Func%onalGastrointes%nalDiseasePediatrics

SmallGroupSession:March1,2020ChristopheFaure,MD,Professor

DivisionofGastroenterology,HepatologyandNutriCon,UniversitédeMontréal(CHUSainte-JusCne)

ElyanneRatcliffe,MD,AssociateProfessorDivisionofGastroenterologyandNutriCon,McMasterUniversity

(McMasterChildren’sHospital)

Conflict of Interest Disclosure (over the past 24 months)

•  NorelevantrelaConshipswithanycommercialornon-profitorganizaCons

Name: Dr. C. Faure

Conflict of Interest Disclosure (over the past 24 months)

Commercial or Non-Profit Interest Relationship

American Neurogastroenterology and Motility Society

Member, ANMS Council

Name: Dr. E. Ratcliffe

✔ Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles, applying medical knowledge, clinical skills, and professional values in their provision of high-quality and safe patient-centered care. Medical Expert is the central physician Role in the CanMEDS Framework and defines the physician’s clinical scope of practice.)

✔ Communicator (as Communicators, physicians form relationships with patients and their families that facilitate the gathering and sharing of essential information for effective health care.)

✔ Collaborator (as Collaborators, physicians work effectively with other health care professionals to provide safe, high-quality, patient-centred care.)

Leader (as Leaders, physicians engage with others to contribute to a vision of a high-quality health care system and take responsibility for the delivery of excellent patient care through their activities as clinicians, administrators, scholars, or teachers.)

✔ Health Advocate (as Health Advocates, physicians contribute their expertise and influence as they work with communities or patient populations to improve health. They work with those they serve to determine and understand needs, speak on behalf of others when required, and support the mobilization of resources to effect change.)

✔ Scholar (as Scholars, physicians demonstrate a lifelong commitment to excellence in practice through continuous learning and by teaching others, evaluating evidence, and contributing to scholarship.)

Professional (as Professionals, physicians are committed to the health and well-being of individual patients and society through ethical practice, high personal standards of behaviour, accountability to the profession and society, physician-led regulation, and maintenance of personal health.)

CanMEDS Roles Covered

LearningObjecCvesAttheendofthissessionparCcipantswillbeableto:1.  RecognizetheconCnuumofclinicalpresentaConsoffuncConal

consCpaConandirritablebowelsyndromeinpediatricpaCents.2.  IdenCfypsychosocialfactorsthatplayaroleinthegenesis/

exacerbaConofpediatricIBS.3.  Describemanagementapproaches,bothpharmacologicandnon-

pharmacologic,usedinthecareofpediatricpaCentswithIBS.

Case•  12yearoldfemale• Referredfor“consCpaCon”•  2yearhistory

•  Abdominalpain•  VomiCng•  ConsCpaCon

Case• MulCpleadmissionsfor“consCpaCon”presenCngwithabdominalpainandvomiCng

•  NGinserted;cleanoutwithPEG+electrolytes• Dailybowelmovements;BristolType6• DecreasedappeCte;feels“full”• Abdominalpaindayandnight;moderate4-7onpainscale

Does she have func-onal cons-pa-on or IBS with cons-pa-on?

FuncConalConsCpaConRomeIVDiagnos%cCriteriaforFunc%onalCons%pa%on(Child/Adolescent)

Mustinclude2ormoreofthefollowingoccurringatleastonceperweekforaminimumof1monthwithinsufficientcriteriaforadiagnosisofirritablebowelsyndrome

1.  2orfewerdefecaConsinthetoiletperweekinachildofadevelopmentalageofatleast4years

2.  Atleast1episodeoffecalinconCnenceperweek3.  HistoryofretenCveposturingorexcessivevoliConalstool

retenCon4.  Historyofpainfulorhardbowelmovements5.  Presenceoflargefecalmassintherectum6.  Historyoflargediameterstoolsthatcanobstructthetoilet

AherappropriateevaluaCon,thesymptomscannotbefullyexplainedbyanothermedicalcondiCon.

HyamsJSGastroenterology2016

IBS–PartofFBDConCnuum

Lacy BE Gastroenterology 2016

IrritableBowelSyndromeRomeIVDiagnos%cCriteriaforIrritableBowelSyndrome(Child/Adolescent)

Mustincludeallofthefollowing:

1.  Abdominalpainatleast4dayspermonthassociatedwithoneormoreofthefollowing:a.  RelatedtodefecaConb.  Achangeinfrequencyofstoolc.  Achangeinform(appearance)ofstool

2.  InchildrenwithconsCpaCon,thepaindoesnotresolvewithresoluConofconsCpaCon(childreninwhomthepainresolveshavefuncConalconsCpaCon)

3.  AherappropriateevaluaCon,thesymptomscannotbefullyexplainedbyanothermedicalcondiCon.

Criteriafulfilledforatleast2monthsbeforediagnosis.

HyamsJSGastroenterology2016

PrevalenceofFGIDsaccordingtoRomeIV

RobinetalJPediatr2018

Case• AddiConalsymptomsofheadaches,blurredvision,dizziness,weaknesses

• Parentsseparated;familystressedbyadmissions/appointmentsandlackofprogress

• DuetoconstellaConofsymptomsandprominenceofabdominalpain–referredtoPediatricChronicPainProgram

Should we worried be about anything else?

ClinicalAssessment•  EstablishaworkingandtherapeuCcalliancewithpaCentandfamily•  TakeCme+++• PaCent’shistory• Painhistory•  StressfullepisodeorinfecCousepisodeassociatedwithonsetofsymptoms

• PsychosocialhistoryofpaCentandfamily•  FamilyhistoryofGIdisorders• DietaryassociaConwithpainepisodes

RedFlags:neithersensiCvenorspecific…•  Pain

! NocturnalPain! Persistantrightupperorrightlowerquadrantpain

•  AssociatedGIsymptoms! PersistentvomiCng! Nocturnaldiarrhea! Dysphagia! Hematochezia! Perirectaldisease

•  Generalsymptoms! Fever,arthriCs,apthousulcers! InvoluntaryWeightloss! DeceleraConoflineargrowth,delayedpuberty

•  FamilyhistoryofIBD

•  Familyhistoryofceliacdisease•  FamilyhistoryofpepCculcer

RasquinetalGastroenterology2006

…butthegreaterthenumberpresent,thegreaterthelikelihoodoforganicdisease

Work-Up?• DirectedbyhistoryofthechildandfamilyandbyphysicalexaminaCon•  IniCalscreeningcaninclude:

•  CBC,CRP,albumin•  IgAtTG•  ALT,lipase/amylase•  Urianalysis•  FecalcalprotecCn•  Stoolforovaandparasites

IBSandCeliacDiseaseIBS:4Cmeshigherriskofhavingceliacdiseasethanthe

generalpediatricpopulaCon(P<.001;oddsraCo,4.19[95%CI,2.03-8.49])

CristoforietalJAMAPediatr2014

What caused her to be like this?

FBD–SensiCzingEvents

HyamsJSGastroenterology2016

Post-infecCousFGID• Norovirus:Nopediatricdata

•  IBS(OR11.40;95%CI3.44–37.82;Zaninietal.AmJGastroenterol2012),

•  FD,consCpaCon(Porteretal.ClinInfectDis2012)

• Giardia:•  IBSRR=3.4(95%CI2.9to3.8)aherinfecCon(Wensaasetal.Gut2012)

•  Diarrhea,flatulenceinpreschoolchildren(Mellingenetal.BMCPublicHealth2010)

• CJejuni(IBS,FD)• Salmonella(IBS,FD)• Shigella(IBS)

Spilleretal.Gastro2009Sapsetal.JPediatr2008Futagamietal.APT2015

But she is not an anxious girl…

VisceralHypersensiCvityandSymptomSeverity

• PsychologicalcomorbidityiscommoninFGIDs• BarostattesCnginadultIBSandFDcohortsdemonstratedincreasingGIsymptomseveritywithincreasingvisceralhypersensiCvity

•  Findingswereindependentofatendencytoreportsymptoms,oranxiety/depressioncomorbidiCes

Simrénetal,Gut.2018Feb;67(2):255-262

VisceralHypersensitvity:RectalSensoryThresholdforPain(RSTP)

IBS Controls0

10

20

30

40

50

RST

P (m

mH

g)

FaureetalJPediatr2007CasCllouxetalJPGN2008

IBS Controls0

10

20

30

40

50R

STP

(mm

Hg)

85% of the pa-ents = RSTP ≤ 30.8 mmHg

(<5th perc. of Normal Children)

Psychologicalco-morbidiCesarefrequent

IBS FAP FD50

60

70

80

90

100STAI-C

CampoetalPediatrics2004FaureetalJPediatr2007CasCllouxetalJPGN2008

Anxiety~50% Depression~10%IBS FAP FD

0

10

20

30

40

CDI

Family-childdynamicsinfluenceseverityofsymptoms

FamilyFactors• Modeling•  Psychologicaldistress•  ParentalpercepConof:

•  Pain•  Child’sself-efficacy

•  ParentalprotecCveness(e.g.keepinghomefromschoolwhenchildinpain)

•  Parentalcatastrophizing

ChildFactors

• Copingstyle/self-efficacy

vanTilburgetal,WorldJGastroenterol2015;21(18):5532-41DuPennetal,Children2016;3(15)

Cunninghametal,JPGN2014;59:732–738

So, how do we treat this?

Treatmentshouldbetailoredto…

•  IBSsubtype:IBS-D,IBS-C•  IBSseverity• Associatedpsychologicalco-morbidiCes•  IBSpathophysiologicalmechanism(?)

ManagementofFGIDs

• PosiCvediagnosis• ProvidepathophysiologicalexplanaCons• Reassurance

•  Symptomsarerealbutarenotlife-threatening• Mustlearntolive/copewiththesymptom

• Avoidtriggers

IBSTreatment:NutriCon•  Reducesorbitol,fructose,lactose?•  LowFODMAPs•  Fibres=age(years)+5g•  Avoid:

•  Fat•  Tea,coffee,Coke•  Spicyandacidicfood

IBS:SymptomaCcTreatments• ConsCpaCon:mineraloil,lactulose,PEG3350• Diarrhea:loperamide(Imodium®),cholestyramine(Questran®)…

• Pain:AnCspasmodics:trimebuCne,dicyclomine,Pepermintoil(KlineJPediatr2001)…

• Gas:simethicone…

IBS:Non-pharmacologicalTreatments

•  ProbioCcs:LactobacillusGG,LactobacillusrhamnosusGGJPGN2010;51:24-30Gut2010;59:325-32

•  HypnosisVliegeretal.Gastroenterology2007

•  CogniCvebehaviouraltherapy(CBT)Youssefetal.JPGN2004

IBS:TreatmentofSevereFormsInmostseverecases(schoolabsenteeism)• Amitriptyline0.2to0.4mg/kgHS,10to50mg/day;or

• Imipramine0.2to0.4mg/kgHS,10to50mg/day(lessanCcholinergic)

• Citalopram(5-HTreuptakeinhibitor)10mg/dayto40mgdie

• Mirtazapine7.5to15mgHS

Baharetal.JPediatr2008(RCT)Sapsetal.Gastroenterology2009(RCT)

TeitelbaumJPGN2011(Open)Campoetal.2004(openstudy)RoohafzaetalNGM2014RCT

Hussainetal.JPGN2014

CheckforSuicidalIdeaConandQT

Placebo

Kaptchuketal.BMJ2010

TheplaceboeffectinIBS(evenwhenplaceboisannounced)

What’snext?•  IBS-C:LinacloCde:Guanylate-cylaseCagonist

•  ImprovesvisceralhypersensiCvity;increaseschloridesecreCon•  IBS-D:Eluxadoline:mu-opioidreceptoragonistandadelta-opioidreceptorantagonist

•  IBS-D:Ondansetron:5-HT3Rantagonist•  LarazoCde:sCmulaConofCghtjuncCons•  EbasCne(Aerius)(H1antagonist):TRPV1desensibilisaCon(Wouters2016)•  Pregabaline(SaitoetalAPT2018)•  And…understandwhysomepaCentsrespondtoFODMAPSandothersdonot

AuricularNeurosCmulaConControls ac-vity of pain areas in the central nervous system par-cularly the amygdala and spinal cord

IB-STIM™

KrasaelapetalClinGastroHepatol2020KovacicetalLancetGastro2017

27IBSadolescents(medianage,15.3y):auricularneurosCmulaCon23IBSadolescents(medianage,15.6y):shamsCmulaCon5days/weekfor4weeks

%with30%improvementinworstpainseverityinPENFSvsshamaher3weeksandatextendedfollow-up8–12weeksaherendoftherapy

MoayyediPJCAG2019HyamsJSGastroenterology2016

IBSManagement-Pediatrics

Linaclotide: Safety and efficacy study of a range of doses administered orally to children aged 7-17 years, with irritable bowel syndrome with constipation (NCT02559817). Study completion date August 2019. Black box warming for < 6 years.