Ida Vind

Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen City and County, 2003-2005 : A population-based study from the danish crohn colitis database

OBJECTIVES:A continuous increase in the incidence of inflammatory bowel disease (IBD), Crohns disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC) has been suggested. Since Denmark provides excellent conditions for epidemiological research, we aimed to describe contemporary IBD incidence rates and patient characteristics in Copenhagen County and City.METHODS:All patients diagnosed with IBD during 2003–2005 were followed prospectively. Demographic and clinical characteristics, such as disease extent, extraintestinal manifestations, smoking habits, medical treatment, surgical interventions, cancer, and death, were registered.RESULTS:Five-hundred sixty-two patients were diagnosed with IBD, resulting in mean annual incidences of 8.6/105 for CD, 13.4/105 for UC, and 1.1/105 for IC. Time from onset to diagnosis was 8.3 months in CD and 4.5 months in UC patients. A family history of IBD, smoking, and extraintestinal manifestations was significantly more common in CD than in UC patients. Only 0.6% of UC patients had primary sclerosing cholangitis. In CD, old age at diagnosis was related to pure colonic disease, whereas children significantly more often had proximal and extensive involvement. Twelve percent of CD patients and 6% of UC patients underwent surgery during the year of diagnosis, significantly less than earlier reported.CONCLUSIONS:The incidence of IBD in Copenhagen increased noticeably during the last decades. Time from onset of symptoms until diagnosis decreased markedly, extent of CD was related to age at diagnosis, and the risk of surgery was low in UC.

Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: A population‐based study from Copenhagen, Denmark

Background: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population‐based IBD cohorts from Copenhagen, Denmark (1962–2005), were assessed and evaluated. Methods: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohns disease (CD) and 1575 patients with ulcerative colitis (UC). Results: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07–1.60). Conclusions: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long‐term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long‐term prognosis.

Does pregnancy change the disease course? A study in a European cohort of patients with inflammatory bowel disease

BACKGROUND AND AIMS:Inflammatory bowel disease (IBD) often affects patients in their fertile age. The aim of this study was to describe pregnancy outcome in a European cohort of IBD patients. As data are limited regarding the effect of pregnancy on disease course, our second objective was to investigate whether pregnancy influences disease course and phenotype in IBD patients.METHODS:In a European cohort of IBD patients, a 10-yr follow-up was performed by scrutinizing patient files and approaching the patients with a questionnaire. The cohort comprised 1,125 patients, of whom 543 were women. Data from 173 female ulcerative colitis (UC) and 93 Crohns disease (CD) patients form the basis for the present study.RESULTS:In all, 580 pregnancies, 403 occurring before and 177 after IBD was diagnosed, were reported. The rate of spontaneous abortion increased after IBD was diagnosed (6.5% vs. 13%, p = 0.005), whereas elective abortion was not significantly different. 48.6% of the patients took medication at the time of conception and 46.9% during pregnancy. The use of cesarean section increased after IBD diagnosis (8.1% vs 28.7% of pregnancies). CD patients pregnant during the disease course, did not differ from patients who were not pregnant during the disease course regarding the development of stenosis (37% vs 52% p = 0.13) and resection rates (mean number of resections 0.52 vs 0.66, p = 0.37). The rate of relapse decreased in the years following pregnancy in both UC (0.34 vs 0.18 flares/yr, p = 0.008) and CD patients (0.76 vs 0.12 flares/yr, p = 0.004).CONCLUSIONS:Pregnancy did not influence disease phenotype or surgery rates, but was associated with a reduced number of flares in the following years.

Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

BACKGROUND YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek association between serum YKL-40 in patients with ulcerative colitis (UC) and Crohn disease (CD) and clinical disease activity. METHODS One-hundred-and-sixty-four patients with UC and 173 patients with CD were studied. The Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw (H-B) score were used to assess disease activity. Serum YKL-40 (determined by ELISA) was related to C-reactive protein (CRP) and disease activity. RESULTS In patients with UC, the median serum YKL-40 rose with increasing disease activity, and patients with severe active disease had higher serum YKL-40 (median 59 microg/L (95% CI: 26-258 microg/L), P < 0.001) than patients with inactive UC (33 microg/L (19-163)) and age-matched controls (43 microg/L (20-124)). Patients with severe active CD had higher serum YKL-40 (59 microg/L (21-654), P < 0.001) than age-matched controls, but not higher than inactive CD patients (43 microg/L (17-306)). Serum YKL-40 was elevated in 41% of the patients with severe UC, in 10% with inactive UC, in 46% with severe CD and in 30% with inactive CD. Serum YKL-40 correlated with SCCAI in UC patients but not with H-B score in CD patients. In both patient groups, low correlations were found between serum YKL-40 and CRP, albumin and leucocytes. CONCLUSIONS Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity.Background: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek association between serum YKL-40 in patients with ulcerative colitis (UC) and Crohn disease (CD) and clinical disease activity. Methods: One-hundred-and-sixty-four patients with UC and 173 patients with CD were studied. The Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw (H-B) score were used to assess disease activity. Serum YKL-40 (determined by ELISA) was related to C-reactive protein (CRP) and disease activity. Results: In patients with UC, the median serum YKL-40 rose with increasing disease activity, and patients with severe active disease had higher serum YKL-40 (median 59 r 7 g/L (95% CI: 26-258 r 7 g/L), P r < r 0.001) than patients with inactive UC (33 r 7 g/L (19-163)) and age-matched controls (43 r 7 g/L (20-124)). Patients with severe active CD had higher serum YKL-40 (59 r 7 g/L (21-654), P r < r 0.001) than age-matched controls, but not higher than inactive CD patients (43 r 7 g/L (17-306)). Serum YKL-40 was elevated in 41% of the patients with severe UC, in 10% with inactive UC, in 46% with severe CD and in 30% with inactive CD. Serum YKL-40 correlated with SCCAI in UC patients but not with H-B score in CD patients. In both patient groups, low correlations were found between serum YKL-40 and CRP, albumin and leucocytes. Conclusions: Serum YKL-40 is elevated in patients with active IBD and may be complementary to inflammatory markers and clinical characteristics in the assessment of disease activity.

Disease Course and Surgery Rates in Inflammatory Bowel Disease: A Population-Based, 7-Year Follow-Up Study in the Era of Immunomodulating Therapy

Objectives:In this population-based 7-year follow-up of incident patients with ulcerative colitis (UC) or Crohns disease (CD), we aimed to describe disease progression and surgery rates in an era influenced by the increased use of immunosuppressants and the introduction of biological therapy.Methods:From 1 January 2003 to 31 December 2004, all incident cases (562) of patients diagnosed with UC, CD, or inflammatory bowel disease unclassified in a well-defined Copenhagen area were registered. Medical records were reviewed from 1 November 2011 to 30 November 2012, and clinical data were registered. Clinical data on surgery, cancer, and death were cross-checked with register data from national health administrative databases in order to include missed data.Results:In total, 513 patients (213 CD and 300 UC) entered the follow-up study. Twenty-six patients changed diagnosis during the follow-up. Changes in disease localization and behavior in CD according to the Vienna classification were observed in 23.9% and 15.0% of the patients, respectively, during follow-up. In total, 28.3% of the 300 UC patients had disease progression during the follow-up. The overall use of systemic steroids, immunomodulators, and anti-tumor necrosis factor agents in CD was 86.4%, 64.3%, and 23.5%, respectively. The rate of first-time intestinal resection in CD was 29.1% (n=62), and the 7-year cumulative risk was 28.5%. The cumulative risk of colectomy in UC was 12.5% at 7 years.Conclusions:UC and CD are dynamic diseases that progress in extent and behavior over time. The resection rate in CD and the colectomy rate in UC are still relatively high, although the rates seem to have decreased compared with historic data, which could be due to an increase in the use of immunomodulating therapy.

The prevalence of genetic and serologic markers in an unselected European population-based cohort of IBD patients

Background and Aim: The aetiology of inflammatory bowel disease (IBD) is unknown, but it has become evident that genetic factors are involved in disease susceptibility. Studies have suggested a north–south gradient in the incidence of IBD, raising the question whether this difference is caused by genetic heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15 and TLR4 and occurrence of anti‐Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (pANCA) in a European population‐based IBD cohort. Methods: Individuals from the incident cohort were genotyped for three mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA were assessed. Disease location and behaviour at time of diagnosis was obtained from patient files. Results: Overall CARD15 mutation rate was 23.9% for CD and 9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7% in UC patients and 12.3% in healthy controls (HC), highest among South European CD patients and HC. ASCA was seen in 28.5% of CD patients with no north–south difference, and was associated with complicated disease. pANCA was most common in North European UC patients and not associated with disease phenotype. Conclusion: The prevalence of mutations in CARD15 varied across Europe, and was not correlated to the incidence of CD. There was no association between mutations in TLR4 and IBD. The prevalence of ASCA was relatively low; however related to severe CD.

Infliximab dependency in a national cohort of children with Crohn's disease.

Aim: The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohns disease (CD) treated in Denmark from 1999 to 2003. Material and Methods: The National Danish Crohn Colitis Database of infliximab was used to identify all Danish CD patients treated at pediatric departments with infliximab. The clinical outcome was assessed by pattern recognition of the disease course 30 days after the first infliximab infusion and 90 days after intended end of treatment. Results: During a 3 year period, infliximab was given to 24 CD patients (9 male/15 female) aged median 15.4 (range 9.8-18.6) years with a median disease duration of 26 (range 0.7-93) months and a median number of infusions of 6 (range 2-11). Five milligrams of infliximab per kilogram infusions were given intravenously. Immediate response was as follows: 8 (33%) patients achieved complete response (CR), 10 (42%) partial response (PR), and 6 (25%) no response (NR). Long-term response was as follows: 7 (29%) patients achieved prolonged response (PRO), defined as maintenance of CR or PR, 10 (42%) were infliximab dependent (ID), defined as relapse of symptoms requiring reinfusions of infliximab to regain CR or PR, and 6 (25%) had NR. Six (25%) patients needed surgery during or after treatment with infliximab. Side effects were seen in four (17%) patients. No serious events were noted. Conclusion: Seventy-one percent of the children appeared to benefit (PRO or ID) from infliximab treatment with minor side effects when given episodically. Among these patients, two response patterns were recognized: PRO after ending infliximab treatment (29%) or dependency on reinfusions of infliximab (42%).

Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease – a population-based study

Aliment Pharmacol Ther 2011; 34: 1217–1224

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: The ECCO-EpiCom cohort

Background:The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. Methods:Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). Results:In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn’s disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. Discussion:In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

Sweet’s Syndrome – An Extraintestinal Manifestation in Inflammatory Bowel Disease

Background/Aims: Sweet’s syndrome (SS) is a severe dermatosis that may be an extraintestinal manifestation of inflammatory bowel disease (IBD). Worldwide, 35 cases of SS associated with IBD have been reported. We present the first case of severe, recurrent SS in combination with amebic infection and ulcerative colitis complicated with multiple other extraintestinal manifestations. Methods: Disease course was monitored by serum YKL-40 and C-reactive protein (CRP), white blood cell count, albumin and the Simple Clinical Colitis Activity Index (SSCAI). The amebic infection was diagnosed by direct microscopy of wet mount scrapings sampled by repetitive sigmoidoscopies. Results: The patient was diagnosed with left-sided ulcerative colitis and SS combined with extraintestinal manifestations: arthropathies, iridocyclitis and erythema nodosum. Cysts of Entamoeba histolytica were detected in the stools in two separate periods of time. Serum YKL-40 increased prior to CRP and correlated with disease activity, SCCAI, CRP, white blood cell count and inversely with serum albumin. Conclusion: This case gives further support for SS being an extraintestinal manifestation of ulcerative colitis. YKL-40 may be useful in monitoring the disease course of IBD.