Dogs can display a variety of clinical manifestations associated with gastrointestinal (GI) distress that can be challenging to differentiate from an acute vs. chronic problem. Generally speaking, dogs exhibiting persistent or intermittent GI signs for more than three weeks are classified as having chronic enteropathy of unknown etiology or chronic inflammatory enteropathy (CIE).1 These GI signs can range in clinical severity and might include non-purposeful weight loss, vomiting, regurgitation, hard swallowing, pica, diarrhea (small bowel, large bowel, mixed), excessive flatulence, abdominal bloating, muscle wasting, hair thinning or poor hair coat, increased borborygmus, appetite changes (decreased or increased), lethargy, with or without increases in water intake and urination, or a combination of these signs.2 Understanding CIE CIE involves a heterogeneous group of intestinal etiopathogenesis arising from complex interactions among diet, the intestinal microbiota, genetic susceptibility, and altered mucosal immune responses. There are several phenotypes within the CIE spectrum that are classified according to the dog’s response to treatment (more about that in Part 2 of this article), although protein-losing enteropathy (PLE) and granulomatous colitis are distinct subtypes of CIE that display different pathophysiological mechanisms. As CIE is a diagnosis of exclusion, a thorough history and diagnostic evaluation are essential to accurate and complete treatment recommendations for that pet. Initial evaluation with a thorough history is imperative for a more concise differential diagnosis, as diagnostic recommendations can be tailored to the patient’s history, the client’s financial limitations, the severity of observed clinical signs, and secondary systemic consequences of fluid, electrolyte, blood, or protein loss. Accurate estimation of the dog's age, breed, reproductive status, current medications and supplements, and environmental/home status (indoor/outdoor) is an essential starting point. Dogs affected with chronic GI disease are generally middle-aged, although inflammation can start as young as puppies, particularly those that are dietary responsive (Figure 1). Figure 1. Veterinary technician (Cassie Padgett) obtaining vitals on a Boxer puppy with food-responsive enteropathy. Photo courtesy of Kasey Mabry Who’s got it bad? Below lists several breed predilections and their associated GI disease3-7: Yorkshire terrier: PLE, primary intestinal lymphangiectasia, lacteal and crypt dilation +/- crypt abscesses with variable degrees of lymphoplasmacytic +/- neutrophilic enteritis Border collie: PLE German shepherd: PLE, antibiotic-responsive enteropathy or small intestinal dysbiosis Rottweiler: PLE Soft-coated wheaten terrier: primary intestinal lymphangiectasia, lymphoplasmacytic enteritis +/- lymphangiectasia and transmural lymphangitis +/- concurrent protein-losing nephropathy Norwegian Lundehund: primary intestinal lymphangiectasia Basenji: immunoproliferative enteropathy +/- concurrent protein-losing nephropathy Chinese Shar-Pei: primary intestinal lymphangiectasia Maltese: primary intestinal lymphangiectasia Boxers: histiocytic ulcerative colitis Taking a closer look More specific questions regarding the aforementioned clinical signs can be explored, including when these symptoms began, their duration, which treatments have historically worked and which have not, and travel history [geographical infectious disease considerations]. An important management aspect of differentiating acute vs. chronic disease is a complete and accurate dietary history, including recent dietary indiscretion (change in diet, addition of new treats, table scraps, new oral preventative) and which dietary modifications have been adjusted, including treats, from the beginning of when the dog’s symptoms first began and their associated clinical response.2,8 Physical examination of the pet can provide important clues for discussing the chronicity of the dog’s gut health, the degree of urgency, the overall diagnostic and treatment approach, and referral considerations. Non-purposeful weight loss decreased muscle mass, and poor coat or skin health can indicate chronicity (Figure 2). However, acute-on-chronic manifestations of their GI disease can prompt immediate evaluation and stabilization. Obtaining vitals, mentation status, mucous membrane color, capillary refill time, pulse assessment, and an estimated hydration status can provide details regarding the dog’s clinical stability and whether inpatient versus outpatient therapy should be considered. Figure 2. Top view of a Yorkshire terrier with muscle wasting, weight loss, and ascites secondary to PLE. Photo courtesy of Kasey Mabry Determining if a patient may be experiencing overt or occult GI bleeding can also change initial recommendations and diagnostic prioritization.4,9 It is important to obtain a thorough medication history, as activated charcoal, metronidazole, bismuth (Pepto-Bismol), and diets high in iron (liver) can result in dark stools and should not be confused with melena.10 Dogs with malabsorptive GI disease can present with an unthrifty or poor hair coat and dermatologic changes, with or without weight loss and muscle wasting. Dogs with PLE can display abdominal distention with or without a palpable fluid wave due to peritoneal effusion, decreased lung sounds or heart sounds due to pleural effusion or pericardial effusion, peripheral edema, genital swelling, chemosis, weight loss, muscle wasting, increased respiratory effort or rate, thready, weak, or normal pulses.11 The canine inflammatory bowel disease activity index (CIBDAI) or Canine Chronic Enteropathy activity index (CCEAI) with the addition of albumin, presence of ascites and peripheral edema, and presence of pruritus can be used for initial and serial monitoring.12 Initial diagnostic evaluation should consist of a complete blood count, serum biochemistry panel, and urinalysis. A total T4 and TSH can be performed to rule out hypothyroidism, as approximately 45 percent of dogs with hypothyroidism have GI signs, most notably constipation and diarrhea.13 Additional testing may include a bile acids test, baseline cortisol +/- adrenocorticotrophic hormone (ACTH) stimulation test, and urine protein: creatinine (UPC) ratio, particularly when excess protein is seen on a urine dipstick with concurrent hypoalbuminemia. Clinical signs Clinical signs of GI disease can overlap considerably with those of pancreatic dysfunction and inflammation. As such, pancreatic markers (trypsin-like immunoreactivity [TLI]), and pancreatic lipase should be assessed in dogs displaying non-specific GI signs.8 Hypocobalaminemia can be noted in up to 61 percent of dogs with CIE, although a normal serum cobalamin level does not exclude CIE.14 If there is concern for intracellular cobalamin deficiency, particularly in dogs with a normal to low serum cobalamin concentration, then a serum methylmalonic acid concentration can be performed.15 Additionally, serum folate levels in dogs with CIE can be low, falsely normal, or elevated secondary to intestinal dysbiosis or hypocobalaminemia; therefore, serum folate levels are not specific for CIE in dogs.16 Hypomagnesemia and hypocalcemia with or without hypovitaminosis D can be detected in a subset of dogs with CIE (particularly PLE) and typically linked to negative outcomes; however, there are many dogs with normalization of their electrolyte status, including vitamin D, once their GI disease is better controlled.17 As hypercoagulability is a common complication of severe CIE and PLE affecting 63 to 100 percent of dogs with PLE, coagulation testing could also be considered in this cohort of dogs.8 Fecal flotation exam A fecal flotation exam and Giardia species antigen should be performed on all dogs with concurrent acute or chronic GI signs, and additional fecal and infectious disease testing (i.e., Histoplasma capsulatum, Heterobilharzia americana, Leishmania infantum, Neorickettsia helminthoeca) could be considered based on the dog’s outdoor prevalence, travel history, geographical origin, and preventative status.8 X-ray and ultrasound Thoracic radiographs, abdominal radiographs, and B-mode abdominal ultrasound should be considered in any dog with concurrent weight loss, peripheral or abdominal lymphadenopathy, severe acute chronic GI signs, or chronic GI signs not responsive to dietary adjustments. Chronic partial GI tract foreign bodies, abdominal lymphadenopathy, peritoneal effusion, or structural lesions may be seen on abdominal radiographs (Figure 3), although ultrasound can be considered if these differential diagnoses cannot be excluded from radiography alone.8 Abdominal ultrasound can further investigate the lining of the GI tract, as intestinal wall thickening, mucosal echogenicity changes, and small intestinal corrugation can be present.18 In dogs with PLE, the presence of hyperechoic mucosal striations has a 75 percent sensitivity and 96 percent specificity for identification of intestinal lymphangiectasia, although hyperechoic mucosal speckling is not as reliable in differentiating between chronic inflammatory disease categories (Figure 4).18,19 Figure 3. Radiographic right lateral view of a Yorkshire terrier with peritoneal effusion secondary to PLE. Photo courtesy of Kasey Mabry Figure 4. Ultrasonographic longitudinal axis view of a segment of small intestine of a dog diagnosed with histopathologically confirmed severe diffuse chronic lymphoplasmacytic and neutrophilic inflammation with lymphangiectasia. Note the thickened mucosal wall, perpendicular hyperechoic striations within the mucosal wall, and surrounding anechoic peritoneal effusion. Photo courtesy of Kasey Mabry Biopsy Dogs that have failed at least three accurately performed dietary trials with persistent or intermittent GI signs, or dogs with concurrent hypocobalaminemia or intestinal wall thickening, can proceed to biopsy consideration. The goal of the diagnostic tests is to exclude extra-GI causes for the dog’s clinical signs, as well as overt fungal or neoplastic processes. When appropriate, endoscopic biopsies via esophagogastroduodenoscopy, ileocolonoscopy, or surgical full-thickness biopsies can be considered. Endoscopic biopsies allow for sample collection of the stomach, duodenum, ileum, and colon with direct visualization of intraluminal abnormalities and adequate grading (Figures 5 and 6). Figure 5. Endoscopic visualization of the duodenum in a dog showing mild to moderate multifocal erythema with friability, granularity, and lymphangiectasia. Photo courtesy of Kasey Mabry Figure 6. Endoscopic visualization of the duodenum in a young dog showing moderate diffuse erythema, edema, and granularity with extreme friability, superficial erosive changes, and adherent pale-yellow fibrinous material. Photo courtesy of Anna Panyutin For lesions beyond the reach of endoscopy or with extra-GI abnormalities that may require biopsy or surgical intervention, surgery would be warranted, pending the degree of hypoalbuminemia. Routine histopathological evaluation with hematoxylin/eosin (H&E) stain is typically appropriate for most GI tract abnormalities, although additional testing in the form of immunohistochemistry (IHC), special stains (periodic acid-Schiff [PAS]), fluorescence in situ hybridization (FISH) or PARR should be considered.8,20 Follow-up endoscopy and histopathology are usually unnecessary for most dogs with CIE. However, dogs without initial clinical resolution or any new or worsening GI signs warrant re-evaluation of recent environmental, behavioral, co-morbidity, or management changes (e.g., diet, supplements, medications, preventatives, etc.). Repeat lab work, imaging, and biopsy with histopathology may be needed depending on clinical progression. Historical treatment that the pet is no longer receiving, or novel therapies can be discussed based on re-evaluation. Conventional and novel therapeutics for managing dogs with CIE will be discussed in next installment of this series. Kasey Mabry, DVM, MS, DACVIM (SAIM), is a small animal internal medicine specialist at South Carolina Veterinary Specialists and Emergency Care in Columbia, S.C. Dr. Mabry completed her small animal internal medicine residency and dual master’s degree in Comparative Biomedical Sciences at The University of Georgia. During this time, Mabry developed an interest in immune-mediated, gastrointestinal, and hepatobiliary diseases, with a strong research focus on canine acute gastrointestinal injury secondary to critical illness and exercise (canine athletes). She currently serves as the Internal Medicine Specialty director of Thrive Pet Healthcare, where she is actively involved in mentoring and teaching. References Dandrieux JR. Inflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same? J Small Anim Pract. Nov 2016;57(11):589-599. doi:10.1111/jsap.12588 Jergens A, et al. . Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987-1990). JAVMA. 1992;201(10):1603-1608. doi:Jergens, A., et al. Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987-1990). JAVMA, 1992. 201(10): p. 1603-1608. Craven MD, Washabau RJ. Comparative pathophysiology and management of protein-losing enteropathy. J Vet Intern Med. Mar 2019;33(2):383-402. doi:10.1111/jvim.15406 Simmerson SM, Armstrong PJ, Wunschmann A, Jessen CR, Crews LJ, Washabau RJ. Clinical features, intestinal histopathology, and outcome in protein-losing enteropathy in Yorkshire Terrier dogs. J Vet Intern Med. Mar-Apr 2014;28(2):331-7. doi:10.1111/jvim.12291 MP Littman DD, SL Vaden, U Giger. Familial protein-losing enteropathy and protein-losing nephropathy in soft coated wheaten terriers. J Vet Intern Med. 2000;14(1):68-80. doi:10.1892/0891-6640(2000)014<0068:fpleap>2.3.co;2 Jablonski S. Pathophysiology, diagnosis, and management of canine intestinal lymphangiectasia: a comparative review. Animals (Basel). 2022;12(20):2791. 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