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Background: Celiac disease has been associated with increased mortality, but data on long-term mortality are scarce. Aims: To determine long-term mortality in celiac disease. Methods: The study cohort consisted of all celiac disease patients (n=1,392) diagnosed in Tampere University Hospital catchment area 1960 – 2000. Patients were categorized into subgroups based on demographic (age, gender, decade of diagnosis) and celiac disease characteristics (e.g., phenotype, severity of villous atrophy) collected from medical records. Overall and cause-specific mortality was compared to those of age-, sex-, and place of residence matched reference individuals (n=4,177) over time. Results: During the 41 years of follow-up (median 26.5 years), 376 celiac disease patients and 1,155 reference individuals died. All-cause mortality was not increased (hazard ratio (HR) 0.96, 95% confidence intervals (CI) 0.85–1.08). Mortality from lymphoproliferative diseases and diseases of the central nervous system was increased (HR 2.42, 95% CI 1.38–4.24 and HR 2.14, 95% CI 1.05–4.36 respectively) while the risk from alcohol related diseases was decreased (HR 0.31, 95% CI 0.09–1.00). Examination of various celiac disease phenotypes revealed no significant differences in mortality Conclusions: Overall mortality was not increased in any celiac disease phenotype during a very long-term follow-up. publishedVersion

Background: An increased risk of kidney disease in patients with celiac disease has been reported, but the association has remained obscure. Only few studies have investigated the association between renal comorbidities and dermatitis herpetiformis, a cutaneous manifestation of celiac disease. Objectives: We investigated whether patients with different phenotypes of celiac disease are at higher risk of kidney diseases than age- and sex-matched references. Methods: The diagnoses of glomerulonephritis, diabetic nephropathy, interstitial nephritis, and end-stage renal disease obtained from the National Hospital Discharge Register between 1970 and 2015 were identified in celiac disease (Marsh III, n = 1072) and dermatitis herpetiformis (n = 368) patients diagnosed at Tampere University Hospital catchment region and in 4296 reference subjects. Using the Cox proportional hazards model, we compared the risk of kidney diseases between patients and references. The study protocol was approved by the Regional Ethics Committee of Tampere University Hospital (R16090). As the study was register based, no consent from patients was required. Results: Even after adjusting for type 1 diabetes, celiac disease was associated with an elevated risk of kidney disease (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.12–3.03), glomerulonephritis (HR 3.37, 95% CI 1.64–6.95), and IgA nephropathy (IgAN) (HR 18.98, 95% CI 2.29–157.63). No similarly elevated risk was found among dermatitis herpetiformis patients (HR 1.50, 95% CI 0.63–3.55; HR 2.21, 95% CI 0.77–6.38; and HR 5.87, 95% CI 0.53–64.79, respectively). Conclusion: Celiac disease patients were at increased risk of kidney diseases, notably IgAN. The risk was dependent on the celiac disease phenotype and was not seen in patients with dermatitis herpetiformis. Awareness of possible renal manifestations is recommended when treating celiac disease patients. publishedVersion

BACKGROUND AND AIMS Albeit the association between renal disorders and celiac disease is still somewhat contradictory, an elevated risk of kidney diseases in patients with celiac disease has been shown [1, 2, 3]. Only case reports have described the link between glomerulonephritis and dermatitis herpetiformis, a cutaneous manifestation of celiac disease [4]. This study aimed to evaluate whether patients with various phenotypes of celiac disease have an increased risk of renal co-morbidities compared with matched references. METHODS: The diagnoses of glomerulonephritis, diabetic nephropathy, interstitial nephritis and end-stage renal disease were collected from the Finnish National Hospital Discharge Register from 1970 to 2015 among 1440 celiac disease patients and 4296 age- and sex-matched references. Further, patients were divided into two cohorts, dermatitis herpetiformis and any other phenotype of celiac disease. We used Cox proportional-hazards model to compare the risk of renal co-morbidities between patients and reference individuals. RESULTS Celiac disease was positively associated with renal disorders even after adjusting for type 1 diabetes [hazard ratio (HR) 1.81, 95% confidence interval (CI) 1.18–2.76]. A 3-fold and 12-fold risk increase were seen for glomerulonephritis and IgA nephropathy, respectively. A similar risk increase for renal co-morbidities in dermatitis herpetiformis was not shown. CONCLUSIONS: Celiac disease was associated with an increased risk of renal co-morbidities, especially glomerulonephritis. The risk depends on the phenotype of celiac disease. The possible association between renal disorders and celiac disease should be investigated more in the future and kept in mind also in clinical practice.

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Summary Background Refractory coeliac disease type 2 is a rare subtype of coeliac disease with high mortality rates; interleukin 15 (IL-15) is strongly implicated in its pathophysiology. This trial aimed to investigate the effects of AMG 714, an anti-IL-15 monoclonal antibody, on the activity and symptoms of refractory coeliac disease type 2. Methods This was a randomised, double-blind, placebo-controlled, phase 2a study of adults with a confirmed diagnosis of refractory coeliac disease type 2. Patients were randomly assigned at a 2:1 ratio to receive seven intravenous doses over 10 weeks of AMG 714 (8 mg/kg) or matching placebo. Biopsy samples were obtained at baseline and week 12 for cellular analysis and histology. The change in the proportion of aberrant intraepithelial lymphocytes from baseline to week 12 with respect to all intraepithelial lymphocytes was the primary endpoint and was quantified using flow cytometry. Secondary endpoints were the change in aberrant intraepithelial lymphocytes with respect to intestinal epithelial cells; intestinal histological scores (villous height-to-crypt depth ratio; VHCD); intraepithelial lymphocyte counts; Marsh score; and patient-reported symptom measures, including the Bristol stool form scale (BSFS) and gastrointestinal symptom rating scale (GSRS). Main analyses were done in the per-protocol population of patients who received their assigned treatment, provided evaluable biopsy samples, and did not have major protocol deviations; only patients with non-atypical disease were included in the analyses of aberrant intraepithelial lymphocytes, including the primary analysis. Safety was assessed in all patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02633020) and EudraCT (2015-004063-36). Findings From April 13, 2016, to Jan 19, 2017, 28 patients were enrolled and randomly assigned to AMG 714 (n=19) and placebo (n=9). Six patients were not included in the primary analysis because of protocol deviation (one in the AMG 714 group), insufficient biopsy samples (one in the AMG 714 group), and atypical intraepithelial lymphocytes (three in the AMG 714 group and one in the placebo group). At 12 weeks, the least square mean difference between AMG 714 and placebo in the relative change from baseline in aberrant intraepithelial lymphocyte percentage was −4·85% (90% CI −30·26 to 20·56; p=0·75). The difference between the AMG 714 and placebo groups in aberrant intraepithelial lymphocytes with respect to epithelial cells at 12 weeks was −38·22% (90% CI −95·73 to 19·29; nominal p=0·18); the difference in change in Marsh score from baseline was 0·09% (95% CI −1·60–1·90; nominal p=0·92); the difference in VHCD ratio was 10·67% (95% CI −38·97 to 60·31; nominal p=0·66); and the difference in change in total intraepithelial lymphocyte count was −12·73% (95% CI −77·57–52·12); nominal p=0·69). Regarding symptoms, the proportion of patients with diarrhoea per the BSFS score decreased from ten (53%) of 19 at baseline to seven (37%) of 19 at week 12 in the AMG 714 group and increased from two (22%) of nine at baseline to four (44%) of nine at week 12 in the placebo group (nominal p=0·0008); and the difference between the groups in change in GSRS score was −0·14 (SE 0·19; nominal p=0·48). Eight (89%) patients in the placebo group and 17 (89%) in the AMG 714 group had treatment-emergent adverse events, including one (11%) patient in the placebo group and five (26%) in the AMG 714 group who had serious adverse events. The most common adverse event in the AMG 714 group was nasopharyngitis (eight [42%] patients vs one [11%] in the placebo group). Interpretation In patients with refractory coeliac disease type 2 who were treated with AMG 714 or placebo for 10 weeks, there was no difference between the groups in terms of the primary endpoint of aberrant intraepithelial lymphocyte reduction from baseline. Effects on symptoms and other endpoints suggest that further research of AMG 714 may be warranted in patients with refractory coeliac disease type 2. Funding Celimmune and Amgen.

Background and aims: Every fifth patient with ulcerative colitis (UC) experiences severe acute flare at some point in the course of the disease. Corticosteroids (Cs) remain the treatment of choice in acute flare. Data on the efficacy of first intravenous Cs in the long-term prognosis of UC are scarce and were investigated here. Materials and methods: All episodes of patients with acute UC admitted to Tampere University Hospital and treated with intravenous Cs between January 2007 and January 2016 were identified from patient records and reviewed. The risks for colectomy and for continuous use of Cs were evaluated. Predictive factors were analysed. Results: The study comprised 217 patients of whom 184 (85%) responded to intravenous Cs at index flare. Of the 33 non-responders, 31 (94%) were treated with intravenous cyclosporine A and 28 responded. Five (2.3%) patients needed emergency colectomy. Twenty-six (12%) patients underwent colectomy within 1 year of index flare. Overall colectomy rate was 56 (26%) during follow-up (median 7.5 years, range 0.1–10.5). Six months after index flare 66 (30%) patients were still on steroids. In this series 149 (69%) required further Cstherapy and 104 (48%) needed rehospitalization for new flare at some point during follow-up. Overall 155 patients were treated with thiopurines, of whom 72% within the first year after admission. A total of 36 patients had infliximab as a first-line biological treatment, nine needed second-line therapy with adalimumab or vedolizumab after infliximab failed. Conclusion: Although intravenous Cs were efficient in inducing clinical response in patients with severe acute UC, only one fifth maintained remission in the long term. Two-thirds of patients required further Cs and the overall colectomy rate remained at 26%. High relapse rate indicates the need for closer monitoring of these patients. Enhancement of maintenance therapy should be considered at early stage after acute flare. publishedVersion

Background The increased risk of malignancies in coeliac disease is well recognised, but data on incidence and predisposing factors are scarce. Our aim was to determine cancer incidence and its prognostic factors in coeliac disease during a long-term follow-up. Methods The study cohort comprised all (n = 1460) coeliac patients diagnosed in Tampere University Hospital catchment area during the period 1960-2000. Demographic data (age, gender, decade of diagnosis) and coeliac disease characteristics (presenting symptoms, signs of malabsorption, severity of villous atrophy) were obtained from medical records, and patients were stratified into subgroups accordingly. Standardised incidence ratios (SIRs) compared to general population of the same area were calculated for malignancies altogether and according to stratifications. Results The overall risk of malignancy was not increased (SIR 0.97; 95% confidence interval (CI) 0.84-1.11). The risk of non-Hodgkin lymphoma was elevated (SIR 3.0; 1.88-4.54) but less so after ≥15 years of follow-up (SIR 1.75; 0.70-3.60). Screen-detected coeliac disease or malabsorption at diagnosis was not associated with increased risk of non-Hodgkin lymphoma. The increased risk of gastrointestinal malignancies (SIR 1.42; 95% CI 1.07-1.85), particularly that of stomach and liver cancers, was associated with females, coeliac disease diagnosis before year 1981 and dermatitis herpetiformis. Conclusions The overall risk of malignancy was not increased in any coeliac disease phenotype. The risk of non-Hodgkin lymphoma was increased but not in screen-detected coeliac disease. publishedVersion

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up.METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery.FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (pINTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease.FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.

Introduction We assessed whether celiac disease-associated mortality is increased in Finland among patients diagnosed in the 21st century, given recent improvements in diagnostic and treatment facilities. Methods Biopsy-proven patients with celiac disease (Marsh III) and dermatitis herpetiformis aged 20-79 years (median 50 years) diagnosed 2005-2014 (n = 12,803) were identified from the national dietary grant registry. Dates and causes of death were obtained from Statistics Finland. Overall mortality and causes of death were compared with reference individuals (n = 38,384) matched for age, sex, and area of residence (at the time of celiac disease diagnosis) selected from the Population Information System. Results During a mean follow-up of 7.7 years (SD ±3.0 years), 884 (6.9%) and 2,613 (6.8%) deaths occurred among the celiac cohort and reference group, respectively. Overall mortality (hazard ratio [HR] 1.01, 95% confidence intervals [CIs] 0.94-1.09), mortality from all malignancies (HR 1.11, 95% CI 0.96-1.27), gastrointestinal tract malignancies (HR 1.21, 95% CI 0.56-1.71), or cardiovascular diseases (HR 0.91, 95% CI 0.77-1.07) were not increased among patients with celiac disease. Overall, mortality from lymphoproliferative diseases (HR 2.36, 95% CI 1.65-3.39) and nonmalignant digestive diseases (HR 2.19, 95% CI 1.40-3.43) was increased, but HRs decreased after the exclusion of the first 2 years of follow-up (HR 1.71, 95% CI 1.10-2.66 and HR 1.75, 95% CI 1.01-3.05, respectively). Discussion The overall mortality in adult celiac disease diagnosed 2005-2014 was not increased. Mortality from lymphoproliferative diseases was increased but lower than previously reported.

Purpose Restorative proctocolectomy (RPC) is the most common operation in ulcerative colitis. Nevertheless, permanent ileostomy will sometimes be unavoidable. The aim was to evaluate the reasons for pouch failure and early morbidity after pouch excision. Methods The number and the reasons for pouch failures were analysed in patients undergoing RPC 1985-2016. Results Out of 491 RPC patients, 53 experienced pouch failure (10 women, 43 men); 52 out of 53 underwent pouch excision. The cumulative risk for excision at 5, 10 and 20 years was 5.6, 9.4 and 15.5%, respectively. The reasons for failure included septic events such as fistula in 12 (23%), chronic pouchitis in 11 (21%) and leakage in 8 (15%) patients. Functional reasons for pouch failure were recorded as poor function in 16 (30%), incontinence in 12 (23%) and stricture in 12 (23%) patients. Multiple causes for pouch failure were recorded for individual patients. Seven cases of Crohn’s disease were found among the failure cases: two before pouch excision and five after. Altogether, 15 Crohn’s disease diagnoses were set in the RPC cohort, giving a percentage of 47% of pouch failure in this disorder. A complication occurred in 23 (44%) patients within 30 days after surgery; 16 were mild (Clavien-Dindo grades I–II). Conclusions Eleven percent of RPC patients suffered pouch failure: more men than women. The reasons were multiple. Crohn’s disease created a risk of failure, but a half of these patients maintained the pouch. Morbidity after pouch excision was moderate, but in most cases slight.

BACKGROUND AND AIMS It remains unclear as to what are the clinical characteristics associated with the presence of anemia at celiac disease diagnosis, and how these are affected by a gluten-free diet. We investigated these issues in a prospective study. METHODS Clinical and demographic data, small-bowel mucosal histology, serology, and laboratory parameters, body mass index (BMI), and bone mineral density (BMD) both at diagnosis and after 1 year on a gluten-free diet were investigated in 163 adults with celiac disease. Gastrointestinal symptoms and psychological well-being were evaluated by validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires. All study variables were compared between participants with and without anemia at celiac disease diagnosis. RESULTS Altogether, 23% of the patients had anemia at diagnosis. Anemic patients were more often women (P=0.001) and had more gastrointestinal symptoms (P=0.004) and were less often screen detected (P=0.009). Further, they had higher celiac antibody values (P=0.007) and a lower total iron (P

GOALS We analyzed from our prospectively collected series of patients with dermatitis herpetiformis (DH) whether small-bowel histologic findings are changing and how serum tissue transglutaminase (TG2) IgA antibodies correlate to mucosal damage. BACKGROUND DH is an extraintestinal manifestation of celiac disease presenting with itchy blistering rash and pathognomonic IgA deposits in the skin. Prominent gastrointestinal symptoms are rare, and small-bowel findings range from severe villous atrophy (SVA) and partial villous atrophy (PVA) to normal mucosa with inflammatory changes. METHODS The cohort included 393 patients (214 male and 179 female) with DH having small-bowel biopsies performed at Tampere University Hospital since 1970. The small-bowel findings were calculated in the three 15-year periods, and in the last period they were correlated with serum IgA class TG2 antibody levels measured by enzyme-linked immunosorbent assay. RESULTS The prevalence of SVA decreased significantly (P=0.032), from 42% in the first study period to 29% in the last study period. A concomitant increase was seen in PVA, from 33% to 41%, and normal villous architecture, from 25% to 30%. The patients with SVA (P

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease. The burden of illness in untreated coeliac disease is known to be considerable, but corresponding evidence for DH is lacking. In this study the burden of DH was evaluated prospectively in 52 patients newly diagnosed with DH using a study questionnaire and a validated Psychological General Well-Being (PGWB) questionnaire. The PGWB scores were compared with those of 110 healthy controls. Quality of life was significantly (p < 0.001) lower among patients with DH at the time of diagnosis, but after 1 year on a gluten-free diet their quality of life was at same level as that of the controls. The presence of gastrointestinal symptoms was shown to significantly increase the burden of untreated DH. We conclude that there is a significant burden related to untreated, but not to treated, DH, and the burden is even greater among DH patients with gastrointestinal symptoms.

Objectives: Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Bone fracture risk is increased in coeliac disease, but little knowledge exists about bone complic...

Dermatitis herpetiformis (DH) is an itchy blistering skin disease with predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by showing granular immunoglobulin A deposits in perilesional skin. DH is one manifestation of coeliac disease; the skin symptoms heal with gluten free diet (GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa; patients with DH have IgA-TG3 in the skin. There are some divergencies between these two phenotypes. One-fourth of DH patients do not have small bowel mucosal villous atrophy, but virtually all have coeliac-type inflammatory changes. The skin symptoms respond slowly to GFD. The incidence of coeliac disease is increasing, whereas the opposite is true for DH. A female predominance is evident in coeliac disease, while DH may be more common in males. Coeliac disease carries the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site may prevail. Adult coeliac disease carries a slightly increased elevated mortality risk, whereas in DH, the relative mortality rate is significantly decreased. Key messages Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease; both conditions are genetically determined and gluten-dependent. Gastrointestinal symptoms and the degree of villous atrophy are less obvious in dermatitis herpetiformis than in coeliac disease. Both show tissue transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa. In addition, TG3-targeted IgA antibodies are found in the skin of DH patients Both conditions carry an increased elevated risk of lymphoma, in coeliac disease small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell lymphoma at various sites. Coeliac disease is currently eight times more common that DH; the incidence of DH is decreasing in contrast to that of coeliac disease, where it is increasing.

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing.MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores.RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053).CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Background and Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH.

Background The revised paediatric criteria for coeliac disease allow omission of duodenal biopsies in symptomatic children who have specific serology and coeliac disease-associated genetics. It remains unclear whether this approach is also applicable for adults with various clinical presentations. Aim To evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for coeliac disease. Methods Three study cohorts comprised adults with high-risk clinical coeliac disease suspicion (n = 421), moderate-risk family members of coeliac disease patients (n = 2357), and low-risk subjects from the general population (n = 2722). Serological and clinical data were collected, and "triple criteria" for coeliac disease comprised transglutaminase 2 antibodies >10x the upper limit of normal, positive endomysium antibodies, and appropriate genetics without requirement of symptoms. The diagnosis was based on intestinal biopsy. Results The diagnosis of coeliac disease was established in 274 subjects. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria". All had histologically proven coeliac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 (33%) of all 274 newly diagnosed patients could have avoided biopsy, including 37% among high-risk, 20% among moderate-risk, and 48% among low-risk patients. No histological findings other than coeliac disease were found in the biopsies of "triple positive" subjects. Conclusions Coeliac disease can reliably and safely be diagnosed without biopsy in adults fulfilling the "triple criteria" regardless of the pre-test probability. Revised criteria would enable the number of endoscopies to be reduced by one-third.

Restorative proctocolectomy is the procedure of choice in the surgical treatment of ulcerative colitis. Functional outcome is the key result of surgery. The aim of this study was to evaluate the long term-functional outcome after the procedure.The study comprised 282 ulcerative colitis patients over 18 years of age who underwent restorative proctocolectomy between1985 and 2009. The median follow-up time was 13 years (range 4-28). Functional outcome of the pouch was evaluated by the disease-specific Öresland questionnaire with a score 0-15; 15 being the worst, and score8 considered well-functioning.The mean functional score was 5.5 (men 5.6, women 5.0). Seventy per cent of the patients had a well-functioning pouch. Those with poor function had had significantly more pouchitis than the patients with well-functioning pouches, 51.0 vs. 25.6% respectively (p = .001). No association was found between functional score and the time since the operation. In multiple regression analysis only the occurrence of pouchitis was associated with poor functional results.The functional results were good and remained stable in the majority of the patients. Pouchitis seemed to have a negative impact on the functional results. Elderly patients especially need careful planning and counselling before restorative proctocolectomy.

Antegrade colonic enemas are used in patients with colorectal dysfunction resistant to conservative therapy. A number of different operative techniques are applied, but their effectiveness is by and large unknown. We therefore evaluated the long-term usefulness of the left-sided percutaneous endoscopic gastrostomy (PEG) tube method in adult patients.Twenty-one patients with colorectal dysfunction underwent insertion of a PEG tube colostomy by laparotomy between 1997 and 2006. In 2014, we evaluated how many of the patients had the tube still in place, how the patients coped with the tube, and what the reasons for the removal were.The main indications were severe constipation or fecal incontinence mainly related to neurological diseases. In 2014, 5 out of 21 patients had the tube still in use (median follow-up 14 years, range 11-17 years) and 4 out of 5 deceased patients had had the tube in use until their death, unrelated to this treatment (median follow-up 7 years, range 0-8 years). Four out of the 5 living patients considered the benefit of the tube to be good or excellent. Tubes were removed in 11 (52%) patients for various reasons, local skin irritation being the most common.A left-sided PEG tube colostomy was removed in over half of the patients, but despite that, it still seems to be a viable long-term option in the treatment of individual patients with colorectal dysfunction, when conservative methods are ineffective.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of celiac disease. Both conditions are treated with a restrictive life-long gluten-free diet (GFD). Treated celiac disease patients have been shown to have more severe gastrointestinal symptoms and inferior quality of life compared with healthy controls, but evidence regarding quality of life in DH is lacking. The aim was to evaluate whether long-term GFD-treated DH patients suffer from persistent gastrointestinal symptoms and if they experience a drawdown in quality of life. Gastrointestinal symptoms and quality of life were assessed in 78 long-term GFD-treated DH patients using the validated Gastrointestinal Symptom Rating Scale, Psychological General Well-Being and Short Form 36 Health Survey questionnaires. The findings were compared with 110 healthy controls, population-based reference values and 371 treated celiac disease controls. The median age of the DH patients at the time of the study was 57 years, and 51 % were male. Significant differences in gastrointestinal symptoms or quality of life were not detected when treated DH patients were compared with healthy controls, but treated DH patients had less severe gastrointestinal symptoms and increased quality of life compared with celiac disease controls. Female DH patients had more severe gastrointestinal symptoms and reduced vitality compared with male DH patients. The presence of skin symptoms and the adherence to or duration of GFD did not have any influence on gastrointestinal symptoms or quality of life. We conclude that long-term GFD-treated DH patients do not suffer from the burden of dietary treatment and have a quality of life comparable to that of controls.

In celiac disease, a follow-up biopsy taken 1 year after diagnosis is considered important in monitoring histological recovery. In many cases, recovery is incomplete, and the clinical significance of this is poorly understood. We now investigated associated factors and the significance of imperfect histological recovery in patients in whom the follow-up had been completed.Two hundred sixty-three biopsy-proven patients were divided into two groups: histological recovery and incomplete recovery after 1 year on gluten-free diet. Serology, laboratory values, bone mineral density, and different clinical variables were measured at diagnosis and after 1 year. Gastrointestinal symptoms and quality of life were assessed by validated questionnaires. Further, long-term follow-up data on mortality, malignancies, and other severe complications were collected.The incomplete recovery group had more severe mucosal damage (P=0.003), higher antibody values (P=0.017), and more signs of malabsorption (P0.001) at diagnosis. There was no difference in gender, symptoms or quality of life, family history of celiac disease, or comorbidities. At follow-up, there was still a difference in antibodies (P=0.018) and femoral T-scores (P=0.024). Histologically recovered patients showed better dietary adherence, although it was excellent in both groups (97% vs. 87%, P0.001). There was no difference in long-term outcomes between groups.The presence of more severe disease in terms of histology, serology, and signs of malabsorption was associated with histological non-response. In patients with high dietary adherence, incomplete villous recovery after 1 year does not affect the clinical response or long-term prognosis. A personalized approach is required to decide the optimal timing of the follow-up biopsy.

Background and Aims: Restorative proctocolectomy is the most common operation in patients with ulcerative colitis. The aim was to evaluate long-term changes in our operative treatment and early and late complications related to restorative proctocolectomy. Material and Methods: The study comprised 352 (149 females) patients over 18 years of age with ulcerative colitis who underwent restorative proctocolectomy in 1985–2009 median follow-up time of 5 years. Results: The indication for surgery was active chronic colitis in 168 (47.7%), acute colitis in 159 (45.2%), and cancer or dysplasia in 25 (7.1%) patients. Ileal pouch-anal anastomosis was performed using hand-sewn anastomosis with mucosectomy in 283 patients and stapled anastomosis in 69. A shift from hand-sewn to stapler ileal pouch-anal anastomosis took place in 2005. Covering ileostomy was carried out in 133 (37.8%) patients. There were 82 (23.3%) J-pouch-related complications. The operative mortality was 0.3%. There were significantly fewer leakages and early re-operations when covering ileostomy was used than when it was omitted: 6.0% versus 16.4% (p = 0.004), 4.5% versus 11.9% (p = 0.02), respectively. There were more strictures in hand-sewn than in stapled ileal pouch-anal anastomoses (17.6% vs. 0%, p = 0.001). Pouchitis occurred at least once in 134 (38.1%) patients. Conclusion: The ileal pouch-anal anastomosis technique used in restorative proctocolectomy had changed over the past years from hand-sewn to stapled anastomosis. Covering ileostomy seemed to protect against major complications. Pouchitis was the most common late complication.

Liver mass lesions are often detected incidentally. Subsequent imaging examinations and surveillance are not only expensive, but may also cause unnecessary concern to patients. The aim of this study was to evaluate retrospectively the possible delay in acquiring the diagnosis of liver mass lesions, and to estimate the number of imaging examinations performed during the diagnostic workup.The study comprised 200 patients with liver mass lesion of unknown etiology. The time needed from referral to final diagnosis was assessed. All imaging examinations and biopsy findings (if available) during the diagnostic workup were recorded.Out of the 200 lesions, 133 were malignant, 65 with hepatocellular cancer and 26 with cholangiocarcinoma. All except one were diagnosed within 8 weeks. Of the 67 benign lesions, there were 20 focal nodular hyperplasias and 20 hemangiomas. For the benign lesions, in 37% the diagnostic workup took8 weeks. Repeated examinations were more common in benign lesions; but often redundant in both benign and malignant conditions in retrospect analysis.To confirm the diagnosis, benign lesions required more follow-up time and more repeated imaging examinations than malignant ones. A long surveillance for liver mass lesions in fear of malignancy seems not to be necessary, since virtually all malignant lesions were diagnosed within 8 weeks. Evaluating all lesions in a multidisciplinary team right from the beginning is advocated by a prospective study design.

Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease. The highest currently reported prevalence of DH is in Finland, but knowledge of diagnostic delay is limited. This study investigated the duration of rash prior to diagnosis in 446 patients with DH, analysing the results in 3 periods of 15 years. The diagnosis was considered delayed when the duration of rash before diagnosis was 2 years or longer. Factors associated with delayed diagnosis were analysed. Within the 45 years, the median duration of rash before diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000 were significantly associated with delayed diagnosis. In conclusion, the present study showed that one-quarter of patients currently have a diagnostic delay of 2 years or more, which is far from ideal.

An increased incidence of thrombosis is suggested in celiac disease. We explored serum levels of antiphospholipid antibodies in untreated and treated adult celiac disease patients.A cohort of 179 biopsy-proven celiac disease patients (89 untreated, 90 on long-term gluten-free diet) and 91 non-celiac controls underwent clinical examination, assessment of celiac serology and enzyme immunoassay testing for anticardiolipin IgG and IgM, prothrombin IgG, and phosphatidylserine-prothrombin IgG and IgM.The level of antiphospholipid antibodies was higher in celiac disease patients compared with controls: anticardiolipin IgG 4.9 (0.7-33.8) vs 2.2 (0.4-9.6) U/ml, antiprothrombin IgG 2.9 (0.3-87.8) vs 2.1 (0.5-187.0) U/ml, antiphosphatidylserine-prothrombin IgG 6.9 (0.0-54.1) vs 2.3 (0.5-15.1) U/ml; p 0.05 for all. Anticardiolipin IgG, antiprothrombin IgG and antiphosphatidylserine-prothrombin IgG were higher in treated compared with untreated patients. The phenotype of celiac disease at presentation (gastrointestinal symptoms, malabsorption or anemia, and extraintestinal symptoms or screen-detected disease) had no effect on the level of serum antiphospholipid antibodies.The serum level of antiphospholipid antibodies is increased in adults with celiac disease. The higher level of antibodies in treated patients suggests that the increase is not gluten-dependent. The prothrombotic role of antiphospholipid antibodies in celiac disease warrants further studies.

Background The presenting symptoms of coeliac disease are often subtle and the diagnosis is frequently delayed or overlooked. Therefore, especially elderly patients may be denied the benefits conferred by gluten free diet which can be dramatically life-changing. Aim To review the occurrence, clinical features, diagnosis and management in coeliac patients detected later in life. Methods To review manuscripts concerned with coeliac disease in the elderly and to derive subgroups of elderly people from publications on the disorder. Results Approximately a quarter of all diagnoses are now made at the age of 60 years or more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or above. Around 60% remain undetected, since their symptoms are often subtle: tiredness, indigestion, reduced appetite. Good compliance with gluten free diet, resolution of symptoms and improvement in laboratory indices can be achieved in over 90% of patients. Conclusions Coeliac disease not uncommonly presents for the first time in older patients and is an important diagnosis to make.

Background and aims: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort.Methods: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria.Results: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed.Conclusions: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

Background: Ward rounds serve as a forum for sharing information between the patient and health care professionals. In order to ensure the multiprofessional nature of the rounds, the nurse’s expertise and knowledge of the patient’s situation is needed. The nurse’s presence during the ward rounds is necessary to ensure patient satisfaction and the quality of the patient’s treatment, even though nurses rarely participate in discussions during the ward rounds. Aim: To describe how active nurses are as discussion openers during ward rounds and to compare the activity of nurses working in different specialities as discussion openers, in addition to investigating the significance of background factors. Methods: The data were collected in a Finnish university hospital in 2012-2013 by observing ward round situations with patients (N=365) on different speciality wards using an observation form. Results: The nurses were fairly passive in initiating discussions about the patient’s physical status and passive in opening a discussion on the patient’s psychological status. The nurses were passive in opening discussions concerning the planning or evaluation of the patient’s treatment. Nurses specializing in gastric surgery or internal medicine in gastroenterology initiated discussions more actively than nurses in other specialties. Nurses opened discussions more often in the context of emergency care patients than in connection with patients who had arrived at the hospital for an elective procedure. Conclusion: Nurses should use their expertise in opening discussions on the patient’s physical and psychological state, as well as decision-making regarding the planning and evaluation of treatment. Support from managers in different professional groups is important for increasing the participation of nurses during ward rounds. In the future, it would be interesting to study the shared experience of nurses, physicians and patients regarding the ward rounds, as well as the patients’ own experiences.

Altered Duodenal Microbiota Composition in Celiac Disease Patients Suffering From Persistent Symptoms on a Long-Term Gluten-Free Diet

The association between celiac disease and malignancies is well recognized. In Finland, the prevalence of clinically diagnosed adult celiac disease is 0.6%. In this large, population-based cohort, we aimed at a realistic projection of the cancer risk.In the period 2002-2011, the register comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer Registry, which covers over 98% of diagnosed malignancies. The standardized incidence ratio (SIR) was calculated for the malignancies, on the basis of incidence figures for the whole population. A time-stratified analysis was made in celiac patients diagnosed after 2004 (n=11,991). Lifestyle factors, including smoking habits and obesity, were not obtainable.The overall incidence ratio of malignant diseases was not increased (SIR 0.94; 95% confidence intervals 0.89-0.98), but it was ≥5 years from the diagnosis of celiac disease (1.31, 1.04-1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62-2.29), small-intestinal cancer (4.29; 2.83-6.24), colon cancer (1.35; 1.13-1.58), and basal cell carcinoma of the skin (1.13; 1.03-1.22) were increased, whereas those for lung cancer (0.60; 0.48-0.74), pancreatic cancer (0.73; 0.53-0.97), bladder cancer (0.53; 0.35-0.77), renal cancer (0.72; 0.51-0.99), and breast cancer (0.70; 0.62-0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37-4.38).There was no increased SIR of cancer in the whole series, but SIR was increased after 5 years from the diagnosis of celiac disease. The risk of breast and lung cancers was decreased. The risk of small-intestinal cancer and NHL was increased, but to a lesser extent than previously described.

Here, we investigated the factors associated with long diagnostic delay in celiac disease and the impact of the national Current Care Guidelines in reducing the delay.This population-based study involved 825 adult celiac disease patients. The diagnosis was considered delayed when the interval between first symptoms and diagnosis was10 years. The patients were asked about the duration and type of symptoms before diagnosis, time and site (tertiary, secondary, or primary care) of the diagnosis, family history of the disease, and presence of significant comorbidities. Analysis was performed by binary logistic regression.Altogether, 261 (32%) out of 825 participants reported a diagnostic delay of10 years. Female gender, neurological or musculoskeletal disorders and presence of diarrhea, abdominal pain, and malabsorption were associated with prolonged delay. Male gender, diagnosis after the introduction of the first Current Care Guidelines in 1997, and being detected by serological screening, and family history of celiac disease were associated with a lower risk of delayed diagnosis. Factors not associated with the delay were site of diagnosis, age, and presence of dermatitis herpetiformis, type 1 diabetes, or thyroidal disease.The number of long diagnostic delays in celiac disease has decreased over the past decades. The shift of diagnostics from secondary and tertiary care to primary care has not been detrimental. National guidelines together with increased awareness and active screening in at-risk groups of celiac disease are important in these circumstances.

Background and Aims: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. Methods: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1. million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. Results: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p.

The aim of the study was to determine the alterations in the occurrence of incontinence and how subjects suffering from incontinence seek and receive healthcare services over a 10-year follow-up period.Postal questionnaires (Wexner Incontinence Score, Fecal Incontinence Quality of Life Scale, a questionnaire to investigate the management of fecal incontinence and the frequency of urinary incontinence) were sent to subjects who had reported anal incontinence in our population-based study in 2003. For each incontinent person (n = 155) from the 2003 series, we identified two control subjects (n = 310) who did not suffer from incontinence.Of the initially incontinent, 47 (58%) had remained incontinent after a follow up of 10 years. Almost 80% of the incontinent subjects in 2012 were female. Of the 152 initially continent, 12 (7.9%) had developed symptoms, all of whom were females. Urinary incontinence was present in approximately 60% of incontinent subjects. The majority (57.8%) of the subjects still incontinent in 2012 felt that they needed help for the complaint, but only 30.9% had received any, and only 7.4% received any benefit. The most common treatment was medication. The subjective incontinence impaired the quality of life.Incontinence is a chronic long-lasting disorder. The current management of anal incontinence is not satisfactory. The primary healthcare system should be more aware of the nature of this condition to find and offer treatment for the patients.

Summary Background Histologically nonresponsive coeliac disease (NRCD) is a potentially serious condition diagnosed during the follow-up of coeliac disease (CD) when patients have persistent villous atrophy despite following a gluten-free diet (GFD). Aim As current assessments of recovery are limited to invasive and costly serial duodenal biopsies, we sought to identify antibody biomarkers for CD patients that do not respond to traditional therapy. Methods Bacterial display peptide libraries were screened by flow cytometry to identify epitopes specifically recognised by antibodies from patients with NRCD, but not by antibodies from responsive CD patients. Deamidated gliadin was confirmed to be the antigen mimicked by library peptides using ELISA with sera from NRCD (n = 15) and responsive CD (n = 45) patients on a strict GFD for at least 1 year. Results The dominant consensus epitope sequence identified by unbiased library screening QPxx(A/P)FP(E/D) was highly similar to reported deamidated gliadin peptide (dGP) B-cell epitopes. Measurement of anti-dGP IgG titre by ELISA discriminated between NRCD and responsive CD patients with 87% sensitivity and 89% specificity. Importantly, dGP antibody titre correlated with the severity of mucosal damage indicating that IgG dGP titres may be useful to monitor small intestinal mucosal recovery on a GFD. Conclusions The finding of increased levels of anti-dGP IgG antibodies in CD patients on strict GFDs effectively identifies patients with NRCD. Finally, anti-dGP IgG assays may be useful to monitor mucosal damage and histological improvement in CD patients on a strict GFD.

Summary Background Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. Aim We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. Methods The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. Results The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of coeliac disease. Untreated coeliac disease patients are known to have transglutaminase 2 (TG2)-targeted IgA deposits in the small bowel mucosa. To evaluate whether similar intestinal IgA deposits are also present in DH and whether the deposits disappear with gluten-free diet, 47 untreated and 27 treated DH patients were studied. Seventy-nine percent of untreated and 41% of the treated DH patients had TG2-specific IgA deposits in the small bowel, and the presence of the deposits showed a significant association with the degree of small bowel villous atrophy (p < 0.001). Other coeliac-disease related inflammatory markers were also investigated, and the density of small bowel mucosal intraepithelial γδ(+) T cells was increased in 91% of untreated and 73% of treated DH patients. The results show that the majority of untreated DH patients have similar gluten-dependent TG2-specific IgA deposits the small bowel mucosa as coeliac disease patients.

Background and aims: Data on the relative risk of colorectal cancer in inflammatory bowel diseases (IBD) are inconsistent. To prevent the development of cancer, endoscopic facilities should be targeted correctly. We report here the results of a 20-year follow-up in Finland and evaluate the efficacy of endoscopic surveillance in cancer prevention. Methods: The data were based on an IBD register in our catchment area in 1986–2007. The population-based cohort comprised 1915 patients, 1254 with ulcerative colitis, 550 with Crohn's disease and 111 with inflammatory bowel unclassified. Colorectal cancer cases were obtained from the IBD register; the colorectal cancer figures in the respective population were obtained from the Finnish Cancer Registry. Results: Colorectal cancer was found in 21 patients, the standardized incidence ratio (SIR) being 1.83 (95% confidence interval (CI) 1.13–2.79) for IBD. Colorectal cancer risk was 3.09 (CI 1.50–5.75) for extensive UC, and 3.62 (CI 2.00–11.87) for Crohn's disease affecting the colon. Eleven (52%) of the colorectal cancer cases were TNM stage 3 or 4. In the same observation period 10 colectomies with ileoanal anastomosis were performed with the indication of cancer risk in ulcerative colitis; of these 10 patients only two had no additional risk factors for colorectal cancer, for example primary sclerosing cholangitis, pseudopolyposis or active disease. Conclusions: The risk of colorectal cancer in the cohort was only moderately increased. In the absence of additional risk factors, endoscopic surveillance was of limited benefit. We therefore suggest intensive endoscopy surveillance to be targeted on patients with definite risk factors.

Background Celiac disease is classically manifested in the gastrointestinal (GI) tract but extraintestinal symptoms, such as dermatitis herpetiformis (DH), are also common. Besides several well-known shared genetic risk factors and an environmental trigger, gliadin, factors determining the clinical outcome of the disease are not known. In this study, the role of duodenal microbiota in the celiac disease outcome was studied by analyzing mucosa-associated microbiota in celiac disease patients with a variety of intestinal and extraintestinal symptoms. Methods Microbiota in duodenal biopsy samples obtained from 33 patients with celiac disease with GI, DH, anemia, or mixed symptoms, as well as screen-detected asymptomatic celiac disease and 18 control subjects were analyzed using PCR denaturing gradient gel electrophoresis and a subset of samples additionally by the 16S ribosomal RNA gene sequencing. Results The composition and diversity of mucosal microbiota was associated with the manifestation of celiac disease when analyzed using PCR denaturing gradient gel electrophoresis and the 16S ribosomal RNA gene sequencing. The patients with celiac disease with GI symptoms or anemia had lower microbial diversity than those with DH. Moreover, the patients with GI symptoms had different intestinal microbiota composition and structure, dominated by Proteobacteria, in comparison to those with DH or control subjects (patients with dyspepsia). The relatively similar intestinal microbiota composition in the control subjects and those with DH was characterized by the high abundance of Firmicutes. Conclusions The two common outcomes of celiac disease, classical GI and extraintestinal manifestations, had marked differences on the diversity and composition of intestinal microbiota. This association suggested that intestinal microbiota may have a role in the manifestation of the disease.

The aim was to evaluate the effects of anterior sphincter repair on faecal incontinence and quality of life.Fifty-six patients who underwent anterior anal sphincteroplasty between January 2003 and December 2005 were asked to complete questionnaires containing the Wexner Incontinence Score (a score of 0 corresponds to full continence and 20 to total incontinence) and Faecal Incontinence Quality of Life Scale preoperatively, in May 2006 (mean follow-up time, 22.8 months) and in August 2011 (mean follow-up time, 89.3 months). Thirty-nine (69.6 %) patients completed the questionnaires before the operation and in 2006, and 36 (64.3 %) in 2011.The overall severity of faecal incontinence improved in 26 patients (67 %), and quality of life improved in 2006 as a whole, but after a longer follow-up (in 2011), the severity of faecal incontinence was about the same as preoperatively (median, 12.0 months) in all the patients. Among younger patients (≤50 years), the situation was better, but older patients (50 years) had an even worse situation than before the operation. In the group of younger patients, the preoperative median of the overall incontinence score was 10.5, and in 2011, it was 9.0, while in the group of older patients, the corresponding numbers were 13.0 and 15.0. In 2011, quality of life was still better than preoperatively as a whole, but the results had deteriorated from those in 2006.Initially, both overall faecal incontinence and quality of life improved, but younger patients achieved a greater benefit. However, the results deteriorated with a longer follow-up. Operative management should be considered preferably in relatively young subjects as their results are better.

Association between celiac disease and type 1 diabetes in adults is still somewhat unclear, and that between celiac disease and type 2 diabetes even less known. We studied these issues in a large cohort of adult celiac disease patients. METHODS: The prevalence of type 1 and type 2 diabetes in 1358 celiac patients was compared with the population-based values. Furthermore, patients with celiac disease and concomitant type 1 or type 2 diabetes and those with celiac disease only underwent comparisons of clinical and histological features and adherence to gluten-free diet. RESULTS: The prevalence of type 1 diabetes (men/women) was 8.0 % /1.8 % in celiac patients and 0.7 % /0.3 % in the population, and that of type 2 diabetes 4.3 % /2.5 % and 4.4 % /3.0 %, respectively. Celiac patients with concomitant type 1 diabetes were younger (45 years vs 65 years and 52 years, P