Equine colitis: etiologies and treatment strategies (should I use antibiotics?) (Proceedings)

Equine colitis can be a diagnostic and therapeutic challenge for both practitioners and owners alike. The presenting clinical signs can be identical regardless of the etiology. Diagnostic investigation is critical to identify infectious causes and ensure appropriate isolation procedures are implemented. Due to the fact that most of the bacteriologic diagnostics may take several days to obtain, routine isolation of all horses with diarrhea is recommended. For the purpose of this presentation, the etiologies of colitis that will be discussed are Salmonella, Clostridium perfringens and difficile, cyathostomes, sand enteropathy, and right dorsal colitis.

Clinical signs

The clinical presentations of colitis can range from peracute fever and death, to depression, inappetance, colic, and profuse diarrhea. Horses with focal colitis or very early in the course of disease may not present with any diarrhea at all. Typical findings on physical examination may include a fever (rectal temperature >102 F), tachycardia, hyperemic mucous membranes with a toxic line, and evidence of dehydration. The character of the diarrhea is generally not helpful in determining the etiology.

Diagnosis

In addition to a thorough physical examination, general diagnostic tests are indicated to aid in the assessment of the patient with colitis. A complete blood cell count, serum chemistry profile, rectal examination, and abdominocentesis should be routinely performed. The complete blood cell count will often reveal a leukopenia characterized by a neutropenia with a left shift. Changes in the serum chemistry profile will frequently include hypoproteinemia, hypoalbuminemia, and electrolyte derangements (hyponatremia, hypochloremia, hypocalcemia, and hypokalemia). The information obtained can ensure that therapy is targeted to specific abnormalities. A venous blood gas or istat can also give a rapid evaluation of acid-base status, bicarbonate, and blood lactate levels. A rectal examination is routinely performed at our hospital to identify impactions of the large colon, cecum, or small colon, and to assess any palpable thickening of the colon wall. Fluid is obtained from the abdomen via abdominocentesis and undergoes cytologic evaluation. Peritonitis has been identified in some cases of colitis, and requires therapy with antimicrobials. Additional diagnostics that should be considered include abdominal ultrasound examination and abdominal radiography. These will be discussed in more detail below, under right dorsal colitis and sand enteropathy.

Salmonella

Salmonella spp. continues to be a significant cause of mortality among horses with colitis. Clinical presentations can include peracute death to protracted chronic diarrhea. The prevalence of fecal shedding of Salmonella among horses in the United States is estimated to be 0.8% (1), and is estimated to be between 1.4% and 20% among horses admitted to veterinary teaching hospitals (2). Diagnostic techniques include culture of five consecutive fecal samples, or PCR of three consecutive fecal samples with subsequent culture. Salmonella are shed intermittently and therefore cannot be consistently isolated with culture or PCR, but PCR is a more sensitive technique. PCR seems to have the greatest agreement (70%) with bacterial culture when two or more positive PCR results are used to define a horse as actively shedding. (3) Risk factors that have been associated with fecal Salmonella shedding in hospitalized horses with gastrointestinal disease include a history of antimicrobial drugs prior to hospitalization and abdominal surgery during hospitalization. (4)

Clostridium

Clostridium difficile and perfringens (types A and C) are the most commonly reported clostridial causes of equine colitis. C difficile is not considered part of the normal flora of the adult gastrointestinal tract and is uncommonly isolated from normal equine manure. Clinically significant disease from C difficile is the result of exotoxin production. Clostridium difficile produces at least five toxins, however, only the effects of toxins A and B are well understood. Toxin A (enterotoxin) and toxin B (cytotoxin) act synergistically to cause intestinal tissue disruption and secondary inflammation with associated clinical signs. (5) Binary toxin, a third toxin, has been identified in human and some equine isolates, however, its current significance is unclear. Laboratory diagnosis of C difficile is based on bacterial culture and toxin assays (ELISA). Culture is a sensitive test but is not specific due to non-toxin producing isolates. Definitive diagnosis of C difficile requires identification of toxin A, toxin B, or both in fecal samples from horses with colitis. Several immunoassays detecting toxins A and B or toxin A alone are commercially available. Although the gold standard for detection involves demonstration of cytotoxicity in cell culture, this technique is expensive and requires specific laboratory facilities. Although a consensus regarding definitive diagnosis has not been established, many authors support the view that positive culture along with toxin assay is consistent with a diagnosis of C difficile colitis. (5)

Clostridium perfringens is an anaerobic gram-positive rod that is widely distributed as spores and vegetative cells in the environment. Clinical signs of disease are more common in neonatal foals than adults. Types of C perfringens are differentiated based on the production of four major toxins: alpha, beta, epsilon, and iota. (6) In addition, isolates may have the gene to produce the enterotoxin, which can be identified with PCR on fecal samles. DNA testing can also be used to identify genotypes of C perfringens types A through E and all the major toxins, β-2 toxin, and enterotoxin. Diagnosis is generally based on fecal culture in combination with identification of the toxin.

Cyathostomes

Strongyles are the most commonly implicated parasite for acute and chronic diarrhea. Small strongyles (cyathostomes) have emerged as a more prevalent cause of diarrhea since the development of effective anthelmintics against the large strongyles. Widespread treatment of horses with rotating anthelmintics has effectively reduced the prevalence of large strongyles, but has not effectively controlled cyathostomes. Cyathostomes are one of the most commonly identified causes of colitis in the horse. Definitive diagnosis is challenging because the disease is caused by the larval stages of the parasite, making fecal egg counts minimally helpful. The larvae may be visible to the naked eye in the manure or on a glove following rectal examination. Histologic examination of biopsies of the cecum or large colon, if exploratory celiotomy has been performed, may show characteristic pathologic changes including edema and eosinophilic inflammation, with or without identification of mucosal larvae. Pre-patent infection infection is problematic, because large numbers of the parasite may exist in a subclinical state and be virtually undetectable. Research has also demonstrated resistance of small stonglyes to several of the currently available anthelmintics including benzimidazoles.(7) Research is in progress to develop the an immunodiagnostic test that allow numbers of mucosal larvae to be estimated. (8) Fecal flotation and egg counts are recommended, but empirical treatment (with high dose fenbendazole or moxidectin) is frequently performed due to the possibility of false negative fecal results.

Sand enteropathy

Sand accumulation can result in diarrhea through irritation of the colonic mucosa. Horses that are pastured in coastal regions of the country and fed on the ground should be considered suspect. Young horses and those on poor quality pasture or dirt lots may be indiscriminate eaters, and consequently ingest more sand. Sand enteropathy cases may present as either acute or chronic colitis, acute or chronic colic evaluation, or for weight loss. Diagnostics include fecal sedimentation in a rectal sleeve or plastic bag, abdominal ultrasound, and abdominal radiography. Abdominal radiographs typically require referral to a hospital with a radiography unit of significantly high mAs. Abdominal ultrasound examination may reveal hyperechoic intestinal contents along the ventral abdomen with various acoustic shadowing and decreased intestinal motility.(9) Colonic haustra may not be visible if a large accumulation is filling the ventral colon. One study found ultrasound examination both 87.5% sensitive and specific for detecting colonic sand when compared to radiography. (9) However, the volume of sand cannot be determined on ultrasound examination, making radiographs the most valuable diagnostic technique in lieu of exploratory celiotomy.

Right dorsal colitis

Right dorsal colitis (RDC) has long been associated with inappropriately high dosages or prolonged use of nonsteroidal anti-inflammatory (NSAID) drugs. However, horses receiving appropriate dosage by weight of NSAIDs can still develop RDC in several days or weeks. The toxic effects of NSAIDs are a result of inhibition of prostaglandin synthesis which disrupts mucosal blood flow and other mucosal-protective mechanisms in the gastrointestinal tract. Diagnosis can often be made on the basis of history, physical examination, and clinocopathologic data. The most common abnormality on serum chemistry profile is hypoproteinemia, characterized by a hypoalbuminemia, due to a protein-losing enteropathy. History and clinical exam findings often reveal NSAID administration, loose cow-patty consistency manure, and sometimes colic or weight loss. Combination therapy with both phenybutazone and banamine may increase the risk of RDC and hypoproteinemia compated to either drug used alone.(10) Right dorsal colonic ulceration may lead to peritonitis, adhesions, and stricture in severe cases. Additional diagnostics include exploratory celiotomy and abdominal ultrasound examination. Abdominal ultrasound examination may reveal a thickened colon wall (> 0.5cm), typically on the right side of the abdomen at the 11th, 12th, and 13th intercostal spaces.(11) One study found mural thickness significantly greater in affected horses (0.63-1.67cm), with the right dorsal colon having a prominent hypoechoic layer associated with submucosal edema and inflammatory infiltrates.(11) Isotope-labeled white blood cell scintigraphy may also identify ulceration of the right dorsal colon, however the sensitivity and availability of the test is limited.(12) Exploratory celiotomy may be necessary to confirm stricture and/or adhesions.

Treatment

Regardless of etiology, supportive care and maintenance of hydration and normal electrolyte status are critical in the successful management of equine colitis. Intravenous polyionic fluid therapy may be required at 100 mls/kg/day or higher for horses with significant fluid losses through diarrhea or with evidence of azotemia on serum chemistry. Of course, fluid support must take into consideration protein losses, and occasionally colloid therapy, such as plasma or hetastarch, is required. Electrolyte supplementation should be based on serum chemistry results or istat analysis.

Endotoxemia

Endotoxemia and its sequelae can result in rapid deterioration in the colitis patient. Thus, therapy targeted against endotoxin is important in the management of these cases. As mentioned above, intravenous fluid therapy and rehydration are essential for management of colitis and endotoxemia. Hypertonic (7.5%) saline solution (4 mls/kg) can be beneficial for improving cardiovascular status in dehydrated horses, but should generally be followed by isotonic fluid therapy and should be used with caution in patients with significant sodium derangements. Polymixin B (1000-5000 units/kg IV every 12h) binds the lipid A portion of circulating endotoxin, and is recommended for use except in cases with significant azotemia. NSAIDs, such as flunixin meglumine (0.25mg/kg every 8 hours), help mitigate the inflammatory cascade by inhibition of cyclooxygenase enzymes. Higher doses of flunixin meglumine may be indicated for colonic pain (1.1 mg/kg). Pentoxifylline (8 mg/kg PO every 8h) is a phosphodiesterase inhibitor that is a rheologic agent, and has been shown to block endotoxin-induced cytokine.

More expensive therapy for endotoxemia includes Endoserum® (Immvac Inc, Colombia, MO) or hyperimmune plasma (E. coli J5 or Salmonella typhimurium). Endoserum® is a hyperimmune serum from horses vaccinated with the Salmonella typhimurium Re mutant, and requires refrigeration. Endoserum® should be diluted in isotonic saline solution or lactated ringers solution (1:10 to 1:20), with the recommended dose of 1.5 ml/kg. Hyperimmune plasma products must be kept frozen prior to use, and the companies should be contacted directly to determine availability (Lake Immunogenics, PulsaVac). One study did not find significant beneficial effects of Endoserum®13; however, this author has occasionally found it useful in conjunction with other therapies.

Horses with acute colitis are at high risk for the development of subclinical disseminated intravascular coagulation (DIC), defined as three out of six abnormal coagulation test results (platelet count, plasma fibrinogen concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and serum fibrin degradation products concentration).14 In adult horses, DIC appears to be associated with severe endotoxemia secondary to gastrointestinal disease. Once subclinical DIC has been identified, treatment with aspirin, heparin, or fresh frozen plasma may improve survival rate.

Antimicrobials

Treatment with antimicrobials is controversial in cases of equine colitis. Antimicrobial therapy can disrupt gastrointestinal microflora and result in colitis, therefore, each patient should be individually assessed prior to antibiotic administration. As a general rule, many clinicians reserve antibiotic therapy for neonates or patients with a marked neutropenia, sepsis at a secondary site, or those with suspected clostridial etiology. The emergence of multidrug-resistant Salmonella (MDR) in documented nosocomial outbreaks of equine patients complicates the selection of antimicrobials when they are indicated5, and results of antimicrobial susceptibility should be considered when available. Metronidazole (25 mg/kg PO every 12h) is often utilized as a specific targeted therapy for Clostridium.

Probiotic and other therapies

Although probiotic therapy is generally not considered harmful, there is a paucity of evidence-based research supporting its use. Saccharomyces boulardii is a commercially available yeast that was found to be effective in decreasing the severity and duration of enterocolitis at a dosage of 25 g orally twice daily for 14 days.15 Di-tri-octahedral smectite (DTO-smectite, Biosponge™; Platinum Performance, Buellton, CA) is a natural hydrated aluminomagnesium silicate that is commercially available for oral use in horses. DTO-smectite absorbs substances in the gastrointestinal tract such as endotoxin, and binds C. difficile toxins A and B, C. perfringens enterotoxin, and endotoxin in vitro while having no effect on bacterial growth or the action of metronidazole.16

Additional recommendations for sand accumulation in the gastrointestinal tract have included treatment with psyllium mucilloid (1 g/kg via nasogastric tube daily) and removal from the offending pasture or site of sand. Although previous reports have not found psyllium to be efficacious, this author attempts treatment with psyllium and environmental management as an alternative to surgical evacuation (in severe cases, although sometimes still required) or benign neglect in mild cases. Psyllium has also been advocated for the management of RDC, in much smaller volumes, to increase the production of short-chain fatty acids in the colon. Short-chain fatty acids are believed to hasten colonic healing and improve the clinical course of RDC.

Additional dietary recommendations for horses with RDC include changing to a complete pelleted feed, adding corn oil, and eliminating all hay from the diet. Additional medical therapies for RDC include sucralfate (20 mg kg PO every 6h), metronidazole for its' anti-inflammatory effects, and plasma transfusion.

Criteria for referral

If treatment is undertaken on the farm, it is important to consider several criteria for referral. Referral to a secondary or tertiary case facility is generally advised if the patient has ongoing signs of endotoxemia, dehydration that cannot be significantly addressed on the farm, severe tachycardia, colic, or protracted diarrhea of several days duration. Any deterioration in the patients' clinical parameters in the face of treatment warrants reevaluation. If daily evaluation of the patient cannot be performed or if additional diagnostics such as radiographs and/or ultrasound examination are indicated, referral is appropriate.

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