inflammatory bowel disease in dogs and cats · diarrhea in dogs and cats • ibd is a histological...
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Inflammatory bowel disease in dogs and cats
BAVSCE2019
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Introduc6on
• IdiopathicIBDisthemostcommoncauseforchronicvomi>ngandordiarrheaindogsandcats• IBDisahistologicaldiagnosis• Commonlyhearahistoryofwaxingandwaningsigns• Unlikelytooccurinanimalslessthanayearofage,middle-agedanimaldisease• Responsetotherapyalonedoesnotconfirmthiscondi>on
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Gastrointes6nal Immunity
• Needaprotec>veimmuneresponse• Remaintoleranttoharmlessenvironmentalan>gens
- Dietarycomponents- Commensalbacteria/microflora
• Poten>alresponseinclude→An>genexclusion→Oraltolerance
→Inflamma>on
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Natural Defenses
• Diges>vesecre>ons-Mucus-Hydrochloricacid-Diges>veenzymes• Peristalsis• Normalmicrobialflora• Epithelial>ghtjunc>ons
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Microbiota • GutcolonizedwithinhoursaUerbirth• Gutmicrobiomeconsistsof>100trillionorganisms• Includesbacteria,fungal,protozoal,andviralorganisms
• Es>matedthat90%ofcellsinthebodyarebacteria• Notculturable• Anindividual’smicrobiotatendstostayconstant• Diversebetweenindividuals• Formabarrieragainstpathogens- RequiredfordevelopmentofIgAproducingBcells
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Dysbiosis
• Composi>onalaltera>on/changeinmicrobiota• SIBOandan'bio'cresponsivediarrheas• Maybeduetodietarychanges,disease,stress,ormedica>ons
• MicrobiomeoUenchangesaUeracuteGIinjury• Parvo
- Whydosomedevelopchronicenteropathy?
- Causeoreffect?Probablyboth
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What causes IBD?
• “Lossoftolerance”Disruptedmucosalbarrier→gene>cpermeabilitydefect→transientorac>veinfec>on
Defec>veimmunoregula>on→depressedsuppressorTcells
• “Normalluminalan>gens”Normalmicroflora→bacteria
→fungalDietaryan>gens
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Defini6on: INFLAMMATORY BOWEL DISEASE
PersistentclinicalsignsofGIdiseaseassociatedwithhistologicevidenceofinflamma>onofundeterminedcauseinthelaminapropriaofthesmallorlargeintes>ne
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Signalment
• Canbehelpfulindecidingifapet’ssymptomsarerelatedtoprimarygastrointes>naldisease• GSD• Englishbulldogs,Frenchbulldogs,Boxers• WheatenTerriers• Siamese• SharPei• Yorkies• Lundehunds• Basenjis
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Clinical signs and clues
• Difficult>metolera>ngnewfoodsortreats• Weightlossdespiteseeminglynormalappe>te• Vomi>ng,chronic(intermifentvs.persistent)• Smallorlargeboweldiarrhea• Hyporexiaoranorexia• Gagging• Ea>ngdifferently• Abdominaldiscomfort• Ascites
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Diagnos6cs • Minimumdatabase-generallymorehelpfultoruleoutextra-gastrointes>naldiseases;• Chem10panelsorlessdonotcons>tuteminimumdatabase(needlytes,calcium,bilirubin)
• Fecal(ideallymorethanonce)• Rectalscrape-largebowelinvolvement• ACTHs>mula>ontes>ng• Fecalα1-proteinaseinhibitor• Therapeu>cdiettrials
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Diagnos6cs- con6nued • GIpanel-ruleoutEPI,diseaselocaliza>on,providetherapeu>cinforma>on• Infec>ousdiseasescreening(heterobilharzia,histoplasmosis,giardia,toxoplasma,mycobacteria,prototheca,Pythium,pathogenicbacteria)• Abdominalimaging-moretoruleoutothercondi>ons• Capsuleendoscopy?• ALICAM,dogsover6kg,retrievalofcapsule
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Biopsy
• Goldstandardfordefini>vediagnosis• Surgicalvs.endoscopic
• Localizedvs.generalizeddisease• Otherlesionspresent• Healingimpairment• Gastricandjejunaldisease• Lymphangiectasia,Lymphoma
• Malabsorp>on–uppervs.lowerendoscopyvs.both• Impera>vetoruleoutothercausesofinflamma>on
• Feedingtubeplacement?Stabiliza>onpriortoanesthesia?
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“Interobservervaria>onamonghistopathologicevalua>onsofintes>nal>ssuesfromdogsandcats”–Willardetal
JAVMA2002;220;1177-1182
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Interpreta6on of biopsies • Qualityin=qualityout• Disagreementbetweenhistopathologists
• Smallcelllymphoma• Secondopinions
• “Normal”biopsy• SIBO,dietaryindiscre>on,foodsensi>vity,toxin,mo>litydisorders,patchydisease,intes>nalsclerosis,undiagnosedEPIorothersystemicdisorder
• Treatmentpriortobiopsycaninfluenceresults
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Interpreta6on of biopsies- con6nued
• Idiopathiccategories• Lymphocy>c-plasmacy>centeri>s(LPE)• Eosinophilicgastroenterocoli>s(EGE)• Neutrophilicenteri>s• Granulomatousenteri>s
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Therapy Diet→lowresidue;hypoallergenic;fiberAn>bio>cs→metronidazole;tylosin;enrofloxacinCor>costeroids→prednisone;dexamethasone;budesonideImmunosuppressivetherapies→azathioprine;chlorambucil;cyclosporineCobalamin
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Treatment con6nued
• Cobalamin• An>-bacterials• Prebio>cs/Probio>cs• Fecaltransplant• Barium
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Diet • Benefitsmayrelatemoretomechanicalfactorsthantoimmunologicfactors• Benefitsderivedfromtheimmunologicaspectmaybetemporary?• Single,highlydiges>ble,protein(novelvs.hydrolyzed)• Highlydiges>ble,gluten-freecarbohydrate• Fibermaybebeneficialifchroniclarge-boweldiarrhea
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First line therapy-steroids
• Prednisone• Dexamethasone• Depomedrol• Injectablevs.oral• Sideeffects• Precau>onsforowners
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Cor6costeroids
• Prednisoneisdrugofchoice• 1mg/lb/daythenreducedoseby1/2every2-4weeksifeffec>ve• Usuallyrequiretherapyforlife• Alterna>veformula>ons(dexamethasone,budesonide)
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Cor6costeroids
Budesonide• Glucocor>coidwithprimarilytopicalac>vity• Removedbyfirst-passeffectthroughliver• Minimalsystemicac>vity• Dose:Cats-1mgPOqdDogs-2mgPOqd
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Metronidazole
• An>protozoal• Inhibitscell-mediatedimmunity
• Broadspectrumagainstanaerobes• Posi>veeffectsonbrushborderenzymelevelsanduptakeofglucoseandaminoacids
• 10-15mg/kgbidPO• UseassingleagentinmildIBD
• Toxicityat>30mg/kg/day-vomi>ng,ataxia,seizures,disorienta>on,centralves>bulardisease
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Tylosin • Macrolide,bacteriosta>can>bio>c• Ac>veagainstmostG(+)andG(-)cocci,G(-)rods,andMycoplasma• Minimalac>vityagainstE.coliandSalmonellaspp.• Mayalsohaveimmunomodulatoryac>vity• 10mg/kgPOq8-24hor25mg/kgPOq24h• Powderformrecons>tutedintocapsulesfordogs
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Azathioprine • Synthe>cpurineanalog-inhibitsDNAreplica>on• Majorsideeffectsarebonemarrowsuppression,pancrea>>s• Dogsonly;Donotuseincats• Dose-2mg/kgq24h(dogs)x5daysthenalternatedaytherapy• 1to3weeklageffect• MonitorCBCevery2weeksfor2-3monthsthenevery1-2months
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Cyclosporine
• InhibitsIL-2produc>onandsubsequentT-cellresponse→InhibitsCMI• Sideeffectsincludeinfec>on,GIupset,gingivalhyperplasia,andrarelynephrotoxicity• Dose5mg/kgPOq24h• Improvementin12/14dogs(AllenspachJVIM2006)• Monitorbloodlevels?
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Chlorambucil
• Alkyla>ngagent• Secondlinetherapyincats• Dose:2mgpercat1-2x/week• Majorsideeffectismyelosuppression
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5-aminosalicylates
• Combina>onof5-aminosalicylicacidand-sulfapyridine(sulfasalazine)-5-aminosalicylate(olsalazine)
• Ac>vityrelatedprimarilytosalicylate• Sideeffectsrelatedprimarilytosulfa• Usewithcau>onincats• Usedonlyforlargeboweldisease
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Other Meds • Cyclophosphamide–alkyla>ngagent• Tetracycline-an>bacterial• Mo>lityModifiers-loperamide,diphenoxylate• Metoclopramide-improveupperGImo>lity• Cisapride
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Prognosis
OUencontrollable,rarelycurable• 26%completeremissionrate• 50%con>nuedtohaveintermifentclinicalsigns• 4%hadunresponsivedisease• 13%euthanizeddTuncontrollabledisease• 8%euthanizeddTunrelatedcauses
Cravenetal2004
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Prognosis
• Noassocia>onbetweensite,type,orseverityofdisease• Hypoalbuminemiaonlypredictorofpooroutcome• cPLImaybeassociatedwithpooroutcome
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Protein-losing enteropathies
• Nonselec>veproteinlossfromtheintes>nes• Anyintes>naldiseasecancauseaprotein-losingenteropathyifsevereenough• Morecommonindogs• Intes>nallymphangiectasia,IBD,neoplasia,fungalinfec>ons,itussuscep>on,parasites
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Clinical signs
• TypicalsignssimilartoIBD• However,somedogswillhavenosignsorsubtleweightlossonly• Respiratorydistress(effusion,PTE)• Edema• Ascites• Muscletremors/seizuresfromlowCa+
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Diagnosis
• Importanttoruleoutothercausesforhypoalbuminemia• Bileacids• Urineprotein:crea>ninera>os• Fecalalpha-1proteinaseinhibitor• Addison’sdisease• Gastriculcera>on• Intes>nalparasites
• Ultrasound• Canseelinearstria>onsinmucosabutdoesnotrevealcauseinmostcases
• Biopsyviaendoscopyvs.laparotomy
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Treatment • Ultralowfat,highlydiges>bledietiskey• Ifverysick,elementaldietssuchasvivonexcanbetried• Homemadediets(turkey,potatoes,rice)• Ifbiopsyrevealsinflammatorycells,immunesuppressingmedica>on• Prednisone,cyclosporine,chlorambucil->preventlympha>cgranulomas
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Addi6onal treatment op6ons
• Calciumsupplementa>on• Suppor>vecare-hetastarch,fluids,feedingtubes• Plavix• Humanalbumin• Plasmatransfusion?• Cobalamin
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Case examples
• SammyBroussard-6yr,MN,Chihmix• Chronicweightloss• Regurgita>on• Eructa>onandseeminguncomfortableatnight
• OccasionalsoUstool,boutsofdiarrheawithstress
• Unremarkablebloodwork,ACTHs>mula>on,fecal,GIpanel
• NotresponsivetoPrednisone,omeprazole,reglan,andcerenia
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LPS Gastri6s and Enteri6s with Lymphangiectasia • Metronidazoleandmycophenolate• Cyclosporineandlowfatdiet• Chlorambucil,prednisone,andcyclosporinewithhomemadelowfatdiet• B12supplementa>on• Fecaltransplanta>on?
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Case examples
• PixieGraceMar>n-5yr,FS,CornishRex
• Severeepisodesofvomi>ngassociatedwithstress2-3>mesperyear->hospitaliza>on
• Hypoallergenicdiettrial• Bloodwork,GIpanel,ultrasound,Felv/FIV,fecaltes>ng,thyroidtes>ngallWNL
• Ondansetronprn• Progressiontoseverelethargyandhematemesis
• EndsocopeaUerhospitaliza>on
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LPS to Eos Gastri6s and enteri6s • Prednisonevs.DexamethasoneSP• Bloa>ng->Reglanvs.cisapride• Gagging->Omeprazole• Con>nuedintermifentvomi>ng
• Metronidazole• Weaningoffomeprazole• Intermifentcerenia• Futureuseofcyclosporinevs.chlorambucil• Considerseconddiettrial
• Secondarypancrea>>s• Feedingtube?
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Thank you for your 6me and aSen6on…….. The End
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