Chronic diarrhoea in cats
Chronic diarrhoea is a frequent complaint in feline medicine. It is defined as enteritis of 3 to 4 weeks duration or relapsing diarrhoea. In contrast to acute diarrhoea which is frequently a self-limiting problem and does not require an extensive workup except in viral/bacterial disease or gastrointestinal obstruction, chronic diarrhoea cases deserve a step by step approach to obtain a diagnosis and propose a specific treatment.
Table 1 presents a list of possible differential diagnosis for chronic diarrhea in the cat. For extensive review consult references (1-3). The most frequent causes are parasitism (especially protozoans since they are not covered by classical deworming medications), inflammatory bowel disease (IBD), hyperthyroidism and alimentary lymphoma. Food hypersensitivity has been reported to account for about 30% of cases in one study (4). This condition is very difficult to differentiate from IBD especially as the majority of affected cats have histological changes of chronic intestinal inflammation (4) and also because the definitive diagnosis requires a food challenge with the initial diet which is frequently declined by the owners. Contrary to most IBD cases, clinical signs have been shown to resolve within 2 to 3 days after the dietary change in food sensitive cats (4).
History and physical examination
Deworming history, characterization of the type of diarrhea (small intestinal versus large intestinal, see Table 2) and a complete dietary history are the key points of the history. Previous treatments should be documented, especially antibiotic therapy since it can be associated with bacterial flora disturbances and secondary chronic diarrhea. Concurrent vomiting must also be documented. Physical examination must be complete and include an abdominal palpation and a careful examination of the ventral neck, searching for a thyroid slip.
A fecal screening for parasites is the first step. A fecal flotation must be done and repeated 3 times to increase the sensitivity of the diagnosis of giardiasis (2) or isosporosis. Other tests include specific staining and immunological or PCR test for Tritrichomonas fetus or Cryptosporidium parvum infections.
Basic laboratory tests include a complete blood count (CBC) and a chemistry panel which should include total T4, especially in older cats. The aim is to rule-out metabolic diseases and to look for any possible consequence of the primary intestinal disease such as hypoalbuminemia, hypocholesterolemia or any electrolyte disturbances. Moderate increases in ALT and ALP are frequently observed in hyperthyroidism and chronic intestinal inflammation.
The next step in the case of non specific findings on the previous tests is to document possible pancreatic diseases including exocrine pancreatic insufficiency and chronic pancreatitis respectively with fTLI (feline Trypsin Like Immunoreactivity) or fPLI (feline Pancreatic Lipase Immunoreactivity) blood measurements. Serum folates and cobalamin concentration should also be measured to diagnose possible malabsorption of these vitamins and start supplementation in case of cobalamin deficiency. Imaging should be performed through ultrasonography to look for any intra-abdominal changes especially in the liver, pancreas, intestinal wall and abdominal lymph nodes. Fine needle aspiration of observed anomalies may help to reach a diagnosis of cancer or pancreatitis. When liver failure is suspected, pre and post-prandial bile acid measurements are recommended. An abnormal test is an indication for a liver biopsy.
After this second step, if no specific diagnosis has been reached then intestinal biopsy helps to differentiate between chronic intestinal inflammation and intestinal neoplasia. If abdominal ultrasonography has revealed any focal lesion, surgery for full thickness biopsy and possible excision of the mass is recommended. Concurrent liver and pancreatic biopsies should be performed since in cats, cholangitis-cholangiohepatitis, pancreatitis and IBD are frequently associated (5). It is recommended to biopsy all the three segments of the small intestine. When ultrasonography is not indicative of any focal change, endoscopic biopsy can be performed. In this case, it is probably better to sample stomach and duodenum via upper endoscopy but also colon and possibly ileum through colonoscopy, especially because intestinal inflammatory or neoplastic lesions can be heterogeneous in their distribution.
Three clinical cases are presented to illustrate the approach of chronic diarrhea in cats.
An 8-month old Domestic Shorthair female spayed cat was presented for a complaint of chronic diarrhea of 4 months duration. The cat had been treated with deworming medications (including praziquantel/pyrantel and milbemycin), dietary changes including a highly digestible diet and a novel protein diet and a course of metronidazole for one month (10 mg/kg bid). No improvement had been observed with these different treatments. From history, the diarrhea seemed to be of mixed origin (small and large intestine) with an increased volume of the stools sometimes associated with straining/urgency and mucus.
The owner did not notice any changes in the cat’s behavior, he was very dynamic, no vomiting had been observed but polyphagia was noticed over the last few weeks. The cat was mostly an indoor cat with a limited access to a patio always under the control of the owner. On physical examination, the cat was bright, alert and responsive, was underweight with a body condition score of 2-3/9, her weight was 2.5 kg. Abdominal palpation revealed gas/fluid filled bowel loops without any pain or significant dilation. Physical examination was otherwise unremarkable.
Fresh fecal smear (Figure 1) and fecal flotation reveals Giardia infection with more than 500 Giardia cysts per gram of feces. FeLV and FIV tests were negative and routine complete blood count and chemistry did not reveal any abnormalities. The cat was treated with metronidazole 25 mg/kg bid for 10 days. When the owners contacted us by telephone, two days after the beginning of the treatment the diarrhea resolved but 10 days after the completion of the treatment the condition relapsed. The fecal parasite screening revealed the cat was still severely infected with Giardia. At this time the feces were also submitted for Cryptosporidium spp. screening and Tritrichomonas fetus PCR. Results were negative for both parasites. Owner questioning revealed that a free roaming cat was sometimes playing with the kitten on the patio. It was recommended to treat both cats with febendazole (50 mg/kg sid) for a course of four days and to recheck the fecal panel after treatment. Disinfection with a quaternary ammonium solution of the litter box and all the roaming areas, where it was possible, was recommended. The two cats were bathed and dried after bathing to remove possible shedding of cysts in the coat. The recheck fecal panel was negative at the end of treatment and also 3 weeks after the end of treatment. No relapse has been reported within more than one year after treatment.
This case illustrates that parasitism should always be high in the list of differentials of chronic diarrhea in cats. Giardia is frequently recovered because the deworming medications routinely used in cats are not effective against Giardia. The reported prevalence of giardiasis in cats varies from 2.4% to up 10.2% with fecal flotation or fecal antigen tests (6-9) but has been reported to be as high as 80% with fecal PCR in Australia (7). The relapse after the first treatment could probably be explained by recontamination in the environment, either through persistent cysts outside or carried by the other cat. Cyst persistence has also been reported owing to carriage on the fur of cats (2). But this relapse can also be explained by resistance to metronidazole since feces were not screened for giardia just at the end of the treatment period. This is why it was decided to change the treatment and give fenbendazole. Even though fenbendazole proved effective in this particular case, the treatment of choice for feline giardiasis should be metronidazole which was recently reported to be very effective in stopping cyst shedding in a group of chronically infected cats (10). Fenbendazole is not approved for cats but stopped shedding in only 4 out of 8 cats with concurrent Giardia and Cryptosporidium infection (11). A study has reported that fenbendazole is safe up to five times the recommended dosage in healthy adult cats (12) but a recent case of possible severe idiosyncratic hypersensitivity reaction to fenbendazole was described in a cat (13). Giardia organisms do require some moisture to survive and are susceptible to dying simply by air drying. But control of cyst persistence in the environment is frequently a problem. The cysts will die if exposed to temperatures above 55°C. Disinfectants containing quaternary ammonium are considered to be the best disinfectants to control Giardia but chlorine bleach diluted 1:32 with water is also effective (2). Besides the round worms, the other fecal parasites which should be documented especially in young cats with persistant diarrhea are Isospora felis, Cryptosporidium parvum and Tritrichomonas fetus. Interestingly, a recent study reported an association with diarrhea in Giardia spp. and Cryptosporidium spp. infected cats but not in Isospora spp. or Toxocara cati infected cats (8). Therefore, diarrhea is not a reliable predictor of active shedding of intestinal parasites.
In cases of chronic diarrhea with no specific diagnostic orientation after the first diagnostic test results and when a complete parasite fecal screening cannot be done (3 fecal flotations with centrifugation), it is probably reasonable to treat with deworming medications and concurrent metronidazole to cover Giardia spp. before going to specialized GI procedures such as endoscopy or surgery for full-thickness biopsies.
A 9-year old male castrated cat was presented with a primary complaint of 5 month duration of diarrhea and weight loss. The owner also reported that the cat had been vomiting 3 times a week over the last 4 weeks. The cat was the only animal of the household and it was a strictly indoor cat. Several dietary changes and a course of antibiotics did not induce any improvement of the clinical condition. The cat had been dewormed twice over the last 6 weeks with fenbendazole (50 mg/kg bid for 4 days) by the referring veterinarian. FeLV and FIV tests were negative 6 weeks before presentation. On physical examination, the cat was bright alert and responsive but the body condition score was decreased (2/9). Otherwise physical examination was unremarkable. No enlargement was palpated in the thyroid gland area. The systolic blood pressure was consistently and repeatedly measured at 210 mmHg with Doppler ultrasonography. Fundic ocular examination was normal and no heart sounds anomalies were found on auscultation. Fecal panel was negative on three different stools. Complete blood count was unremarkable but the full chemistry panel revealed an increase in ALT (140 U/L – reference range: 15-80 U/L) and ALP (130 U/L – reference range: 12-85 U/L). Urinalysis did not reveal any abnormalities on the dipstick and a urinary specific gravity of 1.042 was measured with a refractometer. Abdominal ultrasonography did not reveal any abnormalities. At this time, the main differentials for this cat with chronic diarrhea and concurrent increase in liver enzymes were:
• chronic hepatobiliary disease
• chronic pancreatitis
• IBD or intestinal neoplasia and hyperthyroidism
The concurrent presence of hypertension without any sign of renal failure placed hyperthyroidism high on the list. Plasma total T4 was 75 nmol/L (reference range: 15-52 nmol/L) and hyperthyroidism was diagnosed. A urine culture was performed because of the frequency of urinary tract infection in cats with hyperthyroidism (14). It was negative. The cat was placed on methimazole 2.5 mg bid and concurrently on amlodipine 0.625 mg/ sid for the hypertension because the measured blood pressure was sufficiently high to raise concern about possible target organ damage. Systolic blood pressure was rechecked after one week at 166 mmHg and the diarrhea had improved but the stools were still soft. An echocardiography was performed and did not show any signs of hypertrophy. The total T4 was rechecked after 3 weeks of treatment and was 30 nmol/L. The cat was therefore maintained under the initial dosage of methimazole. No increase in plasma creatinine and urea was observed on chemistry panel and the ALT and ALP values were in the normal range. The stools were normal at this time. The systolic blood pressure was 156 mmHg and the cat was maintained on amlodipine.
This case shows that metabolic diseases should always be on the list of differential diagnoses for chronic diarrhea in cats and that hyperthyroidism must be ruled-out before going further in the diagnostic work-up even in a cat with no palpable cervical mass especially after 7 years of age.
An 8-year old female spayed Domestic Shorthair cat was presented for a history of relapsing diarrhea over the last 8 months. The cat had concurrently been losing weight. Her appetite was variable and she had been occasionally vomiting but no more than three times per week. The diarrhea had been infrequently colored with fresh blood and containing mucus. No straining or urgency were observed and the cat was passing 2-3 stools per day with some very occasional straining. She had been recently tested negative for FeLV and FIV. The cat had been dewormed at the referring veterinarian with an association of praziquantel and pyrantel pamoate twice at one month of interval without any improvement. A one month course of metronidazole had not improved the cat’s clinical condition. Dietary changes did not induce any clinical change. Physical examination was unremarkable, the cat was not dehydrated. Bowel loops were perceived as slightly thickened on abdominal palpation. In front of this clinical presentation of chronic small and large bowel diarrhea in a 8-year old cat, the main initial differentials were:
• parasitism especially Giardia regarding the history of recent deworming
• metabolic causes especially hyperthyroidism and liver diseases
• chronic pancreatitis or exocrine pancreatic insufficiency
• primary intestinal disease including chronic intestinal inflammation and neoplasia.
The complete blood count was unremarkable except for a slight non regenerative anemia which was considered as anemia of chronic disease. A coagulation panel, performed because of the history of fresh blood in the stools, was in the normal range. Fecal flotations performed on three different stools and a Giardia fecal antigen test were negative. Except for a decrease in plasma albumin concentration (20 g/L – reference range: 25-38 g/L) with a normal globulin and a slight increase in ALP (110 U/L – reference range: 12- 85 U/L), the plasma chemistry panel including a total T4 was normal. Urinalysis did not reveal any protein loss and the specific gravity was 1.038. This cat has diarrhea with a concurrent hypoalbuminemia. Liver disease possibly associated with chronic pancreatitis, protein losing enteropathy (due to chronic inflammation or primary intestinal neoplasia) and exocrine pancreatic insufficiency are the main possible causes. A preand post-prandial bile acid test ruled out liver failure. Abdominal ultrasonography did not show any liver or pancreatic changes but the small intestinal mucosa was abnormal (Figure 2) with enlargement of the mesenteric lymph node. Serum feline-TLI was in the reference range ruling out exocrine pancreatic insufficiency but serum cobalamin was markedly decreased (190 ng/L – reference range: 290-1499 ng/L). Serum folate concentration was in the reference range. Due to the severe clinical presentation and the mixed diarrhea, gastro-duodenoscopy and colonoscopy were performed. Only the duodenal mucosa was considered abnormal with increased granularity and friability (Figure 3). Biopsies were taken in the stomach, descending duodenum, colon and blindly in the ileum. The cat was started on an elimination diet with a soy hydrolyzate based diet and placed on metronidazole 10 mg/kg bid for 4 weeks. Because of the decreased serum cobalamin concentration, vitamin B12 was administered (250 μg/kg once a week by SC injection for 6 weeks). The histopathologic report was consistent with severe small intestinal chronic lymphoplasmacytic inflammation with a very severe infiltration and architectural changes but a significant amount of distortion was observed on the biopsies. The pathologist reported he could not rule out lymphoma due to the very superficial nature of the biopsies. Immunohistochemical staining of the biopsies (15) was also not definitely conclusive between both conditions. The stomach and colonic mucosa were considered normal. Regarding the possible diagnosis of lymphoma, it was decided to do full thickness biopsies before starting any immunosuppressive treatment. The three segments of the small intestine, an enlarged lymph node, the pancreas and the liver were biopsied. The hepatic and pancreatic biopsies were considered normal and the small intestinal biopsies confirmed the previous diagnosis of severe chronic intestinal inflammation (Figure 4). The full thickness biopsies ruled-out lymphoma. A final diagnosis of IBD was made in this cat. The cat was treated with prednisolone at 2 mg/kg bid for 5 days, then 1.5 mg/kg bid for one week and 1 mg/kg bid for one week. The cat was rechecked after 3 weeks, the stools were semi-formed but still moist. There was no more straining or mucus. The cat had gained 0.4 kg at that time. The serum cobalamin concentration was in the reference range after 6 weeks. Therefore, the cat was placed on 250 μg of cobalamin SC every 4 to 6 weeks. The prednisolone dosage was progressively tapered and the cat was clinically normal after three months. She was kept on steroids (1 mg/kg every other day) and on the elimination diet for 6 more weeks after complete cure. She has been maintained on the elimination diet since that time but minor yearly relapses required either a course of metronidazole or prednisolone associated with a course of cobalamin supplementation.
IBD is a diagnosis of exclusion when all other causes of possible chronic inflammation have been excluded (e.g. cancer, parasite, infection, food allergy or systemic disease). The etiopathogenesis of IBD remains speculative in cats but IBD is assumed to be associated with a hypersensitivity reaction of the intestinal mucosa. IBD may develop because of the loss of tolerance of the intestinal immune system to i) intraluminal resident antigens such as bacteria of the normal flora or dietary components; or ii) intraluminal occasional antigens such as non resident bacteria or parasites (16).
Dietary modification is usually recommended with IBD treatment. It includes elimination or novel protein diet or highly digestible diet. This dietary treatment is seldom effective alone and should be associated at least initially with a course of antibiotics.
A recent study in cats has shown that the total number of mucosa adherent bacteria was correlated with histological scoring of IBD (17). Moreover, the number of adherent Enterobacteriaceae, E. coli and Clostridium spp. was correlated with up-regulation of cytokines mRNA and clinical signs (17). These findings raise the possibility that bacteria are involved in the pathogenesis of IBD in cats and advocate that antibiotics are useful in the treatment of this condition.
In case of failure with the combination of dietary modification and antibiotic treatment, immunesuppressive drugs are used. It is recommended to start with steroids and then to associate with or switch to another drug in case of failure with steroids alone (Table 3).
Cobalamin deficiency is frequent in cats with gastro-intestinal disease in the USA especially IBD and alimentary lymphoma (18,19). However, the prevalence of hypocobalaminemia may be lower in other countries such as UK (20). Since hypocobalaminemia has been associated with severe metabolic disturbances it must be documented in cats with chronic GI signs and any deficiency should be corrected to normalize the metabolism and to reduce the clinical signs (18).
This case of IBD is unusual because of the possibility of lymphoma on the endoscopic biopsies which pushed us to do full-thickness biopsies to further explore it. Recently, it was reported that endoscopic biopsies are not adequate to differentiate IBD and lymphoma in the small intestine (21). In this particular case full thickness biopsies ruled out lymphoma which was considered mandatory before starting the cat on steroids because of the risk of possible secondary resistance to chemotherapy.
1. Hall EJ, German AJ. Diseases of the small intestine. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine, St Louis: Elsevier-Saunders; 2005; 6: 1332-1377.
2. Marks SL, Willard MD. Diarrhea in kittens. In: August JR, ed. Consultations in Feline Internal Medicine. St Louis: Elsevier-Saunders; 2006, pp.133-144.
3. Washabau RJ, Holt DE. Diseases of the large intestine. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine, St Louis: Elsevier-Saunders; 2005; 6: 1378-1407.
4. Guilford WG, Jones BR, Markwell PJ, et al. Food sensitivity in cats with chronic idiopathic gastrointestinal problems. J Vet Intern Med 2001; 15: 7-13.
5. Weiss DJ, Gagne JM, Armstrong PJ. Relationship between inflammatory hepatic disease and inflammatory bowel disease, pancreatitis, and nephritis in cats. J Am Vet Med Assoc 1996; 209: 1114-1116.
6. Hill SL, Cheney JM, Taton-Allen GF, et al. Prevalence of enteric zoonotic organisms in cats. J Am Vet Med Assoc 2000; 216: 687-692.
7. McGlade TR, Robertson ID, Elliot AD, et al. High prevalence of Giardia detected in cats by PCR. Vet Parasitol 2003; 110: 197-205.
8. Mekaru SR, Marks SL, Felley AJ, et al. Comparison of direct immunofluorescence, immunoassays, and fecal flotation for detection of Cryptosporidium spp. and Giardia spp. in naturally exposed cats in 4 Northern California animal shelters. J Vet Intern Med 2007; 21: 959-965.
9. Tzannes S, Batchelor DJ, Graham PA, et al. Prevalence of Cryptosporidium, Giardia and Isospora species infections in pet cats with clinical signs of gastrointestinal disease. J Feline Med Surg 2008; 10: 1-8.
10. Scorza AV, Lappin MR. Metronidazole for the treatment of feline giardiasis. J Feline Med Surg 2004; 6: 157-160.
11. Keith CL, Radecki SV, Lappin MR. Evaluation of fenbendazole for treatment of Giardia infection in cats concurrently infected with Cryptosporidium parvum. Am J Vet Res 2003; 64: 1027-1029.
12. Schwartz RD, Donoghue AR, Baggs RB, et al. Evaluation of the safety of fenbendazole in cats. Am J Vet Res 2000; 61: 330-332.
13. Jasani S, Boag AK, Smith KC. Systemic vasculitis with severe cutaneous manifestation as a suspected idiosyncratic hypersensitivity reaction to fenbendazole in a cat. J Vet Intern Med 2008; 22: 666-670.
14. Mayer-Roenne B, Goldstein RE, Erb HN. Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease. J Feline Med Surg 2007; 9: 124-132.
15. Waly NE, Gruffydd-Jones TJ, Stokes CR, et al. Immunohistochemical diagnosis of alimentary lymphomas and severe intestinal inflammation in cats. J Comp Pathol 2005; 133: 253-260.
16. Jergens AE, Crandell JM. Clinical staging for inflammatory bowel disease. In: August JR, ed. Consultations in Feline Internal Medicine. St Louis: Elsevier-Saunders; 2006, pp. 127-132.
17. Janeczko S, Atwater D, Bogel E, et al. The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease. Vet Microbiol 2008; 128: 178-193.
18. Ruaux CG, Steiner JM, Williams DA. Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia. J Vet Intern Med 2005; 19: 155-160.
19. Simpson KW, Fyfe J, Cornetta A, et al. Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease. J Vet Intern Med 2001; 15: 26-32.
20. Ibarrola P, Blackwood L, Graham PA, et al. Hypocobalaminaemia is uncommon in cats in the United Kingdom. J Feline Med Surg 2005; 7: 341-348.
21. Evans SE, Bonczynski JJ, Broussard JD, et al. Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats. J Am Vet Med Assoc 2006; 229: 1447-1450.
This article was previously published in 2012.