Inflammatory bowel disease (Proceedings)

Inflammatory bowel disease (IBD) in dogs and cats is the name used for many disorders of the small and large bowel of the gastrointestinal tract. IBD is a term that is an umbrella that covers many mechanisms of disease, many of which have not been discovered and others that have been suspected but not proven. Response to treatment of IBD can often lead to an initiating cause by eliminating other causes with failure of treatment. However, sometimes response to treatment is due to secondary effects of a primary cause such as bacterial overgrowth and inflammation of the gut that can occur secondary to a food allergy with response to antibiotics and immunosuppressive drugs. Diagnosis of IBD in mild cases can be a clinical diagnosis with trial and error of treatments that are not harmful. Definitive diagnosis requires a tissue biopsy of the small and large bowel by endoscopic exam or celiotomy. Differentiating other diseases that look like IBD is critical due to the possibility of neoplasia. Treatment modalities differ based on whether the patient is a dog or cat and whether the clinical signs are primarily small or large bowel or both. Prognosis in mild to moderate IBD patients is very good with proper treatment and owner compliance. Severe cases can also be responsive with more intensive therapy and good owner compliance and good communication and between the clinician and owner. Side-effects of some of the more potent drugs in these cases can be a limiting factor but usually not. Some cases have a poorer prognosis due to the presence of certain cytological inflammatory cells on histopathology.

Etiology of Inflammatory Bowel Disease

The most common causes of IBD as we understand them at this point in time in veterinary medicine are food allergies, hypersensitivity to gut bacteria, overgrowth of bacteria in the gut and a primary immune-mediated disease . There may also be a genetic component as certain breeds are over-represented for IBD. Bacterial overgrowth is hard to prove as this can occur secondary to any inflammation of the intestine. It is hypothesized that any inflammation of the gut causes a more porous mucosa breaking down the gut barrier from ingesta allowing the intestine to absorb or be exposed to antigens that are foreign. This may create a hypersensitivity to the foreign particles in the ingesta and start the inflammatory process. Even eliminating the inciting cause such as a food protein may sometimes not be enough as the immune process may continue inspite of omitting the food protein. It has been hypothesized that in puppies that have had a history of intestinal parasites that are untreated such as in a shelter or stray environment may have had a leaky barrier for a long time and are exposed to many foreign antigens. Later in life when they see that antigen again, even with a healthy intestinal barrier, their immune sytstem may react causing the inflammation to recur.

Clinical Signs of Inflammatory Bowel Disease

The signalment in dogs and cats is usually an adult with most dogs being middle aged at presentation. However, there has been patients as young as 4 months old diagnosed with IBD. Usually there is also a history of the dog or cat having periodic episodes of vomiting and diarrhea that resolved on their own. Many times these patients are presented when the disease has progressed and is not resolving as it did in the past. There are also certain breeds that are predisposed to IBD. The German Shepherd, Shar Pei, basenji, soft-coated wheaten terrier dogs and the Siamese cat. In dogs, there is usually small bowel or large bowel diarrhea or a combination of the two. Vomiting may also occur. Weight loss, depressed appetite, anorexia, hematochezia, melena and sometimes hemetemesis can be present. Other signs that the owner may notice are postprandial pain, borborygamis, abdominal pain and the patient eating grass. Cats may present with the same clinical signs as dogs but one distinguishing feature that is different is that cats may only vomit and have no diarrhea. The majority of dogs have both vomiting and diarrhea. When a dog presents for vomiting only the patient should be tested for more common causes of vomiting with IBD lower on the differential diagnoses list. Cats are also a bit different in that IBD can be a part of what is called "triaditis". Triadiditis includes IBD, cholangitis and chronic pancreatitis. Usually their clinical signs are identical to IBD. It is important to know this when a cat is diagnosed on intestinal biopsy as having IBD but is not responding to traditional treatment for IBD. Further evaluation of the liver and pancreas may be needed to give more specific treatment for all three problems.

Differential Diagnoses of IBD

Intestinal parasites should always be ruled out prior to extensive diagnostics and treatment. A patient presenting for the first time with vomiting, diarrhea and even hematochezia may have been exposed to table food, garbage or a toxin with improvement of clinical signs seen within 1-2 days of supportive care. Cholangiohepatitis, other liver diseases and pancreatitis can also cause these same clinical signs and have a waxing/waning history. Gastrointestinal neoplasia such as lymphoma and adenocarcinoma can start with the identical clinical signs. There are also fungal diseases such as histoplasmosis and pythium that can look like IBD. A patient presenting with ascites and severe hypoproteinemia , hypocholesterolemia, and lymphopenia may have a primary condition called Lymphangiectasia. Lymphangiectasia is caused by inflammation of the lacteals in the mucosa and leakage of its contents such as protein, lymphocytes and cholesterol into the gut. However, this can also occur secondary to any of the above differentials and IBD if severe enough. An intestinal biopsy is needed to distinguish this condition since treatment is to give immunosuppressive therapy as a primary treatment.

Histopathological Forms of IBD

The most common form of IBD in the dog and cat is lymphocytic-plasmocytic. It is also the most treatable form of IBD. Although this is a specific inflammatory response, it does not represent the initiating cause as many causes of inflammation such as in the nasal cavity and liver have the same cytological findings without a primary cause identified. Eosinophilic form of IBD is more severe with a poor prognosis. Many cats get this form and may respond to immunosuppressive therapy for a short time but quickly become resistant. Granulocytic form of IBD is rare and may indicate fungal infection but usually a primary cause is not found and they are not responsive to treatment.

Diagnosis of IBD

Definitive diagnosis requires a tissue biopsy. Endoscopy is usually sufficient for IBD diagnosis because it is a disease of the mucosa. On the other hand, neoplasia requires a full thickness biopsy by laparoscopy or celiotomy because it originates in the submucosa and muscularis layers of the intestinal tract. Neoplasia may not extend to the mucosa giving a false impression on endoscopic mucosal biopsy alone. Many lymphomas can look like lymphocytic-plasmacytic IBD on mucosal biopsy. So if a patient is not responding to treatment of IBD after diagnosis on endoscopy, further investigation by surgical full thickness biopsy is indicated to rule out neoplasia. Hematology can be normal or can show a chronic anemia often an iron deficiency anemia from chronic blood loss. Neutrophilia seems to be present in severe cases but in mild cases neutrophils may be normal. Eosinophilia may be present with intestinal parasites and on occasion with eosinophilic form of IBD. Lymphopenia may be present if there is lymphangectasia (primary or secondary) present. Serum biochemical analysis may reveal hypoalbuminemia with or without hypoglobulinemia (hypoproteinemia), hypocholesterolemia, mild increases in ALT and ALP which in the dog is considered a "reactive hepatopathy" and secondary to the IBD however in the cat liver enzyme increases usually indicate a primary liver disease such as cholangiohepatitis. Fecal flotation much be performed at least 3 times negative before ruling out parasites. It is a good idea in dogs to give Fenbendazole (Panacur) at 50 mg/kg SID for three days even with negative fecals due to the inconsistent egg shedding with tricuris vulpis (whip worm). Giardia can be best evaluated by a ZnSulfate flotation or Giardia ELIZA test on feces. Chronic intestinal disease can cause secondary deficiencies that need to be addressed to get the best outcome with treatment. Serum cobalamin (vitamin ±2) and folate (folic acid) can indicate bacterial overgrowth when cobalamin is low and folate is high. In addition, particularly in cats, low cobalamin can stunt the growth of new endothelial cells of the intestinal mucosa preventing complete recovery and persistant diarrhea. Treatment for Cobalamin is given weekly for 6 weeks to compensate for this loss. Abdominal radiographs may be helpful to rule out an intussusceptions or obstruction but usually do not add much more information than that. Abdominal ultrasound by a skilled untrasonographer can give very valuable information by identifying the layers of the intestinal wall and observing thickness and echogenecity. Focal masses can be found and potentially a fine needle aspirate performed. Messenteric lymphadenopathy can be identified and when very large suggest fungal or neoplastic disease. Definitive diagnosis relies on a tissue diagnosis which can be obtained by endoscopic examination and biopsy if there is no overt suspicion of neoplasia or multi-organ involvement (abdominal masses, enlarged mesenteric lymphnodes, etc.). Limitations of endoscopy are neoplasia which can't be diagnosed on endoscopy due to a mucosal biopsy only obtained, only the proximal small intestine is biopsied (shar pei's tend to have IBD isolated in the ileum) so can miss lesions in the small intestine. Endoscopy is less invasive and usually less expensive than surgery for full-thickness biopsy so it is a very valuable tool in the right patient. Hypoproteinemic patients may not heal their incision from surgical biopsy if edema is present so endoscopy may be chosen however hypoproteinemia is often found with neoplasia and lymphangiectasia which can be difficult to diagnose on endoscopic biopsy so each individual case is must be analyzed for the best procedure in that patient. Surgical biopsy will also allow visualization of masses which can be removed and biopsy of other organs that may be involved such as the liver and pancreas.

Treatment

The treatment of IBD is usually a trial and error task. If a dog or cat is suspected of having IBD based on past history and are not having severe clinical signs, diet change (see diet below) and an antibiotic such as metronidazole at 15-20 mg/kg BID) to control bacterial overgrowth may be all that is needed. In more severe cases with chronic signs that don't resolve on their own, a tissue biopsy will dictate the treatment. With most having lymphocytic-plasmacytic histopathology, immunosuppressive therapy is indicated at least for a few weeks, with some patients needing it long term. Prednisone at 2mg/kg BID for 2 weeks, 2mg/kg SID for 2 weeks, and then 2mg/kg every other day for 2 weeks is a protocol I have found to work well. If at any time there is a relapse in the clinical signs, the higher dosage is used longer. Once an animal responds to prednisone, metronidazole and diet change, the prednisone may be discontinued until another episode occurs. When these episodes are getting closer and closer in frequency, it is time to find the right dose of prednisone that maintains the patient without clinical signs. These patients need long term treatment with immunosuppressive therapy. Because long term use of prednisone at high doses can cause Cushingnoid signs which are miserable for the owner and patient, azathioprine (Imuran®) can be given at 2.2 mg/kg SID x 10 days then every other day with the prednisone for 2 weeks. After two weeks, the prednisone can be tapered off and the azathioprine 2mg/kg every other day maintained. Many animals will respond to azathioprine alone or need a low dose of prednisone with it for optimum results. Azathioprine is not recommended in cats due to the side-effect of bone marrow suppression which can be severe in the cat. CBC checks are recommended for the first few weeks to be sure the dog is not having neutropenia or thrombocytopenia. If these occur the drug should be discontinued. Azathioprine can also cause pancreatitis with long term use and should be discontinued if this occurs. Cyclosporine (Atopica®, Neoral®) is an immunosuppressant drug that is not well studied in IBD but has been successful when the above treatment is not working for a patient. Cyclosporine is given to dogs at 5-10 mg/kg S-BID. There is no published dose in the cat for IBD. This drug is more expensive than the others but in small dogs not cost prohibitive. Renal toxicity is seen in humans but in dogs and cats there are no reported side-effects. Other treatments that can be tried are cyclophosphamide and chlorambucil. The goals of treatment are to maintain body weight, resolve or reduce vomiting and diarrhea, normalize serum albumin and globulin and monitor patient regularly so that resistance to therapy can be caught early and another treatment plan initiated.

IBD Diets

The best diet for an IBD patient is not known. Generally when the GI tract is having inflammation and digesting food is not optimal, the fat content is lowered and the carbohydrate component increased for calories. Carbohydrates are much more easily digested. In the dog or cat that may have food hypersensitivity a novel protein diet may be given. This is a diet that is chosen to give the patient a protein source that they have never had before. Most commercial diets contain chicken and beef and some contain lamb. Giving a dog or cat a diet protein such as fish, venison or duck, etc. may be of great benefit or at least limit the amount of immunosuppression needed. Other diets such as Z/D and ultra Z/D (Hill's Science Diet) contain hydrolyzed proteins that are too small to cause an immune reaction even if they cross the mucosal barrier. No table food or treats should be given. There are hypoallergenic treats and raw vegetables can be given as treats. Although diet alone may not work, it is indicated to try and eliminate possible causes of IBD. In vomiting cats without severe clinical signs, diet change may be all that is needed.