Diagnosis and Management of Refractory Diarrhea
World Small Animal Veterinary Association World Congress Proceedings, 2004
Colin F. Burrows, BVetMed, PhD, MRCVS, DACVIM
University of Florida, College of Veterinary Medicine
Gainesville, FL, USA

Diarrhea, defined as an increase in fecal water content with an associated increase in the frequency, fluidity and volume of bowel movements is one of the most common complaints in veterinary medicine.

If diarrhea has not responded to conventional therapeutic approaches within 10-14 days (i.e., refractory--not yielding readily to treatment) it is then appropriate to re-evaluate the problem and invest time, money, and effort in an attempt to make a specific diagnosis.

There are many causes of chronic diarrhea in the dog and cat (Table 1). A specific diagnosis is based on an understanding of the pathophysiology of diarrhea, on a carefully taken history, and the logical application of appropriate specific diagnostic or gut function tests.

Table 1. Major Causes of Diarrhea in the Dog and Cat

Dog

Cat

Inflammatory bowel disease

Inflammatory

Plasmacytic lymphocytic

Plasmacytic lymphocytic

Eosinophilic

Eosinophilic

Lymphangiectasia

Diffuse intestinal tumors

Intestinal parasites

Bacterial overgrowth
(antibiotic responsive diarrhea)

Intestinal tumors

Bacterial or viral infection

Bacterial overgrowth
(antibiotic responsive diarrhea)

Intestinal parasites

Bacterial or fungal infection

Exocrine pancreatic insufficiency

THE HISTORY

In chronic diarrhea a complete history is critical, in that it indicates the location, nature, severity and probable cause of the disease process.

The history can be divided into 11 categories: 1) duration; 2) weight loss; 3) appetite; 4) progression or worsening; 5) diet; 6) appearance of the feces; 7) frequency of defecation; 8) presence of vomiting; 9) tenesmus; 10) the environment in which the animal is kept; and 11) the animal's breed and character.

It is essential to take the history in a logical and orderly fashion and to avoid snap judgments. It also helps to explain the importance of the questions to the client in advance. A checklist can help to ensure that nothing is forgotten (Table 2). The history also helps differentiate between small and large bowel diarrhea (Table 3). This is important as it determines both specific diagnostic studies and treatment.

Table 2. A Checklist of Questions in Chronic Diarrhea

1. Duration of Diarrhea:

Weeks, months or years; intermittent or continuous.

2. Diet:

Dietary sensitivities or idiosyncracies; recent dietary change, access to garbage. Diarrhea persists with fasting; the effect of dietary change on fecal consistency.

3. Progression or worsening:

If gradually worsening with more diarrhea, decreased appetite and onset of vomiting, suggests severe underlying disease such as lymphoma or severe inflammatory bowel disease.

4. Appetite:

Normal, increased, decreased or ravenous. Pica; coprophagia.

5. Appearance of the Feces:

Volume, color, blood, mucus, flatus.

6. Frequency of Defecation:

Amount increased above normal. Accidents in house at night; urgency.

7. Vomiting:

Presence or absence, frequency, nature of vomitus, relationship to eating.

8. Tenesmus:

Presence or absence; before, during or after defecation. Description of act of defecation.

9. Body Weight and Condition:

Overall appearance of animal; documented weight loss.

10. Environment:

Outdoors or indoors, working dog or pet. Access to parasite infected environment. Obedience trained, change of environment, boarding, new pet, travel.

11. Breed and character:

Breed related disease e.g., German shepherd, Basenji or stress related (irritable bowel syndrome)

Table 3. Differentiation of Small Intestinal from Large Intestinal Diarrhea in the Dogs

Parameter

Small Intestine

Large Intestine

The Feces

Volume

Markedly increased

Normal or increased

Mucus

Rarely present

Common

Melena

May be present

Absent

Hematochezia

Absent except in acute
hemorrhagic diarrhea

Fairly common

Steatorrhea

Present with maldigestive or
malabsorptive disease

Absent

Undigested food

May be present with maldigestion

Absent

Color

Color variations occur, e.g., creamy
brown, green, orange or clay color

Color variations rare,
may be bloody

Defecation

Urgency

Absent except in acute or very
severe disease

Usually but not invariably
present

Tenesmus

Absent

Frequent but not invariably
present

Frequency

2 to 3 times normal for the patient

Usually greater than 3 times
normal

Dyschezia

Absent

Present with distal colonic
or rectal disease

Ancillary Signs

Weight loss

May occur in maldigestive or
malabsorptive disease

Rare except in severe colitis,
diffuse tumors or histoplasmosis

Vomiting

May be present in inflammatory
disease

Uncommon, but occurs in up
to 25-30% of dogs with colitis

Flatulence and
borborygmus

May be reported with maldigestion
and malabsorption

Absent

Halitosis in the
absence of oral
disease

Present with maldigestion or
malabsorption

Absent

THE PHYSICAL EXAMINATION

A complete physical examination may reveal important clues about the cause of diarrhea. The nutritional status of the patient and any evidence of dehydration should be carefully noted. Overt physical abnormalities are uncommon in most dogs with chronic diarrhea. The most common findings are a loss of body weight and condition in dogs with nutrient mal-absorption or protein-losing enteropathy. A thickened intestine and enlarged mesenteric lymph nodes may occasionally be palpated in cats and a few dogs with chronic diarrhea associated with either inflammatory bowel disease or lymphosarcoma (Table 4&5). Physical findings in dogs and cats with colitis are usually normal.

Diffuse intestinal tumors Bacterial overgrowth (antibiotic responsive diarrhea) Bacterial or viral infection Intestinal parasites

Table 4. Clinical Significance of Physical Findings in Intestinal Disease

Physical Finding

Clinical Association

Dehydration

Diarrheal fluid loss (diarrhea, vomit)

Depression, weakness

Electrolyte imbalances, debilitation

Emaciation, malnutrition

Protein calorie malnutrition

Pallor (anemia)

Gastrointestinal blood loss

Anemia of chronic disease

Edema/effusion

Protein losing enteropathy

Table 5. Clinical Significance of Abdominal Palpation Findings in Intestinal Disease

Physical Finding

Clinical Association

Masses

Foreign body, neoplasia, granuloma

Thickened intestinal loops

Tumor, inflammation

Sausage loops

Intussusception

Aggregated loops

Linear foreign body, adhesions

Pain

Inflammation, obstruction, ischemia

Gas, fluid distention

Obstruction, ileus

Mesenteric lymphadenopathy

Inflammation, infection, neoplasia

SPECIFIC DIAGNOSIS OF CHRONIC DIARRHEAL DISEASES

Once the problem has been identified as small or large bowel in origin from the results of the history and physical examination, a specific diagnosis can be made by means of appropriate diagnostic studies (Table 6). It is routine in both chronic small and large bowel diarrhea to obtain a hemogram, blood chemistries, urinalysis and a complete fecal examination.

Table 6. The Sequential Diagnosis of Chronic Diarrhea

Small and Large Bowel Diarrhea

Hemogram
Blood Chemistries
Urinalysis
Fecal Examination

Small Bowel
Diarrhea

Absorption Studies
Digestion Studies
Radiographs
Biopsy
Response to rational
therapy
Refer

Large Bowel
Diarrhea

Diet Change
Colonoscopy
Biopsy
Response to rational
therapy
Refer

Routine Hemogram and Blood Chemistry

Anemia may be present in longstanding cases and is usually ascribed to chronic blood loss. Changes in the white count are uncommon but a lymphopenia is present in about 50% of dogs with lymphangiectasia. Eosinophilia, unexplained by the presence of parasite infection, may suggest eosinophilic enteritis.

Changes in blood chemistries are uncommon but if present may help to differentiate between primary gastrointestinal disorders and systemic or metabolic disease. Mild elevations in liver enzyme activity (AP and ALT) are quite common in inflammatory bowel disease, while hypoproteinemia may be observed in some dogs with protein losing enteropathy (PLE).

Table 7. Diagnostic Studies in Canine and Feline Small Intestinal Disease

Dog

Cat

Rule out EPI (TLI test)

Radiographs and Ultrasound

Radiographs and Ultrasound

Repeat abdominal palpation

Folate and cobalamin

Biopsy

Biopsy

Response to rational therapy

Response to rational therapy

Rule out EPI
Serum cobalamin

The Fecal Examination

A complete fecal examination should always include both macroscopic and microscopic examination. It is often helpful to watch the animal defecate since signs of small or large bowel diarrhea that may be confused by the history may be readily apparent when the veterinarian observes the patient directly. Macroscopic examination of a fresh fecal sample is essential for assessment of bulk, color and consistency, as well as for the detection of blood and mucus.

Microscopic examination of the feces by both direct (smear) and indirect (flotation) techniques for evidence of parasitic infection is mandatory in every dog with diarrheal disease. Special tests may be needed to eliminate infection with Giardia. Bacteriological culture of the feces is unrewarding, but should be considered if infection with Salmonella sp. or Campylobacter sp. is suspected. A test for Clostridium perfringens toxin should be routine in patients with signs of large bowel diarrhea. A direct smear may also identify spores of C. perfringens. Infection with cryptosporidium is emerging as a cause of diarrhea in cats. Fecal samples need to be carefully screened for this organism.

INITIAL APPROACH

After infectious and metabolic causes have been ruled out, it may be appropriate to simply change the patient's diet to a highly digestible and single protein source product.

Treatment with a broad spectrum anthelmintic such as fenbendazole is also appropriate as is a trial course of an antibiotic such as metronidazole or tylosin. Treatment with sulfasalizine (Salazopyrin) may be useful in patients with large bowel diarrhea.

SMALL BOWEL DIARRHEA

After the above studies are concluded it should be possible to decide whether signs of small or large bowel diarrhea predominate. Diagnostic tests for small bowel diarrhea are shown in Table 7.

The TLI Test

Measurement of the concentration of trypsinogen in the serum is the easiest and most reliable test for the diagnosis of exocrine pancreatic insufficiency (EPI). The normal range is between 5 and 35μg/L. Levels below the reference range are compatible with a diagnosis of EPI.

Abdominal Imaging

Radiographs are usually interpreted as normal in most dogs and cats with chronic diarrhea. In some patients however, they may reveal visceral displacement, an unsuspected foreign body or a mass. Survey thoracic radiographs should also be made as part of the initial data base if circumstances permit. An upper gastrointestinal barium series (GI series) is usually unrewarding and not cost-effective. Contrast radiographs play their most important diagnostic role in the evaluation of patients with vomiting caused by gastric diseases or disorders associated with space-occupying lesions of the small intestine.

Abdominal ultrasound allows accurate measurement of intestinal wall thickness with subsequent implications for diagnosis and prognosis. The technique can help pinpoint focal lesions such as intestinal tumors and can help identify diseases associated with diffuse intestinal thickening such as inflammatory bowel disease or diffuse intestinal lymphoma.

Gut Function Studies

Measurement of the concentration of serum folate and cobalamin is useful in the assessment of gut function and in the diagnosis of small intestinal bacterial overgrowth.

Other tests of gut function include the fecal proteolytic activity, the breath hydrogen test, serum unconjugated bile acids for bacterial overgrowth and intestinal permeability tests. All, except the oral fat absorption test are usually only performed at teaching hospitals.

Endoscopic or Surgical Biopsy

Either endoscopic biopsy or an exploratory laparotomy with multiple small intestinal biopsies are valid and effective diagnostic techniques in patients with chronic small intestinal disease. Biopsy reveals the underlying pathology and permits an informed decision about the selection of appropriate therapy.

It is important to take multiple intestinal biopsies along the length of the intestine even if it looks and feels normal. This is because few diffuse intestinal diseases are associated with macroscopic changes and most can only be diagnosed histologically.

Response to Therapy

It could be argued that appropriate dietary or drug therapy, made after a logical attempt to reduce the number of diagnostic possibilities to just one or two is a valid diagnostic "test". A favorable response to dietary manipulation, pancreatic enzymes, corticosteroids or appropriate antibiotics such as metronidazole or tylosin suggests a diagnosis, provides functional or specific control of the diarrhea and will satisfy the client.

As mentioned above, some dogs and a few cats with chronic diarrhea respond well to a change of diet alone and this should be attempted early in the process. The diet should preferably be of a single protein source and highly digestible. A variety of commercial diets that fulfill these criteria are now available. Low fat diets are indicated only after a specific diagnosis and with demonstrated steatorrhea.

Some patients with severe small intestinal disease (usually those with weight loss and hypoproteinemia) may have a secondary pancreatic insufficiency. In these patients the intestinal wall is so damaged that it can no longer play a role in the stimulation of pancreatic secretion and the patient is so malnourished that it cannot synthesize enough enzyme for normal digestion. These patients do better if their meals are supplemented with powdered pancreatic enzyme for the first few weeks of treatment.

If other major causes of diarrhea have been ruled out it can be assumed that the patient may have inflammatory bowel disease (IBD) with secondary bacterial overgrowth. It must be emphasized however, that diffuse intestinal lymphoma is still a possibility if not ruled out by intestinal biopsy. These two problems are treated with immunosuppressive doses of prednisone (1mg/kg q12h for 2-3 weeks and then tapering) and metronidazole (10-15 mg/kg q12h for 2-4 weeks or longer). Tylosin (15-20 mg/kg q12h) or tetracycline (10 mg/kg q12h) are acceptable alternatives. It is important to give some type of gastric mucosal protection (e.g., ranitidine 2 mg/kg q12h) in patients receiving high dose corticosteroid treatment. This is especially true in patients with severe protein calorie malnutrition.

LARGE BOWEL DIARRHEA

Diet Change

Changing the patient's diet to a highly digestible low residue type can be beneficial since it reduces the volume and water content of the diarrhea. Diets containing fermentable fiber (e.g., Iam's low residue) are also recommended by some clinicians since the lower colonic pH produced by fermentation is believed to inhibit the production of clostridial toxin. Some cases of large bowel inflammatory bowel disease in both cats and dogs may also respond to changing the diet to one that contains a protein to which the animal has not been previously exposed. Some clinicians prefer to treat large bowel diarrhea symptomatically with a diet containing a nonfermentable fiber.

Colonoscopy and Biopsy

Examination and biopsy of the colon through a rigid sigmoidoscope or a flexible fiberoptic colonoscope is essential for accurate diagnosis and subsequent management of colonic disease. The ease of the technique and the valuable diagnostic information derived from colonoscopy certainly justifies its use in private practice. Since most colonic disease in the dog appears to involve the whole colon, a rigid sigmoidoscope which allows examination of the descending colon and rectum, will enable a specific diagnosis to be made in most dogs with colonic disease.

Histological examination of a biopsy specimen obtained through the colonoscope provides a specific diagnosis. Most cases of canine colitis are idiopathic, and are treated with sulfasalazine (25 mg/kg q8h), but tumors, and the less common types of colitis such as eosinophilic colitis must have a specific histologic diagnosis for appropriate prognosis and therapy.

Test Feces for Clostridium

If the test has not already been performed the feces should be tested for the presence of clostridial toxin. Recent studies however, have called into question over-reliance on this test since toxin can apparently be found in normal dogs.

Rational Therapy

If the client will not permit diagnostic studies or if a colonoscope is not available, the patient can be treated for colitis with sulfasalazine (Salazopyrin) at a dose of 25-40 mg/kg q8h dog, 20 mg/kg q12h cat. This is the drug of choice for the treatment of colitis and many patients respond favorably after 7-14 days of treatment. Other drugs include tylosin and metronidazole which are used to treat clostridial overgrowth and prednisone which is used to treat eosinophilic colitis. Enrofloxacin is used to treat Boxer colitis.

CONCLUSION

Diagnosing the cause of chronic diarrhea in the dog can be a tedious, frustrating and frequently expensive experience. Nevertheless, specific diagnosis is essential if a cure is to be achieved, because unlike acute diarrhea which is mostly self-limiting, chronic diarrhea needs specific therapy. Long-term symptomatic therapy is both unwarranted and unwise, since it leads to client dissatisfaction and often to the deterioration or death of the patient.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Colin F. Burrows, BVetMed, PhD, MRCVS, DACVIM
University of Florida, College of Veterinary Medicine
Gainesville, FL


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