溃疡性肠炎 共识2010-1

L. Kupcinskas, P.L. Lakatos, G.J. Mantzaris, S. Schreiber, ren Crohn's and Colitis Organisation (ECCO) ; accepted 23 November 2007 ava i l ab l e a t www.sc i enced i rec t . com Journal of Crohn's and Colitis (2008) 2, 1–23 Diagnosis; Histopathology; Classification; Activity indices Contents 1. Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.2. Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.2.1. Distribution of disease (see Section 2.1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.2.2. Active disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.2.3. Remission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2.4. Response. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2.5. Relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2.6. Early relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2.7. Pattern of relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 for the European Received 23 November 2007 KEYWORDS Ulcerative colitis; Definitions; V. Villanacci, B.F. War SPECIAL ARTICLE European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis E.F. Stange ⁎,1, S.P.L. Travis ⁎,1, S. Vermeire, W. Reinisch, K. Geboes, A. Barakauskiene, R. Feakins, J.F. Fléjou, H. Herfarth, D.W. Hommes, ⁎ Corresponding authors. Travis is to be contacted at John Radcliffe Hospital, Oxford, OX3 9DU, UK. Tel.: +44 1865 228753; fax: +44 1865 228763. Stange, Department of Internal Medicine 1, Robert Bosch Krankenhaus, PO Box 501120, Auerbachstr, 110, 70341 Stuttgart, Germany. Tel.: +49 711 81013404; fax: +49 711 81013793. E-mail addresses: Eduard.Stange@rbk.de (E.F. Stange), simon.travis@ndm.ox.ac.uk (S.P.L. Travis). 1 These authors acted as convenors of the Consensus and contributed equally to the work. 1873-9946/$ - see front matter © 2007 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.crohns.2007.11.001 2 E.F. Stange et al. 1.2.8. Steroid-refractory colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2.9. Steroid-dependent colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2.10. Immunomodulator-refractory colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.11. Refractory distal colitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.12. New patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.13. Alternative therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.14. Complementary therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.15. Expert opinion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2. Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.1. Classification according to disease extent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2.2. Classification according to disease severity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2.1. Activity and pattern of disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2.2. Choice of index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2.3. Clinical and laboratory markers of severity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2.4. Remission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.3. Classification according to age at onset or concomitant primary sclerosing cholangitis . . . . . . . . . . . . . 8 2.4. Use of molecular markers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.4.1. Serology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.4.2. Genotyping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3. Diagnosis and imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.2. Clinical features and risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.2.1. Clinical features of ulcerative colitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3.2.2. Risk factors for ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.3. History, examination and diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.3.1. Medical history . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.3.2. Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3.3.3. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.4. Investigation and procedures to establish a diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.4.1. Initial investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.4.2. Microbial investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 3.4.3. Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.4.4. Procedures recommended to establish the diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.5. Assessment of extent, severity and activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.5.1. Signs of discontinuous inflammation in ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 3.5.2. Activity indices in ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.5.3. Investigations for acute severe colitis on admission . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.5.4. Reassessment of extent and severity of ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.6. Endoscopy, ultrasound and colonography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.6.1. Endoscopic features of ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 3.6.2. Abdominal ultrasound and scintigraphy in ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . 13 3.6.3. Virtual colonography in ulcerative colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 3.7. Colonic stenosis in ulcerative colitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4. Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4.1. General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4.1.1. Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4.1.2. Evaluation of the literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 4.2. Microscopic features — definitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4.2.1. Crypt architectural abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4.2.2. Epithelial cell abnormalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4.2.3. Inflammatory features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 4.3. Microscopic features — appraisal of the diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 4.3.1. Early stage disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 4.3.2. Established disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4.4. Microscopic features — disease activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4.5. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Acknowledgement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 1.2.10. Immunomodulator-refractory colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.11. Refractory distal colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.12. New patient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.13. Alternative theraphy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.14. Complementary therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.2.15. Expert opinion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 therapy to cure the disease is not yet available. Within Europe 2. In parallel, the working parties performed a systematic literature search of their topic with the appropriate key words using Medline/Pubmed and the Cochrane database, as well as their own files. The evidence level (EL) was graded (Table 1.1) according to the Oxford Centre for Evidence Based Medicine.8 3. Provisional guideline statements on their topic were then written by the chairmen, based on answers to the question- naire as well as the literature evidence and were circulated Table 1.1 Levels of evidence and grades of recommendation based on the Oxford Centre for Evidence Based Medicine (for details see http://www.cebm.net/levels_of_evidence. asp#refs) Level Diagnostic study Therapeutic study 1a Systematic review (SR) with homogeneity of level 1 diagnostic studies Systematic review (SR) with homogeneity of randomized controlled trials (RCTs) 1b Validating cohort study with good reference standards Individual RCT (with narrow Confidence Interval) 1c Specificity is so high that a positive result rules in the diagnosis (“SpPin”) or sensitivity is so high that a negative result rules out the diagnosis (“SnNout”) All or none 2a SR with homogeneity of level N2 diagnostic studies SR (with homogeneity ) of cohort studies 2b Exploratory cohort study with good reference standards Individual cohort study (including low quality RCT; e.g., b80% follow up) 2c “Outcomes” research; ecological studies 3a SR with homogeneity of 3b and better studies SR with homogeneity of case-control studies 3b Non-consecutive study; or without consistently applied reference standards Individual case-control study 4 Case-control study, poor or non-independent reference standard Case-series (and poor quality cohort and case- control studies) 5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” 3ECCO Consensus on UC: Definitions and diagnosis there is a North–South gradient, but the incidence appears to have increased in Southern and developing countries in recent years.1,2 Patients may live with a considerable symptom burden despite medical treatment (66% describe interference with work and 73%with leisure activities3) in the hope that the aetiology of ulcerative colitis will shortly be revealed and a cure emerges. Although this is conceivable in the next decade, clinicians have to advise patients on the basis of information available today. Despite randomized trials there will always be many questions that can only be answered by the exercise of judgement and opinion. This leads to differences in practice between clinicians, which may be brought into sharp relief by differences in emphasis between countries. The Consensus endeavours to address these differences. The Consensus is not meant to supersede the guidelines of different countries (such as those from theUK,4 or Germany5), which reach broadly the same conclusions since they are, after all, based on the sameevidence.Rather, theaimof theConsensus is topromote a European perspective on the management of ulcerative colitis (UC) and its dilemmas. Since the development of guidelines is an expensive and time-consuming process, it may help to avoid duplication of effort in the future. A European Consensus is also considered important because an increasing number of thera- peutic trials recruit from Central and Eastern European countries where practice guidelines have yet to be published. This document sets out the current European Consensus on the diagnosis andmanagement of UC, reached by the European Crohn's and Colitis Organisation (ECCO) at a meeting held in Berlin on 20th October 2006. ECCO is a forum for specialists in inflammatory bowel disease from 23 European countries. Like the initial Consensus on the management of Crohn's disease,6 the current Consensus is grouped into three parts: definitions and diagnosis; current management; and management of special situations. This first section concerns aims, methods and definitions of the Consensus, as well as classification, diagnosis, imaging and pathology of UC. The second section on current management includes treatment of active disease, maintenance ofmedically-induced remission and surgery ofUC. The third section on special situations includes pouch disorders, cancer surveillance, pregnancy, paediatrics, psychosomatics, extra-intestinal manifestations and alternative therapy. The strategy to reach the Consensus involved five steps: 1. Relevant questions on each of 14 separate topics concern- ing diagnosis and treatment of UC were devised by the chairmen and their working party. The questions were focused on current practice and areas of controversy in the task force topic, sent around to the other chairmen to avoid duplication, and then to all 59 participants in the Consensus conference. Participants were asked to answer the ques- tions basedon their experienceaswell as evidence from the literature (Delphi procedure).7 1. Definitions 1.1. Introduction Ulcerative colitis is a life long disease arising from an interaction between genetic and environmental factors, but observed predominantly in the developed countries of the world. The precise aetiology is unknownand thereforemedical Grades of recommendation A Consistent level 1 studies B Consistent level 2 or 3 studies or extrapolations from level 1 studies C Level 4 studies or extrapolations from level 2 or 3 studies D Level 5 evidence or troublingly inconsistent or inconclusive studies of any level first among the working party and then among the participants. 4. The working parties then met in Berlin on the 20 October 2006 to agree the statements. Participants gathered under the Chairmanship of EF Stange and SPL Travis to agree the final version of each guideline statement. Technically this was donebyprojecting the statements and revising themon screen until a Consensus was reached. Consensus was defined as agreement by N80% of participants, termed a Consensus Statement and numbered for convenience in the document. Each recommendation was graded (RG) accord- ing to the Oxford Centre for Evidence Based Medicine,8 based on the level of evidence (Table 1.1). of ulcerative colitis and Crohn's disease.10,11 It has distinct Table 1.3 Disease activity in ulcerative colitis, adapted from Truelove and Witts'13 Mild Moderate ‘in between mild and severe’ Severe Bloody stools/day b4 4 or more if ≥6 and Pulse b90 bpm ≤90 bpm N90 bpm or Temperature b37.5 °C ≤37.8 °C N37.8 °C or Haemoglobin N11.5 g/dL ≥10.5 g/dL b10.5 g/dL or ESR b20 mm/h ≤30 mm/h N30 mm/h or or CRP Normal ≤30 mg/L N30 mg/L Table 1.4 Mayo score [14,15 and www.gastrojournal.org for full details] Mayo index 0 1 2 3 Stool frequency Normal 1–2/day Nnormal 3–4/day Nnormal 5/day Nnormal Rectal bleeding None Streaks Obvious Mostly blood Mucosa Normal Mild friability Moderate friability Spontaneous bleeding Physician's global assessment Normal Mild Moderate Severe 4 E.F. Stange et al. 5. The final document on each topic was written by the chairmen in conjunction with their working party. Con- sensus guideline statements in bold are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation. The final text was edited for consistency of style by SPLTravis and EF Stangebeforebeing circulated and approved by the participants. In some areas the level of evidence is generally low, which reflects the paucity of randomized controlled trials. Consequently expert opinion is included where appropriate. 1.2. Definitions Common agreement has been reached by ECCO about frequently used terms. While the significance of some terms (such as ‘early-’ or ‘pattern of relapse’) is undetermined, such terms reflect clinical decision-making (such as when to start immunomodulators) and are considered helpful as a conse- quence. The arbitrariness of some of the definitions is recognised, but the Consensus considers it useful to agree the terminology. Ulcerative colitis (UC) is a chronic inflammatory condition causing continuous mucosal inflammation of the colon with- out granulomas on biopsy, affecting the rectum and a variable extent of the colon in continuity, which is characterised by a relapsing and remitting course.9 Colitis yet to be classified is the term best suited for the minority of cases where a definitive distinction between UC, Crohn's disease, or other cause of colitis cannot be made after the history, endoscopic appearances, histopathology of multiple mucosal biopsies and appropriate radiology have been taken into account.9,10 Indeterminate colitis is a termpreserved for pathologists to describe a colecto