Colitis

Acute and chronic colonic inflammation (colitis) commonly results in large bowel diarrhea in dogs and cats. Signs of colitis include excess fecal mucus, hematochezia, tenesmus, increased frequency of defecation, and reduced volume of feces per def­ecation.

Acute colitis is most commonly caused by dietary indiscretion or intolerance (see 9.1), toxin or foreign body ingestion, drug administration (antibiotics or NSAIDs), whipworm infesta­tion (dogs only), Clostridiumperfringens enterotoxicosis, or may be idiopathic. Infections with Salmonella spp. or Campylobacter spp. are uncommon causes of acute colitis, and may cause both small and large bowel diarrhea. Diagnosis is based on history, fecal examination, and response to dietary management with a highly digestible, low fat, and low fiber diet, or exclusion of a source of dietary indiscretion. Colonoscopy and mucosal biopsy are rarely performed, so histological documentation of colonic inflammation is not often acquired, and the specula­tive diagnosis of acute colitis is based on the rapid resolution of diarrhea.

Chronic colitis is usually associated with IBD (see 9.2), or Clostridium perfringens enterotoxicosis (see below). Uncom­mon causes of colitis include histiocytic ulcerative colitis (see below), pythiosis (phycomycosis), and colitis associated with histoplasmosis, the colorless unicellular alga Prototheca spp., or Heterobilharzia americana (schistosomiasis).

6.4.2.1 Histiocytic ulcerative colitis of Boxers

Histiocytic ulcerative colitis (HUC) is an uncommon, chronic, idiopathic disease characterized by progressive colitis and ul­ceration (Figure 6.5), which is histologically associated with an inflammatory mucosal infiltrate of plasma cells, lym­phocytes, and distended PAS-positive macrophages.^20,21 The immunohistochemical characteristics of the inflammatory re­sponse have recently been characterized.⁴ The disease occurs most commonly in young Boxer dogs, less than 2 years of age, but has also been reported in a French Bulldog, a Mastiff, an Alaskan Malamute, and a Doberman Pinscher.²²

Weight loss and debilitation occur as a result of chronic intes­tinal blood and protein loss.

Figure 6.5:

Histiocytic ulcerative colitis. Endoscopic appearance of the descending colon in a 2-year-old Boxer with histiocytic ulcerative colitis. Erosions (arrows) and ulcers were present throughout the entire colon.

treatment with enrofloxacin at 2.5-5.0 mg/kg PO q 12 h for 4-8 weeks, may be more effective.²³ However, more cases with a longer follow-up period need to be studied. Traditionally, if signs of HUC are severe at the time of diagnosis, a poor prog­nosis is warranted. Dogs with mild signs may respond well to traditional therapy.²⁴

6.4.2.2 Clostridium perfringens enterotoxicosis

A preliminary review has associated large bowel diarrhea with Clostridium perfringens type A enterotoxin.³⁴ The disorder oc­curs most commonly in dogs, but can occasionally be seen in cats. Both naturally occurring and hospital acquired cases have been described.³⁵ Recently, several epidemiological studies have characterized the prevalence of Clostridium perfringens fe­cal enterotoxin in dogs with diarrhea, hospitalized dogs with­out diarrhea, and healthy outpatients.^36-39 A concise descrip­tion of this syndrome that is universally accepted has not yet emerged, and some of the syndrome’s characteristics remain controversial. The author believes that Clostridium perfringens enterotoxicosis is a common cause of chronic large bowel di­arrhea in dogs and may also be an important cause of acute diarrhea. Many questions will hopefully be answered after the completion of case-based studies in which a definitive diagno­sis is reached, the animals treated with appropriate antibiotics, and the clinical outcome is assessed.

Traditionally, treatment similar to that for IBD described in

9.2.2.4 has been suggested, with sulfasalazine being the drug of choice.

Figure 6.6:

Clostridium perfringensendospores. Huge numbers of clostridial endospores (ar­rows) in a rectal cytology specimen stained with a rapid Wright stain.

Pathophysiology

Clostridium perfringens is an anaerobic, spore-forming, gram­positive bacillus.³⁹ Five toxigenic types have been differenti­ated based on the production of one to four major toxins. In addition, each type can also produce other toxins. The major­ity of enterotoxin is produced by type A strains. A vegetative form of C.perfringens is a normal inhabitant of the colon.³⁹ The enterotoxin is produced during sporulation and causes intesti­nal fluid accumulation, mucosal inflammation, alterations in mucosal tight junctions, increased mucosal paracellular per­meability, and diarrhea.⁴⁰ In some experimental models, the enterotoxin has its greatest effects within the small intestine. The stimuli for sporulation and enterotoxin production are unknown.

Clinical signs

Acute and chronic large bowel diarrhea commonly occur with Clostridium perfringens enterotoxicosis. Vomiting, weight loss, flatulence, and abdominal pain are seen less frequently. Small bowel diarrhea may also occur, but a causal relation­ship with C. perfringens is somewhat controversial. A syn­drome of acute hemorrhagic diarrhea in dogs has been strongly associated with the presence of both C. perfringens and C. difficile enterotoxins in their feces.³⁶ The syndrome described in that study was characterized by acute hemor­rhagic diarrhea, hematemesis, severe dehydration, and necro­tizing hemorrhagic enteritis and mesenteric lymphadenopa­thy on necropsy.

Diagnosis

The diagnosis is confirmed by identifying the enterotoxin in the feces from a dog or cat with typical clinical signs, which lack evidence of another large bowel disease. The clinical signs should rapidly improve following antibiotic administration.

In the past, it has been suggested that diagnosis of this entero­toxicosis should be suspected when more than 3-5 spores per oil immersion field are seen in a rectal cytology specimen. The spores are larger than most bacteria and assume a “safety pin” appearance (Figure 6.6). However, recent epidemiological studies have not demonstrated a consistent relationship be­tween the number of fecal spores and the presence of entero­toxin.^37,38 However, dogs with signs of large bowel diarrhea have been associated with large numbers of spores on rectal cytology.³⁶ In the author’s experience, large numbers of spores on rectal cytology samples from dogs with typical clinical signs and diagnostic findings are usually associated with a positive test for fecal enterotoxin and rapid clinical response to antibi­otic treatment. However, the presence of fecal enterotoxin, typical clinical signs, and response to antibiotic treatment may also occur in dogs without an increase in spores on a rectal cytology sample. Although endoscopic examination of af­fected animals has been infrequently performed, the colon may be grossly and histologically normal or may show a hy- peremic, hemorrhagic, or ulcerated mucosa with histopatho­logical findings of catarrhal or suppurative colitis.³⁴

Treatment

Clinical signs in acute cases may resolve spontaneously. Af­fected animals usually respond to antibiotic therapy rapidly, within 3-5 days. Metronidazole at 6 mg/kg PO q 8-12 h, ampicillin at 22 mg/kg PO q 8 h, or amoxicillin at 11-22 mg/ kg PO q 8-12 h, for 7-10 days are all effective.³⁴ Animals that develop recurrent clinical signs after treatment may require repeat therapy (1 or 2 additional times) or long-term therapy with tylosin (Tylan® powder) for 3-6 months, at 10-20 mg/kg PO q 12 h.

Figure 6.8:

Tritrichomonas foetus. Appearance of an individual T. foetus organism stained with Lugol's iodine solution. Three anterior flagellae and an undulating membrane that runs the length of the body can be seen. (Image reproduced with permission from www.fabcats.org; photograph by Andy Sparkes.)

Figure 6.7:

Tritrichomonas foetus. This line drawing shows a detailed outline of a Tritri­chomonas foetus organism. As seen in Figure 6.8, the three flagellae and the undulating membrane are defining characteristics that can be used to differen­tiate T. foetus from other protozoal organisms on fecal examination. (Image repro­duced with permission from supplemental visual material posted on the www for Biology 625 at Kansas State University; original line drawing by Jarrod Wood.)

be mixed with a small quantity of canned food or placed into a gelatin capsule. Some chronic recurrent cases benefit from feeding a high fiber diet. The proposed mechanisms of action for dietary fiber include bacterial fermentation of fiber, lead­ing to acidification of the colon, which may inhibit sporula­tion, or an alteration of bacterial flora that inhibits C. perfrin- gens proliferation.

Prognosis

The prognosis for patients with Clostridium pefringens entero­toxicosis is excellent. Most affected animals respond to therapy within several days. At the present time, clinical findings have not been identified that can predict which patients will re­quire long-term therapy.

6.4.2.3 Tritrichomonas foetus infection

Jan S. Suchodolski

Recently, Tritrichomonas foetus (Figures 6.7 and 6.8), a flagel­lated protozoal parasite that is usually associated with venereal trichomoniasis in cattle has been identified as an intestinal pathogen in cats.^42,43 Diarrhea has been reported in cats after both experimental and natural infection.

While cats of any age, breed, or sex can be infected, young cats that are densely housed (e.g., cats in catteries, animal shelters, or multi-cat households) seem to be at an increased risk.⁴³ Infection is most commonly seen in young cats (i.e., those that are less than 12 months of age) but older cats may also be in­fected. Tritrichomonas foetus primarily colonizes the surface of the colonic mucosa, leading to chronic large bowel diarrhea. Without appropriate treatment cats usually remain persistently infected. While the diarrhea may spontaneously resolve, in­fected cats will often experience recurrent bouts of diarrhea after being exposed to stress. Indeed, cats infected with T foetus generally appear healthy but show an increased fre­quency of defecation with loose to liquid stools, which may contain blood and/or mucus. Fecal incontinence is frequently observed. The anal region often appears edematous and may become painful with severe diarrhea. A rectal prolapse may occur in some cases.

Diagnosis

Diagnosis of a Tfoetus infection can be made by the identifica­tion of trophozoites on a direct fecal smear examination (Fig­ure 6.8), fecal culture, PCR analysis of fecal material, or by colonic mucosal biopsy. The disadvantages of direct fecal smear examination include a low sensitivity (14%), low specificity (T foetus can be misdiagnosed as Giardia spp. or the non- pathogenic Pentatrichomonas hominis), and the fact that only fresh fecal samples can be used.

Tritrichomonas foetus can also be cultured in-house using the commercially available culture system In Pouch™ TF (Biomed Diagnostics, San Jose, CA). The pouches should be inoculated with less than 0.1 g of freshly voided feces and then incubated at 25°C. The pouches need to be evaluated under a microscope every couple of days. Results are usually obtained between 1 and 11 days after setting up a pouch. Although fecal culture is more sensitive than direct fecal smear examination, difficulties in the interpretation of results, the necessity of us­ing freshly voided feces, and the fact that the results might not be available for up to 11 days, are important disadvantages of this method.

Tritrichomonasfoetus DNA can be amplified from fecal samples by PCR.⁴⁵ PCR has been shown to be the most sensitive method for detecting Tfoetus in fecal samples, and is ideally suited for the direct diagnosis of Tfoetus infection.⁴⁵ The ad­vantages of PCR testing compared to culture include a higher sensitivity, faster turnaround time, and easier handling and storing of samples since DNA is relatively stable at various temperatures.

Therapy

Until recently, a successful treatment strategy for Tfoetus in­fections in cats was not available. However, a recent study has shown that administration of ronidazole (30-50 mg/kg PO q 12 h for two weeks) is effective in both resolving diarrhea and eradicating Tfoetus.⁴⁶ There has been some anecdotal evidence that ronidazole may cause neurological side effects. However, these side effects appear to be reversible once therapy is dis­continued. It should also be noted that ronidazole is not ap­proved for use in domestic animals and it is recommended to obtain signed consent from the owner before initiating therapy. Recently, several compounding pharmacies have started offering ronidazole.

6.3.5