Controversies in canine and feline IBD (Proceedings)

Histopathologic Evaluation Of Intestinal Biopsy Specimens

Controversy: Histologic evaluation of biopsy specimens is required for definitive diagnosis. No standard microscopic grading system of IBD lesions has been established. Several histologic grading systems for evaluation of endoscopic specimens from dogs and cats with IBD have been described. Endoscopically-obtained GIT mucosal biopsy collection remains the gold standard but presents a variety of challenges for both the clinician and the pathologist. It is recognized that these specimens are small, prone to procurement/processing artifact, and are difficult to optimally orient for accurate morphologic characterization. Note that extensive interobserver variability in interpretation between pathologists can occur.

Histopathologic diagnostic criteria of IBD should clearly define morphologic evidence of mucosal inflammation. These observations might include:

a. Changes in surface/cryptal epithelia – erosions, necrosis, hyperplasia, increased intraepithelial lymphocytes (IELs).

b. Changes in lamina propria (LP) cellularity – there is a need to differentiate pathologic versus physiologic (e.g., dietary, microbial) alterations in LP cellularity which confound interpretation of inflammation from normal. The nature of these inflammatory infiltrates should also be noted (e.g., the relative proportions of lymphocytes, plasma cells, macrophages, neutrophils, etc.).

c. Mucosal architectural alterations – villous blunting/fusion, mucosal edema, fibrosis, and/or lymphatic dilatation are all potential lesions.

d. submucosal cellular infiltration – is this more common with GIT lymphoma?

e. Is there a role for immunophenotyping in ambiguous cases?

Of interest, some recent studies indicate that canine IBD histopathologic lesions may not change in severity in spite of clinical improvement and reduction in disease activity.

Clinical Staging For Canine Ibd

Controversy: The clinical criteria for assessment of canine IBD disease activity have only recently been defined. To date, several different clinical investigators report successful use of this scoring system to assess drug or dietary response in dogs with IBD. Disease activity is presently assessed by numerous factors. However, several problems exist with this system. Firstly, clinical severity is very subjective, depending heavily on the client's perception of the disease. Secondly, diagnosis is often based on poorly standardized histologic grading criteria. Thirdly, evaluation of immune cell populations and select inflammatory mediators is technically cumbersome and impractical for routine clinical use.

A recent study has reported the use of a simple scoring index (e.g., canine IBD activity index or CIBDAI) for assessment of disease activity at diagnosis and following medical therapy. Using this system, 6 prominent gastrointestinal signs (attitude/activity, appetite, vomiting, stool consistency, stool frequency, and weight loss) are scored 0 to 3 based upon the magnitude of their alteration from normal in a given IBD patient. These scores are then summed, yielding a total cumulative CIBDAI score which reflects clinically insignificant disease or the presence of mild, moderate, or severe IBD. Additionally, it was shown that both the CIBDAI score and the serum CRP concentration decreased in dogs following successful medical (e.g., immunosuppressive drug therapy and dietary management) therapy for their disease. These accumulated observations suggest that the CIBDAI is a useful and reliable measure of clinical signs of inflammation in dogs with IBD.

Difficult To Treat Ibd Cases

Controversy: IBD variants, such as eosinophilic enteritis (EE) and histiocytic ulcerative colitis (HUC), may be more difficult to treat versus intestinal inflammation seen with lymphocytic-plasmacytic mucosal inflammation. EE may represent immunologically-mediated disease of the intestines mediated by dietary antigens while HUC may be caused by mucosally-associated (E. coli) bacteria. Therefore, therapeutic strategies for these variants may differ. IBD which is unresponsive to conventional therapy may also be due to a spectrum of other causes including: (1) client/patient compliance; (2) severe intestinal disease; (3) intercurrent illness; and (4) misdiagnosis.

Severe Intestinal Disease

Dogs or cats with severe intestinal inflammation or IBD variants may not respond to medical therapy. Clinical staging in cats is presently problematic, as well-defined criteria for assessment of disease activity have not been published as they have in the dog. Thus, clinicians rely predominantly on histologic assessment, perhaps coupled with severity of signs and endoscopic appearances for measurement of mild, moderate, or severe FIBD. In this regard, those cats having objective evidence of severe mucosal inflammation including significant villus changes, epithelial immaturity/erosion/necrosis, and/or proprial fibrosis will be more difficult to manage - regardless of the predominant infiltrating cell type.

Intercurrent Illness

IBD associated with other gastrointestinal disorders may also be difficult to manage. Both exocrine pancreatic insufficiency (EPI) and inflammatory hepatobiliary disease in cats may cause exacerbation of signs in patients otherwise appropriately treated. Diagnosis of concurrent EPI is straight forward with determination of subnormal TLI concentration; while, hepatopathy may require specific hepatic function testing (eg, resting ammonia concentration or serum bile acids) and biopsy for confirmation. Practically speaking, feline EPI is uncommon but inflammatory hepatobiliary involvement with FIBD likely is not. Indeed, mild to moderate elevations of ALT and ALP (less commonly) are observed in cats with active intestinal inflammation. I attribute these hepatic enzyme elevations to an extension of the benign intestinal inflammation. While enzyme activities often normalize with IBD therapy, those cats which continue to exhibit non-specific signs of vomiting, diarrhea, altered appetite, and weight loss with increased enzyme activities may require more critical diagnostic evaluation. Finally, don't hesitate to repeat baseline diagnostic tests in poorly responsive cats to eliminate metabolic disease (renal disease with uremia), infectious disease (toxoplasmosis), and endocrinopathy (hyperthyroidism) which also cause gastrointestinal signs.

Misdiagnosis

Alimentary lymphosarcoma remains the major misdiagnosis in refractory IBD patients. Well differentiated lymphosarcoma appears very similar morphologically to severe IBD (eg, lymphocytic-plasmacytic enteritis) confounding accurate interpretation of feline disease by pathologists. Even thorough pre-endoscopic examination including serology (FELV testing) and abdominal ultrasonography may fail to discriminate these distinct diseases. Furthermore, as many of these cats are treated with oral glucocorticoids for a variable period prior to the correct diagnosis being made; therapy may "mask" neoplastic infiltrates histologically and render patients minimally responsive to appropriate chemotherapy for their disease. If cats fail to respond following 7-10 days of "traditional" FIBD medical therapy, I repeat endoscopic examination with biopsy or perform laparotomy (or laparoscopy) with full-thickness biopsies to ruleout lymphosarcoma. Lastly, we rely heavily on endoscopic exfoliative cytology to corroborate histologic findings. Previous studies attest to the complementary utility of this diagnostic technique in identification of feline alimentary neoplasia.

Optimal Medical Therapy For Ibd

Controversy: The optimal drug combination or duration of therapy for canine or feline IBD has not been established.

Nutritional Management

There is general agreement that elimination or novel protein, highly digestible diets are beneficial in dogs and cats with IBD. Additionally, the benefits of dietary fiber, the use of polyunsaturated fatty acids (n-3 fatty acids), and prebiotic or probiotic supplementation to effect endogenous gut flora are still being investigated. There is good evidence in veterinary patients that feeding a highly digestible, low-residue diet will reduce the severity of gastrointestinal signs. Selecting a protein (venison, rabbit, lamb, whitefish, or turkey) that is not routinely fed is recommended since it reduces the likelihood that these diets will evoke allergic (hypersensitive) responses. Highly digestible commercial diets, without novel proteins, have also been shown to be effective in the management of IBD colitis. It is likely that both the high digestibility and limited allergen content of these diets contribute to clinical remission in patients. Protein hydrolysate diets containing low-allergen, small molecular weight proteins offer a new dietary strategy for managing adverse reactions to food which may occur with IBD. I generally utilize these diets in patients having severe gastrointestinal signs or histologic lesions, and in those dogs and cats which are non-responsive to novel protein diets.

Drug Therapy

Most pharmacologic therapies interrupt the amplification sequence of inflammation in IBD, explaining why maintenance therapy (via diet and/or drugs) is important. Anecdotal evidence supports the use of oral corticosteroids, sulfasalazine or similar drugs, and metronidazole in therapy of small animal IBD. The administration of potent immunosuppressive drugs, such as azathioprine, cyclophosphamide, and/or cyclosporine is uncommonly required and should only be considered if intestinal biopsies have been performed. The majority of animals are able to maintain remission of signs with dietary management alone following completion of drug therapy.

References:

1. Jergens AE. Inflammatory bowel disease: Current Perspectives. Vet Clin N Am: Small Anim Pract 29:501-521, 1999.

2. Nelson RW, Stookley LJ, Kazacos E. Nutritional management of chronic colitis in the dog. J Vet Intern Med 2:133-137, 1988.

3. Guilford WG: Idiopathic inflammatory bowel diseases. In Guilford WG, et al eds: Strombeck's small animal gastroenterology. Philadelphia: WB Saunders Co, pp 451-486, 1996.