Abstract
Diarrhoea is generally regarded as the most consistent clinical sign of intestinal disease in the cat. The history and physical examination are paramount for determining whether the diarrhoea is due to primary disease of the gastrointestinal tract or secondary to extra-intestinal diseases such as chronic renal failure or hyperthyroidism. In cats, most chronic diarrhoeas involve the small-bowel and diarrhoea due to maldigestion is relatively uncommon.
History
The history can indicate the location, severity and probable cause of the disease process. An important goal of the history is to categorise the diarrhoea into ‘small bowel’ or ‘large bowel’ in origin, because this will have a direct impact on the diagnostic and therapeutic approach to the patient. A careful history should also indicate the presence of extraintestinal disease (renal failure or hyperthyroidism) as the underlying cause of diarrhoea or may identify important predisposing factors, such as diet, environmental factors, exposure to parasites, infectious agents, drugs or toxins. The history should focus on the duration of the diarrhoea, the patient's diet (and diet changes), the appearance of the faeces (colour, volume, mucus, presence of fresh blood), worming and vaccination history, defecation frequency, aggravating or alleviating factors, and defecation urgency. Adverse reactions to food are a relatively common cause of chronic diarrhoea in cats and the history is a simple way to determine incriminating diets or protein sources.
Physical examination
Physical examination should emphasise the detection of fever, cachexia, dehydration, weakness or depression, pallor (blood loss anaemia) and effusions or oedema (hypoalbuminaemia). The thyroid area should be carefully palpated, and the kidneys and liver examined for changes in size. Intestinal loops should be carefully palpated for masses, thickening (inflammatory or neoplastic infiltration), distension, pain or associated lymphadenopathy. Palpation of the rectum may reveal rectal masses or thickening of the rectal wall.
Diagnostic approach
For undiagnosed chronic diarrhoea, the minimum database should include a complete blood count (CBC), a serum biochemistry profile, a urinalysis, a faecal flotation and a direct smear of saline admixed fresh faeces for protozoa. Flotations are excellent for recovering common nematode ova, oocysts of coccidia (including Cryptosporidium sp) and Giardia sp cysts. The main limitation of flotations is their inability to float organisms whose diagnostic stage has a specific gravity higher than that of the flotation medium. Most commonly these are the heavy ova of trematodes and acanthocephalans (thorny-headed worms). Fragile cysts and larvae, though recovered, may be too distorted to identify. It is always preferable to use a centrifugation flotation technique. This is probably the single most important change one can institute to improve routine recovery of parasite stages by flotation. Flotation methods that do not utilise a centrifugation technique are often not sensitive enough to recover small numbers of organisms in the faeces. Always use a coverslip rather than a loop or glass rod to transfer the meniscus to a slide. If your centrifuge has free-swinging buckets, use a coverslip on the final centrifugation to recover parasites. If your centrifuge has a fixed-angle, carefully add more flotation medium after the final spin to create a meniscus and set the coverslip on top for several minutes before lifting it off for examination. If at this point you are still determined to do standing flotations, use a coverslip to transfer the meniscus. Coverglass improves the optics of any microscope. Check the specific gravity of flotation medium. If possible, switch to zinc sulphate (sg 1.18 or 1.2) in order to improve detection and morphology of Giardia sp. Remember that regardless of the flotation solution all eggs do not float. Choice of flotation solution is less important than the actual method of flotation. Examine preparations as soon as possible after preparing them. Delay will result in distortion of some parasite stages and incorrect or missed diagnoses, especially with delicate cysts and oocysts.
Encysted forms of Giardia sp organisms in a faecal specimen may be detected most reliably with zinc sulphate flotation, as opposed to examination of fresh saline smears (Zimmer & Burnington 1986). Preliminary studies in giardiainfected cats at the University of California, Davis, have revealed that the ProSpec T© Microplate ELISA Assay compares favourably in sensitivity and specificity to the zinc sulphate flotation technique; however, the sensitivity of the ProSpec T© Giardia Rapid ELISA Assay is significantly less than that of the Microplate Assay and zinc sulphate flotation methods. Similar studies have been performed in cryptosporidium-infected cats at the University of California, Davis, and preliminary findings have revealed that the ProSpec T© Cryptosporidium microplate assay is equally sensitive and specific to the modified Ziehl-Neelsen acid-fast staining technique; however, the ProSpec T© Cryptosporidium Rapid Assay is far less sensitive than the former two methods. The importance of evaluating two to three consecutively obtained faecal specimens cannot be overemphasised as our studies have shown significant increases in sensitivity in all diagnostic tests when more than one stool specimen is examined.
Macroscopic examination of a fresh faecal specimen is essential for assessment of bulk, colour, consistency and detection of blood and mucus. Small bowel diarrhoea is generally free of grossly visible mucus or red blood, but prominent steatorrhoea may cause the faeces to appear lighter in colour. Acholic or pale faeces can also be seen in association with extrahepatic bile duct obstruction causing a lack of the bile pigment stercobilin in the faeces. Rapid intestinal transit time can be associated with yellow or green stools due to incomplete metabolisation of bilirubin (Guilford 1996).
The CBC may reveal an eosinophilia secondary to endoparasitism, eosinophilic enteritis or abdominal mast cell neoplasia. Anaemia may result from enteric blood loss or from depressed erythropoiesis caused by systemic disease or chronic inflammation. Underlying systemic diseases such as chronic renal failure or liver disease may be detected on the serum biochemical profile. In addition, panhypoproteinemia (low serum albumin and globulin) may be seen with severe infiltrative bowel diseases such as inflammatory bowel disease, intestinal lymphoma and Histoplasmosis. The finding of steatorrhoea and weight loss in the face of a normal to increased appetite is consistent with a malassimilation disorder such as exocrine pancreatic insufficiency. Although this condition is relatively uncommon in cats, it can be confirmed by performing a serum trypsin-like immunoreactivity assay (Williams 1994). Cats exhibiting signs of large bowel diarrhoea should have a rectal scraping and stained faecal smear performed to evaluate for inflammatory cells or fungal hypae (Latimer 1993). Serological screening for FeLV and FIV is advised for those cats that have failed to respond to antiparasitic or dietary therapy. Serum thyroxine measurement should be considered in elderly cats particularly if steatorrhoea is observed.
Survey abdominal radiographs are a relatively low yield procedure in most patients with chronic diarrhoea, but are indicated in cats suspected of having partial obstructions due to foreign bodies, intussusceptions or masses. Abdominal ultrasound is complimentary to survey abdominal radiographs and is more sensitive for the detection of abdominal masses, intestinal mural thickening, intussusceptions and mesenteric lymphadenopathy (Penninck et al 1990). In addition, ultrasound-guided percutaneous biopsy or aspiration of masses is an effective diagnostic procedure. Contrast radiography and fluoroscopy are occasionally indicated for identification of partial obstructions and intestinal motility disorders, respectively.
Faecal culture is typically a low-yield procedure in cats with diarrhoea because the clinical documentation of enteropathogenic bacteria causing diarrhoea is clouded by the presence of these organisms in apparently healthy animals. If bacterial enteritis or enterocolitis is suspected, the faeces should be cultured for specific pathogens such as Salmonella sp, Campylobacter jejuni, Clostridium perfringens and Clostridium difficile (Kruth et al 1989, Twedt 1993, Bartlett 1994). Faecal cultures should be reserved for cats developing diarrhoea after kennelling or show attendance, in cats with an acute onset of bloody diarrhoea in association with evidence of sepsis, or in diarrhoea outbreaks occurring in more than one pet in a household. Caution should be exercised when interpreting the presence of C perfringens endospores in faecal smears obtained from cats with diarrhoea, because healthy cats can harbour large numbers of C perfringens endospores in their stools. In addition, the currently accepted opinion that more than two to three endospores/oil immersion field is associated with enterotoxin appears unsubstantiated in light of recent studies documenting a poor correlation between faecal endospore numbers and the presence of enterotoxin (Marks et al 1999).
The prevalence of C difficile in faecal specimens from cats who were patients at the University of California Veterinary Medical Teaching Hospital was 9.4% (23 of 245 cats) based on culture of selective media and identification by a latex particle agglutination test (Madwell et al 1999). Toxin A and B sequences were identified in eight of 23 isolates and were confirmed by southern blot hybridisation. All of the cats colonised with toxigenic C difficile had risk factors (antibiotic use, antineoplastic therapy) associated with C difficile infection in human patients. Four of the eight cats colonised with toxigenic C difficile were treated with metronidazole and had resolution of the diarrhoea and negative faecal culture on subsequent testing. The significance of isolating nontoxigenic C difficile in asymptomatic human patients is uncertain because the organism is a normal component of the colonic microflora in some individuals. Multiple strains of C difficile are often isolated during outbreaks of C difficile-associated diarrhoea, and AP-PCR can be utilised to identify the different genotypes of C difficile within a hospital population. This method has confirmed the potential role of environmental contamination in bacterial transmission by identifying bacteria in the environment with identical genotypes to those isolated from the patient.
Cats with no evidence of life-threatening disease whose diarrhoea remains undiagnosed after initial laboratory and imaging procedures are further evaluated with controlled diets for 2 to 3 weeks. The diet selected should be free of additives and preservatives, and contain a novel protein source that is highly digestible. High protein diets should be avoided because the excess dietary protein can lead to increased formation of antigen–antibody complexes in the intestinal wall. The protein should be highly digestible because intact proteins are far more antigenic than polypeptides and amino acids. If signs resolve following several weeks of dietary therapy, the diet should be balanced or alternatively a complete and balanced commercial diet with the same novel protein source as the homemade diet should be selected. If signs do not resolve, a more extensive diagnostic approach is warranted.
Endoscopy is a valuable procedure for the diagnosis of intestinal mucosal diseases that are associated with morphologic changes. Endoscopy, however, does not differentiate intestinal motility disorders, secretory diarrhoeas or brush border enzyme defects, and is likely to miss lesions in the intestinal submucosa and muscularis. In addition, endoscopy is limited by the working length of the scope, limiting endoscopic examination of the jejunum. Rigid proctoscopy is preferred over flexible colonoscopy for the initial evaluation of large bowel disease. Rigid proctoscopy entails less risk, time and cost than colonoscopy, and is able to diagnose the majority of large bowel disorders because of the diffuse nature of the disease. Flexible colonoscopy is indicated for evaluation of upper colonic disease, including caecal inversion, ileocolic neoplasia and occult Trichuris sp infection.
Tests for malabsorption do not give a specific causal diagnosis for the diarrhoea, and many of these tests are limited by relatively poor sensitivity and specificity. In contrast to the endoscopic procedure which typically diagnoses abnormal mucosal morphology, malabsorption tests evaluate intestinal function. They identify abnormal carbohydrate or fat assimilation secondary to motility disorders, ‘bacterial overgrowth’ or brush border enzyme deficiencies. Screening tests of malassimilation include the indirect quantitative analysis of faecal fat, the breath hydrogen analysis and the direct/indirect Sudan stain for faecal fat. The use of the fat absorption test is not recommended due to the frequency of misleading results.
Antibiotics for the treatment of bacterial-associated diarrhoeas
Principles of diarrhoea therapy
Symptomatic therapy includes restoration and maintenance of fluid and electrolyte balance, dietary modification and intestinal motility modifiers. Antibiotics and immunosuppressive drugs are introduced based on evidence of inflammatory bowel disease or bacterial enteritis. Motility modifiers are only indicated if the diarrhoea is intractable and should not be used if the diarrhoea is due to invasive microorganisms. The opiate and opioid narcotic analgesics such as loperamide (Imodium; 0.1–0.2 mg/kg TID, PO) are the most effective motility modifiers for managing diarrhoea. Anticholinergic agents are contraindicated because they may cause generalised suppression of all motility and may potentiate ileus.
Oral protectants
Oral protectants such as kaolin-pectin, bismuth, activated charcoal and barium are purported to act locally within the gut lumen to adsorb bacteria and toxins and to provide a protective coating on inflamed mucosal surfaces. Bismuth subsalicylate is the most useful of these agents because it has antienterotoxin, antibacterial, antisecretory and anti-inflammatory actions. Caution should be exercised with the use of salicylate-containing compounds due to the prolonged elimination of this compound in cats. Bismuth dosed at 0.5 to 1 ml/kg BID for 2–3 days is safe in cats.
Antibiotics
Use of antibiotics as empirical therapy in the management of uncomplicated or non-infectious diarrhoea is not recommended because of the adverse effects of the antibiotics on the normal intestinal microflora and their tendency to promote resistant strains of bacteria. Antibiotics are indicated when specific bacterial or protozoan enteropathogens, such as Campylobacter, Clostridium or Giardia sp are isolated from the faeces (Table 1). In addition, antibiotics should be considered in conditions associated with severe mucosal damage and a high risk of secondary sepsis or endotoxaemia (Guilford 1996).
Immunosuppressive drugs
Immunosuppressive drugs are indicated in cats with inflammatory bowel disease. Oral glucocorticoids should be used at immunosuppressive doses (initially 1.5–2 mg/kg BID) and tapered over a 2–3 month course (Tams 1986, 1993). In glucocorticoid resistant cases, the addition of metronidazole (Jergens 1992) and azathioprine (Imuran; 0.3 mg/kg q 48 h) (Tams 1986) or chlorambucil (Leukeran; 2 mg q 4 days) may result in remission of disease.
Dietary therapy
The ideal diet for cats with chronic small bowel diarrhoea is based on a highly digestible single protein and carbohydrate source that is gluten- and lactose-free. There are a limited number of commercial ‘hypoallergenic’ diets currently available that fulfil these requirements, necessitating the use of computer-generated homemade diets in patients failing to respond to commercial diets. Single protein source diets that are commercially available for cats contain either venison, rabbit, chicken, fish or lamb. It is important that the ingredients list of a potentially hypoallergenic diet be thoroughly evaluated, because diets with several protein sources (lamb, beef, rice and wheat are commonly marketed with a claim to hypoallergenicity.
Dietary recommendations for the management of large bowel diarrhoea are controversial. The response to dietary therapy can vary dramatically from one patient to another, with some animals showing improvement on low residue, ‘hypoallergenic’ diets, and others improving on less digestible diets containing soluble or insoluble fibre sources (Guilford 1996, Dimski 1992). There is evidence to suggest that some forms of colitis may be associated with a dietary sensitivity similar to that observed with small bowel disease. The theoretical benefit for utilising highly digestible ‘hypoallergenic’ diets for patients with colitis includes reducing the digestive challenge to the large intestine and minimising the likelihood of dietary antigens actually reaching the colon, thus lessening the likelihood of an immunological reaction (Simpson et al 1994). The author recommends feeding a complete and balanced commercial diet containing moderate amounts of a highly digestible single protein source to which the animal has not been previously exposed. The supplementation of fermentable fibre sources such as psyllium or oat bran may be necessary in patients showing partial resolution of their clinical signs. Failure to respond to these recommendations may necessitate selecting a ‘hypoallergenic’ diet with a different novel protein source or adding insoluble fibre to the diet.