Inflammatory bowel disease in dogs and cats

BAVSCE2019

Introduc6on

•  IdiopathicIBDisthemostcommoncauseforchronicvomi>ngandordiarrheaindogsandcats•  IBDisahistologicaldiagnosis•  Commonlyhearahistoryofwaxingandwaningsigns•  Unlikelytooccurinanimalslessthanayearofage,middle-agedanimaldisease•  Responsetotherapyalonedoesnotconfirmthiscondi>on

Gastrointes6nal Immunity

•  Needaprotec>veimmuneresponse•  Remaintoleranttoharmlessenvironmentalan>gens

-  Dietarycomponents-  Commensalbacteria/microflora

•  Poten>alresponseinclude→An>genexclusion→Oraltolerance

→Inflamma>on

Natural Defenses

• Diges>vesecre>ons-Mucus-Hydrochloricacid-Diges>veenzymes• Peristalsis• Normalmicrobialflora•  Epithelial>ghtjunc>ons

Microbiota •  GutcolonizedwithinhoursaUerbirth•  Gutmicrobiomeconsistsof>100trillionorganisms•  Includesbacteria,fungal,protozoal,andviralorganisms

•  Es>matedthat90%ofcellsinthebodyarebacteria•  Notculturable•  Anindividual’smicrobiotatendstostayconstant•  Diversebetweenindividuals•  Formabarrieragainstpathogens-  RequiredfordevelopmentofIgAproducingBcells

Dysbiosis

•  Composi>onalaltera>on/changeinmicrobiota•  SIBOandan'bio'cresponsivediarrheas•  Maybeduetodietarychanges,disease,stress,ormedica>ons

•  MicrobiomeoUenchangesaUeracuteGIinjury•  Parvo

-  Whydosomedevelopchronicenteropathy?

-  Causeoreffect?Probablyboth

What causes IBD?

•  “Lossoftolerance”Disruptedmucosalbarrier→gene>cpermeabilitydefect→transientorac>veinfec>on

Defec>veimmunoregula>on→depressedsuppressorTcells

•  “Normalluminalan>gens”Normalmicroflora→bacteria

→fungalDietaryan>gens

Defini6on: INFLAMMATORY BOWEL DISEASE

PersistentclinicalsignsofGIdiseaseassociatedwithhistologicevidenceofinflamma>onofundeterminedcauseinthelaminapropriaofthesmallorlargeintes>ne

Signalment

•  Canbehelpfulindecidingifapet’ssymptomsarerelatedtoprimarygastrointes>naldisease•  GSD•  Englishbulldogs,Frenchbulldogs,Boxers• WheatenTerriers•  Siamese•  SharPei•  Yorkies•  Lundehunds•  Basenjis

Clinical signs and clues

•  Difficult>metolera>ngnewfoodsortreats• Weightlossdespiteseeminglynormalappe>te•  Vomi>ng,chronic(intermifentvs.persistent)•  Smallorlargeboweldiarrhea•  Hyporexiaoranorexia•  Gagging•  Ea>ngdifferently•  Abdominaldiscomfort•  Ascites

Diagnos6cs • Minimumdatabase-generallymorehelpfultoruleoutextra-gastrointes>naldiseases;•  Chem10panelsorlessdonotcons>tuteminimumdatabase(needlytes,calcium,bilirubin)

•  Fecal(ideallymorethanonce)• Rectalscrape-largebowelinvolvement• ACTHs>mula>ontes>ng•  Fecalα1-proteinaseinhibitor•  Therapeu>cdiettrials

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

Biopsy

•  Goldstandardfordefini>vediagnosis•  Surgicalvs.endoscopic

•  Localizedvs.generalizeddisease•  Otherlesionspresent•  Healingimpairment•  Gastricandjejunaldisease•  Lymphangiectasia,Lymphoma

•  Malabsorp>on–uppervs.lowerendoscopyvs.both•  Impera>vetoruleoutothercausesofinflamma>on

•  Feedingtubeplacement?Stabiliza>onpriortoanesthesia?

“Interobservervaria>onamonghistopathologicevalua>onsofintes>nal>ssuesfromdogsandcats”–Willardetal

JAVMA2002;220;1177-1182

Interpreta6on of biopsies •  Qualityin=qualityout•  Disagreementbetweenhistopathologists

•  Smallcelllymphoma•  Secondopinions

•  “Normal”biopsy•  SIBO,dietaryindiscre>on,foodsensi>vity,toxin,mo>litydisorders,patchydisease,intes>nalsclerosis,undiagnosedEPIorothersystemicdisorder

•  Treatmentpriortobiopsycaninfluenceresults

Interpreta6on of biopsies- con6nued

•  Idiopathiccategories•  Lymphocy>c-plasmacy>centeri>s(LPE)•  Eosinophilicgastroenterocoli>s(EGE)• Neutrophilicenteri>s• Granulomatousenteri>s

Therapy Diet→lowresidue;hypoallergenic;fiberAn>bio>cs→metronidazole;tylosin;enrofloxacinCor>costeroids→prednisone;dexamethasone;budesonideImmunosuppressivetherapies→azathioprine;chlorambucil;cyclosporineCobalamin

Treatment con6nued

• Cobalamin• An>-bacterials• Prebio>cs/Probio>cs• Fecaltransplant• Barium

Diet • Benefitsmayrelatemoretomechanicalfactorsthantoimmunologicfactors• Benefitsderivedfromtheimmunologicaspectmaybetemporary?•  Single,highlydiges>ble,protein(novelvs.hydrolyzed)• Highlydiges>ble,gluten-freecarbohydrate•  Fibermaybebeneficialifchroniclarge-boweldiarrhea

First line therapy-steroids

• Prednisone• Dexamethasone• Depomedrol•  Injectablevs.oral•  Sideeffects• Precau>onsforowners

Cor6costeroids

• Prednisoneisdrugofchoice•  1mg/lb/daythenreducedoseby1/2every2-4weeksifeffec>ve• Usuallyrequiretherapyforlife• Alterna>veformula>ons(dexamethasone,budesonide)

Cor6costeroids

Budesonide• Glucocor>coidwithprimarilytopicalac>vity• Removedbyfirst-passeffectthroughliver• Minimalsystemicac>vity• Dose:Cats-1mgPOqdDogs-2mgPOqd

Metronidazole

•  An>protozoal•  Inhibitscell-mediatedimmunity

•  Broadspectrumagainstanaerobes•  Posi>veeffectsonbrushborderenzymelevelsanduptakeofglucoseandaminoacids

•  10-15mg/kgbidPO•  UseassingleagentinmildIBD

•  Toxicityat>30mg/kg/day-vomi>ng,ataxia,seizures,disorienta>on,centralves>bulardisease

Tylosin • Macrolide,bacteriosta>can>bio>c•  Ac>veagainstmostG(+)andG(-)cocci,G(-)rods,andMycoplasma• Minimalac>vityagainstE.coliandSalmonellaspp.• Mayalsohaveimmunomodulatoryac>vity•  10mg/kgPOq8-24hor25mg/kgPOq24h•  Powderformrecons>tutedintocapsulesfordogs

Azathioprine •  Synthe>cpurineanalog-inhibitsDNAreplica>on•  Majorsideeffectsarebonemarrowsuppression,pancrea>>s•  Dogsonly;Donotuseincats•  Dose-2mg/kgq24h(dogs)x5daysthenalternatedaytherapy•  1to3weeklageffect•  MonitorCBCevery2weeksfor2-3monthsthenevery1-2months

Cyclosporine

•  InhibitsIL-2produc>onandsubsequentT-cellresponse→InhibitsCMI•  Sideeffectsincludeinfec>on,GIupset,gingivalhyperplasia,andrarelynephrotoxicity• Dose5mg/kgPOq24h•  Improvementin12/14dogs(AllenspachJVIM2006)• Monitorbloodlevels?

Chlorambucil

• Alkyla>ngagent•  Secondlinetherapyincats• Dose:2mgpercat1-2x/week• Majorsideeffectismyelosuppression

5-aminosalicylates

• Combina>onof5-aminosalicylicacidand-sulfapyridine(sulfasalazine)-5-aminosalicylate(olsalazine)

• Ac>vityrelatedprimarilytosalicylate•  Sideeffectsrelatedprimarilytosulfa• Usewithcau>onincats• Usedonlyforlargeboweldisease

Other Meds • Cyclophosphamide–alkyla>ngagent•  Tetracycline-an>bacterial• Mo>lityModifiers-loperamide,diphenoxylate• Metoclopramide-improveupperGImo>lity• Cisapride

Prognosis

OUencontrollable,rarelycurable•  26%completeremissionrate•  50%con>nuedtohaveintermifentclinicalsigns•  4%hadunresponsivedisease•  13%euthanizeddTuncontrollabledisease•  8%euthanizeddTunrelatedcauses

Cravenetal2004

Prognosis

• Noassocia>onbetweensite,type,orseverityofdisease• Hypoalbuminemiaonlypredictorofpooroutcome•  cPLImaybeassociatedwithpooroutcome

Protein-losing enteropathies

• Nonselec>veproteinlossfromtheintes>nes• Anyintes>naldiseasecancauseaprotein-losingenteropathyifsevereenough• Morecommonindogs•  Intes>nallymphangiectasia,IBD,neoplasia,fungalinfec>ons,itussuscep>on,parasites

Clinical signs

•  TypicalsignssimilartoIBD• However,somedogswillhavenosignsorsubtleweightlossonly• Respiratorydistress(effusion,PTE)•  Edema• Ascites• Muscletremors/seizuresfromlowCa+

Diagnosis

•  Importanttoruleoutothercausesforhypoalbuminemia•  Bileacids•  Urineprotein:crea>ninera>os•  Fecalalpha-1proteinaseinhibitor•  Addison’sdisease•  Gastriculcera>on•  Intes>nalparasites

•  Ultrasound•  Canseelinearstria>onsinmucosabutdoesnotrevealcauseinmostcases

•  Biopsyviaendoscopyvs.laparotomy

Treatment • Ultralowfat,highlydiges>bledietiskey•  Ifverysick,elementaldietssuchasvivonexcanbetried• Homemadediets(turkey,potatoes,rice)•  Ifbiopsyrevealsinflammatorycells,immunesuppressingmedica>on• Prednisone,cyclosporine,chlorambucil->preventlympha>cgranulomas

Addi6onal treatment op6ons

•  Calciumsupplementa>on•  Suppor>vecare-hetastarch,fluids,feedingtubes•  Plavix•  Humanalbumin•  Plasmatransfusion?•  Cobalamin

Case examples

•  SammyBroussard-6yr,MN,Chihmix•  Chronicweightloss•  Regurgita>on•  Eructa>onandseeminguncomfortableatnight

•  OccasionalsoUstool,boutsofdiarrheawithstress

•  Unremarkablebloodwork,ACTHs>mula>on,fecal,GIpanel

•  NotresponsivetoPrednisone,omeprazole,reglan,andcerenia

LPS Gastri6s and Enteri6s with Lymphangiectasia • Metronidazoleandmycophenolate• Cyclosporineandlowfatdiet• Chlorambucil,prednisone,andcyclosporinewithhomemadelowfatdiet• B12supplementa>on•  Fecaltransplanta>on?

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

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?

Thank you for your 6me and aSen6on…….. The End