This document summarizes research on the diagnosis and treatment of irritable bowel syndrome (IBS). It begins by defining IBS and reviewing its prevalence in Italy. It then discusses the diagnostic criteria for IBS, emphasizing the importance of a symptom-based positive diagnosis. Various IBS subtypes and comorbidities are also outlined. Regarding treatment, the document examines dietary approaches including low FODMAP diets, the use of probiotics and antibiotics, and the importance of the patient-physician relationship. It stresses the multifactorial nature of IBS and need for multidimensional diagnosis and treatment.
2. FGID: DEFINITION
“ Variable combination of chronic or
recurrent gastrointestinal symptoms
not explained by structural or
biochemical abnormalities”
Drossman et al Gastroenterol Int 1990;3:159
4. IBS PREVALENCE IN ITALY
FACE-FACE INTERVIEW
Physical Ex. & US
Random/Electoral Rolls
n=46,139 Resp. R 63,2%
IBS ROME I CRITERIA
F= 10.7%
M= 5.4%
E Corazziari et al. Digest and Liver Disease 2008;40:944-950 4
6. IBS- DIAGNOSTIC CRITERIA
HOW TO MAKE A DIAGNOSIS OF A
CHRONIC FUNCTIONAL DISORDER
WHEN NO BIOLOGICAL MARKER
EXISTS ?
By exclusion
Positive-Symptom based
7. IBS- DIAGNOSTIC CRITERIA
Exclusion 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
8. 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
9. IBS SUBGROUPS ACCORDING TO ROME
QUESTIONNAIRE AND DIARY CARD
IBS-D
47%
IBS-C
22%
23%
12%
12%
53%
40%
60%
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
10. 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
11. 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
4% M
7%
19. STRESSFUL EVENTS
PREDICT
Onset of FGIDs
Symptom exacerbation and
health seeking
IBS symptom intensity
Bennett EJ et al. Gut 1998: 43:256
Creed FH et al. Gut 1988; 29:235
20. PSYCHOPATHOLOGY IN
IBS DYSPEPSIA COMORBIDITY
Piacentino D et al. 2014 Submitted for publication
21. 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 Gastroenterol
2011;106:1759;doi:10.1038/ajg.2011.201;published online 12 July 2011
22. PSYCHOLOGICAL STATUS IN
IBS-C vs CIC & IBS-D vs FD
40
35
30
25
20
15
10
5
0
IBS-C
IBS-D
CIC
FD
ANXIETY SOMATIZATION
%
* p<0.00
*
*
*
*
Ford AC et al. APT 2014;39:312-321
23. 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 comorbidities
And
Related polytherapy
24. 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
26. PSYCHOLOGICAL
IBS
•GENETIC
•DISEASES
•STRESSORS
PATIENT
BEHAVIOR
CNS
STATUS
GI
ENS
PHYSIOLOGY
PHYSICIAN
THERAPY
27. Doctor-Patient Relationship - FGIDs
What the Patient Hears
23
Just to be
sure . . .
You have
IBS . . .
Nothing to
worry
about . . .
Blah
Cancer
Blah
Blah
28. They
think it’s
all in my
head
IBS - Patient’s Agenda
My symptoms
are worse
Do I have
cancer?
I’m under
more stress
Why am I
not getting
better?
Will
you
believe
me?
Am I crazy?
25
29. IBS - Doctor’s Agenda
Serious
disease
Recent
life stress
Psychologic
comorbidity
Hidden
agenda
narcotics
disability
laxatives
Referral
elsewhere?
Social and
cultural
factors
What do
I do?
26
30. 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
31.
32. 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 FBD
Genetics & Pl response
Cathecol-O-Methyltransferase Val 108 Met Polym.
PFC
33. 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
37. LOW-FODMAP STUDIES
Three studies report symptom improvement with low-FODMAP
diets in IBS patients
1. a significant number of IBS patients report gastrointestinal (GI)
Staudacher et al, 2011: retrospective
mmmmmmmmmmmmmmmmmmmmmsymptom foods containing
2. it has been hypothesized that gluten could act as a trigger for GI
De Roest et al, 2013: observational
symptoms IBS and other clinical conditions s
3. GS is characterized by GI and extra-GI symptoms in the absence of
Halmos et al, 2014:
the typical immunological and mucosal alterations caused by the
ingestion of gluten
- accurate control of nutrients
- 77% fructose malabsorption
- crossover with unblinding effect
(only 17% of IBS patients did not
symptoms in GS patients are similar to those of IBS patients, even
recognize the type of diet)
gluten hypersensitivity has been included among the possible
etiopathogenetic or exacerbating factors for IBS symptoms
38. EFFECTS OF LOW FODMAP DIET IN IBS A
DOUBLE BLIND PARALLEL CONTROLLED CLINICAL TRIAL
BLOATING
PAIN
Piacentino et al. DDW 2014
39. TREATMENTS FOR FBD
Constipation
Fibers (Ispaghula/psyllium)
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function
40. BULK LAXATIVES
Evidence
Level
Recommendation
Grade
Bran 3 C
Methylcellulose 3 C
Psyllium 2 B
Psyllium+Senna* 3 C
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
42. 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
43. 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
43
VERNA E.C. ET AL. THER ADV GASTROENTEROL 2010;5:307-319
44. FBD TREATMENT
WITH PROBIOTICS
DIARRHEA
PAIN BLOATING
GONFIORE DIARREA
CONSTIPATION
BLOATING
GONFIORE
Lactobacillus GG
VSL #3
Lactobacillus
Plantarum
Lactobacillus Reuterii
Bifidobacterium Infantis
Lactobacillus Casei
Saccharomyces Boulardii
B.Longum/Rhamnosus
Acidophilus
L. Casei/Paracasei
/Thermophilus
B. Lactis Animalis
L. Casei Shirota
45. TREATMENTS FOR IBS
Bloating
Antibiotics
Diarrhea
Antibiotics
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function
46. EFFECT OF RIFAXIMIN ON NON-CONSTIPATED
IBS
46
Pimentel M et al. N Engl J Med 2011;364:22-32
49. ANTIDEPRESSIVI NELLA SII
ANTIDEPRESSIVI
Jackson JL et al A J Med 2000
Disordine dell’asse Cervello- Studi controllati
Visceri
Alterata motilità GI
Ipersensibilità viscerale
Alterazione dei
meccanismi centrali di
regolazione
Neuroendocrino
Autonomico
Cognitivo
della percezione del
dolore
50. 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
51. ANTIDEPRESSANTS FOR IBS
CLINICAL CONSIDERATION
TCAs in IBS-D, SSRIs in IBS-C
SSRI/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
1. ACG Task Force on IBS. Am J Gastroenterol 2009;104(suppl 1):S1-S35
2. Ford AC et al. Gut 2009;58:367-378
3. Grover M. Drossman A. Curr Opin Pharmacol 2008;8:715-723
52. TREATMENTS FOR FBD
Constipation
Secretagogs Linaclotide
Bloating /
distention
Abdominal
pain /
discomfort
Altered
bowel
function
53. T53
Chloride Channels in Intestinal Transport
Cl-
Cl-
CFTR
channel
Na+
K+
K+
2Cl K+
-
Tight
junction
H2O
Na+
H2O
Na+
Ion Transport
Na+
Enterocytes
Cl C2
channel
58. EFFECTIVENESS VS INVASIVENESS OF IBS TREATMENT
Less Effective More Effective
58
More Invasive
and/or Less Safe
Less Invasive
and/or Safer
Modified from Simrén M. et al Gut 2013;62:159-176
Linaclotide
Loperamide
Antibiotics
Probiotics
Loperamide
Prebiotics
TCA
Antispasm
Systematic
Exclusion Diets Low FODMAP DIET
Placebo
59. FMT IN REFRACTORY IBS (N=13)
%
Pinn et al. Presented at AM College Gastroenterology 2013
60. EFFECTIVENESS VS INVASIVENESS OF IBS
TREATMENT
Less Effective More Effective
60
More Invasive
and/or Less Safe
Less Invasive
and/or Safer
Modified from Simrén M. et al Gut 2013;62:159-176
Linaclotide
Loperamide
Antibiotics
Probiotics
Loperamide
Prebiotics
TCA
Antispasm
Systematic
Exclusion Diets Low FODMAP DIET
Placebo
61. APPROCCIO MULTIDIMENSIONALE AL PAZIENTE CON MALATTIA
CRONICA
Stabilire una relazione terapeutica
• Valutare la storia medica, la personalità e la famiglia
Valutare la qualità di vita e il livello di attività quotidiana
Valutare la storia psicosociale
Prescrivere test diagnostici
Fare una diagnosi
• Spiegare e rassicurare
• Istituire terapia appropriata
63. 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 Gastroenterol
2011;106:1759;doi:10.1038/ajg.2011.201;published online 12 July 2011
66. LONG DURATION
HIGH
SYMPTOM
SEVERITY
LOW
CONTINUOUS
INTERMITTENT
SHORT DURATION
HIGH
FREQUENCY
LOW
IBS
EPISODE
REASSURANCE ON DEMAND
67. 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