sindrome dell'intestino irritabile: diagnosi e terapia - gastrolearning®
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Sindrome dell'intestino
irritabile: diagnosi e terapia
Relatore: Prof. E. Corazziari (Roma)
FGID: DEFINITION
“ Variable combination of chronic orrecurrent gastrointestinal symptomsnot explained by structural orbiochemical abnormalities”
Drossman et al Gastroenterol Int 1990;3:159
FUNCTIONAL BOWEL DISORDERS ROME EVOLUTION
From the Irritable Colon Syndrome to
Functional Bowel DisordersIrritable Bowel Syndrome (Pain + Bowel Disorders)
Functional Constipation (+/- Pain)
Functional Diarrhea (no Pain)
Functional Abdominal Bloating
Unspecified bowel disorders
IBS PREVALENCE IN ITALY
4E Corazziari et al. Digest and Liver Disease 2008;40:944-950
FACE-FACE INTERVIEWPhysical Ex. & USRandom/Electoral Rollsn=46,139 Resp. R 63,2%
IBS ROME I CRITERIA
F= 10.7%M= 5.4%
LA DIAGNOSI DI IBS
IBS- DIAGNOSTIC CRITERIA
HOW TO MAKE A DIAGNOSIS OF A
CHRONIC FUNCTIONAL DISORDER
WHEN NO BIOLOGICAL MARKER
EXISTS ?
By exclusion
Positive-Symptom based
IBS- DIAGNOSTIC CRITERIAExclusion of the Diseases with
Detectable Diagnostic Markers
useful to detect relevant disorders in few patients
but
it requires to submit many patients to many
investigations with elevated costs and risks of iatrogenic
damage
and
it does not offer any certainty about the origin of
symptoms
IBS-DIAGNOSTIC CRITERIA
Positive symptom-based diagnosis
OFFER CONFIDENT DIAGNOSIS?
Reduce unneeded investigations
Plan treatment
Strengthen patient compliance to
treatment and coping ability with chronic
suffering and daily limitations
IBS-D47%
IBS-C22%
23%
12%
53%
12%
40%
60%
IBS SUBGROUPS ACCORDING TO ROME QUESTIONNAIRE AND DIARY CARD
N=68
K= 0.6
6%
75%
13%
6%
85%
6%
9%IBS-D
IBS-C
IBS-M
IBS-U
Piacentino D et al DDW 2010
ABDOMINAL PAIN AND BLOATING DIFFER IN RELATION TO EATING AND DEFECATION IN IBS PATIENTS
Carboni S, Cantarini R, Badiali D, Pallotta N, Corazziari E. DDW 2007
TWO YEAR (IN)STABILITY OF ROME II IBS
Williams et al APT 2006; 23: 197-205
30% IDENTICAL IBS subtypes
ROME II IBS
N= 697
18% ABD PAIN
37% BOWEL
45% NO
SYMPTOMS
52% NOT IBS
18% CHANGED SUBTYPES
D
C
M4%7%
IBS-C-CIC AND IBS-D-FD OVERLAP
Ford A.C. et al. Aliment Pharmacol Ther 2014;39:312-321
ONE YEAR (IN)STABILITY (%) OF ROME III IBS-C & FC
Wong et al. Am J Gastroenterol 2010;105:2228
FC
WELL
IBS-M
WELL
IBS- C
14 25.5
35.5
39
BOWEL CHARACTERISTICS IN IBS-C vs CIC
0
10
20
30
40
50
60
70
80
90
<3 ev/WK Hard Stools Straining Inc. Empty. Stool block Digital
IBS-C
CIC
%
* p<0.001
*
* * *
Ford AC et al. APT 2014;39:312-321
*
*
THE CONSTIPATION UNIVERSE
Rey E et al. Am J Gastroenterol advance online publication, 4 March 2014;doi:10.1038/ajg.2014.18
THE VANISHING FUNCTIONAL ORGANIC BOUNDARIES
Lactase deficiency
Celiac disease
Gluten sensitivity
Bacterial overgrowth
Bile salt malabsorption
Non specific minimal change inflammation
Subclinical intestinal inflammation
EXTRA-GI CONDITIONS IN DBF (>30%)
URINARY Interstitial cystitis Incontinence Detrusor instability
MUSCOLOSKELETAL Fibromyalgia Backache Headache
Whorwell et al 1986; Nyhlin et al 1993; Triadofilopoulos et al 1991
SEXUAL Dyspareunia Decreased libido Inhibited orgasm
PSYCHOLOGICAL Affective disorders Stress sensitivity Illness behavior Health seeking behavior
COMORBIDITIES ASSOCIATED WITH IBS
*p<0.05
Whitehead WE et al. Am J Gastroenterol 2007;102:2762
COMORBIDITY REPORTED PREVALENCE IN IBS
GI disorders
Gastritis, duodenitis 31.2%
Inflammatory bowel disease 27.9%
Gastroesophageal reflux disease 19.0%
Dyspepsia 17.4%
Oesophagitis 15.5%
Anal disease 15.4%
Psychiatric disorders
Depression 30.5%
Stress reaction 17.2%
Anxiety state 15.5%
Symptom-based somatic diagnoses*
Chronic fatigue, malaise 20.1%
Fibromyositis (myalgia) 14.5%
Pelvic pain, vulvodynia 8.6%
Temporomandibular joint disorder 3.3%
Dysmenorrhoea 2.3%
Cystitis 1.8%
STRESSFUL EVENTS PREDICT
Onset of FGIDs
Symptom exacerbation and health seeking
IBS symptom intensity
Bennett EJ et al. Gut 1998: 43:256Creed FH et al. Gut 1988; 29:235
PSYCHOPATHOLOGY IN IBS DYSPEPSIA COMORBIDITY
Piacentino D et al. 2014 Submitted for publication
IBS SEVERITY
DETERMINED BY PATIENT’S SYMPTOM REPORT AND BEHAVIOR
COMPOSITE OF
GI & EXTRA GI SYMPTOMS
DEGREE OF DISABILITY
ILLNESS-RELATED PERCEPTIONS
ILLNESS-RELATED BEHAVIOR
PSYCHOSOCIAL DISTRESS
GENDER / AGE
Drossman DA et al. Am J Gastroenterol2011;106:1759;doi:10.1038/ajg.2011.201;published online 12 July 2011
PSYCHOLOGICAL STATUS IN IBS-C vs CIC & IBS-D vs FD
0
5
10
15
20
25
30
35
40
IBS-C
IBS-D
CIC
FD
ANXIETY SOMATIZATION
%
* p<0.00
*
**
*
Ford AC et al. APT 2014;39:312-321
THE MULTIDIMENSIONAL DIAGNOSIS OF IBS
Symptom-based diagnosis of IBS
Diagnose IBS-Subtype
Assess IBS severity
Assess Stress and Psychological Status
Assess Gastrointestinal comorbidities
Assess extragastrointestinal comorbiditiesAnd
Related polytherapy
CONSIDERAZIONI SULLA DIAGNOSI DI IBS
I CRITERI DI ROMA
Categorizzano a fini classificativi le grandi sindromi funzionali
Non identificano tutti i sottotipi di pazienti
IBS-C E STIPSI FUNZIONALE, IBS-D E DIARREA FUNZIONALE FANNO PARTE DI
UNO STESSO SPETTRO
NELLA PRATICA
IDENTIFICARE LE SOTTOSINDROMI
E
AGGIUNGERE ALTRE VALENZE CLINICHE
DIAGNOSI MULTI DIMENSIONALE
LA SEVERITÀ DI IBS NON E’ MISURABILE SUI SINTOMO INTESTINALI, MA DA UN
COMPLESSO DI FATTORI. I FATTORI PSICOSOCIALI SONO FORTEMENTE ASSOCIATI ALLA SEVERITÀ DEL DOLORE
NELLA PRATICA
NECESSITÀ DI SISTEMATIZZARE UN METODO SEMPLICE PER VALUTARE IL GRADO
E LE COMPONENTI DELLA SEVERITÀ
LA TERAPIA DELL’IBS
IBS•GENETIC
•DISEASES
•STRESSORS
PATIENT BEHAVIOR
CNS
PSYCHOLOGICAL STATUS
GI PHYSIOLOGY
ENS
PHYSICIAN
THERAPY
What the Patient Hears
Doctor-Patient Relationship - FGIDs
23
Just to be sure . . .
Nothing to worry
about . . .
You have IBS . . .
Blah
Blah
CancerBlah
My symptoms
are worse
Do I have
cancer?
I’m under
more stress
They
think it’s
all in my
head
Why am I
not getting
better?
Will you believe me?
IBS - Patient’s Agenda
Am I crazy?
25
IBS - Doctor’s Agenda
Serious
disease
Recent
life stress
Psychologic
comorbidity
Hiddenagendanarcoticsdisabilitylaxatives
Referral
elsewhere?
Social and
cultural
factors
What do
I do?
26
IBS - RELAZIONE MEDICO-PAZIENTE
Acquisire la fiducia di un paziente stigmatizzato e che non capisce
l’origine dei disturbi
• Capire la sofferenza
• Spiegare i disturbi
• Educare il paziente
• Indicare obiettivi possibili
STRENGTH OF DOCTOR-PATIENT RELATIONSHIP
Owens et al Am Int Med 1995
Placebo Effect: 20-40%
Kathryn T et al. Plos One 2012;7; e48135
Number of FU Visits for FBDGenetics & Pl responseCathecol-O-Methyltransferase Val 108 Met Polym.
PFC
PLACEBO RESPONSE IN IBD
Response %
UC 17-28
CD 18-36
CD Fistula closure* 16-18
Sands B Dig Dis 2009;27:68-75
* Ford AC et al Clin Gastroenterol Hepatol 2014 S1542-3565(14)01315-9.doi 10,1016/j.cgh.2014
TREATMENTS FOR FBD
Bloating Diet
Abdominal pain/discomfortDiet
Diarrhea Diet
Constipation Diet
Bloating /
distention
Abdominal pain /
discomfort
Altered bowel
function
Brandt LJ et al. American J Gastroenterol 2009;104 Suppl 1
DIET IN IBS (EIGHT STUDIES)
FODMAP effects in the IBS patients
LOW-FODMAP STUDIESThree studies report symptom improvement with low-FODMAP diets in IBS patients
1. a significant number of IBS patients report gastrointestinal (GI) mmmmmmmmmmmmmmmmmmmmmsymptom foods containing
2. it has been hypothesized that gluten could act as a trigger for GI symptoms IBS and other clinical conditions s
3. GS is characterized by GI and extra-GI symptoms in the absence of the typical immunological and mucosal alterations caused by the ingestion of gluten
symptoms in GS patients are similar to those of IBS patients, even gluten hypersensitivity has been included among the possible etiopathogenetic or exacerbating factors for IBS symptoms
Staudacher et al, 2011: retrospective
De Roest et al, 2013: observational
Halmos et al, 2014:- accurate control of nutrients - 77% fructose malabsorption
- crossover with unblinding effect (only 17% of IBS patients did not
recognize the type of diet)
BLOATING
EFFECTS OF LOW FODMAP DIET IN IBS A
DOUBLE BLIND PARALLEL CONTROLLED CLINICAL TRIAL
PAIN
Piacentino et al. DDW 2014
TREATMENTS FOR FBD
Constipation Fibers (Ispaghula/psyllium)
Bloating /
distention
Abdominal pain /
discomfort
Altered bowel
function
EvidenceLevel
RecommendationGrade
Bran 3 C
Methylcellulose 3 C
Psyllium 2 B
Psyllium+Senna* 3 C
BULK LAXATIVES
Rankumar, Rao, AJGE 2005;
American College GE, AJGE 2005;
*Marlett et al AJGE, 1987
Aggravate Bloating, Dyspepsia, Bran Ineffective in Slow Rectal Transit,
*Aggravate Bloating & Cramps
TREATMENTS FOR FBD
Bloating Probiotics
Abodminal pain/discomfort Probiotics
Diarrhea Probiotics
ConstipationProbiotics
Bloating /
distention
Abdominal pain /
discomfort
Altered bowel
function
FLOW DIAGRAM OF IDENTIFIED STUDIES FOR
META-ANALYSIS OF PROBIOTICS IN IBS
NNT=7
AC Ford et al. Am J Gastroenterol 29 July 2014;doi:10,1038/ajg.2014,202
LIMITS OF PROBIOTIC STUDIES
LITTLE NUMBER OF PROPERLY-PERFORMED STUDIES
META-ANALYSIS POOL STUDIES WITH
Different Probiotics
Different Probiotic Species Combination
Different Dosages
Different Conditions
Different Patients
Few Patients
Direct-to-consumer marketing and lack of regulation are obstacles to proper clinical studies
43VERNA E.C. ET AL. THER ADV GASTROENTEROL 2010;5:307-319
FBD TREATMENT WITH PROBIOTICS
DIARRHEA PAIN BLOATING
GONFIORE DIARREA
CONSTIPATION BLOATING GONFIORE
Lactobacillus GGVSL #3 Lactobacillus
PlantarumLactobacillus Reuterii Bifidobacterium InfantisLactobacillus Casei
Saccharomyces Boulardii
B.Longum/Rhamnosus Acidophilus
L. Casei/Paracasei/Thermophilus
B. Lactis AnimalisL. Casei Shirota
TREATMENTS FOR IBS
Bloating Antibiotics
Diarrhea Antibiotics
Bloating /
distention
Abdominal pain /
discomfort
Altered bowel
function
EFFECT OF RIFAXIMIN ON NON-CONSTIPATED IBS
46
Pimentel M et al. N Engl J Med 2011;364:22-32
TREATMENTS FOR FBD
Abdominal pain/discomfort Antispasmodics Antidepressants
- TCAs/SSRIs/SNRIsBloating /
distention
Abdominal pain /
discomfort
Altered bowel
function
Poynard T. et al . Aliment Pharmacol Ther 2001;15:355-361
ANTISPASMODICS IN IBS
ANTIDEPRESSIVI NELLA SII
Jackson JL et al A J Med 2000
ANTIDEPRESSIVI
Studi controllatiDisordine dell’asse Cervello-Visceri
Alterata motilità GI
Ipersensibilità viscerale
Alterazione dei meccanismi centrali di regolazione
Neuroendocrino
Autonomico
Cognitivo
della percezione del dolore
EFFICACY OF ANTIDEPRESSANTS AND PSYCHOLOGICAL THERAPIES IN IBS
NNT 95%CI
TCA 4 3-6
SSRI 4 2.5-20
CBT 3 2-6
Hypnot 4 3-8
Ford AC et al. AJG 2014;109:1350-65
ANTIDEPRESSANTS FOR IBS CLINICAL CONSIDERATION
1. ACG Task Force on IBS. Am J Gastroenterol 2009;104(suppl 1):S1-S352. Ford AC et al. Gut 2009;58:367-3783. Grover M. Drossman A. Curr Opin Pharmacol 2008;8:715-723
TCAs in IBS-D, SSRIs in IBS-CSSRI/SNRI for anxiety
Poor response3 Satisfactory response3
Switch to different class antidepressant Combine treatments as augmentation Obtain psychiatry consultation
Continue at minimum effective dose for 6 to 12 months
Long-term therapy may be warranted for some patients
TREATMENTS FOR FBD
ConstipationSecretagogs Linaclotide
Bloating /
distention
Abdominal pain /
discomfort
Altered bowel
function
T53
Cl-Cl-
Na+
K+
K+
K+2Cl-
Tight
junction
H2O
Na+
H2O
Na+
Chloride Channels in Intestinal Transport
Ion Transport
Na+
CFTRchannel
EnterocytesCl C2
channel
Corsetti M, Tack J. UEG Journal 2013;1:7-20
AZIONE DELLA LINACLOTIDE SULL’EPITELIO INTESTINALE
Chey WD et al. AJG 2012;107:1702-12
EFFETTO DELLA LINACLOTIDE NELLA IBS-C
EFFECT OF LINACLOTIDE VS PLACEBO
IBS-C290gNNT
CC 145gNNT
CSBM(3/WK) 8 7
Abd. Pain/Disc. 8 9
CSBM+Abd Pain 12 5
Adequate Relief (>75%) 5 4
TREATMENTS FOR FBD
Bloating Diet Probiotics Antibiotics
Abdominal pain/discomfortProbiotics Antispasmodics Antidepressants
- TCAs/SSRIs/SNRIs
Diarrhea Diet Probiotics Antibiotics Colestyramine Loperamide
Constipation Diet Fibers (Ispaghula/psyllium) Probiotics LinaclotideWater-binding macrogol/Osmotic laxatives Prucalopride
Bloating /
distention
Abdominal pain /
discomfort
Altered bowel
function PsychotherapyCBT
Hypnotherapy
EFFECTIVENESS VS INVASIVENESS OF IBS TREATMENT
58Modified from Simrén M. et al Gut 2013;62:159-176
More Invasive
and/or Less Safe
Less Invasive
and/or Safer
Less Effective More Effective
Linaclotide
Loperamide
Probiotics
Loperamide
Prebiotics
TCA
Antispasm
Systematic
Exclusion Diets Low FODMAP DIET
Placebo
Antibiotics
FMT IN REFRACTORY IBS (N=13)
%
Pinn et al. Presented at AM College Gastroenterology 2013
EFFECTIVENESS VS INVASIVENESS OF IBS
TREATMENT
60Modified from Simrén M. et al Gut 2013;62:159-176
More Invasive
and/or Less Safe
Less Invasive
and/or Safer
Less Effective More Effective
Linaclotide
Loperamide
Probiotics
Loperamide
Prebiotics
TCA
Antispasm
Systematic
Exclusion Diets Low FODMAP DIET
Placebo
Antibiotics
• Valutare la storia medica, la personalità e la famiglia
Valutare la qualità di vita e il livello di attività quotidiana
Valutare la storia psicosociale
• Spiegare e rassicurare
• Istituire terapia appropriata
Stabilire una relazione terapeutica
Prescrivere test diagnostici Prescrivere test diagnostici
APPROCCIO MULTIDIMENSIONALE AL PAZIENTE CON MALATTIA CRONICA
Fare una diagnosi
IBS
GENETIC
HYPERSENSITIVITY
DIETARY FACTORS
INFLAMMATION
IMMUNE RESPONSE
STRESS
PSYCHOSOCIAL FACTORS
ALTERED MOTILITY
BEHAVIOR
DYSBIOSIS
CNS/ENS ALTERATIONS
GI SECRETION
IBS SEVERITY
DETERMINED BY PATIENT’S SYMPTOM REPORT AND BEHAVIOR
COMPOSITE OF
GI & EXTRA GI SYMPTOMS
DEGREE OF DISABILITY
ILLNESS-RELATED PERCEPTIONS
ILLNESS-RELATED BEHAVIOR
PSYCHOSOCIAL DISTRESS
GENDERE / AGE
Drossman DA et al. Am J Gastroenterol2011;106:1759;doi:10.1038/ajg.2011.201;published online 12 July 2011
CO MORBIDITY
SYMPTOM SEVERITY
QOL
EPISODE FREQUENCYIBS
COMORBIDITY
HYPERSENSITIVITY
BILE AC. MALABSORPTION
DIETARY FACTORS
ENVIRONMENTAL FACTORS
PSYCHOLOGICAL ALTERATIONS
SPASM
ILLNESS BEHAVIOR
DYSBIOSISS
RAPID TRANSIT
SLOW TRANSIT
IBS Pain Severity
Episode FrequencyEpisode Duration
QoL
MULTIDIMENSIONAL DIAGNOSTIC ASSESSMENT OF IBS PATIENT
POLY THERAPY
COLESTYRAMINE
PROPER DIET
TCA 5HT3 ANTAGONIST
RELAXATION TRAINING HYPNOSIS
SSRI SNRI PSYCHOTHERAPY
COGNITIVE BEHAVIORAL TH
STRESS
PROBIOTICS ANTIBIOTICS
SPASMOLYTICS
FIBER, LINACLOTIDE LAXATIVES, PRUCALOPRIDE
LOPERAMIDE, TCA
LONG DURATION
HIGH
SYMPTOM SEVERITY
LOW
SHORT DURATION
HIGH
FREQUENCY
LOW
IBS EPISODE
REASSURANCE ON DEMAND
CONTINUOUS
INTERMITTENT
CONSIDERAZIONI SULLA TERAPIA DI IBS
LE TERAPIA FARMACOLOGICHE SONO STATE TESTATE SU IBS, IBS-C E IBS-D. MANCANO STUDI SULLE SOTTOSINDROMI
FONDAMENTALE IL RAPPORTO MEDICO-PAZIENTE E L’EFFETTO PLACEBO
NELLA PRATICA
ESALTARE LE CAPACITÀ DEL MEDICO
LA DIETA LOW-FODMAP OFFRE NOTEVOLE BENEFICIO
LA LINACLOTIDE, PRIMO FARMACO CHE AGISCE TOPICAMENTE SULL’EPITELIO
SIA SU STIPSI CHE DOLORE
NELLA PRATICA
IDENTIFICARE CHI RISPONDE ALLA DIETA LOW-FODMAP E ALLA LINACLOTIDE