Pia Munkholm

Frequency of glucocorticoid resistance and dependency in Crohn's disease.

The outcome of the first steroid treatment course was prospectively studied in a regional cohort of 196 patients with Crohns disease diagnosed 1979-1987. The immediate outcome after 30 days, and the prolonged outcome 30 days after treatment had stopped, are described. In all 109 patients treatment was analysed. Complete remission was obtained in 48%, partial remission in 32%, and no response in 20% within 30 days of treatment. Among primary responders (complete and partial remission), 55% remained in prolonged response after treatment had finished, while 45% relapsed or could not be withdrawn from treatment within one year. Localisation of disease, age, sex or clinical symptoms did not significantly correlate with outcome, which can be summarised as prolonged steroid response in 44%, steroid dependency in 36%, and steroid resistant in 20% of the patients.

Familial Occurrence of Inflammatory Bowel Disease

BACKGROUND AND METHODS We assessed the familial occurrence of inflammatory bowel disease in Copenhagen County, where there has been a long-term interest in the epidemiology of such disorders. In 1987 we interviewed 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, asking whether their first- and second-degree relatives had this disorder. Ninety-six percent of the patients (504 with ulcerative colitis and 133 with Crohns disease) provided adequate information. RESULTS As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohns disease had a 10-fold increase in the risk of having the same disease as the patients, after standardization for age and sex. The risk of having the other of the two diseases was also increased, but less so, and the increase in the risk of having Crohns disease was not significant in the relatives of patients with ulcerative colitis. The risk of ulcerative colitis in first-degree relatives of patients with ulcerative colitis appeared to be virtually independent of the generation to which the first-degree relative belonged and of the sex of the patient and the relative. The risk of ulcerative colitis in first-degree relatives tended to be higher if the disease had been diagnosed in the patient before the age of 50, but the risk seemed to be independent of the current age of the relatives. The prevalence of the same disease as that of the patient (either ulcerative colitis or Crohns disease) among second-degree relatives was increased; the prevalence of the other disease was not increased. CONCLUSIONS The 10-fold increase in the familial risk of ulcerative colitis and Crohns disease strongly suggests that these disorders have a genetic cause.

Colorectal cancer risk and mortality in patients with ulcerative colitis

A regional inception cohort of 1161 ulcerative colitis (UC) patients was followed up from diagnosis to the end of 1987. The follow-up rate for death and occurrence of cancer was 99.9% (median observation time, 11.7 years; range, 0-26 years). One hundred forty-one deaths were observed, 26 caused by UC or complications thereof. No significant excess mortality was found after the first year, but in the year of diagnosis the relative risk of death was 2.4 (P < 0.001). The cumulative colectomy rate 25 years after diagnosis was 32.4%. The initial extent of disease significantly influenced the colectomy probability, being 35% in total colitis, 19% in substantial colitis, and 9% in distal colitis within the first 5 years after diagnosis. Six patients developed colorectal cancer within the observation period. Compared with the expected number of 6.6, the relative risk for patients with UC was 0.9. The calculated cumulative cancer incidence was 3.1% after 25 years (95% confidence limits, 0.0-6.8). The calculated lifetime risk (0-74 years) for development of colorectal cancer was 3.5% for UC patients compared with 3.7% for the Danish population. It is concluded that with an active approach to medical and surgical treatment, as practiced here, patients whose colons are left intact bear no significantly increased risk of colorectal malignancy.

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.

European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations

This third section of the European Crohn’s and Colitis Organisation (ECCO) Consensus on the management of Crohn’s disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn’s disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn’s disease.

Increased Risk of Intestinal Cancer in Crohn's Disease: A Meta-Analysis of Population-Based Cohort Studies

OBJECTIVES:The risk of intestinal malignancy in Crohns disease (CD) remains uncertain since risk estimates vary worldwide. The global CD population is growing and there is a demand for better knowledge of prognosis of this disease. Hence, the aim of the present study was to conduct a meta-analysis of population-based data on intestinal cancer risk in CD.METHODS:The MEDLINE search engine and abstracts from international conferences were searched for the relevant literature by use of explicit search criteria. All papers fulfilling the strict inclusion criteria were scrutinized for data on population size, time of follow-up, and observed to expected cancer rates. STATA meta-analysis software was used to perform overall pooled risk estimates (standardized incidence ratio (SIR), observed/expected) and meta-regression analyses of the influence of specific variables on SIR.RESULTS:Six papers fulfilled the inclusion criteria and reported SIRs of colorectal cancer (CRC) in CD varying from 0.9 to 2.2. The pooled SIR for CRC was significantly increased (SIR, 1.9; 95% CI 1.4–2.5), as was the risk for colon cancer separately (SIR, 2.5; 95% CI 1.7–3.5). Regarding small bowel cancer, five studies reported SIRs ranging from 3.4 to 66.7, and the overall pooled estimate was 27.1 (95% CI 14.9–49.2).CONCLUSIONS:The present meta-analysis of intestinal cancer risk in CD, based on population-based studies only, revealed an overall increased risk of both CRC and small bowel cancer among patients with CD. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

Intestinal cancer risk and mortality in patients with Crohn's disease

BACKGROUND It is important to know about mortality, risk of intestinal cancer, and surgical intervention as well as possible predictive factors for patients with Crohns disease. These prognostic parameters were estimated by regular follow-up of a complete, regional incidence cohort of 373 patients. METHODS Annual assessments of clinical conditions were the basis for statistical evaluation with life table analysis, calculations of relative risk, and lifetime cancer risk. RESULTS Survival curves for the total group of patients with Crohns disease and the background population did not differ. However, a subgroup of patients aged 20-29 years at diagnosis (P = 0.04) and a subgroup of patients with extensive small bowel disease (P = 0.03) showed slightly increased mortality within the first 5 years. Cancer in small and/or large bowel occurred in 3 patients vs. an expected 1.8(P = NS). Small bowel cancer was found in 2 patients vs. the 0.04 expected (P = 0.001). Lifetime risk of intestinal cancer was 4.1% compared with 3.8% for the Danish population in general (P = NS). Probability of surgical resection within 15 years after diagnosis was 70%. The initial extent of disease significantly influenced the probability for resection, which was 78% in ileocecal enteritis and 44% in all other localizations within 5 years after diagnosis. CONCLUSIONS The overall mortality and life-time risk of cancer in patients with Crohns disease was not found increased, although the risk of rare small bowel cancer was significantly increased.

Development of the Crohn's disease digestive damage score, the Lemann score.

Crohns disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohns disease (IPNIC) group. This instrument, called the Crohns Disease Digestive Damage Score (the Lémann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be “diagnostic modality driven”: for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lémann score is expected to be able to portray a patients disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage. (Inflamm Bowel Dis 2011)

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES:The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a “treat-to-target” clinical management strategy using an evidence-based expert consensus process.METHODS:A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7–10 on a 10-point rating scale (where 10=agree completely).RESULTS:The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn’s disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0–1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target.CONCLUSIONS:Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients’ quality of life.

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.