SPECIAL ARTICLE
European evidence-based Consensus on the management of ulcerative colitis:Special situations
Livia Biancone,Pierre Michetti,Simon Travis ?,1,Johanna C.Escher,Gabriele Moser,Alastair Forbes,J?rg C Hoffmann,Axel Dignass,Paolo Gionchetti,Günter Jantschek,Ralf Kiesslich,Sanja Kolacek,
Rod Mitchell,Julian Panes,Johan Soderholm,Boris Vucelic,Eduard Stange ?,1for the European Crohn's and Colitis Organisation (ECCO)
Received 30December 2007;accepted 30December 2007KEYWORDS
Ulcerative colitis;Pouchitis;
Colorectal cancer surveillance;Adolescence;Psychosomatic
Contents 8.
Pouchitis ............................................................658.1.General.............................
............................658.1.1.Symptoms ..................................................658.1.2.Endoscopy (‘pouchoscopy ’)........................................658.1.3.Histopathology of pouchitis ........................................668.1.4.Differential diagnosis ............................................668.1.5.Risk factors for pouchitis and pouch dysfunction
............................668.2.Pattern of pouchitis......................
............................668.2.1.Acute and chronic pouchitis ........................................668.2.2.Scoring of pouchitis.............................................668.2.3.Recurrent pouchitis and complications ......
(67)
?Corresponding authors.Travis is to be contacted at John Radcliffe Hospital,Oxford,OX39DU,UK.Tel.:+441865228753;fax:+441865228763.Stange,Department of Internal Medicine 1,Robert Bosch Krankenhaus,PO Box 501120,Auerbachstr ,110,70341Stuttgart,Germany.Tel.:+4971181013404;fax:+4971181013793.
E-mail addresses:simon.travis@https://www.doczj.com/doc/2918308974.html, (S.Travis),Eduard.Stange@rbk.de (E.Stange).1
These authors acted as convenors of the Consensus and contributed equally to the
work.1873-9946/$-see front matter ?2008European Crohn T s and Colitis Organisation.Published by Elsevier B.V .All rights reserved.doi:
10.1016/j.crohns.2007.12.001
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Journal of Crohn's and Colitis (2008)2,63–92
64L.Biancone et al.
8.3.Medical treatment (67)
8.3.1.Acute pouchitis:antibiotics (67)
8.3.2.Chronic pouchitis:combination antibiotic therapy or budesonide (67)
8.3.3.Acute and chronic refractory pouchitis:other agents (67)
8.3.4.Maintenance of remission:probiotics (68)
8.3.5.Prevention of pouchitis:probiotics (68)
8.4.Cuffitis (68)
9.Surveillance for colorectal cancer (68)
9.1.Risk of cancer (68)
9.1.1.Estimation of risk (68)
9.1.2.Risk factors for cancer development (69)
9.2.Surveillance colonoscopy programmes (69)
9.2.1.Screening and surveillance (69)
9.2.2.Effectiveness (69)
9.2.3.Initial screening colonoscopy (70)
9.2.4.Surveillance schedules (70)
9.3.Colonoscopic procedures (70)
9.3.1.Number and site of biopsies (70)
9.3.2.Chromoendoscopy (71)
9.4.Dysplasia (71)
9.4.1.Risk of progression to cancer (71)
9.4.2.Dysplasia and colectomy (71)
9.4.3.Dysplasia and raised lesions (71)
9.5.Chemoprevention (72)
9.6.Prognosis (72)
10.Children and adolescents (72)
10.1.Introduction (72)
10.2.Diagnosis (73)
10.2.1.Diagnostic threshold (73)
10.2.2.Documentation (73)
10.2.3.Diagnostic procedures (73)
10.3.Induction therapy in children (73)
10.3.1.Distal colitis (73)
10.3.2.Extensive colitis (74)
10.3.3.Severe colitis (74)
10.4.Maintenance therapy in children (75)
10.4.1.Aminosalicylates (75)
10.4.2.Thiopurines (75)
10.5.Surgery in children (75)
10.5.1.Indications (75)
10.5.2.Procedures (75)
10.6.Nutritional support (75)
10.7.Psychosocial support (75)
10.8.Transition of care to adult services (76)
11.Pregnancy (76)
12.Psychosomatics (76)
12.1.Introduction (76)
12.2.Influence of psychological factors on disease (76)
12.2.1.Aetiology (76)
12.2.2.Pattern of disease (76)
12.3.Psychological disturbances in ulcerative colitis (76)
12.4.Approach to psychological disorders (77)
https://www.doczj.com/doc/2918308974.html,munication with patients (77)
12.4.2.Psychological support (77)
12.4.3.Therapeutic intervention (77)
12.4.4.Therapeutic choice (78)
13.Extraintestinal manifestations (78)
13.1.Introduction (78)
13.2.Arthropathies (78)
13.2.1.Pauciarticular peripheral arthropathy (78)
13.2.2.Polyarticular peripheral arthropathy (79)
13.2.3.Axial arthropathy (79)
13.2.4.Therapy of arthropathies (79)
13.3.Cutaneous manifestations (79)
13.3.1.Erythema nodosum (79)
13.3.2.Pyoderma gangrenosum(PG) (80)
13.3.3.Sweet's syndrome (80)
13.4.Ocular manifestations (80)
13.4.1.Episcleritis (80)
13.4.2.Uveitis (80)
13.4.3.Cataracts (80)
13.5.Hepatobiliary disease (80)
13.5.1.Primary sclerosing cholangitis (81)
13.6.Metabolic bone disease (81)
13.6.1.Diagnosis and fracture risk (81)
13.6.2.Management (81)
13.7.Other systems (82)
https://www.doczj.com/doc/2918308974.html,anisation of services for EIMs associated with ulcerative colitis (82)
https://www.doczj.com/doc/2918308974.html,plementary and alternative medicines (82)
14.1.Introduction (82)
14.2.Definitions (82)
https://www.doczj.com/doc/2918308974.html,e of CAM (82)
Contributors (83)
Acknowledgements (83)
References (84)
8.Pouchitis
8.1.General
Proctocolectomy with ileal pouch-anal anastomosis(IPAA) is the procedure of choice for most patients with ulcerative colitis(UC)requiring colectomy.1Pouchitis is a non-specific inflammation of the ileal reservoir and the most common complication of IPAA in patients with UC.2–7Its frequency is related to the duration of the follow-up,occurring in up to 50%of patients10years after IPAA in large series from major referral centres.1–9The cumulative incidence of pouchitis in patients with an IPAA for familial adenomatous polyposis is much lower,ranging from0to10%.10–12 Reasons for the higher frequency of pouchitis in UC remain unknown.Whether the pouchitis more commonly develops within the first years after IPAA or whether the risk continues to increase with longer follow-up remains undefined.
8.1.1.Symptoms
After total proctocolectomy with IPAA,median stool frequency is4to8bowel movements1–4,13,14with700mL of semiformed/liquid stool per day2,13,14.Symptoms related to pouchitis include increased stool frequency and liquidity, abdominal cramping,urgency,tenesmus and pelvic dis-comfort(2,15).Rectal bleeding,fever,or extraintestinal manifestations may occur.Rectal bleeding is more often related to inflammation of the rectal cuff(“cuffitis”),16 than to pouchitis.Poor faecal incontinence may occur in the absence of pouchitis after IPAA,but is more common in patients with pouchitis.Symptoms of pouch dysfunction in patients with IPAA may be caused by conditions other than pouchitis,including Crohn's disease of the pouch,17–19 cuffitis,16and an irritable pouch.20This is why the diagnosis depends on endoscopy and biopsy in conjunction with symptoms.
8.1.2.Endoscopy(‘pouchoscopy’)
Pouchoscopy and pouch mucosal biopsy should be per-formed in patients with symptoms compatible with pouchitis,in order to confirm the diagnosis.15Patients with an ileoanal pouch occasionally have a stricture at the pouch-anal anastomosis,so a gastroscope rather than a colonoscope may better be necessary for pouchoscopy. Endoscopic findings compatible with pouchitis include diffuse erythema caused by inflammation of the ileal pouch,which may be patchy,unlike that observed in UC. Characteristic endoscopic findings include oedema,gran-ularity,friability,spontaneous or contact bleeding,loss of vascular pattern,mucous exudates,haemorrhage,erosions and ulceration.17Erosions and/or ulcers along the staple line do not necessarily indicate pouchitis.Characteristi-cally,these findings are non-specific and lesions may be discontinuous,unlike the colorectal lesions in UC.18,21,22 Biopsies should be taken from the pouch mucosa and from the afferent limb above the pouch,but not along the staple line.
ECCO Statement8A
The diagnosis of pouchitis requires the presence of symptoms,together with characteristic endoscopic and histological abnormalities[EL3a,RGB].Extensive colitis, extraintestinal manifestations(eg primary sclerosing cho-langitis),being a non-smoker,p-ANCA positive serology,and non-steroidal anti-inflammatory drug use are possible risk factors for pouchitis[EL3b,RG D]65
ECCO Consensus on UC:Special situations
8.1.3.Histopathology of pouchitis
Histological findings of pouchitis are also non-specific, including acute inflammation with polymorphonuclear leukocyte infiltration,crypt abscesses and ulceration,in association with a chronic inflammatory infiltrate.21,22 There may be discrepancy between endoscopic and histologic findings in pouchitis,possibly related to sam-pling error.23,24Morphological changes of the epithelium lining the ileal pouch normally develop in the12–18months after ileostomy closure,characterised by flattening and a reduced number,or disappearance of the villi,leading to villous atrophy(“colonic metaplasia”).22–24Although the aetiology of pouchitis remains unknown,it can be inferred from the predeliction for patients with UC and the response to antibiotic therapy that the bacterial flora and whatever predisposes to UC itself are involved in the pathogenesis of tissue damage in the ileoanal pouch.25,26 Pouchitis tends to occur only after colonic metaplasia has developed in the pouch,although a causal association is unproven.
8.1.4.Differential diagnosis
The clinical history and biopsies help discriminate between pouchitis,ischaemia,Crohn's disease(CD)and other rare forms of pouch dysfunction such as collagenous pouchitis, Clostridium difficile or cytomegalovirus pouchitis.27–29 Secondary pouchitis,caused by pelvic sepsis,usually causes focal inflammation and should be considered.Biopsies taken from the ileum above the pouch may reveal pre-pouch ileitis as a cause of pouch dysfunction,although this usually causes visible ulceration that may be confused with Crohn's disease.30The possibility of non-specific ileitis caused by NSAIDs should be considered.31
8.1.5.Risk factors for pouchitis and pouch dysfunction Reported risk factors for pouchitis include extensive UC,1,32 backwash ileitis,32extraintestinal manifestations(especially primary sclerosing cholangitis),5,19,33being a non-smoker34 and regular use of NSAIDs.31,35Interleukin-1receptor antago-nist gene polymorphisms36and the presence of perinuclear neutrophil cytoplasmic antibodies37are also associated with pouchitis.Not surprisingly studies are discordant with regard to the role of each risk factor.Some of the best data on risk factors come from the Cleveland Clinic.38240consecutive patients were classified as having healthy pouches(n=49), pouchitis(n=61),Crohn's disease(n=39),cuffitis(n=41),or irritable pouch syndrome(n=50).The risk of developing pouchitis was increased3–5fold when the indication for IP AA was dysplasia(OR3.89;95%CI1.69–8.98),or when the patient had never smoked(OR5.09;95%CI1.01–25.69),or used NSAIDs(OR3.24;95%CI1.71–6.13),or(perhaps surprisingly) had never used anxiolytics(OR5.19;95%CI1.45–18.59).The risk of turning out to have Crohn's disease of the pouch was greatly increased by being a current smoker(OR4.77;95%CI,1.39–16–25),and modestly associated by having a pouch of long duration(OR 1.20;95%CI 1.12.–1.30).Cuffitis was associated with symptoms of arthralgia(OR4.13;95%CI1.91–8.94)and a younger age(OR1.16;95%CI1.01–1.33).Irritable pouch syndrome is probably under-recognised,although is a common cause of pouch dysfunction when other causes (including a small volume pouch,incomplete evacuation and pouch volvulus)have been excluded and investigations are normal.The principal risk factor is the use of antidepressants (OR4.17;95%CI1.95–8.92)or anxiolytics(OR3.21;95%CI 1.34–7.47),which suggests that these people may have had irritable bowel syndrome contributing to symptoms of colitis before pouch surgery.38
These risk factors should not preclude proctocolectomy if surgery is appropriate,but should inform pre-operative discussions with the patient and family.In particular the possibility that IBS may be contributing to symptoms of refractory UC should be considered and objective evidence of treatment refractory colitis obtained before surgery.If there is a disparity between preoperative and endoscopic appearance,or if the patient is on antidepressants,then the risk of pouch dysfunction after IPAA needs particularly careful consideration.Similarly,if a patient has primary sclerosing cholangitis,then it is appropriate to discuss the higher risk of pouchitis.This is appropriate management of expectations rather than a contraindication to appropriate surgery.
8.2.Pattern of pouchitis
8.2.1.Acute and chronic pouchitis
On the basis of symptoms and endoscopy,pouchitis can be divided into remission(normal pouch frequency)or active pouchitis(increased frequency with endoscopic appear-ances and histology consistent with pouchitis).15,39Active pouchitis may then be divided into acute or chronic, depending on the symptom duration.The threshold for chronicity is a symptom duration of N4weeks.Up to10%of patients develop chronic pouchitis requiring long-term treatment,and a small subgroup has pouchitis refractory to medical treatment.3
8.2.2.Scoring of pouchitis
The Pouchitis Disease Activity Index(PDAI)has been developed to standardize diagnostic criteria and assess the severity of pouchitis.15,39,40The PDAI is a composite score that evaluates symptoms,endoscopy and histology.Each component score has a maximum of6points.Patients with a total PDAI score≥7are classified as having pouchitis,so a patient has to have both symptoms and endoscopic or histological evidence of pouchitis and,ideally,all three. The problem is that about a quarter of patients with a high symptom score suggestive of pouchitis may not fulfil criteria for the diagnosis of pouchitis,as assessed by the PDAI,since endoscopic or histological criteria may be absent.Conse-quently a relatively large number of patients may be unnecessarily treated for puchitis when symptoms are due to other conditions.Other scoring systems have been devised,including that by Moskowitz21and an index from https://www.doczj.com/doc/2918308974.html,parisons with the PDAI41,42show that they are not interchangeable,but this affects clinical trials rather than clinical practice.
ECCO Statement8B
The most frequent symptoms of pouchitis are increased
number of liquid stools,urgency,abdominal cramping
and pelvic discomfort.Fever and bleeding are rare[EL1c,
RG B].Routine pouchoscopy after clinical remission is not
required[EL5,RG D]
66L.Biancone et al.
8.2.3.Recurrent pouchitis and complications
Pouchitis recurs in more than50%.3,15,39Patients with recurrent pouchitis can broadly be grouped into three categories:infrequent episodes(b1/yr),a relapsing course (1–3episodes/yr)or a continuous course.Pouchitis may further be termed treatment responsive or refractory,based on response to single-antibiotic therapy(see8.3.2).7,9 Although these distinctions are largely arbitrary,they help both patients and their physicians when considering manage-ment options to alter the pattern of https://www.doczj.com/doc/2918308974.html,plications of pouchitis include abscesses,fistulae,stenosis of the pouch-anal anastomosis and adenocarcinoma of the pouch.7,27,39This latter complication is exceptional and almost only occurs when there is pre-exiting dysplasia or carcinoma in the original colectomy specimen.
8.3.Medical treatment
8.3.1.Acute pouchitis:antibiotics
Treatment of pouchitis is largely empirical and only small placebo-controlled trials have been conducted.Antibiotics are the mainstay of treatment,and metronidazole and ciproflox-acin are the most common initial approaches,often with a rapid response.The odds ratio of inducing a response using oral metronidazole compared with placebo in active chronic pouchitis was26.67(95%CI 2.31–308.01,NNT=2).43The randomised trials of both metronidazole and ciprofloxacin are, however,small.44–46The two have been compared in another small randomised trial.47Seven patients received ciproflox-acin1g/day and nine patients metronidazole20mg/kg/day for a period of2weeks.Ciprofloxacin lowered the PDAI score from10.1±2.3to3.3±1.7(p=0.0001),whereas metronidazole reduced the PDAI score from9.7±2.3to5.8±1.7(p=0.0002). There was a significantly greater reduction in the ciprofloxacin compared to metronidazole in terms of the total PDAI (p=0.002),symptom score(p=0.03)and endoscopic score (p=0.03),as well as fewer adverse events(33%of metronida-zole-treated patients reported side-effects,but none on ciprofloxacin).Combination antibiotic therapy is an option for persistent symptoms(below).
8.3.2.Chronic pouchitis:combination antibiotic therapy or budesonide
For patients who have persistent symptoms,alternative diagnoses should be considered,including undiagnosed Crohn's disease,pouch-anal or ileal-pouch stricture,infec-tion with CMV or Cl difficile,collagenous pouchitis,cuffitis, anatomical disorders,or irritable pouch syndrome.Approxi-mately10–15%of patients with acute pouchitis develop chronic pouchitis,which may be“treatment responsive”or “treatment refractory”to single-antibiotic therapy.39 Patients with chronic,refractory pouchitis do not respond to conventional therapy and often continue to suffer symptoms,which is a common cause of pouch failure. Combination antibiotic therapy or oral budesonide may work.16consecutive patients with chronic,refractory pouchitis(disease N4weeks and failure to respond to N4weeks of single-antibiotic therapy)were treated with ciprofloxacin1g/day and tinidazole15mg/kg/day for 4weeks.47A historic cohort of ten consecutive patients with chronic refractory pouchitis treated with5–8g oral and topical mesalazine daily was used as a comparator.These refractory patients had a significant reduction in the total PDAI score and a significant improvement in quality-of-life score(p b0.002) when taking ciprofloxacin and tinidazole,compared to base-line.The rate of clinical remission in the antibiotic group was 87.5%and for the mesalazine group was50%.
In another study,18patients non-responders to metroni-dazole,ciprofloxacin or amoxycillin/clavulanic acid for 4weeks were treated orally with rifaximin2g/day(a nonabsorbable,broad spectrum antibiotic)and ciprofloxacin 1g/day for15days.Sixteen out of18patients(88.8%)either improved(n=10)or went into remission(n=6).48Median PDAI scores before and after therapy were11(range9–17) and4(range0–16),respectively(p b0.002).A British group observed similar benefit in just8patients.49In another combination study,44patients with refractory pouchitis received metronidazole800mg–1g/day and ciprofloxacin 1g/day for28days.5036patients(82%)went into remission and median PDAI scores before and after therapy were12and 3respectively(p b0.0001).The alternative is oral budeso-nide CIR9mg daily for8weeks,which achieved remission in 15/20(75%)patients not responding after1month of ciprofloxacin or metronidazole.51The message is simple enough,even if the trials are underpowered:if ciprofloxacin does not work,then try it in combination with an imidazole antibiotic or rifaximin,or try oral budesonide.
8.3.3.Acute and chronic refractory pouchitis:other agents
The variety of approaches illustrates the challenges of trying to find treatment that works for a new disorder.These are largely of historic interest.Budesonide enemas were as effective as metronidazole for acute pouchitis in a rando-mised controlled trial.52Ciclosporin enemas were successful for chronic pouchitis in a pilot study53and oral azathioprine may help if patients relapse become budesonide-dependent. Uncontrolled studies of short-chain fatty acid enemas54,55 showed little value.Glutamine and butyrate suppositories have been compared for chronic pouchitis.56Of more recent interest,infliximab has been tried in patients with chronic, (very)refractory pouchitis not responding either to metro-nidazole or ciprofloxacin1g/day for4weeks or oral budesonide CIR9mg/day for8weeks.10/12(83.3%)such patients treated with infliximab5mg/kg at0,2and6weeks went into remission.57The median PDAI score before therapy was13(range8–18)and2(range0–9)after infliximab (p b0.001)and the IBDQ also significantly improved from96
ECCO Statement8C
The majority of patients respond to metronidazole or ciprofloxacin,although the optimum modality of treat-ment is not clearly defined[EL1b,RG B].Side-effects are less frequent using ciprofloxacin[EL1c,RG B].Antidiar-rhoeal drugs may reduce the number of daily liquid stools in patients,independent of pouchitis[EL5,RGD]
ECCO Statement8D
In chronic pouchitis,combined antibiotic treatment is effective[EL1b,RG B]67
ECCO Consensus on UC:Special situations
(range 74–184) to 196 (92–230) ( p b 0.001). 57 Infliximab has been used when the cause of pouch dysfunction is Crohn's disease, or fistulation.58 Benefit been also been reported from alicaforsen enemas(an inhibitor of intercellular adhesion molecule(ICAM)-1)in an open-label trial.59
8.3.4.Maintenance of remission:probiotics
In chronic pouchitis,once remission has been obtained, treatment with the highly concentrated probiotic mixture VSL#3is able to maintain remission.T wo double-blind, placebo-controlled studies have shown the efficacy of VSL#3(450billion bacteria of8different strains/g)to maintain remission in patients with chronic pouchitis.In the first study,40patients who achieved clinical and endo-scopic remission after one month of combined antibiotic treatment(rifaximin2g/day+ciprofloxacin1g/day),were randomised to receive either VSL#3,6g/day(18×1011 bac t eri a/ d ay), or placebo for 9 mo n ths.60 All 20 patient s who received placebo relapsed,while17of the20patients (85%)treated with VSL#3remained in clinical and endo-scopic remission at the end of the study.Interestingly,all17 patients relapsed within four months after stopping VSL#3.60In the second study,36patients with chronic, refractory pouchitis who achieved remission(PDAI=0) after1month of combined antibiotic treatment(metroni-dazole+ciprofloxacin)received6g/once a day of VSL#3or placebo for1year.Remission rates at one year were85%in the VSL#3group and6%in the placebo group(p b0.001).61 8.3.5.Prevention of pouchitis:probiotics
The same probiotic preparation(VSL#3)has been shown to prevent pouchitis within the first year after surgery,in a randomised,double-blind,placebo-controlled study.Forty consecutive patients undergoing IPAA for UC were rando-mised within a week after ileostomy closure,to VSL#33g (9 × 10 11 ) per day or placebo for 12 months. Patients were assessed clinically, endoscopically and histologically at 1, 3, 6, 9 and 12 months. Patients treated with VSL#3 had a si g ni f i c an t ly l o wer i n c i de n c e o f a c u t e pou c hi t i s ( 10 %) compared with those treated with placebo (40%) ( p b 0.05), and experienced a significant improvement of quality of life.62The mechanism by which therapy with probiotics works remains elusive,but has been investigated.63Mucosa-associated pouch microbiota before and after therapy with VSL#3shows that patients who develop pouchitis while treated with placebo have low bacterial and high fungal diversity.Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3(p=0.001).Real time PCR experiments demon-strated that VSL#3increased the total number of bacterial cells(p=0.002)and modified the spectrum of bacteria towards anaerobic species.Taxa-specific clone libraries showed that the spectrum of Lactobacillus sp.and Bifido-bacter sp.was altered on probiotic therapy.The diversity of the fungal flora was repressed.Restoration of the integrity of a“protective”intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract.
8.4.Cuffitis
Cuffitis,especially after double-stapled IPAA(see Section 7,preceding paper same issue)can cause pouch dysfunction with symptoms that mimic pouchitis or irritable pouch syndrome(IPS).Unlike IPS(which may coexist)bleeding is a characteristic feature of cuffitis.Endoscopy by an informed endoscopist is diagnostic,but care has to be taken to examine the cuff of columnar epithelium between the dentate line and pouch-anal anastomosis(Section7.2.3, preceding paper same issue).64In an open-label trial,14 consecutive patients with cuffitis were treated with mesa-lamine suppositories500mg twice daily.16Mesalazine suppositories significantly reduced the total Cuffitis Activity Index(derived from the PDAI)from11.9±3.17to6.21±3.19 (p b0.001).Symptom subscore(from 3.24±1.28to 1.79±1.31),endoscopy subscore(from3.14±1.29to1.00±1.52) and histology subscore(4.93±1.77to3.57±1.39)were all significantly reduced.92%of patients with bloody bowel movements and70%with arthralgia(a characteristic clinical feature of cuffitis,Section8.1.5)improved on therapy.No systemic or topical adverse effects were reported.
9.Surveillance for colorectal cancer
9.1.Risk of cancer
9.1.1.Estimation of risk
Patients with long standing UC have a higher risk of developing colorectal carcinoma(CRC)than the average population.The magnitude of this risk,however,is still the subject of a debate.Indeed,while older reports included in two meta-analyses65,66confirmed a rapid increase of the risk after ten years of disease,the magnitude of the risk in recent population-based studies appears much smaller.67,68In fact, although Eaden and colleagues computed a cumulative CRC risk of18%in UC patients after30years of disease,risks of only7.5%and2.1%respectively were observed in two studies published since2004.67,68Furthermore,in the largest report of surveillance colonoscopy in at-risk population of patients with extensive UC to date(600patients over a30year period),the cumulative incidence of CRC by colitis duration
ECCO Statement8E
VSL#3 (18 × 10 11 of 8 bacterial strains for 9 or 12 months) has shown efficacy for maintaining antibiotic-induced remission [EL1b, RG B]. VSL#3 (9 ×1011 bacteria) has also shown efficacy for preventing pouchitis [EL2b, RG C]ECCO Statement8E
Rectal cuff inflammation(cuffitis)may induce symptoms similar to pouchitis or irritable pouch syndrome,although bleeding is more frequent[EL2a,RG B].T opical5-ASA has shown efficacy[EL4,RGD]
ECCO Statement9A
Patients with longstanding ulcerative colitis appear to have an increased risk of colorectal cancer(CRC)as compared to the general population[EL2]
68L.Biancone et al.
was 2.5%at20years,7.6%at30years,and10.8%at 40years.69In this study from St Mark's,only30/600patients (5%)developed CRC.The reasons for such an improvement in the risk of CRC are still unclear but may include improved control of mucosal inflammation,more extensive use of5-ASA compounds,the implementation of surveillance pro-grammes and timely colectomy.70Taken together these studies suggest that the CRC risk in UC patients should be kept under scrutiny.Nevertheless,the best evidence,as provided by concordant meta-analyses,indicates that the risk of CRC development is increased in UC[EL2].The ECCO Consensus working party,through their answers to ques-tionnaires,supported this evaluation of the data.
9.1.2.Risk factors for cancer development
Several independent factors affect the magnitude of the risk of malignant transformation.The duration of disease and extent of mucosal inflammation are the most prominent. There is no uniform definition of the duration of disease, although onset of symptoms has generally been used in the studies that have identified this parameter as a risk factor.In a review of19practice and population-based studies,Eaden confirmed that the CRC risk appears to increase8–10years after the onset of UC related symptoms65and subsequently increases in later decades of the disease[EL2].
The extent of mucosal inflammation(including backwash ileitis)has been correlated with the risk of CRC in several studies,as well as in a systematic review[EL2].66,67,71–75 Other factors have also been associated with a high CRC risk in all or part of these studies.These include young age at onset of the disease(less than20years of age at the time of diagnosis)65and an association with primary sclerosing cholangitis(PSC)[EL2].76However,there was no difference in median age at onset of colitis for those with or without CRC in the600-patient study from St Mark's(p=0.8,Mann–Whitney)years.69The persistence of mucosal inflamma-tion72,73or a family history of CRC77may also contribute to an increased risk,but the association has been less consistent across the studies[EL3].In a nested case-control study from two well-defined,population-based IBD cohorts(Copenhagen County,Denmark and Olmsted County,Minnesota)43cases of IBD-associated CRC were matched on six criteria to1–3 controls(n=102).Significant associations were found between PSC(OR6.9,95%CI1.2–40.0),the percentage of time with clinically active disease(OR per5%increase1.2,95%CI1.0–1.4),and≥12months of continuous symptoms(OR 3.295%CI1.2–8.6).78The presence of pseudopolyps,which can be considered a marker of severity of inflammation,have been associated with double the risk of CRC(OR2.5;95%CI: 1.4–4.6),73,79which is a useful practice point for clinicians.
9.2.Surveillance colonoscopy programmes
9.2.1.Screening and surveillance
Since dysplastic changes in colonic mucosa are associated with an increased risk of CRC in UC,surveillance colonoscopy programmes have been developed with the aim of reducing morbidity and mortality due to CRC,while avoiding unnecessary prophylactic colectomy.Surveillance for CRC in patients with UC amounts to more than just performing repeated colonoscopies,but includes reviewing patient symptoms,medication use and laboratory values as well as updating personal and familial medical history.At the onset of these programmes,an initial screening colonoscopy is performed,with the goal of reassessing disease extent and confirming the absence of dysplastic lesions.Thereafter surveillance colonoscopies are regularly performed at defined intervals(below).
9.2.2.Effectiveness
The effectiveness of these programmes has been eval-uated in some prospective studies,systematically reviewed by the Cochrane collaboration.66An American consensus conference,held under the auspices of the Crohn's and Colitis Foundation of America,also reviewed the usefulness of screening and surveillance colonoscopies in2005.80The Cochrane collaboration used death related to CRC as the primary endpoint for the evaluation of surveillance pro-grammes in UC,limiting their analysis to prospective randomised studies that included a control group.The authors were unable to demonstrate a benefit of surveillance programmes for preventing CRC-related death in UC by these strict parameters,but included only two studies in their final analysis.81,82An earlier meta-analysis included a third study yet to be published in full,but concluded that there was an improved5-year survival in patients undergoing surveillance, compared to UC patients outside surveillance programmes.83 Furthermore,in the largest and most meticulous screening programme reported to date,involving600patients,2627 colonoscopies,5932patient-years of follow-up and a caecal intubation rate of98.7%,with no significant complications, 16/30cancers were interval cancers.69
Unequivocal evidence for the benefit of these programmes is therefore lacking and the apparent benefit could still be linked to lead-time bias.Patients in surveillance programmes may have an earlier diagnosis of CRC even if CRC is detected independently of surveillance colonoscopy.Diagnosis of CRC in patients outside such programmes may arise from later,
ECCO Statement9B
Risk is highest in patients with extensive colitis, intermediate in patients with left-sided colitis,and not increased in proctitis[EL2].
ECCO Statement9C
Patients with early onset of disease(age b20years at onset of disease)and patients with UC-associated primary sclerosing cholangitis(PSC)may have a particularly increased risk[EL2]. Persistent inflammation and family history of CRC may contribute to the risk of CRC in patients with UC[EL3]ECCO Statement9D
Surveillance colonoscopy may permit earlier detection of CRC,with a corresponding improved prognosis[EL3,RG B].Unequivocal evidence that surveillance colonoscopy prolongs survival in patients with UC is lacking[EL3,RG B]
69
ECCO Consensus on UC:Special situations
symptom-driven investigation[EL3].These issues are best discussed with patients before entry into a surveillance programme.
The Consensus had divided opinions regarding the ability of surveillance colonoscopy programmes to improve survival in UC patients,in keeping with the contrasting results of the meta-analyses.Only one third of the voting experts considered that the procedure could achieve this goal, while two-thirds remained unconvinced or attributed any benefit to potential lead-time bias.Nevertheless,it should be noted that any benefit estimated in years of life saved may be much greater in UC patients than for general population screening.This is because UC-related CRC tends to occur earlier in life and with a higher frequency than in the general population.Mathematical models have evaluated that the duration of life saved per case screened ranges from 1.2to5years in UC patients,compared to1.2to4months in general population screening,66,84depending on the para-meters included in the calculation.
9.2.3.Initial screening colonoscopy
As duration of disease is a major risk factor for the development of CRC in UC patients,it is rational to propose a screening colonoscopy when the risk starts to increase,i.e. after8–10years from the onset of disease[EL2].This initial colonoscopy also aims to reassess the extent of disease,since this parameter also impacts on the risk of CRC.Nevertheless, the appropriateness of screening colonoscopy as a way of reassessing disease extent and potential risk has not been formally established.It has been proposed in reviews and a prior consensus report,80as well as being agreed during the present Consensus conference by the participating experts [EL5].
9.2.4.Surveillance schedules
The surveillance schedule is also arbitrary,but because CRC has been observed within2years of surveillance colono-scopy,85,86intervals between repeat investigations should not exceed this and should be shorter in patients with particularly high risks such as those with longstanding disease or PSC.
Furthermore,although disease extent is central to CRC risk assessment,this parameter may be difficult to define, implying that surveillance may be offered to large groups of patients.Considerable differences between extent assessed by colonoscopy and histology have been reported,87as well as variations in extent over time.88Neoplasia has been reported in areas of microscopic involvement without endoscopically visible inflammation.Thus,disease extent should be defined not only by the outcome of screening colonoscopy,but also by the results of previous procedures. In contrast,there is good evidence that the CRC risk is lower in patients with limited disease71,75as defined by colono-scopy or barium enema,so a reasonable compromise is to defer surveillance until later time points in patients with limited macroscopic disease[EL2].This all assumes that a decision has been made with the patient that surveillance is appropriate.If the risk of CRC complicating colitis is thought to be no higher than the general population,surveillance may be considered unnecessary.
In other situations,such as patients with UC-associated PSC,the risk of developing a CRC is not only particularly high, but has been reported to occur early(median2.9years)in the course of the disease.89These patients should enter in a more intensive surveillance programme once the diagnosis of PSC has been established.
The recommendations by ECCO(Statements9E–9G)are contingent on a perceived increased risk of CRC in UC (Statements9A–9C)and widespread acceptance in several European countries that screening for CRC in the general population is appropriate.If the latter applies,it is difficult to justify failure to screen a group of patients with higher risk of CRC more closely.The recommendation grades are appropriate to the strength of the evidence.
9.3.Colonoscopic procedures
9.3.1.Number and site of biopsies
Evidence for procedural techniques during surveillance colonoscopy is better documented than the benefit of the programme itself.At least33biopsies should be obtained from the various segments of the colon to achieve90–95% sensitivity for the detection of dysplasia.90–93A reasonable approach would therefore to perform4random biopsies every10cm around the colon.Extra biopsies should be obtained from strictured or raised areas and from other abnormal areas in the colon.Full colonoscopy is necessary because about a third of UC-associated CRC develop in the proximal colon.85This strategy is further supported by the observation that most dysplastic lesions are visible during careful colonoscopy.In a study performed on525patients who underwent2204surveillance colonoscopies,Rutter detected110neoplastic areas in56patients.94Eighty-five (77.3%)were macroscopically visible at colonoscopy and25 (22.7%)were macroscopically invisible.Fifty patients (89.3%)had macroscopically detectable neoplasia,while only6(10.7%)had macroscopically invisible lesions.The value of random biopsies,however,is limited compared to optical techniques that enhance detection of dysplastic epithelium.
ECCO Statement9E
Screening colonoscopy should be offered8–10years after the onset of UC symptoms to all patients to reassess disease extent[EL5,RG D]
ECCO Statement9F
In extensive colitis,surveillance should start after screening colonoscopy and be performed every other year up to year20of disease,then annually[EL2,RG B]. Surveillance should start15years after onset of disease in left-sided or distal UC.Proctitis does not require further surveillance[EL2,RG B]ECCO Statement9G
If primary sclerosing cholangitis(PSC)is associated to UC,surveillance should be performed annually from the time of PSC diagnosis[EL3,RG B]
70L.Biancone et al.
9.3.2.Chromoendoscopy
The yield of surveillance colonoscopy can be improved by spraying dyes(such as methylene blue or indigo carmine)that highlight subtle changes in the architecture of the colonic mucosa.95–101All studies have confirmed an improved diag-nostic yield for dysplasia detection using chromoendoscopy. With this method,random biopsies of apparently normal mucosa is of no additional value compared to targeted biopsies obtained after dye staining of the mucosa.101Comparable diagnostic yields from chromoendoscopy have been obtained with both methylene blue and indigo carmine.97,98Despite these good results,a single from experienced investigators found that no dysplasia was missed even without dye spraying.94 However,trained endoscopists in chromoendoscopy may even further distinguish neoplastic from non-neoplastic changes, based on surface crypt architecture based on pit pattern recognition with a sensitivity of93%and97%,respectively. Colonoscopy with dye staining did not take significantly longer than conventional colonoscopy.98This endoscopic approach may not only improve the yield of screening and surveillance colonoscopies,but also decrease the workload of pathologists because fewer biopsies are needed per procedure.
9.4.Dysplasia
The ultimate goal of surveillance colonoscopy is to identify whether the colonic mucosa has already undergone the early steps of malignant transformation(i.e.to detect dysplasia), which identifies UC patients at the highest risk of CRC development.102,103Dysplasia in UC is stratified as low grade, high grade or indefinite for dysplasia,according to the presence or absence of specific histological changes in the epithelium.If biopsies are indefinite for dysplasia and this is confirmed by an experienced pathologist,then follow-up surveillance colonoscopy within3to6months is recom-mended,with intensification of UC therapy in the meantime.
9.4.1.Risk of progression to cancer
The grade of dysplasia is important because it impacts on the sensitivity and specificity of the presence or future development of CRC.Dysplasia of any grade has been reported to have a74%sensitivity and74%sensitivity for CRC development,while in the same series from the Mayo Clinic,high grade dysplasia had lower sensitivity(34%)but 98%specificity for CRC detection.104In the most recent meta-analysis,low-grade dysplasia was found to be asso-ciated with a9-fold increased risk of developing CRC and a 12-fold risk of developing advanced neoplasia.105Therefore, the finding of low-grade dysplasia carries a substantial risk: such a finding has important prognostic implications.For this reason,dysplasia should be confirmed by an experienced pathologist,because interobserver variation for the detec-tion of dysplasia is high.106–108Furthermore,individual studies that do not show an increased risk of malignant transformation in low-grade dysplasia109need to be placed in the context of the meta-analysis.
9.4.2.Dysplasia and colectomy
Once dysplasia is found,the rationale of such a surveil-lance programme demands that colectomy is performed, because the risk of CRC is appreciably increased.105If high grade dysplasia is present,the decision is easier,because the risk of concomitant CRC may be as high as32%,106assuming that the biopsies were indeed obtained from flat mucosa and not from an adenoma.If low-grade dysplasia is detected,the 9-fold increased risk of developing CRC reported in the most recent meta-analysis105could reasonably be viewed as justification for colectomy as well,and this option should be discussed with the patient.110However,because some follow-up studies of patients with\low-grade dysplasia have shown a low rate of CRC development,86,111it seems a reasonable compromise to continue surveillance with exten-sive biopsy sampling at shorter(perhaps3–6month)intervals in those who will adhere strictly to the surveillance program. This remains controversial in the literature and was discussed during the conference as well.66,112
9.4.3.Dysplasia and raised lesions
Raised lesions on a background of UC have been tradition-ally referred to as“Dysplasia Associated Lesion or Mass”or DALM.Until recently this finding has been considered an absolute indication for colectomy.It is increasingly recognised, however,that some of these raised lesions may resemble sporadic adenomas and that they may be amenable to complete endoscopic resection.97,113–115If the polypectomy is confirmed complete by histology and if biopsies obtained
ECCO Statement9H
Random biopsies(4every10cm)and targeted biopsies of any visible lesion should be performed during surveillance colonoscopy[EL2b,RG B].Methylene blue or indigo carmine chromoendoscopy is an alternative to random biopsies for appropriately trained endoscopists and is superior to random biopsies in the detection rate of neoplastic lesions [EL1b,RG B]
ECCO Statement9I
A finding of dysplasia should be confirmed by an independent pathologist[EL2b,RG B]ECCO Statement9J
High grade dysplasia in flat mucosa and adenocarcinoma are indications for proctocolectomy[EL2,RG B].A patient with low-grade dysplasia in flat mucosa should be offered proctocolectomy or repeat surveillance biopsies within3–6months[EL2b,RG B]
ECCO Statement9K
A raised lesion with dysplasia should be completely resected. In the absence of dysplasia in the flat surrounding mucosa, meticulous endoscopic surveillance should be proposed [EL2b,RG B].If endoscopic resection is not possible or if dysplasia is found in the surrounding flat mucosa, proctocolectomy should be recommended[EL2b,RG B]
71
ECCO Consensus on UC:Special situations
from the flat mucosa immediately adjacent to the polypect-omy site show no dysplasia and if,in addition,no dysplasia is found elsewhere in the colon,then colectomy may be safely deferred.Careful follow-up,preferably with surveillance colonoscopy at3months and then6monthly,is needed if this strategy is followed,because at least half of such patients in the four studies quoted developed further raised lesions.If the lesion does not resemble typical adenoma,is not respectable,or is associated with dysplasia in the adjacent mucosa,then colectomy is indicated due to the high risk of concomitant CRC.90,113
9.5.Chemoprevention
The risk of developing CRC has been shown to be higher in patients with persistent mucosal inflammation,73and thus appropriate therapy may reduce the risk of CRC associated with chronic UC.Several studies suggest that sulfasalazine or mesalazine may lead to a risk reduction,referred to as a chemoprotection.Velayos et al.performed a meta-analysis that included334cases of CRC,140cases of dysplasia and a total of1932subjects extracted from3cohort studies and6 case-control studies.79This suggested that in a population matched for extent and duration of UC,aminosalicylates may reduce the risk of colorectal cancer.The risk reduction was significant for CRC development(OR0.51,95%CI0.37–0.69),but not for dysplasia(OR1.18,95%CI0.41–3.43).In view of the low toxicity of mesalazine and considering that the number of patients needed to treat(NNT)to prevent one CRC may be as low as7in patients with30years of disease,116 the Consensus felt that such a therapy should be considered and potentially offered to all UC patients in the absence of contraindications.The limitations of the data are,however, recognised and some large studies have shown no benefit.78 When76cases of CRC and UC in a cohort of18,969patients in the UK General Practice Research Database were compared to six matched control cases,regular users of5ASA(defined as six or more prescriptions in the preceding12months)had a trend towards a lower risk of CRC compared with irregular uses(unadjusted OR0.7,95%CI0.44–1.03).For mesalazine, but not sulfasalazine,the effect was significant depending on the total number of prescriptions:OR1.13(0.49–2.59)for 6–12prescriptions,OR0.30(0.11–0.83)for13–30prescrip-tions and OR0.31(0.11–0.84)for N30prescriptions.117 Patients with UC-associated PSC appear to be at particu-larly high risk of developing CRC.75In follow-up to a randomised trial evaluating the benefit of ursodeoxycholic acid in these patients,patients assigned to active medication for their biliary disease had a lower incidence of dysplasia and CRC development compared to patients assigned to placebo.118This study confirmed prior data from a cross-sectional study119in the setting of a prospective randomised trial.The Consensus considered these data sufficient evidence to recommend this therapy in all patients with UC and PSC,considering the potential benefit of the drug on both conditions and low toxicity.Nevertheless,the limita-tions of the data are again recognised,since not all studies have identified an association between PSC and CRC in patients with UC.79Interestingly,when the same group examined population-based as opposed to hospital-based cohorts,a significant association between PSC and CRC was identified(OR6.9,95%CI1.2–40),although a protective effect of aminosailcylates could not be discerned(cumula-tive dose of sulfasalazine(OR per kg1.1,95%CI1.0–1.3)and mesalazine(OR per kg1.3,95%CI0.9–1.9).78
9.6.Prognosis
The prognosis of CRC complicating UC has generally been considered worse than for sporadic CRC.This may not be valid.In a report from the Mayo Clinic,290patients with IBD-associated CRC(241with chronic ulcerative colitis and49 with Crohn's disease)were matched with an equal number of age-and sex-matched sporadic CRC patients between1976 and1996.55%of IBD-related tumours were distal to the splenic flexure compared to78%of sporadic CRC,but during a median follow-up period of5years,163IBD-associated CRC patients died(56%),compared with164sporadic CRC patients(57%).The5-year survival rates were54%in the IBD-CRC subgroup vs.53%in the sporadic CRC subgroup (p=0.94).120This is not that dissimilar to experience from St Mark's Hospital.In the largest experience of surveillance colonoscopy in600patients during5932patient–years of follow-up,30patients(5%)developed CRC,with a5-year survival rate of73.3%.69
The prognosis of colorectal dysplasia in IBD is also debated (Section9.4.1).In a population-based study from Minnesota, 29/725(4%)IBD patients developed flat dysplasia(n=8),a Dysplasia Associated Lesion or Mass(DALM,n=1),or an adenoma-associated lesion or mass(ALM n=18)in an area of IBD,or an ALM outside the area of IBD(n=2).Among6 patients with flat low-grade dysplasia(fLGD)who did not undergo colectomy,none progressed during a median of17.8 (range6–21)years of observation with a median of3(range 0–12)surveillance colonoscopies.Four(22%)patients with ALMs in areas of IBD who did not undergo surgery developed low-grade dysplasia or DALMs.Dysplasia located proximal to the splenic flexure was significantly associated with a risk of recurrence or progression of dysplasia.This population-based cohort did not confirm an increased risk of cancer related to flat low-grade dysplasia,78which is at odds with the meta-analysis.105
10.Children and adolescents
10.1.Introduction
About10–15%of patients with inflammatory bowel disease are diagnosed before the age of18years.121During puberty the incidence is7per100000per year and increases further during adolescence to about12per100000at age20–29, consistent with a peak around the age of30years.122In children most cohort studies show a lower incidence of ulcerative colitis(UC)compared to Crohn's disease(CD),123 but the incidence of CD has clearly increased over the past ECCO Statement L
Chemoprevention with5-ASA compounds may reduce the incidence of colorectal cancer in UC patients and should be considered for all UC patients[EL2,RG B].Colorectal cancer chemoprevention with ursodeoxycholic acid should be given to patients with PSC[EL1b,RG B]
72L.Biancone et al.
decade.In contrast,the incidence of UC is stable in some studies,124–126but increasing in other cohorts.127–129The median age of onset of symptoms in UC is12years in most paediatric studies,122,130,131but the diagnostic delay is considerably shorter than for CD.In contrast to adults,the clinical presentation of UC is often more severe in children, which may be explained by the predominance of pancolitis (70–80%of children)at the time of diagnosis.131,132
10.2.Diagnosis
10.2.1.Diagnostic threshold
In contrast to paediatric CD and its diverse symptomatol-ogy,the clinical manifestation of UC is almost uniformly bloody diarrhoea(84–94%of children),accompanied by tenesmus.132Although an infective aetiology should be excluded,its presence does not exclude a diagnosis of UC or CD.The combination of rectal bleeding,anaemia and increased ESR identified86%of patients with IBD prior to an endoscopic procedure.133Other retrospective case series have confirmed the diagnostic value of increased inflamma-tory markers and anaemia for IBD.134,135
A shorter interval from symptoms to diagnosis of UC probably explains why growth failure is half as common compared to CD.As with adults,the greatest risk factor for developing UC in childhood is to have a family member with ulcerative colitis(relative risk7–17).137,138The risk for CD in
a family member with Crohn's disease is a relative risk of15–
35.The stronger the family history,the earlier the onset of symptoms.For patients with early-onset UC(b5years'age), 26%–44%have a family history of UC,compared to older patients or children with CD.139,140Genetic factors are likely to have a stronger influence in paediatric IBD,especially in early-onset acute severe UC,compared to older children or adults.141,142Nevertheless,most children with IBD have no family history and are considered sporadic.
10.2.2.Documentation
Growth failure is a unique complication of paediatric IBD, caused by a combination of inadequate calorie intake,increased losses and active inflammation.Efficacy of medical treatment and concomitant mucosal remission is characterised by normal linear growth and pubertal development.In contrast,when catch-up growth does not occur after growth failure at diagnosis,or when height velocity decreases during mainte-nance treatment,it is highly likely that there is persistent disease activity,so therapy should be more aggressive and an adequate calorie intake ensured.136,143,144
10.2.3.Diagnostic procedures
The IBD working group of the European Society of Paediatric Gastroenterology Hepatology and Nutrition(ESPGHAN)has reached a consensus on the diagnosis of IBD in children,which has been summarised in the‘Porto Criteria’.145This group feels it essential to establish a diagnosis of the type of disease,as well as to determine severity,localisation,and extent of the disease, before treatment is started.Paediatric patients with UC have more extensive disease and rectal sparing in up to30%,146so a complete diagnostic work-up is warranted in children with bloody diarrhoea.Evidence supporting colonoscopy with ileal intubation and multiple biopsies,rather than sigmoidoscopy alone,is provided by retrospective cohort studies.146–148In cases with extensive colitis that cannot be classified,gastro-duodenoscopy may allow definitive diagnosis.149
The ECCO Consensus agrees that a paediatric gastroenter-ologist,rather than a specialist in adult endoscopy,should best perform endoscopy in children suspected of IBD.The most important argument is quality of care,particularly because endoscopy in children is preferably done under general anaesthesia:this is preferred for reasons of comfort and care and has been shown to be safe.150–155Moreover,the treatment and follow-up of children and adolescents with IBD should be in the hands of a paediatric gastroenterologist who is aware of age-related differences in disease presentation and treat-ment.Such specialists are experienced in handling problems such as linear growth retardation and pubertal delay.156 10.3.Induction therapy in children
10.3.1.Distal colitis
ECCO Statement10A
Ulcerative colitis should be suspected in a child with chronic (≥4weeks)or recurrent(≥2episodes in6months)bloody diarrhoea,after exclusion of infective or other causes.This applies particularly when there is growth failure and/or pubertal delay,a family history of IBD,increased markers of inflammation,or if anaemia is present[EL2b,RG B] ECCO Statement10B
In all children with UC,the height,weight(and pre-diagnosis growth curve)and pubertal stage,should be recorded at diagnosis,and regularly during follow-up[EL3b,RG B]ECCO Statement10C
Ileocolonoscopy and biopsies should be performed in all children or adolescents with a suspicion of inflammatory bowel disease(IBD).Upper gastrointestinal endoscopy is recommended when ileocolonoscopy does not confirm a diagnosis of ulcerative colitis[EL2a,RG B]
ECCO Statement10D
In children and adolescents(up to16–18years of age), endoscopy should be performed by a specialist with experience in paediatric gastroenterology,preferably by a paediatric gastroenterologist[EL5,RG D],in a setting that is suitable for diagnosing and treating children with IBD (paediatric hospital,with access to general anaesthesia) ECCO Statement10E
Oral[EL2b,RGB]aminosalicylates and/or topical aminosalicylates(suppositories in proctitis,enemas in left-sided colitis)[EL5,RGD]are appropriate initial induction therapy for mild to moderate distal colitis in children or adolescents
73
ECCO Consensus on UC:Special situations
No studies have been performed in children with distal colitis.A questionnaire sent to members of the IBD working group of ESPGHAN,however,revealed great variation of care in the treatment of distal colitis.The first choice was either oral treatment alone(mesalazine21%,sulfasalazine36%),or in combination with topical treatment(mesalazine36%, corticosteroids7%).Considering the rarity of proctitis in children,no standard treatment protocols exist.
10.3.2.Extensive colitis
Only one prospective study has confirmed the efficacy of oral aminosalicylates in children with active ulcerative colitis.157In this trial,a clinical response at8weeks was seen in79%of patients receiving sulfasalazine(60mg/kg/ day)and50%of patients on olsalazine(30mg/kg/day). Retrospective studies have also shown that oral aminosali-cylates effectively induce clinical remission.158–162 Although sulfasalazine may cause more gastrointestinal side-effects,it is the preferred aminosalicylate treatment in young children who cannot swallow tablets,because it is available as a suspension.Alternatively,mesalazine can be given as an enteric-coated granule formulation.Based on expert opinion and extrapolation from pharmacokinetic studies,159,161,163the advised dose(oral and rectal mesalazine combined)in children aged12years or older of mesalazine,is 50–75mg/kg/day with a maximum of4g/day.For sulfasala-zine it is100mg/kg/day with a maximum of6g/day.
Concerning oral corticosteroids,no studies have been performed in children with UC.Nevertheless,prospectively collected data from the US Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry database provides a useful insight.164In97children(age b16yr)with newly diagnosed UC between2002and2005,with a minimum of1year of follow-up,79%received corticosteroids,most (62/77)within30days of diagnosis.For those treated within 30days,disease activity at3months was inactive in60%,mild in27%,and moderate or severe in11%.At12months,31of62 (50%)of the early corticosteroid-treated patients were considered corticosteroid responsive and28(45%)were corticosteroid-dependent.A total of4patients receiving corticosteroids required colectomy in the first year.Immu-nomodulators were used in61%of all corticosteroid-treated patients.This is similar to adults:early response is excellent, but dependence is common,even with immunomodulators. Evaluation among the IBD working group of ESPGHAN demonstrated that46%favoured addition of corticosteroids if response to aminosalicylates was found to be insufficient. Oral prednisolone is given as a once daily dose of1–2mg/kg/ day,with a maximum dose of40mg,for2–4weeks(until clinical remission),then tapered to zero in6–8weeks. Although not supported by clinical evidence from randomised clinical trials,calcium and vitamin D are usually supplemen-ted during a course of steroid treatment.10.3.3.Severe colitis
Although no randomised clinical studies have been per-formed in children with acute severe UC,all respondents to the ESPGHAN questionnaire agreed that corticosteroids are the first line therapy in severe pancolitis.In a meta-regression of response to steroids in32studies involving1991patients (1974–2006),only43children were included.165T o evaluate the outcome in children,a retrospective study of74admissions in63children(57%males,age at diagnosis10.9±4yr,79% extensive colitis)treated at T oronto SickKids Hospital1995–99 was performed.16641%failed intravenous steroids by discharge and23(37%)came to colectomy on that admission.By one year,54%and by5yr59%had come to colectomy.There was no clear consensus from ESPGHAN as to whether corticosteroids should be given as the only treatment(25%of respondents),or in combination with oral mesalazine(25%),or intravenously with adjunctive parenteral nutrition(50%).Given the similar-ity in the response of children to steroids compared to adults (Section5.2.4,preceding paper same issue),it seems unlikely that mesalazine is necessary.Although nutritional support is particularly appropriate in children,TPN in adults has not been shown to offer any advantage when managing acute severe colitis(Section5.2.4,preceding paper same issue).
When3–5days of intravenous corticosteroids are inef-fective,rescue therapy with ciclosporin,tacrolimus,or infliximab are the only two options to avoid or postpone colectomy.An objective assessment of the response to steroids facilitates management as it does in adults(see Section5.2.5,preceding paper same issue).A paediatric index of severity as been developed166and when calculated on day3,strongly predicts failure of intravenous steroids.167 As with adults,stool frequency(p=0.001)and CRP(p=0.045) on day3(but not day1)predict failure,along with temperature(p=0.001).Case studies with intravenous ciclosporin in children with severe,steroid-refractory colitis who are candidates for surgery,have shown remission of the disease in up to80%of cases.168–172In many children, however,tapering of oral ciclosporin resulted in a relapse and was followed by colectomy within a year of cessation of treatment.In occasional patients,short term ciclosporin treatment can effectively induce remission while waiting for azathioprine maintenance treatment to take effect.170 Infliximab has not been studied prospectively,but small retrospective studies in new-onset steroid-refractory patients show complete remission in75–88%of patients.173–175With the small numbers of patients studied and limited follow-up,it is currently unknown whether infliximab therapy is effective in avoiding colectomy,or whether it simply defers it.The Consensus view is that rescue therapy with either ciclosporin, tacrolimus,or infliximab should only be initiated in a specialist centre where a paediatric and/or colorectal surgeon are available and involved in the treatment of these severely sick children.
ECCO Statement10F
For mild to moderate pancolitis in children,oral mesalazine/sulfasalazine is recommended as first line therapy[EL2b,RG B].Oral steroids are appropriate if the response is insufficient[EL4,RG D]ECCO Statement10G
For severe pancolitis in children,corticosteroids are first line therapy[EL4,RG D].If the response is insufficient, intravenous ciclosporin[EL4,RG C]or infliximab[EL4,RG C],or colectomy are appropriate options
74L.Biancone et al.
10.4.Maintenance therapy in children
10.4.1.Aminosalicylates
The efficacy of mesalazine or sulfasalazine maintenance treatment has not been studied in children with UC.From the IBD working group of ESPGHAN questionnaire respondents, 57%advised continuing the same mesalazine dose as used for induction,while43%advised a lower dose.The Consensus view is based on results from adult studies that indicate that high dose5-ASA is effective maintenance treatment.Long-term corticosteroids are absolutely contraindicated,because they do not maintain remission and have a negative effect on linear growth and bone mineralisation.Ciclosporin main-tenance treatment is ineffective and inappropriate,because serious,sometimes irreversible,side-effects may occur. 10.4.2.Thiopurines
Retrospective cohort studies have demonstrated that main-tenance with azathioprine/mercaptopurine is effective,while achieving a steroid-sparing effect.176–179This steroid-sparing effect is more evident when azathioprine treatment is started early in the course of disease,within2years after diagnosis.179 The advised dose for azathioprine in children is2–3mg/kg/day and that for mercaptopurine is1–1.5mg/kg/day.
10.5.Surgery in children
10.5.1.Indications
In acute severe colitis,the decision to perform colectomy should be evaluated on a day-to-day basis by both the medical and surgical team.If the disease is not responding to7–10days of either calcineurin inhibitors(ciclosporin,tacrolimus)or infliximab,colectomy is indicated.
Colectomy is also indicated for persistently active disease, when corticosteroid dependency exists despite concomitant therapy with azathioprine/mercaptopurine,or when immu-nosuppressive treatment has side-effects.Growth failure despite apparently adequate maintenance therapy is also an indication for colectomy,even when clinical symptoms appear mild.180–184Preliminary(and anecdotal)experience with infliximab in children suggests that it may be more effective in acutely ill patients,compared to patients with chronic refractory disease.173,175,185It rarely achieves steroid-free remission.Therefore,infliximab cannot be recommended for chronic steroid-dependent disease in children.
10.5.2.Procedures
Depending on the local circumstances,a child needing colectomy should be referred for expert care at a specialist centre.Case series of IPAA in children show good results in terms of quality of life,continence and incidence of pouchitis.181,182,186–189However,in very young children (b10years),pouchitis is reported in75%of the patients.190 Because IPAA decreases female fecundity,191,192colectomy with ileorectal anastomosis until later IPAA may be a better option in girls.193Expert advice should be sought.
10.6.Nutritional support
It has not been shown that enteral nutrition has a primary therapeutic role in ulcerative colitis.There are many theories that suggest that diet may be implicated in the aetiology of inflammatory bowel disease.However,there is,as yet,no dietary approach proven to reduce the risk of developing IBD. Children with IBD have increased calorie and protein require-ments,so intake should be at least120%of recommended daily allowances(RDA).If oral intake is poor due to anorexia during a period of disease activity,high-calorie supplements may be indicated and specialist dietetic advice is appropriate.
10.7.Psychosocial support
ECCO Statement10H
Oral mesalazine or sulfasalazine are recommended maintenance treatment in the same dose as for induction therapy[EL5,RG D].For difficult patients with extended and/or relapsing disease,who are steroid-refractory or steroid-dependent,azathioprine/mercaptopurine is
recommended[EL4,RG C].Long-term steroids are contraindicated and ciclosporin is inappropriate ECCO Statement10I
Colectomy is indicated for severe colitis with acute complications not responding to medical therapy; persistently active disease with failure or toxicity of medical treatment;failure to taper corticosteroid treatment despite immunosupressant use;growth retardation or pubertal delay despite medical treatment[EL4,RG C]ECCO Statement10J
Colectomy should be performed by an experienced paediatric surgeon,ideally with the assistance of a colorectal surgeon with paediatric experience;ileo-pouch-anal anastomosis(IPAA)should only be performed in a highly specialised centre[EL4,RG C]
ECCO Statement10K
Enteral or parenteral nutritional therapy is inappropriate primary treatment.However,a nutritional evaluation is essential and nutritional support should be provided when required[EL5,RG D]
ECCO Statement10L
There is no indication for a“special diet”for ulcerative colitis,because none are effective and there is a risk of nutritional deficiencies[EL5,RG D]
ECCO Statement10M
Psychosocial support is important adjunctive treatment, because depressive symptoms are frequent and psychosocial support may be associated with a better outcome and a better quality of life[EL3b,RG B]
75
ECCO Consensus on UC:Special situations
Children and adolescents with IBD are at greater risk of developing behavioural difficulties or emotional dysfunction and depression in particular(in almost25%of patients),as well as anxiety,social dysfunction and low self-esteem compared to healthy children.194–197The quality of life in adolescents with IBD is generally lower than healthy controls.198–201T wo large randomised studies have demon-strated that psychosocial support by a patient-orientated self-management approach can have a beneficial influence on the course of disease.202,203Therefore,appropriate medical information and mental health support are recom-mended,because this may influence disease activity.195
10.8.Transition of care to adult services
A careful transition of patients from the paediatric service to adult gastroenterologists is vital,because it may reinforce treatment adherence and improve quality of life.204There are many differences between paediatric and adult care.In the paediatric service,children and adolescents with IBD are usually seen together with their parents and often receive more attention,because the disease is uncommon in children compared to adults.A paediatric specialist nurse may be on hand to advise and be a point of contact for the child or parents. Endoscopy is performed under general anaesthesia,whereas this is exceptional in adults.On the other hand,the paediatric gastroenterologist rarely discusses long-term issues,such as cancer risk or surveillance.Close collaboration between the paediatric and adult services will overcome these differences. The ideal setting for this is a transitional clinic where adolescent patients are seen by both specialists.205The alternative is to establish a parallel clinic,where paediatric and adult IBD clinics run independently but at the same time,so that when a suitable patient is seen,it is then a simple matter for the paediatric or adult gastroenterologist to go down the corridor to contact their opposite number so that the young person can be introduced or seen together.A trained IBD nurse specialist can play an important role coordinating care between the service,the patient and the family during the transitional period.
11.Pregnancy
The section on pregnancy and ulcerative colitis will be published subsequently.The principles of managing pregnancy, delivery,breast-feeding and Crohn's disease also apply to ulcerative colitis.206See also Cornish J,T an E,T eare J,et al.A meta-analysis on the influence of inflammatory bowel disease on pregnancy.Gut2007;56:830–7.
12.Psychosomatics
12.1.Introduction
While psychosocial factors are generally considered important in ulcerative colitis,controversy still exists about their role.This leads to potential inconsistencies in clinical practice.A biopsychosocial model207,208represents an advantage over a biomedical model,because it embodies the complex biological and psychosocial interactions that explain human illness or its effects.Attention to psychosocial factors associated with ulcerative colitis may have consequences not only on psychoso-cial well-being and quality of life,but also on the activity of the disease itself.The key words used in the systematic literature review of Medline and Embase for this review were ulcerative colitis as well as inflammatory bowel disease and irritable bowel syndrome—psychology;psychosocial;psychotherapy;quality of life;doctor patient relationship;and psychopharmaceuticals.
12.2.Influence of psychological factors on disease 12.2.1.Aetiology
Studies about the influence of psychological factors on the development of ulcerative colitis are very limited.There are a few studies with hypothetical interpretations about the influence of psychosocial factors on the aetiology of the disease.209–212Many studies on psychosocial factors relate to inflammatory bowel disease (IBD)rather than ulcerative colitis or Crohn's disease in particular.
12.2.2.Pattern of disease
Psychological factors are considered to have an influence on the course of the disease,which is consistent with evidence in the recent literature about the influence of subjective perceived psychological distress on disease activity of ulcerative colitis.213–217Studies about the influence of major life events on the biological disease activity have yielded contradictory results.218–220Patients themselves and the majority of European experts at the Consensus conference consider psychosocial distress as influencing the risk of relapse.221,222One study shows a heightened response to stressors and the greater epithelial damage in IBD patients,which suggests that stress-induced activation of the brain-gut axis and of mucosal mast cells may be important in the initiation and/or flare up of IBD.223
12.3.Psychological disturbances in ulcerative colitis
ECCO Statement10N
Transitional clinics represent optimal care and are highly recommended[EL5,RG D]ECCO Statement12A
A speculated association between psychological factors and the aetiology of ulcerative colitis cannot be proven.There is,however,an influence of psychological distress and mood disorders on the course of the disease[EL1b,RG B] ECCO Statement12B
There is evidence of an interaction between psychological factors and IBD activity.Depression and perceived chronic distress represent risk factors for relapse of the disease.It remains controversial whether acute life events trigger relapses[EL1b,RG B].Most patients consider stress to have an influence on their illness[EL4,RG C]
ECCO Statement12C
Psychological disturbances seem to be a consequence of the illness rather than the cause of,or specific to ulcerative colitis. The degree of psychological distress and disturbances correlates with the disease severity,predicts health-related quality of life and influences the course of disease[EL1b,RG B]
76L.Biancone et al.
Patients with ulcerative colitis seem to have no more,or only slightly more,psychological disturbances compared to patients with other chronic diseases.211,224–229A consistent association between psychological factors and the preva-lence of IBS-like symptoms in patients in remission has been reported.229–232There is also evidence that children and adolescents with IBD comprise a population at high risk of developing a psychiatric disorder.233,234A recent study with a large IBD population has shown that IBD patients experience a rate of depression that is triple that of the general population(16.3%vs.5.6%).235In this study17%of depressed patients had considered suicide in the past12months and an additional30%had considered suicide at an earlier time.In individuals who were currently depressed,female patients were more likely than males ever to have considered suicide (50%vs.31%).Depressive coping strategies are positively associated and predict health-related quality of life.236 Furthermore,the psychosocial consequences of the illness become more significant with increasing severity of the disease and quality of life is related to disease activity, symptoms218,224,237–243and female gender.237,244,245
12.4.Approach to psychological disorders
https://www.doczj.com/doc/2918308974.html,munication with patients
Health perceptions impact on the experience of the illness.226Increasing physician awareness of the fact that psychologically distressed patients have difficulty in proces-sing clinically relevant information246may lead to improved doctor–patient communication.247It is important that patients are informed about their condition through an individual interview,in conjunction with emotional support. This is because a lower level of information is associated with greater concern,248despite the impression of some doctors that more information increases the level of anxiety. Psychosocial factors are strongly correlated with health care utilization.249Self-management guidebooks together with patient-centred consultations improve patients'disease control.250,251It should however be recognised that educa-tional booklets on their own do not seem to be helpful and may even worsen the health-related quality of life of patients attending tertiary centres.252In addition,patient education programmes seem to have very limited or even no influence on the course of their illness,their health-related quality of life,or their psychological affect.253–255Almost all experts at the Consensus(91%)are convinced that a good doctor–patient relationship is helpful psychologically and take psychosocial factors into account for both diagnosis and therapy.Most experts at tertiary centres have the opportu-nity for integrated somatic and psychological care of patients.However,patients describe deficiencies in the care of family members,insufficient information and inadequate access to healthcare resources.256
12.4.2.Psychological support
For assessment of quality of life,two validated IBD-specific questionnaires have been shown to be sensitive,reproducible and responsive for use in clinical trials:the Inflammatory Bowel Disease Questionnaire(IBDQ)257and the Rating Form of Inflammatory Bowel Disease Patient Concerns(RFIPC).258 Detection and treatment of psychological distress has the potential to improve health-related quality of life.259The presence of psychological disorders contributes to poor quality of life and the number of doctor visits,regardless of the severity of the condition.249This is the common experience of doctors caring for patients with IBD,even if the potential or need to treat this aspect of the illness is perceived.
To assess the demand for psychological care in chronic diseases,a validated questionnaire is available,developed and based on inflammatory bowel disease.260Most experts (80%)feel themselves able to recommend psychotherapy during a discussion with patients.There is no study on their competence at doing this,but this is consistent with the experience of participants in the European Consensus on the management of Crohn's disease,206the German Consensus on Crohn's disease,56and that on ulcerative colitis.261,262Since strategies aimed at improving social support can have a favourable impact on psychological distress,263training of gastroenterologists to integrate psychosocial factors in clinical practice should be taken into consideration.
12.4.3.Therapeutic intervention
Psychotherapy and relaxation methods have a positive influence on IBD,mainly affecting the psychological dimen-sions of the illness such as psychological well-being,coping strategies and psychological distress,264–268as well as perception of pain.269This underpins the recommendation (Statement12G).The diagnosis of ulcerative colitis is insufficient alone to recommend psychotherapy,since studies of psychotherapy on patients without psychological
ECCO Statement12D
Clinicians should particularly assess depression among their patients with active disease and those with abdominal pain in remission[EL2b,RG B]
ECCO Statement12E
The psychosocial consequences and health-related quality of life of patients should be taken into account in clinical practice at regular visits.Individual information and explanation about the disease should be provided through a personal interview.The course of the disease can be improved by combining self-management and patient-centred consultations[EL1b and3b,RG B]ECCO Statement12F
Physicians should assess the patient's psychosocial status, quality of life and demand for additional psychological care and recommend psychotherapy if indicated.Integrated psychosomatic and gastroenterology care should be available[EL2b,RG B].Patients should be informed of the existence of patient associations[EL5,RG D]
ECCO Statement12G
Psychotherapeutic interventions are indicated for psychological disorders associated with ulcerative colitis [EL1b,RG B]
77
ECCO Consensus on UC:Special situations
disturbance show little or no benefit.270One study that combined patients with Crohn's disease and ulcerative colitis reported an influence of psychotherapy on disease activity, but there was inhomogeneity in randomisation of the treatment and control groups,so the results are not included in the evidence-based recommendation.
12.4.4.Therapeutic choice
There is no evidence that one psychotherapeutic method should be preferred over another.Relaxation exercises are useful,since they are easy to learn and perform.Expert opinion believes that there is an advantage if the psy-chotherapist has experience in the treatment of patients with chronic inflammatory bowel diseases and works closely with the patient's gastroenterologist.There are no specific studies on the use of individual psychopharmaceuticals in ulcerative colitis.271In spite of this,almost all experts believe that there are clinical situations in which antide-pressants should be recommended for treatment of psycho-logical distress associated with ulcerative colitis.
13.Extraintestinal manifestations
13.1.Introduction
Extra-intestinal manifestations(EIMs)occur in up to30%of patients affected by ulcerative colitis or Crohn's disease,272–274 although it is probable that studies from referral centres have over-estimated the prevalence and community studies suggest that their prevalence may be much lower.What is interesting is that the occurrence of one EIM appears to predispose to others.This suggests an underlying generic susceptibility in some patients that is largely genetically determined,although may yet be prone to environmental influence.Female patients with colitis(either ulcerative or Crohn's colitis)appear to be particularly susceptible.275
Scoring systems such as the Crohn's disease activity index (CDAI)include EIMs in the assessment.This is a weakness, although not widely recognised,since only some EIMs are related to disease activity and a genetic susceptibility in a minority of patients introduces bias.Those EIMs broadly related to the activity of colitis include oligoarticular peripheral arthritis,erythema nodosum,oral aphthous ulcers and episcleritis.274Polyarticular peripheral arthritis,pyo-derma gangrenosum[PG],uveitis and spondylarthropathy tend to pursue a course independent of disease activity,while primary sclerosing cholangitis[PSC]is most prevalent in patients with colitis that follows an apparently mild course.
For those EIMs closely related to ulcerative colitis activity, treatment can parallel that of the underlying disease. Treatment otherwise is mainly on a case-by-case basis as randomised controlled trials are mostly lacking.Specific therapy for EIMs is strongly influenced by current IBD treatment,and may include increasing dosage of existing drugs or the addition of new agents.
Consensus review indicates that gastroenterologists will be comfortable diagnosing and treating the more common extraintestinal manifestations,unless they prove resistant, with the exception of eye involvement for which the advice of an ophthalmologist is selected in a great majority of cases (93%).It is noted however that the frequency with which routine dermatological(46%)and rheumatological(31%) advice would be sought has increased since the review panel was interrogated on their approach to EIMs of Crohn's disease in2004.206This section concentrates on the more frequently encountered EIMs,for which at least some quantifiable data exist.Thrombotic complications of colitis and their prevention are considered in the section on acute management of colitis.Anaemia in colitis(as in Crohn's disease)is too frequently neglected:authorative guidelines have been published separately.276
13.2.Arthropathies
The diagnosis of non-axial arthritis and arthropathy associated with inflammatory bowel disease(IBD)is made on clinical grounds and t types have been defined by the Oxford group.The distinction is supported by differences in genetic susceptibility.277Type I is a large joint pauciarticular arthropathy that occurs at times of IBD activity,while type II is a polyarticular small joint arthropathy,whose activity is largely independent of IBD activity.Axial arthritis includes sacroiliitis and ankylosing spondylitis which are diagnosed clinically,supported by characteristic radiological changes. Magnetic resonance imaging is the diagnostic tool of choice.
13.2.1.Pauciarticular peripheral arthropathy
Type I arthropathy277predominantly affects weight-bearing joints,including the ankles,knees,hips,wrists,elbows and shoulders.Pauciarticular means that fewer than five joints are affected.The arthritis is usually acute,self-limiting, resolves within weeks as disease activity decreases,and leaves no permanent joint damage.Clinical examination reveals painful,tender,swollen joints.Aspiration is unne-cessary unless an alternative diagnosis is suspected.The differential diagnosis includes osteoarthritis,septic arthritis, pyrophosphate arthropathy,coincidental rheumatoid
ECCO Statement12G
The choice of psychotherapeutic method depends on the
psychological disturbance and should best be made by
specialists(Psychotherapist,Specialist for Psychosomatic
Medicine,Psychiatrist).Psychopharmaceuticals should be
prescribed for defined indications[EL5,RG D]
ECCO Statement13A
Diagnosis of non-axial arthritis and arthropathy associated
with UC is made on clinical grounds based on characteristic
features and exclusion of other specific forms of arthritis
[EL3b,RG C].T ype I is pauciarticular and affects large joints
acutely at times of UC activity.T ype II is polyarticular,
affecting a larger number of peripheral joints independently
of UC activity[EL2b,RG B]Axial arthritis,including sacro-
iliitis and ankylosing spondylitis,is diagnosed on conventional
rheumatological grounds,and is supported by characteristic
radiological changes,magnetic resonance imaging being the
most sensitive[EL2b,RG B].Although HLA B-27is over-
represented in axial arthritis related to UC this is not of
diagnostic value[EL2b,RG B]
78L.Biancone et al.
arthritis,or occasionally,gout.If just one hip joint is affected then steroid-induced osteonecrosis should be considered.279 13.2.2.Polyarticular peripheral arthropathy
Type II arthritis predominantly affects the small joints of both hands as a symmetrical arthropathy.Pain is commonly disproportionate to the signs of arthritis.It usually persists for months or years and follows a course independent of IBD activity.It may persist after colectomy or start after ileo-pouch-anal anastomosis.The differential diagnosis includes osteoarthritis,but also includes treatment side-effects such as steroid-induced pseudorheumatism(which is common after withdrawal of long-term steroids)and mesalazine-or azathioprine-induced arthropathy.278
13.2.3.Axial arthropathy
Asymptomatic sacroiliitis is common,with up to50%of colitis patients having abnormal radiography.279Symptomatic sacroiliitis is characterised by pain in the buttocks after rest,which then improves with movement.The clinical sign of discomfort in the sacroiliac joints during bilateral pressure on the pelvic brim is indicative.The principal symptom of ankylosing spondylitis is persistent low back pain,usually beginning before the age of30.Clinical examination reveals loss of the lumbar lordosis and limited spinal flexion. Conventional radiographs of the back are usually normal in the early stages of disease.Spinal CT scans and radionuclide bone scans are more sensitive than plain radiographs,but the gold standard is now magnetic resonance imaging (MRI).280,281There is however an impression that minor abnormalities of little or no clinical consequence may be seen on MRI;this remains to be determined by longer-term follow-up.In advanced cases there may be squaring of the vertebral bodies,marginal syndesmophytes and bony pro-liferation,with ankylosis producing the classical“bamboo spine”.HLA B-27associations is found in a majority(up to 75%)of patients with axial arthritis,but is less common than in patients with ankylosing spondylitis not associated with IBD.It is unrelated to sacroiliitis and HLA typing has no role in the management of individual patient.282,283
13.2.4.Therapy of arthropathies
Treatment of arthritis and arthropathy associated with IBD is largely empirical.This includes the use of simple analgesics,sulfasalazine,local steroid injections and phy-siotherapy,but whether or not to use non-steroidal anti-inflammatory agents is a continuing dilemma,even though short term use appears not to exacerbate colitis.284 For Type I peripheral arthritis the emphasis should be on the treatment of active disease,including steroids,immu-nomodulation,and anti-TNF therapy as appropriate.Resolu-tion of the arthropathy can be expected.The joint-specific drug of first choice for all forms of IBD-related arthritis appears to be sulfasalazine,but convincing evidence to support this is lacking.Nevertheless,it was favoured by the greatest minority of panel members(41%).Symptomatic relief may be obtained from simple analgesics,rest and physiotherapy.279,284,285,286Although there is concern that non-steroidal anti-inflammatory agents(conventional and COX II inhibitors)may aggravate the underlying colitis,287,288 they have been used by many gastroenterologists to good effect with limited risk of exacerbating colitis.A previous history of flare related to NSAID intake seems to be the best indicator of individual risk.A randomised study of the safety of celecoxib in colitis283indicated that short-term use (b2weeks)did not exacerbate colitis.Local steroid injection into the worst-affected joints often provides rapid,but temporary relief.Type II arthritis generally resolves with effective treatment of the colitis.289
Treatment of axial arthritis should include intensive physiotherapy,together with disease modifying drugs such as sulfasalazine,and methotrexate.279,285,289The safety and efficacy of infliximab in ankylosing spondylitis is estab-lished,but is best reserved for intractable or severely debilitating symptoms.290,291This is because of the15% prevalence of immunogenicity and the small,but definable risk of notable adverse events such as sepsis,tuberculosis,or demyelination.
13.3.Cutaneous manifestations
13.3.1.Erythema nodosum
Erythema nodosum is usually readily recognised.It is characterised by raised,tender,red or violet subcutaneous nodules of1to5cm in diameter.It commonly affects the extensor surfaces of the extremities,particularly the anterior tibial area,and usually occurs at times of activity of the colitis.A firm clinical diagnosis can normally be made, and biopsy is not normally appropriate.If performed,the histology reveals a non-specific focal panniculitis.292,293 Because erythema nodosum is closely related to disease activity,despite a genetic link,294treatment is based on that of the underlying colitis.Systemic steroids are usually required(76%Consensus view).In resistant cases or when there are frequent relapses,immunomodulation with azathioprine and/or infliximab may be added,but it is exceptional to need such measures just because of erythema nodosum.Oral potassium iodide has been used successfully in refractory cases.295
ECCO Statement13B
Treatment of arthritis and arthropathy associated with UC is based almost entirely on extrapolation from that for other forms of arthritis.There is some support for use of sulfasalazine,simple analgesics,non-steroidal anti-inflammatory agents,local steroid injections,and physiotherapy[EL4,RG D].In Type I peripheral arthritis the emphasis should be on that of the underlying colitis [EL2c,RG C].In axial arthritis the arguments in favour of intensive physiotherapy[EL2a,RG B],sulfasalazine[EL2a, RG C],methotrexate[EL3b,RG C],and infliximab[EL2a, RG C],are somewhat stronger ECCO Statement13C
Diagnosis of the cutaneous manifestations of UC is made on clinical grounds,based on their characteristic features and(to some extent)the exclusion of other specific skin disorders;biopsy is rarely appropriate or necessary[EL3b, RG C]
79
ECCO Consensus on UC:Special situations
13.3.2.Pyoderma gangrenosum(PG)
Lesions are often preceded by trauma at the site(which may have been many years earlier)through a phenomenon known as pathergy.PG can occur anywhere on the body,including the genitalia,but the commonest sites are the shins and adjacent to stomas.Initially they take the form of single or multiple erythematous papules or pustules,but subsequent necrosis of the dermis leads to the development of deep excavating ulcerations that contain purulent material that is sterile on culture unless secondary infection has occurred.
Treatment of pyoderma gangrenosum has relied on topical and systemic steroids.Steroids were considered the most effective treatment for pyoderma gangrenosum (54%Consensus view),with intravenous ciclosporin or tacrolimus reserved for refractory cases.296–298There are, however,no reliable trials to support the use of high dose steroids or calcineurin inhibitors and these drugs have appreciable potential side-effects.Infliximab has changed the management of PG.In the first controlled trial in pyoderma(which also included patients without IBD) infliximab5mg/kg or placebo was given at week0.299At week2(the primary end point),significantly more patients in the infliximab group had improved(46%(6/13))compared with the placebo group(6%(1/17),p=0.025).Overall,29 patients received infliximab with69%(20/29)demonstrat-ing a beneficial clinical response.Remission at week6was 21%(6/29).There was no response in31%(9/29)of patients. Infliximab is still reserved for more troublesome cases,but is highly effective.
13.3.3.Sweet's syndrome
Sweet's syndrome is characterised by tender,red inflamma-tory nodules or papules,usually affecting the upper limbs, face or neck.It has only been recognised as an extraintestinal manifestation of IBD relatively recently.300,301It is part of the group of acute neutrophilic dermatoses that includes pyoderma gangrenosum,but can be distinguished by its appearance,distribution and histological features.There is a strong predilection for women(87%),patients with colonic disease(100%)and those with other extraintestinal features (77%).The rash is associated with active disease in67–80%, but may precede the onset of intestinal symptoms in21%and has been reported3months after proctocolectomy for ulcerative colitis.
13.4.Ocular manifestations
Uveitis and episcleritis are probably the most common extraintestinal manifestations of IBD.273,30213.4.1.Episcleritis
Episcleritis may be painless,presenting simply with hyperaemic sclera and conjunctiva,but itching and burning sensations may also occur.303Diagnosis of simple episcleritis depends on the exclusion of the more sinister features of uveitis.When this is not possible referral to an ophthalmologist for an expert opinion and slit-lamp examination is essential.Episcleritis usually does not require specific treatment other than for underlying disease activity.It will respond to topical steroids if symptoms are troublesome—but take care that infection (including herpetic),ulceration,and uveitis are not overlooked.
13.4.2.Uveitis
Uveitis is less common,but has potentially severe consequences.When related to ulcerative colitis it is frequently bilateral,insidious in onset and long-lasting.304 Patients complain of eye pain,blurred vision,photophobia and headaches.Potential progression to loss of vision should prompt urgent referral to an ophthalmologist.Slit-lamp examination will confirm the diagnosis and differ-entiates between anterior and posterior uveitis.Uveitis is treated with steroids,and it may be necessary to use both topical and systemic routes.Infliximab is rapidly effec-tive,304but treatment should be guided by specialists. 13.4.3.Cataracts
Chronic corticosteroid use for treatment of UC is associated with numerous complications and may result in posterior subcapsular cataracts develop in a significant proportion (25%)of patients receiving15mg or more of prednisone for 1year.305Although steroids do not prevent relapse and have no place in the long-term management of UC,any patient on long-term steroids should undergo routine(probably annual) slit lamp examination.
13.5.Hepatobiliary disease
Hepatobiliary disease is relatively common in IBD and magnetic resonance cholangiography(MRC)indicates that it may be more prevalent than currently estimated in ulcerative colitis.306Primary sclerosing cholangitis(PSC) constitutes the most important condition relatively specific to the underlying IBD.Other conditions associated with IBD more commonly than in the general population include pericholangitis,steatosis,chronic hepatitis,cirrhosis,and gallstone formation.Hepatotoxicity from some drugs used for colitis should always be considered,although usually presents within3weeks of starting medication and not at later stages.
The finding of abnormal liver function tests,rather than symptoms or signs of liver disease,is the most common presentation.Diagnosis of hepatobiliary disorders then follows the standard investigatory pathways for abnormal liver function tests,with ultrasound scanning,serology to identify specific auto-immune or infective causes,and liver biopsy.Predominantly cholestasis or the biliary-type pain will prompt ultrasonographic assessment,which may reveal gall stones,steatosis,be consistent with cirrhosis, or(less often)show an abnormal duct pattern suggestive of PSC.
ECCO Statement13D
A confident diagnosis of simple episcleritis may not
require specific treatment,but if necessary will usually
respond to topical steroids[EL4,RG D].When diagnosis is
uncertain referral to an ophthalmologist for expert
opinion and slit-lamp examination is recommended[EL4,
RG D].Uveitis is treated with steroids,and it may be
necessary to use both topical and systemic routes[EL3b,
RG C].Immunomodulatory therapy has been thought
helpful in resistant cases[EL4,RG D]
80L.Biancone et al.
13.5.1.Primary sclerosing cholangitis
For patients with cholestasis the probability of PSC is appreciably increased if the ultrasound scan is normal,if drug side-effects are thought unlikely,and if serological tests for primary liver disease are negative.Magnetic resonance cholan-giography(MRC)is now established as the first-line diagnostic test for PSC.307The characteristic pattern shows irregular bile ducts,with zones of both narrowing and dilatation.If MRC is normal and PSC still suspected(such as otherwise unexplained cholestasis in a patient with IBD),then it is safer and probably more effective to do a liver biopsy rather than diagnostic ERCP, since this will detect predominant small duct disease.PSC substantially increases the risk of both cholangiocarcinoma and colorectal carcinoma(Section9.1.2,9.5).
PSC appears to respond to ursodeoxycholic acid(ursodiol), which improves abnormal liver function tests308and may,at 20mg/kg,possibly improve prognosis.It is possible that it also reduces the risk of colonic cancer in these patients118(Section 9.5).T acrolimus has yielded a rapid decrease in liver enzymes, but no histological improvement.309ERCP may be used to treat dominant strictures by dilatation and/or stenting.Advanced liver disease may necessitate transplantation,but recurrence of PSC in the transplanted liver occurs in approximately20%of patients.308,310Specialist advice is appropriate when managing a patient with PSC and IBD.Because of the higher risk of colorectal cancer,it is generally considered appropriate to perform annual screening colonoscopy from the time of diagnosis.
13.6.Metabolic bone disease 13.6.1.Diagnosis and fracture risk
Osteoporosis and osteopenia are common in patients with IBD(20–50%),but the actual number of fractures in IBD is only slightly increased to the general population.311,312In a study using the general practice research database,the relative risk of hip fracture was1.62(95%CI1.24–2.11)for all IBD, 1.49(1.04–2.15)for ulcerative colitis and 2.08 (1.36–3.18)for Crohn's disease.312Contributing factors include age,steroid treatment,smoking,low physical activ-ity(including that from hospitalisation),inflammatory cytokines,and probably also resection with pouch formation.
Diagnosis is conventionally based on bone densitometry (DEXA scanning),osteoporosis being defined as a T score of less than?2.5.Ultrasound has been suggested as method of screening,but is not yet reliable.The presence of osteo-porosis increases the risk of fracture of long bones and of the spine,although probably a great deal less in young patients than was once thought.It is conventional to use a radiological diagnosis of osteoporosis as an indication for specific therapy.
Osteopenia(T score less than?1.0)is thought by some to be an important risk factor for fracture in its own right,but this is increasingly questioned.313It is,however,probable that it is a marker of increased risk of later osteoporosis even if the risk is not absolute.Therapeutic intervention is probably not justified on present knowledge,but continued surveillance for bone loss is appropriate.It is important to put risks into perspective when discussing with patients.
The risks of osteoporosis(and the potential risks from osteopenia)should be explained.The recommended dietary calcium intake should be1000–1500mg/day,which often means supplementation even in patients not taking corticosteroids.It should be noted that recommendations for the treatment of osteoporosisapplyonlytoadultsovertheageof25years,andthat evidence for treating oestopenia is circumstantial.The diagnosis of osteoporosis in children and long-term consequences of treatment with bisphosphonates are unknown.
13.6.2.Management
The risks of osteoporosis(and the potential risks from osteopenia)should be explained.The treatment of osteoporosis is based on studies that are not specific to IBD.314Weight-bearing,isometric exercise,stopping smoking,avoiding alcohol excess and maintaining adequate dietary calcium(N1g/day) are beneficial,but such advice is often overlooked.Hormone replacement treatment is no longer generally advised in post-menopausal women with osteoporosis,because studies have demonstrated a slightly increased risk of breast cancer and of
ECCO Statement13E
PSC appears to respond to ursodeoxycholic acid,which improves abnormal liver function tests[EL1b,RG B]and may,at20mg/kg,improve liver histology and prognosis [EL2a,RG C].It is possible that ursodeoxycholic acid also reduces the risk of colonic cancer in PSC patients[EL2a, RG C].ERCP may be used to treat dominant strictures by dilatation and/or stenting[EL4,RG C].Advanced liver disease may necessitate transplantation[EL2a,RG B]
ECCO Statement13E
Diagnosis of osteoporosis in adults is best made from a T score of less than?2.5on radiographic bone densitometry [EL1a,RG A],all other diagnostic methods having current limitations[EL2b,RG B].The presence of osteoporosis identifies patients at above average risk for fracture and who should receive treatment[EL2b,RG B]
ECCO Statement13F
Osteopenia may be a prognostic marker for future osteoporosis,but presents little direct risk[EL2b,RG C]. However if the T score is less than?1.5,treatment with calcium,vitamin D and a bisphosphonate should be considered[EL4,RG C].Pre-existing history of fracture is of substantial adverse prognostic significance and such patients should be treated for osteoporosis even if the T score is normal[EL4,RG C]ECCO Statement13G
Weight-bearing exercise[EL2b,RG B],stopping smoking [EL3b,RG C],avoiding alcohol excess[EL4,RG D],and maintaining adequate dietary calcium(N1g/day)[EL2b, RG B]are beneficial.In post-menopausal women with osteoporosis,regular use of bisphosphonates,calcitonin and its derivatives,and raloxifene reduce or prevent further bone loss[EL2b,RG C].Data in males with osteoporosis are less secure but bisphosphonates are probably of value[EL3b,RG C].Newer data also support the use of strontium salts[EL2a,RG B]
81
ECCO Consensus on UC:Special situations
cardiovascular events.315Regular use of bisphosphonates, calcitonin and its derivatives,and raloxifene(a selective oestrogen receptor modulator)may reduce or prevent further bone loss.Data in males with osteoporosis are few,but bisphosphonates are probably of value and an important practice point is that testosterone should be measured.Those with low testosterone may benefit from supplementation. Routine administration of vitamin D is not warranted.Patients on corticosteroids for short periods do not merit routine use of bone protection with bisphosphonates,assuming a normal calcium intake and all other risk factors being equal.315
13.7.Other systems
Other systems are found to be abnormal in UC more often than would be expected by chance and these associations may therefore be considered to be extra-intestinal manifestations. Examples include respiratory complaints(especially asthma), cardiac and pericarditic conditions,nephrological disease(both nephritis and amyloidosis),neurological conditions(especially multiple sclerosis)and urinary tract stones.274,302Their diag-nosis and management is not considered in further detail, because the routes to diagnosis are no different from those in general medical practice and because their management is fundamentally independent of that of the colitis.The issue of interstitial nephritis associated with5-ASA therapy316is considered in the section on colitis therapy(Section5.4.1, preceding paper same issue.)289Anaemia and ulcerative colitis deserves greater proactive management by gastroenterologists than it generally receives,because it is associated with substantial impairment of the quality of life.Reasons for not treating anaemia effectively often dwell on intolerance to oral iron therapy and difficulty in delivering or risks associated with parenteral iron,but this is no longer tenable and expectations of both patients and physicians should be raised.276
https://www.doczj.com/doc/2918308974.html,anisation of services for EIMs associated with ulcerative colitis
The more common extra-intestinal manifestations affecting joints and skin may be profitably managed by a close working relationship between the gastroenterologist and rheumatolo-gist or dermatologist respectively.It is easier to ensure that inter-disciplinary knowledge is used to best advantage for the patient by the existence of periodic clinics for rheumatology, dermatology and other specialties held in parallel,and in some cases by joint consultations.Awareness of atypical presenta-tions and of new exploratory therapies is therefore enhanced.
https://www.doczj.com/doc/2918308974.html,plementary and alternative medicines 14.1.Introduction
The use of complementary and alternative medicine among UC patients is common,and physicians are frequently confronted with questions about their use.Reasons for using such therapies are worries about conventional treat-ment,including perceived lack of effectiveness and fear about side-effects,in addition to subjective benefit from complementary or alternative therapies.However,evidence for the efficacy and safety of CAMs is often lacking,because there are very few controlled trials that assessed these therapies in UC and even these are underpowered for what they aim to establish.Consequently,because of the lack of power and other methodological problems in the reported studies,it is difficult for physicians to inform their patients adequately.Nevertheless,complementary and alternative treatments warrant further evaluation from public interest alone.Although complementary medicine appears to be generally safe and non-toxic,this cannot be assumed and potential side-effects should be considered for each sub-stance,particularly when microorganisms are used in conjunction with conventional immunomodulators.
14.2.Definitions
Complementary and alternative medicines represent a diverse group of medical and non-medical products and therapeutic approaches that are not presently considered part of conventional therapy.Products that have established efficacy in UC,such as specific probiotics(E.coli Nissle1917,for example),are not considered complementary or alternative medicines and are described elsewhere(Section6.2.4,preced-ing paper same issue).On the other,hand remedies from different,often non-Western,cultures are included in this group of therapies,as well as those that are unproven.An important distinction between alternative and complementary medicine is its relation to conventional therapy.Alternative medicine explicitly excludes concomitant conventional therapy,but complementary medicine allows the complementary approach in conjunction with conventional therapy.It is helpful if patients are aware of this distinction,not least because alternative medicine for a serious,potentially life-threatening condition such as acute severe colitis would be dangerous.
https://www.doczj.com/doc/2918308974.html,e of CAM
Since alternative medicine by definition does not allow conventional therapy,even when necessary,this type of UC therapy can lead to severe complications from the underlying condition.In contrast,complementary medicine is usually safe and is possible if patients want to use it.From a practical point of view,if patients discuss complementary therapy in the context of conventional medical consultation,it is usually an indicator
ECCO Statement13G
Organisation of services to facilitate expert management of extra-intestinal manifestation may include combined or parallel specialist clinics conducted with clinicians from the other relevant disciplines[EL4,RG D]ECCO Statement13A
Alternative medicines for ulcerative colitis(UC)exclude the possibility of using conventional therapy at the same time[EL5,RG D].Complementary medicines for UC allow concomitant conventional therapy[EL5,RG D]
ECCO Statement13B
Alternative medicine for UC as defined above is strongly discouraged[EL5,RG D]
82L.Biancone et al.
2020溃疡性结肠炎（UC）科普知识（完整版） 导语： 溃疡性结肠炎（Ulcerative Colitis，UC），常简称溃结，主要临床表现为腹泻、黏液脓血便、腹痛和里急后重等。病情轻重不等，多反复发作或长期迁延呈慢性经过。是以结直肠黏膜连续性、弥漫性炎症改变为特点的慢性非特异性肠道炎性疾病。 虽然其病因尚不十分明确，但普遍认为发病与免疫、遗传、环境及肠道感染等多因素有关。我国的发病率＜5/10?。 因UC治愈难度大，迁延不愈，发病率呈逐年升高趋势，且有癌变倾向，已被WHO列为现代难治性疾病，被称为“绿色癌症”。 1. 什么是溃疡性结肠炎？ 溃疡性结肠炎（Ulcerative Colitis，UC），常简称溃结，是一种病因尚不明确的直肠以及结肠慢性非特异性炎症性疾病。病变主要限于大肠黏膜与粘膜下层。临床主要表现为腹泻、粘液脓血便、腹痛，多成反复发作，迁延不愈。 2. 溃疡性结肠炎病因有哪些？ 溃疡性结肠炎的病因尚不明确，目前认为可能与环境因素、遗传因素、感染因素、精神因素和自身免疫因素有关系。
3. 什么样的人容易的溃疡性结肠炎？ 直系亲属患有溃疡性结肠炎的人得溃结的可能性会增加，除此之外，经常处于紧张焦虑或者抑郁状态以及肠道感染等都有可能增加溃结的风险。 4. 溃疡性结肠炎能预防么？ 由于溃结的发病原因和发病机制尚未明确，所以并没有特效的方法可以预防溃结的发生。但是对于进入缓解期的溃结患者，可以通过有效的方法预防溃结的复发。避免焦虑、情绪低落等精神刺激，避免辛辣、生冷食物对肠道的刺激，减少肠道感染机会，加强身体锻炼提高自身的免疫力等均可以有效的预防溃结的复发。 5. 溃疡性结肠炎有什么临床表现？ 粘液脓血便是溃疡性结肠炎活动期的重要表现，症状轻的患者每日可排便2-4 次，重者可以达每日10 次以上。除此之外的症状都不够典型，可有腹痛、腹胀或者出现食欲减退、恶心呕吐，严重的患者还会出现口腔反复溃疡、外周关节炎等肠外表现以及衰弱、贫血、消瘦等全身表现。 6. 出现哪些症状可以怀疑得了溃疡性结肠炎？
溃疡性结肠炎的中医认识及治疗(一) 作者：安贺军于玫王新月林芳冰沉静 【关键词】溃疡性结肠炎；痢疾；病因病机 溃疡性结肠炎（UlcerativeColitis，UC）又称慢性非特异性溃疡性结肠炎，是一种以慢性炎症和溃疡形成为主要病理特点的消化道疾病。 1病名归属 中医学中无溃疡性结肠炎病名，历代医籍中有“休息痢”、“久痢”、“滞下”、“肠澼”等相关记载。早在《内经》中肠澼是以便血、腹痛、下利白冻脓血、并发痔疾为主症，这与溃疡性结肠炎症状相似，但肠澼的病名后世未被延续下来使用。汉代张仲景《伤寒杂病论》中泻痢并论，统称为“下利”，如“下利已差，至其年、月、日、时复发者，以病不尽故也，当下之”。《古今医统大全·滞下门》谓：“休息痢者，乃乍作乍止，或因邪气未曾涤尽，遽止而复作者是也。有因初愈不禁饮食，恣用厚味，及妄作劳而复作者是也。凡犯此者，皆名休息”。在中医古籍中相关论述较多，根据其对病名的解释，我们很容易将它们和溃疡性结肠炎的部分症状联系起来。由上可见，时发时止的休息痢与溃疡性结肠炎中最常见的慢性复发型的发病特点是相似的，而慢性持续型溃疡性结肠炎又与病程较长之久痢症情类似，只是这一类型在临床上较少见。 2病因病机 2.1病因认识 （1）感受外邪。外感六淫之邪引发痢疾，如得不到正确治疗则会迁延为休息痢。（2）饮食不节。饮食是摄取营养、维持人体生命活动所不可缺少的物质，因食物靠脾胃消化，故饮食不节主要是损伤脾胃，导致脾胃升降失常，水谷不能正常运化而为湿、滞，因此，饮食不节是痢疾发病的重要因素。（3）七情内伤。思虑劳神过度，伤神损脾而致脾运化无力，水谷停滞肠胃之中而致病。 2.2发病机理 （1）脾肾亏虚。《诸病源候论》中指出“由脾胃大肠虚弱，风邪乘之，则泄痢。虚损不复，遂连滞涉引岁月，则为久痢也”。脾传肾为贼邪难疗，先痢而后泻者，肾传脾为微邪易医，是知在脾者病浅，在肾者病深，肾为胃关，开窍于二阴，未有久痢而肾不损者。故治痢不知补肾，非其治也”。（2）积滞内停。积滞是痢疾主要致病因素，邪滞于肠，以致气血壅滞，大肠通降不利，肠道传化失司，脂膜血络受伤，腐败化为脓血而成痢。六腑以降为顺，休息痢是在脾肾亏虚基础上，治疗之初未用推下之法，而不能使邪气尽去，积滞壅于肠中，使肠道正常通降功能不能恢复，在诱发因素作用下，痢下时作时止积年累月缠绵不愈。
溃疡性结肠炎（UC） 溃疡性结肠炎（ulcerative colitis，UC）是一种病因尚不十分清楚的直肠和结肠慢性非特异性炎症性疾病。病变主要限于大肠黏膜与黏膜下层。临床表现为腹泻、黏液脓血便、腹痛。病情轻重不等，多呈反复发作的慢性病程。本病可发生在任何年龄，多见于20～40岁，亦可见于儿童或老年。男女发病率无明显差别。本病在我国较欧美少见，且病情一般较轻，但近年患病率有明显增加，重症也常有报道。 【病理】 病变位于大肠，呈连续性弥漫性分布。范围多自肛端直肠开始，逆行向近段发展，甚至累及全结肠及末段回肠。 活动期黏膜呈弥漫性炎症反应。固有膜内弥漫性淋巴细胞、浆细胞、单核细胞等细胞浸润是UC的基本病变，活动期并有大量中性粒细胞和嗜酸性粒细胞浸润。大量中性粒细胞浸润发生在固有膜、隐窝上皮（隐窝炎）、隐窝内（隐窝脓肿）及表面上皮。当隐窝脓肿融合溃破，黏膜出现广泛的小溃疡，并可逐渐融合成大片溃疡。肉眼见黏膜弥漫性充血、水肿，表面呈细颗粒状，脆性增加、出血，糜烂及溃疡。由于结肠病变一般限于黏膜与黏膜下层，很少深入肌层，所以并发结肠穿孔、瘘管或周围脓肿少见。少数暴发型或重症患者病变涉及结肠全层，可发生中毒性巨结肠，肠壁重度充血、肠腔膨大、肠壁变薄，溃疡累及肌层至浆膜层，常并发急性穿孔。 结肠炎症在反复发作的慢性过程中，黏膜不断破坏和修复，致正常结构破坏。显微镜下见隐窝结构紊乱，表现为腺体变形、排列紊乱、数目减少等萎缩改变，伴杯状细胞减少和潘氏细胞化生。可形成炎性息肉。由于溃疡愈合、瘢痕形成、黏膜肌层及肌层肥厚，使结肠变形缩短、结肠袋消失，甚至肠腔缩窄。少数患者发生结肠癌变。 【临床表现】 起病多数缓慢，少数急性起病，偶见急性暴发起病。病程呈慢性经过，多表现为发作期与缓解期交替，少数症状持续并逐渐加重。部分患者在发作间歇期可因饮食失调、劳累、精神刺激、感染等诱因诱发或加重症状。临床表现与病变范围、病型及病期等有关。 （一）消化系统表现 1．腹泻和黏液脓血便见于绝大多数患者。腹泻主要与炎症导致大肠黏膜对水钠吸收障碍以及结肠运动功能失常有关，粪便中的黏液脓血则为炎症渗出、黏膜糜烂及溃疡所致。黏液脓血便是本病活动期的重要表现。大便次数及便血的程度反映病情轻重，轻者每日排便2～4次，便血轻或无；重者每日可达10次以上，脓血显见，甚至大量便血。粪质亦与病情轻重有关，多数为糊状，重可至稀水样。病变限于直肠或累及乙状结肠患者，除可有便频、便血外，偶尔反有便秘，这是病变引起直肠排空功能障碍所致。 2．腹痛轻型患者可无腹痛或仅有腹部不适。一般诉有轻度至中度腹痛，多为左下腹或下腹的阵痛，亦可涉及全腹。有疼痛便意便后缓解的规律，常有里急后重。若并发中毒性巨结肠或炎症波及腹膜，有持续性剧烈腹痛。 3．其他症状可有腹胀，严重病例有食欲不振、恶心、呕吐。 4．体征轻、中型患者仅有左下腹轻压痛，有时可触及痉挛的降结肠或乙状结肠。重型和暴发型患者常有明显压痛和鼓肠。若有腹肌紧张、反跳痛、肠鸣音减弱应注意中毒性巨结肠、肠穿孔等并发症。 （二）全身表现 一般出现在中、重型患者。中、重型患者活动期常有低度至中度发热，高热多提示合并症或见于急性暴发型。重症或病情持续活动可出现衰弱、消瘦、贫血、低蛋白血症、水与
溃疡性结肠炎相关实验研究进展 【关键词】溃疡性结肠炎相关实验研究进展述评 慢性溃疡性结肠炎(UC)是以腹泻、黏液脓血便、腹痛和里急后重等为主要症状,以结肠黏膜慢性炎症和溃疡形成为病理特点的一种消化道疾病。随着人们生活水平的不断提高和饮食结构、习惯的改变,其发病率呈现逐年上升趋势。本病治愈难度大,且愈后易再发,与结肠癌的发病存在一定关系,被世界卫生组织列为现代难治病之一。近年对于本病的中西医实验研究取得了较大的进展。现针对国内近7年的实验研究大体进展综述如下。 1 动物模型的建立 理想的慢性溃疡性结肠炎实验动物模型应具备如下特点:(1)肠道炎症的发生,以及病程、病理生理学改变与UC相同或相似;(2)实验动物应具有明确的遗传背景;(3)以已知抗原能诱导免疫反应;(4)用传统UC治疗药物治疗有效;(5)实验动物在没有遗传或化学药物干预情况下,能自发形成肠道炎症。实际上很少有如此理想的动物模型,目前所制作和使用的肠道炎症实验动物模型一般所选用的动物为大鼠(SD或Wistar大白鼠)、小鼠、豚鼠;实验模型分为4类,即化学药物诱导型动物模型3类和依据中医证型特点开发的实验研究模型1类。 化学药物诱导型动物模型3类。(1)葡聚糖硫酸钠(dextran sulfate sodium,DSS):DSS是一种由蔗糖合成的硫酸多醣体,具有与肝素相同的抗止血和抗凝血作用,其诱发的病理改变更接近人类UC特点,通过不同时间段给予BALB/c 小鼠5%DSS溶液和蒸馏水,造建急性、慢性、急慢性交替期UC模型,已取得较理想的病理结果。(2)过氧化亚硝酸钠法:过氧化亚硝酸钠诱导大鼠溃疡性结肠炎建立Wistar UC实验模型,结果显示,应用过氧化亚硝酸钠造模具有制作简便、重复性好、制作成本低廉的优点,其形态学改变能反映UC发病的部分本质机制。(3)三硝基苯磺酸(TNBS)/乙醇模型:TNBS与大分子组织蛋白合成一种抗原物质致T 细胞致敏,溶解与半抗原结合的自身细胞,导致炎症的发生。朱峰等用TNBS 30mg/50% 乙醇制作实验性IBD的动物模型,结果显示造模成功,该模型的优势在于重现性好、造模时间短、成功率高,但存在炎症发生机制为单一T细胞介导,炎症持续时间短的特点。对该研究模型宫建伟进行改进,采用混合方法造模,即于大鼠足跖、腹股沟注射两次抗原乳化剂(每次含抗原8mg)致全身致敏、发生免疫异常的前提下,再用TNBS与无水乙醇等体积配比的混合液按100mg/kg剂量局部灌肠,使肠道发生炎症变化。此方法既达到全身免疫异常与局部炎症病变共存,
多年溃疡性结肠炎终于治好了 5年前，刘大妈从工厂里退休，本来想含饴弄孙，好好享享清福，谁知道却一直被溃疡性结肠炎纠缠，痛苦不已。 说起自己的结肠炎，刘大妈说，自己年轻的时候因为饮食不卫生，得过几次急性肠胃炎，但是因为那时候又要忙工厂里的工作，还要照顾家里的儿女，所以治疗都不彻底，每次就是吃点药症状消失了就不管了，长期下来，便形成了现在的慢性结肠炎。年轻时候抵抗力好点，还不是很严重，老了以后、特别是退休以后，活动量小了，抵抗力差了，结肠炎就严重起来了，真的让她寝食难安，几乎天天腹痛、拉稀，脓血便，有时还便秘，人也瘦得没人形，特别是半夜拉肚子，连觉都睡不安稳。别说带孙子了，自己都要老伴天天照顾，身体也是越来越差。为此，刘大妈也吃了各种药，但都是刚开始有效，到后来完全不管用。实在没办法，只得定期到医院灌肠，把多年积蓄都快用光了。有时候感到异常烦恼，刘大妈甚至都不想治了，心想随它去吧。 好在儿女们没有放弃希望，到处为刘大妈打听好的医院和药物，几经周折，女儿帮她打听到大同消化病医院，得知这里是专门治疗肠胃疾病的地方，就赶紧带着刘大妈来到位于四中岗往北200米路东（翰林别院右侧）的大同消化病医院检查治疗。 大同消化病医院首席胃肠专家赵研教授接诊时了解到刘大妈结肠炎已经多年，且年纪较大，不适合采用传统的插管肠镜检查，便为其采用了先进的智能胶囊消化道内镜系统检查，不需插管，安全无痛，很快赵教授就确诊了刘大妈的病情，她的结肠炎已经非常严重了。 据赵教授介绍，结肠炎是一种慢性疾病，并且非常顽固，常反复发作并逐步加重，少数急性爆发。结肠炎不是普通炎症，其病十分复杂，同时结肠炎也是一种不易根治的疾病，究其原因，是因为传统治疗方法不当，没有全面详细检查准确诊断，盲目用药，盲目治疗，易引起误诊、误治，目前治疗结肠炎的药物不少，但主要是以抑菌消炎为目的，只能治标，不易治本。结肠炎如果不及时治愈，可能导致肠穿孔、结肠癌、便血、中毒性肠扩张等严重后果。 了解刘大妈的情况后，赵教授告诉她，现在的情况不能轻易使用西药，也不能单纯靠中药来治疗，应该采用中西结合的方式，才能帮助她快速的好起来，并且不复发。抱着将信将疑的态度，刘大妈接受了该院特色疗法——“三维胃粘膜修复疗法”进行治疗。赵教授用西药帮她消除炎症，再用中药调理养护，两个疗程以后，刘大妈就感觉到效果非常好，一天只拉2、3次，而且腹痛、腹胀的感觉减轻了不少，晚上也能安稳的睡一个好觉。再巩固治疗了一个疗程，脸上红润了很多，气色也非常好，身体的的精力恢复得不错，如今是每天一次大便。刘大妈说，这几年来从来没有这样舒适过，没想到自己十多年的结肠炎真的治好了，现在她终于能好好地享享清福了。 究竟什么是“三维胃粘膜修复疗法”呢？据了解，三维胃粘膜修复疗法是大同消化病医院赵研教授结合多年临床经验独创的特有疗法，应用中西医结合全新理念，促进人体胃肠血液循环，维护胃肠道菌株平衡，改善胃动力，修复胃粘膜再生功能，提高机体免疫力，彻底清除胃肠疾病，达到“治胃、护胃、养胃”三维一体的治疗目的。三维胃粘膜修复疗法解决了传统西医治疗以抑菌消炎为目的，只能治标，不易治本的弊端，将中西医各自优势结合，在快速治病的同时，消除结肠炎复发的隐患，达到多重修复肠道黏膜，恢复肠道功能的效果，具有起效快、安全无痛、快速全面、无毒副作用、不受季节影响等特点，临床效果极佳。 笔者提醒，如有像刘大妈这样被结肠炎等胃肠疾病困扰的患者可以拨打健康热线5354555和赵教授直接交流了解病情。
国内外溃疡性结肠炎研究现状 溃疡性结肠炎(UC)1859年由Wilks首先描述，1920年被医学界公认，我国于1956年首次报道．过去认为该病欧美多见，亚非少见，但近几十年研究表明，UC在我圆也是一种较常见的消化道疾病，并且正在逐渐成为消化病学研究的一个新热点，尽管我国目前还缺乏UC的流行病学资料，但据《世界华人消化杂志》2000年3月[1]对1978年以来几次重要的全国性消化会议的资料统计，该病发病率和患病率在我国有明显增加趋势：1978年杭州第一次全国消化系统疾病学术会议报告的病例为337例，1999年西安第六次全国消化系统疾病学术会议报告病例为例达1627例；1986年成都全国慢性腹泻研讨会报告的病例为581 例，1996年江西全国肠病研讨会报告的病例为1412例；特别是1993年太原全国慢性非感染性肠道疾病学术研讨会上报告的病例达3065例，远远超过UC高发区全欧洲同期(1991／1993)新诊断的惠者数1397例．尽管这些资料统计还不够全面，有些未必符合诊断标准，但仅以济南军区总医院住院资料分析，1980／1989为57例，1990／1999为213例，这除与UC诊治水平提高有一定关系外，说明其患病率可能明显升高，这是促使UC逐渐成为消化病学研究热点的客观原因， 我国在UC流行病学方面的研究几乎是空白，缺乏流行病学的资料，尽管国内近年来报道的病例数明显增多，但大多数为住院病例和临床分析，对该病在我国确切的发病率，患病率，高峰年龄，种族地理分布，发病规律，环境及致病危险因素等知之甚少，进行系统的流行病学研究已经成为一个迫切需要解决的问题． 氨基水杨酸类药物和皮质类固醇类药物目前仍然是治疗溃疡性结肠炎的主要药物，具有起效快，近期临床缓解率高等优点，但停药后易复发，长期用药副反应增多，部分顽固性患者疗效并不理想． 目前临床普遍认为药物治疗是IBD的首选疗法，外科手术则主要用于药物治疗无效或需外科处置的并发症治疗。治疗方法主要有西医药疗法、中医药疗法和中西医结合疗法3种。给药途径有口服、保留灌肠和口服加保留灌肠。 西医的药物治疗仍以抗炎及调节免疫反应为主，治疗药物主要有糖皮质激素和以柳氮磺胺吡啶(Sulfasalazine，SASP，SAZ)为代表的5-氨基水杨酸(5．aminosanicylic acid，5-ASA)类药物。 氨基水杨酸类药物中的柳氮磺胺吡啶(SASP)第一个应用于临床，早在40年代就开始应用，目前仍然为治疗炎症肠病的首选药物。SASP是磺胺吡啶与5-氨基水杨酸(5-ASA)以偶氮键相结合的产物，口服后大部分在结肠内被细菌的偶氮还原酶裂解为磺胺吡啶和5-ASA，5-ASA为SASP的主要有效成份，主要作用机制是抑制肠黏膜释放炎性介质，减少局部炎症细胞浸润，抑制炎症细胞趋化因子的合成和释放而达到治疗作用,其滞留在结肠内，与肠上皮接触，发挥其药效作用，对于轻～中度UC，无论诱导缓解或维持缓解，氨基水杨酸类药物效果肯定、安全、耐受性良好，有资料分析表明对远端UC，局部给予氨基水杨酸(5-ASA)是最佳方法。SASP的副作用是由磺胺吡啶（SP）引起，SASP裂解后剩余的SP会使血中乙酰化物浓度高，且尿中SP及乙酰化物的溶解度均比较低，易在肾脏析出结晶损害肾脏。此外还会引起头痛、胃肠道症状、荨麻疹、呼吸困难、关节痛等。
结肠炎治疗一绝 1.半枝莲治疗慢性结肠炎 取半枝莲15g泡水经常服用。一般用上2个月，就能痊愈。我在临床上治愈了很多这样的病人，希望在此给大家共同学习。互相交流。 2.喝酸奶治结肠炎 得了结肠炎反复发作，让人很烦恼。一天一瓶酸奶，就可以治疗结肠炎。 涧西区王女士致电本刊说，八年前，她的爱人由于工作原因，经常在外面吃饭。久而久之，患上了结肠炎，一天能上四五次厕所，人明显消瘦。他到多家医院治疗过，抗生素、消炎药等用了个遍。但是，结肠炎总是不能治愈，反复发作令他很痛苦。 后来，一名医生推荐王女士的爱人喝酸奶，说对治疗结肠炎有一定作用。王女士的爱人坚持每天喝一瓶酸奶，过了一段时间，他的结肠炎竟然不治而愈。 此后，每天喝一瓶酸奶，成了王女士爱人的生活习惯。王女士后来查询资料了解到，结肠炎患者的肠
道菌群会发生变化，而酸奶中含有大量的乳酸菌，可以维持肠道正常菌群平衡。 3.黑矾加鸡蛋治疗结肠炎 对于由结肠炎引起的长期慢性腹泻，可吃黑矾加鸡蛋进行治疗。此偏方由瀍河回族区的金山和虎齿提供。 具体操作方法如下： 1. 将鸡蛋打开一个小口，把蛋清倒出来一点儿。 2. 把约6克黑矾粉倒进鸡蛋里，然后用筷子轻轻搅匀（黑矾较苦，搅匀可以减少苦味）。 3. 用面糊把鸡蛋包起来，面糊适当厚一些。 4. 将鸡蛋放进烤箱，当面糊烤至发黄微焦时取出，把面糊、鸡蛋全部吃掉；也可以蒸着吃，像蒸馒头一样，蒸15分钟即可。 金山介绍，连续吃3天，就会有效果，不成形的大便就会成形了。（因个人体质有差异，效果会有所不同）
4. 结肠炎治疗一绝 结肠炎治疗一绝这是我在上卫校时，我的恩师告诉我的治疗慢性结肠炎的偏方，可谓一绝！ 现在拿出来供大家分享，因为我也是受益者，所以有好东西也应该献出来，大家共同学习。 其方为：栗壳10g 金银花10g 放于新瓦上小火倍干，共同研面，温水一次冲服。一般两次即可，效果神速，可治愈。 注意：是(板)栗壳不是罂粟壳. 5.溃疡性结肠炎临床验方 我献出一临床验方。慢性溃疡性结肠炎，主要症状为腹泻者，可以使用如下方法：诺氟沙星胶囊两粒、复方地芬诺酯片（又名复方苯乙哌啶片）一片、次苍片（次炭酸铋片或次硝酸铋片）两片，维生素B6片两片，地塞米松片一片，维生素K3片两片，上述各药同时服用，一日三次，饭后服。临床效果真实可靠。
溃疡性结肠炎临床表现研究进展分析 摘要】目的：观察溃疡性结肠炎临床表现，结合现有技术，分别用中医辩证施 治和西医治疗对溃疡性结肠炎临床研究进展进行分析。对溃疡性结肠炎临床表现 和各种治疗方法进行评价。方法：选取我院自2006年1月~2008年12月收治的 病理证实的的63例小肠淋巴瘤和63例小肠腺癌病灶。分析其治疗效果、临床表 现情况等。结果：近3年来患者溃疡性结肠炎住院患者数量和内镜检测出的数量 呈明显增加趋势。溃疡性结肠炎患病率大约为0.01%.住院的溃疡性结肠炎患者中 以轻度和中毒患者为主分别占到35%到42%。临床表现类型以慢性复发和初发型 为主。暴发的患者比例仅仅占到2.4%。其主要临床表现为腹泻、腹痛、血便等等 遇到多数肠道疾病的病理表现较为相似。结论：溃疡性结肠炎是容易复发的，以 轻中度为主的，肠道外病变较少见的多发性肠道疾病。国内以柳氮磺胺吡啶及激 素治疗为主，手术死亡率及癌变率较低。 【关键词】溃疡性结肠炎；临床表现；进展；分析 【中图分类号】R156.3【文献标识码】B【文章编号】1005-0515(2011)12-0363-02据有关资料显示，溃疡性结肠炎在国外较为常见，患病率也较高，一般在 0.8%左右，而在我国溃疡性结肠炎比较少见，然而，近年来溃疡性结肠炎的患病 率呈现逐年增加的趋势，根据近15年的临床资料显示，溃疡性结肠炎已经成为 肠道主要疾病。所以，在治疗溃疡性结肠炎方面我们该加强和提高诊断水平、治 疗水平和技术，为患者解除痛苦，提高患者生活质量。溃疡性结肠炎一般临床表 现为腹痛，腹泻，血便等症状。从文献资料和临床资料来看溃疡性结肠炎容易复发，西医治疗见效快却不治本，中医治疗需要长期观察，不能立竿见影。这对医 生的治疗提出了较高的要求。本文就患者临床表现为主要参考，溃疡性结肠炎临 床表现进行分析。 1资料与方法 1.1一般资料：选取我院自2006年1月~2008年12月收治的病理证实的溃 疡性结肠炎患者。其中，93例男性，33例女性，年龄19-78岁，平均55.4岁， 48例。男性51例，女性12例。年龄18-70，平均年龄44岁63例小肠腺癌，病 变部位在十二指肠38例，空场1例，回肠1例。男42例，女21例。年龄18-70岁，平均年龄42岁。采用西门子公司sensation16层螺旋CT机。腹部器官多样，检查前后需做必要的准备以利于检查顺利进行。 1.2影像检查：使用西么子螺旋CT，挑选受试者，首先对容积扫描的双期 增强原始数据进行回顾性重建。对其进行6h的空腹准备，或者饮用受检用药（5%的甘露醇1000ml）以充填胃肠道减少气体伪影干扰，肠道准备充分，充盈度基本满意，以回肠充盈最佳，病变周围肠段充盈良好，符合诊断要求。静脉高压注射70-100ml，扫描采纳数130-150mas，螺旋距离为1.5，速度0.5，备好抢救药品和 氧气，与患者积极沟通，病人如果有心里障碍，可以全麻，通知其家属为其解释 检查过程中的注意事项等等。准备事项完毕，开始进行扫描。扫描时应注意观察 扫描对象的体征反映，及时处理。扫描结束后，将数据传至工作站后采用MPR进行后处理。 1.3钡剂灌肠： 126例溃疡性结肠炎患者中14例做了钡剂灌肠检查,主要是 表现为黏膜紊乱的溃疡性结肠炎的患者为9例,糜烂、溃疡3例、肠管短缩1例，肠腔狭窄无，息肉1例。 1,4 内镜表现：境内表现分析，126例溃 疡性结肠炎患者进行肠镜检查，其中112例溃疡性结肠炎患者镜下病变范围及主
1.患者女性，41岁，诊断为“溃疡性结肠炎”收住入院，每天腹泻5～6次，有少量脓血便，对此类患者饮食护理应注意 A.给予易消化、富含纤维素饮食 B.低蛋白饮食 C.进食无渣流质或半流质饮食 D.多进食新鲜水果 E.多吃蔬菜 【答案】:C 【解析】:考察溃疡性结肠炎的饮食护理。应给予高热量、富营养而少纤维、易消化、软食物，禁食生、冷食物及含纤维素多的蔬菜水果，忌食牛乳和乳制品。急性发作期病人应进食无渣流质或半流质饮食，病情严重者应禁食，并给以胃肠外营养，使肠道得以休息，利于减轻炎症，控制其症状。 2.患者女性，36岁，间断发作下腹部疼痛伴腹泻2年，每天排便3～4次，为脓血便，常有里急后重，排便后疼痛缓解。该患者最可能的诊断是 A.慢性腹泻 B.阿米巴脓肿 C.肠结核 D.肠易激综合征 E.溃疡性结肠炎 【答案】:E 【解析】:考察溃疡性结肠炎的临床表现。消化系统表现：腹泻，轻度、中度腹痛，便后疼痛可减轻或缓解；全身表现：发热重者可有高热、贫血、消瘦、水与电解质平衡失调、低蛋白血症及营养不良。 3.溃疡性结肠炎的发病目前多数认为与下列哪一种因素关系最大 A.遗传 B.感染 C.过敏 D.精神紧张 E.免疫异常
【答案】:E 【解析】:考察溃疡性结肠炎的病因。病因尚未完全清楚，多数研究认为与免疫因素关系最大。研究认为溃疡性结肠炎病人的肠黏膜存在异常的上皮细胞，分泌异常黏液糖蛋白，正常防御功能被削弱，影响肠黏膜屏障的完整性，使一般不易通过正常肠黏膜及对人体无害菌群、食物等抗原，可以进入肠黏膜，激发一系列免疫反应与炎性变化。 4.溃疡性结肠炎的首选治疗药物是 A.地塞米松 B.柳氮磺胺吡啶 C.前列腺素 D.甲硝唑 E.阿莫西林 【答案】:B 【解析】:考察溃疡性结肠炎的治疗原则。氨基水杨酸制剂柳氮磺胺吡啶为溃疡性结肠炎患者的首选药物，适用于轻、中型及重型经治疗已有缓解者，发作时每天4～6g，分4次口服，病情缓解后改为每天2g维持，疗程1～2年。 5.男性，38岁，左下腹间断发作性腹痛伴腹泻3年，便后疼痛缓解，以“溃疡性结肠炎”收入院。护士对该患者的健康教育不包括 A.指导患者和家属注意饮食和休息 B.了解化验指标 C.按时复查 D.掌握用药方法及注意不良反应 E.学会观察各种并发症 【答案】:B 【解析】:考察溃疡性结肠炎的健康教育。溃疡性结肠炎患者的健康教育包括：(1)心理护理，调节良好的心态。(2)药物用法和观察。(3)并发症的观察。(4)注意饮食和休息，按时复查。了解化验指标是医护人员的责任。 6.患者男性，43岁，腹痛腹泻1年，诊断为溃疡性结肠炎，服用柳氮磺胺吡啶治疗。护士告知患者服药注意事项，下列不属于该药常见的不良反应的是 A.恶心、呕吐 B.食欲不振 C.心律失常
2016蚌埠市级继续教育《溃疡性结肠炎治疗新进展》考试题 单位：姓名：得分： 1．溃疡性结肠炎内镜下的典型表现是（） A.盲肠可见多发浅溃疡 B.回肠末端可见纵行溃疡并狭窄 C.乙状结肠可见节段性分布的浅溃疡，易出血 D.直肠可见菜花样隆起性病变 E.直肠、乙状结肠可见连续性分布的病变，病变处结肠粘膜充血、水肿、血管网消失， 可见多发糜烂或浅溃疡，质脆，易出血 2．溃疡性结肠炎的主要病理特点为（） A.结肠壁全层性炎症 B.病变是节段性分布 C.病变主要限于大肠黏膜 D.病变主要限于大肠黏膜及黏膜下层 E. .病变先发生于盲肠。后向下侵犯远端结肠 3．治疗溃疡性结肠炎的常用药物是（） A.左旋多巴 B.庆大霉素 C.吡哌酸 D.甲氰咪胍 E.柳氮磺嘧啶 4. 溃疡性结肠炎的好发部位是（） A.十二指肠降段 B.回肠 C.直肠和结肠 D.回盲部 E.小肠 5．关于溃疡性结肠炎的病理改变错误的是（） A.病变呈广泛性小溃疡 B.病变常侵入肌层易出现穿孔及巨结肠 C.炎症反复发作可形成炎性息肉 D.病变反复发作可致结肠变形缩短 E.溃疡性结肠炎可出现癌变 6．患者，女性，28岁。腹泻半年就诊。大便每日3~4次，果酱色，排便前下腹疼，排便后减轻。纤维结肠镜检查，见直肠及全部结肠充血、水肿、质脆、易出血，散在多个浅小溃疡及小息肉。下列处理中哪项是不恰当的( ) A.口服水杨酸偶氮磺胺吡啶 B.地塞米松
C.阿托品肌肉注射 D.必要时加用硫唑嘌呤 E.大便检查白细胞增多时加用抗生素 7．治疗轻中度溃疡性结肠炎的主要口服药物有( ) A.泼尼松 B.环磷酰胺 C.SASP D.甲硝唑 E.抗生素 8．下列不支持溃疡性结肠炎的诊断的是( ) A.黏液脓血便 B.粪便镜检有红细胞、白细胞 C.结肠镜检查无器质性病变证据 D.结肠镜检查发现较多的炎性息肉 E.可并发结节性红斑 9.患者，男性，25岁。反复腹泻2年。粪常规除见少许红、白细胞外无异常，粪细菌培养(—)，纤维结肠镜检查见直肠及乙状结肠黏膜充血、水肿、质地脆、易出血。最可能的诊断是( ) A.阿米巴痢疾 B.细菌性痢疾 C.克隆病 D.慢性溃疡性结肠炎早期 E.直肠乙状结肠癌症早期 10．下列不是溃疡性结肠炎的X线表现的是（） A.肠壁边缘呈锯齿样 B.结肠袋消失，肠壁变硬 C.病变部位呈跳跃现象 D.肠腔见圆形或卵圆形充盈缺损 E.肠管缩短，肠腔变窄，呈铅管状 11．对溃疡性结肠炎的治疗，柳氮磺吡啶主要用于（） A.减少激素的用量 B.轻中型患者或重型用糖皮质激素治疗后已缓解者 C.避免出现中毒性巨结肠症 D.防止并发症的出现 E.活动期病例欲激素合用 12．门诊对有便血伴有腹泻或便秘的患者，首先应进行的检查是( ) A.直肠镜检 B.纤维结肠镜检 C.直肠镜检
溃疡性结肠炎的病因与发病机制研究进展 溃疡性结肠炎是一种病因尚不十分清楚的直肠和结肠慢性非特异性炎症性疾病。本病多见于20～40岁年龄患者。目前，其病因及发病机制仍未完全阐明，现将其病因与发病机制作综述如下。 标签：溃疡性结肠炎；病因；发病机制 溃疡性结肠炎是一种病因尚不十分清楚的直肠和结肠慢性非特异性炎症性疾病[1]。病变主要限于大肠黏膜与黏膜下层。临床表现为腹泻、黏液脓血便、腹痛。本病可发生在任何年龄，多见于20～40岁。目前，溃疡性结肠炎的病因及发病机制仍未完全阐明，大多数学者认为是免疫、遗传、环境、肠道菌群等多因素共同作用的结果，现将其病因及发病机制作综述如下。 免疫因素 研究发现，UC的发病与免疫因素关系密切，主要原因：①大多数UC患者的病史或家族史中常合并关节炎、结节性红斑、眼的葡萄膜炎与血管炎病变；②UC患者血清中可检测到多种自身抗体（如抗中性粒细胞胞浆抗体（ANCA）、原肌球蛋白抗体）存在；③UC的发病与CD4+T细胞密切相关，人体内有Th1和Th2两种T细胞，他们在免疫反应中发挥了重要的效应，在DSS诱导的结肠炎急性期，Th1型反应占优势，而在DSS诱导的结肠炎慢性期，Th2型免疫反应占优势。因此，Th1/Th2比例失衡是导致UC发病的重要原因[2-3]。 遗传因素 有调查统计显示，UC患者的血缘家族发病率高，大概是5%～15%，且血缘关系越近，发病率越高；UC患者有家族史，丹麦调查表明，单卵双生者，UC 发病率为18.2%，双卵双生者发病率为4.5%，由此不难看出，单卵双生者UC发病率要明显高于双卵双生者，因而证实了UC的遗传倾向性，且其具有复杂性、多重联合基因性和不纯一性。从全球分布情况来看，UC发生有地区差异，欧美国家要高于亚非国家，城市要高于农村，UC发病率在种族间差异明显，欧美白种人发病率要高于黄种与黑种人[4]。 饮食因素 自80年代以后，随着人们生活水平的提高及饮食结构的改变，尤其是肉类、蛋奶类增加是导致UC患病率增高的主要原因。有调查显示，UC的诱发因素与饮食不节或不洁关系最为密切，尤其是以生冷、辛辣、肥甘之品最易导致UC的发生[5]。高糖、高脂肪、高蛋白尤其是奶制品摄入过多而纤维素摄入减少与UC 发病和复发有关，而补充益生菌、膳食纤维、鱼油则具有保护作用[6]。丁酸盐对结肠黏膜具有保护作用[7]，丁酸盐是结肠上皮的主要能量来源，其主要由麦麸、燕麦、黄豆、高纤维素谷类等食物在肠道内经细菌酵解后产生，蔬菜和水果
溃疡性结肠炎疾病诊疗指南 【病史采集】 病史的内容主要包括：腹泻腹痛、粘液脓血便、里急后重、发热、消瘦、贫血及其它相关症状，同时要描述发病、复发及加重的诱因、既往的诊疗过程。 【物理检查】 要注意腹膜刺激征及关节、眼、口腔、肝、脾等肠外表现。 【辅助检查】 1．常规检查血、尿、粪及肝、胆、脾等B超。 2．大便培养连续三次，大便中找阿米巴。 3．肠镜及肠粘膜活检。 4．钡灌肠检查。 【诊断要点】 1．临床表现：有持续性或反复发作性粘液血便、腹痛伴不同程度的全身症状。既往史及体检中要注意关节、眼、口腔、肝胆等肠道外表现。 2．肠镜所见： （1）粘膜有充血、水肿、多发性浅表溃疡。病变大多以直肠开始，呈弥漫性分布。 （2）粘膜粗糙呈颗粒状、脆、易出血，或附有脓性分泌物。
（3）可见假息肉，环形皱襞变钝或消失。 3．粘膜活检：呈炎症性反应，同时常可见糜烂、隐窝脓肿、腺体排列异常及上皮变化。 4．钡灌肠所见： （1）粘膜粗乱及/或有细颗粒变化。 （2）多发性溃疡或有假息肉。 （3）肠管狭窄、缩短、结肠袋消失可呈管状。 5. 在排除菌痢、阿米巴肠炎、慢性血吸虫病、肠结核、克隆氏病、放射性肠炎的基础上，可按下列条件诊断：（1）根据临床及肠镜所见三项中之一项及／或粘膜活检可以诊断本病。 （2）根据临床及钡灌肠所见三项中之一项可以诊断本病。 （3）临床症状不典型而有典型肠镜所见或钡灌肠所见者可以诊断本病。 （4）一个完整的诊断应包括临床表现、严重程度、病变范围及病变分期。 【鉴别诊断】 1．慢性细菌性痢疾、慢性阿米巴痢疾、慢性血吸虫病、肠结核、真菌性肠炎。 2．结肠癌、克隆病、过敏性肠炎、缺血性肠炎、放射性肠炎等。
溃疡性结肠炎的中医临床研究进展 发表时间：2015-08-07T15:34:17.137Z 来源：《医药前沿》2015年第16期供稿作者：王磊谷云飞（通讯作者） [导读] 溃疡性结肠炎是一种常见的慢性肠道疾病，也是一种多因素、多层次的原因不明的非特异性炎症。 王磊谷云飞（通讯作者） (南京中医药大学第一临床医学院江苏南京 210000) 【摘要】阐述了溃疡性结肠炎的中医病因病机，从辩证施治、分期论治、中成药治疗及中药灌肠综述了中医治疗溃疡性结肠炎的临床进展，认为中医治疗溃疡性结肠炎的前景辽阔。 【关键词】溃疡性结肠炎；中医治疗；临床进展 【中图分类号】R242 【文献标识码】A 【文章编号】2095-1752（2015）16-0010-02 Clinical research progress of Ulcerative colitis of traditional Chinese medicine Wang lei, Gu Yunfei (corresponding author). Nanjing University of Chinese Medicine, Jiangsu Province, Nanjing 210000, China 【Abstract】This paper expounds the etiology and pathogenesis of ulcerative colitis using traditional Chinese medicine, from the dialectical treats, staging treatment, proprietary Chinese medicine treatment, and traditional Chinese medicine enema, summarized the progress of Chinese medicine in the treatment of ulcerative colitis, thought the prospect is very vast of treatment ulcerative colitis by traditional Chinese medicine. 【Key words】Ulcerative colitis; Traditional Chinese medicine treatment; Clinical progress 溃疡性结肠炎是一种常见的慢性肠道疾病，也是一种多因素、多层次的原因不明的非特异性炎症。病变主要在结肠的黏膜及黏膜下层，呈连续性弥漫性分布。临床以腹泻、粘液脓血便，腹痛为特征，部分患者有肠外表现[1]。兹将近年来中医治疗溃疡性结肠炎临床研究进展进行综述。 1.病因病机 溃疡性结肠炎一般属于中医学“泄泻”、“痢疾”范畴。中医认为溃疡性结肠炎的病因主要包括外邪侵袭、饮食不节、情志不畅和体虚劳倦。本病的病位主要在脾胃与大小肠，且与肝肾关系密切。湿邪内蕴，气血壅滞，脾肾亏虚，乃本病发病的关键所在。其中湿邪内蕴为其标实，脾肾亏虚为其本虚，二者互为因果关系。 2.中医治疗 2.1辩证施治 邵荣世教授将溃疡性结肠炎分为四个主要证型，包括脾虚寒湿证、肾阳亏虚证、肝旺脾虚证、肠道湿热证［2］。印会河教授将溃疡性结肠炎分为湿热积滞证、湿渍肠道证、脾胃虚弱证三个证型［3］。张林祥将溃疡性结肠炎分为三型，包括湿热蕴结型、气滞血瘀型和脾肾两虚型。常见溃疡性结肠炎六个证型，包括:湿热内蕴证治以清热利湿，佐以调气行血，代表方有白头翁汤、芍药汤等。脾胃虚弱证治以健脾益气，除湿升阳，代表方为参苓白术散。脾肾阳虚证治以健脾补肾，温阳化湿，代表方有附子理中汤、四神丸等。肝郁脾虚证治以疏肝理气，健脾和中，代表方有痛泻要方、四逆散等。阴血亏虚证治以滋阴养血，清热化湿，代表方有驻车丸等。气滞血瘀证治以行气活血，佐以健脾益气，代表方为膈下逐瘀汤等。 2.2分期论治 李乾构教授将溃疡性结肠炎分为二期：急性活动期证属脾胃虚弱，大肠湿热，以健脾助运，清化湿热之法，用自拟清化溃结汤；缓解期证属脾肾俱虚，湿邪留滞，以健脾补肾，除湿导滞之法，用自拟健脾溃结汤。谢建群教授［4］认为溃疡性结肠炎治疗可分为早、中、后三期，早期应以攻邪为法，兼顾胃气；中期应攻补兼施，佐以活血化瘀祛痰；后期应以补虚固涩为主，兼祛余邪。可魏志军[5]亦将溃疡性结肠炎分两期，认为急性发作期寒热错杂而正气虚，用乌梅丸加减；缓解期属脾虚湿盛兼肾虚，用自拟二术汤加减。黄德亚[6]认为溃结的治疗应分三步,第一步用下法，方用增液承气汤加减，以下污秽之物；第二步用消法，方用大安丸加减，以期腹痛消失、大便次数减少或逐渐成形；第三步用补法，方用参苓白术散加减，以补气培土,健脾固肠。 2.3中药灌肠 用中药灌肠治疗溃疡性结肠炎是临床常用的方法，灌肠可以使药物直达病所，局部药物浓度高，而且通过药物作用使肠道溃疡面得到保护，促进其修复，改善局部血运，又可避免胃酸对药物的影响，所以药物灌肠法得到临床的重视。赵立群［7］用菊花煎保留灌肠治疗溃疡性结肠炎86例，菊花煎方药组成为菊花20g、紫参30g、蒲公英30g、诃子15g、白芨30g、赤石脂20g、黄柏15g、赤芍15g、地榆炭 30g，水煎200mL，保留灌肠，每晚1次，每次灌肠时灌肠液保留时间不小于2h。临床痊愈59例，好转23例，无效4例，总有效率为95%。谢晶日等［8］用三白灌肠液灌肠治疗溃疡性结肠炎34例，痊愈9例，好转3例，总有效率为94.12%。此方由焦白术30g、白头翁30g、白及10g、蒲公英30g、酒大黄10g、黄芪15g等组成。刘金华等［9］用自拟中药结肠清方保留灌肠治疗溃疡性结肠炎，主方药物为苦参20g、黄柏15g、白头翁10g、白及6g、地榆20g、石榴皮15g、当归10g、白芍10g、甘草5g、党参10g、茯苓10g、白术10g。每日1剂，水煎后每次取150mL保留灌肠，每晚1次，2周为1个疗程，共治疗2个疗程，有效率为96%。 2.4中成药治疗 治疗溃疡性结肠炎的常用中成药：香连丸、香连化滞丸、葛根芩连片、肠胃康冲剂等治疗溃疡性结肠炎湿热下注型；戊己丸、逍遥丸等治疗肝旺脾虚型；参苓白术丸、人参健脾丸、启脾丸、补脾益肠丸等治疗脾胃虚弱型；固本益肠片、四神丸、脾肾双补丸、附子理中丸等治疗脾肾阳虚型。 2.5 其他疗法 溃疡性结肠炎的中医治疗方法还包括艾灸疗法、温针灸、穴位埋线等针灸疗法和外敷法。诸多研究表明均有一定疗效。 3.结语 中医药治疗溃疡性结肠炎疗效显著，通过中医药辨证施治，不仅能有效改善患者的症状，还可以促进胃肠道消化吸收，调节机体免疫功能，从而提高机体抗病能力、改善机体营养状况。且无明显不良反应。 中医学界在溃疡性结肠炎的病因病机、辨证分型、单方、验方、外治法等诸多方面进行了有益的探索，在治疗本病上取得了较大的进
大肠癌研究进展 (综述) 1国内外对大肠癌的研究现状 1.1关于发病率： 结直肠癌在我国是常见恶性肿瘤且发病率明显上升。根据全国12 个县市登记结直肠癌死亡率已居第4～5 位。从发病率看,20 世纪90 年代与70 年代相比,城市上升了31.95 %.[1] 根据美国近30 年的统计, 20 世纪70 年代的结直肠癌死亡率为28/10万, 2000 年为20/10万, 下降了29%, 其主要原因为近二、三十年来美国大力开展无症状人群普查, 检出了大量“早期癌”并对癌前病变进行干预治疗。[2] 每年美国结肠癌的发病率接近148，300（72，600男性，75，700女性）名患者，占中人口的5-6%.患者具有家族性危险，也就是说其地带与第二代亲属中有两个或以上的患有结肠癌的患者。20%的患者具有此类情况，反之近5-10%的每年患有结肠癌的在自然界遵从孟德尔遗传- 他们以常染色体显性的表现形式遗传。[8] 1.2发病机理研究[3] 目前研究表明,大肠癌的发生发展是一个多因素、多阶段、多基因变异所致的病理过程和结果. 结肠癌的发生机制 (参考:[3]于旨平沈志祥罗和生主编,《实用消化病学》2007年1月第二版 p50)
结肠癌是人群中常见的肿瘤之一,该病发生的传统模型为良性腺瘤息肉引起的肿瘤,然后通过多步突变发展成腺癌.亦有少部分病例(8%)对结肠癌的易感性是明显遗传的,称之为遗传性非息肉性结肠癌HNPCC (HEREDITARY NON-POLYPOSIS COLON CANCER).. 2目前临床对结肠癌的认知情况？ 2.1人群普查开展得比较好的国家, 结直肠癌死亡率相对较低。 2.1.1 大规模人群普查资料表明, 35 岁以上的人群中, 结直肠癌的发病率约为24～32/10 万( 不含香港和台湾地区) [1～3]。早期结直肠癌根治术后, 患者5 年存活率可达90%以上, 而晚期癌5 年存活率不足10%。[2] 2.1.2 美国明尼苏达州1993 年公布了该地区46 551 名自然人群的13 年普查结果, 每年普查者结直肠癌死亡率下降33%; 1999 年公布了18 年普查结果, 每两年普查一次者结直肠癌死亡率下降21%。Towler 等[9]对4 项随机试验进行了荟萃分析, 每两年普查一次, 明尼苏达州结直肠癌死亡率下降6%, 英国诺丁汉下降15%, 丹麦下降18%, 瑞典下降12%, 综合各研究结果, 人群普查使结直肠癌死亡率下降16%, 按实际参与普查人数计算, 死亡率下降23%。 2.2提高早期诊断率是提高结直肠癌患者存活率的关键。 美国国家息肉研究工作组提示, 切除普查发现的息肉可明显减低结直肠癌的发病率。 日本应用免疫法粪便隐血试验( FOBT) 进行的病例对照研究提示, 普查可使结直肠癌死亡率下降81%。 以上结果说明, 普查不但能降低结直肠癌的死亡率, 还可降低其发病率。 2.3将高危人群视为结直肠癌筛查的重点人群 北京市15 家医疗机构的普查结果显示, SFOBT 的阳性率为5.6%; 北京地区普通人群的结直肠癌患病率为36.57/10万, 共检出结直肠癌14 例( 2 例为非本地常住人口, 统计时予以排除) , 其中Dukes A 期4 例, B 期7 例, C 期1 例, Dukes A、B期患者占91.66%; 40 岁以下人群未检出结直肠癌, 50 岁以上人群检出结直肠癌的比例随年龄增高而逐渐增加。 高危人群: 包括本人患过结直肠癌或结直肠腺瘤、患重症溃疡性结肠炎10 年以上未愈、胆囊切除10 年以上、曾有妇科肿瘤并接受过下腹部放疗、不明原因反复便血、直系亲属患结直肠癌) 2.4自然人群普查是发现早期结直肠癌的有效方法 李世荣等[17]拟应用SFOBT 对3002 名51～92 岁的自然人群进行连续16 年( 1987～2002 年, 1 次/年) 的结直肠癌普查。共2251 人接受了普查(A 组) , 751 人未能接受普查(B 组) , 普查率为74.98%。16 年共发现结直肠癌44 例, 年平均结直肠癌发生率为91.61/10万。 A 组检出结直肠癌21 例, 漏诊6 例, 结直肠癌发生率为74.97/10万, 检出率为91.61/10万; B组检出结直肠癌17 例, 发生率为141.48/10万。