irritabel tarm syndrom - lab1 symposium...
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Irritabel Tarm Syndrom
Diagnoseverktøyet ROMA IV og biomarkører
Per G Farup
Professor, NTNU, Trondheim
Forskningsrådgiver, Sykehuset Innlandet HF, Gjøvik
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Rome III: Functional GI Disorders
Rome IV: Disorders of the Gut-Brain Interaction
Mage-tarm plager av ukjent årsak
Gastrointestinal disorders
……“without a structural basis to explain its clinical features, our understanding of
these disorders adhere to a biopsychological model wich is best represented for
these disorders in the growing field of neurogastroenterology.
Symptoms are generated based on a complex interaction among factors such as
microbial dysbiosis within the gut, altered mucosal immune function, altered gut
signalling (visceral hypersensitivity) and central nervous system dysregulation of
the modulation of gut signalling and motor function.
Drossmann DA, Hasler WL. Gastroenterology 2016; 150: 1257-61
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The ROME Criteria
Kongress i Roma i 1988
Rome III – 2006 Rome IV - 2016
1048 sider
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Rome IV – Classification of
Disorders of the Gut-Brain Interaction
8 hovedgrupper 32 undergrupper 32 under-undergrupper
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IBS – Rome: Diagnostic criteria
ROME III
Recurrent abdominal pain or discomfort at least 3 day/month in the last 3 months, associated with 2 or more of the following:
1. Improvement with defecation
2. Onset associated with a change in frequency of stool
3. Onset associated with a change in form (appearance) of stool
Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
ROME IV
Recurrent abdominal pain, on average, at least 1 day per week in the last 3 months, associated with 2 or more of the following criteria:
1. Related to defecation
2. Associated with a change in frequency of stool
3. Associated with a change in form (appearance) of stool
Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis
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IBS: Undergrupper og avgrensning til FC og FD
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IBS- Diagnose
• Tilfredsstille Rome IV kriteriene
• Diagnostiske tester hos alle (NICE anbefalinger april 2017)
– Blodstatus (full blood count)
– SR
– CRP
– Cøliaki test (endomysium antistoff eller vevs transglutaminse)
• Ikke nødvendig hos alle (NICE 2017)
– Ultralyd; recto/sigmoideoskopi; coloscopi/ rtg. colon; stoffskiftetester; tarmbakterier/parasitter;
blod i avføringen; Hydrogen pusteprøve (laktose intoleranse, bakteriell overvekst [2008]).
• Bør utredes videre («red flags»)
– Debutalder > 50 år
– Vekttap
– Blod i avføringen
– Feber
– Kvalme / oppkast
– Magesmerter uten relasjon til avføringen
– Vedvarende eller nattlig diare
– Anemi (jernmangel)
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Biomarkør – Definition og bruk
• Biologisk markør (biological marker /biomarker):
– A characteristic that is objectively measured and evaluated as an
indicator of normal biological processes, pathogenic processes,
or pharmacologic responses to a therapeutic intervention
Biomarkers Definitions Working Group 2001
• Bruksområder
– Diagnostikk
– Type og stadieinndeling av sykdom
– Prognose
– Behandlingseffekt
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IBS - Biomarkører
Gut 2009; 58: 1571-5
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IBS - Biomarkører
Krav til en god biomarkør
• Akseptabel for pasientene
• Enkel i bruk for helsevesenet
• Høy reproduserbarhet
• Lav variabilitet (innen definerte
pasientgrupper)
• Diskriminere godt mellom grupper
• Billig
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IBS – biomarkør - blodprøver
Lembo et al. AP&T 2009; 29: 834-42
Sensitivity 50%; specificity 88%; accuracy 70%.
Jones MP et al. AP&T 2014; 39: 426-37 34 blodprøver + 4 psykologiske markører
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IBS – biomarkører – tarmfunksjon
• Motilitet i tynn- og tykktarm (manometri)
• Trykk og elastisitet (barostat)
• Følsomhet en lovende metode
– Sensitivitet 63-96%; Spesifisitet 71-90%
Ludidi et al. Neurogastroenterol Motil (2012) 24, 729–e346
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IBS – biomarkører – CNS bilder
A striking finding among interventions was the
substantial influence that patient variables (e.g., sex,
psychological and disease related factors) had upon the
identification of neuroanatomical differences in structure
and connectivity.
CONCLUSION:The field of neuroimaging can provide
insight into underlying physiological differences that
distinguish patients with IBS from a healthy population
CNS bildediagnostikk:
• Ikke egnet til diagnostikk av IBS
• Kan kanskje få en plass som prediktiv biomarkør for effekt av antidepressiv og psykologisk behandling
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IBS – biomarkører – feces
Inflammasjonsmarkører
• Kalprotektin og laktoferin
– Skiller IBS fra IBD, men ikke fra friske
• Graniner – for lite undersøkt
• Gallesyrer
– Gallesyremalabsorpsjon - egen sykdom?
• Tarmfloraens sammensetning
• Tarmfloraens funksjon
– Korte fettsyrer
Aasbrenn M et al. Bennet et al. Gut and Liver 2015; 9: 318.31 Farup PG et al. BMC Gastro 2016 16:51
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IBS – biomarkører - tarmveggen
• Biopsier
– Mastceller, T- og B-lymfocytter
– Cytokiner (TNF og Il10?)
– Økt mengde celler: Kromogranin A, Peptid YY, Somatostatin
• Ultralydmålinger av veggtykkelse
• Tarmpermeabilitet
– In subsets of IBS patients, increased intestinal permeability, brought on by a variety of different triggers, is likely connected to facilitating mucosal inflammation and activation of visceral pain.
Camilleri et al. Am J Physiol 2012; 303:G775-85
El-Sahly et al. Gastro Res Pract 2014; ID 462856 Redusert menge Kromogranin A celler i duodenum Sens: 86%; Spec 96%
El-Sahly et al. Peptides 2015; 67: 12-9 Redusert menge PYY og økt mengde Somatostatin celler i rektum Sens: 86%; Spec 96%
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IBS – biomarkører - psykologi
• Psykologisk komorbiditet er hyppig
• Uegnet som biomarkør fordi
– Stor interindividuell variasjon
– Stor variasjon over tid
Sood R, et al.
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IBS – diagnostiske biomarkører
Hvorfor har ikke forskningen funnet diagnostiske biomarkører for IBS?
• IBS er en bio-psyko-sosial lidelse med et mangfoldig sykdomsbilde.
• IBS har ukjent etiologi
• IBS har en meget kompleks patofysiologi
• IBS er ikke en sykdom, men flere sykdommer med felles symptomatologi.
Hva bringer fremtiden?
• En kombinasjon av noen få biomarkører??
• Vi diagnostiserer flere sykdommer slik at IBS blir en mindre gruppe?
– Mikroskopisk colitt
– Gallesyreindusert diare
– Ikke-cøliaki gluten/hvete intoleranse?
– FODMAP intoleranse??
– Matvareintoleranse????
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Litteratur
• s
https://www.bioingenioren.no/contentassets/c7e53886e4d841ac94c12f56320fbb27/diagnostikk-av-irritabel-tarmsyndrom-_-finnes-det-gode-biomarkorer.pdf
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