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Crohnin taudin hoito

Käypä hoito
4.4.2005
Suomalaisen Lääkäriseuran Duodecimin ja Suomen Gastroenterologiayhdistys ry:n asettama työryhmä

Suosituksen tulostettava versio (pdf) «»1

Tiivistelmä suomeksi «Crohnin taudin hoito»1 ja englanniksi «Treatment of Crohn´s disease»2

Keskeinen sanoma

  • Crohnin taudin hoidon tavoitteina ovat oireettomuus sekä komplikaatioiden ja taudin uusiutumisen esto.
  • Lievän Crohnin taudin hoitoon ja uusiutumisen estoon käytetään 5-aminosalisyylihappo- eli 5-ASA-valmisteita.
    • Vaihtoehtona lievästi aktiivisen taudin hoitoon on metronidatsoli.
  • Keskivaikean ja vaikean taudin lääkehoitona käytetään kortikosteroidia, ja lisäksi tarvitaan usein ravitsemushoitoa ja kirurgiaa.
  • Kortikosteroideista riippuvaisilla ja hoitoon huonosti reagoivilla käytetään immunomoduloivia lääkkeitä, kuten atsatiopriinia ja infliksimabia.
    • Atsatiopriini ja infliksimabi soveltuvat myös ylläpitohoitoon näillä potilailla.
  • Vaikea Crohnin tauti hoidetaan tähän sairauteen hyvin perehtyneissä sairaaloissa.
  • Perusterveydenhuollon tehtävänä on havaita riittävän varhain Crohnin taudin mahdollisuus ja ohjata kyseiset potilaat jatkotutkimuksiin.
    • Rauhallisessa vaiheessa olevaa sairautta potevaa voidaan seurata perusterveydenhuollossa erikoissairaanhoidosta saatujen ohjeiden mukaisesti.

Tavoitteet ja kohderyhmät

  • Tämän suosituksen tavoitteena on, että
    • Crohn-potilaat hoidetaan tutkimusten ja kokemuksen mukaan parhaiten vaikuttavalla lääkityksellä sekä ravitsemus- ja leikkaushoidolla ja
    • perusterveydenhuollon ja erikoissairaanhoidon hoitohenkilökunnalla on riittävä tieto Crohnin taudin hoidosta.
  • Kohderyhmänä ovat erityisesti erikoissairaanhoidon poliklinikoissa, perusterveydenhuollossa ja yksityissektorilla työskentelevät lääkärit ja muu hoitohenkilökunta.

Esiintyvyys ja ilmaantuvuus

Etiologia ja patogeneesi

Crohnin taudin kulku ja kliininen kuva

Diagnostiikka

Oireet sekä kliiniset ja laboratoriolöydökset

Erotusdiagnostiikka

Endoskopia ja histologia

Kuvantamistutkimukset

Taulukko 1. Crohnin taudin kliinisiä ilmentymiä.
Yleisiä oireita Yleisiä kliinisiä löydöksiä Yleisiä laboratorio- ja röntgenlöydöksiä
Vatsakipu Vatsan aristus Lievä anemia
Suolentukosoireet Palpoitava massa vatsan alueella Lievä leukosytoosi
Ripuli Perianaalifistelit ja fissuurat Suurentunut lasko
Tihentynyt ulostamistarve Ohutsuolen striktuurat Hypoalbuminemia
Kuumeilu
Verenvuoto peräsuolesta
Laihtuminen
Anaalialueen vaivat
Kasvun hidastuminen
Taulukko 2. Crohnin taudin erotusdiagnostiikka.
Tauti Tärkeimmät erotusdiagnostiset tutkimukset
Suolistotuberkuloosi Tuberkuloosivärjäys ja -viljely (tai PCR ) biopsianäytteestä
Haavainen koliitti Kolonoskopia ja biopsiat
Infektioiden aiheuttamat Ulosteviljely, taudinkulku, kolonoskopia, biopsiat
Antibioottiripuli Anamneesi, klostridiumtoksiini ja klostridiumviljely ulosteesta
Iskeeminen koliitti Anamneesi, kolonoskopia, biopsiat, tietokonetomografia
Sädehoidon aiheuttama koliitti Anamneesi, endoskopia, biopsiat
Periappendikulaarinen absessi Anamneesi, tietokonetomografia, leikkaus?
Tuumorit Endoskopia, tietokonetomografia, biopsia
Divertikuliitti Tietokonetomografia, kolonoskopia
Vaskuliitti Endoskopia, biopsia, ANCA-vasta-aineet
Tulehduskipulääkkeen aiheuttama vaurio Anamneesi, endoskopia, biopsia, kapselikuvaus
Taulukko 3. Crohnin taudin ja haavaisen koliitin erotusdiagnostiikkaa.
Diagnoosi Haavainen koliitti Crohnin tauti
Kliininen kuva Verinen ripuli Vatsakivut, ripuli, perianaalimuutokset
Endoskopia/radiologia Peräsuolesta alkaen diffuusi tulehdus Segmentaarinen tulehdus, usein terve peräsuoli, fistelit, striktuurat, ohutsuolitulehdus
Histologia Diffuusi pinnallinen, epäspesifinen tulehdus Fokaalinen syvä tulehdus, granuloomat

Lääkehoito

5-ASA ja sulfasalatsiini

Kortikosteroidihoito

Antibiootit

Immunomoduloiva hoito

Atsatiopriini

Metotreksaatti

Syklosporiini A, takrolimuusi ja mykofenolihappo

TNF-alfaan vaikuttavat hoidot

Infliksimabi

Muut hoidot

Probiootit

Taulukko 4. Crohnin taudin hoidossa käytetyt immuunivasteeseen vaikuttavat lääkkeet.
Lääke Annos Käyttöaiheet
1. Käytetään vain erityistapauksissa, kun muilla ei ole vaikutusta tai ne ovat vasta-aiheisia
Immunosupressiiviset lääkkeet
atsatiopriini 2 – 2.5 mg/kg/vrk aktiivinen tauti, remission ylläpito, fistelit
6-merkaptopuriini 1 – 1.5 mg/kg/vrk aktiivinen tauti, remission ylläpito, fistelit
metotreksaatti 15 mg suun kautta tai 25 mg lihakseen viikossaaktiivinen vaihe, remission ylläpito
6-tioguaniini1) aktiivinen vaihe, fistelit
syklosporiini1) 4 – 8 mg/kg aktiivinen vaihe, fistelit
mykofenolihappo1) aktiivinen vaihe, fistelit
takrolimuusi1) aktiivinen vaihe, fistelit
Sytokiinivälitteiset lääkkeet
infliksimabi 5 mg/kg infuusiona useaan kertaan aktiivinen vaihe, remission ylläpito, fistelit
talidomidi1) aktiivinen vaihe, fistelit
Taulukko 5. Infliksimabihoidon aiheet ja vasta-aiheet.
Aiheet Vasta-aiheet
  • CDAI = Crohn's disease activity index
  • H-BI = Harvey–Bradshaw´n indeksi
  • Vaikea aktiivinen Crohnin tauti (CDAI yleensä yli 300 tai H-BI 8), kun tavanomainen kortisonin ja immunosuppressiivisen lääkehoidon yhdistelmä ei tehoa tai aiheuttaa haittavaikutuksia eikä leikkaus tule kyseeseen (esimerkiksi laaja-alainen tauti, lyhytsuolioireyhtymä leikkauksen seurauksena)
  • Oireinen fistuloiva Crohnin tauti, kun tavanomainen antibiootti- ja immunosuppressiivinen lääkehoito ei tehoa eikä leikkaus tule kyseeseen (esimerkiksi laaja-alainen tauti, lyhytsuolioireyhtymä leikkauksen seurauksena)
  • Aktiivinen infektio
  • Epäily piilevästä tuberkuloosista, kunnes se on suljettu pois
  • Vaikea sydämen vajaatoiminta
  • Tiukka suolistriktuura, kunnes se on hoidettu

Ravitsemus

Anemia

Osteoporoosi

Tupakointi

Leikkaushoito

Leikkaushoidon aiheet ja periaatteet

Perianaalitauti

Crohnin taudin uusiutuminen leikkauksen jälkeen

Endoskooppinen hoito

Hoidon valinta ja toteutus

Lievän ja keskivaikean Crohnin taudin hoito

Vaikean Crohnin taudin hoito

Fistuloivan Crohnin taudin hoito

Ruoansulatuskanavan yläosan Crohnin taudin hoito

Crohnin taudin hoito raskauden ja imetyksen aikana

Taulukko 6. Suositus aikuisten Crohnin taudin hoidosta.
Taudin sijainti ja vaikeusaste Ensisijainen hoito Vaihtoehtoja tai lisälääkitys
Lievä ileosekaalinen tulehdus 5-ASA 3 – 4 g/vrk jatkuvasti «5-ASA ja sulfasalatsiini ilmeisesti ovat tehokkaita lievän ja keskivaikean Crohnin taudin aktiivisen vaiheen hoidossa.»B Budesonidi 9 mg/vrk 8 viikkoa, sitten 6 mg/vrk 2 viikkoa, sitten 3 mg/vrk 2 viikkoa «Budesonidi annoksella 9 mg/vrk on tehokas ileokekaalisen Crohnin taudin hoidossa.»A
Keskivaikea ileosekaalinen tulehdus Prednisoloni 40 – 80 mg/vrk pienennettävin annoksin noin 2 – 3 kuukauden kuluessa «Kortikosteroidihoito on tehokas Crohnin taudin aktiivisessa vaiheessa.»A + 5-ASA 3 – 4 g/vrk jatkuvasti Budesonidi 9 mg/vrk 8 viikkoa, sitten 6 mg/vrk 2 viikkoa, sitten 3 mg/vrk 2 viikkoa «Budesonidi annoksella 9 mg/vrk on tehokas ileokekaalisen Crohnin taudin hoidossa.»A
Kortikosteroideista riippuvaiset tai niille resistentit:
  1. Atsatiopriini 2 – 2.5 mg/kg/vrk «Atsatiopriini tai merkaptopuriini kannattaa aloittaa, jos kyseessä on kortisoniriippuvainen aktiivinen Crohnin tauti.»A
  2. Metotreksaatti 15 – 25 mg/viikko «Metotreksaatti voi auttaa, ellei hoito atsatiopriinilla tai merkaptopuriinilla onnistu.»B
  3. Infliksimabi 5 mg/kg infuusioina «Kertainfuusio infliksimabia annoksella 5 mg/kg on tehokas, mutta vain uusimalla infuusio säännöllisin välein voidaan osa potilaista pitää turvallisesti remissiossa.»A, ks. taulukko «Crohnin taudin hoidossa käytetyt immuunivasteeseen vaikuttavat lääkkeet. »4
Lievä koliitti
  1. Metronidatsoli 400 mg x 2/vrk noin 2 – 3 kuukauden ajan «Metronidatsolista saattaa olla on hyötyä Crohnin taudin koliitin hoidossa.»C
Keskivaikea koliitti
  1. Metronidatsoli 400 mg x 2/vrk noin 2 – 3 kuukauden ajan «Metronidatsolista saattaa olla on hyötyä Crohnin taudin koliitin hoidossa.»C
  2. Metronidatsoli 400 mg x 2/vrk + siprofloksasiini 500 mg x 2/vrk noin 2 – 3 kuukauden ajan «Siprofloksasiini ja siprofloksasiinin ja metronidatsolin yhdistelmä saattavat ovat vaihtoehtoja kortikosteroidihoidolle Crohnin taudin aktiivisessa vaiheissa, mutta luotettava näyttö niiden tehosta puuttuu.»D
Kortikosteroideista riippuvaiset tai niille resistentit:
  1. Atsatiopriini 2 – 2.5 mg/kg/vrk «Atsatiopriini tai merkaptopuriini kannattaa aloittaa, jos kyseessä on kortisoniriippuvainen aktiivinen Crohnin tauti.»A
  2. Metotreksaatti 15 – 25 mg/viikko «Metotreksaatti voi auttaa, ellei hoito atsatiopriinilla tai merkaptopuriinilla onnistu.»B
  3. Infliksimabi 5 mg/kg infuusioina «Kertainfuusio infliksimabia annoksella 5 mg/kg on tehokas, mutta vain uusimalla infuusio säännöllisin välein voidaan osa potilaista pitää turvallisesti remissiossa.»A
Remission ylläpito
  1. Atsatiopriini 2 – 2.5 mg/kg/vrk «Atsatiopriini tai merkaptopuriini kannattaa aloittaa, jos kyseessä on kortisoniriippuvainen aktiivinen Crohnin tauti.»A
  2. Metotreksaatti 15 – 25 mg/viikko «Metotreksaatti voi auttaa, ellei hoito atsatiopriinilla tai merkaptopuriinilla onnistu.»B
  3. Infliksimabi 5 mg/kg 2 – 3 kuukauden välein «Kertainfuusio infliksimabia annoksella 5 mg/kg on tehokas, mutta vain uusimalla infuusio säännöllisin välein voidaan osa potilaista pitää turvallisesti remissiossa.»A

Lasten Crohnin taudin erityispiirteitä

Taulukko 7. Suositus lasten Crohnin taudin hoidosta.
Taudin vaikeusaste tai hoidon aihe Hoito Vaihtoehtoja tai lisälääkitys
Lievä 5-ASA 50 – 80 mg/kg/vrk Koliitissa sulfasalatsiini 60 mg/kg/vrk
Keskivaikea ja vaikea
Kortikosteroideista riippuvaiset tai niille resistentit, toistuvat relapsit:
  1. Atsatiopriini 2 – 2.5 mg/kg/vrk «Atsatiopriini/ 6-merkaptopuriini on ilmeisesti tehokas lasten Crohnin taudin hoidossa ja auttaa kortisonista vieroittamisessa.»B
  2. Metotreksaatti 15 mg/m2/vk
Vaikea Enteraalinutritiohoito 6 – 8 viikkoa «Enteraalinutritio on yhtä tehokas kuin prednisoloni lasten Crohnin taudin hoidossa.»B + 5-ASA 50 – 80 mg/kg/vrk Yllä olevat + infliksimabi 5 mg/kg infuusiona «infliksimabi on tehokas lasten Crohnin taudin hoidossa ainakin lyhytkestoisesti ja auttaa kortisonista vieroittamisessa.»B
Remission ylläpito 5-ASA 50 mg/kg/vrk, distaalisen proktokoliitin paikallishoito 5-ASA 500 mg – 1 g/vrk
  • Atsatiopriini 2 – 2.5 mg/kg/vrk
  • Metotreksaatti 15 – 25 mg/viikko
  • Infliksimabi 5 mg/kg 2 – 3 kuukauden välein

Seuranta ja hoidon porrastus

Hoidon porrastus

  • Perusterveydenhuollon ensisijainen tehtävä on todeta riittävän varhain Crohnin taudin mahdollisuus ja ohjata potilaat jatkotutkimuksiin.
  • Crohnin taudin diagnostiikka ja hoito kuuluvat yleensä erikoissairaanhoitoon.
  • Kun Crohnin tauti on rauhallisessa vaiheessa eikä tarvetta immunosuppressiiviseen lääkitykseen ole, voidaan seuranta toteuttaa myös perusterveydenhuollossa paikalliset olosuhteet huomioon ottaen.
    • Erikoissairaanhoidon tulee antaa perusterveydenhuollon lääkärille riittävät ohjeet hoidosta potilaan siirtyessä jatkoseurantaan perusterveydenhuoltoon.
    • Lasten Crohnin taudin vaikeat muodot keskitetään lastengastroenterologille, ja lievemmissäkin muodoissa suositellaan herkästi konsultaatiota ja hoitolinjojen tarkistusta yhdessä lastengastroenterologin kanssa.
Taulukko 8. Crohnin taudin laboratorio seuranta.
Kliinisen aktiivisuuden laboratorioseuranta Lääkehoidon seuranta
  • veren hemoglobiini
  • lasko
  • CRP
  • seerumin albumiini
5-aminosalisyylihappo
  • laboratoriokokeet ennen hoidon aloitusta
  • kolmen kuukauden kuluttua hoidon alusta ja
  • sitten noin vuoden välein: veren hemoglobiini, leukosyytit ja trombosyytit, seerumin ALAT, AFOS ja kreatiniini, virtsan sedimentti
Atsatiopriini tai metotreksaatti
  • laboratoriokokeet ennen hoidon aloitusta
  • hoidon alussa kahden viikon välein kahden kuukauden ajan ja
  • jatkossa 3 kuukauden välein: veren hemoglobiini, leukosyytit, neutrofiilit ja trombosyytit, seerumin ALAT ja AFOS

Lääkehoidon sairausvakuutuskorvaukset

  • Crohnin taudin lääkehoito kuuluu sairausvakuutuksessa alempaan erityiskorvausryhmään (75 %).
  • Diagnoosin ja arvion lääkehoidon tarpeesta edellytetään perustuvan sisätautien, lastentautien tai kirurgian erikoislääkärin tutkimuksiin tai sairaalatutkimuksiin.
  • Erityiskorvausta varten tarvitaan B-lausunto ja potilaan hakemus.
    • Lääkehoitona korvataan 5-ASA-valmisteet (mesalatsiini ja olsalatsiini), sulfasalatsiini, kortikosteroidit, metronidatsoli, atsatiopriini, merkaptopuriini, metotreksaatti ja syklosporiini.
  • Infliksimabi on peruskorvattava vaikean Crohnin taudin hoidossa, kun muut hoidot ovat osoittautuneet riittämättömiksi.
  • Kliinisistä ravintovalmisteista voi saada peruskorvauksen, jos on todettu imeytymishäiriö.
  • On huomattava, että Crohnin taudin hoidossa kokeelliset lääkkeet, kuten takrolimuusi ja mykofenolihappo tai anemian hoitoon käytetty erytropoietiini, eivät kuulu SV-korvauksen piiriin.

Suomalaisen Lääkäriseuran Duodecimin ja Suomen Gastroenterologiayhdistys ry:n asettama työryhmä

Puheenjohtaja:

Seppo Niemelä, dosentti, osastonylilääkäri; OYS:n sisätautien klinikka, gastroenterologian yksikkö

Käsikirjoituksen laatija, sihteeri:

Airi Jussila, LL, erikoislääkäri; Seinäjoen keskussairaala, sisätaudit

Jäsenet:

Heikki Järvinen, professori, osastonylilääkäri; HYKS:n gastroenterologia ja yleiskirurgia

Anna-Liisa Karvonen, dosentti, erikoislääkäri; TAYS:n gastroenterologian vastuualue

Martin Rasmussen, LL, ylilääkäri; Tampereen terveyskeskus

Tarja Ruuska, dosentti, erikoislääkäri; TAYS:n lastentautien klinikka

Alpo Vuorio LT, tutkija; HYKS:n sisätautien klinikka (Käypä hoito -toimittaja)

Sidonnaisuudet

Airi Jussila: Toistuvia luentoja eri lääketehtaiden tilaisuuksissa (AstraZeneca, Wyeth-Lederle). Ulkomaan kongressimatka lääketehtaiden kustantamana (Ferring, Schering-Plough). Osallistunut lääketutkimukseen korvausta vastaan (InDex Pharmaceutical AB). Saanut avustusta tieteellistä tutkimustyötä varten (Leiras Finland).

Heikki J. Järvinen: Toiminut luennoitsijana lääketehtaan koulutustilaisuuksissa (AstraZeneca). Antanut asiantuntijalausunnon lääkekorvattavuuteen liittyen (Pfizer).

Anna-Liisa Karvonen: Toiminut luennoitsijana eri lääketehtaiden järjestämissä koulutustilaisuuksissa, joihin myönnetty koulutuspisteet (yliopistojen koulutustoimikuntien hyväksymiä erikoistumiskoulutukseen). Osallistunut lääkeyrityksen gastroenterologian alan tukiryhmän työhön (AstraZeneca) ja toiminut NSAID-Advisory Boardin gastroenterologian asiantuntijajäsenenä lääkeyritykselle (Pfizer).

Seppo Niemelä: Toistuvia luentoja eri lääketehtaiden järjestämissä koulutuksissa (AstraZeneca, Pfizer). Osallistunut ulkomaisiin kongresseihin eri lääketehtaiden rahoittamana (Schering-Plough, Roche). Toiminut lääkeyritysten asiantuntijana (Ferring, Leiras Finland, Orion).

Martin Rasmussen: Ei sidonnaisuuksia.

Tarja Ruuska: Osallistunut lääketutkimukseen palkkiota vastaan (sisapriditutkimus, Janssen-Cilag). Ulkomaan kongressimatka lääketehtaan kustantamana (Schering-Plough).

Alpo Vuorio: Ei sidonnaisuuksia.

Vastuun rajaus

Käypä hoito -suositukset ovat parhaiden asiantuntijoiden laatimia yhteenvetoja yksittäisten sairauksien diagnostiikan ja hoidon vaikuttavuudesta. Ne eivät korvaa lääkärin tai muun terveydenhuollon ammattilaisen omaa arviota yksittäisen potilaan parhaasta mahdollisesta diagnostiikasta ja hoidosta hoitopäätöksiä tehtäessä.

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