Chronic Enteropathies - Proceedings - Library - VIN

http://www.vin.com/Members/Proceedings/Proceedings.plx?CI...

Front Page : Library : ACVIM 2003 : ABVP : Chronic Enteropathies Back to ABVP Back to Table of Contents

Chronic Enteropathies: How Should I Treat Them?

ACVIM 2003
Kenneth W. Simpson, BVM&S, PhD, MRCVS, DipACVIM, DipECVIM Ithaca, NY

IDIOPATHIC INFLAMMATORY BOWEL DISEASE

Idiopathic inflammatory bowel disease is the term used to describe a diverse group of intestinal disorders which are characterised by cellular infiltrates of the intestinal mucosa. Diagnosis is based on the description of histological findings in intestinal biopsies and the exclusion of known causes of intestinal inflammation e.g., endoparasites, dietary sensitivity. The most common inflammatory infiltrates are lymphocytes and plasma cells or eosinophils. Neutrophils or granulomatous inflammation are encountered less commonly.

Lymphoplasmacytic enteritis
Lymphoplasmacytic enteritis is the most common type of inflammatory bowel disease in dogs and cats. It is characterised by the accumulation of excessive numbers of lymphocytes and plasma cells in the lamina propria of the intestine. The degree of cellular accumulation is variable and is subjectively categorised as mild, moderate and severe. Moderate to severe lymphoplasmacytic enteritis is often associated with a protein losing enteropathy. A severe form of the condition has been reported in Basenjis. The extent of inflammation appears variable and ranges from the duodenum to the small and large bowel.

Clinical findings
Chronic small bowel diarrhea accompanied by weight loss or vomiting are the most frequent findings in dogs whereas vomiting is the most common clinical sign in cats. Vomitus often contains bile. Hairballs are frequent in cats. Other findings include changes in appetite, excessive borborygmi and abdominal discomfort. The severity of disease is variable, ranging from intermittent diarrhoea and vomiting in mild cases to intractable small bowel diarrhea, inappetance and weight loss in severe ones. The severity of the disease is thought to reflect the degree of cellular infiltrate. Physical findings range from normal to thickened intestines mesenteric lymphadenopathy, marked weight loss, and ascites or oedema in animals with severe protein losing enteropathy.

Diagnosis
A diagnosis of idiopathic lymphoplasmacytic enteritis is made by excluding systemic, parasitic, infectious, pancreatic and structural causes of chronic diarrhea and demonstrating excessive numbers of lymphocytes and plasma cells in intestinal biopsies.

Treatment
Treatment of IBD is usually based on dietary modification, antibiotics and immunosuppression. Treatment is to some extent based on the severity of the disease. Mild to moderate intestinal inflammation may be associated with dietary sensitivity or intolerance, or potentially idiopathic small intestinal bacterial overgrowth. A therapeutic dietary trial can be performed with either: 1) a highly digestible diet which is restricted in fat and gluten-free, 2) a diet limited to a single novel protein source or 3) a diet containing protein hydrolysate, to determine if dietary sensitivity or intolerance are present. A response is usually observed within 2 wks. Similarly a therapeutic trial (21days) with Tylosin (10mg/kg PO TID), metronidazole (15mg/kg PO BID) or oxytetracycline (10-20mg/kg PO TID) for antibiotic responsive enteropathy /small intestinal bacterial overgrowth may be warranted. In patients who fail these trials and in those with moderate to severe infiltrates, or hypoproteinaemia the administration of immunosuppressive agents is usually required to achieve a response. Oral prednisolone (1-2mg/kg PO BID) is the initial drug of choice. It is usually administered at an immunosuppressive dose for 2-3 wks and then decreased by 50% every 2-3wks, and then continued on an alternate day basis for 2-3 months. If clinical response is poor or the adverse effects of prednisolone predominate azathioprine can be added to the regimen. In dogs it is usually given every day (2mg/kg PO SID) for five days and then on alternate days to prednisolone. Cats are more sensitive to azathioprine (0.3mg/kg PO SID) and may be better managed with chlorambucil (6mg/m2 PO PO EOD (@2mg/5.3kg cat) and prednisone (5mg PO /cat/day). Supplemental cobalamin (1ml SC q 2-3wks) and folate / B complex vitamins should also be given if serum concentrations are low. Metronidazole (15mg/kg PO BID 10-14d then SID 10-14d) can also be used in conjunction with corticosteroids and has effects on bacteria and possibly the immune system. Successful treatment is accompanied by a decrease in clinical signs and an increase in plasma proteins. Once a patient has had 2-3 months remission from signs it may be possible to gradually withdraw immunosuppressive therapy. If signs recur daily medication is continued until signs resolve then gradually reduced. In patients who respond poorly to therapy or relapse after an initial response lymphoma should be ruled out.

Prognosis
The prognosis for lymphoplasmacytic enteritis is variable and depends on its severity. Many patients require prolonged treatment with glucocorticoids and diet. As no accurate criteria exist for predicting response it is wise to give a guarded prognosis.

Eosinophilic enteritis
Eosinophilic enteritis is characterised by the excessive accumulation of eosinophils in the lamina propria. It is speculated that it may result from an immunologic reaction to parasites or diet. the disease may also involve other areas of the gastrointestinal tract.

Clinical findings
Chronic small bowel diarrhoea accompanied by vomiting or weight loss are the principal clinical signs. Large bowel signs or vomiting predominate in some cases. Physical findings range from normal to focally or diffusely thickened intestines and marked weight loss.

Diagnosis
Intestinal biopsy. Clinicopathologic abnormalities may include peripheral eosinophilia. Mast cell neoplasms, hypoadrenocorticism and endoparasites can produce a similar spectrum of clinical signs and should be ruled out. The degree of eosinophilia can be extreme in cats and may be associated with eosinophilic infiltrates in the spleen, liver, lymph nodes and bone marrow. Intestinal protein loss is less common than lymphoplasmacytic enteritis.

Treatment
Some patients may respond to a strict exclusion diet, though prednisolone (2mg/kg PO SID) is usually required. In dogs signs usually resolve within a couple of weeks and prednisolone can be tapered. Feeding an easily digestible diet that is restricted to a single novel protein source or is hydrolyzed may help to maintain clinical remission. Prophylactic administration of an anthelminthic such as fenbendazole (50mg/kg PO SID 3 days) is warranted to treat potential visceral larval migrans which has been associated with eosinophilic gastroenteritis. Cats with hypereosinophilic syndrome often respond very poorly to treatment with immunosuppressive agents, diet and anthelminthics.

Prognosis
The prognosis is guarded as relapse is common. The prognosis in cats with hypereosinophilic syndrome is poor.

OTHER

INFLAMMATORY ENTEROPATHIES

Other enteropathies which are characterised by neutrophilic or granulomatous inflammation have also been described infrequently small animals. Some of these may be associated with bacterial infections such as Streptococcus, Campylobacter, Yersinia and Mycobacteria and fungal infections such as Histoplasma. Special stains and culture of mucosal biopsies and intestinal lymph nodes and other abdominal organs should be undertaken in cases of granulomatous enteritis to detect infectious organisms. Serology, chest radiographs and bone marrow biopsies may help to diagnose systemic fungal disease. The prognosis for idiopathic granulomatous or neutrophilic enteropathies is guarded to poor.

GI Lymphoma
Lymphosarcoma (LSA) is characterised by the mucosal and sub-mucosal infiltration of neoplastic lymphocytes which cause malabsorption. Focal forms of lymphosarcoma may cause obstruction. The tumor is often thought to be related to feline leukemia virus in cats though cats with GI lymphoma are usually FeLV negative, and is of unknown etiology in dogs. In cats LSA has been classified as lymphocytic or lymphoblastic, with the lymphocytic form responding well to chemotherapy. In some animals lymphoplasmacytic enteritis may progress to LSA.

Clinical findings
Weight loss, chronic small bowel diarrhea and progressive inappetance are common features of intestinal LSA. Vomiting may also be noted. Physical examination may reveal diffusely thickened or nodular intestines mesenteric lymphadenopathy. Acute abdominal pain and shock may be present if intestinal perforation has occurred. Hepatosplenomegaly and generalised lymphadenopathy are less frequently detected. Signs of hypoproteinemia may be evident.

Diagnosis
Middle aged or older dogs and cats are most commonly affected. Routine biochemistry often reveals a protein losing enteropathy in dogs with LSA. Anaemia which is either normocytic normochromic non-regenerative or microcytic and hypochromic, and neutrophilia may also be present. Ultrasound is useful for evaluating intestinal thickness and detecting mesenteric lymphadenopathy. Diagnosis can be made by demonstrating neoplastic lymphocytes in aspirates or biopsies from enlarged intestinal or peripheral lymph nodes, but is more often made by intestinal biopsy. Endoscopic biopsies may miss the lesion or show lymphoplasmacytic enteritis. Serum concentrations of cobalamin are often very low in cats with GI lymphoma and serum folate concentrations may also be reduced.

Treatment and prognosis

Dogs respond poorly to therapy. Cats with lymphocytic lymphoma may show a dramatic and lasting response (av. 17-20 mo.) to treatment with chlorambucil (6mg/m2 PO PO EOD (@2mg/5.3kg cat) and prednisone (5mg PO /cat/day). Supplemental cobalamin (1ml SC q 2-3wks) and folate / B complex vitamins should also be given. Lymphoblastic lymphoma is much less responsive.

Lymphangiectasia
Intestinal lymphangiectasia is characterised by the abnormal distension of lymphatic vessels within the mucosa. Lymphangiectasia is a consequence of a localised or generalised lymphatic abnormality or increased portal pressure e.g., right-sided heart failure, caval obstruction or hepatic disease. Lymphatic abnormalities are often associated with lipogranulomatous inflammation which is visible as small white granules on the intestinal mesentery. Tumour infiltration of lymphatics or lymph nodes can also cause lymphangiectasia. In some cases lymphangiography reveals a generalised lymphatic abnormality. Dilatation of lymphatics is associated with the exudation of protein rich lymph into the intestine and severe malabsorption of long chain fats. Yorkshire Terriers and Soft Coated Wheaten Terriers and the Lundehound seem to be over represented, suggesting a possible familial cause in some dogs.

Clinical findings
Intestinal lymphangiectasia is fairly common in dogs, but rare in cats. The clinical findings are essentially a consequence of the intestinal loss of protein and range from weight loss to chronic diarrhoea, ascites, oedema and chylothorax.

Diagnosis

1 de 2

30-05-2008 10:36

Chronic Enteropathies - Proceedings - Library - VIN

http://www.vin.com/Members/Proceedings/Proceedings.plx?CI...

Usually presents as a protein losing enteropathy, Endoscopic appearance of white blebs on the mucosa- dilated lymphatics, endoscopic biopsies are often adequate. Surgical biopsy should be undertaken carefully with appropriate precautionary measures for dehiscence.

Treatment
The cause of lymphangiectasia is usually not determined. Treatment is usually supportive and symptomatic. Dietary recommendations are the similar to those for other causes of small bowel diarrhoea, but fat restriction may have to be more severe. Medium chain triglyceride (MCT oil, coconut oil 0.5-2ml/kg body weight per day added to food) can be added to the diet to provide an easily assimilable source of calories. Prednisolone is often necessary (1-2mg/kg PO BID) and may work by decreasing lipogranulomatous inflammation. Prednisolone is tapered to the lowest effective dose once remission is achieved. Adjunct therapy with metronidazole or tylosin can also be given.

Prognosis
The response to therapy is variable with some patients staying in remission for several years while others pursue a path towards fulminant hypoproteinaemia. The prognosis is always guarded.

SMALL INTESTINAL BACTERIAL OVERGROWTH / ANTIBIOTIC RESPONSIVE ENTEROPATHY

Small intestinal bacterial overgrowth (SIBO) = an abnormal accumulation of bacteria in the small bowel.

The intestinal flora of healthy dogs and cats

Humans have total bacterial counts less than 5 (log10 cfu/ml or gram) small intestinal juice/tissue and anaerobic bacterial counts less than 4 5 (log10 cfu/ml or gram). Gram positive aerobic bacteria such as Streptococci and Staphylococci predominate; anaerobic bacteria such as Clostridia and Bactericides are extremely uncommon. Those findings in humans are not applicable to healthy dogs and cats. At least 24 papers have been published which describe the small intestinal bacterial flora of healthy dogs or cats. The majority of studies indicate that both the healthy dog and cat harbor a large number of diverse bacteria in the small intestine. The total bacterial counts in the proximal small intestine of healthy dogs ranges from 0-9.43 (log10 cfu/ml or gram) and anaerobes from 0 to 8.18 (log10 cfu/ml or gram). Similarly cats have total duodenal bacterial counts ranging from 2 to 8.3 (log10 cfu/ml or gram), and anaerobic bacteria from 2 to 8.05 (log10cfu/ml). Common aerobic bacterial species in dogs and cats include Streptococcus species, Staphylococcus spp, Bacillus spp, Escherichia coli, Corynebacterium spp, Enterobacter cloacea, Pseudomonas spp, and Pasturella multocida. Clostridium spp, Bifidobacterium spp, Eubacterium spp and Bacteroides spp are common anaerobes. Lactobacillus spp, are also common.

SIBO in dogs and cats

The syndrome of small intestinal bacterial overgrowth has been used to describe patients with signs such as diarrhea and weight loss that are associated with a gastrointestinal abnormality which is considered to cause small intestinal bacterial proliferation. It has also been applied to patients with similar clinical signs without an obvious cause for bacterial proliferation that respond to antibiotics. The literature on the normal flora of dogs and cats indicates that SIBO can be defined as: bacterial counts > 9.43 (log10 cfu/ml or gram) in dogs, > 8.3 (log10 cfu/ml or gram) in cats OR anaerobic bacterial counts > 8.18 (log10cfu/ml or gram) in dogs, > 8.05 (log10 cfu/ml or gram) in cats. Interestingly a disease, which fulfills those criteria, has yet to be described in the dog and cat.

Diseases other than SIBO which may improve with antibiotic therapy
I. Occult pathogens: Giardia, coccidia, Salmonella, Campylobacter, enteropathogenic E. Coli? II. Unknown pathogens e.g., Helicobacter spp. III. Increased host susceptibility to endogenous flora: 1. Breakdown of immune tolerance to indigenous microflora: Conventionally reared IL-10 knockout mice develop IBD whereasgerm free mice, do not. A similar loss of tolerance to a normal bacterial flora, or increased susceptibility to the potentially harmful effects of abnormal flora may also explain why Basenji dogs with immunoproliferative small intestinal disease respond to antibiotic therapy. 2. Increased susceptibility to endogenous flora arising from mucosal IgA deficiency could explain the antibiotic responsive chronic diarrhea in GSD. 3. Altered balance between damage and repair: Decreased synthesis of mucosal enzymes in the face of increased degradation e.g., EPI

Does idiopathic SIBO occur in dogs and cats?

In 1983 Batt et al. described small intestinal bacterial overgrowth in German Shepherd dogs which had no obvious underlying cause of SIBO. This study compared bacterial counts from German Shepherd dogs with diarrhea, with those obtained in six healthy dogs. Those investigators proposed that SIBO was present based on the presence of >5 (log10 cfu/ml) of bacteria in dogs with diarrhea. Unfortunately the intestinal fluid aspirated from the dogs was variably diluted or frozen before culture. The abnormal clinical signs and the associated intestinal mucosal changes in affected dogs were responsive to antibiotic therapy, suggesting that the bacterial flora was an important cause of the diarrhea. However, whether the clinical signs were caused by excessive numbers of bacteria or an enteropathy which renders the intestine more susceptible to damage by a normal flora, is unresolved. Subsequent investigators have used the cut-off value described by Batt et al., despite clear evidence indicating higher bacterial numbers in healthy dogs and cats. Further confusion over the reality of idiopathic SIBO in dogs was caused by a report which described a group of healthy GSD with duodenal bacterial counts >5 (log10 cfu/ml) as having SIBO.The authors explicitly stated that 'All dogs appeared clinically normal" and '...one would not expect that these dogs had alimentary tract disease by observing or working with them.' The lack of clinical signs in these dogs is in stark contrast to the syndrome of SIBO in humans, experimental animals, and the GSD originally described by Batt et al. that was characterized by diarrhea, weight loss and altered concentrations of cobalamin and folate. The authors refuted the suggestion that they had cultured intestinal fluid from healthy dogs. More recently in a study of 107 dogs, 52 were diagnosed as having idiopathic SIBO (intestinal bacteria greater than >5 (log10 cfu/ml)) and no identifiable underlying cause. Such a high prevalence of idiopathic SIBO serves to further question the validity of the 5 (log10 cfu/ml) cut-off vale for the diagnosis of SIBO.

Treatment
Treatment of suspected SIBO is directed at correcting underlying anatomic or structural abnormalities, treating EPI, and controlling the abnormal flora with antibiotics. Suitable antibiotics include oxytetracycline (20mg/kg TID PO), tylosin (10mg/kg TID PO), or metronidazole (15 mg/kg BID PO). In dogs with idiopathic SIBO/ intolerance antibiotic therapy is usually given for 28 days. Dietary modification also appears to be important and anecdotal evidence supports the use of highly digestible, low fat diets.

Prognosis
Many animals with undefined antibiotic responsive enteropathies relapse when antibiotics are stopped and require further courses, or long term maintenance therapy Prognosis for secondary SIBO depends on the underlying disease.

SPEAKER INFORMATION
(click the speaker's name to view other papers and abstracts submitted by this speaker) Kenneth W. Simpson, BVM&S, PhD, MRCVS, DipACVIM, DipECVIM-CA Clinical Sciences, NYS, CVM Cornell University VMC 2001 Ithaca, NY 14853

Front Page : Library : ACVIM 2003 : ABVP : Chronic Enteropathies 800.700.4636 | VINGRAM@vin.com | 530.756.4881 | Fax: 530.756.6035 777 West Covell Blvd, Davis, CA 95616 Copyright 1991-2008, Veterinary Information Network, Inc.

2 de 2

30-05-2008 10:36