gender predisposition occurs, but in both dogs and cats, IBD is most common in middle-aged animals with intermittent signs sometimes seen at an earlier age. Although IBD can potentially occur in any breed, certain predispositions are recognized.

CLINICAL SIGNS

Vomiting and diarrhea are the most common clinical signs and sometimes an obvious precipitating event (e.g., stress, dietary change) is present in the history, but clinical signs may wax and wane spontaneously. The nature of signs crudely correlates with the region of the gastrointestinal tract affected: Gastric signs are more common if gastric or upper smalI intestinal inflammation is present; in cats, vomiting is often the predominant sign of small intestinal inflammatory bowel disease. Large intestinal type diarrhea may be the result of primary colonic inflammation, or it may be secondary to prolonged small intestinal diarrhea. Severe disease is associated with weight loss and protein losing enteropathy, with consequent hypoproteinemia and ascites. Appetite is variable; polyphagia (increased hunger) may be present in the face of significant weight loss, whereas anorexia occurs with severe inflammation. Milder inflammation may not affect appetite, although postprandial pain can be significant even without other signs.

ETIOLOGY

The underlying etiology of small-animal IBD is unknown but the breakdown of immunologic tolerance to luminal antigens (bacteria and dietary components) is thought to be critical, perhaps resulting from disruption of the mucosal barrier, dysregulation of the immune system, or disturbances in the microbiome. Antigens derived from the endogenous microflora are likely to be important in disease pathogenesis, and a potential role for diet-related factors is suggested by the clinical benefit of dietary therapy in some cases of IBD. Undiagnosed infection remains a possibility, considering the recent identification of attaching and invading E. coli in histiocytic ulcerative colitis of Boxers and human Crohn's disease. Genetic factors are likely to contribute to the pathogenesis of inflammatory bowel disease.

DIAGNOSTIC TESTING

Intestinal biopsy is necessary for a diagnosis of intestinal inflammation. The term idiopathic IBD is limited to cases in which histologic evidence of inflammation is found without an obvious underlying cause. All other etiologies—including infectious, diet-responsive, and antibacterial-responsive conditions—must be excluded. Therefore, before intestinal biopsy is undertaken, laboratory evaluation and diagnostic imaging are performed. Such tests cannot prove idiopathic IBD, but they can help eliminate the possibility of anatomic intestinal disease (e.g., tumor, intussusception), extraintestinal disease (e.g., pancreatitis), and known causes of intestinal inflammation. Furthermore, by determining whether focal or diffuse intestinal disease is present, the clinician can choose the most appropriate method of intestinal biopsy. Imaging studies document whether focal or diffuse disease is present and whether other organs are affected. Such information, together with specific clinical signs, allows the choice of the most appropriate biopsy method. Plain radiographs may be useful for detecting anatomic small intestinal disease; contrast studies rarely add further specific information. Ultrasonographic examination is superior to radiography for identifying focal small intestinal disease and is particularly useful in cats with IBD. It permits evaluation of intestinal-wall thickness and can document mesenteric lymphadenopathy, while ultrasound-guided fine needle aspiration (FNA) can provide samples for cytologic analysis. However, increased intestinal-wall thickness is not a feature of all cases of canine idiopathic IBD.

DIAGNOSIS

Intestinal biopsy is necessary to document intestinal inflammation. Endoscopy is the easiest method of biopsy, but it has limitations: samples are superficial and in most cases can be collected only from the proximal small intestines. In some cases full-thickness surgical biopsy is necessary, although the procedure is more invasive and can be problematic if severe hypoproteinemia is present. Histopathologic assessment of biopsy material remains the gold standard for the diagnosis of intestinal inflammation, and the pattern of histopathologic change depends on the type of IBD present. ,Whatever the type of IBD, treatment usually involves a combination of dietary modification and antibacterial and immunosuppressive therapy. Unfortunately, objective information on efficacy is lacking, and most recommendations are based on clinical experience. The author recommend a staged approach to therapy whenever possible; sequential treatment trials of antiparasiticides, an exclusion diet, and antibacterials must be tried before immunosuppressive medication is used. Mild cases frequently respond to diet change and metronidazole, especially in cats. However, in some cases, clinical signs or mucosal inflammation are so severe that early intervention with immunosuppression is essential.

TREATMENT

IBD patients with mild to moderate clinical disease activity and normal serum albumin concentrations are first treated sequentially with dietary and antibiotic trials. Patients with protein loss should proceed to endoscopic biopsies if indicated and initiated on immunosuppressive therapy if indicated based on the histopathology.

Diet

A positive response to a dietary trial allows the patient’s disease to be classified as diet-responsive IBD, a term that includes both dietary allergy and intolerance. The primary option for a dietary trial is switching to a diet that leads to antigenic modification (eg, novel protein source, protein hydrolysate). The diet must be palatable and introduced in gradually increasing amounts. In dogs with diet-responsive IBD, a clinical response is usually observed within 1 to 2 weeks of changing the diet.

Antibiotics

An antibiotic trial typically involves administration of tylosin, or metronidazole. A positive response suggests ARD. The patient is typically maintained on antibiotics for 28 days. If signs recur after discontinuation of therapy, long-term antibiotic therapy may be instituted with tylosin.

Anti-inflammatory and Immunosuppressive Therapy

Patients that do not respond to a diet or antibiotic trial are usually administered prednisolone or prednisone. However, as the side effects of glucocorticoids are usually more marked in large-breed dogs than in small breeds, azathioprine may be combined with glucocorticoid treatment for a faster taper period in dogs weighing >30 kg. If there is poor response to immunosuppression or a relapse is seen after tapering, cyclosporine may be considered. Budesonide is a glucocorticoid medication that has been shown to be successful in the treatment of canine IBD. However, hypothalamic–pituitary– adrenal suppression and development of steroid hepatopathy has been demonstrated in dogs. Therefore, the hepatic first-pass effect of this drug in dogs may not be as beneficial as in human beings. An optimal dose of budesonide has not yet been determined. The response rate to budesonide has been shown to be similar to prednisone; however, this drug should be reserved for dogs that are known to respond to steroids but suffer severe side effects. Some dogs still develop side effects of steroid administration while on budesonide, and owners should be warned about this.

Protein-Losing Enteropathy

PLE is a recognized complication in a subset of chronic enteropathy cases, and hypoalbuminemia has been shown to be a poor prognostic indicator. Patients with albumin concentrations <1.5 g/dL are at greatest risk of developing ascites, pleural effusion, and subcutaneous edema. Many of these patients succumb to PLE within the first 1 to 2 months of starting prednisone treatment. Some studies have shown a better outcome with single-therapy cyclosporine, making it a better option for some of these patients.

Adjunctive Therapy With Probiotics

The use of probiotics in people with IBD has led to some promising results, although there is still an insufficient number of large, multicenter, randomized, double-blind, placebo-controlled trials to determine its utility.

PROGNOSIS

The main negative prognostic indicator for chronic enteropathy in dogs has been identified as (low blood albumin) hypoalbuminemia. More prospective treatment trials are necessary, especially in severely affected and hypoproteinemic animals, to improve long-term survival in these cases.

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