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: To determine the long-term risk of intestinal and extra-intestinal malignancies in Crohn's disease patients in Copenhagen County, Denmark. : In Copenhagen County, a strictly population-based cohort of 374 patients with Crohn's disease diagnosed between 1962 and 1987 was followed until 1997 in order to determine the long-term risk of intestinal and extra-intestinal malignancies. Information on cancer occurrence was provided by the Danish National Cancer Registry and confirmed by the examination of hospital files. The observed number of cases was compared with the expected number, calculated from individually computed person-years at risk and 1995 cancer incidence rates for the background population. : The risk of small bowel adenocarcinoma was significantly increased, independent of age and gender (standardized morbidity ratio, 66.7; 95% confidence interval, 18.1–170.7). The risk of colorectal cancer was not increased, either in the total group of patients or in patients with colonic Crohn's disease exclusively (standardized morbidity ratio, 1.64; 95% confidence interval, 0.20–5.92). Extra-intestinal cancer did not occur more frequently than expected. : This population-based study of patients with Crohn's disease revealed no increase in colorectal cancer risk, possibly due to maintenance treatment with 5-aminosalicylic acid preparations and surgery in treatment failure. In contrast, the risk of small bowel cancer was increased more than 60-fold, but the numbers were small. The risk of extra-intestinal cancer was not increased and no lymphomas were observed. [ABSTRACT FROM AUTHOR]

Background and Aims: The highest reported incidence rate of inflammatory bowel disease [IBD], and especially of ulcerative colitis [UC], is found in the Faroe Islands. This study aimed to assess the incidence rate and temporal trends in prevalence over six decades., Methods: All incident and prevalent patients diagnosed with IBD between 1960 and 2020 from the nationwide and population-based Faroese IBD cohort were included in this study. All patients fulfilled the Copenhagen Diagnostic Criteria., Results: Overall, 873 individuals were diagnosed with IBD during the study period, 559 [64%] with UC, 151 [17%] with Crohn's disease, and 163 [19%] with IBD unclassified. A total of 59 patients had paediatric-onset IBD. The incidence of IBD continued to increase throughout the study period, as the age-standardized incidence rate started at 8 per 100 000 person-years [py] [European Standard Population, ESP] in 1960-79 and reached 70 by 2010-20. In 2021, the age-standardized period prevalence was 1414 per 100 000 persons. The IBD incidence was unevenly distributed among the islands with Sandoy having the highest rate of 106 per 100 000 py in 2010-2020., Conclusions: The incidence of IBD continues to increase in the Faroe Islands, mainly driven by UC. The incidence shows an uneven geographical distribution, which suggests an adverse interaction between unknown environmental factors and genetic traits. The prevalence in 2021 corresponded to 1.3% of the Faroese population. Environmental risk factors are suspected to impact this homogeneous high-risk population; however, the reason for this is unclear., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Few studies have assessed the contemporary patterns of disease activity in patients with inflammatory bowel disease [IBD]. We aimed to describe the disease patterns and their long-term outcomes., Methods: All Danish individuals with IBD between 1995 and 2018 were identified using information about IBD-related hospitalizations, surgeries and redeemed prescriptions. The disease activity patterns for 5- and 10-year periods were assessed., Results: In incident patients with Crohn's disease [CD], severe disease activity occurred in the year of diagnosis in 80% of patients; for ulcerative colitis [UC] this figure was 75%, in addition to 3.4% of UC patients who underwent a colectomy within the first year. After 20 years of disease, the proportion of CD and UC patients in remission increased to 89% and 72%, respectively. The proportion of prevalent patients in remission each year was stable, despite the introduction of biological therapies. A decreasing activity pattern was the most common in both CD and UC patients [both 45%]. The distribution of the disease activity patterns was seen to be stable over time. A quiescent disease pattern was accompanied by a significantly higher risk of intestinal cancer [HR: 3.37, 95% CI: 1.23-9.19] for CD patients, according to a Cox proportional hazards model. In UC patients, increasing disease activity [HR: 0.67, 95% CI: 0.31-1.48] was associated with an increased risk of intestinal cancer., Conclusions: We report the distribution of disease patterns among IBD patients. Patients with quiescent CD, as well as UC patients with chronic continuous or increasing activity, were at increased risk of developing intestinal cancer., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Despite the increasing use of biologics in patients with inflammatory bowel disease (IBD), real-world data about outcomes in the era of biologics remain inconclusive., Aims: To investigate trends in surgeries, hospitalisations and medication use in patients with IBD in a multinational, population-based cohort METHODS: We included 42,894 patients with ulcerative colitis (UC) and 24,864 with Crohn's disease (CD) who were diagnosed between 2010 and 2017 in Denmark, Norway and Sweden. We extracted data about surgeries, hospitalisations and medications from national registries and compared across countries and diagnosis years., Results: Between 2010 and 2017, 2-year surgery rates were 4-7% in UC and 10-15% in CD and were stable over time. Two-year hospitalisation rates increased in Denmark (UC: 20% to 35%; CD: 27% to 32%) but were stable in Norway and Sweden (fluctuating between 33% and 37% in UC, and 46% and 52% in CD). Two-year rates of biologic use increased in both UC (7% to 16% in Denmark, 8% to 18% in Norway) and CD (22% to 26% in Denmark; 21% to 35% in Norway). Two-year rates of immunomodulator use increased in Norway (from 14% to 23% in UC; 37% to 45% in CD) and Sweden (from 41% to 52% in CD), but were stable in Denmark (between 17% and 21% in UC; 39% to 46% in CD)., Conclusion: Between 2010 and 2017, surgery rates among Scandinavian patients with IBD remained stable, with no clear changes in hospitalisation rates despite the increasing use of immunomodulators and biologics., (© 2022 John Wiley & Sons Ltd.)

Background: Long-term data on the natural disease course of unselected patients with ulcerative colitis (UC) are limited., Aims: To determine the long-term course and prognosis of UC, including patients' risks of surgery, cancer and mortality, in a population-based cohort followed for over 50 years METHODS: All incident patients with UC diagnosed between 1962 and 1987 in Copenhagen County, Denmark were included in a population-based cohort. We extracted information about IBD-related surgeries, cancers and mortality from patient files from 1962 to 1987, and from the Danish National Patient Registry, Cancer Registry, and Register of Causes of Death during 1988-2017. Patients were matched with up to 50 individuals from the general population., Results: We followed 1161 patients for a median of 34 years (range: 0.1-56.0). Median age at diagnosis was 33 years (range: 2-88). The cumulative probability of colectomy 10, 20, 30, 40 and 50 years after diagnosis was 22% (95% CI: 20%-25%), 27% (95% CI: 25%-30%), 31% (95% CI: 28%-34%), 34% (95% CI: 31%-37%), and 40% (95% CI: 36%-44%), respectively. The risk of small intestinal, colon, rectal and anal cancer was higher than among controls, as was cancer of the skin, pancreas and thyroid. All-cause mortality was lower than controls (adjusted RR: 0.90, 95% CI: 0.82-0.99)., Conclusion: In this population-based cohort of UC patients diagnosed between 1962 and 1987, 40% underwent colectomy within 50 years of diagnosis. Physicians need to be aware that UC patients are at increased risk of intestinal and extra-intestinal cancers. However, UC patients' risk of mortality is comparable to that of the background population., (© 2021 John Wiley & Sons Ltd.)

Background: Few population-based studies have investigated the long-term prognosis of Crohn's disease (CD)., Aim: To determine the long-term natural disease course of CD with regard to surgery, cancer and mortality in a population-based cohort followed for more than 50 years., Methods: All patients diagnosed with CD from 1962 to 1987 in Copenhagen County, Denmark were included in a population-based cohort. Information about surgeries, cancers and mortality was collected from patient files from 1962 to 1987 and from the Danish National Patient Registry, Cancer Registry, and from the Register of Causes of Death, 1987-2017. Patients were matched with individuals from the general population., Results: A total of 373 patients were followed for a median of 33 years (range: 0-56 years). The cumulative probability of surgery 10, 20, 30, 40 and 50 years after diagnosis was 62% (CI 95%: 57%-67%), 71% (CI 95%: 66%-75%), 72% (CI 95%: 67%-76%), 74% (CI 95%: 69%-79%) and 74% (CI 95%: 69%-79%), respectively. A total of 142 patients (54%) were operated upon at least twice: 69 (26%) needing two surgeries and 73 (28%) needing three or more. Patients with CD were found to be at increased risk of intestinal (small bowel, rectum and anus) and extra-intestinal (respiratory organs and skin) cancer. All-cause mortality among CD patients was higher than among controls (RR: 1.22, CI 95%: 1.04-1.43), whereas mortality due to gastrointestinal cancer was not., Conclusion: After 50 years of follow-up, 75% CD patients had undergone surgery, with most needing repeat surgery. The risk of intestinal and extra-intestinal cancers, as well as mortality, was higher among CD patients than the background population., (© 2021 John Wiley & Sons Ltd.)

The risk of colorectal cancer (CRC) and dysplasia in patients with inflammatory bowel disease (IBD) has been highly debated as risk estimates from different studies vary greatly. The present national Danish guideline on colonoscopy surveillance for dysplasia and colorectal cancer in patients with IBD is based on a thorough review of existing literature with particular focus on recent studies from Denmark revealing a lower risk of CRC than previously assumed. The overall risk of CRC in the Danish IBD population does not appear to be different from that of the background population; however, in some subgroups of patients the risk is increased. These subgroups of patients, who should be offered colonoscopy surveillance, include patients with ulcerative colitis having extensive disease and a long disease duration (10-13 years); early age at onset (less than 19 years of age) of ulcerative colitis; and patients with ulcerative colitis as well as Crohn's disease with a concomitant diagnosis of primary sclerosing cholangitis. A colonoscopy surveillance program is recommended in these subgroups with intervals ranging from every 3-6 months to every 5 years, using chromoendoscopy with targeted biopsies of the lesion and adjacent mucosa, instead of conventional colonoscopy with random biopsies. Preferably, the colonoscopy should be performed during clinical remission. If a lesion is detected the endoscopical resectability together with the pathology of the lesion and the adjacent mucosa determine how the lesion should be treated.

Introduction: Treatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a population-based cohort., Methods: 48 967 individuals were diagnosed with IBD (Crohn's disease (CD), 13 185; ulcerative colitis (UC), 35 782) during 1979-2011. Cumulative probability of receiving 5-aminosalicylic acids (5-ASA), topical, oral corticosteroids, thiopurines, and tumour necrosis factor-α (TNF-α) blockers, and of first minor or major surgery according to period of diagnosis, was estimated. Medication use and risk of surgery was examined by Cox regression., Results: 5-year cumulative probability of first major surgery decreased from 44.7% in cohort (1979-1986) to 19.6% in cohort (2003-2011) (p < 0.001) for CD, and from 11.7% in cohort (1979-1986) to 7.5% in cohort (2003-2011) (p < 0.001) for UC. Minor surgery risk decreased significantly in CD. From cohort (1995-2002) to cohort (2003-2011), a significant increase in use of thiopurines and TNF-α blockers was observed, paralleled by a significant decrease in use of 5-ASA and corticosteroids. Comparing use of azathioprine (or oral corticosteroids) to never-use, no convincing surgery-sparing effect was found. Comparing use in 3+ months of a given drug with use <3 months, only 3+ months use of oral corticosteroids reduced the risk of surgery in patients with disease duration of >1 year., Conclusions: Parallel to an increasing use of thiopurines and TNF-α blockers in IBD over time, a persistent significant decrease in surgery rates was observed along with a significant decrease in use of 5-ASA and corticosteroids. However, no convincing surgery-sparing effect of newer medications was found., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Infliximab (IFX) maintenance therapy for Crohn's disease (CD) is administered every 8 weeks, but inter-patient variation in optimal treatment intervals may exist., Aim: To assess, in a prospective pilot study, the efficacy, safety and quality of life (QoL) of IFX maintenance treatment scheduled through web-based self-monitoring of disease activity., Methods: Twenty-seven CD patients in IFX maintenance therapy were enrolled and received a standardised disease education and web-training. Using the http://www.cd.constant-care.dk concept, patients recorded their disease activity and faecal calprotectin weekly. From this, the inflammatory burden (IB) score was calculated, placing patients in the green, yellow or red zones of a ‘traffic light’ system. If placed in the yellow or red zones, the computer directed these patients to consult their physician for IFX infusion., Results: Seventeen patients (63%) completed 52 weeks of follow-up, 6 (22%) completed 26 weeks and 4 (15%) were excluded due to loss of response, patient decision or non-adherence. In total, 121 IFX infusions were given with a median interval of 9 (range: 4–18) weeks. Only 10% of infusions were given at 8-week intervals, whereas 39% were administered with shorter and 50% with longer intervals respectively. The mean IB and the QoL remained stable during the web-treatment. One mild infusion reaction and one case of folliculitis were observed, while three patients underwent surgery., Conclusions: The program http://www.cd.constant-care.dk appears to be a practical and safe concept for the individualised scheduling of maintenance treatment with IFX in patients with Crohn's disease. Larger studies are awaited to confirm this preliminary outcome.

Background: The natural history of ulcerative colitis requires continuous monitoring of medical treatment via frequent outpatient visits. The European health authorities' focus on e-health is increasing. Lack of easy access to inflammatory bowel disease (IBD) clinics, patients' education and understanding of the importance of early treatment at relapse is leading to poor compliance. To overcome these limitations a randomised control trial 'Constant-care' was undertaken in Denmark and Ireland., Methods: 333 patients with mild/moderate ulcerative colitis and 5-aminosalicylate acid treatment were randomised to either a web-group receiving disease specific education and self-treatment via http://www.constant-care.dk or a control group continuing the usual care for 12 months. A historical control group was included to test the comparability with the control group. We investigated: feasibility of the approach, its influence on patients' compliance, knowledge, quality of life (QoL), disease outcomes, safety and health care costs., Results: 88% of the web patients preferred using the new approach. Adherence to 4 weeks of acute treatment was increased by 31% in Denmark and 44% in Ireland compared to the control groups. In Denmark IBD knowledge and QoL were significantly improved in web patients. Median relapse duration was 18 days (95% CI 10 to 21) in the web versus 77 days (95% CI 46 to 108) in the control group. The number of acute and routine visits to the outpatient clinic was lower in the web than in the control group, resulting in a saving of 189 euro/patient/year. No difference in the relapse frequency, hospitalisation, surgery or adverse events was observed. The historical control group was comparable with the control group., Conclusion: The new web-guided approach on http://www.constant-care.dk is feasible, safe and cost effective. It empowers patients with ulcerative colitis without increasing their morbidity and depression. It has yet to be shown whether this strategy can change the natural disease course of ulcerative colitis in the long term.

Ulcerative colitis (UC) is believed to carry a predisposition to colorectal cancer (CRC) development. International clinical guidelines suggest that UC patients should have a colonoscopy performed every year or up to every third year from approximately eight years after diagnosis for early detection of CRC/dysplasia. However, according to the Danish epidemiological data available, such recommendations are dubious. The present mini review focuses on this matter for the UC population in 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 Crohn's 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.

Objectives: Population-based data on risk factors and protective factors for colorectal dysplasia and cancer in patients with inflammatory bowel disease (IBD) are sparse. We conducted a nested case-control study of such factors in two well-described IBD cohorts from Copenhagen County, Denmark and Olmsted County, Minnesota., Methods: Forty-three neoplasia cases were matched on six criteria to 1-3 controls (N = 102). Medical records were scrutinized for demographic and clinical data. For each variable, the odds of neoplasia were estimated using conditional logistic regression., Results: Primary sclerosing cholangitis (PSC) (odds ratio [OR] 6.9, 95% confidence interval [CI] 1.2-40), percentage of disease course with clinically active disease (OR [per 5% increase] 1.2, 95% CI 0.996-1.4), and >or=1 yr of continuous symptoms (OR 3.2, 95% CI 1.2-8.6) were associated with neoplasia, whereas a borderline association with median number of small-bowel x-rays (OR 1.3, 95% CI 0.96-1.6) was observed. We did not observe a protective effect of frequency of physician visits (OR 1.4, 95% CI 0.96-2.0), number of colonoscopies (OR 1.4, 95% CI 1.0-2.1), cumulative dose of sulfasalazine (OR [per 1,000 g] 1.1, 95% CI 1.0-1.3) and mesalamine (OR [per 1,000 g] 1.3, 95% CI 0.9-1.9), or partial intestinal resections (OR 1.5, 95% CI 0.3-7.1)., Conclusions: Subgroups of IBD patients-those with PSC, severe long-standing disease, and exposure to x-ray-were at greater risk of colorectal neoplasia. The protective effect of close follow-up, colonoscopy, and treatment with 5-aminosalicylates was questionable.

Background & Aims: Ulcerative colitis (UC) is associated with an increased risk for colorectal cancer (CRC) and possibly also increased risk for cancers outside the intestinal tract. We followed-up a population-based cohort of 1160 patients with UC diagnosed in Copenhagen County between 1962 and 1987 for up to 36 years to analyze the overall and site-specific cancer risk., Methods: Observed vs. expected cancers were presented as standardized morbidity ratio (SMR) with 95% exact confidence intervals (CI) calculated by using individual person-years at risk and sex- and age-specific incidence rates for the Danish background population in 1995., Results: The cohort was followed-up for a median of 19 years, or 22,290 person-years. A total of 124 malignancies were observed compared with 139.85 expected (SMR, .89; 95% CI, .74-1.07). The observed number of CRCs was almost exactly equal to expected: 13 cases vs. 12.42 (SMR, 1.05; 95% CI, .56-1.79). The cumulative probability of CRC was .4% by 10 years, 1.1% by 20 years, and 2.1% by 30 years of disease. Among men, melanoma was increased (SMR, 3.45; 95% CI, 1.38-7.10); otherwise, no increased risk for cancer could be detected. No hepatobiliary cancers and no increased risk for lymphoma or leukemia were found., Conclusions: Neither the overall cancer risk, nor the CRC risk, were increased in this population-based cohort after a median of 19 years of follow-up evaluation. An active surgical approach in medical treatment failures and long-term use of 5-aminosalicylic acid (5-ASA) as relapse prevention may explain this remarkable result.

Background & Aims: A population-based cohort comprising 374 patients with Crohn's disease diagnosed in Copenhagen County between 1962 and 1987 was observed until 1997 for mortality and causes of death., Methods: Observed deaths were compared with expected deaths calculated by using individually computed person-years at risk and 1995 rates for Copenhagen County. Cumulative survival curves were calculated., Results: A total of 84 deaths occurred vs. 67 expected (standardized mortality ratio [SMR], 1.3; 95% confidence interval [CI], 1.01-1.56): 45 women vs. 31.8 expected (SMR, 1.4; 95% CI, 1.03-1.89) and 39 men vs. 35.2 expected (SMR, 1.1; 95% CI, 0.79-1.51). An excess mortality was observed among women observed for 21-25 years after diagnosis. Among women aged <50 years at diagnosis, 25 deaths were observed vs. 7.3 expected (SMR, 3.42; 95% CI, 2.21-5.04). Fourteen (31%) of the observed deaths among women and 8 (21%) among men had a certain or possible connection to Crohn's disease. Among causes of death unrelated to Crohn's disease, an overrepresentation of gastrointestinal diseases, infections, and diseases of the urinary organs was observed., Conclusions: An increased mortality was observed late in the disease course that was most pronounced among women younger than 50 years at diagnosis and was attributed to death associated with severe Crohn's disease.

From an incidence cohort diagnosed during 1962-1987 we identified all patients with onset of IBD before the age of 15 in order to describe the course and to compare course and prognosis with adult onset IBD. The mean incidence of IBD among children below 15 years was 2.2/10(5), 2.0 for ulcerative colitis (UC), and 0.2 for Crohns disease (CD). At diagnosis, UC children had more extensive disease compared to adults (p < 0.05). Abdominal pains were also more frequent. The cumulative colectomy probability was 6% after one year and 29% after 20 years, not different from adults. Regarding disease activity, it was found that 60-70% of UC patients were in remission in the first 10 years of disease, for CD about 50% were in remission. One UC patient developed carcinoma of the sigmoid colon. Time between onset and development of carcinoma was 12 years. For CD no differences in clinical appearance at diagnosis and course between children and adults were found. No deaths occurred among CD patients. Three CD patients were found to have severe growth retardation already at diagnosis. In conclusion, the incidence of IBD is low in childhood. At diagnosis children with UC have more widespread disease than adults. Children with CD do not differ in clinical presentation, course or prognosis compared to adult onset CD. However, growth retardation is a problem among CD patients.

Background: The study was a follow-up of an inception cohort of 373 patients with Crohn's disease., Methods: Annual assessments, life table analyses, and Markov chain analyses, estimating the probability for remission and relapse with time, and working capacity were carried out., Results: The clinical course of Crohn's disease differs markedly over time, from ever-relapsing cases to a quiescent course with remission for several years, interrupted by years with relapse. No predictive factors have been found for the subsequent course with regard to age, sex, extent of disease at diagnosis, and treatment in the year of diagnosis. The relapse rate within the year of diagnosis and the following 2 years, however, does correlate positively (p = 0.00001) with the relapse rate in the following 5 years. Furthermore, the relapse rate for 1 year during the disease course influences the relapse rate the following year, indicating a disease pattern over time with waves of at least 2 years' duration. A slight tendency towards burning out was found. The disease course reflected in working capacity for the patients showed that a minor part--up to 15% after 15 years--will become incapable and obtain disablement pension, while 75% of the patients each year are fully capable of work. Within 10 years 50% of the patients will not have experienced any year with impaired capacity for work.

A regional inception cohort of 1161 ulcerative colitis patients was followed from diagnosis to the end of 1987. Follow-up rate for death and occurrence of cancer was 99.9%. Median observation time 11.7 years, range 0-26 years. One hundred and forty-one deaths were observed, 26 due to ulcerative colitis 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 was 32.4% 25 years after diagnosis. 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 five years after diagnosis. Six patients developed colorectal cancer within the observation period. Compared to the expected number of 6.6 the relative risk for patients with ulcerative colitis 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 to 74 years) for development of colorectal cancer was 3.5% for the patients compared to 3.7% for the Danish population. We conclude that with an active approach to medical and surgical treatment as was practiced here, those patients who are left with their colon intact bear no significantly increased risk of colo-rectal malignancy.

The incidence of Crohn's disease was assessed in a population based study in Copenhagen County from 1962-1987. The incidence increased six fold during the study period from 0.62/10(5) in 1962 to a mean of 4.1/10(5) from 1979-1987, equally in both sexes. The highest incidence was found in the age group 15-24 years: 12.8/10(5) for women and 6.0/10(5) for men (as mean of the period 1979-1987). The prevalence at the end of the study was 54/10(5). The clinical symptoms and extent of disease at diagnosis did not change over the time, but a significantly higher disease activity was found in the 1980's, 74% (1962-1979) vs 84% (1980-1987), p = 0.04. The increase in incidence of Crohn's disease is well established in most parts of the industrialized world. The analysis shows that it is not due to a new disease entity, since the extent of disease, the age and sex distribution, and the symptoms remained unchanged during the 26 year study period.

Objective: To investigate the mode of inheritance of ulcerative colitis and Crohn's disease by complex segregation analysis., Design: Cross sectional population based survey of familial occurrence of chronic inflammatory bowel disease., Setting: Population of the Copenhagen county in 1987., Subjects: 662 patients in whom inflammatory bowel disease had been diagnosed before 1979, of whom 637 (96%) provided adequate information. Of 504 patients with ulcerative colitis, 54 had 77 relatives with ulcerative colitis and of 133 patients with Crohn's disease, five had seven relatives with Crohn's disease., Main Outcome Measures: Patterns of segregation of either disease as assessed by complex segregation analysis performed with the computer program POINTER., Results: The analysis suggested that a major dominant gene with a penetrance of 0.20-0.26 is present in 9-13% of adult patients with ulcerative colitis. The analysis did not allow for other components in the familial aggregation. For Crohn's disease the best fitting model included a major recessive gene with complete penetrance, for which 7% of the patients are homozygous. However, this model was not significantly different from a multifactorial model., Conclusions: The segregation pattern indicates that a major dominant gene has a role in ulcerative colitis, and suggests that a major recessive gene has a role in Crohn's disease.

The incidence of Crohn's disease increased sixfold from 1962 to 1987 in the county of Copenhagen. The mean annual incidence for 1979-87 was 4.1 per 10(5) inhabitants. The increase was found equally in both sexes, with an approximately 40% higher incidence in women. The maximal incidence was found in the 15- to 24-year age group, being 12.8 per 10(5) per year for women and 6.0 per 10(5) per year for men, as mean of the period 1979-87. The prevalence at the end of the study was 54 per 10(5) inhabitants, 46 per 10(5) in men and 63 per 10(5) in women. The clinical appearance of the disease at the time of diagnosis was remarkably similar during the study period with regard to both the localization of disease and the clinical symptoms and signs. A slightly higher percentage of the patients, however, were in high disease activity at diagnosis in the later years of the study.

The incidence of ulcerative colitis was estimated during the period 1962 to 1987 in the county of Copenhagen. Within this area of approximately 550,000 inhabitants, 1161 patients were diagnosed. The mean annual incidence for the period was 8.1 per 10(5) inhabitants. There were significant increases in incidence in the early 1970s and in the early 1980s, both of which were followed by significant decreases. A bimodal age distribution was found in men, with incidence peaks in young adult life and late in life. In women a peak incidence was found in the young adult age group. The interval from onset of symptoms to diagnosis in terms of years remained unchanged over the period, with a median of 1 year (range, 0-37 years). The extent of disease at diagnosis was total colon in 18% of the patients, a substantial part of the colon in 36%, and distal colon in 44%--with no changes during the study period. The distribution of different localizations did not differ among age groups except for a tendency towards more extensive disease in young patients, below 20 years of age. The disease activity in the 1st year was fulminant in 9.1% of the cases, moderate to high in 70.7%, and low in 20.2%, with a tendency towards higher activity in patients diagnosed late in the study period. The prevalence of ulcerative colitis increased steadily during the study period, reaching a value at the end of the study (31 December 1987) of 161 per 10(5) inhabitants.

An epidemiologic study was performed 1) to estimate the occurrence of epithelioid granulomas in the appendix wall among patients in whom an appendectomy had been performed, 2) to identify patients with granulomas in the appendix who had symptoms and history compatible with Crohn's disease, and 3) to estimate the long-term prognosis. Within a 5-year period 6051 patients in Copenhagen County underwent appendectomy. Six patients (0.1%) had epithelioid granulomas of the appendix (0.2 per 10(5) inhabitants per year). Follow-up of the six patients for 9-11 years (median, 9.5 years) showed that all had been free of gastrointestinal symptoms since the operation. Among the 373 patients diagnosed as having Crohn's disease in Copenhagen County between 1962 and 1987, 3 patients had their disease initially confined to the appendix. Follow-up in these patients showed no recurrence within a median of 6 years (range, 4-7 years). Patients with epithelioid granulomas of the appendix have an excellent long-term prognosis, which could be explained by the fact that the condition seems to be unrelated to Crohn's 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 Crohn's disease) provided adequate information., Results: As compared with the general population, the first-degree relatives of the 637 patients with ulcerative colitis or Crohn's 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 Crohn's 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 Crohn's 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 Crohn's disease strongly suggests that these disorders have a genetic cause.