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Sindrome dell'intestino 
irritabile: diagnosi e terapia 
Relatore: Prof. E. Corazziari (Roma)
FGID: DEFINITION 
“ Variable combination of chronic or 
recurrent gastrointestinal symptoms 
not explained by structural o...
FUNCTIONAL BOWEL DISORDERS 
ROME EVOLUTION 
From the Irritable Colon Syndrome to 
Functional Bowel Disorders 
 Irritable ...
IBS PREVALENCE IN ITALY 
FACE-FACE INTERVIEW 
Physical Ex. & US 
Random/Electoral Rolls 
n=46,139 Resp. R 63,2% 
IBS ROME ...
LA DIAGNOSI DI IBS
IBS- DIAGNOSTIC CRITERIA 
HOW TO MAKE A DIAGNOSIS OF A 
CHRONIC FUNCTIONAL DISORDER 
WHEN NO BIOLOGICAL MARKER 
EXISTS ? 
...
IBS- DIAGNOSTIC CRITERIA 
Exclusion of the Diseases with 
Detectable Diagnostic Markers 
 useful to detect relevant disor...
IBS-DIAGNOSTIC CRITERIA 
Positive symptom-based diagnosis 
OFFER CONFIDENT DIAGNOSIS? 
 Reduce unneeded investigations 
...
IBS SUBGROUPS ACCORDING TO ROME 
QUESTIONNAIRE AND DIARY CARD 
IBS-D 
47% 
IBS-C 
22% 
23% 
12% 
12% 
53% 
40% 
60% 
N=68 ...
ABDOMINAL PAIN AND BLOATING DIFFER 
IN RELATION TO EATING AND 
DEFECATION IN IBS PATIENTS 
Carboni S, Cantarini R, Badiali...
TWO YEAR (IN)STABILITY OF ROME II IBS 
Williams et al APT 2006; 23: 197-205 
30% 
IDENTICAL 
IBS subtypes 
ROME II 
IBS 
N...
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 
35.5 
FC 
WELL 
IBS-M 
W...
BOWEL CHARACTERISTICS IN 
IBS-C vs CIC 
90 
80 
70 
60 
50 
40 
30 
20 
10 
0 
<3 ev/WK Hard Stools Straining Inc. Empty. ...
THE CONSTIPATION UNIVERSE 
Rey E et al. Am J Gastroenterol advance online publication, 4 March 2014;doi:10.1038/ajg.2014.1...
THE VANISHING FUNCTIONAL 
ORGANIC BOUNDARIES 
 Lactase deficiency 
 Celiac disease 
 Gluten sensitivity 
 Bacterial ov...
EXTRA-GI CONDITIONS IN DBF (>30%) 
 URINARY 
 Interstitial cystitis 
 Incontinence 
 Detrusor instability 
 MUSCOLOSK...
COMORBIDITIES ASSOCIATED WITH IBS 
COMORBIDITY REPORTED PREVALENCE IN IBS 
GI disorders 
Gastritis, duodenitis 31.2% 
Infl...
STRESSFUL EVENTS 
PREDICT 
 Onset of FGIDs 
 Symptom exacerbation and 
health seeking 
 IBS symptom intensity 
Bennett ...
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 DIS...
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 SOMA...
THE MULTIDIMENSIONAL DIAGNOSIS OF IBS 
Symptom-based diagnosis of IBS 
 Diagnose IBS-Subtype 
 Assess IBS severity 
As...
CONSIDERAZIONI SULLA DIAGNOSI DI IBS 
 I CRITERI DI ROMA 
 Categorizzano a fini classificativi le grandi sindromi funzio...
LA TERAPIA DELL’IBS
PSYCHOLOGICAL 
IBS 
•GENETIC 
•DISEASES 
•STRESSORS 
PATIENT 
BEHAVIOR 
CNS 
STATUS 
GI 
ENS 
PHYSIOLOGY 
PHYSICIAN 
THERA...
Doctor-Patient Relationship - FGIDs 
What the Patient Hears 
23 
Just to be 
sure . . . 
You have 
IBS . . . 
Nothing to 
...
They 
think it’s 
all in my 
head 
IBS - Patient’s Agenda 
My symptoms 
are worse 
Do I have 
cancer? 
I’m under 
more str...
IBS - Doctor’s Agenda 
Serious 
disease 
Recent 
life stress 
Psychologic 
comorbidity 
Hidden 
agenda 
narcotics 
disabil...
IBS - RELAZIONE MEDICO-PAZIENTE 
Acquisire la fiducia di un paziente stigmatizzato e che non capisce 
l’origine dei distur...
STRENGTH OF DOCTOR-PATIENT 
RELATIONSHIP 
Owens et al Am Int Med 1995 
Placebo Effect: 20-40% 
Kathryn T et al. Plos One 2...
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 ...
TREATMENTS FOR FBD 
Bloating 
 Diet 
Abdominal pain/discomfort 
Diet 
Diarrhea 
 Diet 
Constipation 
 Diet 
Bloating /...
DIET IN IBS (EIGHT STUDIES) 
Brandt LJ et al. American J Gastroenterol 2009;104 Suppl 1
FODMAP effects in the IBS patients
LOW-FODMAP STUDIES 
Three studies report symptom improvement with low-FODMAP 
diets in IBS patients 
1. a significant numb...
EFFECTS OF LOW FODMAP DIET IN IBS A 
DOUBLE BLIND PARALLEL CONTROLLED CLINICAL TRIAL 
BLOATING 
PAIN 
Piacentino et al. DD...
TREATMENTS FOR FBD 
Constipation 
 Fibers (Ispaghula/psyllium) 
Bloating / 
distention 
Abdominal 
pain / 
discomfort 
Al...
BULK LAXATIVES 
Evidence 
Level 
Recommendation 
Grade 
Bran 3 C 
Methylcellulose 3 C 
Psyllium 2 B 
Psyllium+Senna* 3 C 
...
TREATMENTS FOR FBD 
Bloating 
 Probiotics 
Abodminal pain/discomfort 
 Probiotics 
Diarrhea 
 Probiotics 
Constipation ...
FLOW DIAGRAM OF IDENTIFIED STUDIES FOR 
META-ANALYSIS OF PROBIOTICS IN IBS 
NNT=7 
AC Ford et al. Am J Gastroenterol 29 Ju...
LIMITS OF PROBIOTIC STUDIES 
LITTLE NUMBER OF PROPERLY-PERFORMED STUDIES 
META-ANALYSIS POOL STUDIES WITH 
 Different Pro...
FBD TREATMENT 
WITH PROBIOTICS 
DIARRHEA 
PAIN BLOATING 
GONFIORE DIARREA 
CONSTIPATION 
BLOATING 
GONFIORE 
Lactobacillu...
TREATMENTS FOR IBS 
Bloating 
 Antibiotics 
Diarrhea 
 Antibiotics 
Bloating / 
distention 
Abdominal 
pain / 
discomfor...
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 
Abdominal 
pain / 
discomfort 
Bloatin...
ANTISPASMODICS IN IBS 
Poynard T. et al . Aliment Pharmacol Ther 2001;15:355-361
ANTIDEPRESSIVI NELLA SII 
ANTIDEPRESSIVI 
Jackson JL et al A J Med 2000 
Disordine dell’asse Cervello- Studi controllati 
...
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 ...
ANTIDEPRESSANTS FOR IBS 
CLINICAL CONSIDERATION 
TCAs in IBS-D, SSRIs in IBS-C 
SSRI/SNRI for anxiety 
Poor response3 Sati...
TREATMENTS FOR FBD 
Constipation 
Secretagogs Linaclotide 
Bloating / 
distention 
Abdominal 
pain / 
discomfort 
Altered...
T53 
Chloride Channels in Intestinal Transport 
Cl- 
Cl- 
CFTR 
channel 
Na+ 
K+ 
K+ 
2Cl K+ 
- 
Tight 
junction 
H2O 
Na+...
AZIONE DELLA LINACLOTIDE 
SULL’EPITELIO INTESTINALE 
Corsetti M, Tack J. UEG Journal 2013;1:7-20
EFFETTO DELLA LINACLOTIDE NELLA 
IBS-C 
Chey WD et al. AJG 2012;107:1702-12
EFFECT OF LINACLOTIDE 
VS PLACEBO 
IBS-C 
290g 
NNT 
CC 
145g 
NNT 
CSBM(3/WK) 8 7 
Abd. Pain/Disc. 8 9 
CSBM+Abd Pain ...
TREATMENTS FOR FBD 
Bloating 
 Diet 
 Probiotics 
 Antibiotics 
Abdominal pain/discomfort 
Probiotics 
Antispasmodics...
EFFECTIVENESS VS INVASIVENESS OF IBS TREATMENT 
Less Effective More Effective 
58 
More Invasive 
and/or Less Safe 
Less I...
FMT IN REFRACTORY IBS (N=13) 
% 
Pinn et al. Presented at AM College Gastroenterology 2013
EFFECTIVENESS VS INVASIVENESS OF IBS 
TREATMENT 
Less Effective More Effective 
60 
More Invasive 
and/or Less Safe 
Less ...
APPROCCIO MULTIDIMENSIONALE AL PAZIENTE CON MALATTIA 
CRONICA 
 Stabilire una relazione terapeutica 
• Valutare la storia...
GENETIC 
IBS 
DIETARY FACTORS 
INFLAMMATION 
HYPERSENSITIVITY 
IMMUNE RESPONSE 
STRESS 
CNS/ENS ALTERATIONS 
PSYCHOSOCIAL ...
IBS SEVERITY 
DETERMINED BY PATIENT’S SYMPTOM REPORT AND BEHAVIOR 
COMPOSITE OF 
 GI & EXTRA GI SYMPTOMS 
 DEGREE OF DIS...
CO MORBIDITY 
SYMPTOM 
SEVERITY 
EPISODE 
FREQUENCY IBS 
QOL
MULTIDIMENSIONAL DIAGNOSTIC ASSESSMENT OF IBS PATIENT 
COMORBIDITY 
BILE AC. MALABSORPTION 
DIETARY FACTORS 
HYPERSENSITIV...
LONG DURATION 
HIGH 
SYMPTOM 
SEVERITY 
LOW 
CONTINUOUS 
INTERMITTENT 
SHORT DURATION 
HIGH 
FREQUENCY 
LOW 
IBS 
EPISODE ...
CONSIDERAZIONI SULLA TERAPIA DI IBS 
 LE TERAPIA FARMACOLOGICHE SONO STATE TESTATE SU IBS, IBS-C E IBS-D. 
MANCANO STUDI ...
Sindrome dell'intestino irritabile: diagnosi e terapia - Gastrolearning®
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Sindrome dell'intestino irritabile: diagnosi e terapia - Gastrolearning®

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Sindrome dell'intestino irritabile: diagnosi e terapia

Relatore: Prof. Enrico Corazziari (Roma)

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Sindrome dell'intestino irritabile: diagnosi e terapia - Gastrolearning®

  1. 1. Sindrome dell'intestino irritabile: diagnosi e terapia Relatore: Prof. E. Corazziari (Roma)
  2. 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
  3. 3. FUNCTIONAL BOWEL DISORDERS ROME EVOLUTION From the Irritable Colon Syndrome to Functional Bowel Disorders  Irritable Bowel Syndrome (Pain + Bowel Disorders)  Functional Constipation (+/- Pain)  Functional Diarrhea (no Pain)  Functional Abdominal Bloating  Unspecified bowel disorders
  4. 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
  5. 5. LA DIAGNOSI DI IBS
  6. 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. 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. 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. 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. 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. 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%
  12. 12. IBS-C-CIC AND IBS-D-FD OVERLAP Ford A.C. et al. Aliment Pharmacol Ther 2014;39:312-321
  13. 13. ONE YEAR (IN)STABILITY (%) OF ROME III IBS-C & FC Wong et al. Am J Gastroenterol 2010;105:2228 35.5 FC WELL IBS-M WELL IBS- C 14 25.5 39
  14. 14. BOWEL CHARACTERISTICS IN IBS-C vs CIC 90 80 70 60 50 40 30 20 10 0 <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 * *
  15. 15. THE CONSTIPATION UNIVERSE Rey E et al. Am J Gastroenterol advance online publication, 4 March 2014;doi:10.1038/ajg.2014.18
  16. 16. THE VANISHING FUNCTIONAL ORGANIC BOUNDARIES  Lactase deficiency  Celiac disease  Gluten sensitivity  Bacterial overgrowth  Bile salt malabsorption Non specific minimal change inflammation Subclinical intestinal inflammation
  17. 17. EXTRA-GI CONDITIONS IN DBF (>30%)  URINARY  Interstitial cystitis  Incontinence  Detrusor instability  MUSCOLOSKELETAL  Fibromyalgia  Backache  Headache  SEXUAL  Dyspareunia  Decreased libido  Inhibited orgasm  PSYCHOLOGICAL  Affective disorders  Stress sensitivity  Illness behavior  Health seeking behavior Whorwell et al 1986; Nyhlin et al 1993; Triadofilopoulos et al 1991
  18. 18. COMORBIDITIES ASSOCIATED WITH IBS 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 p<0.05 8.6% Temporomandibular joint disorder 3.3% Dysmenorrhoea 2.3% Cystitis 1.8% Whitehead WE et al. Am J Gastroenterol 2007;102:2762
  19. 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. 20. PSYCHOPATHOLOGY IN IBS DYSPEPSIA COMORBIDITY Piacentino D et al. 2014 Submitted for publication
  21. 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. 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. 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. 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
  25. 25. LA TERAPIA DELL’IBS
  26. 26. PSYCHOLOGICAL IBS •GENETIC •DISEASES •STRESSORS PATIENT BEHAVIOR CNS STATUS GI ENS PHYSIOLOGY PHYSICIAN THERAPY
  27. 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. 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. 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. 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. 31. 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
  32. 32. 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
  33. 33. TREATMENTS FOR FBD Bloating  Diet Abdominal pain/discomfort Diet Diarrhea  Diet Constipation  Diet Bloating / distention Abdominal pain / discomfort Altered bowel function
  34. 34. DIET IN IBS (EIGHT STUDIES) Brandt LJ et al. American J Gastroenterol 2009;104 Suppl 1
  35. 35. FODMAP effects in the IBS patients
  36. 36. 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
  37. 37. EFFECTS OF LOW FODMAP DIET IN IBS A DOUBLE BLIND PARALLEL CONTROLLED CLINICAL TRIAL BLOATING PAIN Piacentino et al. DDW 2014
  38. 38. TREATMENTS FOR FBD Constipation  Fibers (Ispaghula/psyllium) Bloating / distention Abdominal pain / discomfort Altered bowel function
  39. 39. 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
  40. 40. TREATMENTS FOR FBD Bloating  Probiotics Abodminal pain/discomfort  Probiotics Diarrhea  Probiotics Constipation Probiotics Bloating / distention Abdominal pain / discomfort Altered bowel function
  41. 41. 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
  42. 42. 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
  43. 43. 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
  44. 44. TREATMENTS FOR IBS Bloating  Antibiotics Diarrhea  Antibiotics Bloating / distention Abdominal pain / discomfort Altered bowel function
  45. 45. EFFECT OF RIFAXIMIN ON NON-CONSTIPATED IBS 46 Pimentel M et al. N Engl J Med 2011;364:22-32
  46. 46. TREATMENTS FOR FBD Abdominal pain/discomfort  Antispasmodics  Antidepressants Abdominal pain / discomfort Bloating / - TCAs/SSRIs/SNRIs distention Altered bowel function
  47. 47. ANTISPASMODICS IN IBS Poynard T. et al . Aliment Pharmacol Ther 2001;15:355-361
  48. 48. 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
  49. 49. 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
  50. 50. 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
  51. 51. TREATMENTS FOR FBD Constipation Secretagogs Linaclotide Bloating / distention Abdominal pain / discomfort Altered bowel function
  52. 52. 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
  53. 53. AZIONE DELLA LINACLOTIDE SULL’EPITELIO INTESTINALE Corsetti M, Tack J. UEG Journal 2013;1:7-20
  54. 54. EFFETTO DELLA LINACLOTIDE NELLA IBS-C Chey WD et al. AJG 2012;107:1702-12
  55. 55. EFFECT OF LINACLOTIDE VS PLACEBO IBS-C 290g NNT CC 145g NNT CSBM(3/WK) 8 7 Abd. Pain/Disc. 8 9 CSBM+Abd Pain 12 5 Adequate Relief (>75%) 5 4
  56. 56. TREATMENTS FOR FBD Bloating  Diet  Probiotics  Antibiotics Abdominal pain/discomfort Probiotics Antispasmodics  Antidepressants - TCAs/SSRIs/SNRIs Diarrhea  Diet  Probiotics  Antibiotics  Colestyramine  Loperamide Constipation  Diet  Fibers (Ispaghula/psyllium)  Probiotics  Linaclotide Water-binding macrogol/Osmotic laxatives  Prucalopride Bloating / distention Abdominal pain / discomfort Altered bowel function Psychotherapy CBT Hypnotherapy
  57. 57. 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
  58. 58. FMT IN REFRACTORY IBS (N=13) % Pinn et al. Presented at AM College Gastroenterology 2013
  59. 59. 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
  60. 60. 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
  61. 61. GENETIC IBS DIETARY FACTORS INFLAMMATION HYPERSENSITIVITY IMMUNE RESPONSE STRESS CNS/ENS ALTERATIONS PSYCHOSOCIAL FACTORS GI SECRETION ALTERED MOTILITY DYSBIOSIS BEHAVIOR
  62. 62. 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
  63. 63. CO MORBIDITY SYMPTOM SEVERITY EPISODE FREQUENCY IBS QOL
  64. 64. MULTIDIMENSIONAL DIAGNOSTIC ASSESSMENT OF IBS PATIENT COMORBIDITY BILE AC. MALABSORPTION DIETARY FACTORS HYPERSENSITIVITY ENVIRONMENTAL FACTORS RAPID TRANSIT POLY THERAPY LOPERAMIDE, TCA FIBER, LINACLOTIDE LAXATIVES, PRUCALOPRIDE SPASMOLYTICS COGNITIVE BEHAVIORAL TH STRESS PSYCHOLOGICAL ALTERATIONS SLOW TRANSIT SPASM DYSBIOSIS S ILLNESS BEHAVIOR IBS Pain Severity Episode Frequency Episode Duration QoL COLESTYRAMINE PROPER DIET TCA 5HT3 ANTAGONIST RELAXATION TRAINING HYPNOSIS SSRI SNRI PSYCHOTHERAPY PROBIOTICS ANTIBIOTICS
  65. 65. LONG DURATION HIGH SYMPTOM SEVERITY LOW CONTINUOUS INTERMITTENT SHORT DURATION HIGH FREQUENCY LOW IBS EPISODE REASSURANCE ON DEMAND
  66. 66. 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

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