F. Gaschen
School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
Clinical Presentation
Middle-aged to older cats with vomiting, anorexia, diarrhea and weight loss, and general malaise are the most commonly observed clinical signs. 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, lethargy 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, possible palpation of thickened bowel loops and/or abdominal pain.
Diagnostic Approach
Because the clinical signs may be very non-specific, the first step is to rule out diseases originating outside GI tract that may present with a similar clinical picture. These include conditions such as hyperthyroidism, chronic kidney disease, liver disease and pancreatitis. A minimal database is recommended that consists of CBC, chemistry profile, serum thyroxin concentration and abdominal imaging (radiographs, 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 empirical 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. Several commercially available immunoassays detect Giardia cyst antigen in feces and are helpful diagnostic tools.
Diagnostic Imaging
In chronic enteropathies, the most common abnormality of the small intestine is thickening of the tunica muscularis. It is seen equally frequently in inflammatory bowel disease (IBD) and alimentary lymphoma, and cannot be used to differentiate these 2 diseases. Norsworthy et al. (JAVMA 2015) reported that jejunal wall thickness >2.8 mm at 2 sites or >3.0 mm at one site correlates with clinically relevant histopathological disease.
Empirical Treatment Trial
Cats with mild to moderately severe clinical signs and maintained appetite may respond to a diet change using highly digestible, novel protein or hydrolyzed peptide diets within 2 weeks. In cats that do not respond to a dietary approach, antimicrobials have been successful in some instances, presumably to correct intestinal dysbiosis (e.g., metronidazole 10–15 mg/kg PO q12 h or tylosin 10–15 mg/kg PO q12h). Improvement is usually noticeable within a few days. In cats that respond to treatment, there are no reports about the optimal duration of antimicrobial treatment, and the author usually attempts to discontinue treatment after 3–4 weeks.
Collection and Evaluation of Intestinal Biopsies
In cats that do not respond or only partially respond to dietary or antimicrobial treatment, it is often necessary to obtain intestinal biopsies for histopathological evaluation to differentiate between enteropathy-associated T-cell lymphoma (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. In difficult cases when the pathologist cannot easily differentiate between inflammation and neoplasia, immunohistochemistry for T- and B-cell markers and PCR assay for antigen receptor rearrangement (PARR) have been used successfully to rule in or out the possibility of enteropathy-associated T-cell lymphoma (EATL) type II. Unfortunately, the sensitivity of PARR is 78% for T cell lymphoma and 50% for B cell lymphoma, and false-negative results are therefore possible.
Inflammation of Multiple Digestive Organs
Inflammatory bowel disease, neutrophilic or lymphocytic cholangitis and chronic pancreatitis or any combination of these diseases have been reported to occur concurrently in middle-age to older cats. Simultaneous occurrence of all 3 diseases has been described as “triaditis.” This multiorgan inflammation may be a consequence of the unique pancreaticobiliary anatomy of the cat with fusion of pancreatic and common bile ducts prior to the duodenal papilla. It is suspected that bacteria may penetrate and ascend the pancreatic and bile ducts and permit extension of inflammation to these organs. Diagnosis is suspected based on finding changes suggestive of IBD (see above), increased serum liver enzymes and possibly bilirubin, and ultrasound abnormalities in the pancreas and/or increase serum fPL or DGGL lipase. Confirmation of diagnosis relies on histopathologic analysis of intestinal, liver and pancreatic biopsies. Treatment is based on prednisolone at immune-suppressive (IBD) or anti-inflammatory (chronic pancreatitis) doses, and possible broad-spectrum antibiotics in case of neutrophilic cholangitis (e.g, amoxicillin and clavulanic acid 20 mg/kg q12h).
Management and Prognosis
- Inflammatory bowel disease: 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 generally administered at a dose of 2 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-quarter to 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) q14 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. In one study, 80% of 7 cats with IBD treated with diet and prednisolone had a positive response to treatment. 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. Owners must understand that feline IBD is a disease that can be managed, but not cured.
- Treatment of small cell alimentary 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 depending on the study. 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 rescue treatments. Large cell lymphomas are associated with a much less favorable response and survival (a few months). Surgical removal may be a prerequisite 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.
- It has been demonstrated that cobalamin (vitamin B12) deficiency may be a consequence of feline gastrointestinal disease due to decreased absorption in the ileum with IBD or EATL type II. Hypocobalaminemia is easily confirmed by evaluation of serum cobalamin concentration. B12-deficient cats may experience a delayed recovery, or treatment failure after immune suppressive therapy. Cobalamin may be administered SC at 250 mg SC per cat (see http://vetmed.tamu.edu/gilab for full treatment protocol) or orally (0.25 mg/ cat PO q24h).
Further Reading
Jergens AE, Allenspach K. Feline inflammatory gastrointestinal disease. In: Little SE, ed. August’s Consultations in Feline Internal Medicine. Volume 7. 2016:129–138.