Vet Clin Equine 22 (2006) e1–7

Infiltrative Intestinal Disease

Bonnie S. Barr, VMDRood & Riddle Equine, PO Box 12070, 2150 Georgetown Road Hospital,

Lexington, KY 40580-2070, USA

A 19-year-old Arabian gelding used for pleasure riding presented witha history of weight loss, recurrent colic, and diarrhea of 3 weeks’ duration.The horse was vaccinated appropriately and recently had been dewormedwith a larvicidal 5-day course of fenbendazole. He had been treated withBanamine, Fastrack (an oral probiotic), potassium penicillin, and Gentocin,and there was minimal response to this treatment.

Physical examination

The horse had a body score of 3 out of 9. His temperature, heart, and re-spiratory rate were within normal limits. Auscultation of his heart and lungsfailed to detect any abnormalities. Gastrointestinal motility was increasedand sounded fluid-like primarily in the ventral quadrant. Fecal consistencywas loose and fibrous. There was pitting ventral edema that extended to hissheath/prepuce area. He ambulated well around the stall.

Case assessment

The most concerning problems were weight loss and chronic diarrhea. Ingeneral, weight loss can result from a variety of disorders, but in this casethe most likely cause was a chronic enteropathy. Causes of chronic diarrheainclude chronic parasitism, peritonitis, nonsteroidal anti-inflammatory drugtoxicity (right dorsal ulceration/colitis), infiltrative intestinal disease, salmo-nellosis, chronic liver disease, and sand enteropathy. Chronic parasitismwith larval cyathosomes or large strongyles can cause weight loss and diar-rhea. The recent deworming history with larvicidal doses of fenbendazolemade chronic parasitism unlikely as the cause of the clinical signs seen inthis horse. Nonsteroidal anti-inflammatory drugs (NSAID) frequentlyare administered to horses because of their antipyretic, analgesic, and

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anti-inflammatory properties, but in addition to these therapeutic proper-ties, NSAID also exhibit toxic properties manifested most commonly inthe gastrointestinal tract. Nonsteroidal toxicity was ruled out based onthe lack of a history of frequent or chronic nonsteroidal drug usage. Themost common signs associated with liver failure are chronic weight loss, de-pression, variable icterus, and progressive neurologic signs. In this case, themucous membranes were not icteric, and no neurologic signs were noted onphysical examination; thus, chronic liver disease was ruled out. Liver diseasealso was ruled out based on the presence of normal activities for liver en-zymes on the serum chemistry profile. Large amounts of sand in the coloncan cause irritation to the mucosal wall resulting in diarrhea. Sand enterop-athy becomes a problem in those areas in which the soil type is sandy, but inthis case, the horse was not from one of these areas. A few causes for chronicdiarrhea and weight loss still exist, including peritonitis, infiltrative intestinaldisease, and salmonellosis; in the author’s opinion, these cannot be ruled outconfidently without further diagnostics.

Procedures

A complete blood count and chemistry panel revealed hypoproteinemia(5.0 g/dL; normal range, 5.8–7.6 g/dL), hypoalbuminemia (1.7 g/dL; normalrange, 2.4–5.0 g/dL), neutrophilia (10,764 cells/mL; normal range, 3500–8400cells/mL), and mild hyperfibrinogenemia (500 mg/dL; normal range, 200–400mg/dL), which are common laboratory abnormalities noted in chronic enter-opathies. These laboratory abnormalities are the result of the inflammationto the intestinal tract. The rest of the laboratory work was normal. Feceswere examined for parasite ova and multiple fecal cultures were performed.It is important to perform multiple (5–10) fecal cultures if looking for in-fectious agents (salmonella) in cases of chronic diarrhea. If salmonella iscultured, there likely is an underlying cause; thus, a complete work-up stillmust be performed. The results were negative for parasite ova and other in-fectious agents. An abdominocentesis was performed and grossly the fluidappeared normal; the cell count also was normal. Cytologic examinationof the peritoneal fluid revealed only a few epithelial cells and macrophages.In the absence of bacteria and an increased number of inflammatory cellson the cytologic analysis of the peritoneal fluid, peritonitis was ruled out.The most likely diagnosis was infiltrative intestinal disease, but further diag-nostics were needed to confirm the diagnosis. Rectal palpation did not iden-tify any abnormalities. Occasionally, thickened bowel wall or enlargedmesenteric lymph nodes are palpated per rectum but are considered nonspe-cific findings when trying to differentiate between different types of infiltra-tive intestinal diseases. A transabdominal ultrasound was performed witha low-frequency transducer (2.5 MHz or 5.0 MHz), which allows maximaldepth of penetration in an adult (Fig. 1). The ultrasound identified lymph-adenopathy near the cecocolic vessels, with an increase in small intestinal

e3INFILTRATIVE INTESTINAL DISEASE

thickness. Sonographic thickening of the intestinal wall was indicative of in-filtrative intestinal disease, although it did not give a specific diagnosis in thetype of infiltrative disease. A rectal biopsy was performed because it is a safeand easy procedure to perform, but this procedure results only in a diagnosisif the infiltrative lesion extends to the rectum. In approximately one third ofpatients, a rectal biopsy is diagnostic. A human rectal or cervical biopsy in-strument or a mare uterine biopsy instrument can be used [1]. To performa rectal biopsy, the horse is restrained as for rectal palpation and a lubricatedsleeved hand is introduced into the rectum [1]. The closed end of the sterilizedinstrument is passed into palm of the hand that is in the rectum; the otherhand is used to operate the handle of the instrument. A mucosal fold is pal-pated and held between the finger, and the instrument is used to obtain thesample [1]. It is best to obtain a sample from the dorsolateral position (the1-o’clock or 11-o’clock position) [1]. The sample is placed in fixative; oftenan additional sample is submitted for culture. In this patient, the rectal bi-opsy identified lymphocytic plasmacytic infiltrative disease. An oral carbohy-drate absorption test also could have been performed and the results wouldindicate involvement of the small intestine. In the author’s experience, thetest is time consuming, the result is nonspecific, and other diagnostic testssuggested involvement of the small intestine. Glucose and D-xylose are thecarbohydrates used most commonly for absorption tests. Full thicknessbowel wall biopsies are more likely to be useful diagnostically, but obtainingsuch biopsies is possible only through a surgical approach. Horses withchronic diarrhea often are not the best candidates for major exploratory sur-gery, because complications are common in the postoperative period becauseof hypoproteinemia and the catabolic state of the patient.

Discussion of differential diagnosis

Infiltrative intestinal diseases can be caused by infiltrative organisms, suchas Mycobacterium sp or Lawsonia intracellularis, or those disease processes

Fig. 1. Abdominal ultrasound identifying thickening of the wall of the small intestine.

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in which an etiologic agent is not identified, such as granulomatous enteritis(GE), lymphocytic plasmacytic enterocolitis, multisystemic eosinophilicepitheliotropic disease, eosinophilic enterocolitis, and alimentary lympho-sarcoma. Mycobacterium sp rarely causes clinical disease in horses, andthe clinical signs are the result of granulomatous lesions found in the gutwall [2,3]. Other organ systems often are involved, such as the skin, lungs,and skeleton. The best method of diagnosis is the acid-fast staining of intes-tinal biopsy samples or lymph nodes (mesenteric or colonic lymph nodes)[2,3]. L intracellularis bacterium causes a proliferative enteropathy describedin 4- to 7-month-old foals [4,5]. Clinical signs include colic, diarrhea, andweight loss; the most common blood work finding is hypoproteinemia[4,5]. This organism is found to affect older adult horses. GE is reportedmost frequently in young Standardbred horses. Diffuse granulomatous le-sions, predominantly in the small intestine, characterize GE [6–9]. The causeof GE is unknown, although those horses infected with Mycobacterium sphave similar diffuse granulomatous lesions. A definitive association betweenGE and Mycobacterium sp infections, however, has not been determined[6–9]. Common clinical signs of GE include weight loss and anorexia, withthe most consistent finding hypoalbuminemia [6–9]. Occasionally, dermatitisalso may be noted. The characteristic lesions from histopathologic evalua-tion of an intestinal biopsy establish the diagnosis. Lymphocytic plasmacyticenterocolitis has few reports in the literature [6–9]. This disorder is charac-terized by an excessive infiltration of lymphocytes and plasma cells in thelamina propria of the gastrointestinal tract [6–9]. Clinical signs includeweight loss, diarrhea, inappetence, depression, and thin body condition.Horses of all ages can be affected. A definitive diagnosis is confirmed byan intestinal biopsy. Multisystemic eosinophilic epitheliotropic disease is re-ported most often in young Standardbreds and is characterized by eosino-philic infiltration, not only of the intestines but also of other organs [6–9].An exudative dermatitis is a common feature, most often involving theface, limbs, and ventral portion of the abdomen [6–9]. The hepatobiliary sys-tem also may be affected. Definitive diagnosis is through biopsy and histo-pathologic identification of the characteristic eosinophilic infiltration [6–9].Eosinophilic enterocolitis is restricted to the intestinal tract and the mostcommon clinical sign is recurrent colic rather than diarrhea or weight loss.Histopathologic findings are similar to multisystemic eosinophilic epithelio-tropic disease, except the pathology is restricted to the gastrointestinal tract[6–9]. Occasionally, eosinophils can be noted on cytologic evaluation of theperitoneal fluid [10]. Alimentary lymphosarcoma can affect horses of anyage. It may be a primary neoplastic disease or it can spread from a primaryfocus elsewhere in the body [11]. Recurrent colic and weight loss are the mostcommon clinical signs. Small and large intestine may be affected; in addition,mesenteric lymph nodes often are involved [11]. Lesions can vary from dis-crete focal tumor masses to diffuse intestinal infiltrates; histopathology ofthe gastrointestinal tract is the only way to make a definitive diagnosis.

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Treatment and outcome

Management of adult horses with infiltrative bowel disease typically isunsuccessful long term. A variety of treatments are reported, including ad-ministration of corticosteroids, anthelmintic drugs with larvicidal activity,vitamins, anabolic steroids, antibiotics, clioquinol (iodochlorohydroxy-quine), and sulfasalazine (salicylazosulfapyridine) (Table 1) [6–9]. Cortico-steroids are the drugs used most commonly to treat horses withinfiltrative bowel disease, because they are believed to reduce intestinal in-flammation [6–9]. A prolonged course often is required; thus, the horsemust be monitored closely for any adverse clinical signs, such as increasedsusceptibility to infection and laminitis. Parenteral administration is be-lieved a more effective route of administration because of the potential formalabsorption of drugs administered orally [6–9]. The dose often is taperedto effect. Metronidazole is an antibiotic and anti-inflammatory agent, whichis used in humans who have infiltrative bowel disease [8,9]. It is used to treathorses with infiltrative bowel disease, because it is an inexpensive drug withfew adverse effects, although its efficacy is unreported. In some cases of eo-sinophilic enteritis or multisystemic eosinophilic epitheliotropic disease, an-thelmintics with larvacidal activity are administered because the presence ofeosinophils in intestinal tissue often is attributed to parasitism [8,9]. Sulfasa-lazine, an antibacterial and anti-inflammatory drug, is used to treat humanswith Crohn’s disease, but is not proven to be useful in horses [8,9]. Althoughclioquinol’s mechanism of action is unknown, it sometimes is used in casesof chronic diarrhea. Some short-term response has been seen using antineo-plastic drugs, such as hydroxyurea [8]. Appropriate nutrition also is impor-tant in treating a horse with infiltrative intestinal disease. The most benefit isobtained from a highly digestible and well-balanced feed. Often, a smalleramount fed more frequently allows for better digestion and absorption. Inaddition, oral corn oil may provide extra fat and calories. High-quality fiberis easiest to digest. Free access to fresh water and electrolytes helps maintainhydration. In horses that are severely hypoproteinemic, a plasma transfu-sion may be beneficial. In cases of severe compromise and not eatingwell, intravenous (IV) dextrose (5% solution) or total parenteral nutritioncan be administered. Response to therapy is noted by improvement in lab-oratory work and resolution of clinical signs. The reports in the literatureindicate long-term survival is not possible [6–10].

Table 1

Typical therapies used in the management of infiltrative intestinal disease in horses

Drug Dose Route Frequency

Dexamethasone 0.02–0.2 mg/kg PO, IM, IV q 24 h

Prednisolone 0.2–4.4 mg/kg PO q 12–24 h

Metronidazole 15 mg/kg PO q 6–8 h

Clioquinol 10–20 g PO q 24 h

Sulfasalazine 15 mg/kg PO q 6 h

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Initial treatment of this horse included IV fluids, metronidazole tablets,and clioquinol. The IV fluids were administered because the horse initiallyseemed dehydrated. IV fluids were discontinued once it was believed thehorse was maintaining hydration by oral intake. Once the results of the rec-tal biopsy identified lymphocytic-plasmacytic enteritis, corticosteroids wereadded to the treatment. Corticosteroid treatment was continued for 8 weeks.Dexamethasone was administered daily (starting at a dose of 0.1 mg/kg IVdaily). This dose was tapered by 10 mg weekly until a dose of 10 mgwas reached; then the horse was maintained on the 10-mg dose. Throughoutthe 8-week treatment, the diarrhea improved for short periods of timeand then returned. There was minimal improvement in laboratory values(Table 2). The horse became anorexic, however, and continued to have ep-isodes of abdominal discomfort. Because of the minimal response to treat-ment and overall deterioration, the horse was euthanized humanely. Anecropsy was not performed.

Infiltrative intestinal disease carries a poor prognosis for life. Com-mon clinical signs include weight loss, chronic diarrhea, and chronic colic.Definitive diagnosis is based only on the results of an intestinal biopsy or,occasionally, rectal biopsy. Treatment includes dietary modification and ste-roids, with little success for a good outcome.

References

[1] Lindberg R, Nygren A, Persson SGB. Rectal biopsy diagnosis in horses with clinical signs of

intestinal disorders: a retrospective study of 116 cases. Equine Vet J 1996;28:275–84.

[2] Mair T. Chronic weight loss. In: Manual of equine gastroenterology. Philadelphia: WB Sa-

unders; 2002. p. 367–402.

[3] Mair T. Chronic diarrhea. In: Manual of equine gastroenterology. Philadelphia: WB Saun-

ders; 2002. p. 427–46.

[4] Frank N, Fishman CE, Genhart CJ, et al. Lawsonia intracellularis proliferative enteropathy

in a weanling foal. Equine Vet J 1998;30:549–52.

[5] Lavoie JP, ParsonsD, Drolet R. Proliferative enteropathy in foals: a cause of colic, diarrhea,

and protein-losing enteropathy. Proc Am Assoc Equine Pract 1998;44:134–5.

Table 2

Laboratory values obtained for the horse reported here with lymphocytic-plasmacytic infiltra-

tive bowel disease

Date Neutrophils (cell/mL) TP (g/dL) Albumin (g/L) Fibrinogen (mg/dL)

7/3/04 10,764 5.0 1.3 500

7/6/04 7584 5.6 1.5 500

7/9/04 d 4.5 1.6 d

7/15/04 11,154 6.4 2.0 500

7/22/04 12,636 5.6 2.5 d7/29/04 9940 5.2 2.5 d

8/10/04 9750 4.8 2.8 d

8/17/04 9792 5.0 2.6 d8/26/04 10,920 4.8 2.4 d

e7INFILTRATIVE INTESTINAL DISEASE

[6] Scott EA, Heidel JR, Synder SP, et al. Inflammatory bowel disease in horses: 11 cases (1988–

1998). J Am Vet Med Assoc 1999;214:1527–30.

[7] Roberts MC. Small intestinal malabsorption in horses (tutorial article). Equine Vet Educ

2000:269–74.

[8] Schumacher J, Edwards JF, Cohen ND. Chronic idiopathic inflammatory bowel disease of

the horse. J Vet Intern Med 2000;14:258–65.

[9] Schumacher J. Infiltrative bowel disease. In: Current therapy in equine med. 5. Philadelphia:

Saunders; 2003. p. 144–8.

[10] Southwood LL, Kawcak CE, Trotter GW, et al. Idiopathic focal eosinophilic enteritis asso-

ciated with small intestinal obstruction in 6 horses. Vet Surg 2000;29:415–9.

[11] Mari TS, HillyerMH. Clinical features of lymphosarcoma in the horse: 77 cases. Equine Vet

Educ 1991;4:108–13.