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Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine Chronic Diarrhoea in Cats Common Causes of Chronic Diarrhoea • Dietary Responsive gastrointestinal (GI) disease • Infectious Causes: Viruses, Protozoa , Bacteria • Inflammatory Bowel Disease • Neoplasia - Diffuse well-differentiated lymphosarcoma • Chronic diarrhoea with 3rd eyelid protrusion • Hyperthyroidism – older cats • (Exocrine Pancreatic Insufficiency – rare cause) Diet Responsive GI Disease Dietary hypersensitivity and dietary intolerance are very common causes of vomiting, diarrhoea , poor appetite, weight loss. Use a diet trial EARLY in the course of investigation and treatment Short term( 1-2 week) use of a minimum ingredient diet: o Home cooked - Single ingredient, protein only, novel protein if possible o Commercial exclusion diet e.g. Hill’s Z/D, D/D o No extras, No treats, No vitamin supplements o Water only to drink o Consider keeping indoors to avoid hunting and scavenging Food sensitivity in cats with chronic idiopathic gastrointestinal problems. Guilford WG, et al (2001) JVIM 15: 7-13 55 cats with chronic idiopathic GI disease o 49% responded to use of a commercial single source protein / carbohydrate diet Diarrhoea resolved within 2 to 3 days In 41% of those cases signs did not recur when re-challenged with original diet In 59% signs did recur - within 3-4 days of re-challenge Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine For cats that have been affected for some time, consider supplementing B12 during the diet trial: Serum cobalamin (Vit B12): o Deficiency: Marker of chronic distal SI disease (or severe chronic pancreatic disease). Also a cause of small intestinal malabsorption leading to persistence of signs despite appropriate treatment of the primary cause Infectious Causes of Diarrhoea Protozoa: Giardia, Cryptosporidium, Tritrichomonas foetus, Isospora , Sarcocystis, Toxoplasma Bacteria: Campylobacter, Clostridium spp , E. Coli, Salmonella Viruses: Feline Panleukopoenia , Coronavirus , Rotaviruses, Reoviruses, Astroviruses, Torovirus Many pathogens are shed in low numbers or are only intermittently shed. Faecal Analysis: Amalgamate three samples collected on consecutive days, or samples from multiple cats in order to reduce the risk of false negative results Many potential pathogens are also part of the normal gut flora of the cat e.g. E. coli, Pseudomonas, Clostridium Asymptomatic carriers are common Attention to diet, hygiene and general health is essential and more important than specific treatment Probiotics and Prebiotics may also be helpful Broad spectrum antibiotics will not be helpful and may promote further diarrhoea Factors suggesting a clinically significant bacterial enteritis: Haemorrhagic diarrhoea and/or fever Outbreak of diarrhoea in multi-cat household Diarrhoea and systemic signs in litters of kittens Diarrhoea in kittens Diet: Simplified diet, stable diet. E.g. Hill’s I/D Litter tray hygiene Pre-biotics and Pro-biotics: e.g. Pro-kolin paste, Synbiotic DC, Fortiflora etc... Fenbendazole ref possible Giardia If signs persist: Faecal Analysis - Multiple pooled samples from affected kittens Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine Tritrichomonas Foetus A protozoal infection previously thought to be part of the normal commensal flora of the feline GI tract, but now recognised to have pathogenic potential especially in young cats living in multi-cat households or in poor conditions. Clinical signs are of chronic waxing and waning large bowel diarrhoea which responds to antibiotic treatment but then recurs when treatment ceases. Diarrhoea can be severe in some cases and may cause scalding of the perineum, but most affected cats remain well in themselves and there is usually little or no effect on appetite or bodyweight. Spread is by direct contact with infected faeces. Although there is little evidence of zoonotic spread this cannot currently be ruled out. The organism can sometimes be identified on direct examination of a wet preparation faecal smear but this is an insensitive diagnostic test. Mix fresh diarrhoeic faeces / mucus with a similar volume of warmed saline. Place a drop on a warmed glass slide and examine immediately. The motile trophozoites can be seen under the x20 or x40 lens swimming across the visual field with a “jerky forward motility” as compared to the “falling leaf” or “rolling” motility of the Giardia trophozoite. Direct microscopy is estimated to be identify the organism in only 14% of infected cats. Confirmation of the diagnosis is by PCR on faecal samples that must be free of cat litter. PCR is most reliable when used in cats that have diarrhoea but have not been treated with antibiotics within the previous 7 days and has the advantage that it can detect both live and dead organisms. Even so the sensitivity is not 100% (although it probably does exceed 90%) so a negative result in a cat suspected of being an asymptomatic carrier can still be difficult to interpret and repeated testing or testing of multiple cats in the household may be recommended. Treatment is difficult as the organism is resistant to all standard antibiotics. Affected cats will eventually spontaneously clear the infection especially if they are removed from the multi-cat environment. The only effective treatment is with ronidazole, which can be formulated on request by Nova Labs (0116 223 0100). It can cause serious neurological side effects especially at higher doses, so precise dose calculation is required and the capsules must be formulated to an appropriate size for each cat that is being treated. Ronidazole powder has a very bitter taste so reformulation into a liquid is not recommended and the capsules should be dosed whole and not opened to sprinkle the contents onto food (this is also important advice for owners who must avoid accidental ingestion of the powder themselves. The recommended dose of ronidazole is 30 mg/kg once daily for 14 days. All cats in the household should be treated as asymptomatic carriers are common. However this drug must only be used in cats over 12 weeks of age and must not be used in pregnant or lactating queens. For young kittens (< 12 weeks) use of lower doses has been recommended but in the absence of any data on safety and efficacy this is best avoided. While cats are being treated they must be observed closely by their owners for any signs of weakness or ataxia. If signs develop treatment must be stopped immediately, and most cats will Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine then make a full recovery as long as the problem has been identified early enough before permanent damage has occurred. If treatment has to be ceased due to adverse effects re-testing is recommended as many cats will clear the infection despite a truncated course of treatment. In most cases clinical signs will resolve during or shortly after completion of the 14 day course of treatment, however in some cases signs may persist for some weeks due to secondary inflammation. Re-testing is required to confirm persistence of infection before considering using a second course of treatment. For more information visit: http://www.fabcats.org/breeders/infosheets/tritrichomonas.html http://www.cvm.ncsu.edu/docs/documents/ownersguide_tfoetus_revised_120909.pdf Inflammatory Bowel Disease The World Small Animal Association GI Standardization group (www.wsava.org/StandardizationGroup.htm) has defined inflammatory bowel disease as gastrointestinal (GI) signs of more than 3 weeks duration that have not resolved after a dietary trial and anthelmenthic treatment, in which there is histological evidence of mucosal inflammation, and a clinical improvement on immunomodulatory treatment. In cats: The small intestine is usually more severely affected than the colon or the stomach Lymphocytic-plasmacytic infiltrates are most commonly identified, but eosinophilic and neutrophilic / granulomatous infiltrates also occur. Eosinophilic IBD is often particularly refractory to treatment. It seems likely that the pathogenesis involves a breakdown in the normal systems for preventing immune reactions to dietary antigens and to the normal bowel flora. The cause(s) of this breakdown are, as yet, unexplained. NB: There are also a number of other conditions which will cause similar signs and which result in the infiltration of inflammatory cells in the bowel. These include bacterial and protozoal infections (e.g. Giardia), dietary allergies and intolerances, and even some cases of diffuse intestinal lymphosarcoma. Simply identifying increased inflammatory cells in the bowel lining is therefore not sufficient to justify a diagnosis of IBD and it is particularly important that appropriate diagnostic tests are used to rule out infectious and dietary causes before bowel biopsies are taken. Clinical Features Inflammatory bowel disease can affect cats of any age. Clinical signs may include vomiting, diarrhoea and/or weight loss and the cat may have suffered signs for a prolonged period. Vomiting is a common clinical sign and may occur in intermittent bouts, or more consistently. The vomiting is not always related to eating, and the vomitus may consist of food, mucoid froth or bile. Diarrhoea is a common but not invariable finding, and in many cases the owner may be unaware that diarrhoea is present. The diarrhoea is highly variable in nature and severity. Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine Weight loss occurs in the majority of cases and may be associated with either decreased or increased appetite. In some cases weight loss may be the only clinical sign. Skin lesions (alopecia, miliary dermatitis and pruritus) may be present in up to 20% of cases. Most cats with inflammatory bowel disease remain bright and active unless the clinical signs are very severe. Clinical examination is generally unrewarding; mesenteric lymph node enlargement may be detected, and pruritic skin lesions are present in some cases. Treatment Treatment of lympho-plasmacytic enteritis is usually with a combination of corticosteroids and dietary modification. In refractory cases adjunctive treatment may be required. Dietary manipulation: By definition cats with IBD do not respond to dietary manipulation alone, but it is still an important adjunct to corticosteroid treatment. A highly digestible, “hypoallergenic” diet, containing a single source of protein and a single source of carbohydrate, or composed of hydrolysed proteins is appropriate. Use of a “sacrificial” protein may have some benefit. This is based on the assumption that, since mucosal lesions are present when the restricted protein source diet is first introduced, there will be abnormal exposure to this potential dietary antigen with possible development of hypersensitivity to it. Therefore, at the time of diagnosis a diet based on a “novel” protein source is used, and when the signs are controlled and drug therapy is ceased, or reduced to a minimum level, the cat is switched to a diet based on another protein (novel, if possible). Immunosuppression: First line treatment is with immunosuppressive doses of corticosteroid. Oral prednisolone (2-4 mg/kg/day initially, in single or divided doses) is preferred as it allows much better control of dosage than the use of depot injections. In most cases clinical signs resolve within 1-2 weeks of initiating treatment but long-term treatment is required to prevent relapse. There are no data available regarding the optimum time for which the initial dose of corticosteroid should be maintained. It is probably appropriate to continue to use the initial dose for 1-2 weeks after remission has been achieved and thereafter the dose can be gradually tapered, usually over a period of at least 2-3 months, depending on the response to treatment. If treatment is tapered too abruptly relapse is likely. In some cases it may eventually be possible to cease steroid treatment and maintain control by dietary means alone, but many cats will relapse and require subsequent courses of treatment. Fortunately most cats tolerate long-term corticosteroid treatment well. Potential adverse effects include gastric ulcers, obesity, urinary tract infections, diabetes mellitus and iatrogenic hyperadrenocorticism, but the more severe of these adverse effects are rare. Budesonide is an orally administered corticosteroid which is mostly eliminated by first pass metabolism in the liver, and therefore has reduced potential to cause systemic side effects. It appears to have value in the treatment of cats with IBD, especially those in which use of systemic corticosteroid is contra-indicated e.g. diabetic cats. It is less potent than prednisolone and response Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine to treatment is often slow. Suggested doses are 2 mg per cat once daily, or 3 mg per cat every other day. Adjunctive Treatment: If treatment with immunosuppressive doses of corticosteroids in conjunction with an appropriate diet does not produce an adequate response then adjunctive treatment will be required. Cobalamin deficiency occurs as a result of chronic distal SI disease and will itself contribute to small intestinal diarrhoea. In some cats parenteral supplementation of cobalamin will be required in order to achieve remission of diarrhoea. Dose rates are empirical; a subcutaneous injection of 150-250 μg once a week for 4-6 weeks, then every other week for a further 6 weeks appears to be effective in most cases. Metronidazole (10-15 mg/kg twice daily) is useful in some cases. In addition to its antibacterial and antiprotozoal activity metronidazole modulates cell mediated immune responses, and has some anti-inflammatory properties. It is rarely effective alone but can be a useful addition to immunosuppression with corticosteroids. Long term treatment should be avoided as metronidazole may itself be carcinogenic. In refractory cases in which a biopsy diagnosis of IBD has been reached, additional immunosuppression with chlorambucil (Leukeran; dose equivalent to 2-6 mg/m2 every 24 hours, wear gloves, do not crush or divide the tablets, keep refrigerated. ) is usually well tolerated and effective. Myelosuppression is possible so white cell counts should be monitored Prognosis Most cases respond well to treatment, but prolonged treatment is required and relapses may occur. This is a condition which can be managed, but not necessarily “cured”. In some cases uncontrolled plasmacytic-lymphocytic IBD appears to “progress” to diffuse GI lymphoma. It is currently not clear whether this is an example of genuine neoplastic transformation due to chronic inflammation, or whether affected cats were originally “mis-diagnosed” as having lymphocytic IBD. Diffuse Intestinal Lymphocytic Lymphosarcoma For diffuse, or low grade lymphosarcoma the prognosis is fairly good (Fondacero et al,1999), with around 70% of cats achieving complete remission and mean survival time ranging from 16 to 20 months (depending on whether complete remission was achieved). Both drugs are inexpensive, readily available and usually well tolerated in cats. Prednisolone: 5 mg p/o twice daily initially. Chlorambucil (Leukeran; GlaxoSmithKline): Dose 2 mg every 2-3 days. Wear gloves to handle the tablets. Tablets must be stored in the fridge. Usually well tolerated. May cause leukopenia, nadir occurs after about 3 weeks. Monitor white blood cells every 3-4 weeks; increase the dose interval if leukopenia develops. Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine A practical approach to chronic diarrhoea in cats where a full diagnostic investigation cannot be undertaken. Full investigation of cases of chronic diarrhoea can be prolonged and costly, and interpretation of results is not always straightforward. In some cases a more pragmatic approach may be justifiable, based on the most likely causes of the problem, and the likelihood that those conditions will respond to treatment. NB: This approach is not appropriate in all cases. It should be reserved for cats that are in good general clinical condition, and in which initial assessment has failed to identify evidence of any specific underlying cause. Step 1: Use pre- and pro-biotics and implement a dietary trial for around 2 weeks; if strict adherence to the diet is in doubt, continue for up to 4 weeks. It may be beneficial to confine the cat within the house during this period to prevent hunting and scavenging behaviour. An ideal diet is palatable, highly digestible and low in fat. Home cooked diets composed of a single protein source (i.e. chicken only, or white fish only) are ideal, and for owners who do not wish to home cook, commercial diets based on chicken and rice are a good first choice. If there is good response to the diet other food sources can be introduced one at a time. Most adverse reactions will be seen within 7 days of re-introducing the offending food source. If there is no response to the diet repeat the 2 week trial using a different diet which eliminates the ingredients present in the first diet. A positive response to an elimination diet may indicate an adverse food reaction as the primary cause of the problem, but some mild cases of IBD will also respond to such treatment. Step 2: Treatment with fenbendazole (50 mg/kg once daily for 3-5 to five days) to eliminate Giardia. Step 3: Treatment with systemic vitamin B supplementation and oral metronidazole (10 mg/kg twice daily, or 20 mg/kg once daily, depending on the preparation used). Continue treatment for around three weeks. The antibacterial action of metronidazole may be effective for small intestinal bacterial overgrowth – a controversial subject in feline medicine, for which no practical diagnostic tests exist. If this condition exists in cats it is most likely to involve anaerobic organisms, so metronidazole is a logical choice of antibiotic. The immunomodulatory effect of metronidazole may be beneficial for some cats with IBD. Oxford Cat Clinic 01865 243000 [email protected] Martha Cannon, BA VetMB DSAM(Fel,) RCVS Specialist in Feline Medicine Step 4: Further investigations should be recommended at this stage, particularly if the clinical signs are of significant frequency or severity. At the least faecal analysis, using an amalgamation of three consecutive faecal samples, must be performed at this stage. If faecal analysis is unremarkable, IBD and neoplasia are the most common remaining differential diagnosis and GI biopsies are recommended, especially to differentiate between IBD and diffuse alimentary lymphosarcoma. If collection of GI biopsies is not possible then empirical treatment with a combination of prednisolone and dietary manipulation may be used. It is essential to rule out infectious causes of diarrhoea (including Tritrichomonas foetus in cats with colitis signs). Use of additional immunosuppressive agents should be reserved for cases in which a definitive diagnosis has been reached. Oxford Cat Clinic 01865 243000 [email protected]