Overview

The general term "chronic enteropathies" (CE) has been used frequently in recent years to describe dogs and cats with chronic intestinal diseases of unknown origin. Diet-responsive diarrhea (DRD), antibiotic-responsive diarrhea (ARD), and inflammatory bowel disease (IBD) are different forms of chronic enteropathies. They may form a continuum, with DRD being a mild form of CE, and IBD that requires immunosuppressive treatment representing the severe form of the disease.

In a study published 8 years ago, 56% of 70 dogs with chronic diarrhea responded to an elimination trial with a novel protein diet. Of those 39 diet-responsive dogs, 27 (69%) exclusively showed large bowel diarrhea while 9 (23%) had mixed large and small bowel signs. Based on this data, an elimination trial with hydrolyzed peptide or novel protein diets chosen on the basis of the animal's dietary history should be initiated in all dogs with mild to moderate chronic idiopathic colitis. Clinical signs generally abate within 10–14 days of treatment.

Etiology

Based on research in rodent models, people, and dogs, IBD results from a combination of factors that include dysregulation of the immune system and its interactions with intestinal microbiota and/or dietary components, and compromised integrity of the intestinal mucosal barrier.

Specific forms of IBD have been recognized to occur more frequently in several canine breeds. Examples of established breed associations include lymphangiectasia and duodenal crypt inflammation with protein-losing enteropathy (PLE) in Yorkshire Terriers, PLE and protein-losing nephropathy in Soft-Coated Wheaton Terriers, and cobalamin deficiency in Shar Peis. German Shepherd Dogs (GSD) have a high prevalence of intestinal dysbiosis/antibiotic-responsive diarrhea and IBD.

Pathophysiology

Chronic intestinal inflammation in dogs results from disturbed recognition of commensal intestinal microbiota by the innate immune system. In addition, significant changes in the intestinal microbiota were detected using molecular biological approaches that do not rely on microbial culture. In dogs and people, IBD reduces the diversity of the intestinal microbiome. Furthermore, in dogs with IBD, the several bacterial taxa are diminished, while others are increased. It is not clear whether these changes are at the origin of intestinal inflammation, or if they reflect the altered environment in the chronically inflamed gut, or both.

Clinical Presentation

Chronic or chronic-intermittent diarrhea of more than 3 weeks duration. Mild CE may cause intermittent clinical signs, whereas progressive and severe clinical signs are common in severe IBD. Poor body condition with poor hair coat is frequent with severe disease. Dehydration is possible. Thickened small intestinal loops may occasionally be palpated. Animals may show pain or discomfort on abdominal palpation. Ascites, hydrothorax, and peripheral edema may occur in case of significant protein loss (protein-losing enteropathy or PLE).

Diagnosis

Diagnosis of CE consists of an elimination process to rule out other diseases of known etiology that may cause similar clinical signs: fecal flotation and Giardia antigen test should be performed in all dogs. Alternately, empiric parasiticide treatment can be administered (e.g., fenbendazole 50 mg/kg q 24 h for 3–5 days). Subsequently, the diagnostic process is different for dogs with mild clinical signs and no evidence of systemic complication such as hypoproteinemia, and for dogs that are more severely affected.

Mildly affected dogs can undergo a treatment trial with a novel protein or hydrolyzed peptide diet (see management below), while severely affected dogs should be evaluated more thoroughly with collection of a minimal database including CBC, serum biochemistry and urinalysis. Presence of hypoalbuminemia, often accompanied by hypoglobulinemia suggests PLE. Sensitivity of abdominal ultrasound is intermediate, and scans may be normal or show focal or diffuse loss of wall layering, presence of mucosal striations or spicules, wall thickening, enlarged and/or hypoechoic mesenteric lymph nodes. If lesions are present, localization to a specific intestinal segment may be helpful.

Upper GI endoscopy and exploratory celiotomy are both good methods to collect intestinal mucosal biopsy samples, and each offers different advantages and drawbacks. Procurement of biopsy samples is necessary to further evaluate disease severity. The most important justification for histology is to rule out a neoplastic infiltrate. However, it is also useful to evaluate the magnitude of intestinal mucosal inflammation based on the severity and type of the infiltrate and on the severity of the architectural mucosal changes. A newly established scoring system takes both architectural and inflammatory mucosal changes into account. Inflammatory infiltration may be of varying severity and consist of lymphocytes and plasma cells (lymphoplasmacytic enteritis), eosinophils, neutrophils or macrophages or combinations thereof. Examples of small intestinal mucosal architectural changes include villus stunting, surface epithelial injury, crypt distension, lacteal dilation, and mucosal fibrosis. It is noteworthy that in animals responding to treatment histopathologic lesions do not seem to improve in correlation with clinical signs. This finding may suggest that CE can be controlled clinically, but not healed.

Differential Diagnoses

General differentials include chronic intestinal foreign body, intestinal parasitosis, bacterial enteritis, fungal enteritis, and diseases originating outside the GI tract such as chronic kidney disease, chronic liver disease, chronic pancreatitis, exocrine pancreatic insufficiency, and atypical hypoadrenocorticism.

Management

In most instances, the goal of treatment is to manage the clinical signs. Full recovery is possible in mild cases.

1.  Treatment trials: The standard approach for a dog with mild to moderate chronic recurrent diarrhea of unknown origin without systemic repercussions is to initiate a food trial with a novel protein or hydrolyzed peptide diet. A majority of dogs presented with chronic diarrhea of unknown origin respond at least partially within 10 to 14 days. For those who don't, the next step may consist of another treatment trial with another novel protein or hydrolyzed peptide diet, and/or antimicrobials. Dysbiosis (change in the composition of the intestinal microbiota) occurs in most dogs with IBD. Young large breed dogs with CE (particularly but not exclusively German Shepherd Dogs) respond to prolonged treatment with antimicrobials such as tylosin (20 mg/kg PO BID) or metronidazole (10–15 mg/kg PO BID). Clinical experience accumulated over the past decades indicates that prolonged treatment (4 to 8 weeks) is necessary, and that relapses are common. In refractory cases, and in dogs with severe disease and evidence of systemic involvement a more thorough work up with acquisition of a minimal database should be initiated (see diagnosis above).

2.  In dogs that do not respond to the dietary and antimicrobial trails, with histopathologic evidence of IBD immunosuppressive doses of prednisone or prednisolone are generally the mainstay of initial treatment. Initially, very high doses (e.g., 2 mg/kg q 12 h) are recommended for a few days, followed by a regular immunosuppressive dose (2 mg/kg/day, in 1 dose or divided in 2 doses). The dietary treatment consists of hydrolyzed peptide or novel protein diet, which has been shown to be superior to easily digestible low fat diet for long-term maintenance of moderate to severe canine IBD. A recheck is scheduled after 1–2 weeks to re-assess the situation. In cases showing good response, the dose of prednisone should be maintained for another 2 weeks beyond improvement, then slowly decreased in 2–4 weeks steps. It is noteworthy that in a recent study from Italy dogs with IBD did equally well if they received steroids or a concentrated probiotic cocktail registered for use in people.

3.  Approach to refractory cases: treatment failure should prompt the clinician to review the diagnosis and ascertain that no mistakes or erroneous assumptions were made in the diagnostic process. Refractory IBD patients must be examined thoroughly to detect intercurrent diseases that may be contributing to treatment refractoriness. For instance, cobalamin deficiency may cause a delayed or lacking response to adequately designed immune-suppressive treatment. Serum cobalamin concentration should be determined. Subcutaneous supplementation is essential in these animals (see http://vetmed.tamu.edu/gilab for full treatment protocol). Relatively frequently, dogs with moderate to severe IBD require treatment with a combination of immunosuppressive agents that include cyclosporine (5 mg/kg PO q 12 h), or chlorambucil (initially 4–6 mg/m² q 24 h for the first 7–21 days, then the dose can be decreased by 25–33%, or the dosage interval may be increased to every 2 to 3 days). In cases with unacceptable corticosteroid side effects, another immunosuppressive drug may be added in the hope to decrease the prednisone dose. Alternately, budesonide can be used (3 mg/m² body surface area PO q 24 h). It is a glucocorticoid that undergoes high first pass hepatic metabolism after intestinal absorption, but still affects the pituitary-adrenal axis. Budesonide may cause less side effects than prednisone, and has been used in large breed dogs, which tend to be more prone to severe polyuria and polydipsia. There is no documented benefit in using the controlled release formulation compared to the generic substance.

Prognosis

Good in mild cases that respond to dietary trials. Return to a less expensive commercial food may be possible after 2–3 months of dietary treatment; however, some dogs require life-long administration of an elimination diet. Guarded to poor in dogs requiring medical treatment.