IBD

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The mesenteric lymph node is greatly swollen, and the bowel loops are hyperemic and distended. This cat was diagnosed with IBD based on full-thickness biopsy of the bowel and lymph node

Inflammatory bowel disease (or irritable bowel disease) (IBD) is an umbrella term for any chronic diarrhoea in cats that is non-responsive to food-elimination trials (food-responsive enteropathy)[1] or antimicrobial therapy (Antibiotic-responsive enteropathy). However, categorizing cats is mostly academic from a clinical viewpoint.

IBD is one of the most common intestinal disorders of cats and a major diagnosis in cats presented with chronic vomiting, weight loss and diarrhoea/constipation. IBD is essentially a diagnosis of exclusion.

Causes

The etiology of feline IBD remains largely unknown, although a number of factors, such as stress, are either directly or indirectly involved. The role of nutrition cannot be excluded due to responses seen with dietary changes.

In humans, IBD appears to have a hereditary component. In cats, a genetic link has yet to be determined. What is known is that in cats, there is concurrent activation of both proinflammatory and immunomodulatory cytokines, and the immune reactions associated with feline IBD can not be classified as either Th1 or Th2-modulated event. Furthermore, an increase in class II major histocompatibility complex (MHC) expression was documented in the mucosa of cats with IBD, suggesting intense antigen processing and presentation by macrophages and intestinal epithelial cells. This may be a consequence of a breakdown in the barrier function of the intestinal mucosa and/or an inappropriate immune response to commensal bacteria or food antigens[2][3].

Cats with gastrointestinal (GI) signs were found to have significantly more mucosa-associated Enterobacteriaceae than healthy controls, with increased numbers of E. coli and Clostridium spp bacteria. Additionally, Inness et al (2007) report that in feline irritable bowel disease, Bacteroides spp populations are significantly reduced, replaced by an increased population of Desulfovibrio spp (producers of toxic sulphides). The cause and effect relationship is yet to be proven[4].

This correlated with histopathological abnormalities in the mucosa, proinflammatory cytokine up-regulation, and the number of clinical signs. These mucosa-associated bacteria may play a role in the pathogenesis of IBD or represent an interesting epiphenomenon of intestinal inflammation[5]. Based on our current knowledge it is probable that feline IBD represents a group of diseases of different etiology resulting in chronic intestinal mucosal inflammation[6][7].

Clinical signs

Cats affected by IBD are usually middle-aged to older animals, but the age range is wide and includes very young animals as well. There is no documented breed or sex predilection, although purebred cats, such as the Abyssinian, Siamese, Persian, and Himalayan breeds, may be at an increased risk.

The clinical signs vary with the location of the inflammatory process; duodenal and gastric lesions usually present as vomiting and weight loss while small and large intestinal lesions present as diarrhoea and/or weight loss[8]. Older cats with muscularis layer thickening are more likely to have T-cell lymphoma than IBD[9].

There are also some cats in which the inflammatory response extends beyond the intestinal tract and affects the liver (+/- gallbladder) and pancreas, causing cholangitis, hepatitis and pancreatitis. This is fondly termed 'triaditis'.


Area affected Symptoms
Small intestine +/- vomiting, normal frequency of motions, little pain associated, smelly, may be black if bleeding involved, often watery
Large intestine Frequent and 'urgent', usually cow-pat appearance, bright-red if bleeding involved
Triaditis (small intestine, liver and pancreas) vomiting, and symptoms of small intestinal involvement (i.e. watery and smelly +/- black blood)

Diagnosis

Mucosal biopsies collected from the stomach and duodenum via endoscopy, are relatively non-invasive and less expensive than laparoscopy. Unfortunately, mucosal biopsies alone may miss a diagnosis of lymphoma in cats, especially in individuals with intestinal but not gastric involvement. In addition, standard GI endoscopy does not allow evaluation of the jejunum or ileocecocolic junction.

Full-thickness biopsies obtained by abdominal exploratory laparotomy or laparoscopy are ideal for diagnosis of IBD and the exclusion of lymphoma, but may allow fine needle aspiration of a lymph node or a focal area of intestinal thickening for a cytological diagnosis of lymphoma. Lack of normal intestinal wall layering suggests neoplasia and warrants surgical excision or full-thickness biopsies for clients who would pursue chemotherapy for lymphoma[10].

Serum folate and cobalamin concentrations may also be useful in planning biopsies. Low serum folate is consistent with proximal small intestinal malabsorption. This finding, along with duodenal thickening on ultrasonography, suggests that endoscopy might be adequate to sample the affected area. A decreased serum cobalamin suggests ileal cobalamin malabsorption, either due to infiltrative ileal disease or pancreatic insufficiency.

Exocrine pancreatic insufficiency is rare in cats, but a serum feline trypsin-like immunoreactivity (fTLI) test should be submitted if weight loss and polyphagia are present in a euthyroid, non-diabetic cat. If fTLI is normal, ruling out pancreatic insufficiency, cats with low serum cobalmin concentrations may be best taken to surgery for full thickness biopsies of the duodenum, jejunum and ileum. Because pancreatitis can be present concurrently with IBD, cats with chronic GI signs should also be screened for elevated serum feline pancreatic lipase immunoreactivity (fPLI), especially if the pancreas appears mottled on ultrasound examination or abdominal discomfort is detected on physical examination.

Unfortunately, a long duration of signs (> 1 year) does not rule out lymphoma.

When considering a diagnosis of IBD, other causes of chronic diarrhoea need to be considered, especially small intestinal lymphoma. Based on ultrasonographic studies, older cats with muscularis layer thickening are more likely to have T-cell lymphoma than IBD. The ultrasonographic pattern is associated with histologic infiltrates in the mucosal and submucosal layers of small intestine. Lymphadenopathy is associated with lymphoma or IBD.[11].

There are many causes of diarrhoea in cats, including small and large intestine and combinations:

Causes of small intestinal diarrhoea (in order of likelihood) Causes of large intestinal diarrhoea
Protozoa - Isospora spp, Sarcocystis spp, Besnoitia spp, Hammondia hammondi, Toxoplasma spp, Giardia spp, Tritrichomonas spp, Entamoeba histolytica, Balantidium coli, Cryptosporidium spp Tritrichomonas foetus, Cryptosporidium spp
Worms - round worms (Toxascaris leonina and Toxocara cati), tapeworms (Dipylidium spp), stomach worm (Ollulanus tricuspis)
Hormonal - Hyperthyroidism, End stage uraemia
Nutritional - allergy to protein, preservatives (#220-228 are sulphites), gluten (dry food)
Lymphangiectasia, Antibiotic responsive diarrhea/bacterial flora

imbalances, Short bowel syndrome

Chronic pancreatitis, Exocrine pancreatic insufficiency
Bacteria - Salmonella spp, Campylobacter spp, E. coli., Clostridium spp, Helicobacter spp, Mycobacterium spp, Shigella spp, Anerobiospirillum, Histoplasma, Pythium,
Viruses - rotavirus, Feline leukemia virus (FeLV), Feline Aids (FIV), Coronavirus (FIP), Feline Panleucopenia
Fungi - Histoplasma spp, Aspergillus spp, Candida spp, Phycomycetes
Cancer - small intestinal Lymphoma, lymphosarcoma, Pancreatic neoplasia

Treatment

Dietary manipulation is a critical first step in the management of IBD in cats. Although idiopathic IBD is defined in part by an incomplete response to dietary trials, some cats with even severe inflammatory changes on GI histology may respond to dietary manipulation alone.

Novel protein (elimination) diets are designed to avoid exposure to proteins to which the cat's gut mucosal immune system may have been previously sensitised. Most commercial elimination diets contain a novel protein source, are milk-, corn- and wheat-free, and are highly digestible with a moderate amount of soluble fibre.

Dietary manipulation alone has a fairly high efficacy in treating chronic GI disease in cats, and avoids the side effects associated with immunosuppressive therapy. In fact, up to 50% of referred cats with idiopathic (unknown) GI signs will respond very well to an elimination diet trial, using a home-cooked novel protein source or one of the many commercial elimination diets now available. A commitment to a 4-6 week dietary trial has previously been recommended, which may dissuade some clinicians and owners. However, in most cases, many cats respond in a much shorter time (within 2-3 days), so a shorter dietary trial is acceptable (e.g. 1 week to allow for dietary transition).

An alternative to elimination diets are hydrolysed protein diets (e.g Hill's Z/D, Royal Canin HP Hypoallergenic diet). They minimise the antigenicity of intact dietary protein. Hydrolysed protein diets may be ideal as 'sacrificial diets' during initial induction therapy, while glucocorticoids are used to try to avoid sensitisation to any formerly novel intact proteins.

In cats that are not responsive to dietary change, immunosuppressive therapy remains the standard of care, but will hopefully be replaced in future by more specific therapies.

- chlordiazepoxide - a benzodiazepine drug with anti-anxiolytic and muscle relaxant effects
- Prednisolone - standard first-line of treatment for IBD, given at 1-3 mg/kg/day, tapered.
- Chlorambucil - a chemotherapy agent useful in refractory cases of idiopathic IBD and intestinal lymphoma at 2mg/cat every 48-72 hrs. Is well tolerated by cats compared with cyclophosphamide.
- Budesonide - low dose glucocorticoid used anecdotally in cats at 0.5-0.75 mg/cat/day
- Cyclosporin - an effective immunosuppresant that inhibits T-cell function, specifically IL-2 production. Anecdotally effective in cats with refractory IBD at doses of 5mg/kg once or twice daily. Inappetance and vomiting are common side effects.
- Probiotics, omega-3 polyunsaturated fatty acids and cobalamin are also strongly recommended as adjuncts to any therapy for IBD.

Approximately 80% of cats treated with diet and prednisolone have a positive clinical response, although clinical signs do not completely resolve. Cats with severe histological lesions, or eosinophilic inflammation may be more difficult to manage. In addition, failure to respond to treatment may indicate refractory IBD or lymphoma.

References

  1. Jergens AE et al (2010) A clinical index for disease activity in cats with chronic enteropathy. J Vet Intern Med 24(5):1027-1033
  2. Roccabianca P, Vernau WL, Caniatti M, Moore PF. (2006) Feline large granular lymphocyte (LGL) lymphoma with secondary leukaemia: primary intestinal origin with predominance of a CD3/CD 8αα phenotype. Vet Pathol 43: 15-28.
  3. Nguyen Van N, Tatlinger K, Helps CR, Tasker S, Gruffdd-Jones TJ & Day MJ (2005) Quantitative measurement of cytokine mRNA levels in duodenal biopsies in cats with inflammatory bowel disease (IBD). Immunology 116: 96.
  4. Inness VL, et al (2007) Molecular characterisation of the gut microflora of healthy and inflammatory bowel disease cats using fluorescence in situ hybridisation with special reference to Desulfovibrio spp. Anim Physiol Anim Nutr (Berl) 91(1-2):48-53
  5. Sturgess CP, Manoussaka MS, Stokes CR, Gruffydd-Jones TJ. (2003) Antibody responses to commensal intestinal bacterial flora in normal cats, and cats with inflammatory bowel disease. (Abstract) J Vet Intern Med 16: 383.
  6. Inness, VL, McCartney AL, Khoo C, Goss KL & Gibson GR (2007) Characterisation of the gut microflora of healthy and inflammatory bowel disease cats using fluorescence in situ by hybridization with special reference to Desulfovibrio spp. J. Anim. Physiol. Anim. Nutr. 91: 48-53
  7. Janeczko S, Atwater D, Bogel E, Greiter-Wilke A, Gerold A, Baumgart M, Bender H, McDonough PL, McDonough SP, Goldstein RE & Simpson KW (2008) The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease. Vet. Microbiol. 128:178-193
  8. Evans SE, Bonczynski JJ, Broussard JD, Han E, & Baer KE (2006) Comparison of endoscopic and full-thickness biopsy for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats. J Amer Vet Med Assoc 229: 1447-1450
  9. Zwingenberger AL, et al (2010) Ultrasonographic evaluation of the muscularis propria in cats with diffuse small intestinal lymphoma or inflammatory bowel disease. J Vet Intern Med 24(2):289-92
  10. Kleinschmidt, S et al (2010) Chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract in cats: diagnostic advantages of full-thickness intestinal and extraintestinal biopsies. JFMS 12:97-103
  11. Zwingenberger AL et al (2010) Ultrasonographic evaluation of the muscularis propria in cats with diffuse small intestinal lymphoma or inflammatory bowel disease. J Vet Intern Med 24(2):289-292