Definitions

Inflammatory Bowel Disease (IBD)

IBD is an idiopathic chronic enteropathy that affects cats, dogs and people. The intestinal microbiome (microorganisms present in the intestinal lumen), the innate immune system and its ability to interact with luminal content (e.g., microbiome), the integrity of the intestinal mucosal barrier, and the animal's diet all play essential roles in maintaining gastrointestinal health. Single or multiple issues affecting these parameters are likely involved in the pathogenesis of IBD. Chronic inflammation results in infiltration of the mucosa with inflammatory cells such as lymphocytes and plasma cells, eosinophils and/or neutrophils and architectural changes such as villus atrophy and fusion that lead to a significant decrease of the gastrointestinal absorptive capacity.

GI Lymphoma

The etiology of feline alimentary lymphoma is unknown. Chronic antigenic stimulation (e.g., diet), environmental carcinogens (e.g., tobacco residues on haircoat ingested during grooming), and chronic intestinal inflammation (IBD) all have a place in current hypotheses about the pathogenesis. Adaptation of the most recent WHO classification to the feline disease divided GI lymphoma in 3 types. Enteropathy-associated T-cell lymphoma (EATL) type II with neoplastic cells consisting of monomorphic small lymphocytes arising from the mucosa-associated lymphoid tissue. The biological behavior is indolent, and EATL type II is the most difficult form to differentiate from IBD. EATL type I is a more aggressive tumor consisting of large cells with high mitotic index. Affected cats often have transmural small intestinal infiltration that is often segmental and may result in partial or complete luminal obstruction. B-cell lymphoma is an aggressive tumor which consists of large B cells and also causes transmural infiltration. Stomach, small intestine and the ileo-colic junction may be affected.

Clinical Presentation

The most commonly observed clinical signs are vomiting, anorexia, diarrhea and weight loss, and general malaise. However, some cats may have a normal to increased appetite. Unlike in dogs, diarrhea is only occasionally a presenting complaint. Many cats will be presented for hyporexia/anorexia and weight loss. These non-specific signs are often waxing and waning, and the owners may seek veterinary attention only late in the course of disease. Abnormal findings on physical exam include loss of body condition, dehydration, palpation of thickened bowel loops and/or abdominal pain.

Diagnostic Approach

As stated above, the clinical signs may be very non-specific, and the first step is to rule out diseases originating outside GI tract that may present with a similar clinical picture. They include conditions such as hyperthyroidism, diabetes mellitus, chronic kidney disease, and heartworm disease, but also liver disease and pancreatitis. A minimal database is recommended that consists of CBC, chemistry profile, serum thyroxin concentration and abdominal imaging (particularly ultrasound).

Once the GI tract has been confirmed as the origin of the disease, several steps should be considered in view of the most common causes of chronic intestinal diseases in cats. Parasitic diseases should be ruled out with fecal analysis or appropriate trial treatment with broad-spectrum anthelminthics. Diagnosis of giardiasis using direct fecal smears (trophozoites) or zinc sulfate flotation (cysts) may be difficult. Analysis of several fecal samples may be required due to the erratic shedding of cysts.

Immunotests detect Giardia cyst antigen in feces and are helpful diagnostic tools. Cats infected with T. foetus are young and live in large groups, signalment and history that rarely resemble those of most cats with chronic intestinal diseases.

Dietary Trial

Many cats with mild to moderately severe clinical signs and maintained appetite will respond to a diet change within 2 weeks. Highly digestible, novel protein or hydrolyzed peptide diets are appropriate for such a trial. Improved absorption results in improved nutrition, decreased substrate available to intestinal bacteria, and decreased luminal osmotic potential. Some diets contain added omega-3 fatty acids in an effort to decrease substrate for inflammatory prostaglandins and leukotrienes. While few cats with the clinical presentation discussed above have true food allergy caused by a hypersensitivity reaction to specific food allergens, it is likely that some cats may have food intolerance that may be associated with lower quality diets, and that most cats with diet-responsive enteropathies have a mild underlying inflammation that gets worse when the mucosa is exposed to specific food proteins. Their disease can generally be controlled with an appropriate diet change.

Antimicrobial Trial

IBD is thought to result from abnormal interactions between the intestinal microbiota and the intestinal immune system. The intestinal microbiota is usually significantly altered with inflammation, and treatment of cats with chronic intestinal diseases using antimicrobials has been successful in some instances. While metronidazole (10–15 mg/kg PO q 12 h) has been popular, its therapeutic margin in cats is narrow, and risks of neurological side effects and genotoxicity (with potential to be mutagenic) make it less desirable. Tylosin (20–40 mg/kg PO q 12 h) is a good alternative, although the drug needs to be compounded for use in cats. Both drugs also have immunomodulating effects. In patients with mild disease, a 2–4 week antimicrobial trial may be instituted before starting immune-suppressive therapy.

Differentiating IBD From Alimentary Lymphoma

Several retrospective studies have eloquently shown that cats with IBD and EATL type II share a very similar signalment (middle-aged to older), history and clinical presentation. Abdominal ultrasound may be useful in evaluating the thickness and architecture of the small intestinal wall. It also allows visualization of other organs such as liver and pancreas, which may be concomitantly involved. However, in the end it is necessary to obtain intestinal biopsies for proper histopathological evaluation to differentiate between EATL type II and IBD. Endoscopic mucosal biopsies and surgical full thickness biopsies are both appropriate, and each sampling method has its strengths and weaknesses. When the pathologist cannot easily diagnose EATL immunohistochemistry and PCR assay for antigen receptor rearrangement (PARR) have been used successfully to rule in or out the possibility of EATL type II. Unfortunately, the sensitivity of PARR is 78% for T cell lymphoma and 50% and for B cell lymphoma, and false negative results are therefore possible.

Management

IBD

If dietary or antibiotic trials fail, or in severely affected cats, immune suppressive therapy is the mainstay of IBD treatment. It is best initiated when histological evidence of intestinal mucosal infiltration is available, but could also be the final option of the empirical treatment sequence started with dietary trial, and antimicrobials. Prednisolone is administered at a dose of 2–4 mg/kg PO (once daily or divided into two daily doses) for 2 weeks. Once the clinical signs have been controlled for 2 weeks or longer, the dose is reduced by one-half every 2 weeks. The final goal is to maintain the cat on the lowest effective dose, or even to consider discontinuation of steroid treatment if feasible. Refractory cases are usually treated with chlorambucil. Chlorambucil, an alkylating agent, is generally used in combination with prednisolone at a dosage of 2 mg PO per cat every other day (in cats >4 kg body weight) or every 3 days (in cats <4 kg body weight) and then tapered to the lowest effective dose. Alternately, a pulse treatment with administration of chlorambucil at 20 mg/m² body surface area (BSA) q 14 days can also be used (for most cats the BSA is between 0.25 and 0.3 m²). A CBC should be checked 2 weeks after initiation of treatment for signs of myelosuppression. Owners must understand that feline IBD is a disease that is managed and often not cured.

Lymphoma

Treatment of small cell lymphoma (EATL type II) with prednisolone and chlorambucil is associated with a good rate of complete remissions, and survival times between 16 and 30 months. Recommended doses are identical to those listed above for the treatment of IBD. When a cat comes out of remission after having initially responded to prednisolone and chlorambucil, it is advised to reinitiate the treatment at the full doses for both drugs. If the cat does not come into remission during induction, alternative protocols include lomustine (CCNU) and prednisolone, cyclophosphamide and prednisolone, COP (cyclophosphamide, vincristine or vinblastine and pred). However, it is recommended to consult with an oncologist or refer the cat prior to starting these more intensive treatments.

Large cell lymphomas are associated with a much less favorable response and survival (a few months). Surgical removal may be a pre-requisite in the presence of intestinal masses obstructing transit. Generally, protocols such as COP or CHOP (COP + doxorubicin) are initiated. Consultation with or referral to an oncologist is advised.

Vitamin B₁₂ Supplementation

It has been demonstrated that cobalamin (vitamin B₁₂) deficiency may be a consequence of gastrointestinal disease due to decreased absorption in the ileum in cats with IBD and EATL type II. This can easily be confirmed by evaluation of serum cobalamin concentration. B₁₂ deficient cats may experience a delayed recovery, or treatment failure after immune suppressive therapy.

Cobalamin must be administered SC to these patients at a dosage of 250 mg SC per cat (see http://vetmed.tamu.edu/gilab for full treatment protocol).