Erling Aadland

Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study)

Objective. Cohort studies of unselected and newly diagnosed patients are essential for a better understanding of the prognosis in ulcerative colitis (UC). The aim of this study was to evaluate the course of UC in a population-based inception cohort during the first 10 years, and to identify prognostic risk factors based on information gathered at diagnosis. Material and methods. From 1990 to 1994, a population-based cohort of 843 patients with inflammatory bowel disease was enrolled in South-Eastern Norway. The cohort was systematically followed-up at 1, 5 and 10 years after diagnosis. Results. Of 519 patients with UC, 423 completed the 10-year follow-up, 53 died and 43 were lost to follow-up. The mortality risk was not increased compared with that in the general population. The cumulative colectomy rate after 10 years was 9.8% (95% CI: 7.4–12.4%). Initial presentation with extensive colitis and erythrocyte sedimentation rate (ESR) ≥30 mm/h was associated with an increased hazard ratio (HR) (3.57, 95% CI: 1.60–7.96) and age ≥50 years at diagnosis, with reduced HR (0.28, 95% CI: 0.12–0.65) for subsequent colectomy. Relapsing disease was noted in 83%, but half (48%) of the patients were relapse free during the last 5 years. One-fifth (69/288) of patients with proctitis or left-sided colitis had progressed to extensive colitis. Conclusions. The prognosis for UC during the first 10 years was generally good. The colectomy rate was low, and a large proportion of patients were in remission as time progressed. Patients with initially extensive colitis and elevated ESR could benefit from an early potent medical treatment strategy.

Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein.

This study comprised 62 outpatients with ulcerative colitis who underwent 64 colonoscopies. The disease activity was evaluated according to endoscopic and histological criteria. The results revealed a significant correlation between both the endoscopic as well as the histological gradings of disease activity and faecal calprotectin. The median faecal calprotectin levels in the control group (6 mg/l) and in the patients with no or low disease activity (11.5 mg/l) were significantly different (p < 0.0001). The median calprotectin level among patients with active disease was 68 mg/l which was significantly different from the latter group (p < 0.0001). Furthermore, we suggest that the degree of inflammation rather than the extent of the disease determined the faecal calprotectin levels. In conclusion, assessment of faecal calprotectin seems to be a marker of disease activity in patients with ulcerative colitis.

Primary Sclerosing Cholangitis: A Long-Term Follow-up Study

During the 10-year period from 1 January 1975 to 31 December 1984, primary sclerosing cholangitis (PSC) was diagnosed in 45 patients. Twelve of the patients have died (26.7%), 10 of them of causes related to PSC. Inflammatory bowel disease was found in all patients; ulcerative colitis was found in 37, Crohns disease in 6, and unclassified colitis in 2 patients. Of the patients alive, 27 were submitted to a follow-up study in 1985. At the follow-up examination no general progression of the liver disease, as measured on the basis of clinical examination and levels of transaminases, alkaline phosphatases, and bilirubin, was found. Cholangiographic evaluation in 24 patients showed that the stage of ductal changes progressed from mild to moderate in 3 patients; in the other patients the stage was not altered. Morphologic examination of liver biopsy specimens in patients with a benign clinical course usually showed portal inflammation, fibrosis, and minor signs of piecemeal necrosis, whereas widespread piecemeal necrosis was found in patients who deteriorated and died. The 50% survival since diagnosis of liver disease was calculated to be 17 years in patients with PSC and 50 years in a comparable group among the general population. The estimated survival curve in PSC was displaced to the left, indicating a reduced life expectancy of about 30 years.

Vitamin D Status, Parathyroid Hormone and Bone Mineral Density in Patients with Inflammatory Bowel Disease

Background: Although the pathogenesis of osteoporosis in inflammatory bowel disease (IBD) is not established, vitamin D deficiency and disturbances in calcium metabolism are thought to be of importance, especially in Crohn disease (CD). Vitamin D status is assessed and the relation between indices of calcium metabolism, including 25-hydroxyvitamin D and parathyroid hormone concentrations, and bone mineral density (BMD) in CD and ulcerative colitis (UC) are examined. Sixty patients with CD and 60 with UC were investigated. Each group comprised 24 men and 36 women. Methods: Vitamin D metabolites, parathyroid hormone and biochemical markers of bone metabolism were measured in blood and urine. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA) and Z-scores were obtained by comparison with age- and sex-matched normal values. Results: Vitamin D deficiency (25-hydroxyvitamin D3 <30 nmol/l) was present in 27% of patients with CD and in 15% with UC. Furthermore, CD patients had a significantly lower mean concentration of 25-hydroxyvitamin D3 compared with UC patients. Vitamin D status was not related to BMD at any of the skeletal sites measured. Secondary hyperparathyroidism was found in 10 out of 27 patients with CD after small-bowel resections. No differences were found in serum osteocalcin and urine pyridinoline between patients with CD and those with UC. Conclusions: Hypovitaminosis D is common in CD patients. Patients with CD and small-bowel resections are at risk of developing secondary hyperparathyroidism and low BMD.

Incidence of Crohn's Disease in Four Counties in Southeastern Norway, 1990–93 A Prospective Population-Based Study

BACKGROUND Standardized criteria for Crohns disease (CD) have only recently been developed, and prospective community-based incidence studies have been performed only during the past 3 decades. Geographic variations in incidence may therefore be due to differences in study design. METHODS From 1 January 1990 to 31 December 1993 all new cases of CD in four counties in southeastern Norway were prospectively registered. RESULTS A total of 225 new cases yielded an annual incidence of 5.8/10(5), with the highest incidence in mixed rural-urban areas. A peak of 11.2/10(5) in the annual incidence was found for the age group 15 to 24 years, with no significant differences in the overall annual incidence by gender. An average duration of 6 months of disease before diagnosis was unchanged during the 4 years. About half of the patients had isolated colonic disease, and one-quarter had isolated small-bowel disease. CONCLUSIONS This study confirms the high incidence figures for Scandinavia, with a particularly high incidence in mixed rural-urban areas. Ileocolonoscopy improves the accuracy of the diagnosis and of the determination of disease extent, which may have therapeutic implications for the treatment and follow-up of patients.

Clinical course in Crohn's disease: Results of a five-year population-based follow-up study (the IBSEN study)

Background. There are few population-based, prospective studies on the clinical course in patients with Crohns disease (CD). Aim. To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification. Methods. All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990–1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy. Results. Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period. Conclusions: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.

Clinical Course during the 1st Year after Diagnosis in Ulcerative Colitis and Crohn's Disease: Results of a Large, Prospective Population-based Study in Southeastern Norway, 1990-93

BACKGROUND The clinical course and prognosis in ulcerative colitis (UC) and Crohns disease (CD) have been described in many studies, mostly retrospective. Such studies are hampered by problems such as inclusion over a long time period, proper definitions, incomplete case records, and outdated methods of diagnosis. In a prospective study we identified 846 patients with inflammatory bowel disease (IBD) over a 4-year period from 1990 to 1993. Uniform diagnostic and therapeutic strategies were used as a basis for later assessment of the short-term clinical course in different subgroups of UC and CD and analysis of potential risk factors for relapse or surgery. METHODS At the time of follow-up, a mean of 16.2 months after diagnosis, 496 UC patients and 232 CD patients, altogether 98%, were available for evaluation. A colonoscopy was performed in 88% (410 of 465) of the UC patients attending a clinical examination and in 76% (164 of 216) of the CD patients. RESULTS Eleven patients with UC and five patients with CD died during follow-up, four of complications related to IBD. The cumulative 1-year relapse rate in the remaining patients was 50% for UC and 47% for CD. Of the patients with relapses 11 % of the UC patients and 10% of the CD patients had a chronic relapsing course without any difference with regard to the various disease categories in UC or CD. An increased risk of relapse was found in patients less than 50 years old only in UC. In UC a higher risk for surgery was found in patients with extensive colitis compared with left-sided colitis (P = 0.011), and CD patients with small-bowel involvement had a higher risk of surgery than patients with disease confined to the colon (P = 0.021). There was no excess risk of relapse or surgery in smokers as compared with non-smokers or former smokers, nor did the risk of relapse vary with the level of cigarette consumption in either UC or CD patients. CONCLUSION The high relapse rate of around 50% for both UC and CD calls for a review of the existing treatment. Further follow-up will be necessary to improve our ability to make clinical decisions relating to medical and surgical treatment options.

Relationship between sick leave, unemployment, disability, and health‐related quality of life in patients with inflammatory bowel disease

Background The goal of this study was to determine the rate of work disability, unemployment, and sick leave in an unselected inflammatory bowel disease (IBD) cohort and to measure the effect of working status and disability on the patients health‐related quality of life (HRQOL). Materials and Methods All eligible patients were clinically examined and interviewed at the 5‐year follow‐up visit. In addition, they completed the 2 HRQOL questionnaires, the Short Form‐36 Health Survey (SF‐36) and the Inflammatory Bowel Disease Questionnaire validated for use in Norway (N‐IBDQ). Data regarding sick leave, unemployment, and disability pension (DP) also were collected. Results All together, 495 patients were or had been in the workforce during the 5‐year follow‐up period since diagnosis. Forty‐two patients (8.5%) were on DP compared with 8.8% in the background population. Women with Crohns disease (CD) had the highest probability of receiving DP (24.6%). A total of 58 patients (11.7%) reported they were unemployed at 5 years. This was equally distributed between men and women but was more frequent in patients with ulcerative colitis. Sick leave for all causes was reported in 47% with ulcerative colitis and 53% with CD, whereas IBD‐related sick leave was reported in 18% and 23%, respectively. A majority (75%) had been sick <4 weeks, and a relatively small number of patients (25%) contributed to a large number of the total sick leave days. Both unemployment and DP reduced HRQOL scores, but the most pronounced effect on HRQOL was found in patients reporting IBD‐related sick leave, measured with SF‐36 and N‐IBDQ. The observed differences also were highly clinically significant. Multiple regression analysis confirmed that IBD‐related sick leave was the independent variable with the strongest association to the observed reduction in HRQOL scores. Conclusions Unemployment or sick leave is more common in IBD patients than in the Norwegian background population. The number of patients receiving DP is significantly increased in women with CD but not in the other patient groups. Unemployment, sick leave, and DP are related to the patients HRQOL in a negative way, but this effect is most pronounced in patients reporting IBD‐related sick leave.

Faecal Calprotectin: A Novel Test for the Diagnosis of Colorectal Cancer?

Calprotectin, a prominent cytosol protein in neutrophil granulocytes, was present in increased concentrations in stools from 50 of 53 patients with colorectal cancer, 32 of 40 patients with colorectal polyps, and all of 18 patients with gastric cancer. After radical surgery, faecal calprotectin levels reverted to the normal range in all but one patient with colorectal cancer. Calprotectin determinations are simplified by the stability of this protein in stools. Reliable estimates can be obtained in samples of only 5 g. On the basis of data from the literature, the test for calprotectin seems better than that for occult blood for the detection of gastrointestinal neoplasms.

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

OBJECTIVES:Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohns 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.