Ulcerative Colitis: Ekbom A

Moum B, Ekbom A. · Medical Department SØ Fredrikstad, NO-1601 Fredrikstad, Norway. · Scand J Gastroenterol. · Pubmed #16170896 No free full text.

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Ekbom A. · Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden. · Inflamm Bowel Dis. · Pubmed #15168828 No free full text.

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Ekbom A, Montgomery SM. · Clinical Epidemiology Unit, Department of Medicine, Karolinska Hospital, M9:01, Stockholm SE-171 76, Sweden. · Best Pract Res Clin Gastroenterol. · Pubmed #15157823 No free full text.

Abstract: The increase in incidence in both ulcerative colitis and Crohn's disease during the 20th century has led to an abundance of different hypotheses on what sort of exposures are responsible. There has been a special focus on dietary factors, as well as on other exposures introduced on a population-based level, including fast food, cola drinks, toothpaste, antibiotics and oral contraceptives. The aim of this review is to critically assess the results from the different observational studies that have investigated these hypotheses, and also to propose research agendas that should be pursued in the future. The conclusion is that infectious exposures and early bacterial colonization, which are associated with better hygiene early in life and that influence immune function, and possibly oral contraceptives, remain the only exposures of interest for future research into the aetiology of ulcerative colitis and Crohn's disease.

Moum B, Ekbom A. · Medical Department, County Hospital Ostfold Fredrikstad, Norway. · Dig Liver Dis. · Pubmed #12118955 No free full text.

Abstract: The causes and mechanisms of action of inflammatory bowel disease have, so far, eluded discovery. Epidemiological studies have shown that ulcerative colitis tends to level off, whereas Crohn's disease tends to increase. Some of these changes may be due to diagnostic practices and increasing awareness of the disease and Crohn's colitis. The disease varies according to geographical location and a distribution along a north-south axis has been suggested. The differences may be due to study design, or may reflect differences in lifestyle, diet or be due to genetic predisposition triggered by environmental factors. Epidemiological studies designed to investigate such interactions may provide clues to its aetiology. Inflammatory bowel disease could, therefore, serve as a model for the importance of epidemiology when to test or reject the hypothesis of aetiology.

Ekbom A. · Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. · Nestle Nutr Workshop Ser Clin Perform Programme. · Pubmed #11490629 No free full text.

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Bergquist A, Montgomery SM, Bahmanyar S, Olsson R, Danielsson A, Lindgren S, Prytz H, Hultcrantz R, Lööf LA, Sandberg-Gertzén H, Almer S, Askling J, Ehlin A, Ekbom A. · Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institute, Huddinge and Solna, Stockholm, Sweden. · Clin Gastroenterol Hepatol. · Pubmed #18674735 No free full text.

Abstract: BACKGROUND & AIMS: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. METHODS: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. RESULTS: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). CONCLUSIONS: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

Ekbom A, Brandt L, Granath F, Löfdahl CG, Egesten A. · Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Lung. · Pubmed #18330638 No free full text.

Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n=180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n=1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.

Ludvigsson JF, Askling J, Ekbom A, Montgomery SM. · Department of Pediatrics, Orebro University Hospital, Sweden. · Dig Liver Dis. · Pubmed #16914396 No free full text.

Abstract: BACKGROUND: Earlier studies suggest that appendectomy is associated with a substantially reduced risk of certain types of bowel inflammation such as ulcerative colitis, particularly where the underlying diagnosis is acute appendicitis. Previous research on appendectomy and coeliac disease is inconsistent, based on small numbers with retrospective data collection, and has not differentiated between different diagnoses underlying appendectomy. OBJECTIVE: To investigate the association of diagnosis underlying appendectomy with coeliac disease. METHODS: We used Cox regression to study the risk of later appendectomy in more than 14,000 individuals with coeliac disease and 68,000 referents without coeliac disease, identified through the Swedish National Registers 1964-2003, and conditional logistic regression to study the risk of coeliac disease associated with a history of prior appendectomy. Appendectomy was categorised according to the underlying diagnosis: perforated appendicitis, non-perforated appendicitis, and appendectomy without appendicitis. RESULTS: Overall, coeliac disease was negatively associated with perforated appendicitis (hazard ratio=0.78, 95% confidence interval=0.60-1.01), not associated with non-perforated appendicitis (hazard ratio=1.11, 95% confidence interval=0.99-1.25), but positively associated with appendectomy without appendicitis (hazard ratio=1.58, 95% confidence interval=1.32-1.89). The magnitudes of the relative risks were similar irrespective of whether coeliac disease occurred prior to or after appendectomy. CONCLUSION: Coeliac disease and perforated appendicitis are negatively associated irrespective of the timing of the conditions. Not surprisingly, CD increases the risk for appendectomy without appendicitis.

Askling J, Brandt L, Lapidus A, Karlén P, Björkholm M, Löfberg R, Ekbom A. · Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet and Hospital, SE-171 76 Stockholm, Sweden. · Gut. · Pubmed #15831904 links to  free full text

Abstract: BACKGROUND AND AIMS: Several chronic inflammatory conditions are associated with an increased risk of lymphoma. Whether this applies to inflammatory bowel disease (IBD) is still unclear but of paramount interest, particularly in the safety evaluation of newer immunosuppressive drugs. Reports also indicate a possible increase in the risk of leukaemia in IBD. We therefore assessed the risk of haematopoietic cancers in a large cohort of patients with IBD.Subjects and METHODS: We performed a population based cohort study using prospectively recorded data, including 47 679 Swedish patients with Crohn's disease (CD) or ulcerative colitis (UC) assembled from regional cohorts of IBD from 1955 to 1990 (n = 8028) and from the Inpatient Register of 1964-2000 (n = 45 060), with follow up until 2001. Relative risks were expressed as standardised incidence ratios (SIR). RESULTS: Overall, we observed 264 haematopoietic cancers during follow up, which corresponded to a borderline significant 20% increased risk in both UC and CD. In UC, lymphomas occurred as expected (SIR 1.0, n = 87) but myeloid leukaemia occurred significantly more often than expected (SIR 1.8, n = 32). In CD, there was a borderline significant increased lymphoma risk (SIR 1.3, n = 65), essentially confined to the first years of follow up. Proxy markers of disease activity had little impact on lymphoma risk. CONCLUSION: On average, patients with IBD have a marginally increased risk of haematopoietic cancer. In UC, this is accounted for by an excess of myeloid leukaemia. In CD, a modest short term increase in the risk of lymphoma of unknown significance cannot be excluded but any long term risk increase seems unlikely.

Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J. · Department of Women and Child Health, Astrid Lindgren Children's Hospital, Stockholm, Sweden. · Gut. · Pubmed #12970135 links to  free full text

Abstract: BACKGROUND: An increased incidence of paediatric Crohn's disease was reported recently by our group. AIMS: To assess the incidence and characteristics of inflammatory bowel disease (IBD) in northern Stockholm between 1990 and 2001. METHODS: All records of individuals 0-15 years of age with suspected IBD in the population based catchment area of 180000 individuals were scrutinised using defined diagnostic criteria. Patient files were searched for relatives with IBD, and for concomitant autoimmune diseases. RESULTS: A total of 152 children were diagnosed with IBD, corresponding to an overall incidence (per 100000) of IBD of 7.4. The incidence of Crohn's disease (CD) was 4.9, ulcerative colitis (UC) 2.2, and indeterminate colitis 0.2. Between 1990 and 2001, there was a marked increase in the incidence of CD while the incidence of UC was almost unchanged, leading to a net increase in the overall occurrence of IBD. There was a male dominance of CD. Fourteen per cent and 11% of patients with CD and UC, respectively, had a first or second degree relative with IBD. Eighteen per cent and 10% of patients with CD and UC, respectively, had a concomitant autoimmune disease. Ten patients with CD (10%) underwent surgery. CONCLUSIONS: The incidence of CD has increased in northern Stockholm. The current incidence is higher than that reported from other areas. Our results suggest a shift in presentation and diagnosis from UC towards CD, but also a net increase in IBD. Concomitant autoimmune disorders and family history are common in paediatric IBD.

Ehlin AG, Montgomery SM, Ekbom A, Pounder RE, Wakefield AJ. · Enheten för Klinisk Epidemiologi, Institutionen för medicin vid Karolinska Sjukhuset, Karolinska Institutet, Stockholm, Sweden. · Gut. · Pubmed #12865268 links to  free full text

Abstract: BACKGROUND: Few studies have investigated the prevalence of multiple gastrointestinal diseases in the general British population. AIM: To examine the prevalence of Crohn's disease (CD), ulcerative colitis (UC), irritable bowel syndrome (IBS), gall stones (GS), and peptic ulcer disease (PUD). SUBJECTS: The 1970 British Cohort Study (BCS70) and the National Child Development Study (NCDS) are two one week national birth cohorts born in 1970 and 1958, respectively. All cohort members living in Great Britain were interviewed in 1999/2000. METHODS: The prevalence rates of the five diseases were calculated, and associations with sex and childhood social class were investigated using logistic regression. RESULTS: At age 30 years, the prevalence rates per 10,000 (95% confidence interval (CI)) in the 1970 and 1958 cohorts, respectively, were: CD 38 (26-49), 21 (13-30); UC 30 (20-41), 27 (18-37); IBS 826 (775-877), 290 (267-330); GS 88 (71-106), 78 (62-94); and PUD 244 (214-273), 229 (201-256). There was a significantly higher proportion with CD (p=0.023) and IBS (p=0.000) in the 1970 cohort compared with the 1958 cohort at age 30 years. Comparing the cohorts in the 1999/2000 sweep, UC, GS, and PUD were significantly (p=0.001, p=0.000, p=0.000) more common in the 1958 cohort. There was a statistically significant trend for a higher risk of GS with lower social class in both cohorts combined (p=0.027). CONCLUSION: The study indicates an increasing temporal trend in the prevalence of CD and suggests a period effect in IBS, possibly due to adult life exposures or variation in recognition and diagnosis of IBS.

Peters U, Askling J, Gridley G, Ekbom A, Linet M. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-7273, USA. · Arch Intern Med. · Pubmed #12860579 links to  free full text

Abstract: BACKGROUND: Patients with celiac disease have an increased risk of death from gastrointestinal malignancies and lymphomas, but little is known about mortality from other causes and few studies have assessed long-term outcomes. METHODS: Nationwide data on 10 032 Swedish patients hospitalized from January 1, 1964, through December 31, 1993, with celiac disease and surviving at least 12 months were linked with the national mortality register. Mortality risks were computed as standardized mortality ratios (SMRs), comparing mortality rates of patients with celiac disease with rates in the general Swedish population. RESULTS: A total of 828 patients with celiac disease died during the follow-up period (1965-1994). For all causes of death combined, mortality risks were significantly elevated: 2.0-fold (95% confidence interval [CI], 1.8-2.1) among all patients with celiac disease and 1.4-fold (95% CI, 1.2-1.6) among patients with celiac disease with no other discharge diagnoses at initial hospitalization. The overall SMR did not differ by sex or calendar year of initial hospitalization, whereas mortality risk in patients hospitalized with celiac disease before the age of 2 years was significantly lower by 60% (95% CI, 0.2-0.8) compared with the same age group of the general population. Mortality risks were elevated for a wide array of diseases, including non-Hodgkin lymphoma (SMR, 11.4), cancer of the small intestine (SMR, 17.3), autoimmune diseases (including rheumatoid arthritis [SMR, 7.3] and diffuse diseases of connective tissue [SMR, 17.0]), allergic disorders (such as asthma [SMR, 2.8]), inflammatory bowel diseases (including ulcerative colitis and Crohn disease [SMR, 70.9]), diabetes mellitus (SMR, 3.0), disorders of immune deficiency (SMR, 20.9), tuberculosis (SMR, 5.9), pneumonia (SMR, 2.9), and nephritis (SMR, 5.4). CONCLUSION: The elevated mortality risk for all causes of death combined reflected, for the most part, disorders characterized by immune dysfunction.

Ekbom A. · Unit of Clinical Epidemiology, Department of Medicine, Karolinska Hospital, Stockholm, Sweden. · Can J Gastroenterol. · Pubmed #12605251 links to  free full text

Abstract: There are insufficient data upon which to base recommendations about surveillance colonoscopy and prophylactic colectomy for the prevention of colorectal cancer in patients with ulcerative colitis. Case series, analyses of intermediate results and extrapolations from other patient groups do not constitute reliable evidence. Available studies are susceptible to several biases: the 'healthy worker' effect, surveillance bias and selection bias. Patients who are enrolled in surveillance programs are more likely to be thoroughly evaluated beforehand, are more likely to be given a diagnosis of dysplasia or neoplasm even when asymptomatic and are more likely to comply with medical treatment, including maintenance anti-inflammatory medication. Comparisons of the rates of neoplasia or death between surveyed and nonsurveyed patients are, therefore, of questionable validity. Prophylactic colectomy, unlike surveillance colonoscopy, prevents death from colorectal cancer. Moreover, it is difficult to keep patients in surveillance programs, and those who withdraw from programs appear to be at high risk of developing cancer. Prophylactic colectomy should be strongly considered for patients with dysplasia, sclerosing cholangitis, longstanding pancolitis (especially if it began early in life) or a positive family history of colorectal cancer. This procedure is underused in clinical practice and is a good alternative to colonoscopic surveillance in high risk patients.

Andersson RE, Olaison G, Tysk C, Ekbom A. · Department of Surgery, County Hospital Ryhov, SE-551 85 Jönköping, Sweden. · Gastroenterology. · Pubmed #12512028 No free full text.

Abstract: BACKGROUND & AIMS: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. METHODS: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. RESULTS: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37; 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. CONCLUSIONS: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.

Montgomery SM, Lambe M, Wakefield AJ, Pounder RE, Ekbom A. · Enheten för klinisk epidemiologi, Institutionen för medicin vid Karolinska sjukhuset, Karolinska Institutet, Stockholm, Sweden. · Scand J Gastroenterol. · Pubmed #12465729 No free full text.

Abstract: BACKGROUND: Environmental exposures in early life have been implicated in the aetiology of inflammatory bowel disease (IBD). Siblings are used as proxy markers to characterize patterns of exposure relevant to the risk of IBD. METHODS: Some 15,823 patients with ulcerative colitis and 12,668 with Crohn disease from the Swedish In-patient Register were compared with 79,546 and 63,035 controls, respectively, in a case-control study. Multiple logistic regression was used to investigate associations with older and younger siblings, and adjustment was made for sex, year of birth, mother's age, region and, additionally, father's social class. RESULTS: Older siblings are associated with a graded increased risk for ulcerative colitis (P for trend <0.001) and an adjusted odds ratio of 1.15 (95% CI 1.07-1.24) for three or more older siblings. Younger siblings are associated with a graded decreased risk for Crohn disease (P for trend <0.001) with an adjusted odds ratio of 0.83 (0.76-0.90) for three or more younger siblings. The greatest protective association with Crohn disease was seen for younger siblings born within 2 years of the subject. Older maternal age is independently associated with a decreased risk of Crohn disease, with P for trend <0.001. Additional adjustment for social class did not substantially alter the results. CONCLUSIONS: Having siblings is associated with the risk and phenotype of developing IBD, possibly through their influence on patterns of antigenic exposure in early life. The association of maternal age with Crohn disease may reflect age-related changes in maternal immune profile.

Bentsen BS, Moum B, Ekbom A. · Dept of Paediatrics, Ostfold Central Hospital, Fredrikstad, Norway. · Scand J Gastroenterol. · Pubmed #12059055 No free full text.

Abstract: BACKGROUND: Most incidence studies of ulcerative colitis (UC) and Crohn disease (CD) have dealt with adults and there are have been few population-based prospective studies of the incidence of inflammatory bowel disease (IBD) in children. The aim of this study was to determine the incidence after re-evaluation of the diagnosis of UC and CD in childhood and adolescence in a prospective population-based survey. METHODS: From 1 January 1990 to 31 December 1993, all newly diagnosed patients with UC and CD under the age of 16 years were registered. On 1 January 1992 there were 174,482 children in the study population. The diagnosis was based on internationally accepted criteria and all clinical data were reviewed by two gastroenterologists independently of each other. All patients were subjected to a second evaluation 1 year after inclusion in the study. Patients initially diagnosed as indeterminate colitis (IND) were also reassessed. RESULTS: A total of 14 cases of UC, 13 cases of CD and 2 cases of IND were registered during the study period. At re-evaluation of the two patients diagnosed as IND, one was reclassified as having UC and one as having CD. This yielded a mean annual incidence of 2.14 (95% CI 1.20-3.54) per 100,000 for UC and 2.00 (95% CI 1.10-3.36) per 100,000 for CD. The male:female ratio in UC was 4.0 and 1.8 in CD. Median time interval from onset of symptoms to diagnosis was 4 months for UC and 5 months for CD. A high proportion of the children with UC (80%; 12/15) had extensive colitis. Four patients with CD had a first-degree relative with IBD. CONCLUSION: This study does not support an increased incidence of paediatric CD over the past decade. The incidence of paediatric UC seems to have remained stable over the past 30 years. In the CD group, we find a high incidence of IBD in first-degree relatives.

Askling J, Dickman PW, Karlén P, Broström O, Lapidus A, Löfberg R, Ekbom A. · Department of Medical Epidemiology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. · Gastroenterology. · Pubmed #11313305 No free full text.

Abstract: BACKGROUND & AIMS: Familial colorectal cancer (CRC) is a risk factor for CRC in healthy individuals and, as indicated by case-control studies, possibly in ulcerative colitis. Little is known about the cancer risk in familial inflammatory bowel disease (IBD). We assessed the significance of familial CRC, or IBD, on the risk for CRC in patients with IBD. METHODS: Population-based cohort study of 19,876 individuals with ulcerative colitis or Crohn's disease born between 1941 and 1995. Registry-based follow-up and assessment of familial CRC, and IBD. Risk of CRC assessed as incidence proportion ("absolute risk," IP) and relative risk (RR). RESULTS: Familial CRC was associated with a more than 2-fold risk of CRC (adjusted RR = 2.5, 95% confidence interval 1.4-4.4) and an increase in the IP of CRC at 54 years of age from 3.8% to 6.9%. Patients with a first-degree relative diagnosed with CRC before 50 years of age had a higher RR (9.2, 95% confidence interval 3.7-23) and the highest IP (29%). No association with familial IBD was observed. CONCLUSIONS: Information on family history of CRC may be a simple way to identify individuals with IBD at elevated risk of developing CRC.

Blomqvist P, Feltelius N, Löfberg R, Ekbom A. · Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. · Aliment Pharmacol Ther. · Pubmed #11284775 links to  free full text

Abstract: BACKGROUND: Drug therapy for Crohn's disease and ulcerative colitis is based on anti-inflammatory and immunodulating drugs, nutritional support and surgical resection. Recently, new drugs have been introduced. AIM: To report drug prescriptions, costs and adverse reactions among inflammatory bowel disease patients in Sweden between 1988 and 1997. METHODS: Drug use was calculated from the national Diagnosis and therapy survey and drug costs from prescriptions and drug sales. Adverse drug reactions were obtained from the Medical Products Agency's National Pharmacovigilance system. RESULTS: The annual drug exposure for Crohn's disease was 0.55 million daily doses per million population, mainly supplementation and aminosalicylic acids. Mesalazine and olsalazine had 61% within this group. For ulcerative colitis patients, drug exposure was 0.61 million daily doses per million per year and aminosalicylic acids fell from 70% to 65%. For inflammatory bowel disease patients, corticosteroids and nutritional supplementation were common. The annual average cost for inflammatory bowel disease drugs was 7.0 million US dollars. Annually, 32 adverse drug reactions were reported, mainly haematological reactions such as agranulocytosis and pancytopenia (60%), followed by skin reactions. Only two deaths were reported. Aminosalicylic acids were the most commonly reported compounds. CONCLUSIONS: Drug use for inflammatory bowel disease in the pre-biologic agent era rested on aminosalicylic acid drugs and corticosteroids with stable levels, proportions and costs. The level of adverse drug reactions was low but haematological reactions support the monitoring of inflammatory bowel disease patients.

Andersson RE, Olaison G, Tysk C, Ekbom A. · Department of Surgery, County Hospital Ryhov, Jönköping, Sweden. · N Engl J Med. · Pubmed #11248156 links to  free full text

Abstract: BACKGROUND: A history of appendectomy is rare in patients with ulcerative colitis. This suggests a protective effect of appendectomy or that appendicitis and ulcerative colitis are alternative inflammatory responses. We sought to characterize this inverse relation further. METHODS: We studied a cohort of 212,963 patients who underwent appendectomy before the age of 50 years between 1964 and 1993 and a cohort of matched controls who were identified from the Swedish Inpatient Register and the nationwide census. The cohort was followed until 1995 for any subsequent diagnosis of ulcerative colitis. RESULTS: Patients who underwent appendectomy for appendicitis and mesenteric lymphadenitis had a low risk of ulcerative colitis (for patients with perforated appendicitis, the adjusted hazard ratio was 0.58 [95 percent confidence interval, 0.38 to 0.87]; for those with nonperforated appendicitis it was 0.76 [95 percent confidence interval, 0.65 to 0.90]; and for those with mesenteric lymphadenitis it was 0.57 [95 percent confidence interval, 0.36 to 0.89]). In contrast, patients who underwent appendectomy for nonspecific abdominal pain had the same risk of ulcerative colitis as the controls (adjusted hazard ratio, 1.06; 95 percent confidence interval, 0.74 to 1.52). For the patients who had appendicitis, an inverse relation with the risk of ulcerative colitis was found only for those who underwent surgery before the age of 20 years (P<0.001). CONCLUSIONS: Appendectomy for an inflammatory condition (appendicitis or lymphadenitis) but not for nonspecific abdominal pain is associated with a low risk of subsequent ulcerative colitis. This inverse relation is limited to patients who undergo surgery before the age of 20 years.

Askling J, Dickman PW, Karlén P, Broström O, Lapidus A, Löfberg R, Ekbom A. · Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. · Lancet. · Pubmed #11214128 No free full text.

Abstract: BACKGROUND: Inflammatory bowel disease (IBD) and colorectal cancer might share a common cause and, therefore, relatives of patients with IBD could be at increased risk of this malignant disease. We aimed to assess cancer rates among first-degree relatives of patients with IBD to try to determine whether an association between the two diseases exists. METHODS: In a population-based study, we identified 114,102 first-degree relatives by registry linkage and followed them up for cancer occurrence. We used standardised incidence ratio (SIR) of cancer as relative risk. FINDINGS: 560 colorectal cancers were identified among relatives. First-degree relatives of patients with Crohn's disease or ulcerative colitis were not at increased risk of cancer (SIR 0.90, 95% CI 0.82-0.97). The relative risk was 0.96 (0.87-1.06, n=379) for colon cancer and 0.78 (0.68-0.91, 181) for rectal cancer. The SIRs were not affected by age, relation to patient, or type or extent of IBD in the patient. Relatives of patients with both IBD and colorectal cancer had an 80% increased risk of colorectal cancer. INTERPRETATION: Our results do not endorse a common cause of IBD and colorectal cancer. The slightly decreased relative risk for colorectal cancer among relatives could indicate the proportion of all colorectal cancer cases attributable to IBD.

Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J. · The Gastrointestinal Research Unit, Leicester General Hospital, Leicester, UK. · Aliment Pharmacol Ther. · Pubmed #10651654 links to  free full text

Abstract: BACKGROUND: The risk of colorectal cancer (CRC) in ulcerative colitis (UC) increases with extent and duration of disease. Identifying other risk factors would allow targeting of sub-groups at greatest risk, enabling more cost-effective surveillance. METHODS: We conducted a case-control study comparing 102 cases of CRC in UC with matched controls. Odds ratios (OR) for cancer risk were estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables. RESULTS: Regular 5-aminosalicylic acid (5-ASA) therapy reduces cancer risk by 75% (OR 0.25, 95% CI: 0.13-0.48, P < 0.00001). Adjusting for other variables, taking mesalazine regularly reduces risk by 81% (OR 0.19, 95% CI: 0.06-0.61, P=0.006) and visiting a hospital doctor more than twice a year also reduces risk (OR 0.16, 95% CI: 0.04-0.60, P=0.007). Considering variables independently, having a family history of sporadic CRC in any relative increases risk fivefold (OR 5.0, 95% CI: 1.10-22.82, P < 0.04). CONCLUSIONS: CRC risk among UC patients can be reduced by regular therapy with 5-ASA medication. Colonoscopic surveillance may be best targeted on those unable to take 5-ASAs (e.g. due to allergy) and those with a positive family history of CRC.

Moum B, Ekbom A, Vatn MH, Elgjo K. · Department of Internal Medicine, Ostfold Central Hospital, Fredrikstad, Norway. · Am J Gastroenterol. · Pubmed #10364026 No free full text.

Abstract: OBJECTIVE: Colonoscopy has replaced barium enema as the method for determining the extent of disease in patients with ulcerative colitis (UC). Normally, the extent of disease is determined by direct visualization of the mucosa, but biopsies are also used with increasing frequency. Very little is known about the extent to which these two ways of assessing the extent of disease are correlated and whether the correlation differs over time. The aim of this study was to determine the changes in extent of disease assessed by direct visualization and by histological examination of the mucosa at the time of diagnosis and after 1 yr of follow-up in a cohort of incident cases of UC patients. METHODS: All new cases of UC in a defined population were identified during a 4-yr period (496 patients). Of these, 384 patients (78%) were available for follow-up and were subjected to a second colonoscopy with representative biopsies taken from both normal and affected mucosa. RESULTS: After 1 yr there were macroscopical signs of progression in 14%; 22% showed regression, and 30% had a normal colonoscopy. The histological changes from diagnosis until follow-up showed progression in 20%, 24% showed regression, and 24% had normal histological findings. Histological examination showed more extensive disease than did direct visualization in 4% of patients at diagnosis and in 28% at follow-up, whereas direct visualization showed more extensive disease than did histological examination in 18% of patients at diagnosis and 12% at follow-up. The best correlation at both diagnosis and follow-up was seen in pancolitis (99% and 88%, respectively). CONCLUSIONS: With regard to the extent of colonic involvement in the UC patients, we found less agreement between endoscopic and histological evaluation at the follow-up examination than at the start of the study. This could indicate that biopsies represent a better indicator than endoscopical examination for long term prognosis. Further studies are needed to confirm this finding.

Askling J, Grahnquist L, Ekbom A, Finkel Y. · No affiliation provided · Lancet. · Pubmed #10513717 No free full text.

Abstract: We report an increase in the incidence of Crohn's disease in northern Stockholm, Sweden.