Publications by authors named "Pekka Collin"

139 Publications

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids.

Scand J Gastroenterol 2021 Mar 26;56(3):234-238. Epub 2021 Jan 26.

Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.

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.
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http://dx.doi.org/10.1080/00365521.2020.1867892DOI Listing
March 2021

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

United European Gastroenterol J 2020 10 26;8(8):949-960. Epub 2020 Jul 26.

Hull University Teaching Hospitals NHS Trust, Hull, UK.

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.
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http://dx.doi.org/10.1177/2050640620945949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707880PMC
October 2020

Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century.

Am J Gastroenterol 2020 07;115(7):1117-1124

Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

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.
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http://dx.doi.org/10.14309/ajg.0000000000000665DOI Listing
July 2020

Pouch failures following restorative proctocolectomy in ulcerative colitis.

Int J Colorectal Dis 2020 Nov 26;35(11):2027-2033. Epub 2020 Jun 26.

Faculty of Medicine and Health Technology, Tampere University, P.O. Box 100, FI-33014, Tampere, Finland.

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.
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http://dx.doi.org/10.1007/s00384-020-03680-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541371PMC
November 2020

Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study.

Lancet Gastroenterol Hepatol 2020 05 13;5(5):454-464. Epub 2020 Feb 13.

Hull University Teaching Hospitals NHS Trust, Hull, UK; Hull York Medical School, Hull, UK.

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 (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001).

Interpretation: 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.
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http://dx.doi.org/10.1016/S2468-1253(20)30012-1DOI Listing
May 2020

Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study.

Lancet Gastroenterol Hepatol 2019 12 4;4(12):960-970. Epub 2019 Sep 4.

Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Medical Centre, Amsterdam, Netherlands.

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.
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http://dx.doi.org/10.1016/S2468-1253(19)30265-1DOI Listing
December 2019

Risk of fractures in dermatitis herpetiformis and coeliac disease: a register-based study.

Scand J Gastroenterol 2019 Jul 7;54(7):843-848. Epub 2019 Jul 7.

Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University , Tampere , Finland.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Bone fracture risk is increased in coeliac disease, but little knowledge exists about bone complications in DH. This study aimed to evaluate the risk of hip and other hospital-treated fractures in DH and coeliac disease in a high prevalence area with good adherence to a gluten-free diet. Hip, proximal humerus, wrist and ankle fractures in 368 treated DH and 1076 coeliac disease patients between 1970 and 2015 were reviewed from the National Hospital Discharge Register. Hip fracture incidence rates for DH and coeliac disease patients were compared to those for the general population. The overall fracture risk for DH was compared to coeliac disease. The hip fracture incidence rates for DH and coeliac disease patients did not differ from the general population. In females aged 80-89, the hip fracture incidence was higher in DH than in coeliac disease, but the risk for any hospital-treated fracture was lower in DH compared to coeliac disease (adjusted HR 0.620, 95% CI 0.429-0.949). The DH and coeliac disease patients with hospital-treated fractures were diagnosed at an older age, but the degree of small bowel mucosal damage did not significantly differ between patients with and without fractures. The incidence of hip fracture is not increased in treated DH or coeliac disease in an area with high awareness and dietary compliance rates. However, patients with DH seem to have a lower risk for fractures overall compared to coeliac disease.
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http://dx.doi.org/10.1080/00365521.2019.1636132DOI Listing
July 2019

Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities.

Aliment Pharmacol Ther 2019 02 27;49(3):277-284. Epub 2018 Dec 27.

Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

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 >10× 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.
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http://dx.doi.org/10.1111/apt.15109DOI Listing
February 2019

Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort: An Epi-IBD study.

J Gastroenterol Hepatol 2019 Jun 21;34(6):996-1003. Epub 2019 Jan 21.

Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.

Background And Aim: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years.

Methods: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period.

Results: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.

Conclusions: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
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http://dx.doi.org/10.1111/jgh.14563DOI Listing
June 2019

Long-term functional outcome after restorative proctocolectomy: a cross-sectional study.

Scand J Gastroenterol 2018 Oct - Nov;53(10-11):1245-1249. Epub 2018 Oct 22.

c School of Medicine , University of Tampere , Tampere , Finland.

Objective: 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.

Material And Methods: 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 score <8 considered well-functioning.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1080/00365521.2018.1518479DOI Listing
April 2019

Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study.

J Crohns Colitis 2019 Feb;13(2):198-208

IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.

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.
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http://dx.doi.org/10.1093/ecco-jcc/jjy154DOI Listing
February 2019

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

Eur J Gastroenterol Hepatol 2018 11;30(11):1297-1303

Pekka Collin Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.

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.
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http://dx.doi.org/10.1097/MEG.0000000000001238DOI Listing
November 2018

Prognosis of Dermatitis Herpetiformis Patients with and without Villous Atrophy at Diagnosis.

Nutrients 2018 May 19;10(5). Epub 2018 May 19.

Department of Dermatology, Tampere University Hospital, 33521 Tampere, Finland.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. At diagnosis, the majority of patients have villous atrophy in the small bowel mucosa. The objective of this study was to investigate whether the presence or absence of villous atrophy at diagnosis affects the long-term prognosis of DH. Data were gathered from the patient records of 352 DH and 248 coeliac disease patients, and follow-up data via questionnaires from 181 DH and 128 coeliac disease patients on a gluten-free diet (GFD). Of the DH patients, 72% had villous atrophy when DH was diagnosed, and these patients were significantly younger at diagnosis compared to those with normal small bowel mucosa (37 vs. 54 years, < 0.001). Clinical recovery on a GFD did not differ significantly between the DH groups, nor did current adherence to a GFD, the presence of long-term illnesses, coeliac disease-related complications or gastrointestinal symptoms, or quality of life. By contrast, the coeliac disease controls had more often osteopenia/osteoporosis, thyroid diseases, malignancies and current gastrointestinal symptoms compared to the DH patients. In conclusion, villous atrophy at the time of DH diagnosis does not have an impact on the clinical recovery or long-term general health of DH patients.
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http://dx.doi.org/10.3390/nu10050641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986520PMC
May 2018

Dermatitis Herpetiformis: A Common Extraintestinal Manifestation of Coeliac Disease.

Nutrients 2018 May 12;10(5). Epub 2018 May 12.

Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 33521 Tampere, Finland.

Dermatitis herpetiformis (DH) is a common extraintestinal manifestation of coeliac disease presenting with itchy papules and vesicles on the elbows, knees, and buttocks. Overt gastrointestinal symptoms are rare. Diagnosis of DH is easily confirmed by immunofluorescence biopsy showing pathognomonic granular immunoglobulin A (IgA) deposits in the papillary dermis. A valid hypothesis for the immunopathogenesis of DH is that it starts from latent or manifest coeliac disease in the gut and evolves into an immune complex deposition of high avidity IgA epidermal transglutaminase (TG3) antibodies, together with the TG3 enzyme, in the papillary dermis. The mean age at DH diagnosis has increased significantly in recent decades and presently is 40⁻50 years. The DH to coeliac disease prevalence ratio is 1:8 in Finland and the United Kingdom (U.K.). The annual DH incidence rate, currently 2.7 per 100,000 in Finland and 0.8 per 100,000 in the U.K., is decreasing, whereas the reverse is true for coeliac disease. The long-term prognosis of DH patients on a gluten-free diet is excellent, with the mortality rate being even lower than for the general population.
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http://dx.doi.org/10.3390/nu10050602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986482PMC
May 2018

Self-Reported Fractures in Dermatitis Herpetiformis Compared to Coeliac Disease.

Nutrients 2018 Mar 14;10(3). Epub 2018 Mar 14.

Coeliac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, 33014 Tampere, Finland.

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 ( = 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.
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http://dx.doi.org/10.3390/nu10030351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872769PMC
March 2018

Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.

Gut 2019 03 23;68(3):423-433. Epub 2018 Jan 23.

IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.

Objective: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD).

Design: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

Results: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).

Conclusion: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.
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http://dx.doi.org/10.1136/gutjnl-2017-315568DOI Listing
March 2019

Elevated serum antiphospholipid antibodies in adults with celiac disease.

Dig Liver Dis 2018 May 2;50(5):457-461. Epub 2017 Dec 2.

Faculty of Medicine and Life Sciences, University of Tampere, and Department of Internal Medicine, Tampere University Hospital, Finland; Celiac Disease Research Center, University of Tampere, Finland.

Background And Aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.dld.2017.11.018DOI Listing
May 2018

Diagnostic Delay in Dermatitis Herpetiformis in a High-prevalence Area.

Acta Derm Venereol 2018 Feb;98(2):195-199

Department of Dermatology, Tampere University Hospital, PO Box 2000, FIN-33521 Tampere, Finland.

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.
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http://dx.doi.org/10.2340/00015555-2818DOI Listing
February 2018

Occurrence of Anaemia in the First Year of Inflammatory Bowel Disease in a European Population-based Inception Cohort-An ECCO-EpiCom Study.

J Crohns Colitis 2017 Oct;11(10):1213-1222

Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

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.
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http://dx.doi.org/10.1093/ecco-jcc/jjx077DOI Listing
October 2017

Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease.

Ann Med 2017 02 14;49(1):23-31. Epub 2016 Dec 14.

b Department of Dermatology , Tampere University Hospital , Tampere , Finland.

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.
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http://dx.doi.org/10.1080/07853890.2016.1222450DOI Listing
February 2017

Type 1 and type 2 diabetes in celiac disease: prevalence and effect on clinical and histological presentation.

BMC Gastroenterol 2016 Jul 25;16(1):76. Epub 2016 Jul 25.

Tampere Centre for Child Health Research, University of Tampere and Tampere University Hospital, Biokatu 10, 33520, Tampere, Finland.

Background: 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 < 0.001) and more often screen-detected (43 % vs 13 % and 14 %, P < 0.001), had less other gastrointestinal diseases (8 % vs 40 % and 25 %, P = 0.028), more thyroidal diseases (18 % vs 16 % and 13 %, P = 0.043) and lower dietary adherence (71 % vs 95 % and 96 %, P < 0.001) compared with celiac patients with concomitant type 2 diabetes and patients with celiac disease only. Patients with concomitant type 2 diabetes had more hypercholesterolemia than the other groups (8 % vs 6 % and 4 %, P = 0.024), and both diabetes groups more hypertension (47 % and 31 % vs 15 %, P < 0.001) and coronary artery disease (29 % and 18 % vs 3 %, P < 0.001) than the patients with celiac disease only.

Conclusions: Type 1 diabetes was markedly overrepresented in celiac disease, especially in men, whereas the prevalence of type 2 diabetes was comparable with the population. Concomitant type 1 or type 2 diabetes predisposes celiac patients to severe co-morbidities and type 1 diabetes also to poor dietary adherence.
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http://dx.doi.org/10.1186/s12876-016-0488-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960881PMC
July 2016

Gastrointestinal Symptoms in Celiac Disease Patients on a Long-Term Gluten-Free Diet.

Nutrients 2016 Jul 14;8(7). Epub 2016 Jul 14.

Centre for Child Health Research, University of Tampere and Tampere University Hospital, Tampere 33014, Finland.

Experience suggests that many celiac patients suffer from persistent symptoms despite a long-term gluten-free diet (GFD). We investigated the prevalence and severity of these symptoms in patients with variable duration of GFD. Altogether, 856 patients were classified into untreated (n = 128), short-term GFD (1-2 years, n = 93) and long-term GFD (≥3 years, n = 635) groups. Analyses were made of clinical and histological data and dietary adherence. Symptoms were evaluated by the validated GSRS questionnaire. One-hundred-sixty healthy subjects comprised the control group. Further, the severity of symptoms was compared with that in peptic ulcer, reflux disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Altogether, 93% of the short-term and 94% of the long-term treated patients had a strict GFD and recovered mucosa. Untreated patients had more diarrhea, indigestion and abdominal pain than those on GFD and controls. There were no differences in symptoms between the short- and long-term GFD groups, but both yielded poorer GSRS total score than controls (p = 0.03 and p = 0.05, respectively). Furthermore, patients treated 1-2 years had more diarrhea (p = 0.03) and those treated >10 years more reflux (p = 0.04) than controls. Long-term treated celiac patients showed relatively mild symptoms compared with other gastrointestinal diseases. Based on our results, good response to GFD sustained in long-term follow-up, but not all patients reach the level of healthy individuals.
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http://dx.doi.org/10.3390/nu8070429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963905PMC
July 2016

Clinical Characteristics and the Dietary Response in Celiac Disease Patients Presenting With or Without Anemia.

J Clin Gastroenterol 2017 May/Jun;51(5):412-416

*School of Medicine ‡School of Health Sciences §Tampere Centre for Child Health Research, University of Tampere Departments of †Internal Medicine #Gastroenterology and Alimentary Track Surgery ∥Tampere Centre for Child Health Research, Tampere University Hospital ¶The UKK Institute for Health Promotion Research, Tampere, Finland.

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<0.001), BMI (P=0.003), and density of mucosal γδ+ intraepithelial lymphocytes (P=0.033). After 1 year on a gluten-free diet, the anemia group had a lower mucosal villous height-crypt depth ratio (P=0.008) and BMI (P=0.050), and higher antibody values (P=0.012) and densities of CD3 (P=0.008) and αβ+ intraepithelial lymphocytes (P=0.022). There was no significant difference between the groups in their bone mineral density, Gastrointestinal Symptom Rating Scale and Psychological General Well-Being.

Conclusions: Celiac patients with anemia had more severe disease than nonanemic patients in terms of the serology and a lower BMI. Further, they evinced a slower histologic response to the dietary treatment. An early diagnosis and careful follow-up are important in these patients.
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http://dx.doi.org/10.1097/MCG.0000000000000556DOI Listing
April 2019

Gastrointestinal Symptoms Increase the Burden of Illness in Dermatitis Herpetiformis: A Prospective Study.

Acta Derm Venereol 2017 01;97(1):58-62

School of Medicine, University of Tampere, Tampere, Finland.

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.
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http://dx.doi.org/10.2340/00015555-2471DOI Listing
January 2017

The Decreasing Prevalence of Severe Villous Atrophy in Dermatitis Herpetiformis: A 45-Year Experience in 393 Patients.

J Clin Gastroenterol 2017 Mar;51(3):235-239

Departments of *Dermatology ¶Internal Medicine #Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital †School of Medicine, University of Tampere, Tampere ‡Unit of Primary Health Care, Helsinki University Central Hospital §Department of General Practice, University of Helsinki, Helsinki ∥Unit of Primary Health Care, Kuopio University Hospital, Helsinki and Kuopio, Finland.

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<0.001) and PVA (P=0.046) had significantly higher TG2 antibody levels than those with normal villous architecture.

Conclusions: This long-term study in patients with DH disclosed a significant decrease in the occurrence of SVA. Serum IgA TG2 antibody levels correlated to damage in the small bowel. The trend toward milder small-bowel histology in DH suggests that a similar pattern could occur in the pool of undiagnosed celiac disease from which DH develops.
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http://dx.doi.org/10.1097/MCG.0000000000000533DOI Listing
March 2017

Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis.

Dig Liver Dis 2016 Jun 9;48(6):632-7. Epub 2016 Mar 9.

School of Medicine, University of Tampere, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.

Background: Transglutaminase (TG)2 is the autoantigen in celiac disease, but also TG3 antibodies have been detected in the serum of celiac disease patients.

Aims: To investigate the correlations between serum TG3 antibodies and clinical and histological manifestations of celiac disease and to assess gluten-dependency of TG3 antibodies.

Methods: Correlations between serum TG3 antibody levels measured from 119 adults and children with untreated coeliac disease and the demographic data, clinical symptoms, celiac antibodies, histological data and results of laboratory tests and bone mineral densities were tested. TG3 antibodies were reinvestigated in 97 celiac disease patients after 12 months on a gluten-free diet (GFD).

Results: TG3 antibody titers were shown to correlate with the age at celiac disease diagnosis. Further, negative correlation with TG3 antibodies and intestinal γδ+ cells at diagnosis and on GFD was detected. Correlations were not detected with the clinical manifestation of celiac disease, TG2 or endomysial autoantibodies, laboratory values, severity of mucosal villous atrophy, associated diseases or complications. TG3 antibody titers decreased on GFD in 56% of the TG3 antibody positive patients.

Conclusion: Serum TG3 antibody positivity in celiac disease increases as the diagnostic age rises. TG3 antibodies did not show similar gluten-dependency as TG2 antibodies.
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http://dx.doi.org/10.1016/j.dld.2016.03.003DOI Listing
June 2016

Diagnosis for liver fibrosis - noninvasively.

Duodecim 2016;132(18):1714-8

Noninvasive tests are utilized in chronic liver diseases to assess excessive connective tissue. Blood tests such as the N-terminal peptide of procollagen (PIIINP) and APRI (ASAT/platelet count) measure the formation and degradation of connective tissue or liver function. Elastography (Fibroscan) is based on the propagation of ultrasound in liver tissue, accelerated by fibrosis: the results are more sensitive and accurate than those based on blood tests. Reliable detection of severe fibrosis and cirrhosis is possible with Fibroscan along with determining normal liver tissue.
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January 2018

Quality of Life and Gastrointestinal Symptoms in Long-Term Treated Dermatitis Herpetiformis Patients: A Cross-Sectional Study in Finland.

Am J Clin Dermatol 2015 Dec;16(6):545-52

School of Medicine, University of Tampere, Tampere, Finland.

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1007/s40257-015-0149-1DOI Listing
December 2015

Dermatitis Herpetiformis Refractory to Gluten-free Dietary Treatment.

Acta Derm Venereol 2016 Jan;96(1):82-6

Department of Dermatology, Tampere University Hospital and University of Tampere, FIN-33240 Tampere, Finland.

Dermatitis herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study documents for the first time refractory DH, in which the rash is non-responsive to a gluten-free diet, but the small bowel mucosa heals. This differs from refractory coeliac disease, in which the small bowel mucosa does not heal on a gluten-free diet.
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http://dx.doi.org/10.2340/00015555-2184DOI Listing
January 2016

Predictors and Significance of Incomplete Mucosal Recovery in Celiac Disease After 1 Year on a Gluten-Free Diet.

Am J Gastroenterol 2015 Jul 2;110(7):1078-85. Epub 2015 Jun 2.

1] Medical School, University of Tampere, Tampere, Finland [2] Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.

Objectives: 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.

Methods: 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.

Results: The incomplete recovery group had more severe mucosal damage (P=0.003), higher antibody values (P=0.017), and more signs of malabsorption (P<0.001) 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%, P<0.001). There was no difference in long-term outcomes between groups.

Conclusions: 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.
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http://dx.doi.org/10.1038/ajg.2015.155DOI Listing
July 2015