Ulcerative Colitis: Askling J

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.

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.

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.

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.

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.

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.