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Crohnin tauti

Käypä hoito
2.5.2011
Suomalaisen Lääkäriseuran Duodecimin, Suomen Gastroenterologiayhdistys ry:n ja Crohn ja Colitis ry:n asettama työryhmä

Tiivistelmä suomeksi «Crohnin tauti»1 ja lyhyt yhteenveto englanniksi «Crohn's disease»2

Potilasversio «Crohnin tauti»3, potilasversio tulostettavassa muodossa (pdf) «»2

Keskeinen sanoma

  • Crohnin taudin hoidon tavoitteina ovat oireettomuus sekä komplikaatioiden ja taudin uusiutumisen esto. Lievän Crohnin taudin hoitoon voidaan käyttää 5-aminosalisyylihappo- eli 5-ASA-valmisteita.
    • Keskivaikean ja vaikean taudin lääkehoitona käytetään kortikosteroidia, ja lisäksi tarvitaan usein ravitsemushoitoa ja kirurgiaa.
  • Kortikosteroideista riippuvaisilla ja hoitoon huonosti reagoivilla käytetään immunomoduloivia lääkkeitä.
  • Vaikea Crohnin tauti hoidetaan tähän sairauteen hyvin perehtyneissä sairaaloissa.
  • Perusterveydenhuollon tehtävänä on havaita riittävän varhain Crohnin taudin mahdollisuus ja ohjata kyseiset potilaat jatkotutkimuksiin.
    • Taudin rauhallisessa vaiheessa potilasta voidaan seurata perusterveydenhuollossa erikoissairaanhoidon 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

Taulukko 1. Crohnin taudin kliinisiä ilmentymiä.
OireitaKliinisiä löydöksiäLaboratoriolöydöksiä
VatsakipuVatsan aristusLievä anemia
Suolen tukosoireetPalpoitava massa vatsan alueellaLievä leukosytoosi
RipuliPerianaalifistelit ja fissuuratSuurentunut lasko/CRP-arvo
Tihentynyt ulostamistarveOhutsuolen striktuuratHypoalbuminemia
KuumeiluSuun aftatSuurentunut kalprotektiinipitoisuus (ks. tausta-aineisto «Ulosteen kalprotektiini tulehduksellisissa suolistosairauksissa»3)
Verenvuoto peräsuolesta
Laihtuminen
Anaalialueen vaivat
Kasvun hidastuminen

Erotusdiagnostiikka

Taulukko 2. Crohnin taudin erotusdiagnostiikka.
TautiTärkeimmät erotusdiagnostiset tutkimukset
SuolistotuberkuloosiTuberkuloosivärjäys ja -viljely (tai PCR ) biopsianäytteestä
Haavainen koliittiKolonoskopia ja biopsiat
Infektioiden aiheuttamat tauditUlosteviljely, kolonoskopia, biopsiat, taudinkulun seuraaminen
AntibioottiripuliAnamneesi, klostridiumtoksiinin määritys ja klostridiumviljely ulosteesta
Iskeeminen koliittiAnamneesi, kolonoskopia, biopsiat, tietokonetomografia
Sädehoidon aiheuttama koliittiAnamneesi, endoskopia, biopsiat
Periappendikulaarinen absessiAnamneesi, tietokonetomografia, leikkaus
TuumoritEndoskopia, tietokonetomografia, biopsia
DivertikuliittiTietokonetomografia, kolonoskopia
VaskuliittiEndoskopia, biopsia, ANCA-vasta-aineiden määritys
Tulehduskipulääkkeen aiheuttama vaurioAnamneesi, endoskopia, biopsia, kapselikuvaus
Taulukko 3. Crohnin taudin ja haavaisen koliitin erotusdiagnostiikkaa.
Diagnoosi
Haavainen koliittiCrohnin tauti
Kliininen kuvaVerinen ripuliVatsakivut, ripuli, perianaalimuutokset
Endoskopia / radiologiaPeräsuolesta alkaen diffuusi tulehdusSegmentaarinen tulehdus, usein terve peräsuoli, fistelit, striktuurat, ohutsuolitulehdus
HistologiaDiffuusi pinnallinen epäspesifinen tulehdusFokaalinen syvä tulehdus, granuloomat

Endoskopia ja histologia

Kuvantamistutkimukset

Lääkehoito

5-ASA ja sulfasalatsiini

Kortikosteroidihoito

Antibiootit

Immunomoduloiva hoito

Taulukko 4. Crohnin taudin hoidossa tavanomaisesti käytetyt immuunivasteeseen vaikuttavat lääkkeet.
LääkeAnnosKäyttöaiheet
Immunosuppressiiviset
Atsatiopriini2–2.5 mg/kg/vrkaktiivinen tauti, remission ylläpito, fistelit
6-merkaptopuriini1–1.5 mg/kg/vrkaktiivinen tauti, remission ylläpito, fistelit
Metotreksaatti15 mg tai 25 mg viikossaaktiivinen vaihe, remission ylläpito
Sytokiinivälitteiset
Infliksimabi5 mg/kg infuusiona
8 viikon välein induktion (0, 2, 6 viikkoa) jälkeen		aktiivinen vaihe, remission ylläpito, fistelit
Adalimumabi40 mg ihon alle 2 viikon välein induktion (160–80 mg) jälkeenaktiivinen vaihe, remission ylläpito, fistelit

Immunosuppressiiviset lääkkeet (solunsalpaajat)

Tiopuriinit

  • Tiopuriinien – atsatiopriinin ja sen metaboliittien 6-merkaptopuriinin (6-MP) ja 6-tioguaniinin – vaikutus perustuu nopeasti uusiutuvien solujen puriinisynteesin estoon.
  • Auttaja-T-lymfosyyttien (Th-1) tuottamien proinflammatoristen sytokiinien määrä suolessa vähenee, mikä johtaa tulehduksen rauhoittumiseen.

Atsatiopriini

Merkaptopuriini (6-MP)

Tioguaniini

Metotreksaatti

Syklosporiini A, takrolimuusi ja mykofenolihappo

Biologiset hoidot

TNF-alfaan vaikuttavat hoidot

Taulukko 5. TNF-alfa -vasta-ainehoidon aiheet ja vasta-aiheet.
AiheetVasta-aiheet
Vaikea aktiivinen Crohnin tauti, kun tavanomainen kortikosteroidin ja immunosuppressiivisen lääkehoidon yhdistelmä ei tehoa tai aiheuttaa haittavaikutuksia eikä leikkaus tule kyseeseen (esimerkiksi laaja-alainen tauti, lyhytsuolioireyhtymä leikkauksen seurauksena)Aktiivinen infektio
Oireinen fistuloiva Crohnin tauti, kun tavanomainen antibiootti- ja immunosuppressiivinen lääkehoito ei tehoa eikä leikkaus tule kyseeseen (esimerkiksi laaja-alainen tauti, lyhytsuolioireyhtymä leikkauksen seurauksena)Epäily piilevästä tuberkuloosista, kunnes se on suljettu pois
Sydämen vaikea vajaatoiminta
Tiukka suolistriktuura, kunnes se on hoidettu
Multippeliskleroosi, optikusneuriitti
Lymfooma

Infliksimabi

Adalimumabi

Sertolitsumabi

Natalitsumabi

Biologisten lääkkeiden haittavaikutukset

Muut hoidot

Afereesihoito

Ravitsemus

Anemia

  • Crohn-potilaan anemia johtuu tavallisesti verenvuodon aiheuttamasta raudanpuutteesta, B12-vitamiinin imeytymisen häiriöstä tai kroonisesta tulehduksesta (sekundaarianemia).

Osteoporoosi

Tupakointi

Leikkaushoito

Leikkaushoidon aiheet ja periaatteet

Perianaalitaudin leikkaushoito

  • Ks. kohta perianaalitaudin hoito «»1.

Crohnin taudin uusiutuminen leikkauksen jälkeen

Endoskooppinen hoito

Hoidon valinta ja toteutus

Lievän ileosekaalisen Crohnin taudin hoito

Lievän koliitin hoito

  • 5-ASA 3–4 g/vrk tai sulfasalatsiini 3–4 g/vrk ja prednisoloni 40 mg/vrk pienennettävin annoksin 2–3 kuukauden kuluessa.
  • Seurantaa voidaan lievässä taudissa aktiivivaiheen jälkeen jatkaa ilman lääkitystä.

Keskivaikean ja vaikean Crohnin taudin hoito

Taulukko 6. Crohnin taudin vaikeusasteet «Hanauer SB, Sandborn W, Practice Parameters Committee of the American College of Gastroenterology. Management of Crohn's disease in adults. Am J Gastroenterol 2001;96:635-43 »40, «Seiderer J, Herrmann K, Diepolder H ym. Double-balloon enteroscopy versus magnetic resonance enteroclysis in diagnosing suspected small-bowel Crohn's disease: results of a pilot study. Scand J Gastroe»49, «Lee SD, Cohen RD. Endoscopy in inflammatory bowel disease. Gastroenterol Clin North Am 2002;31:119-32 »185.
LieväKeskivaikeaVaikea
Vähäiset oireet:
ripulia
ajoittain vatsakipua		Päivittäiset oireet:
ripulia useita kertoja vuorokaudessa
vatsakivut		Päivittäiset oireet:
jatkuvia tai aterioiden jälkeen toistuvia vatsakipuja
osalla veristä ripulia tai suolen tukkeutumisen oireita
Ei merkittäviä yleisoireita (laihtumista, kuumeilua)Yleisoireet:
laihtuminen
väsymys
lievä kuume		Yleisoireet:
väsymys
kuume
Laboratoriolöydöksiä:
Lievä anemia
Lasko- ja CRP-arvot voivat olla koholla
Seerumin albumiinipitoisuus voi olla matala
Ulosteen kalprotektiinipitoisuus voi olla koholla		Laboratoriolöydöksiä:
Lievä anemia
Lasko- ja CRP-arvot voivat olla koholla
Seerumin albumiinipitoisuus voi olla matala
Ulosteen kalprotektiinipitoisuus voi olla koholla		Laboratoriolöydöksiä:
Anemia
Suuret lasko- ja CRP-arvot
Seerumin pieni albumiinipitoisuus
Ulosteen suuri kalprotektiinipitoisuus

Ei-perianaalisen fistuloivan Crohnin taudin hoito

Perianaalitaudin hoito

Ruoansulatuskanavan yläosan Crohnin taudin hoito

Crohnin taudin hoito raskauden ja imetyksen aikana

Taulukko 7. Suositus aikuisten keskivaikean ja vaikean Crohnin taudin hoidosta.
Taudin sijainti ja vaikeusasteEnsisijainen hoitoVaihtoehtoja tai lisälääkitys
Keskivaikea/
vaikea ileosekaalinen tulehdus		Budesonidi 9 mg/vrk 8 viikkoa, sitten 6 mg/vrk 2 viikkoa, sitten 3 mg/vrk 2 viikkoa «Budesonidi annoksella 9 mg/vrk on lähes yhtä tehokas kuin prednisoloni ja tehokkaampi kuin lume ileokekaalisen Crohnin taudin hoidossa.»APrednisoloni 40–80 mg/vrk pienennettävin annoksin noin 2–3 kuukauden kuluessa «Kortikosteroidihoito on tehokas Crohnin taudin aktiivisessa vaiheessa.»A
Kortikosteroideista riippuvaiset tai niille resistentit:
Atsatiopriini 2–2.5 mg/kg/vrk «Atsatiopriini tai merkaptopuriini kannattaa aloittaa, jos kyseessä on kortisoniriippuvainen aktiivinen Crohnin tauti.»A tai merkaptopuriini 1.0–1.5 mg/kg/vrk
Metotreksaatti 15–25 mg/viikko «Metotreksaatti voi auttaa, ellei hoito atsatiopriinilla tai merkaptopuriinilla onnistu.»B
Infliksimabi 5 mg/kg viikoilla 0, 2 ja 6 «Kertainfuusio infliksimabia annoksella 5 mg/kg on tehokas, mutta vain uusimalla infuusio säännöllisin välein voidaan osa potilaista pitää turvallisesti remissiossa.»A tai adalimumabi 160–80–40 mg 2 viikon välein s.c. «Adalimumabilla saadaan aikaan remissio aktiivisessa Crohnin taudissa.»A; ks. taulukko «Crohnin taudin hoidossa tavanomaisesti käytetyt immuunivasteeseen vaikuttavat lääkkeet.»4
Keskivaikea/vaikea koliittiPrednisoloni 40–80 mg/vrk pienennettävin annoksin 2–3 kuukauden kuluessa «Kortikosteroidihoito on tehokas Crohnin taudin aktiivisessa vaiheessa.»A
Kortikosteroideista riippuvaiset tai niille resistentit:
Atsatiopriini 2–2.5 mg/kg/vrk «Atsatiopriini tai merkaptopuriini kannattaa aloittaa, jos kyseessä on kortisoniriippuvainen aktiivinen Crohnin tauti.»A tai merkaptopuriini 1–1.5 mg/kg/vrk
Metotreksaatti 15–25 mg/viikko «Metotreksaatti voi auttaa, ellei hoito atsatiopriinilla tai merkaptopuriinilla onnistu.»B
Infliksimabi 5 mg/kg viikoilla 0, 2 ja 6 «Kertainfuusio infliksimabia annoksella 5 mg/kg on tehokas, mutta vain uusimalla infuusio säännöllisin välein voidaan osa potilaista pitää turvallisesti remissiossa.»A tai adalimumabi 160–80–40 mg 2 viikon välein «Adalimumabilla saadaan aikaan remissio aktiivisessa Crohnin taudissa.»A
Remission ylläpitoAtsatiopriini 2–2.5 mg/kg/vrk «Atsatiopriini tai merkaptopuriini kannattaa aloittaa, jos kyseessä on kortisoniriippuvainen aktiivinen Crohnin tauti.»A tai merkaptopuriini 1–1.5 mg/kg/vrkMetotreksaatti 15–25 mg/viikko «Metotreksaatti voi auttaa, ellei hoito atsatiopriinilla tai merkaptopuriinilla onnistu.»B
Infliksimabi 5 mg/kg 8 viikon välein «Kertainfuusio infliksimabia annoksella 5 mg/kg on tehokas, mutta vain uusimalla infuusio säännöllisin välein voidaan osa potilaista pitää turvallisesti remissiossa.»A tai adalimumabi 40 mg 2 viikon välein «TNF-alfa -vasta-aineet ovat tehokkaita remission ylläpitämiseksi.»A

Lasten Crohnin taudin erityispiirteitä

Taulukko 8. Suositus lasten Crohnin taudin hoidosta.
Taudin vaikeusaste tai hoidon aiheHoitoVaihtoehtoja tai lisälääkitys
Lievä5-ASA 50–80 mg/kg/vrkKoliitissa sulfasalatsiini 60 mg/kg/vrk
Keskivaikea ja vaikeaEnteraalinen ravitsemushoito 6–8 viikon ajan «Enteraalinutritio on yhtä tehokas kuin prednisoloni lasten Crohnin taudin hoidossa.»B
Proktiitin hoito paikallisesti 5-ASAlla tai steroidilla kerran päivässä
Fistelit ja perianaaliabsessit: metronidatsoli 15–20 mg/kg/vrk ja/tai siprofoksasiini 250–500 mg x 2/vrk		Prednisoloni 1–2 mg/kg/vrk pienennettävin annoksin viikoittain
Budenosidi 9 mg/vrk ileosekaalisissa taudeissa, myöhemmin 6 mg/vrk «Budenosidi lienee yhtä tehokas kuin prednisolon lievän-keskivaikean Crohnin taudin hoidossa.»C
Kortikosteroideista riippuvaiset tai niille resistentit, toistuvat relapsit:
Atsatiopriini 2–2.5 mg/kg/vrk «Atsatiopriini/6-merkaptopuriini on ilmeisesti tehokas lasten Crohnin taudin hoidossa ja auttaa kortisonista vieroittamisessa.»B
Metotreksaatti 10–15 mg/m2/viikko
VaikeaEnteraalinen ravitsemushoito 6–8 viikkoa «Enteraalinutritio on yhtä tehokas kuin prednisoloni lasten Crohnin taudin hoidossa.»B ja 5-ASA 50–80 mg/kg/vrkYllä olevat ja infliksimabi 5 mg/kg infuusiona «Infliksimabi on tehokas lasten Crohnin taudin hoidossa ainakin lyhytkestoisesti ja auttaa kortisonista vieroittamisessa.»B tai
adalimumabi 80–40 mg 2 viikon välein
Remission ylläpito5-ASA 50 mg/kg/vrk, distaalisen proktokoliitin paikallishoito 5-ASA 500 mg – 1 g/vrkAtsatiopriini 2–2.5 mg/kg/vrk
Metotreksaatti 10–15 mg/m2/viikko
Infliksimabi 5 mg/kg 4–8 viikon välein tai adalimumabi 40 mg 2 viikon 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 9. Crohnin taudin laboratorioseuranta.
Kliinisen aktiivisuuden seurantaLääkehoidon seuranta
Veren hemoglobiini
Lasko
CRP
Seerumin albumiini
Ulosteen kalprotektiini		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
myöhemmin 3 kuukauden välein: veren hemoglobiini, leukosyytit, neutrofiilit, lymfosyytit ja trombosyytit, seerumin ALAT ja AFOS

Lääkehoidon sairausvakuutuskorvaukset

  • Crohnin taudin lääkehoito kuuluu sairausvakuutuksessa alempaan erityiskorvausryhmään (72 %).
  • Diagnoosin ja arvion lääkehoidon tarpeesta edellytetään perustuvan sisätautien, gastroenterologian, lastentautien tai kirurgian erikoislääkärin tutkimuksiin tai sairaalatutkimuksiin.
  • Erityiskorvausta varten tarvitaan B-lausunto ja potilaan hakemus.
  • Erityiskorvattavia ovat 5-ASA-valmisteet (mesalatsiini ja olsalatsiini), sulfasalatsiini, kortikosteroidit, metronidatsoli, atsatiopriini, merkaptopuriini, metotreksaatti ja syklosporiini.
  • Adalimumabihoidosta saa peruskorvauksen erillisellä lääkärin B-lausunnolla, joka on voimassa toistaiseksi kaksi vuotta kerrallaan.
  • Kliinisistä ravintovalmisteista voi saada peruskorvauksen, jos on todettu imeytymishäiriö. Lapsilla enteraalinen ravitsemushoito jatkuvana letkuruokintana oikeuttaa erityiskorvattavuuteen.
  • On huomattava, että Crohnin taudin hoidossa kokeelliset lääkkeet, kuten takrolimuusi ja mykofenolihappo ja osteoporoosilääkkeet, eivät kuulu erityiskorvauksen piiriin.

Suomalaisen Lääkäriseuran Duodecimin, Suomen Gastroenterologiayhdistys ry:n ja Crohn ja Colitis ry:n asettama työryhmä

Suosituksen historiatiedot «Crohnin taudin hoito, Käypä hoito -suosituksen historiatiedot»12

Puheenjohtaja:

Airi Jussila, LL, erikoislääkäri; TAYS:n gastroenterologian vastuualue

Jäsenet:

Heikki Järvinen, professori, osastonylilääkäri; HYKS:n gastroenterologinen kirurgia

Anna-Liisa Karvonen, dosentti, erikoislääkäri; Tampereen yliopisto, lääketieteen laitos

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

Taina Sipponen, LT; HYKS:n gastroenterologian klinikka

Alpo Vuorio LT, työterveyslääkäri; Lääkäriasema Airport Mehiläinen, Vantaa (Käypä hoito -toimittaja)

Sidonnaisuudet

Airi Jussila: Kutsuttuna luennoitsija lääkealan yritysten järjestämissä tilaisuuksissa ja saanut niistä luentopalkkion (Abbot, MSD). Osallistunut ulkomaisiin kongresseihin lääkealan yritysten maksamana; matkat ja/tai osallistumismaksu (Abbot, Ferring, MSD, Tillotts Pharma AB). Antanut asiantuntija-apua lääkealan yrityksille ja saanut siitä palkkion (Ferring, Tillotts Pharma AB). ABBOT:n ja MSD:n ns. Advisory boardin jäsen.

Heikki Järvinen: Luennoinut lääketieteellisenä asiantuntijana lääkealan yritysten tilaisuuksissa (Sanofi-Aventis Oy, Roche Oy).

Anna-Liisa Karvonen: Ei sidonnaisuuksia.

Tarja Ruuska: Luennoinut terveydenhuollon tilaisuuksissa ja saanut luennoista palkkion (MSD, Schering-Plough, Otsuka Pharma Scandinavia).

Taina Sipponen: Toistuvia luentoja eri terveydenhuollon ja/tai lääkealan yritysten koulutuksissa (Abbott, MSD ja Tillotts Pharma). Ulkomaan kongressimatka terveydenhuollon ja/tai lääkealan yritysten rahoittamana (Abbott ja Algol).

Alpo Vuorio: Oma yritys Skyleron Oy.

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.

Kirjallisuutta

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