Veterinary Healthcare - Chronic large bowel diarrhea in dogs: what's new? (Proceedings)
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Chronic large bowel diarrhea in dogs: what's new? (Proceedings)


CVC IN SAN DIEGO PROCEEDINGS

Chronic large bowel diarrhea is a common problem in dogs. Diarrhea is often accompanied by hematochezia, excess fecal mucus, and tenesmus. The frequency of defecation is increased and the quantity of feces / defecation may be reduced. Weight loss is uncommon. Common causes include highly digestible diet responsive diarrhea, whipworms, Clostridium perfringens enterotoxicosis, irritable bowel syndrome, fiber-responsive large bowel diarrhea, and neoplasia. A thorough diagnostic plan should be followed to reach an accurate diagnosis efficiently. The author's diagnostic plan includes multiple fecal examinations, rectal cytology, elimination of dietary indiscretion, feeding a highly digestible diet for 3-4 weeks, treatment for whipworms, laboratory evaluation consisting of a CBC, biochemical profile, and UA, flexible colonoscopy with multiple mucosal biopsies.

After following the above diagnostic plan it is common to identify no abnormalities and hence make the diagnosis chronic idiopathic large bowel diarrhea. In a recent review of dogs with chronic large bowel diarrhea, idiopathic cases were the most common diagnosis and represented 25% of dogs that underwent colonoscopy. In the author's experience, these dogs have either irritable bowel syndrome, fiber-responsive large bowel diarrhea, or Clostridium perfringens enterotoxicosis in which rectal cytology has not identified an abnormal number of spores. The purpose of this presentation is to review these three conditions and demonstrate how they can be diagnosed, and successfully treated in practice.

Portions of the following discussion are reprinted from the author's chapter in Leib MS and Monroe WE (ed.) Practical Small Animal Internal Medicine. WB Saunders, Philadelphia, PA, 1997: 736-738.

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a commonly diagnosed but poorly described functional disorder of the intestines that occurs in dogs. Synonyms include spastic colon, nervous colitis, and mucus colitis. Colonic dysfunction exists in the absence of structural, biochemical, or microbiologic abnormalities.

Diarrhea is often intermittent and hematochezia is uncommon. Bloating, nausea, vomiting, and abdominal pain may occur. Often stressors can be identified that are associated with development of cyclic clinical signs. Dogs may be nervous, high-strung, or have abnormal personality traits.

The identification of abnormal personality traits or stressors that initiate episodes of diarrhea in a dog with chronic idiopathic large bowel diarrhea is strongly suggestive of IBS. If the dog responds to dietary fiber supplementation, I call the condition fiber-responsive large bowel diarrhea. If the dog does not respond to fiber supplementation, I treat in a trial and error fashion with antispasmodics, CNS sedatives, and opioids and have the owner attempt to reduce stress. The intermittent nature of clinical signs may make assessment of therapy difficult.

Pain can often be relieved by antispasmotic agents and the effects of stressors can be reduced by sedatives. Librax® (Roche) contains the sedative chlordiazepoxide (5 mg) and clidinium bromide (2.5 mg), an anticholinergic agent. A suggested dosage is 0.1-0.25 mg/kg of clidinium or 1-2 capsules PO BID-TID. The drug can be given when the owner first notices abdominal pain or diarrhea or when stressful conditions are encountered, and can usually be discontinued after a few days. Other anticholinergics such as propantheline (Pro-Banthine®, Searle), 0.25 mg/kg PO BID-TID, hyoscyamine (Levsin®, Schwarz Pharma Kremers Urban), 0.003-0.006 mg/kg PO BID-TID, or dicyclomine (Bentyl®, Lakeside Pharmaceuticals), 0.15 mg/kg PO BID-TID have been suggested. Anticholinergics can decrease or inhibit GI motility which may worsen diarrhea. In people, side effects include xerostomia, urinary retention, blurred vision, headache, psychosis, nervousness, and drowsiness.

The prognosis for cure of IBS in dogs is guarded. Affected dogs may have intermittent clinical signs for years. However, environmental and pharmacologic therapy may result in control or reduction of clinical signs. Dogs that respond to fiber supplementation have a very good to excellent prognosis.

Fiber-responsive large bowel diarrhea

The author routinely adds fiber to a highly digestible diet in dogs with chronic idiopathic large bowel diarrhea, even if irritable bowel syndrome has been diagnosed. In cases of fiber-responsive large bowel diarrhea (FRLBD), chronic intermittent or continuous large bowel diarrhea is usually accompanied by hematochezia, excess fecal mucus, and tenesmus. Abdominal pain and vomiting can occur in some dogs. Nervousness, abnormal personality factors, and stressors have been identified in approximately 40% of cases. However, in some of these cases, a temporal relationship to the diarrhea could not be established.

Soluble fiber, psyllium hydrophilic mucilloid (Metamucil®, Procter & Gamble), added to a highly digestible diet (i/d® Hills), has resulted in excellent or very good results in approximately 80% of dogs with chronic idiopathic large bowel diarrhea. In the authors' cases, the median amount of Metamucil® added to the diet was two TBSP / day which was approximately 1.3 g psyllium / kg / day. I have not been able to identify any clinical findings that help to predict whether a dog will respond to fiber supplementation. In some dogs, the amount of fiber added to the diet can be reduced or withdrawn entirely, while in others the highly digestible diet can be replaced with a grocery store brand of food after the diarrhea resolves.

Some of the dogs with FRLBD have classic signs of IBS. However, many of the dogs have hematochezia, a clinical sign considered uncommon in dogs with IBS. In addition, it has been reported that only rarely do dogs with IBS respond to dietary fiber supplementation alone.

Dietary fiber is a collective term for a wide variety of plant polysaccharides and lignins that are resistant to mammalian digestive enzymes. There are many types of dietary fiber, each with diverse chemical, physical, and physiologic properties. Water soluble fibers include pectin, gums, mucilages, and some hemicelluloses. They are found in the parenchymatous portions of fruit and vegetables, and in the seeds of leguminous plants. Water insoluble fibers includes cellulose, lignin, and some hemicelluloses. They are found in cereal grains and seed coats.

There are several potential mechanisms by which dietary fiber supplementation may result in clinical improvement in dogs with FRLBD. Soluble fiber adsorbs a large quantity of water, improving fecal consistency. Colonic bacteria, which make up approximately 40-55% of the dry stool mass, ferment soluble fiber, which results in a vast increase in the numbers (but not types) of colonic bacteria and quantity of bacterial byproducts. Insoluble fiber greatly adds to fecal volume. Thus, dietary fiber can increase fecal bulk which increases colonic distention, the major stimulus for normal colonic motility. With increased colonic distention, an improved motility pattern in dogs with FRLBD may result in resolution of clinical signs. In fact, dietary fiber has been shown to normalize colonic myoelectrical activity and colonic motility in people. Bacterial fermentation of fiber leads to the production of short chain fatty acids, of which butyrate serves as an energy source for colonocytes.

Psyllium comes from the seeds or husks of the plant ispaghul and consists of approximately 90% soluble fiber. Although there are no other reported studies evaluating the use soluble fibers in dogs with diarrhea, there are in human beings. Treatment with psyllium has been shown to be beneficial in children with nonspecific chronic diarrhea of childhood, adults with chronic idiopathic diarrhea, patients with ulcerative colitis in remission, and some with irritable bowel syndrome. Psyllium has also been shown to improve diarrhea in human burn patients receiving enteral nutrition and in another group of tube-fed patients. Psyllium also improved fecal consistency in humans with experimentally induced secretory diarrhea and also reduced the acceleration of colonic transport in those with lactulose-induced diarrhea.

Clostridium perfringens enterotoxicosis

Acute and chronic large bowel diarrhea has been associated with Clostridium perfringens type A enterotoxin. Vomiting, weight loss, flatulence, and abdominal pain occur less frequently. The disorder occurs most commonly in dogs. Both naturally occurring and hospital acquired cases have been detected. Diagnosis is commonly based on finding increased numbers of spores in rectal cytology specimens, or demonstrating the toxin in the feces (which is primarily done at referral hospitals). The reason for including this syndrome within this discussion of chronic idiopathic large bowel diarrhea is that in the author's hospital approximately 25% of toxin positive cases are negative on rectal cytology. Thus, in practices in which toxin is not analyzed, a case of Clostridium perfringens could easily be diagnosed as idiopathic. If fecal toxin cannot be routinely tested in a private practice, it may be indicated to treat a dog with chronic large bowel diarrhea with an appropriate antibiotic as described below to eliminate the presence of C. perfringens enterotoxicosis.

Diagnosis can be confirmed by identifying enterotoxin in a fecal sample. Most commonly this was done with a reverse latex agglutination test (PET-RPLA Kit, Oxoid USA, Columbia MO). However, the test is not available at the present time. An ELISA test (Clostridium perfringens Enterotoxin Test, TechLab, Blacksburg, VA) is now being used in the author's hospital, but we have not had enough experience to comment on test results. Diagnosis should be suspected when greater than 3-5 spores per oil immersion field are found in a rectal cytology specimen. The spores are larger than most bacteria and assume a "safety pin" appearance. However, a preliminary study has recently shown a poor relationship between fecal toxin and spores in rectal cytology samples.

A vegetative form of C perfringens is a normal inhabitant of the colon. The enterotoxin is a component of the spore coat and causes intestinal fluid accumulation, mucosal damage, and diarrhea. The stimuli for sporulation and enterotoxin production are unknown. Enterotoxin has also been identified in some cases of hemorrhagic gastroenteritis syndrome (HGE), parvovirus, giardiasis, and IBD. The author has also demonstrated toxin in the feces of dogs without diarrhea!

This syndrome is controversial and not all authors accept the clear description of the clinical presentation presented above. Several epidemiologic studies looking at groups of dogs with diarrhea, sick hospitalized dogs without diarrhea, and healthy outpatients have not found a difference between these groups in the percentage of dogs that are positive for fecal enterotoxin. Some of this data was obtained with the reverse passive latex agglutination test (RPLA), which is no longer available. An additional study using the currently available ELISA test did find that more dogs with diarrhea were positive for fecal enterotoxin than controls. In addition, these epidemiologic studies also found a poor relationship between the presence of fecal enterotoxin and endospores in rectal cytology samples in dogs with and without diarrhea.

Until a universal description of this syndrome emerges, the author suggests that a diagnosis should be confirmed by identifying enterotoxin in a fecal sample. An ELISA test (Clostridium perfringens Enterotoxin Test, TechLab, Blacksburg, VA) is currently available at commercial and Veterinary Diagnostic laboratories. However, a recent study utilizing the RPLA showed that there were 14% discordant results in dogs with diarrhea after feces were either refrigerated or frozen for 24 hours when compared to immediate analysis. Until a similar study is performed with the ELISA test, this study suggests that shipment of refrigerated or frozen feces to a laboratory could lead to erroneous results. In cases with typical signs of large bowel disease without GI parasites or dietary indiscretion, diagnosis should be suspected when greater than 3-5 spores per oil immersion field are found in a rectal cytology specimen if enterotoxin analysis cannot be performed. A recent study showed that in dogs with diarrhea, there was a relationship between large bowel signs and spore numbers.

Acute cases may resolve spontaneously. Chronic cases respond to antibiotic therapy in 3-5 days. Metronidazole at 6 mg/kg BID-TID for 7 days is often effective. Ampicillin 22 mg/kg PO TID or amoxicillin 11-22 mg/kg PO BID-TID are also effective treatments. Cases that show intermittent clinical signs require long term therapy. Tylosin can be used in these cases at 10-20 mg/kg BID. Some cases respond to feeding a high fiber diet.

The prognosis is excellent. Most affected animals respond to therapy within several days. Clinical findings have not been identified that predict which animals need long-term therapy.

Chronic diarrhea: Case 1

Signalment
     • 11 yr SF mixed breed dog

History
     • Diarrhea of 3 months duration
     • Recurrent episodes (2-4 days) of diarrhea, normal in between
     • Characteristics: mucus, Grade III
     • Volume / defecation decreased
     • Frequency: moderately increased
     • No weight loss. Normal appetite.

Previous therapy
     • i/d® (3 weeks), d/d® (3 weeks)
     • Fenbendazole (50 mg/kg SID for 3 days), No improvement
     • Diphenoxylate (0.1 mg/kg TID during episodes).

Past history
     • Nervous dog, Afraid of thunderstorms, became inside dog 3 years ago

Physical examination
     • Bright, alert, apprehensive. Normal abdominal palpation. Rectal examination normal.

Localization of diarrhea (circle one)
     • Small bowel - Large bowel Mixed bowel

Differential diagnosis
     • Irritable bowel syndrome
     • Fiber responsive large bowel diarrhea
     • Clostridium perfringens enterotoxicosis
     • Neoplasia
     • IBD

Diagnostic plan
     • Fecal x3
     • Rectal cytology
     • RX Clostridium
     • ± Clostridium enterotoxin
     • CBC, biochemical profile, UA
     • Colonoscopy

Diagnostic results / diagnosis
     • Dog developed mucoid stool
     • Fecal x2 neg
     • Rectal cytology neg
     • Clostridium enterotoxin neg
     • AP 222
     • Colonoscopy and histopathology normal
     • DX - chronic idiopathic large bowel diarrhea

Therapy
     • i/d + 2 TBSP Metamucil/day
     • FU 6 wks - 3 mild episodes - not using fiber
     • FU 11 wks - no diarrhea
     • FU 9 mons - no diarrhea
     • Abdominal pain, exploratory laparotomy, hepatic neoplasia, colon - grossly and microscopically normal

Chronic diarrhea: Case 2
Signalment
     • 11 Yr old MN cockapoo

History
     • DIARHEA OF 5 MONTHS DURATION
     • Progressive with flare-ups every 2-4 weeks
     • Episodes with hematochezia, excess fecal mucus, and tenesmus
     • Frequency up to 13x/day
     • Volume / defecation decreased
     • Stool grade 2-3, sometimes 1
     • Softening of stool between episodes, currently has diarrhea 50% of days

Previous therapy
     • Hills i/d diet
     • Cimetidine
     • Sulfasalazine
     • Prednisone 5-10 mg/day
     • Milbemycin monthly

Physical examination
     • Good body condition
     • Grade II/VI holosystolic murmur, PMI mitral
     • Rectal examination: bloody mucus

Localization of diarrhea (circle one)
     • Small bowel
     • Large bowel
     • Mixed bowel

Differential diagnosis
     • Chronic idiopathic large bowel diarrhea
     • Fiber responsive large bowel diarrhea
     • C. perfringens enterotoxicosis
     • Inflammatory bowel disease
     • Irritable bowel syndrome
     • Neoplasia
     • Whipworms

Diagnostic plan
     • Fecal x3
     • Rectal cytology
     • ± Clostridial enterotoxin
     • ± RX Clostridium – amoxicillin
     • CBC, biochemical profile, UA
     • Colonoscopy / biopsy

Diagnostic results / diagnosis
     • No stool in hospital
     • Fecal x 2 neg
     • Rectal cytology 2-3+ spores
     • Clostridial enterotoxin positive
     • AP 894
     • Colonoscopy – lacked submucosal blood vessels, increased mucosal friability, stippled blood vessels
     • Histopathology mild PL colitis, dilation of glands with necrotic debris
     • DX C. perfringens colitis?

Therapy
     • Amoxicillin 20 mg/kg BID x 14 days

Notes / comments
     • Next stool normal
     • FU 3 weeks soft stool, RX amoxicillin 3 more weeks
     • FU 5 mons normal

Selected References

Leib MS. Chronic colitis in dogs. In: Bonagura JD, Kirk RW (ed.). Current Veterinary Therapy XIII. Philadelphia, W. B. Saunders Company, 1999; in press.

Leib MS, Matz ME. Diseases of the large intestine. In: Ettinger SJ, Feldman EC (ed.). Textbook of Veterinary Internal Medicine. Philadelphia, W B Saunders, 1995; 1232-1260.

Tams TR. Irritable bowel syndrome. In: Kirk RW, Bonagura JD (ed.). Current Veterinary Therapy XI. Philadelphia, W B Saunders Company, 1992; 604-608.

van Wijk HJ, Smout JPM. The puzzling pathogenesis of the irritable bowel syndrome. Scand J Gastroenterol 1988; 23(suppl 154): 66-71.

Johnson SE. Clinical pharmacology of antiemetics and antidiarrheals. Proc Eighth Kal Kan Sym Treat Sm Anim Dis. 1984. Columbus, OH: 7-15.

Leib MS. Treatment of chronic idiopathic large-bowel diarrhea in dogs with a highly digestible diet and soluble fiber: A retrospective review of 37 cases. J Vet Int Med 14: 27-32, 2000.

Dimski DS, Buffington CA. Dietary fiber in small animal therapeutics. J Am Vet Med Assoc 1991; 199: 1142-1146.

Twedt DC. Clostridium perfringens-associated enterotoxicosis in dogs. In: Kirk RW, Bonagura JD (ed.). Current Veterinary Therapy XI. Philadelphia, W B Saunders Company, 1992; 602-604.

Kruth SA, Prescott JF, Welch MK, et al. Nosocomial diarrhea associated with enterotoxigenic Clostridium perfringens infection in dogs. J Am Vet Med Assoc 1989; 195: 331-334.

Niilo L. Clostridium perfringens in animal disease: A review of current knowledge. Can Vet J 1980; 21: 141-148.

Turk J, Fales W, Miller M, et al. Enteric Clostridium perfringens infection associated with parvoviral enteritis in dogs: 74 cases (1987-1990). J Am Vet Med Assoc 1992; 200: 991-994.

Weese J, Staempfil H, Prescott J, et al. The roles of Clostridium difficile and enterotoxigenic Clostridium perfringens in diarrhea in dogs. J Vet Intern Med 2001; 15: 374-378.

25. Niilo L. Clostridium perfringens in animal disease: A review of current knowledge. Can Vet J 1980; 21: 141-148.

Turk J, Fales W, Miller M, et al. Enteric Clostridium perfringens infection associated with parvoviral enteritis in dogs: 74 cases (1987-1990). J Am Vet Med Assoc 1992; 200: 991-994.

Cave N, Marks S, Kass P, et al. Evaluation of a routine diagnostic fecal panel for dogs with diarrhea. J Am Vet Med Assoc 2002; 221: 52-59.

Marks SL, Melli A, Kass PH, et al. Evaluation of methods to diagnose Clostridium perfringens-associated diarrhea in dogs. J Am Vet Med Assoc 1999; 214: 357-360.

Marks S, Melli A, Kass P, et al. Influence of storage and temperature on endospore and enterotoxin production by Clostridium perfringens in dogs. J Vet Diag Invest 2000; 12: 63-67.