Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), depending upon how you define it, is not the most common cause of chronic small or large bowel diarrhea in dogs and may not be as common in cats as was once believed. In this discussion, we will define IBD as "idiopathic inflammation of the intestines." This means that you cannot diagnose IBD just by histopathology. You diagnose IBD by finding intestinal inflammation and showing that it is idiopathic by eliminating diet, parasites, bacteria and fungal agents as the cause. You cannot eliminate dietary causes and bacterial causes by histopathology or blood tests; therapeutic trials are necessary. This is very important because diagnosing IBD generally results in antiinflammatory or immunosuppressive drugs being used. However, if the patient has dietary-responsive or antibiotic-responsive disease, then these drugs are generally unnecessary. I stress this point because many patients have been erroneously diagnosed, improperly treated, and significantly harmed because IBD is a "fashionable" or "trendy" diagnosis. IBD is a real syndrome and is important for the veterinary practitioner to understand. However, it often degenerates into an excuse of convenience rather than a real diagnosis. More and more evidence is accumulating that shows that bacteria are probably a major source of the inflammation in dogs and cats with this disease. See below, under Antibiotic-Responsive Enteropathy.

Antibiotic-Responsive Enteropathy

Antibiotic-responsive enteropathy (ARE) seems to be a relatively common problem in dogs. It can best be described as a syndrome in which there are substantial numbers of bacteria in the upper small intestines and the host responds to them in such a manner as to cause intestinal dysfunction. These bacteria are not usually obligate pathogens. These bacteria are probably commensals or they may represent contamination from ingested material which is not eliminated by normal host defense mechanisms. The signs they produce, if any, seemingly depend upon at least two factors: a) which bacteria are present and b) how the host responds to them. The relationship of ARE to IBD is unclear, but it seems very possible that bacteria could be responsible for either initiating and/or perpetuating the intestinal inflammation we call IBD. The term "dysbiosis" has been suggested as the bridge between ARE and IBD.

Antibiotic-responsive enteropathy is hard to definitively diagnose with laboratory tests. Histopathology and cytology of the intestinal mucosa are extremely insensitive at detecting ARE. Measuring serum cobalamin and folate concentrations is relatively insensitive and nonspecific for detecting ARE. There are many dogs with chronic GI disease that respond to antibiotic administration but which have normal cobalamin and/or normal folate concentrations. It would seem that treatment for ARE is justified regardless of whether the serum cobalamin and folate concentrations are normal or abnormal, leading one to ask whether there is any benefit to measuring them to diagnose this disorder. Finding hypocobalaminemia or low serum folate levels is beneficial when looking for otherwise occult gastrointestinal disease. Supplementing cobalamin can clearly make cats feel better and diarrhea diminish. In fact, it is almost getting to the point where it is never wrong to give any sick cat cobalamin injections, regardless of blood values of the vitamin. Severe hypocobalaminemia has been suggested to be a poor prognostic signs. While the value of supplementing cobalamin to cats is clear (in fact, it is almost never wrong to give any sick cat supplemental cobalamin), the clinical value of administering cobalamin to dogs with low serum cobalamin concentrations is very uncertain.

Because of the apparent difficulty in diagnosing ARE with lab tests, empirical antibiotic therapy is often chosen as a means to diagnosis instead of laboratory tests. The obvious drawbacks to this approach are a) clinical "response" of the patient to the administered antibiotics may be due to the antibiotics or may be due to something else, b) if the patient did not respond to the antibiotic, it may be that you used the wrong antibiotics, and c) even if the patient does have ARE, there may be yet another disease present (e.g., a tumor causing a partial intestinal obstruction) which predisposed the patient to the ARE.

Because any bacteria can be present in the upper small intestine, the species of bacteria in the upper small intestine may change from week to week, and we seldom know which bacteria we are treating, broad spectrum antibiotics designed to lessen bacterial numbers seem to be indicated. You can never sterilize the GI tract. However, because clinical signs are due to a combination of large numbers plus an altered host response, simply lessening the numbers of bacteria often seems beneficial. Oral aminoglycosides were generally considered a poor choice to treat ARE because anaerobic bacteria (which have been suggested to be more of a problem) are resistant to aminoglycosides. However, this opinion is not clearly correct as there are occasional patients that clearly improve when given amikacin orally. Tetracycline is often effective; but, giving tetracycline is inconvenient. Tetracycline must be administered alone (i.e., without any food) and yet be washed down with water to ensure that the capsule to tablet does not stick in the esophagus and cause esophagitis. Tylosin powder has also been useful and is revered by many clinicians. Some clinicians like metronidazole; however, I have not been impressed with the efficacy of metronidazole for ARE. Metronidazole seems to have real benefit in many GI disorders, probably because it is so effective in eliminating many anaerobic bacteria. For patients that are extremely ill in which we need to know right now whether or not it will respond to antibiotics (i.e., that patient is so ill that you cannot take a chance of being 2–3 weeks from now and not having a response to therapy), I use a combination of enrofloxacin and metronidazole. I did not say that I used this combination for long periods of time. I use this combination when I absolutely must know whether or not I will have a clinical response within the next 2–3 weeks or take a chance on losing the patient.

Regardless of which drug is used, such a therapeutic trial should be performed for at least 2–3 weeks before a decision is made as to its efficacy. Remember, you must not only suppress the numbers of bacteria, but you must also allow the intestinal mucosa time to heal. Finally, it appears that concurrently feeding a high quality elimination diet can substantially enhance the efficacy of the antibiotic therapy. Therefore, we now routinely use both in our therapeutic trials.

If the patient appears to respond to this therapeutic trial of elimination diet and antibiotics, then it appears best to continue everything unchanged for an additional 2–4 weeks to be sure that the patient responded to this therapy (as opposed to the patient having some fortuitous, transient response to who-knows-what). If the patient is still doing well at that time, then you either a) stop the antibiotics and see if they diet alone is sufficient to control signs or b) slowly wean the antibiotics to their lowest effective dose (e.g., once a day or even once every other day). It all depends upon how frequently the clinical signs occur.

If the signs occur once every 2 + months, then it obviously makes sense to only treat when the patient is symptomatic. If the signs consistently recur within a few days of stopping the antibiotics, then you are probably stuck with treating almost constantly. This latter situation is one of the two times in veterinary medicine that I am aware of in which it is reasonable to look for the lowest effective dose of an antibiotic. Some patients only need antibiotic administration every 2 to 3 days in order to maintain control. In some cases, the patient will breakthrough and re-develop clinical signs after several weeks or months, and a different antibiotic must be used. If the decision is made to stop administering the antibiotics, then the owners should be warned that it is possible that the signs are likely to recur at some point. For ARE to occur, there is probably some defect in host defense mechanisms that allowed the commensal bacteria to cause the clinical signs, and this defect is unlikely to disappear. The question is how severe is the defect (i.e., is the dog likely to have problems continually or only once in a while)? You should warn the clients that they are likely to have to deal with this problem repeatedly and you need to explain the difference between "cure" and "control."

It may be a good idea to routinely treat all dogs with chronic small intestinal disease for ARE, even if you have histologic evidence of IBD or other disease. I will treat for ARE almost every time I diagnose a dog with a malabsorptive disease since there is no test for ARE that is reliable in ruling this disorder out, including cobalamin and folate determinations.

References

1.  Dandrieux JRS, Noble PJM, Scase TJ, et al. Comparison of a chlorambucil-prednisolone combination with an azathioprine-prednisolone combination for treatment of chronic enteropathy with concurrent protein-losing enteropathy in dogs: 27 cases (2007–2010). J Am Vet Med Assoc. 2013;242:1705–1714.

2.  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;27:1385–1391.

3.  Igarashi H, Maeda S, Ohno K, et al. Effect of oral administration of metronidazole or prednisolone on fecal microbiota in dogs. Plos One. 2014;9(9):e107909.

4.  Marks SL. Diarrhea. In: Washabau RJ, Day MJ, eds. Canine and Feline Gastroenterology. St. Louis, MO: Elsevier; 2013:99–108.

5.  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;9(4):e94699.