Feline Inflammatory Bowel Disease

Feline IBD is characterised by persistent clinical signs of gastrointestinal disease, associated with histological evidence of inflammation, of undetermined cause, in the small or large intestinal mucosa. The severity of feline IBD, and the clinical response to therapy, may be graded clinically using the feline chronic enteropathy activity index (FCEAI), which is based on assessment of clinical signs, endoscopic changes, serum total protein, serum ALT and ALP and serum phosphorous concentration.¹

Classification and Diagnosis of Feline IBD

These diseases are most often classified histologically according to the nature of inflammation present with the most common being idiopathic lymphoplasmacytic enteritis. Inflammation is accompanied by characteristic histopathological changes including: villus atrophy and fusion, enterocyte damage or loss and crypt abscessation. The severity of microarchitectural and inflammatory changes may now be evaluated using the standardized templates produced by the WSAVA Gastrointestinal Standardization Group for endoscopically-obtained biopsies.²

This system may be equally applied to canine or feline biopsy samples, with the main difference between the two species being the higher baseline number of intraepithelial lymphocytes present in the feline small intestinal mucosa. Such standardized scoring should make it simpler to conduct research with clinical populations and to perform multicentre investigations. The FCEAI appears to correlate with the histological severity of changes in intestinal mucosal tissue as defined by the WSAVA guidelines.¹ One of the major challenges in the histopathological diagnosis of feline IBD is in making a clear distinction between IBD and early small T-cell alimentary lymphoma. The application of immunohistochemistry and molecular evaluation of lymphocyte receptor clonality can now assist in differentiating between these diseases.^3-5 It is also clear that collection of full-thickness, rather than endoscopic samples, aids in the characterization of neoplastic disease, particularly by allowing evaluation of infiltration of the submucosa and muscularis propria.⁶

Immunopathogenesis of Feline IBD

The proposed immunopathological basis of human and canine IBD has been discussed in an earlier presentation. Recent studies have begun to characterise the immunological abnormalities that occur in feline IBD, but knowledge currently lags behind understanding of the canine disease complex. Immunohistochemical investigations did not reveal alterations in overall cellularity of the mucosa in affected cats, and there were no significant differences in IgG⁺ or IgA⁺ plasma cells or CD3⁺ T cells compared with normal mucosa. However, there were significantly more MHC class II⁺ antigen-presenting cells and specific induction of expression of this molecule by enterocytes. Unlike in dogs, where gut epithelium normally expresses MHC class II, feline enterocytes have no baseline expression of these molecules, but they may be induced in the presence of inflammatory or neoplastic disease.⁷ Elevated numbers of mast cells are also documented in biopsies from cats with IBD.⁸

Real-time RT-PCR has revealed elevation of gene expression for cytokines related to inflammation (IL-6, TNF-α), type 1 immunity (IL-12p40) and regulation (IL-10, TGF-β) in mucosal biopsies from cats with intestinal inflammation.⁹

The most recent investigation of feline IBD relates the clinical signs of chronic diarrhoea, the changes in mucosal architecture and the increased expression of cytokine genes (IL-1, IL-8 and IL-12) to increased numbers of mucosal bacteria - specifically Enterobacteriaceae, E. coli and Clostridium spp.¹⁰ It is now clear that the composition of the intestinal microbiota alters in IBD and that these population changes are more important than simple elevation in number of organisms per se.

References

1.  Jergens AE, Crandell JM, Evans R, et al. A clinical index for disease activity in cats with chronic enteropathy. J Vet Intern Med 2010;24:1027–1033.

2.  Day MJ, Bilzer T, Mansell J, et al. Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group. J Comp Pathol 2008;138:S1–S43.

3.  Waly NE, Gruffydd-Jones TJ, Stokes CR, et al. Immunohistochemical diagnosis of alimentary lymphomas and severe intestinal inflammation in cats. J Comp Pathol 2005;133:253–260.

4.  Kiupel M, Smedley RC, Pfent C, et al. Diagnostic algorithm to differentiate lymphoma from inflammation in feline small intestinal biopsy samples. Vet Pathol 2011;48:212–222.

5.  Briscoe KA, Krockenberger M, Beatty JA, et al. Histopathological and immunohistochemical evaluation of 53 cases of feline lymphoplasmacytic enteritis and low-grade alimentary lymphoma. J Comp Pathol, in press. 2011.

6.  Kleinschmidt S, Harder J, Nolte I, et al. Chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract in cats: diagnostic advantages of full-thickness intestinal and extraintestinal biopsies. J Feline Med Surg 2010;12:97–103.

7.  Waly NE, Stokes CR, Gruffydd-Jones TJ, et al. Immune cell populations in the duodenal mucosa of cats with inflammatory bowel disease. J Vet Intern Med 2004;18:816–825.

8.  Kleinschmidt S, Harder J, Nolte I, et al. Phenotypical characterization, distribution and quantification of different mast cell subtypes in transmural biopsies from the gastrointestinal tract of cats with inflammatory bowel disease. Vet Immunol Immunopathol 2010;137:190–200.

9.  Nguyen Van N, Taglinger K, Helps CR, et al. Measurement of cytokine mRNA expression in intestinal biopsies of cats with inflammatory enteropathy using quantitative real-time RT–PCR. Vet Immunol Immunopathol 2006;113:404–414.

10. Janeczko S, Atwater D, Bogel E, et al. The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease. Vet Immunol Immunopathol 2008;128:178–193.