European Crohn's And Colitis Organisation Research Articles

French national consensus clinical guidelines for the management of Crohn’s disease

BackgroundCrohn’s disease (CD) is a chronic and disabling condition. There is no curative medical treatment but current treatments provide increasingly sustainable control of the disease and allow patients a better quality of life. There is limited evidence supporting CD management in specific clinical situations, thus precluding an evidence-based approach. AimsTo help clinicians in making informed treatment decisions, a group of 59 French gastroenterologists with experience in the management of CD met to develop straightforward and practical algorithms based on the European Crohn’s and Colitis Organisation (ECCO) recommendations. MethodsThis experts’ opinion was developed following a Nominal Group consensus methodology. Nine clinical situations were identified: mildly active CD; uncomplicated moderately active CD, with, and without poor prognostic factors; uncomplicated severely active CD; perianal CD with a single fistula; perianal CD with complex fistula with or without abscess; complicated CD with abscess; intestinal stricture; and post-operative CD. Two working groups were formed and proposed algorithms that were then approved by a two-thirds majority of the Nominal Group. ResultsThese algorithms represent the pragmatic consensus of a group of experts in gastroenterology on the modalities of therapeutic care in different clinical situations in CD. They are available via a web application at: www.algorithmici.com.

PTH-088 We’re Still not Immune to Immunisations in IBD: Abstract PTH-088 Table 1

Introduction Over the past decade, there has been an increasing uptake of immunomodulator therapy in the treatment of Inflammatory Bowel Disease (IBD). The current British Society of Gastroenterology (BSG) and European Crohn’s and Colitis Organisation (ECCO) guidelines highlight the importance of influenza, pneumococcal, human papilloma virus, varicella and hepatitis B vaccination. Our previous audit in 2014 described 75% uptake of any vaccination in these patients. Here we present the re-audit after an intervention, where a letter was sent to general practitioners (GPs) to promote immunisation awareness. Methods 100 consecutive IBD patients attending the general gastroenterology outpatient clinic were asked to complete a questionnaire. All forms of IBD were included. Information regarding medication, infections and immunisation status were recorded. Results were analysed using the statistical package for the social sciences (SPSS). Results Of the 100 questionnaires returned, 3 were excluded due to incomplete completion. Median age was 46 (19–84). Of the IBD subtypes, 48 (49%) patients had Crohn’s, 34 (35%) had ulcerative colitis and 15 (16%) had colitis of unknown aetiology (CUTE); male to female ration was 48:52%. 92% of patients with IBD had medication prescribed in the past 6 months. Within this group, 59% had been on mesalazine, 38% on thiopurines, 36% on steroids and 12% on anti tumour necrosis factor (anti-TNF) agents. Overall, 68% of immunosuppressed patients received some form of immunisation in the preceding 6 months and, of these, 28% had some form of infection reported. In total, 44% of patients had immunosuppressant advice given and 29% of patients had vaccination advice. There was no statistical difference in the baseline characteristics of patients and prescribed medication compared to 2014. Despite engagement with primary care, there was no significant difference in the uptake of immunisation in the IBD population. In fact, there were statistically lower rates of Influenza and Pneumovax vaccination in the 2015 cohort (P see table ). Conclusion Current guidelines state that influenza, pneumococcal and HPV vaccination be considered for all IBD patients. Despite the results of our previous audit there does not appear to be an improvement in vaccination rates. A weakness in the current approach is that information is received by GPs at differing intervals to when a patient is seen. It may be that a targeted, patient-specific letter is sent to GPs with an attached acknowledgement receipt to improve vaccination rates. Disclosure of Interest None Declared

Tools for Controlling Activity of Neural Circuits Can Boost Gastrointestinal Research.

We thank Prof U. G. Knaus and T. C. Collin for critical reading of the manuscript. GA is supported by the European Crohn's and Colitis Organization (ECCO) (J/15/2) and by the National Childrens' Research Centre (K/12/1). GD is supported by the University of Aberdeen Wellcome Trust Institutional Support Fund (105625/Z/14Z).

Heterogeneity in endoscopic treatment of Crohn's disease-associated strictures: An international inflammatory bowel disease specialist survey.

Crohn's disease (CD) is frequently complicated by intestinal strictures, which are commonly treated by endoscopic balloon dilation (EBD). However, available data on this area of treatment is limited. The aim of this study was to depict the heterogeneity of endoscopic management of CD-associated strictures among international CD specialists to identify common treatment standards. IBD experts of the International Organization for the Study of Inflammatory Bowel Disease (IOIBD), the European Crohn's and Colitis Organization (ECCO), and from the Prospective Value In IBD trials (PROVIT) completed a web-based questionnaire to evaluate their endoscopic experience, practice setting, and number of EBDs performed annually. Additionally, two case scenarios and technical practice parameters were investigated. A total of 126 subjects from 15 countries completed the survey. The maximal length of dilated stricture was 4.5±1.7cm. The most commonly used maximal balloon size was graded as 15-18mm. While 87.2% of the participants favored EBD for anastomotic strictures, only 58.6% did so in the case of naïve strictures. Only 35.7% of physicians dilated actively inflamed strictures. Interventional endoscopists were more likely to dilate only clinically symptomatic strictures (p=0.046). Surgeons favored surgical treatment of de novo ileocecal strictures compared to gastroenterologists (p=0.026), reported a shorter stricture length being amendable by EBD (p=0.045), and more frequently used concomitant therapies (p=0.001). Operator experience increased the likelihood of EBD use in actively inflamed strictures (p=0.002), maximum length of stricture, and maximum balloon size (p=0.001). EBD is a widely used treatment approach for stricturing CD. Individual approaches differ significantly based on background of the operator, experience level, and practice setting.

Results of the first survey for the current status of inflammatory bowel disease management in Asian countries.

Results of the first survey for the current status of inflammatory bowel disease management in Asian countries.

Results of the Fifth Scientific Workshop of the ECCO (II): Pathophysiology of Perianal Fistulizing Disease.

The fifth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of fistulas to the disease course of patients with Crohn's disease (CD). The objectives were to reach a better understanding of the pathophysiological mechanisms underlying the formation of CD fistulas; to identify future topics in fistula research that could provide insights into pathogenesis; to develop novel therapeutic approaches; and to review current therapeutic strategies (with clarification of existing approaches to prevention, diagnosis and treatment). The results of the workshop are presented in two separate manuscripts. This manuscript describes current state-of-the-art knowledge about fistula pathogenesis, including the roles of epithelial-to-mesenchymal transition and cytokine matrix remodelling enzymes, and highlights the common association between fistulas and stenosis in CD. The review also considers the possible roles that genetic predisposition and intestinal microbiota play in fistula development. Finally, it proposes future directions and needs for fistula research that might substantially increase our understanding of this complex condition and help unravel novel therapeutic strategies and specific targets for treatment. Overall, it aims to highlight unanswered questions in fistula research and to provide a framework for future research work.

The role of budesonide in the management of Crohn's disease

Inflammatory bowel disease encompasses two main conditions: ulcerative colitis (UC) and Crohn's disease (CD). These are chronic debilitating conditions, characterised by relapsing inflammation of the gastrointestinal tract. Approximately 620 000 people in the UK are affected by these conditions. The management of CD can be complex, which presents challenges to both patients and clinicians. Treatment of CD is evolving in tandem with an improved understanding of the disease. However, there is currently no cure for this disease. The mainstay of treatment is to induce and maintain clinical remission. Steroid therapies are used in the induction of remission. Current European Crohn's and colitis Organisation (ECCO) guidelines recommend the use of budesonide as the first-line treatment of mild to moderate ileo-caecal CD. This article provides an overview of CD and the current strategies used in its pharmacological management, placing specific focus on the role of budesonide in the treatment pathway.

Endoscopic Scores for Evaluation of Crohn's Disease Activity at Small Bowel Capsule Endoscopy: General Principles and Current Applications

The small bowel is affected in the vast majority of patients with Crohn's Disease (CD). Small bowel capsule endoscopy (SBCE) has a very high sensitivity for the detection of CD-related pathology, including early mucosal lesions and/or those located in the proximal segments of the small bowel, which is a major advantage when compared with other small bowel imaging modalities. The recent guidelines of European Society of Gastrointestinal Endoscopy (ESGE) and European Crohn's and Colitis Organisation (ECCO) advocate the use of validated endoscopic scoring indices for the classification of inflammatory activity in patients with CD undergoing SBCE, such as the Lewis Score or the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). These scores aim to standardize the description of lesions and capsule endoscopy reports, contributing to increase inter-observer agreement and enabling a stratification of the severity of the disease. On behalf of the Grupo de Estudos Português do Intestino Delgado (GEPID) – Portuguese Small Bowel Study Group, we aimed to summarize the general principles and clinical applications of current endoscopic scoring systems for SBCE in the setting of CD, covering the topic of suspected CD as well as the evaluation of disease extent (with potential prognostic and therapeutic impact), evaluation of mucosal healing in response to treatment and evaluation of post-surgical recurrence in patients with previously established diagnosis of CD.

Cogan's Syndrome in Patients With Inflammatory Bowel Disease--A Case Series.

Cogan's syndrome (CSy) is a very rare autoimmune disorder, mainly affecting the inner ear and the eye, and is associated with inflammatory bowel disease (IBD). This was a European Crohn's and Colitis Organisation (ECCO) retrospective observational study, performed as part of the CONFER project. A call to all ECCO members was made to report concomitant CSy and inflammatory bowel disease (IBD) cases. Clinical data were recorded in a standardized questionnaire. This international case series reports on 22 concomitant CSy-IBD cases from 14 large medical centres. Mean duration of IBD until diagnosis of CSy was 8.7 years (range 0.0-38.0) and mean age at CSy diagnosis was 44.6 years (range 9.0-67.0). Six patients had underlying ulcerative colitis (UC) and 16 had Crohn's disease. Eleven patients (50%) had active disease at CSy diagnosis. Sixteen patients were under IBD treatment at the time of CSy diagnosis, of whom 6 (37.5%) were on anti-tumour necrosis factor (TNF). Seven out of 10 patients, who were treated for CSy with immunomodulators (mostly with corticosteroids), demonstrated at least partial response. This is the largest CSy-IBD case series so far. Although CSy is considered to be an autoimmune disease and is associated with IBD, immunomodulatory IBD maintenance treatment and even anti-TNF therapy do not seem to prevent disease onset. Moreover, IBD disease activity does not seem to trigger CSy. However, vigilance may prompt early diagnosis and directed intervention with corticosteroids at inception may potentially hinder audiovestibular deterioration. Finally, vigilance and awareness may also offer a better setting to study the pathophysiological mechanisms of this rare but debilitating phenomenon.

PTU-074 Optimising crohn’s disease treatment based on the rutgeerts’ score 12 months after ileo-colic resection improves clinical outcomes at 3 years compared to standard practice

<h3>Introduction</h3> Clinical relapse of Crohn’s Disease (CD) occurs in 20–30% of patients at 1 year following intestinal resection, increasing by 10% per year without treatment.¹Work by Rutgeerts’ <i><i>et al</i>.</i>²within a tertiary centre supports the practice of ileo-colonoscopy 12 months post-resection to assess endoluminal recurrence, however the validity of this practice is unclear in a general hospital setting. The European Crohn’s and Colitis Organisation (ECCO) recommend the use of the Rutgeerts’ score at 12 months following ileo-colic resection to guide treatment decisions. This is not supported by the current BSG guidelines. The aim of this study is to assess the utility of the 12-month Rutgeerts’ score to improve clinical outcomes at 3 years following ileo-colic resection. <h3>Method</h3> Prospective analysis of 50 patients with CD requiring ileo-colic resection and primary anastomosis in a District General Hospital (DGH) between 2005–2011. Thirty eight of fifty patients underwent endoscopic appraisal of the pre-anastomotic ileum by a single expert observer (AWH) 12 months following resection. Patients with high risk lesions (≥ i3) were offered a step-up in treatment. Patients with low risk-lesions (i0-i1) had their treatment stopped completely or continued on their current regimen. Clinical outcomes at 3 years were compared between these 38 patients and 12 of 50 patients who refused 12 month endoscopic appraisal and received standard care. Fisher’s Exact Test was used to compare groups. <h3>Results</h3> Thirty six of thirty eight patients whose treatment was guided by 12 month endoscopic appraisal remained in steroid and symptom-free remission at 3 years. In comparison 5 of 12 patients receiving standard care suffered recurrence. The difference in clinical outcomes at 3 years between groups was significant (P = 0.0059, OR 12.86 (95% CI 2.064–80.09); Fisher’s Exact Test). There was trend towards higher Rutgeerts’ scores (≥ i3, <i>n = 2</i>0) being associated with a higher risk of disease relapse at 3 years as compared to low Rutgeerts’ scores (i0-i1, <i>n = 1</i>7) but this did not reach statistical significance (P = 0.0606, OR 10.00 (95% CI 0.993–100.7)). <h3>Conclusion</h3> In comparison with standard practice, optimising treatment paradigms guided by the Rutgeerts’ score 12 months following ileo-colic resection improves clinical outcomes at 3 years in DGH practice. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Carter MJ, <i>et al</i>. Gut 2004;<b>53</b>(Suppl V):v1-v16 Rutgeerts P, <i>et al</i>. Gastroenterology 1990;99(4):956–63

Diagnosis and management of Crohn's disease.

Diagnosis and management of Crohn’s disease is based on clinical signs and symptoms combined with laboratory tests, endoscopy and imaging techniques. Endoscopy is the gold standard for the evaluation of patients with Crohn’s disease. Nevertheless, a correct diagnosis requires radiological examinations to define the extent and stage of the disease and especially to diagnose transmural complications including fistulae, abscesses and phlegmons. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently indicated in the study of the gastrointestinal tract. Diagnostic sensitivity and specificity of these two methods are similar and both also present certain limitations. CT is widely used and execution time is short, whereas MRI is much less common and requires a longer execution time. However, patients with Crohn’s disease are often young, and the frequency with which they have to undergo radiological examinations should be taken into account, as several trials have suggested that a total exposure to radiation exceeding 50 mSv carries a risk of neoplastic disease. Over the past decade, ultrasound (US) has gradually been introduced to support clinical examination in the diagnosis and monitoring of patients with Crohn’s disease. Several trials have assessed the diagnostic accuracy of US compared to that of CT and MRI, and the results have led to the recommendations contained in the updated guidelines (2013) of the European Crohn’s and Colitis Organisation (ECCO). The role of endoscopy and biopsy as first-line procedures in patients with suspected Crohn’s disease is reaffirmed, and CT and MRI still remain the gold standard imaging methods in the diagnosis of intestinal involvement and transmural lesions. However, US is recommended for assessing the extent of the disease and possible inflammation of the intestinal wall, particularly referred to bowel segments, which are not reachable by the endoscope owing to strictures. Furthermore, thanks to the widespread availability and short examination time, US imaging is useful also in emergencies to obtain immediate and important diagnostic information required for management decisions. The ECCO guidelines also focus attention on the role of US in the diagnosis of extramural complications. Abscesses, fistulas and phlegmons are frequent and sometimes fatal, but they are easily detected by US with a sensitivity of over 90 %. Several applications are still being assessed, and some studies show a greater diagnostic efficacy of contrast enhanced US (CEUS) and small intestine contrast ultrasonography (SICUS) associated with power Doppler in the diagnosis of the disease and its complications. These results, as well as the encouraging results obtained by US imaging for predicting the risk of recurrence after surgery, require further confirmation. However, the obtained data suggest that US imaging could be further implemented in the study of Crohn’s disease and that this diagnostic method might become a procedure of choice in inflammatory bowel disease (IBD). The limitations of US imaging, which are linked to the patient’s bodily features and the difficult visualization of some portions of the GI tract, are not relevant to the study of Crohn’s disease. US has become one of the most user- and patient-friendly methods for assessment of the gastrointestinal tract thanks to the elevated dynamism and usability of US as well as the continuous training of increasingly specialized US operators. In line with the multidisciplinary approach, which is characteristic of SIUMB, the society and JUS have therefore requested some of the greatest experts to write a series of articles on the role of US in the study of various medical, surgical and radiological aspects of Crohn’s disease, comparing US with other diagnostic methods. We thank the Authors for the time they have dedicated to this task and for the completeness and originality of the articles. In our opinion, the result is very good. We hope you will enjoy the reading.

Azathioprine in Crohn's disease therapy--guidance against the background of recent studies

Thiopurines (azathioprine and 6-mercaptopurine) are the most frequently used drugs in the treatment of patients with Crohn's disease. In current guidelines published by the German Society of Gastroenterology, Nutritional and Metabolic Diseases (DGVS) in 2014 and by the European Crohn´s and Colitis Organisation (ECCO) in 2010 different indications have been suggested. However, efficacy of azathioprine has been substantially questioned by recent publications in adults as well as in children examining the efficacy of early initiation of this treatment. These articles were published after release of the aforementioned guidelines. Therefore, in this survey recently published data are discussed on the background of our knowledge on the efficacy of azathioprine and 6-mercaptopurine developed in many years, and suggestions for the future use of these substances in the treatment of patients with Crohn's disease will be provided.

Magnetic resonance imaging and clinical assessments for perianal Crohn's disease: Gain and limits

BackgroundAssessment of perianal Crohn's disease remains challenging. European Crohn's and Colitis Organisation (ECCO) recommend magnetic resonance imaging (MRI) as a gold standard, but both accuracy and advantages remain limited compared to systematic clinical assessment. The aim of this study was to define their actual diagnostic value. MethodsWe performed a retrospective analysis of a prospective database of consecutive patients with perianal Crohn's disease assessed by magnetic resonance imaging and clinical examination from 2006 to 2012. At each outpatient visit, perianal activity (Perianal Disease Activity Index) and perianal phenotype (Cardiff-Hughes classification) were noted. MRI was interpreted according to Cardiff-Hughes and Van Assche classifications. ResultsOverall, 122 combined evaluations were assessed in 70 patients. Radiological imaging failed to show superficial ulcerations in 20/21 patients (95%) and severe ulcerations in 13/15 patients (87%). It consistently failed to diagnose anal stenosis (n=21, 100%). For fistulising lesions, the global agreement between the two methods was 71/122 (58%) in assessing complex fistulas. Clinical assessment underestimated 44/68 (65%) of multiple or ramified fistula tracts. Clinical examination failed to diagnose half of the radiological abscesses. ConclusionsCurrent ECCO guidelines should be applied with some caution because of the low sensitivity of MRI for the diagnosis of non-fistulising perianal disease. Combining clinical and MRI assessments improves diagnostic accuracy.

PWE-101 Imaging The Small Bowel In Ulcerative Colitis-relevant Or Still ‘’unclassified”?

IntroductionIt is widely accepted that Ulcerative Colitis (UC) is a mucosal inflammatory disease confined to the colon. Bolder disease definitions coupled with novel and evolving imaging paradigms have led to...

Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee

ObjectiveAlthough paediatric-onset IBD is becoming more common, few medications have a registered paediatric indication. There are multiple hurdles to performing clinical trials in children, emphasising the importance of choosing an...

Endoscopic postoperative recurrence rates in Crohn's disease in Korea: the beginning of a new approach?

Dear sir, It was with great interest that we read the article entitled Clinical and Endoscopic Recurrence after Surgical Resection in Patients with Crohn's Disease, recently published in this journal by Yang Woon Lee and colleagues.1 The article describes one of the first retrospective experiences with Korean patients regarding the rates of both clinical and endoscopic recurrence (ER) after surgical abdominal procedures for CD. In this study, the authors found an overall rate of ER of 71.4% (15 from 21) patients, in a mean follow-up period of 50.5 months. Although the study adds very important real world data and represents one of the first experiences on the topic of ER in Korean patients, some considerations are important in this data analysis and must be taken into consideration. First, the population of the study is somehow heterogeneous. A myriad of operations was performed as they fulfilled the inclusion criteria. Most of the western studies were performed only after ileocecal resections,2,3 and in this interesting Korean retrospective study, small bowel resections, segmental colectomies and other different procedures were also included. The Rutgeerts's score is not fully validated after different procedures, it is mostly widely used after ileocecal resections, and there is significant controversy if it can be applied after other operations, even with capsule endoscopy to detect recurrence.4 Moreover, most of the western studies consider the definition of ER as a Rutgeerts' score ≥i-2, considering the i-1 score as mucosal normality, differently of the criteria of the Korean study.1,2,3,4 However, only one patient in the sample presented as an i-1 after surgery, what would not influence significantly the final results of recurrence. There is quite a consensus in the literature that smoking, previous resections and penetrating CD are significant risk factors for ER in CD patients.3,5 The study did not find any risk factor, despite meticulous statistical analysis, maybe for 2 reasons: the small number of patients in the sample, or the possibility of a different genetic background in Korean CD patients, that can alter the phenotype of the disease in the country, as previously stated by the authors. We recently presented at the European Crohn's and Colitis Organisation (ECCO) congress the results from a database with patients from 7 referral centers from South America, Europe and Asia regarding the same topic as this interesting Korean study.6 In our experience, ER was observed in aproximately 32% of patients treated in Brazil, 38% of those treated in Japan and in 14% of patients treated in Italy (Fig. 1). These lower numbers, as compared to the Korean study, probably were observed due to the shorter follow-up period of 12 months in this database. However, they could also be a consequence of a similar strategy of postoperative prevention of recurrence that is actively practised in these referral centers.6 The differences between the Korean study as compared to ours, are also basically related to the different populations analyzed. Fig. 1 Early postoperative endoscopic recurrence (PER). Early PER rates from the observational MULTIPER database, with data compiled from 3 different countries. Despite these few considerations, we would like to congratulate the staff from the Catholic University of Korea for this new interesting information on ER after CD surgical procedures in Asian patients. We also hope that this data can impact in a near future in the prospective management of surgically-treated CD patients in Korea, increasing the number of colonoscopies or other endoscopic examinations performed 6 to 12 months after surgery, in order to detect early ER, optimize medical therapy if needed, and possibly to lead to a lower rate of recurrence in the long term and better control of the disease.

Differences in the management of pediatric and adult onset ulcerative colitis — lessons from the joint ECCO and ESPGHAN consensus guidelines for the management of pediatric ulcerative colitis

An expert panel of the European Crohn's and Colitis Organisation (ECCO) and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) initiated a consensus process to produce the first pediatric specific ulcerative colitis (UC) guidelines based on a systematic literature review. Treatment strategies must reflect that pediatric-onset UC has a slightly different phenotype than adult-onset disease with more often extensive (pancolitis) and more aggressive disease course. Other pediatric-specific aspects include growth, puberty, bone density accrual and emotional development and body image acquisition. These differences and others influenced the development of pediatric treatment algorithms. It is recommended that virtually all children with UC must be treated with some maintenance therapy and 5-ASA requirement and dosing are often higher in children. A larger number of children are at risk for steroid-dependency, and this should not be tolerated; steroid sparing strategies with early use of immunosuppressors are recommended in high-risk patients. On the other hand, the safety profile of immunosuppressive therapy in children includes the rare forms of lymphomas and many future treatment years. Colectomy and pouch formation should be balanced in the treatment algorithms against the higher rate of future infertility in girls. The acute and on-going management of pediatric UC should be guided by evidence- and consensus-based balanced decisions, reflecting a vision of long-term treatment goals.

The Significance of Varicella Exposure History and Correlation with Serology among Patients with Inflammatory Bowel Disease: Presidential Poster

Purpose: Varicella zoster virus (VZV) infection is a significant concern in immunosuppressed IBD patients with reports of severe, disseminated, and occasionally fatal infection. The European Crohn's and Colitis Organization (ECCO) guidelines on IBD immunization recommend using patient-reported varicella exposure history as an indicator to VZV immunity, and immunization of those with a negative exposure or vaccination history. Data on accurate recall of infection with corroborative serology are scarce. We analysed the significance of prior varicella exposure in predicting VZV seroprotection in IBD patients. Methods: We conducted a retrospective review of 220 consecutive patients attending our IBD clinic from October, 2012 to May, 2013. Data including patient demographics, disease phenotype, and prior VZV exposure (infection or vaccination), including VZV antibody titres, was obtained from electronic or case notes review. Ongoing medical therapy for IBD at the time of testing was also recorded. Results: Data for VZV exposure status and tests for VZV titres was available in 71 IBD patients (Crohn's disease n=39, ulcerative colitis n=32). Of these, 55% were females, the median age was 42 years (range 21-79), and mean disease duration was 8.7 years.Twenty-seven percent of patients were on no treatment, 24% were on aminosalicylates, and 49% were on effective immunosuppression. This included 16 (46%) patients on thiopurines, one (3%) on methotrexate, five (14%) on infliximab, two (6%) on adalimumab, three (8%) on infliximab + thiopurine combination, one (3%) on infliximab + methotrexate, six (17%) on corticosteroids, and one (3%) on infliximab + prednisolone. Two-third of patients (69%) were uncertain about a prior exposure to varicella; 28% gave a definitive history, and 3% stated no previous exposure. The overall prevalence of seropositivity for VZV IgG was 62/71 (87%), with 85% seropositivity in patients receiving immunosuppressive treatment. Despite definitive VZV exposure history, 10% patients were seronegative; these patients were on combined immunosuppressive therapy with infliximab and thiopurine. A total of 14% patients on immunomodulation were VZV IgG seronegative; 40% of these on bi-modal immunosuppressive therapy. Conclusion: A significant number of patients are seronegative, despite a positive history for varicella exposure, suggesting a loss of seroprotection possibly from immunosuppression. A strategy combining varicella exposure history with serology may identify history-positive yet seronegative individuals who merit vaccination, but arguably also identify history-negative yet seropositive individuals, resulting in a lower rate of unnecessary vaccination. There is an urgent need for more data, which could influence guideline development in this area.

Letter: inflammatory bowel disease guidelines and conflicts of interest - authors' reply

We thank Drs. Eliakim, Dignas and Travis for their comments1 concerning our manuscript.2 We commend the European Crohn's and Colitis Organisation (ECCO) for having a standard procedure for the development of guidelines, and insisting on disclosure of conflicts of interest (COI) from those involved in the guideline development process. As we noted in our manuscript, we can all agree that ECCO has taken many important steps in improving the guideline development process. However, we would like to note that while ECCO has updated their website, the webpage at the time of our study (30 September 2012) was ECCO's prior version of their website. As one may note, reference 25 in our manuscript is misquoted by Eliakim et al. The reference in our manuscript is https://www.ecco-ibd.eu/publications/ecco-guidelines-publications.html. The link we referenced has been taken down by ECCO and is no longer available. The new web page, as referenced in their letter, is https://www.ecco-ibd.eu/publications/ecco-guidelines-science/published-ecco-guidelines.html. The old website did not have any disclosures or comments regarding COI. Archived copies of the webpage cited in our manuscript are available at http://goo.gl/6AJbC. Additionally, we fundamentally disagree with the notion that if evidence was present, there would be, ‘no need for guidelines.’1 Authors of guidelines utilise the available evidence to form recommendations. Evidence is critical to the development of strong guidelines that clinicians rely on as the accepted standard of care. When evidence is not available, recommendations may be made, but it must be clear that the recommendations are only based on expert opinion. In this situation, a current best practice may be more appropriate than a guideline. As mentioned in our manuscript, this differentiation is key so that clinicians are aware when evidence is lacking, and if and when studies are performed, current practice may very well change. Use of the GRADE system would help differentiate between recommendations where the evidence is strong and further studies will not change current practice from recommendations where future studies are likely to change current practice. The authors' declarations of personal and financial interests are unchanged from those in the original article.2

Letter: international IBD practice guidelines - authors’ reply

SIRS, We thank Drs Mowat and Bloom for their comments concerning our manuscript 2 We agree that clinical practice guidelines require greater attention to transparency regarding potential conflicts of interest (COI) and grading of evidence for the recommendations. However, we do not agree with the critique regarding the decision to assign a Grade D to highlight recommendations that did not provide any indication of the supporting evidence. We felt that any statement marked with a bullet point separated from the body of the manuscript could be considered a recommendation. These statements could have been graded, even if the level of evidence was only expert opinion. When a guideline does not cite the level of evidence, there is no way for the clinician to know the quality of evidence or the strength of the recommendation. While many recommendations lack evidence from randomised control trials, we suggest that it is not acceptable to make recommendations without an indication of the grade of evidence. The example cited by Mowat and Bloom regarding methotrexate exemplifies this point. Despite a lack of randomised trials, there is an abundance of data concerning the dangers associated with taking methotrexate during pregnancy. Had the GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) been used, it would have graded ‘methotrexate is absolutely contra-indicated in pregnancy’ as a strong recommendation based on the certainty of the available evidence. We disagree that we misquoted the BSG level of evidence regarding checking thiopurine methyltransferase levels. The British Society of Gastroenterology (BSG) cites evidence level EL4. Evidence level 4 refers to case– control study or poor/non-independent reference standards. This merges into a level C evidence – consensus opinions of experts, case studies or standard of care. With regard to use of methotrexate in ulcerative colitis (UC) and the BSG’s discordant recommendation, the European Crohn’s and Colitis Organisation (ECCO) guideline cites seven manuscripts related to methotrexate in UC. The additional paper that the BSG references is the Cochrane review from 2009 that comments “the available evidence is not sufficient to recommend the use of methotrexate,” which is identical to the ECCO guidelines. BSG is alone in recommending methotrexate in UC. Lastly, we fully agree that potential conflicts of interest (COI) do not equate to bias. However, when COI are present in the development process there is the potential for the COI to bias recommendations. 11 Having a rigorous review process of the manuscript’s drafts does not obviate the need for transparency regarding COI and a well-defined process to mitigate potential bias prior to guideline development. We all agree that the goal of practice guidelines is to create a safer and more effective medical system. To this end, the guidelines development process must be transparent regarding potential COI, have a system in place to minimise potential bias, base recommendations on the best available evidence, and provide a grading of the quality of the evidence for all recommendations.