The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study

OBJECTIVE: The aim of this study was to determine the prevalence of the major extraintestinal manifestations of inflammatory bowel disease (IBD) and their relation to disease diagnosis and gender. METHODS: We used the population-based University of Manitoba IBD Database, which includes longitudinal files on all subjects of all health system contacts identified by International Classification of Diseases, 9th Revision, Clinical Modification codes for visit diagnosis. We extracted a cohort from our database, which included subjects with a known diagnosis of IBD for at least 10 yr. We then determined how many contacts each subject had for each of the following extraintestinal IBD-associated immune diseases: primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, and erythema nodosum. We calculated the prevalence of the extraintestinal diseases using an administrative definition of having at least five health system contacts for the diagnosis in question. This administrative definition has previously been validated in Crohn's disease and ulcerative colitis (UC). RESULTS: A total of 6.2% of patients with IBD had one of six major extraintestinal diseases studied in this report. Only 0.3% of patients had multiple extraintestinal diseases. Iritis/uveitis was the most common extraintestinal disease of all assessed (2.2% of women and 1.1% of men). Iritis/uveitis was more common among women, particularly those with UC (3.8%). Primary sclerosing cholangitis was most common among men with UC (3%). Ankylosing spondylitis was more common among men, and the highest rate was seen among men with Crohn's disease (2.7%). Pyoderma gangrenosum was more common in Crohn's (1.2%) with no gender predilection. Erythema nodosum was similarly present in Crohn's and UC but was more common among women (1.9%). CONCLUSIONS: The associations of immune mediated diseases in extraintestinal sites may help us to further our understanding of IBD pathogenesis, and it may help us in developing a paradigm of disease subsets.     

The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden

Previous population-based incidence studies of inflammatory bowel disease are limited by small numbers, short duration, or inadequate case-finding. To address these problems, we identified all persons with confirmed ulcerative colitis (n = 2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965 to 1983. Age-specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with Crohn's disease. Incidence rates for ulcerative colitis and Crohn's disease were higher in urban than rural areas. The annual incidence rate of ulcerative colitis increased from less than 7 per 100,000 to more than 12 per 100,000 during the study period, while the rate for Crohn's disease remained between 5 and 7 per 100,000. The increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis. Analyses by 5-year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and Crohn's disease, and that this effect was accounted for by those born in the first half of the year. The seasonality in the cohort effect, combined with the urban preponderance of disease, suggests that environmental causes may be involved in ulcerative colitis and Crohn's disease.     

Mortality in inflammatory bowel disease: a population-based cohort study

BACKGROUND & AIMS: There is no consensus regarding any increase in mortality with inflammatory bowel disease (IBD). In general, previous studies were not contemporary and were unable to correct for likely confounders. We have performed a large cohort study to examine contemporary IBD related mortality in the United Kingdom. METHODS: We selected subjects within the General Practice Research Database with a coded diagnosis of inflammatory bowel disease and up to 5 matched controls for each. We derived the date of recorded deaths and information on smoking and a variety of medical conditions. We calculated both the absolute risk of death and the relative risk as a hazard ratio corrected for available confounders by Cox regression. RESULTS: We included 16,550 IBD cases with 1047 deaths and 82,917 controls with 3758 deaths. The mortality rate was 17.1 per 1000 person-years overall for IBD cases and 12.3 for controls; this difference was greatest in the elderly. Conversion of these figures to hazard ratios by Cox regression gave hazard ratios of 1.54 (1.44-1.65) for all IBD, 1.44 (1.31-1.58) for ulcerative colitis (UC), and 1.73 (1.54-1.96) for Crohn's disease. The greatest hazard ratio for UC was among the 40-59-year age group (1.79 [1.42-2.27]) and for Crohn's disease among 20-39-year-olds (3.82 [2.17-6.75]). CONCLUSIONS: IBD is associated with an overall small increase in mortality rate greatest in relative terms in younger subjects but in absolute terms in the elderly.     

The epidemiology of inflammatory bowel disease in Canada: a population-based study

BACKGROUND: Previously, we have demonstrated a high incidence and prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in the Canadian province of Manitoba. However, the epidemiology of inflammatory bowel disease (IBD) in other regions of Canada has not been defined. The aim of this study was to estimate the incidence and prevalence of CD and UC in diverse regions of Canada and the overall burden of IBD in Canada. METHODS: We applied a common case identification algorithm, previously validated in Manitoba to the provincial health databases in British Columbia (BC), Alberta (AB), Saskatchewan (SK), Manitoba (MB), and Nova Scotia (NS) to determine the age-adjusted incidence rates per 100,000 person-years for 1998-2000 and prevalence per 100,000 for mid 2000 and to estimate the IBD burden in Canada. Poisson regression was used to assess differences in incidence rates and prevalence by gender, age, and province. RESULTS: The incidence rate for CD ranged from 8.8 (BC) to 20.2 (NS), and for UC ranged from 9.9 (BC) to 19.5 (NS). The prevalence of CD was approximately 15- to 20-fold higher than the incidence rate, ranging from 161 (BC) to 319 (NS). This was similar for the prevalence of UC, which ranged from 162 (BC) to 249 (MB). Adjusting for age and province, the female:male ratio for incidence ratio was 1.31 (p < 0.0001) for CD and 1.02 (n.s.) for UC and was mostly stable across the five provinces. CONCLUSIONS: Approximately 0.5% of the Canadian population has IBD. Canada has the highest incidence and prevalence of CD yet reported.     

Body composition in patients with inflammatory bowel disease: a population-based study

OBJECTIVE: Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohn's disease (CD) and ulcerative colitis (UC) and to evaluate possible differences between the patient groups and healthy subjects. METHODS: A total of 60 patients with CD, 60 patients with UC, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. Body composition was measured by dual x-ray absorptiometry and Z scores were obtained by comparison to age- and sex-matched normal values. RESULTS: Bone mineral content and lean body mass were significantly lower in patients with CD compared with patients with UC and healthy subjects. The body composition of CD men was more strongly affected than that of women. UC patients had significantly higher fat mass and body mass index than patients with CD and healthy subjects. There was no difference in the percentage of fat mass between the two patient groups. Corticosteroid treatment and smoking had a negative impact on bone mineral content and lean body mass in CD patients independently of each other. CONCLUSIONS: CD was associated with disturbances in body composition: both bone mineral content and lean body mass were significantly reduced, especially in men with CD. Corticosteroid therapy and smoking had a significant influence on body composition in patients with CD. When studying the effects of inflammatory bowel disease on body composition and nutritional status, patients with CD and UC should be evaluated separately.     

The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study

BACKGROUND & AIMS: We aimed to discern the relative risk for several chronic inflammatory conditions in patients with ulcerative colitis (UC) and Crohn's disease. METHODS: We used the population-based University of Manitoba IBD Database that includes longitudinal files on all patients from all health system contacts identified by International Classification of Diseases, 9th revision, Clinical Modification codes for visit diagnosis. From the provincial database we extracted a control cohort matching the IBD patients 10:1 by age, sex, and geography. We considered a potential comorbid disease to be present if the patient had 5 or more health system contacts for that diagnosis. The comorbid disease period prevalence was analyzed separately for patients with UC and Crohn's disease and a prevalence ratio was calculated comparing the IBD populations with the matched cohort. RESULTS: There were 8072 cases of IBD from 1984 to 2003, including UC (n = 3879) and Crohn's disease (n = 4193). There was a mean of approximately 16 person-years of coverage for both patients and control patients. Both UC and Crohn's disease patients had a significantly greater likelihood of having arthritis, asthma, bronchitis, psoriasis, and pericarditis than population controls. An increased risk for chronic renal disease and multiple sclerosis was noted in UC but not Crohn's disease patients. The most common nonintestinal comorbidities identified were arthritis and asthma. CONCLUSIONS: The finding of asthma as the most common comorbidity increased in Crohn's disease patients compared with the general population is novel. These may be diseases with common causes or complications of one disease that lead to the presentation with another. Studies such as this should encourage further research into the common triggers in the organ systems that lead to autoimmune diseases.     

Low prevalence of Helicobacter pylori in inflammatory bowel disease: association with sulphasalazine.

The prevalence of IgG antibodies to Helicobacter pylori was examined in 110 patients with inflammatory bowel disease (IBD) (63 ulcerative colitis, 47 Crohn's disease) and compared with 100 age and sex matched control patients. The overall prevalence of H pylori seropositivity in the IBD patients was 22%, which was significantly less than that of 52% in the controls (p < 0.002). There was no difference in prevalence between ulcerative colitis and Crohn's patients. The low seropositivity in the IBD patients resulted from a very low prevalence of 10% in those currently receiving sulphasalazine (n = 40) and similarly low prevalence of 7% in those previously receiving sulphasalazine (n = 30). In those receiving olsalazine or mesalazine and who had never had sulphasalazine, the prevalence of seropositivity was 45%. Further studies using 14C urea breath test and microscopy of antral biopsy specimens confirmed that the negative serology in patients receiving sulphasalazine resulted from absence of the infection rather than absence of humoral immune response to it. In six control patients with H pylori infection, a two week course of sulphasalazine (500 mg four times daily) only caused slight suppression of the 14C urea breath test. In vitro studies failed to show any direct antibacterial effect of sulphasalazine on H pylori. These findings indicate that longterm treatment with sulphasalazine leads to eradication of H pylori infection and that this does not result from a direct antibacterial effect. It may be caused by the drug treating the gastritis and thereby depriving the bacterium of essential nutrients exuded by the inflamed mucosa.     

Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a population-based study, 1978-2002

OBJECTIVES: Although incidence rates of inflammatory bowel disease have been reported worldwide, few long-term population-based studies with current time-trend analyses exist. We therefore examined time trends in the incidence rate of inflammatory bowel disease in a 25-year study period, and estimated the prevalence in 2002. All patients diagnosed between 1978 and 2002 were included as incident cases (n=2,326) and all patients living in North Jutland County on 31 December 2002 were used to estimate prevalent cases (n=2,205). METHODS: Medical records of all patients diagnosed with ulcerative colitis and Crohn's disease in the North Jutland County Hospital Discharge Registry were reviewed to examine if the diagnostic criteria were fulfilled. Age-specific and gender-specific standardized incidence rates were calculated. RESULTS: For ulcerative colitis, incidence rates in women increased from 8.3 (95% confidence interval (CI): 6.7-9.9) in 1978-1982 to 17.0 (95% CI: 14.7-19.3) per 100,000 person-years in 1998-2002. The corresponding figures for men were 7.7 (95% CI: 6.1-9.3) and 16.7 (95% CI: 14.4-18.8) per 100,000 person-years. For Crohn's disease, the incidence rates in women increased from 4.1 (95% CI: 3.0-5.2) in 1978-1982 to 10.7 (95% CI: 8.8-12.5) per 100,000 person-years in 1998-2002. The corresponding figures for men were 3.2 (95% CI: 2.1-4.2) and 8.5 (95% CI: 6.9-10.2) per 100,000 person-years. The prevalence of ulcerative colitis and Crohn's disease was 294 and 151 per 100,000 inhabitants, respectively. CONCLUSIONS: A marked and parallel increase was seen in both ulcerative colitis and Crohn's disease in both genders during the last 25 years, with a corresponding high prevalence of both diseases.     

The costs of early inflammatory joint disease: a population-based study in southern Sweden

OBJECTIVE: To study the costs and use of healthcare for patients during the first months with early joint inflammation, in a population-based prospective referral study in Southern Sweden. METHODS: Adult patients with arthritis for < 3 months and with onset of symptoms between 1 May 1999 and 1 May 2000 were referred from primary health centres to rheumatologists. Four clinical assessments were performed during a 6-month follow-up period. The direct medical costs for inpatient stays, outpatient visits, visits to general practitioners, and visits to health professionals, as well as costs for medication, radiographs, and laboratory tests were recorded from the onset of the disease up to 6 months of follow-up. Indirect costs for sick leave were also recorded. RESULTS: Fifty-six of 71 referred patients agreed to participate. Thirteen (23%) had RA, 21 (38%) had reactive arthritis (ReA), 14 (25%) had undifferentiated arthritis, and eight (14%) had other arthritides. The median cost per patient in the entire group was USD 3362. The median cost per patient in the RA group was USD 4385, and USD 4085 in the ReA group. There was no statistically significant difference in the median costs per patient in the different diagnostic groups. Sick leave accounted for 44% of the total costs in the entire group, and 46% and 47%, respectively, in the RA and ReA groups. CONCLUSION: The costs of early arthritis are already considerable during the first months of the disease following the onset of the symptoms. The indirect costs due to sick leave accounted for nearly half of the costs.     

Iron deficiency anemia in inflammatory bowel disease

Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.     

Increased risk of atrial fibrillation in patients with inflammatory bowel disease: A nationwide population-based study

BACKGROUND Inflammatory bowel disease (IBD), a chronic inflammatory disease of the gastrointestinal tract, could play a role in the pathophysiology of atrial fibrillation (AF). AIM To investigate the association between IBD and AF development. METHODS We performed a population-based cohort study using records in the Korean National Health Insurance Services database between 2010 and 2014. A total of 37696 patients with IBD (12349 with Crohn’s disease and 25397 with ulcerative colitis) were identified. The incidence rate of newly diagnosed AF in patients with IBD was compared with that in a 3 times larger cohort of 113088 age- and sex-matched controls without IBD. RESULTS During 4.9 ± 1.3 years of follow-up, 1120 patients newly diagnosed with AF (348 in the IBD group and 772 in controls) were identified. After adjustments using multivariable Cox proportional hazards, patients with IBD were at a 36%[95% confidence interval (CI) 20%-54%] higher risk of AF than controls. The association between IBD and the development of AF was stronger in younger than in older patients. Patients without cardiovascular risk factors showed a higher risk of AF primarily. Additionally, patients receiving immun-omodulators [Hazard ration (HR) 1.46, 95%CI 1.31-1.89], systemic corticosteroids (HR 1.37, 95%CI 1.10-1.71), or biologics agents (HR 2.38, 95%CI 1.51-3.75) were at higher risk of AF than patients without them. CONCLUSION IBD significantly increased the risk of AF, and the impact of IBD on developing AF was in patients with moderate to severe disease.     

Risk of inflammatory bowel disease in patients with chronic obstructive pulmonary disease: A nationwide,population-based study

BACKGROUND There is a growing evidence regarding an increased risk of inflammatory bowel disease(IBD) among patients with airway diseases.AIM To investigate the influence of chronic obstructive pulmonary disease(COPD) on the risk of IBD.METHODS A nationwide, population-based study was conducted using data from the National Health Insurance Service database. A total of 1303021 patients with COPD and 6515105 non-COPD controls were identified. The COPD group was divided into the severe and the mild COPD group according to diagnostic criteria. The risk of IBD in patients with COPD compared to controls was analyzed by Cox proportional hazard regression models. The cumulativeincidences of IBD were compared between the groups.RESULTS The COPD group had higher incidences of IBD compared to non-COPD controls(incidence rate, 9.98 vs 7.18 per 100000 person-years, P 0.001). The risk of IBD in the COPD group was increased by 1.38(adjusted hazard ratio(HR); 95%CI: 1.25-1.52). The incidence rate of IBD was higher in the severe COPD group than in the mild COPD group(12.39 vs 9.77 per 100000 person-year, P 0.001). The severity of COPD was associated with an increased risk of IBD(adjusted HR 1.70 in severe COPD, 95%CI: 1.27-2.21 and adjusted HR 1.35 in mild COPD, 95%CI: 1.22-1.49)CONCLUSION The incidences of IBD were significantly increased in COPD patients in South Korea and the risk of developing IBD also increased as the severity of COPD increased.     

Hyperhomocysteinemia and inflammatory bowel disease: prevalence and predictors in a cross-sectional study

OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the demethylation of methionine. Vitamin B12 and folate deficiency and therapy with antifolate drugs may predispose patients with inflammatory bowel disease (IBD) to hyperhomocysteinemia. The known associations between hyperhomocysteinemia and smoking, osteoporosis, and thrombosis make it an interesting candidate as a pathogenetic link in IBD. The aim of this study was to identify the prevalence and risk factors of hyperhomocysteinemia in patients with IBD. METHODS: Sixty-five consecutive IBD patients were recruited from a tertiary outpatient gastroenterology practice. Fasting plasma homocysteine levels were measured, along with vitamin B12 and folate. Data regarding medication use, multivitamin use, disease location and severity, and extraintestinal manifestations of IBD were gathered. Homocysteine levels in 138 healthy control subjects were compared with the IBD cohort, and adjustments for age and sex were made using logistic regression. Multivariate analysis was performed to seek predictors of homocysteine levels. RESULTS: The mean age in the IBD cohort was 42+/-13.4 yr (+/-SD), and 43% were male. The mean disease duration was 13.8+/-9.4 yr, and 32% had used steroids within the last 3 months. Immunomodulator therapy had been used in 32%, and 75% had had an intestinal resection. Osteoporosis was present in 33% of patients. Five patients had experienced venous thrombosis or stroke, but only one of these had hyperhomocysteinemia. Of the 10 IBD patients (15.4%) with hyperhomocysteinemia, only two had vitamin B12 deficiency. The homocysteine levels in the IBD cohort cases and controls were 8.7 and 6.6 micromol/L, respectively (p < 0.05). IBD significantly increased the risk of hyperhomocysteinemia (adjusted odds ratio = 5.9 [95% CI: 1.5-24]). Advanced age, male sex, vitamin B12 deficiency or lower vitamin B12 serum levels, and multivitamin therapy were independently associated with higher homocysteine levels in the multivariate analysis (R2 = 0.55; p = 0.001). CONCLUSIONS: Hyperhomocysteinemia is significantly more common in patients with IBD compared with healthy controls, and is associated with lower (but not necessarily deficient) vitamin B12 levels.     

Association of inflammatory bowel disease with ankylosing spondylitis and rheumatoid arthritis: A nationwide population-based study

Objectives: Tantalizing connections between autoimmune rheumatic diseases (ARDs) and inflammatory bowel disease (IBD) have become evident with regard to their genetic and immunologic background. However, the association between these two disease entities remains unclear. The aim of this study is to investigate the association between each ARD and IBD.

Methods: A nationwide population-based cross-sectional study was performed using the Korean National Health Insurance Claims database. The data of patients with IBD and age- and sex-matched controls between 2009 and 2013 were collected from the database. The prevalence of ARDs, including systemic lupus erythematosus (SLE), inflammatory myositis (polymyositis and dermatomyositis), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), ankylosing spondylitis (AS), and rheumatoid arthritis (RA), was determined. The associations between each ARD and IBD were analyzed using multivariate logistic regression models.

Results: A total of 40,843 IBD patients (28,197 patients with ulcerative colitis and 12,646 with Crohn’s disease) and 122,529 controls were enrolled. The nonstratified analysis revealed that patients with IBD had significant risk of being concomitantly affected by AS (odds ratio [OR] 5.140, 95% confidence interval [95% CI] 4.069–6.492) and RA (OR: 3.474, 95% CI: 2.671–4.519) after adjusting for age and sex. No significant association was observed between IBD and other ARDs including SLE, inflammatory myositis, SSc, and SjS.

Conclusion: IBD is significantly associated with AS and RA in the large-scaled population-based study. This result suggests that etiopathogenesis of IBD might be shared with AS and RA.