Feline diarrheal syndromes: Common and not-so-common disorders (Proceedings)

There are many potential causes of acute diarrhea in cats, but a smaller number of etiologies are associated with the development of feline chronic diarrhea. Primary intestinal diseases (malignancy, inflammatory bowel disease, food sensitivity, and infection) account for most of the causes of feline chronic diarrhea, but chronic diarrhea may also develop with extra-intestinal disease (hepatobiliary disease, exocrine pancreatic insufficiency, and hyperthyroidism). The syndrome of small intestinal bacterial overgrowth is an important cause of chronic diarrhea in the dog, but cats may be refractory to the development of this syndrome.

Inflammatory Bowel Disease (IBD)1-4

Chronic inflammation of the gastrointestinal tract (inflammatory bowel disease; IBD) is the most important cause of chronic diarrhea (and vomiting) in cats. Inflammatory bowel disease is not a single disease entity per se, but simply the culmination of chronic, sustained inflammation of the gut. A complete medical investigation should always be performed to consider all of the known causes of chronic diarrhea in the cat. A diagnosis of IBD is considered only after known causes (e.g., infection, toxicity, neoplasia, metabolic disorders, allergy/sensitivity reactions, maldigestion of exocrine pancreatic insufficiency) of chronic diarrhea have been carefully excluded.

Clinical findings in feline IBD may include reduced body mass, thickened bowel loops, fever, abdominal pain, mesenteric lymphadenopathy, and, hepato/splenomegaly in cats with eosinophilic enteritis and hypereosinophilic syndrome. Hematologic and serum biochemical abnormalities are occasionally observed but are fairly non-specific. Abdominal radiographic and ultrasonographic studies are also usually non-diagnostic with occasional findings of fluid or gas-filled loops of bowel, intestinal wall abnormalities, and mesenteric lymphadenopathy.4 Intestinal biopsy (endoscopy or laparotomy) may help differentiate this spectrum of disorders from other known causes of enteritis.4 Dietary manipulation alone or in combination with drug therapies are the basis of therapy in this disorder. The prognosis is good for control in most cases, but not always curative.

Intestinal Neoplasia5-7

Lymphosarcoma, adenocarcinoma, and mast cell tumors are the most common tumors of the gastrointestinal tract in cats. Lymphosarcoma quite often involves diffuse segments of the bowel, whereas adenocarcinomas and mast cell tumors are usually more focal. Weight loss, anorexia, and diarrhea are the most important clinical signs.

Intestinal lymphoma may develop over many months, and affected animals usually present with clinical signs of weight loss and diarrhea. Histologically, lymphosarcoma is usually characterized by diffuse mucosal and submucsoal infiltration of neoplastic lymphocytes. Malabsorption results from progressively reduced absorptive area in intestinal villi. Diffuse thickening of the small intestine and mesenteric lymphadenopathy are frequent physical examination findings, although these same findings can be observed in cats with moderate to severe inflammatory bowel disease. Ultrasonography is useful in evaluating intestinal thickness and mesenteric lymph nodes, but definitive diagnosis requires endoscopic or full thickness biopsies.

Food Sensitivity8-11

Adverse reactions to food (food sensitivities) include those mediated by the immune system (food allergies) and those without an immunological basis (food intolerances). 9 Until recent times, objective evidence for food sensitivity has been somewhat lacking in the cat. Adverse reactions to food are usually suspected when an association is made between the ingestion of a certain food and the appearance of a clinical sign. The diagnosis is then confirmed by dietary elimination-challenge studies. 9 Alternative methods of diagnosis have been proposed in other species, including assay of serum antigen-specific IgE and gastroscopic food sensitivity testing. A commercial assay of cat antigen-specific IgE in serum is now available, but the sensitivity and specificity of the assay have not yet been determined. Gastroscopic food sensitivity testing has been applied to G.I. diagnosis in the dog, but has the distinct disadvantage of diagnosing just one type of food sensitivity – immediate type I hypersensitivity. 10

In a recent study of 55 cats with chronic idiopathic gastrointestinal problems (diarrhea and/or vomiting for > 2 weeks), 29% of cats were diagnosed with food sensitivity based on dietary elimination/challenge studies.8 Another 20% of cats had resolution of clinical signs on the elimination diet but did not recur after challenge with their original diet. The foods or food ingredients responsible for the clinical signs were dietary staples (e.g., beef, wheat, and corn gluten). Fifty % of affected cats were sensitive to more than one food ingredient. Assays of serum antigen-specific IgE had limited value as screening tests, and gastroscopic food sensitivity testing was not helpful. The authors concluded that adverse reactions to dietary staples were common in their population of cats, and that affected cats responded well to selected-protein (e.g., chicken or venison-based) diets.8

Exocrine Pancreatic Insufficiency12,13

Exocrine pancreatic insufficiency (EPI) is an uncommon cause of chronic diarrhea in cats. Insuffiency results from failure of synthesis and secretion of pancreatic digestive enzymes. The natural history of feline exocrine pancreatic insufficiency is poorly understood, but many cases are thought to result from chronic pancreatitis. As with dogs, clinical signs reported in cats with EPI include weight loss, soft voluminous feces, and greasy soiling of the haircoat. Affected cats may also have an antecedent history of recurring bouts of acute pancreatitis (e.g., anorexia, lethargy, vomiting) culminating in chronic pancreatitis and EPI. 13

The diagnosis of EPI in cats has been technically difficult. Clinical signs in affected cats are not pathognomonic for EPI, clinicopathologic data are fairly non-specific, imaging findings are inconsistent, and the severity of pancreatic histologic changes are not always directly related to the severity of clinical signs. A feline-specific radioimmunoassay for trypsin-like immunoreactivity (TLI) has been developed, and a recent paper suggests that it may prove useful in the diagnosis of this disease.12 In that study, TLI concentrations less than 8 µg/L (reference range = 17-49 µg/L) were reported in 17/20 cats with clinical signs compatible with EPI (e.g., weight loss, loose voluminous feces, greasy soiling of the hair coat) and at least one other finding, e.g., decreased fecal proteolytic activity, exploratory laparotomy or necropsy findings compatible with EPI, or favorable response to pancreatic enzyme replacement therapy.12

Hyperthyroidism14,15

Hyperthyroidism is a well-documented endocrine disorder of aging cats that is frequently accompanied by gastroenterologic signs, e.g., weight loss (88% of cats), polyphagia (49%), vomiting (44%), and diarrhea (15%).14 Clinical signs are related to the effects of thyroid hormone on metabolic rate and gastrointestinal motility. Diagnosis of feline hyperthyroidism is fairly straightforward, and involves the quantitation of serum thyroid hormones, T3 suppression test, TRH stimulation test, and/or radionuclide thyroid imaging.15 Chronic diarrhea associated with hyperthyroidism is readily reversible with appropriate therapy, e.g., thyroidectomy, 131 I radiotherapy, or methimazole chemotherapy.15

Hepatobiliary Disease16,17

Cats experience several types of hepatobiliary disease including cholangiohepatitis, lymphocytic portal hepatitis, hepatic and biliary neoplasia, hepatic amyloidosis, and hepatic lipidosis. Diarrhea may be an important clinical sign in any of these disorders, particularly those with inflammatory liver disease. Cholangiohepatitis and lymphocytic portal hepatitis, for example, are frequently accompanied by gastroenterologic signs, e.g., anorexia (74%), weight loss (74 % of cats), vomiting (54%), and diarrhea (15%).17 Definitive diagnosis of any of these disorders requires the use of clinical pathology data, imaging studies (e.g., ultrasonography), and tissue biopsy. Clinical signs, laboratory data, and imaging findings are often quite similar between the various hepatobiliary disorders, thus histopathology is needed to differentiate these disorders.

Concurrent Disorders: Cholangiohepatitis, Pancreatitis, Inflammatory Bowel Disease18-21

Many cats have concurrent cholangitis, pancreatitis, and inflammatory bowel disease, and it may be difficult, if not impossible, to attribute individual clinical signs (e.g., diarrhea) to one organ system in affected cats.18-20 Pre-existing inflammatory bowel disease (IBD) likely contributes to the pathogenesis of pancreatitis and cholangiohepatitis in many, but perhaps not all, cats. There are several reasons, or contributing factors, for this association:

1. High incidence of feline IBD – IBD is a common disorder in the domestic cat. In some veterinary hospitals and specialty referral centers, IBD is the most common gastrointestinal disorder in cats.4

2. Clinical symptomatology – Vomiting is the most important clinical sign in cats affected with IBD. Chronic vomiting predisposes cats to raised intra-duodenal pressure and pancreaticobiliary reflux.

3. Pancreaticobiliary anatomy – Unlike the dog, the sphincter of Oddi is a common (physiological and anatomic) channel at the duodenal papilla. Thus, reflux of duodenal contents perfuses both pancreatic and biliary systems.21

4. Intestinal Microflora – Compared to the dog, cats have a high much higher bacterial load (108 vs. 104 organisms/ml) in the proximal small intestine. Thus, duodenal reflux is theoretically more pathologic in the cat.22

Gastrointestinal Infection23-27

Any of the acute infectious diseases of the gastrointestinal tract can develop into chronic disease and/or carrier states. The most important of these are Campylobacter sp., Salmonella sp., Trichomonas sp., Toxocara sp., Toxoplasma sp., Cryptosporidium sp., Giardia sp., and feline corona (FIP), leukemia (FeLV), and immunodeficiency (FIV) viruses. Therefore, the routine medical investigation of any cat affected with chronic diarrhea should include direct and indirect fecal examinations for helminths (Toxocara) and protozoa (Toxoplasma, Giardia, Trichomonas, Cryptosporidium), bacterial culture of feces (Salmonella, Campylobacter), and serologies (FeLV, FIV, Toxoplasma, Cryptosporidium). It should be pointed, however, that cats with chronic diarrhea do not necessarily have a greater incidence of any of these infectious agents when compared to healthy cats without diarrhea or other G.I. clinical signs.23,25 In other words, a positive result does not necessarily imply that the infectious agent is the underlying cause of the clinical signs.

References

Inflammatory Bowel Disease

1. Jergens AE, Moore FM, Haynes JS, et al. Idiopathic IBD in dogs and cats. J. Amer. Vet. Med. Assoc. 1992; 201: 1603-1608.

2. Hart JR, Shaker E, Patnaik AK, et al. Lymphocytic-plasmacytic enterocolitis in cats. J. Amer. Vet. Med. Assoc. 1994; 30: 505-514.

3. Dennis JS, Kruger JM, Mullaney TP. Lymphocytic/plasmacytic colitis in cats. J. Amer. Vet. Med. Assoc. 1993; 202: 313-318.

4. Baez JL, Hendrick MJ, Walker LM, Washabau RJ. Radiographic, ultrasonographic, and endoscopic findings in cats with inflammatory bowel disease of the stomach and small intestine. J. Amer. Vet. Med. Assoc. 1999, 215: 349-354.

Intestinal Neoplasia

5. Straw RC. Tumors of the intestinal tract. In, Small Animal Clinical Oncology, Withrow SJ and MacEwen EG, editors. WB Saunders, Philadelphia, 1996, pp. 252-278.

6. Kosovsky JE, Matthiesen DT, Patnaik AK. Small intestinal adenocarcinoma in cats. J. Amer. Vet. Med. Assoc. 1988; 192: 233-235.

7. Head KW, Else RW. Neoplasia and allied conditions of the canine and feline intestine. Vet. Ann. 1981; 21: 190-208.

Food Sensitivity

8. 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.

9. Hall EJ. Gastrointestinal aspects of food allergy: a review. J. Small Anim. Practice 1994; 35: 145-152.

10. Guilford WG, Strombeck DR, Rogers Q, et al. Development of gastroscopic food sensitivity testing in dogs. J. Vet. Intern. Med. 1994; 8: 414-422.

11. Paterson S. Food sensitivity in 20 dogs with skin and gastrointestinal signs. J. Small Anim. Practice 1995; 36: 529-534.

Exocrine Pancreatic Insufficiency

12. Steiner JM, Williams DA. Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency. J. Vet. Intern. Med. 2000; 14: 627-629.

13. Steiner JM, Williams DA. Feline exocrine pancreatic disorders. Vet. Clin. North America 1999; 29: 551-575.

Hyperthyroidism

14. Broussard J, Peterson ME. Changes in clinical and laboratory findings in cats with hyperthyroidism from 1983-1993. J. Amer. Vet. Med. Assoc. 1995; 206: 302-306.

15. Peterson ME. Hyperthyroidism. In, Textbook of Veterinary Internal Medicine, Ettinger SJ and Feldman EC, editors. WB Saunders, Philadelphia, 2000, pp. 1401-1419.

Hepatobiliary Disease

16. Gagne JM, Weiss DJ, Armstrong PJ. Histopathologic evaluation of feline inflammatory liver disease. Vet. Pathol. 1996; 33: 521-526.

17. Weiss DJ, Armstrong PJ, Gagne J. Inflammatory liver disease. Sem. Vet. Med. Surg. 1997; 12: 22-27.

Concurrent Disorders: Pancreatitis, Cholangiohepatitis, and IBD

18. Weiss DJ, Gagne JM, Armstrong PJ. Relationship between inflammatory hepatic disease and IBD, pancreatitis, and nephritis in cats. J. Amer. Vet. Med. Assoc. 1996; 209: 1114-1116.

19. Hill RC and Van Winkle TJ. Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat. J. Vet. Intern. Med. 1993; 7: 25-33.

20. Akol KG, Washabau RJ, Saunders HM, et al. Acute pancreatitis in cats with hepatic lipidosis. J. Vet. Intern. Med. 1993; 7: 205-209.

21. Thune A, Friman S, Conradi N, et al. Functional and morphological relationships between the feline main pancreatic and bile duct sphincters. Gastroenterology 1990; 98: 758-765.

22. Johnston KL, Lamport A, Batt RM. An unexpected bacterial flora in the proximal small intestine of normal cats. Vet. Rec. 1993; 132: 362-363.

Gastrointestinal Infection

23. Hill SL, Cheney JM, Taton-Allen GF, et al. Prevalence of enteric zoonotic organisms in cats. J. Amer. Vet. Med. Assoc. 2000; 216: 687-692.

24. Gookin JL, Breitschwerdt EG, Levy MG, et al. Diarrhea associated with trichomonosis in cats. J. Amer. Vet. Med. Assoc. 1999; 215: 1450-1454.

25. Spain CV, Scarlett JM, Wade SE, et al. Prevalence of enteric zoonotic agents in cats less than 1 year old in central New York State. J. Vet. Intern. Med. 2001; 15: 33-38.

26. Kirkpatrick CE, Green GA. Susceptibility of domestic cats to infections with Giardia lamblia cysts and trophozoites from human sources. J. Clin. Microbiol. 1985; 21: 678-680.

27. Mtambo MMA, Nash AS, Blewett DA, et al. Cryptosporidium infection in cats: prevalence of infection in domestic and feral cats in the Glasgow area. Vet. Rec. 1991; 129: 502-504.