Colitis in Small Animals

The colon helps to maintain fluid and electrolyte balance and absorb nutrients; it is also the major site of fecal storage until expulsion and provides an environment for the GI microbiota, the population of bacteria and other organisms that live in the GI tract and serve several beneficial functions. In colitis, disruptions to normal colonic function lead to changes in both absorption and motility; clinically, this manifests as large bowel diarrhea.

Inflammation of the colon decreases the amount of water and electrolytes absorbed and changes colonic motility by suppressing normal colonic contractions and by stimulating giant migrating contractions.

After initial mucosal injury, submucosal lymphocytes and macrophages become exposed to luminal antigens and subsequently trigger inflammation. An exaggerated reaction to dietary or bacterial factors within the lumen of the bowel, genetic predisposition, and sequelae of previous infectious or parasitic disease have also been implicated.

Goblet cells are stimulated to secrete excessive quantities of mucus. Absorption of water and electrolytes is impaired, and motility is decreased. Inflammation disrupts intracellular tight junctions and decreases the transmucosal electrical potential difference, interrupting the colon's ability to absorb sodium. Normal segmentation is inhibited; giant migrating muscular contractions proceed down the length of the colon and rapidly expel luminal contents. The inflamed bowel is more sensitive to stretch, and contents entering the colon stimulate strong, migrating muscular contractions, an urge to defecate, and abdominal discomfort.

Acute colitis develops with mucosal infiltration with neutrophils and epithelial disruption and ulceration.

Chronic colitis is most often characterized by mucosal infiltration of plasma cells and lymphocytes, fibrosis, and sometimes ulceration.

Granulomatous colitis is histologically characterized by granulomatous infiltration and bacterial invasion of the colonic wall. A correlation between granulomatous colitis and Escherichia coli invasion within colonic mucosal macrophages has been found on the basis of culture-independent molecular analysis. Adherent and invading E coli replicating within macrophages have been identified. Gross lesions are typified by a segmental, thickened, partially obstructed segment of bowel (ileum and colon most commonly), and/or colonic hemorrhage and ulceration.

C difficile–associated pseudomembranous colitis is characterized by formation of pseudomembranes, which are necrotic mucosal plaques. C difficile can produce several toxins that lead to clinical signs; toxin A and toxin B are the most common in dogs and cats. Pseudomembranous colitis is a very rare condition in dogs and cats.

Supplementing the diet with fiber (1–6 teaspoons of psyllium hydrophilic mucilloid or 1–4 tablespoons of coarse wheat bran/feeding), or feeding a commercial high fiber diet, improves diarrhea in many animals with colitis.

Dietary fiber decreases free fecal water, prolongs luminal transit time (increasing the opportunity to absorb water), absorbs toxins, increases fecal bulk and stretches the colonic smooth muscle, and improves contractility. Over time, the fiber dose can be decreased or eliminated, and a standard food can be substituted without causing the diarrhea to return.

Novel protein diets have effectively controlled clinical signs of colitis in both dogs and cats. The protein source used should be one to which the animal has not previously been exposed. Alternatively, a hydrolyzed diet may be used. These specialized diets disrupt the protein structure sufficiently to remove any allergens and allergenic epitopes, thereby preventing immune recognition.

If feeding a high-fiber or hypoallergenic (novel protein or hydrolyzed protein) diet is not beneficial, a commercial low-residue diet may be tried, especially one that contains fructooligosaccharides (FOSs).

FOSs enhance the colonic microbiota and assist in preventing and treating colonic disease. These complex carbohydrates are not digested in the small intestine. They are fermented by specific colonic bacteria that use them as an energy source. FOSs promote growth of beneficial bacteria and inhibit growth of potentially harmful bacteria. They are responsible for the production of short-chain fatty acids.

Short-chain fatty acids (acetate, propionate, butyrate) are an important energy source essential for maintenance of normal mucosal health. They help maintain intestinal motility and ameliorate intestinal inflammation. Alteration of fatty acids leads to mucosal atrophy and injury.

Cats (like dogs) with lymphocytic-plasmacytic colitis may respond to dietary management alone (eg, novel protein or commercially available hydrolyzed protein diet). In one study, cats were initially treated with dietary fiber or with dietary fiber and pharmacological intervention (prednisolone, tylosin, or sulfasalazine). Most cats were eventually maintained on high-fiber diets or a highly digestible diet (1).

Metronidazole (10–15 mg/kg, PO, every 12 hours, long-term) is often used for chronic colitis in cats. Its therapeutic effects include antiprotozoal and antimicrobial activity and inhibition of some aspects of cell-mediated immunity. It is not usually used as a sole agent but rather in combination with either dietary management or another drug. Although metronidazole is well tolerated in both dogs and cats, adverse effects can occur (mostly neurological; eg, nystagmus, ataxia, vestibular signs, seizures), either with chronic therapy or at high dosages. However, neurotoxicoses should be reversible within 5–7 days after treatment is discontinued.

Tylosin (10–15 mg/kg, PO, every 8–12 hours, for 4–6 weeks, then tapered to the lowest effective dosage), a macrolide antimicrobial used primarily in food animals, is useful in chronic enteropathies because it interferes with bacterial adhesion to the mucosa and has some antimicrobial and immunomodulating effects and minimal adverse effects. It targets mainly facultative and obligate anaerobic gram-positive bacteria and some gram-negative bacteria. However, E coli and Salmonella are resistant to tylosin.

Current treatment recommendations for granulomatous colitis require antimicrobials that are effective against E coli and that penetrate intracellularly, such as enrofloxacin (dogs only: 5–20 mg/kg, PO, every 24 hours), with reassessment every 2 weeks and total treatment duration of 8 weeks. Due to increasing reports of resistance to enrofloxacin in patients with granulomatous colitis, culture and susceptibility testing is recommended to ensure appropriate antimicrobial treatment.

Cats are susceptible to retinal damage and blindness when exposed to enrofloxacin (especially at higher dosages) due to a genetic polymorphism in the feline ABCG2 ocular blood barrier. Therefore, this drug should avoided in cats wherever possible.

The use of antimicrobials in patients with chronic diarrhea is debatable and should be avoided where possible (with the exception of granulomatous colitis) due to often short-lived responses coupled with concerns about lasting dysbiosis and development of resistance. Alternative ways to manipulate the microbiota (including through probiotics, prebiotics, and/or fecal microbiota transplantation) could be considered instead.

Fecal microbiota transplantation has been used to treat dogs and cats with chronic colitis, usually in conjunction with standard treatment, although it has been a sole treatment in some patients. Specific protocols for donor screening and administration can be found in For More Information. Methods for fecal microbiota transplantation include oral administration, endoscopic channel delivery, and retention enema, with retention enema typically being the most commonly used approach due to ease of administration. Further studies are warranted on the use of fecal transplantation in dogs and cats with chronic colitis.

Similarly, probiotics have been used in dogs and cats with diarrhea and are usually well tolerated. Evidence of their beneficial effect is mostly anecdotal. Further studies are warranted.

Anti-inflammatory medications may also be used in chronic colitis patients in which dietary change and deworming have been unsuccessful, especially if histological evidence of inflammation is present. Sulfasalazine (dogs), prednisone or prednisolone, and azathioprine (dogs) are used most commonly.

Sulfasalazine (15–30 mg/kg [maximum 3 g], PO, every 8–12 hours; then taper by 50% or to lowest effective dose when response occurs) can be used to treat lymphocytic-plasmacytic colitis in dogs. Long-term use is discouraged because it predisposes patients to keratoconjunctivitis sicca.

Sulfasalazine is a prostaglandin synthetase inhibitor and has antileukotriene activity. It consists of mesalamine linked to sulfapyridine in an azochemical bond; this linkage prevents absorption in the upper GI tract and allows most of the drug to be transported to the large intestine. Once sulfasalazine has reached the large intestine, it is metabolized by cecal and colonic bacteria, releasing both components.

Mesalamine acts locally to decrease colonic mucosal inflammation.

The sulfonamide component of sulfasalazine, sulfapyridine, is believed to be systemically absorbed and therefore does not have any local therapeutic effect in colitis but is blamed for the adverse effects of sulfasalazine.

Salicylates are metabolized in the liver by hepatic enzymatic processes involving glucuronyl transferase. Because cats are deficient in this enzymatic pathway, salicylates have prolonged half-lives in this species. Therefore, sulfasalazine is not recommended for colitis in cats.

Glucocorticoids (typically prednisolone), in combination with dietary management with or without modulation of the microbiome, are the treatment of choice for chronic colitis due to inflammatory bowel disease in cats.

Glucocorticoids may be introduced into the therapeutic plan for dogs when other therapies are not successful or if the 5-aminosalicylates result in adverse effects. For dogs, prednisone (2 mg/kg, PO, every 24 hours, for 2 weeks; after resolution of clinical signs, decrease dosage by 25% every 2–4 weeks) can usually maintain remission.

Cats usually tolerate glucocorticoids very well; however, adverse effects are common in dogs and include polyuria, polydipsia, polyphagia, GI bleeding, increased susceptibility to infection, iatrogenic hyperadrenocorticism, and pituitary-adrenocortical suppression.

Budesonide is a nonhalogenated glucocorticoid used in treatment of Crohn disease in humans. Budesonide undergoes extensive first-pass metabolism in the liver; theoretically, this should decrease the adverse effects that often occur with other glucocorticoids because little of the active drug is systemically available. In one study of 10 healthy dogs, the pituitary-adrenocortical axis was suppressed; however, no other adverse effects were observed. In some patients, systemic effects may still be appreciated.

Immunosuppressive drugs are mostly used in combination with glucocorticoids when the response is not satisfactory with the latter alone. The most commonly used are azathioprine (dogs only) and chlorambucil (cats).

Azathioprine (2–2.5 mg/kg, PO, every 24–48 hours; then tapered to lowest effective dose), alone or in combination with prednisone/prednisolone, has been used to control clinical signs associated with lymphocytic-plasmacytic colitis in dogs. Azathioprine may be considered in dogs that are poorly responsive to prednisone/prednisolone alone or with sulfasalazine.

The serious adverse effects of azathioprine in cats (myelosuppression and hepatotoxicity) preclude its use in feline colitis.

Chlorambucil (0.1–0.2 mg/kg or 2 mg/cat, PO, every 48–72 hours for 4–8 weeks or until clinical signs are markedly improved) is used in cats in combination with prednisolone if needed.

Cyclosporine (5 mg/kg, PO, every 24 hours, long-term) has been effective in steroid-refractory cases of colitis in dogs; however, it has not been evaluated in cats with chronic colitis. Adverse effects include GI disturbances, gingival disease, and alopecia.

Some animals also require short-term use of motility modifiers until inflammation is controlled. Loperamide (0.1–0.2 mg/kg, every 6–12 hours) stimulates segmental activity and slows passage of fecal contents. It also decreases colonic secretion, enhances salt and water absorption, and increases anal sphincter tone. Loperamide should not be used in dogs with the ABCB1-delta genetic polymorphism, and it is contraindicated in cases of infectious colitis (eg, caused by Salmonella, Campylobacter, or Clostridium).