Canine Chronic Enteropathy: serological markers to guide diagnosis and treatment success
Canine chronic enteropathy (CE), also known as inflammatory bowel disease (IBD), is a chronic, relapsing, inflammatory intestinal disease caused by abnormal interactions with the immune system, the gastrointestinal (GI) microbiome, dietary and/or environmental factors. It’s a complex disease: diagnosing and identifying its underlying cause can be a lengthy process that’s both expensive and frustrating for clinicians and pet owners alike. All the while, patient suffering continues.
Rapid access to effective treatment for CE/IBD is the goal. It’s also essential as the disease can have a serious impact on a dog’s health and overall well-being. An affected dog generally experiences vomiting and/or diarrhea, poor appetite, weight loss, flatulence and abdominal discomfort for approximately at least 3 weeks before CE/IBD can be ruled in with certainty, though many practitioners may begin to suspect the condition earlier based on clinical experience. By then, a dog’s intestines are often inflamed, resulting from an increase in the inflammatory cell population in the intestinal mucosa. An altered GI microbiome (dysbiosis) may also exist. When CE/IBD interferes with digestion and nutrient absorption, a dog’s nutritional status could become compromised: anorexia can also occur. Early access to effective treatment is essential but often delayed due to the inherent challenges associated with diagnosis.
A diagnosis of exclusion
Historically, CE/IBD has been a diagnosis of exclusion that required significant resources: new approaches have long been desired. The traditional diagnostic path involved expensive testing to rule out all other primary gastrointestinal diseases (infectious, neoplastic and surgical conditions) as well as extra-gastrointestinal diseases such as liver disease or hypoadrenocorticism. The diagnostic work up, also extensive, includes the following: a minimum database (complete blood count, biochemical profile, complete urinalysis), fecal examination (O and P, giardia antigen testing, +/- fecal PCR analysis), baseline cortisol/ACTH stimulation test, GI panel (TLI, cobalamin, folate), abdominal imaging/ultrasonography (+/- cytology and/or histopathology). Confirmatory diagnosis is achieved only by endoscopic or surgically obtained intestinal biopsies and histopathology consistent with the disease.
Human medicine as a model for veterinary medicine
The ability to identify CE/IBD earlier—or rule it out—would hasten the path to effective treatment and avoid the long-term negative impact on a dog’s health and pet owner well-being. In human medicine, the use of serological markers to aid in the diagnosis of ulcerative colitis and/or Crohn’s disease, two of the main types of IBD in people, is well established: Human gastroenterologists use non-specific markers for inflammation and more specific serologic markers for IBD with excellent success, which inspired the investigation in canine medicine. A recent study evaluated novel serologic markers to diagnose CE/IBD in dogs with gastrointestinal disease. In the manuscript, “Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease,” researchers demonstrated the value of three combined markers to rule in/rule out CE/IBD. These findings informed the development of a novel assay that quantifies the presence of serum antibodies against 3 specific targets (Anti-OmpC Porin IgA (ACA), Anti-Calprotectin IgA (ACNA) and Anti-Gliadin IgA (AGA). All three markers have been validated in canine clinical IBD trials (manuscript pending).
The use of biomarkers in diagnosing CE/IBD
All three combined markers together had increased sensitivity (84%) and specificity (96%). This is a robust assay and good at ruling in CE/IBD and very good at ruling out CE/IBD. The single most important marker to aid in a diagnosis of consistent with CE/IBD is antibodies to ACA. The presence of ACA antibodies has a sensitivity and specificity of 91% and 89%, respectively, for the diagnosis of CE/IBD. In the absence of or very low ACA antibodies, the diagnosis is not consistent with CE/IBD. Further diagnostic testing and imaging are recommended to investigate underlying cause of chronic gastrointestinal signs.
In the presence of high levels of ACA antibodies, the patient has signs consistent with CE/IBD and while the results support a diagnosis of IBD/chronic enteropathy, other causes of mucosal barrier disruption such as infectious disease, ulcers and neoplasia can cause elevation in these markers, additional diagnostics such as imaging and endoscopic biopsy should be considered. It is also recommended to recheck all the biomarkers in two to four weeks after medical therapy and/or dietary change.
When ACA antibody levels are intermediate, the combination of AGA and ACNA results help to confirm or exclude a diagnosis that is consistent with CE/IBD. The presence of ACNA antibody has been associated with gut inflammation. Antibodies to AGA may suggest a food sensitization is possible. It is recommended to consider an elimination dietary trial, including treats, with a diet formulated with novel or hydrolyzed proteins (excluding gliadin-containing ingredients such as wheat, rye, corn, barley, oats, quinoa, millet, couscous, spelt and bulgur) It is also worth noting that gliadin-free diets are not the same as grain-free diets in veterinary medicine. Gliadin diets are diets that have consistency of product and ingredient sourcing and are more likely to be therapeutic diets. Diets specifically formulated for elimination trials are recommended because they provide a consistent product with increased quality.
A fast, easy way to rule in/rule out CE/IBD earlier
Antech’s Canine CE-IBD assay is a non-invasive test that measures ACA, AGA and ACNA biomarkers to determine if a dog’s symptoms are “consistent with CE/IBD” or “not consistent with CE/IBD.” The assay offers rapid turn-around time, offering a fast, affordable way to accelerate the time to additional diagnostic testing and effective treatment for a dog that’s been suffering. While the assay is not a screening test, clinicians can use the biomarker readings to ascertain whether inflammatory disease is present, reinforce the need for further diagnostic procedures, develop more personalized treatment plans and even monitor a dog’s response to therapy. The assay is a first in veterinary medicine and facilitates a higher level of care for dogs with GI symptoms, supporting a more rapid return to health.
“One of the most frustrating experiences for a veterinarian is being unable to relieve symptoms which are chronic, recurrent and cause distress to the animal,” said Kelly Cairns DVM, MS, DACVIM, director of specialty and emergency medicine and national director of internal medicine at Pathway Vet Alliance. “A dog with chronic vomiting and diarrhea can be quite ill and may have underlying nutritional deficiencies; additionally, these symptoms can be quality of life limiting for both the dog and the pet parents. With the Antech Canine CE-IBD assay, we can now help and help quickly. Knowing if a dog’s symptoms are consistent with IBD, and the potential underlying cause, has allowed us to get the right treatment to a dog faster, making the new test an incredibly welcome addition to our hospitals’ strong arsenal of innovative diagnostics.”
The novel assay exclusively from Antech offers a rapid, non-invasive way to rule in or rule out CE/IBD. It requires a small (50uL) serum sample, which is evaluated for specific IgA antibody levels against targets found in canine IBD. IgA is highly stable, making it ideal for sampling and collection with limited interference issues. As a result, no specific sample handling is necessary. As antibiotics and corticosteroids can affect the results, these drugs should be withdrawn for a minimum of 5-7 days given that IgA levels can remain high 3 to 5 days after withdrawal of therapy.
Beyond diagnosis: identifying cause and monitoring treatment success
Beyond its ability to rule in or rule out CE/IBD early, the new assay provides data that allows veterinarians to deliver effective treatment faster by allowing them to identify possible causes of a dog’s gastrointestinal clinical signs and monitor a dog’s response to therapy. Causes of CE/IBD can range from diet or immune system issues to problems in the microbiome. Chronic enteropathies are characterized clinically based on the patient’s response to treatment as food responsive (FRE), antibiotic responsive (ARE) and immunosuppressant responsive (IRE). Therefore, treatment could include dietary manipulation, gastrointestinal microbiome manipulation or immunosuppressive use. Veterinarians can use biomarker levels to recommend and explain additional diagnostic recommendations (e.g., diagnostic imaging, GI endoscopy for biopsies) to pet owners to further define their pet’s disease. Biomarker information also allows them to create personalized treatment plans that address possible causes. The ability to monitor serial biomarker levels over time permits the use of data to evaluate treatment effectiveness, making adjustments as needed. If serology results show CE/IBD is not the cause of a dog’s symptoms, veterinarians can use data to reinforce the need for additional diagnostic recommendations to identify the correct issue.
“Veterinarians have long needed a simpler way to help rule in or rule out IBD as a differential diagnosis for dogs presenting with chronic vomiting and/or diarrhea,” said Todd Tams, DVM, DACVIM, chief medical officer for external affairs for Mars Veterinary Health and author of several books on veterinary gastroenterology and endoscopy. “Biomarkers give us incredibly valuable, objective data that we can use to support a diagnosis that is consistent with IBD early and with confidence, further localize the cause, provide recommendations for more invasive diagnostics if needed, develop individualized treatment plans and potentially monitor how well a dog responds over time. The opportunity to care for dogs with this level of confidence and ability through earlier and more accurate detection significantly elevates the level of care we can provide our canine patients presenting with common GI symptoms.”
Chronic vomiting and diarrhea are two of the most common reasons dog owners visit the veterinarian. While common clinical signs of IBD, they are also associated with a wide range of gastrointestinal disorders. With the rapid turnaround time of Antech’s new test, veterinarians can now identify the appropriate treatment for both IBD and non-IBD dogs, using data to explain why a treatment path or additional diagnostic procedures are needed and monitor a dog’s response to therapy over time.
“Diagnosing IBD and identifying the underlying cause used to be a lengthy, expensive process that was incredibly frustrating for both clinicians and pet owners,” said Jennifer Ogeer, BSc., DVM, MSc., MBA, MA, Vice President Medical Affairs at Antech Diagnostics. “The opportunity to rule in or rule out IBD early, identify possible causes and use evidence-based medicine to help pet owners understand care recommendations—all quickly and cost-effectively—allow us to treat a dog who is suffering faster. We can inspire confidence in a worried pet owner and gain ongoing commitment to our care recommendations, ultimately supporting a dog’s rapid return to health.”
For additional reading:
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; 34:1177–1186. https://doi.org/10.1111/jvim.15761