10/22/2015
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Canine Inflammatory Bowel Disease Maureen Finke, DVM, DACVIM
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Canine Inflammatory Bowel Disease Maureen Finke, DVM, DACVIM Wheat Ridge Veterinary Specialists
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Overview Definition / Causes When to biopsy How to interpret histopathology How to manage difficult cases
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Definition Chronic (> 3 weeks) persistent or recurrent GI signs Inadequate response to diet, antibiotics, anthelmintic therapy Histopathologic evidence of mucosal inflammation Clinical response to anti-inflammatory or immunosuppressive medications
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Cause Unknown Altered interaction between gut microbes and the mucosal immune system Aggressive host immune response directed against bacteria or their products Genetic predisposition
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Chronic Small Bowel Diarrhea Diet-responsive enteropathy Antibiotic-responsive enteropathy Idiopathic IBD Lymphangectasia Fungal enteropathy (histoplasmosis, pythiosis) Neoplasia (LSA, carcinoma, MCT)
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Canine IBD Activity Index
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Canine Chronic Enteropathy Activity Index Additional information Albumin > 2.0 0 1.5 – 1.9 1 1.2 – 1.49 2 < 1.2 3 Ascites or peripheral edema None 0 Mild 1 Moderate 2 Severe 3
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When to Biopsy? CCEAI shown to be the best indicator of prognosis Activity score is highly correlated with predicting response to therapy (food, antibiotics, steroids) and outcome Histopath and endoscopy NOT predictive of response or outcome
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When to Biopsy? 65 dogs with IBD and diarrhea of 6 weeks duration 39 dogs (60%) responded to dietary modification alone Remaining dogs needed corticosteroids No difference in CIBDAI scores or histopathology scores between groups
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Prognosis Poor prognostic indicators • Hypoalbuminemia • Ascites or Edema • High Activity Score • Initial Hypocobalaminemia 2.0 “SICK” Little to no appetite Lethargy Vomiting Severe weight loss Ascites/Edema Dehydration Albumin < 2.0
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Dietary Trial
Antibiotic Trial
Steroids
Other Immunosuppressives
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Dietary Trial
Antibiotic Trial
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Steroids
Other Immunosuppressives
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Dietary Trial Hydrolyzed or antigen-restricted diet GI sign improvement usually seen in 2 weeks Consider re-challenge to confirm diagnosis and single-ingredient challenge to determine offending ingredients
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Novel Protein Diets – Home Cooked Closer the relationship between meat sources – higher risk of reaction (Ruminants, poultry) Home cooked diet • Often not balanced but may be fine for 2 week trial • Purchased ground meat may be contaminated by another meat source • Keep it simple – one protein, one carbohydrate • Develop balanced diet with nutritionist if successful •
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Novel Protein Diets – OTC Recent study – looked at 4 OTC venison diets • All contained other proteins not on label • 3 positive for soy, poultry, and/or beef Contamination at processing Food additives – allergen source?
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Novel Protein Diets - Prescription Protein sources tested prior to manufacture • Mass spectrometry and ELISA Steps taken at manufacturing plants Random testing for contaminants If cost is an issue, consider prescription diet for trial and later OTC challenge
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Hydrolyzed Diet Small peptides that are less likely to be allergenic than full size proteins Many dogs that are hypersensitive to corn, soy or chicken can tolerate it in the hydrolyzed form Be careful of flavored medications – HW preventative, antibiotics, compounded meds
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Antibiotic Responsive Diarrhea – Cause? Aberrant mucosal immune response to bacteria Change in the enteric bacterial flora (dysbiosis) Defects in mucosal barrier NOT an overgrowth of bacteria as previously though (SIBO)
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Antibiotic trial
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Tylosin or metronidazole for 2 weeks If good response, maintain on antibiotics for at least 28 days then discontinue Some dogs will outgrow the problem Some require indefinite therapy 23
Histopathologic Standards for Diagnosis of IBD World Small Animal Veterinary Association Gastrointestinal Standardization Group Disagreement among pathologists up to 50% of the time. Set of standards characterizing mucosal inflammation and morphologic change
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Endoscopic Guidelines 6-7 adequate samples or 10-15 marginal samples are required to diagnose lesions Consider ileal biopsies Only 27% of dogs had the same histopathologic diagnosis in both duodenum and ileum
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Not just lymphocytic-plasmacytic enteritis/colitis anymore Morphologic changes are important too • Crypt distension/abscesses – May be only lesion with PLE • Villous stunting/atrophy – correlates with clinical severity, degree of proinflammatory cytokine upregulation • Goblet cell mucus content – loss of mucus and goblet cells correlate with clinical signs
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WSAVMA Guidelines Anatomic localization Adequate tissue sample? Morphologic changes (fibrosis, villous blunting, crypt lesions) Inflammation (cell type, location, number) Final diagnosis Comments
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Treatment – Case Based Examples
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“Molly” – 5y FS Cocker Severe “sick” chronic diarrhea, vomiting, weight loss, ascites for 3 weeks ALB – 0.2 CIBDIA score 7 (moderate) CCEIA score 13 (severe) Histopath – Mild inflammation, severe crypt lesions
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Molly – 5y FS Cocker Started on combination of prednisone, tylosin, novel protein diet – no improvement Also failed cyclosporine trial Finally responded to • Cobalamin • Azathioprine • Weaned off of prednisone
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Cobalamin Distal small intestinal/ileal disease decreases cobalamin absorption
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Cobalamin Initial cobalamin level < 200 is associated with a significantly poorer prognosis
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Some patients will not respond to other treatments until normal cobalamin levels are restored Must be given subcutaneously 32
Azathioprine Major effect is decreased lymphocyte numbers and T-cell antibody synthesis No clinical studies using it for IBD Anecdotally good results in my experience Major side effects are hepatotoxicity, myelosuppression and acute pancreatitis
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Cyclosporine Effective for steroid responsive IBD in humans Prospective study of 14 dogs on 5mg/kg q 24 hours for 10 weeks 12/14 showed clinical improvement with 8 showing resolution of all clinical signs No improvement in histopathology scores
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Breanna – 13y FS Basenji Severe weight loss, Ascites, Albumin – 1.5 No other GI signs, good appetite Acute onset neurologic signs – suspected vascular event CIBDAI score = 3 (insignificant disease) CCEAI score = 7 (moderate disease) Histopathology – Severe LP gastritis, severe eosinophilic enteritis
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Hypercoagulability in Dogs with PLE 15 dogs with protein losing enteropathy Significantly hypercoagulable compared to healthy controls using thromboelastography (TEG) – did not improve with treatment Risk of thromboembolic events Consider aspirin, plavix, or heparin therapy in PLE dogs
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Breanna – 13y FS Basenji Failed prednisone, diet trial, metronidazole, azathioprine, cyclosporine, Switched to injectable dexamethasone – showed mild improvement with resolution of ascites but still hypoalbuminemic Additional improvement after adding cobalamin
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Injectable Dexamethasone Severe lesions may result in severe malabsorptive deficiencies Inability to absorb oral medications Consider injectable steroids at equivalent prednisone doses to bypass GI tract
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Breanna – Failing therapy Repeat intestinal biopsies recommended – suspect possible lymphoma Owners willing to do surgical biopsies but internist wimped out due to very poor BCS, severe hypoalbuminemia, poor surgical candidate Repeat endoscopic biopsies – Minimal inflammation but glandular crypt lesions seen
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Breanna Significant improvement with chlorambucil Weight gain Resolution of hypoalbuminemia Maintained on clopidrogel (Plavix)
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Chlorambucil Chemotherapeutic alkylating agent
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Anecdotal evidence in Inflammatory Bowel Disease. More commonly used in cats Minimally toxic Myelosuppression and GI upset 41
Prospective study • Comparison of pred-azathioprine to pred-chlorambucil • Chlorambucil group • greater increases in albumin concentration • Greater increase in body weight • Longer survival times
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“Gibson” 5 year MN Boxer with 6 month history of mixed bowel diarrhea from Crested Butte, CO Unremarkable bloodwork, thickened colon on abdominal ultrasound Failed diet, metronidazole, panacur, prednisone trials
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“Gibson” - Endoscopy Endoscopic findings Histopathology: • Lymphacytic plasmacytic enteritis • Granulomatous colitis suggestive of boxer colitis (PAS stain-positive)
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Granulomatous colitis of Boxer Dogs (French Bulldogs) Usually < 4 years old with large bowel diarrhea Histopathology – granulomatous inflammation Macrophages stain positive with periodic acid-Schiff (PAS) stain Infectious cause suspected – signs cured after course of enrofloxacin
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Mucosally invasive E. coli found with FISH (florescence in situ hybridization) - Cornell
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Granulomatous colitis Treatment is 5-10mg/kg/d enrofloxacin for a minimum of 6 weeks Other floroquinolones? Re-biopsy to ensure eradication Enrofloxacin-resistance has been documented – poor prognosis
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“Gibson” Failed enrofloxacin, enrofloxacin + TMS Immunosuppressive prednisone trial attempted due to lymphocytic plasmacytic enteritis – signs worsened Recommended repeat endoscopy and biopsy
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“Gibson” Histopathology Granulomatous colitis with Histoplasmosis organisms Oops… Patient has travel history to TX When in doubt Re-visit history and physical exam Repeat diagnostics … things change
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Questions??
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