May 2024
How to Treat Feline Chronic Enteropathy
By Adam J. Rudinsky, DVM, MS, DACVIM (Internal Medicine)
In this VETgirl online veterinary continuing education blog, Adam Rudinsky, DVM, MS, DACVIM (Internal Medicine) from the Department of Veterinary Clinical Sciences and the Comparative Hepatobiliary and Intestinal Research Program (CHIRP) at the College of Veterinary Medicine at the Ohio State University, reviews how to treat feline chronic enteropathy. If you’re about to see a cat with chronic vomiting and diarrhea, or that thin cat that just can’t gain weight back, you’ll want to tune in!
In clinical practice we encounter cats with chronic gastrointestinal signs commonly and need to identify the underlying etiology in each patient. One of the most common outcomes of this process is establishing a diagnosis of feline chronic enteropathy (CE). Chronic enteropathy is defined in a recent consensus statement (Marsilo S, et al.) as chronic (3 weeks or more) gastrointestinal signs with no attributable extraintestinal (GI), metabolic, or infectious cause. So that begs the question, how do we arrive at a diagnosis of chronic enteropathy? This simply means that a thorough evaluation of the patient was performed and differential diagnoses including infectious disease, parasitism, metabolic disease, endocrinopathies, etc… have been ruled out. The most traditional diagnostic approach, and in my opinion the easiest, is to remember and consider differentials both in the ‘GI’ category and the ‘non-GI’ category. In terms of prevalence, chronic enteropathy is typically the primary differential in the GI category. However, even though it is common, it is still a diagnosis of exclusion and requires extensive diagnostics and treatments to confidently arrive at this end point.
Diagnostically, I start this process with a CBC, biochemistry profile, urinalysis, fecal analysis, and thyroid level (cats over 6 years of age). If abnormalities are discovered, I then evaluate whether they could be resulting in the presenting clinical signs for that patient (e.g. undiagnosed hyperthyroidism). If they are a potential explanation, these are addressed prior to pursuing additional CE diagnostic evaluation. If no abnormalities are observed, the likelihood of diagnosing a non-GI cause of the symptoms is decreased. In general, the yield of all these initial diagnostics increases with age. However, this is not an absolute rule, and it is still advisable to recommend these tests if feasible for your client. If limited by owner constraints, I prioritize fecal floatation, endocrine testing, and biochemical panels in my patients due to the greater likelihood of being a high yield diagnostic or resulting in significant alterations to my treatment recommendations.
Depending on the signalment and presentation, my second tier of diagnostics are quite variable regarding what I recommend for each individual patient. For example, in younger cats with large bowel signs I will prioritize testing for Tritrichomonas foetus or cats with signs with weight loss and voluminous stool (suspicious for exocrine pancreatic insufficiency), a TLI. In summary, these are tests for specific disease processes which fit the patient presentation. As is the case with all diagnostics, these should be tailored to each individual patient.
At this point, the next diagnostic step for CE involves abdominal imaging (e.g. abdominal radiographs, abdominal ultrasound). Abdominal radiographs, although routinely available in practice are unlikely to be helpful in the diagnosis of a CE. Instead, their value is most closely tied to ruling out potential problems (e.g. obstructed foreign body, abdominal mass, etc.). Alternatively, in my ideal situation, an abdominal ultrasound would be performed by a boarded radiologist. Experience is extremely important regarding ultrasound imaging of the feline gut, pancreas, and liver, specifically, as it is highly susceptible to user interpretation. Like screening diagnostics, abdominal ultrasound yield increases with age. It’s also important to remember that, even with ultrasound, you are unable to arrive at a definitive diagnosis of CE. In many circumstances, CE will look completely normal or only have subtle changes in intestinal wall layer thickness. Ultrasound is much more sensitive at identifying mass lesions or other changes that would argue against a diagnosis of CE. If significant abnormalities are noted on ultrasound, it has the added benefit of aiding in targeted acquisition of cytologic samples.
The final laboratory diagnostics I consider are aimed directly at evaluating the GI tract by assaying serum cobalamin and folate levels. Cobalamin and folate are necessary for intestinal health and are often low in CE cats. Therefore, assessing for whether there is a deficiency and supplementing may impact your treatment outcomes. For owners that are willing, assessment of these vitamins should be performed in all cats with CE. However, if cost is a concern to an owner, it is reasonable and safe to empirically supplement cobalamin or folate during treatment.
Once other differentials have been ruled out, a diagnosis of CE is established and the most likely explanation for the CE is either chronic inflammatory enteropathy (CIE) or low-grade intestinal lymphoma (LGIL). Other primary gastrointestinal diseases (e.g. large cell lymphoma, eosinophilic sclerosing fibroplasia, etc…) are possible but occur at much lower population prevalence. Additional diagnostic evaluation, most often including intestinal biopsy, is required to differentiate these disorders as laboratory testing and imaging studies will be nonspecific. In this sense, intestinal biopsy allows the best chance at establishing a definitive diagnosis which affords the clinician, pet owner, and most importantly the feline patient prognostic information as well as treatment guidelines. However, even with biopsy of the intestinal tract some cases remain uncertain in diagnosis. This is most frequently seen when trying to make the distinction between CIE and LGIL. So what is the benefit of the biopsy? In truth, it should be noted that there is conflicting evidence on whether a biopsy is absolutely necessary in all cases as it may or may not change the prognosis or treatment for our common differentials CIE and LGIL. As stated before, the main benefits of biopsy include ruling out more severe disease (lymphoma), diagnosing diseases which require specific treatment, procuring a definitive diagnosis of intestinal inflammation prior to empirical therapy, and potentially diagnosing non-inflammatory chronic enteropathies (IBS). This is vital information, especially if response to treatment is not as anticipated.
After diagnostic evaluation, this means that we as clinicians are often treating cases either definitively or presumptively as CIE or LGIL. Signalment, clinical signs, diagnostic testing, abdominal imaging, and even biopsy present challenges in differentiating these disorders. However, luckily there is also significant overlap in terms of how CIE and LGIL are treated and the prognosis for the affected cat. Both CIE and LGIL are treated using nutritional management, modulating bacterial populations in the gut, pharmacologic therapy to decrease inflammation and cellular infiltrates, and environmental enrichment to decrease the role of stress.
In general, I commonly start with an empirical trial of a broad spectrum dewormer (e.g. fenbendazole). This will treat for many parasitic differentials which may be missed on fecal examination (e.g. Physaloptera). Otherwise in most cases the exact cause of CIE is unknown but likely involves at least 3 factors: the cat’s immune system, what is entering the GI tract (diet), and also who is living there (the microbiota). Conceptually, this is a very important idea as it forms the foundation for our core therapeutic approaches to this disease syndrome as well as LGIL.
On average approximately half of cats with CIE will respond to nutritional management alone (e.g., food-responsive enteropathy) emphasizing why there is so much focus on dietary selection in these cats. Response time to nutritional management can be impressively fast (one study reporting average response within 4-8 days) which is why most gastrointestinal diet trials are performed for two weeks. There is also evidence that nutritional management allows for less dependency on pharmacologic management in cats requiring multimodal management. As such, all CIE and LGIL patients should receive dietary recommendations. CIE dietary approach typically involves selection of either limited ingredient, hydrolyzed, easily digestible, or fiber enhanced diets. Low-fat diets have been shown to be less important in feline CIE. More specifically, studies have shown that limited ingredient, hydrolyzed, as well as easily digestible diets have utility for treating feline CIE with small bowel signs. Alternatively, if signs of large bowel disease predominate, there is limited evidence for easily digestible, limited ingredient, as well as fiber enhanced diets. In the studies documenting the large bowel outcomes, the most common diet type utilized was fiber enhanced which is why this is my preferred first line diet option in this situation. Returning cats to their original diet can result in relapse, therefore once again I recommend long-term use of the therapeutic diet.
True immunologic food allergy, which would require longer dietary trials of a minimum of 8 weeks, appear to occur much less commonly than other forms of food-responsive enteropathies. Food allergy cats often display a wide variety of clinical signs, however vomiting and small bowel diarrhea with concurrent dermatologic signs is common and increase my suspicion that this is the cause of the cat’s signs. If a food allergy is suspected, limited ingredient or hydrolyzed diets based on a complete diet history should be used to avoid potential previous exposure to allergens.
Once a patient has failed appropriate diet trials (i.e. food responsive enteropathy ruled out), the main differentials become microbiome responsive CIE, steroid responsive CIE, as well as LGIL. Newer evidence has documented gastrointestinal dysbiosis (relative changes in bacterial populations within the GI tract) in CIE and LGIL cats. Historically, a syndrome of chronic diarrhea responsive to antibiotic therapy was termed antibiotic CIE. However, recent understanding has refocused this away from antimicrobials and towards probiotics and fecal transplants (FMT) as more holistic methods of modulating the microbiome. Antibiotics are no longer recommended in CIE management. Data for probiotics and FMT are only preliminary in feline medicine, but this is an active area of research in veterinary medicine. In general, it is rare that cats will respond solely to probiotics. This is based on the lack of conclusive evidence that supports the use of probiotics for feline CIE. However, anecdotal success stories are reported in individual cases and limited research with the predominant probiotics show some promise. In my practice, I believe probiotics are best used as an adjunctive therapy alongside more traditional therapy. There is currently no data on which probiotic is best and in what circumstance. Furthermore, as probiotics are not held to strict manufacturing standards, I recommend veterinary products with quality assurance standards and evidence of efficacy. FMT are the cutting edge of microbiome modulation. Once again, evidence is emerging that this can be successful in managing some feline CIE patients. However, knowledge in this area is too early to make definitive recommendations of FMT implementation. We employ FMT in refractory CIE cases rather than as a first line therapy before traditional approaches.
The second largest group of responders belong in a category often referred to as immunomodulatory responsive CIE. This type of CE is presumed to be associated with an immune response leading to an inappropriate inflammatory response. As no underlying cause is identified in these cases, we utilize immunomodulating medications to stop the inflammation. Choosing an immunosuppressant is best done based on what is important to you as a clinician and what is important to the owner. Specifically, as a clinician, time to action (i.e. how quickly does the drug work), side effects for the patient, and lastly evidence-based medicine for each drug individually are important considerations. Commonly, owners care about the side effects for their pet as well as the cost of the medication. Therefore, there are some general rules for drug selection, however each drug plan must be tailored to your specific patient and client.
Glucocorticoids, which include prednisolone and budesonide, are the mainstay of immunomodulatory drugs due to their minimal expense and multi-factorial effects on suppressing the immune system. However, they have a predictable and extensive list of side effects. The majority of cats will be adequately controlled on monotherapy with glucocorticoids. However, the two biggest reasons for adding a secondary drug (see below) are to provide control in cases where monotherapy with a glucocorticoid is insufficient to provide disease symptom control or to reduce side effects associated with glucocorticoids.
Alkylating agents (chlorambucil and cyclophosphamide) are the most used anti-neoplastic drugs in veterinary gastroenterology and my second line choice for feline patients with CIE and LGIL. I lean toward chlorambucil using standard dosing. For cats which are resistant to oral medications, there are also every 2-week dosing programs which may improve client compliance and more importantly reduce patient stress. Cyclophosphamide is less commonly used and at our institution is reserved for refractory cases. The most common side effect that requires monitoring is bone marrow suppression and CBCs assist in monitoring during therapy. Other immunosuppressants including cyclosporine, mycophenolate, etc. can be used as well.
Finally, stress is an important factor in gastrointestinal health. Interestingly, in feline interstitial cystitis studies, the same environmental management and modification used to improve urinary signs also improved gastrointestinal signs in those cats. In addition, irritable bowel syndrome which can be influenced by patient stress and anxiety, is challenging to diagnose in veterinary medicine. Therefore, I choose to recommend environmental enrichment and modification to all feline CIE patients and have seen anecdotal success in my practice which may be related to stress or underlying irritable bowel syndrome. The specific recommendations are no different than those used for feline interstitial cystitis.
Image by Kim Newberg from Pixabay
Feline CE can be effectively managed with diet, microbial modification, immunosuppressants, environmental management and each approach offers potential advantages or disadvantages compared to other therapies. Considering all these factors will allow you to tailor an ideal program for each individual cat and their caretaker during treatment planning. In my hands, I estimate that I can achieve control in roughly 95% or more of my CIE and LGIL patients with these tools. For the remaining refractory cases, other experimental approaches and techniques can be used to attempt disease control.
Want to learn more? Check out this YouTube LIVE event from Dr. Rudinsky from May 9, 2024 HERE:
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Today’s VETgirl blog is sponsored by Royal Canin. Please note the opinions in this blog are the expressed opinion of the speaker(s)/sponsor, and not directly endorsed by VETgirl.
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