Describes disorders of the gastrointestinal tract characterized by chronic or recurrent gastrointestinal signs and histologic evidence of inflammation
Inflammatory cell type is variable; nomenclature is based on the predominant cell type present and the anatomic distribution
Lymphocytic-plasmacytic inflammation is most common
Currently, no single diagnostic test or biomarker can identify inflammatory bowel disease (IBD) or differentiate it from neoplasia
A diagnosis of is based on the following criteria:
Chronic (i.e., > 3 weeks in duration) gastrointestinal signs (e.g., anorexia, vomiting, weight loss, diarrhea, hematochezia, mucoid feces); these signs may wax and wane
Histopathologic evidence of mucosal inflammation
Diagnostic evaluation and failure to identify other causes of gastroenterocolitis
Inadequate response to appropriate therapeutic trials (i.e., dietary, antibacterial, antiparasitic)
Clinical response to anti-inflammatory or immunosuppressive agents
Cause is unknown; loss of immunologic tolerance to luminal antigens is thought to play a role
Treatment is aimed at correcting the underlying disease, if possible, decreasing inflammation, and ameliorating clinical signs
Prognosis is variable and often depends on disease severity and response to treatment
In cats, IBD may progress to small-cell intestinal lymphoma over time
Causes and Risk Factors
Causes
Loss of gastrointestinal mucosal immune tolerance, resulting in influx of inflammatory cells (e.g., lymphoplasmacytic infiltrate), cellular alterations (e.g., villous stunting and fusion) and corresponding clinical signs
Often considered idiopathic if an underlying cause is not identified
Secondary causes of inflammation in the small intestine may include:
Pathogenic bacteria (e.g., E coli, Salmonella, Campylobacter)
Histopathology is considered the most reliable diagnostic tool for IBD, but ambiguous results are possible
Can be collected via endoscopy, laparoscopy, or laparotomy (for full-thickness specimens); method chosen may depend on severity of disease as well as patient and client factors
If laparoscopy or surgery are pursued in cats with severe disease, consider obtaining liver and pancreatic biopsy samples as well, to look for concurrent cholangitis and pancreatitis (i.e., triaditis)
Because inflammatory (and neoplastic) lesions occur in the lamina propria, mucosal samples obtained via endoscopy are acceptable for histopathologic examination
Laparotomy facilitates the collection of samples from the jejunum
Variations in tissue processing, sample quality, and subjective interpretation between pathologists can make diagnosis difficult
Grading schemes and standardized criteria for diagnosis have been proposed but not widely adopted
Biopsies should be obtained prior to use of glucocorticoids or other immunosuppressive drugs
There is no correlation between histopathology and severity of clinical signs
There is no correlation between histopathology and response to therapy
Inflammatory cell type is variable; nomenclature is based on the predominant cell type present and the anatomic distribution
Lymphocytic-plasmacytic inflammation is most common; eosinophilic, granulomatous, or neutrophilic inflammation is also possible
It is sometimes difficult to distinguish chronic inflammation from emerging small cell lymphoma (canine, feline) particularly in cats; immunophenotyping, assessment of the Ki67 proliferation index, or clonality testing by polymerase chain reaction (PCR) should be considered in these cases
Immunohistochemistry: uses specific antibodies (linked to a fluorescent dye) to bind to antigens in tissue samples; antigen-antibody binding activates the dye, facilitating microscopic identification of the antigen
Clonality testing: can help differentiate IBD from neoplasia
With neoplasia, lymphocytes (and their subsequent daughter cells) tend to derive from a single precursor cell, or clone; in contrast, clonality for inflammatory lesions tends to be mixed/diverse
Imaging
Abdominal radiography
Mesenteric lymphadenopathy (in cats)
May reveal other problems or causes for clinical signs, such as organomegaly or intestinal obstruction
Abdominal ultrasongraphy
Useful in identifying intestinal wall abnormalities (e.g., mucosal and submucosal thickening, loss of wall layering), whether disease is focal or generalized, and to look for presence of concurrent issues, such as pancreatitis and lymphadenopathy
Can guide fine-needle aspiration of the intestinal wall, lymph nodes or abdominal organs
Normal ultrasound does not rule out the possibility of inflammatory bowel disease
Other Diagnostic Tests
Polymerase chain reaction (PCR) testing of fecal samples; PCR for antigen receptor rearrangement (PARR)
May be considered for patients with hemorrhagic diarrhea, pyrexia, or an inflammatory leukogram
Multiplex tests may screen for Clostridium perfringens enterotoxin, Cryptosporidium spp., giardiasis, salmonellosis, and Campylobacter spp.
Fluorescent In Situ Hybridization (FISH) assay of tissue samples
Recommended to identify bacterial pathogens in patients with histopathologic evidence of predominantly neutrophilic or granulomatous inflammation
Testing can often be performed on the same samples used to make the diagnosis; contact reference laboratory for more information
Cytological exam of rectal wall scraping
May reveal presence of Histoplasma, neutrophilia, or increased numbers of gram-positive rods suggestive of bacterial overgrowth
Serum folate and cobalamin concentrations
Hypocobalaminemia is common with small intestinal disease; may require supplementation
A Level 3 study found folate to be a poor marker for chronic enteropathy in dogs, and folate concentrations may be low, normal or elevated in cats with IBD
Other testing will depend on history and clinical signs; may include:
Sequential therapy is recommended, when possible, with trials of antiparasiticides, diet, antimicrobials, and immunosuppressive therapy, depending on response to treatment
Antiparasiticide and dietary therapy alone are recommended as initial therapy for patients with predominantly eosinophilic inflammation
If clinical signs and intestinal inflammation are severe, immunosuppressive treatment may be required early in therapy
For cats with severe triaditis, hospitalization for supportive care and nutritional support is recommended
Prednisone (Dogs) 2 to 4 mg/kg PO once daily, or divided and given twice daily
Prednisolone (Cats) 2 to 8 mg/kg PO once daily, or divided and given twice daily
Use for 10 to 14 days then taper over several weeks to lowest effective dose depending on clinical response
Most patients will require chronic prednisone/prednisolone to manage their disease
In cats, use prednisolone in place of prednisone when possible
Azathioprine 2 mg/kg PO once daily; use for 2 weeks, then taper to 2 mg/kg PO every other day for 2 to 4 weeks, then 1 mg/kg PO every other day
Use only in dogs
Therapy may be needed for 2 to 6 weeks before beneficial effects are noted
Consider adding azathioprine if no response to prednisone after 3 to 4 weeks
May cause bone marrow suppression
Owners should wear gloves when handling this medication and tablets should not be broken
Cyclosporine
Dogs: 5 mg/kg PO once daily, or divided and given twice daily
Cats: 5 to 7 mg/kg PO once daily, or 3 to 4 mg/kg PO every 12 hours
Can be used in addition to prednisone for dogs who are not responding to glucocorticoid therapy alone
Cyclosporine levels may be monitored if there is an inadequate response to therapy or cyclosporine-induced side effects are suspected (e.g., hepatoxicity); optimal therapeutic levels are unknown
Levels should be measured 1 to 2 hours post-pill
If level is > 700 ng/ml, decrease the dose by 50%
Chlorambucil
For cats: 2 mg per cat, PO every 48 hours for cats weighing > 4 kg; or 2 mg per cat, PO every 72 hours for cats weighing < 4 kg
When remission occurs, reduce dosing interval to every 3 to 4 days as needed to control the condition
Can be considered in combination with prednisolone for cats who are refractory to steroid therapy alone
A small case series (Level 3) found an association between chlorambucil therapy and acquired Fanconi syndrome in cats; cats should be monitored for the development of glucosuria
Budesonide 0.12 to 0.15 mg/kg PO every 8 to 12 hours; reduce dosing interval to once daily when condition improves
May be used in place of prednisone or prednisolone
Optimal dose has not yet been established
Originally thought to have limited systemic absorption; however, suppression of the hypothalamic-pituitary-adrenal axis and steroid hepatopathy may still occur with this drug
Other Therapies
Dietary intervention
There is no consensus of opinion on the optimal diet for therapy
In dogs, fat-restricted diets based on a novel protein source or hydrolyzed peptides can be beneficial
In a Level 3 (IND) study of dogs with chronic enteropathy that failed to improve on other therapies, 70% responded well to an elemental diet (e.g., protein in amino acid form, rather than polypeptide form)
In cats, hydrolyzed protein or novel protein diets have been recommended
Diets with increased fermentable fiber such as beet pulp, psyllium, and/or fructooligosaccharides (FOS) may be considered for patients with large-intestinal disease
Psyllium may be added to a highly digestible diet for pets with large bowel disease:
1 teaspoonful per 5 to 10 kg, added to each meal; OR
Dogs: 2 tablespoons per day Cats: 1 to 4 teaspoons per day
Start at ¼ to ½ of the dosage and gradually titrate upward to effect
Make sure the pet is adequately hydrated
Dogs with food-responsive diarrhea may see improvement in their clinical signs within 1 to 2 weeks with dietary therapy alone
There are limited clinical studies to support the use of probiotics; quality control issues with product formulations may be a concern
Cobalamine
Use for dogs or cats with hypocobalaminemia
Dogs: 25 µg/kg SC once per week, for 4 to 6 weeks; then, once per month for 3 months
For daily oral dosing:
Dogs weighing < 10 kg: 250 µg per dog, PO, daily
Dogs weighing 10 to 20 kg: 250 to 500 µg per dog, PO, daily
Cats: 250 µg per cat SC once weekly for 6 weeks, then once every 1 to 2 months, based on blood levels
For daily oral dosing: 250 µg per cat, PO once daily for 12 weeks
A Level 2 study found that oral cobalamin supplementation in dogs was equally as effective as parenteral supplementation
Follow-up
Tapering or discontinuation of medications will depend on clinical response to therapy and treatment of underlying disease, if identified; some patients will require life-long management with medications and/or diet
Prognosis
Depends on response to therapy and disease severity
Hypoalbuminemia has been associated with a poor prognosis
Dogs with an elevated pancreatic lipase immunoreactivity concentration have been shown to have a poor response to steroid therapy
Older pets with severe disease may have a poor prognosis
In cats, IBD may progress to small-cell intestinal lymphoma over time
Prognosis for cats with triaditis is variable, literature suggests that cats with 2 or more component manifestations may have a worse prognosis
Evidence
Guidelines and Consensus Statements
Marsilio S, Freiche V, Johnson E, et al. ACVIM consensus statement guidelines on diagnosing and distinguishing low-grade neoplastic from inflammatory lymphocytic chronic enteropathies in cats. J Vet Intern Med. 2023 May-Jun;37(3):794-816. Level B (IND) Article
Washabau RJ, Day MJ, Willard MD, et al. Endoscopic, biopsy, and histopathologic guidelines for the evaluation of gastrointestinal inflammation in companion animals. J Vet Intern Med. 2010 Jan-Feb;24(1):10-26. Level B (IND) Article
Systematic Reviews/Meta-analyses
Jergens AE, Sonea IM, O’Connor AM, et al. Intestinal cytokine mRNA expression in canine inflammatory bowel disease: a meta-analysis with critical appraisal. Comp Med. 2009 Apr;59(2):153-62. Level 2Article
Randomized, Controlled Trials (RCTs)
Simpson KW, Miller ML, Loftus JP, et al. Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy. J Vet Intern Med. 2023 Nov-Dec;37(6):2334-43. Level 2 (IND) Article
Dye TL, Diehl KJ, Wheeler SL, et al. Randomized, controlled trial of budesonide and prednisone for the treatment of idiopathic inflammatory bowel disease in dogs. J Vet Intern Med. 2013 Nov-Dec;27(6):1385-91. Level 2Abstract
Other Studies or Reviews
Dor C, Nixon S, Salavati Schmitz S, et al. Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial. J Small Anim Pract. 2024 May;65(5):317-28. Level 2 (IND) Article
Collier AJ, Gomez DE, Monteith G, et al. Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study. PLoS One. 2022 Oct 18;17(10):e0276295. Level 2Article
Suchodolski JS, Xenoulis PG, Paddock CG, et al. Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease. Vet Microbiol. 2010 May 19;142(3-4):394-400. Level 2Abstract
Jergens AE, Schreiner CA, Frank DE, et al. A scoring index for disease activity in canine inflammatory bowel disease. J Vet Intern Med. 2003 May-Jun;17(3):291-7. Level 2Abstract
Ing NH, Steiner JM. The use of diets in the diagnosis and treatment of common gastrointestinal diseases in dogs and cats. Adv Exp Med Biol. 2024;1446:39-53. Level 3
Manchester AC, Dow S, Chow L, et al. Efficacy of an elemental diet in achieving clinical remission in dogs with chronic enteropathy. J Vet Intern Med. 2023 Nov-Dec;37(6):2322-33. Level 3 (IND)
Karra DA, Chadwick CC, Stavroulaki EM, et al. Fecal acute phase proteins in cats with chronic enteropathies. J Vet Intern Med. 2023 Sep-Oct;37(5):1750-9. Level 3
Riehm MD, Mayhue EJ, Jugan MC. Plasma glucagon-like peptide-2 concentrations are lower in dogs with chronic enteropathies than in healthy dogs. Am J Vet Res. 2023 Sep 5;84(11):ajvr.23.06.0149. Level 3
Collins-Webb AG, Chong D, Cooley SD. Ultrasonographic intestinal muscularis thickening in dogs with histologically confirmed inflammatory bowel disease: 13 cases (2010-2021). Vet Radiol Ultrasound. 2023 Mar;64(2):345-50. Level 3
Langlois DK, Pritchard JC, Tolbert MK, et al. Clinical utility of an immunoglobulin A-based serological panel for the diagnosis of chronic enteropathy in dogs. J Vet Intern Med. 2023 Mar;37(2):446-54. Level 3
Ullal TV, Marks SL, Huebner SN, et al. Association of folate concentrations with clinical signs and laboratory markers of chronic enteropathy in dogs. J Vet Intern Med. 2023 Mar;37(2):455-64. Level 3
Papich MG. Papich Handbook of Veterinary Drugs, 5th Edition. St Louis, MO: Elsevier; 2021. Level 3
Kathrani A. Dietary and nutritional approaches to the management of chronic enteropathy in dogs and cats. Vet Clin North Am Small Anim Pract. 2021 Jan;51(1):123-36. Level 3
Marsilio S. Differentiating inflammatory bowel disease from alimentary lymphoma in cats: Does it matter? Vet Clin North Am Small Anim Pract. 2021 Jan;51(1):93-109. Level 3
Estruch JJ, Barken D, Bennett N, et al. Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease. J Vet Intern Med. 2020 May;34(3):1177-86. Level 3
Tørnqvist-Johnsen C, Campbell S, Gow A, et al. Investigation of the efficacy of a dietetic food in the management of chronic enteropathies in dogs. Vet Rec. 2019 Oct 29. pii: vetrec-2018-105172. doi: 10.1136/vr.105172. [Epub ahead of print]. Level 3 (IND)
Salavati Schmitz S, Gow A, Bommer N, et al. Diagnostic features, treatment, and outcome of dogs with inflammatory protein-losing enteropathy. J Vet Intern Med. 2019 Sep;33(5):2005-13. Level 3
Hall EJ. Diseases of the large intestine. In: Ettinger SJ, Feldman EC, Cote E, ed's. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. 8th ed. St. Louis: Elsevier;2017:1565-92. Level 3
Hall EJ, Day MJ. Diseases of the small intestine. In: Ettinger SJ, Feldman EC, Cote E, ed's. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. 8th ed. St. Louis: Elsevier;2017:1516-64. Level 3
Reinert NC, Feldman DG. Acquired Fanconi syndrome in four cats treated with chlorambucil. J Feline Med Surg. 2016 Dec;18(12):1034-40. Level 3
Sabattini S, Bottero E, Turba ME, et al. Differentiating feline inflammatory bowel disease from alimentary lymphoma in duodenal endoscopic biopsies. J Small Anim Pract. 2016 Aug;57(8):396-401. Level 3
Fragkou FC, Adamama-Moraitou KK, Poutahidis T, et al. Prevalence and clinicopathological features of triaditis in a prospective case series of symptomatic and asymptomatic cats. J Vet Intern Med. 2016 Jul;30(4):1031-45. Level 3
Maunder CL, Reynold ZF, Peacock L, et al. Campylobacter species and neutrophilic inflammatory bowel disease in cats. J Vet Intern Med. 2016 Jul;30(4):996-1001. Level 3
Carrasco V, Rodriguez-Bertos A, Rodriguez-Franco F, et al. Distinguishing intestinal lymphoma from inflammatory bowel disease in canine duodenal endoscopic biopsy samples. Vet Pathol. 2015 Jul;52(4):668-75. Level 3
Nakashima K, Hiyoshi S, Ohno K, et al. Prognostic factors in dogs with protein-losing enteropathy. Vet J. 2015 Jul;205(1):28-32. Level 3
Allenspach K, Kathrani A. Inflammatory bowel disease. In: Bonagura JD, Twedt D, ed’s. Kirk’s Current Veterinary Therapy XV. Philadelphia: Elsevier Saunders;2014:536-40. Level 3
Jergens AE. Current veterinary therapy: Antibiotic responsive enteropathy. In: Bonagura JD, Twedt D, ed’s. Kirk’s Current Veterinary Therapy XV. Philadelphia: Elsevier Saunders;2014:518-22. Level 3
Procoli F, Motsküla PF, Keyte SV, et al. Comparison of histopathologic findings in duodenal and ileal endoscopic biopsies in dogs with chronic small intestinal enteropathies. J Vet Intern Med. 2013 Mar-Apr;27(2):268-74. Level 3
Casamian-Sorrosal D, Willard MD, Murray JK, et al. Comparison of histopathologic findings in biopsies from the duodenum and ileum of dogs with enteropathy. J Vet Intern Med. 2010 Jan-Feb;24(1):80-3. Level 3
Willard MD, Moore GE, Denton BD, et al. Effect of tissue processing on assessment of endoscopic intestinal biopsies in dogs and cats. J Vet Intern Med. 2010 Jan-Feb;24(1):84-9. Level 3
Day MJ, Bilzer T, Mansell J, et al. Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group. J Comp Pathol. 2008 Feb-Apr;138 Suppl 1:S1-43. Level 3
Allenspach K, Wieland B, Grone A, et al. Chronic enteropathies in dogs: evaluation of risk factors for negative outcome. J Vet Intern Med. 2007 Jul-Aug;21(4):700-8. Level 3
Craven M, Simpson, JW, Ridyard AE, et al. Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995-2002). J Small Anim Pract. 2004 Jul;45(7):336-42. Level 3
Additional Reading
Agulla B, Villaescusa A, Sainz Á, et al. Peripheral and intestinal T lymphocyte subsets in dogs with chronic inflammatory enteropathy. J Vet Intern Med. 2024 May-Jun;38(3):1437-48.
Teshima T. Heterogeneity of mesenchymal stem cells as a limiting factor in their clinical application to inflammatory bowel disease in dogs and cats. Vet J. 2024 Apr;304:106090. doi: 10.1016/j.tvjl.2024.106090.
Maggiar A, Andréjak-Bénit J, Miclard J, et al. Intestinal full-thickness needle-core biopsy via laparotomy is safe, rapid, and effective and less invasive than standard incisional biopsy in dogs and cats. J Am Vet Med Assoc. 2023 Dec 8;262(4):1-7.
Irving JR, Hiron TK, Davison LJ, et al. Characterization of canine intestinal microRNA expression in inflammatory bowel disease and T-cell lymphoma. J Comp Pathol. 2023 Jul;204:23-9.
Yu J, Boland L, Catt M, et al. Serum proteome profiles in cats with chronic enteropathies. J Vet Intern Med. 2023 Jul-Aug;37(4):1358-67.
Yu J, Ruaux C, Griebsch C, et al. Serum proteome of dogs with chronic enteropathy. J Vet Intern Med. 2023 May-Jun;37(3):925-35.
Linta N, Pey P, Baron Toaldo M, et al. Contrast-enhanced ultrasonography in dogs with inflammatory bowel disease. J Vet Intern Med. 2021 Sep;35(5):2167-76.
Niina A, Kibe R, Suzuki R, et al. Improvement in clinical symptoms and fecal microbiome after fecal microbiota transplantation in a dog with inflammatory bowel disease. Vet Med (Auckl). 2019 Dec 2;10:197-201.
Dias IE, Pinto PO, Barros LC, et al. Mesenchymal stem cells therapy in companion animals: useful for immune-mediated diseases? BMC Vet Res. 2019 Oct 22;15(1):358.
Segarra S, Martinez-Subiela S, Cerdà-Cuéllar M, et al. Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial. BMC Vet Res. 2016 Mar 10;12:49.
Toresson L, Steiner JM, Suchodolski JS, et al. Oral cobalamin supplementation in dogs with chronic enteropathies and hypocobalaminemia. J Vet Intern Med. 2016 Jan;30(1):101-7.
Rossi G, Pengo G, Caldin M, et al. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease. PLoS One. 2014 Apr 10;9(4):e94699.
Walker D, Knuchel-Takano A, McCutchan A, et al. A comprehensive pathological survey of duodenal biopsies from dogs with diet-responsive chronic enteropathy. J Vet Intern Med. 2013 Jul-Aug;27(4):862-74.