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PubMed2000

Helicobacter hepaticus does not induce or potentiate colitis in interleukin-10-deficient mice.

Helicobacter hepaticus has been reported to induce colitis, hepatitis, and hepatocellular carcinoma in several different murine models. The aim of this study was to determine if H. hepaticus will cause colitis in monoassociated mice lacking the interleukin-10 gene (IL-10(-/-) mice) and potentiate colitis in specific-pathogen-free (SPF) IL-10(-/-) mice. Germfree IL-10(-/-) mice on either a mixed (C57BL/6 x 129/Ola) or inbred (129/SvEv) genetic background were monoassociated with H. hepaticus ATCC 51448 by oral feeding and rectal enemas. In a second experiment, germfree IL-10(-/-) mice were colonized with stool from SPF mice that harbored or did not harbor endogenous H. hepaticus. After 7 to 9 weeks of colonization, weight loss and mortality were assessed, the colon was isolated for histology and IL-12 secretion, and mesenteric lymph node cells were assessed for T-cell activation markers. It was found that IL-10(-/-) mice monoassociated with H. hepaticus for up to 16 weeks showed almost no histologic colitis or increased IL-12 production. SPF IL-10-knockout mice had no significant difference in weight loss, mortality rate, histologic scores, colonic IL-12 secretion, or T-cell activation with or without H. hepaticus. We conclude that H. hepaticus does not induce or potentiate disease in our IL-10(-/-) mice and therefore is not required to induce colitis in genetically susceptible hosts.

Animals↗
PubMed2001

Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis.

The rat tapeworm Hymenolepis diminuta was used to test the hypothesis that helminth infection could modulate murine colitis. Mice were infected with five H. diminuta cysticercoids, and colitis was evoked via free access to 4% (wt/vol) dextran sulfate sodium (DSS)-containing drinking water for 5 days. BALB/c mice were either infected with H. diminuta and 7 days later exposed to DSS (prophylactic strategy) or started on DSS and infected with H. diminuta 48 h later (treatment strategy). Naive and H. diminuta-only-infected mice served as controls. On autopsy, colonic segments were processed for histological examination and myeloperoxidase (MPO) measurement or mounted in Ussing chambers for assessment of epithelial ion transport. Cytokines (gamma interferon [IFN-gamma], interleukin 12 [IL-12], and IL-10) were measured in serum and colonic tissue homogenates. DSS treatment resulted in reduced ion responses (indicated by short-circuit current [Isc]) to electrical nerve stimulation, the cholinergic agonist carbachol, and the adenylate cyclase activator forskolin compared to controls. H. diminuta infection, either prophylactic or therapeutic, caused a significant (P < 0.05) amelioration of these DSS-induced irregularities in stimulated ion transport. In contrast, the histopathology (i.e., mixed immune cell infiltrate, edema, and ulcerative damage) and elevated MPO levels that accompany DSS colitis were unaffected by concomitant H. diminuta infection. Similarly, there were no significant differences in levels of IFN-gamma, IL-12, or IL-10 in serum or tissue from any of the treatment groups at the time of autopsy. We suggest that abolishment of colitis-induced epithelial ion transport abnormalities by H. diminuta infection provides proof-of-principle data and speculate that helminth therapy may provide relief of disease symptoms in colitis.

Animals↗
PubMed1979

Campylobacter colitis.

Eleven consecutive patients with diarrhoea from whose stools campylobacter were isolated were investigated by sigmoidoscopy and rectal biopsy. Eight had definite proctitis, and in seven biopsy specimens were abnormal with histological changes ranging from non-specific colitis to gross colitis with goblet-cell depletion and crypt-abscess formation. Nine of the patients passed blood in their stools, and in all but one abdominal pain was a feature of the illness. Severe campylobacter colitis may be clinically, sigmoidoscopically, and histologically difficult to differentiate from ulcerative colitis and is a differential diagnosis in acute colitis.

Adolescent↗
PubMed1987

Acute colitis in a district general hospital.

A review of all patients who had been admitted to hospital with acute ulcerative colitis in one health district between 1975 and 1984 showed that 96 had required 114 admissions with acute colitis: 42% (40) were admitted during their first attack, and 20% (19) required urgent surgery. A further nine patients underwent surgery after responding initially to intensive medical treatment that did not check the attack. There were no deaths from acute colitis. Thirteen patients underwent elective surgery for ulcerative colitis, and there were no deaths. The prognosis for acute colitis in district general hospitals has improved.

Colitis↗
PubMed1992

Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

OBJECTIVE: To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN: One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING: Outpatient clinics of five hospitals. SUBJECTS: 79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE: Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS: For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS: Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.

Azathioprine↗
PubMed1970

Arthropathy, ankylosing spondylitis, and clubbing of fingers in ulcerative colitis.

In a retrospective study of 399 patients with ulcerative colitis, 27 patients had colitic arthritis, 17 had ankylosing spondylitis, and 20 had clubbing of the fingers. Colitic arthritis and ankylosing spondylitis were not related to severity, extent of involvement, or duration of colitis. A significant association between colitic arthropathy and other complications of ulcerative colitis, such as pseudopolyposis, perianal disease, eye lesions, skin eruptions, aphthous ulceration, and liver disease has been demonstrated. The outcome of the first referred attack of colitis in the presence of colitic arthritis and ankylosing spondylitis remained uninfluenced. Clubbing of fingers was related to severity, extent of involvement, and length of the history of colitis. A significant association between clubbing of the fingers and carcinoma of the colon, pseudopolyposis, toxic dilatation, and arthropathy has been shown. The frequency of surgical intervention in patients with clubbing was higher but the overall mortality was not significantly different from the patients without clubbing.

Adolescent↗
PubMed1973

Electrical potential difference and sodium and potassium fluxes across rectal mucosa in ulcerative colitis.

The transmucosal electrical potential difference (pd) and the sodium and potassium flux rates (using a dialysis method) have been measured in the rectum and distal sigmoid colon of patients with ulcerative colitis and compared with measurements made in individuals having normal bowel function. In active colitis, a very low transmucosal pd was found and was associated with loss of the characteristic ability of the mucosa to absorb sodium against considerable electrochemical gradients; a marked increase in the plasma-to-lumen sodium flux rate, suggesting increased leakiness of the mucosa; and loss of the active sodium absorption mechanism. In resolving colitis, the pd was higher and all these changes of sodium transport tended to return towards normal. With full recovery, epithelial function was normal to the present tests. Potassium secretion rate showed little difference at various stages of the disease, but the nearly normal secretion of potassium in ulcerative colitis when the pd was low suggested that potassium loss to the lumen was excessive. Mucus collected from patients with ulcerative colitis had a relatively high sodium and potassium content. Measurement of pd and absorption by using a dialysis tube offers a simple means of rapid assessment of mucosal functional integrity.

Adult↗
PubMed1979

Light and electron microscopic studies of antibiotic associated colitis in the hamster.

Lincomycin and its analogue, clindamycin, are capable of producing mild to severe colonic mucosal injury in humans (antibiotic associated colitis). Patients with the disorder may have severe diarrhoea, pseudomembranous plaques, confluent pseudomembranes, and/or a frank, diffuse haemorrhagic colitis. The present study was designed to assess the Golden Syrian hamster as an animal model for antibiotic associated colitis and to describe lesions seen in the animal model by light, transmission electron, and scanning electron microscopy. A colitis was produced in Golden Syrian hamsters by oral or parenteral administration of lincomycin, clindamycin, or N-demethyl clindamycin. Animals were killed at intervals and microscopic studies made of sequential morphological changes in the ileum, caecum, and colon. The microscopic lesions in the early stages of the disorder were abnormalities within the brush border, cellular oedema, and hyperaemia. Changes in the intracellular organelles were observed in more severely damaged epithelial cells. Epithelial hyperplasia resulted in the piling up of cells on the mucosal surfaces. In specimens with the most severe damage, complete loss of epithelium from the mucosal surface was observed. Pseudomembranous plaques were occasionally seen. Comparison of the clinical, gross, and histological features of the animal disease with the human disorder suggest that, although minor differences are present, the hamster model is suitable for experimental studies of antibiotic associated colitis.

Animals↗
PubMed2004

Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients.

BACKGROUND: Lymphocytic colitis is characterised by chronic diarrhoea and specific microscopic changes in a macroscopically normal colonic mucosa. We report clinical features and treatment outcome in a large patient cohort. METHODS: Patients were searched for in 24 Swedish gastroenterology clinics. The biopsy material was reassessed using strict histopathological criteria. Clinical data were obtained from medical notes. RESULTS: Lymphocytic colitis was diagnosed in 199 cases. The female:male ratio was 2.4:1. Median age at diagnosis was 59 (48-70) years. The most frequent symptoms were diarrhoea (96%), abdominal pain (47%), and weight loss (41%). The course was chronic intermittent in 30% of patients, chronic continuous in 7%, and a single attack in 63%, and in these cases the disease duration was 6 (4-11) months. Seventy nine (40%) patients reported associated diseases, of which thyroid disorders, coeliac disease, and diabetes mellitus were the most common. In 34 first or second degree relatives of 24 (12%) patients, a family history of ulcerative colitis, Crohn's disease, collagenous colitis, or coeliac disease was reported. Drug induced disease was suspected in 19 (10%) patients. A non-significant peak of disease onset was seen in December-January. More than 80% of treated patients improved on corticosteroids, including budesonide. CONCLUSIONS: A family history of other bowel disorders is a new finding. The sudden onset and single attack of limited duration may support a possible infectious cause in some cases. Drugs may cause lymphocytic colitis.

Aged↗
PubMed2005

Amelioration of 2,4,6-trinitrobenzene sulphonic acid induced colitis in angiotensinogen gene knockout mice.

BACKGROUND: A number of recent studies have demonstrated a protective effect of renin-angiotensin system (RAS) antagonism against immune mediated diseases such as myocarditis, chronic allograft rejection, and antiglomerular basement membrane nephritis. To our knowledge, there has been no report on the immunological contribution of the RAS in colonic tissue. AIMS: We evaluated the direct effect of angiotensin II (AII) on the pathogenesis of immune mediated colitis using angiotensinogen deficient homozygous (Atg-/-) mice. SUBJECTS: 2,4,6-Trinitrobenzene sulphonic acid (TNBS) colitis was induced in Atg-/- and wild-type (Atg+/+) mice. METHODS: Levels of proinflammatory cytokines in the colon were determined by enzyme linked immunosorbent assay. Histological analysis was performed simultaneously. RESULTS: Although Atg-/- mice developed colitis, the degree was much milder than that in Atg+/+ mice (p<0.05). Colonic cytokine analysis showed that the production of proinflammatory cytokines (interleukin (IL)-1beta, interferon gamma (IFN-gamma)) was impaired in Atg-/- mice. Furthermore, expression of cytokines such as IL-4 and IL-10 in the colon was predominant in Atg-/- compared with Atg+/+ mice after TNBS instillation (p<0.005, p<0.01, respectively). Similarly, subcutaneous infusion of losartan suppressed colitis (p<0.05) and the production of proinflammatory cytokines (IL-1beta, IFN-gamma). These results indicate that the RAS is directly involved in the pathogenesis of TNBS colitis through regulation of proinflammatory and anti-inflammatory cytokines in the colon. CONCLUSIONS: This study revealed that the RAS is involved in the immune system in the colon. Antagonism of the RAS is a potential prophylactic strategy for the treatment of human inflammatory bowel disease.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

In vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4+CD62L+ T cells which prevent intestinal inflammation in the SCID transfer model of colitis.

BACKGROUND AND METHODS: Cytosin-guanosin dinucleotide (CpG) motifs of bacterial DNA are known to be potent activators of innate immunity. We have shown previously that administration of CpG containing oligodeoxynucleotide (CpG-ODN) to mice before the onset of dextran sodium sulphate induced colitis ameliorated colitis and inhibited induction of proinflammatory cytokines. To investigate the possible involvement of CD4(+) T cells in the prophylactic CpG-ODN effects, we used the SCID transfer model of colitis. RESULTS: CD4(+)CD62L(+) T cells from CpG-ODN treated donors did not induce significant intestinal inflammation in SCID recipients, in contrast with control cells. Additionally, cotransfer of these cells with CD4(+)CD62L(+) cells from normal mice protected recipient animals from colitis, indicating regulatory activity. Also, CD4(+)CD62L(+) cells from toll-like receptor 9 deficient animals induced a significantly more severe colitis in SCID recipients than cells from wild-type littermate controls, suggesting a similar protective role of "endogenous" bacterial DNA leading to a less "aggressive" phenotype of these cells. There was no detectable difference in regulatory T cell surface markers between aggressive and attenuated cell pools but attenuated cell pools showed reduced proliferation in vitro and in vivo and produced less interferon gamma, interleukin (IL)-5, and IL-6 after anti-CD3 stimulation. CONCLUSIONS: Collectively, our data support the concept that both endogenous bacterial DNA and exogenously supplied CpG motifs of bacterial DNA induce regulatory properties in CD4(+) T cells. Therefore, bacterial DNA derived from the normal gut flora may contribute essentially to the homeostasis between effector and regulatory immune mechanisms in healthy individuals to protect them from chronic intestinal inflammation.

Animals↗
PubMed2005

Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis.

BACKGROUND: The resident flora plays a critical role in initiation and perpetuation of intestinal inflammation, as demonstrated in experimental models of colitis where animals fail to develop disease under germ free conditions. However, the importance of exposure to commensal bacteria before the onset of colitis is unclear. Our aim was to investigate the influence of previous exposure of donor animals to bacterial antigens on colitis development using a transfer model. METHODS: Clinical course and histology were evaluated after transfer of CD4(+)CD62L(+) lymphocytes from germ free and conventionally housed donor mice into SCID recipients. Cotransfer of CD4(+)CD62L(+) cells with CD4(+)CD62L(- )lymphocytes from both groups of mice was initiated. Lymphocytes were analysed by FACS, polarisation potential of cells determined, and cytokines measured within the supernatant by enzyme linked immunosorbent assay. RESULTS: Animals that received cells from germ free donors developed an earlier onset of colitis compared with mice reconstituted with lymphocytes from conventionally housed animals. Additionally, CD4(+)CD62L(- )cells from germ free mice were not able to abrogate colitis induced by cotransfer with CD4(+)CD62L(+) lymphocytes whereas CD4(+)CD62L(- )T cells from normal mice ameliorated disease. The higher percentage of CD4(+)GITR(+) expressing lymphocytes and the production of interleukin 10 after priming by dendritic cells suggests the presence of T(reg) cells within the CD4(+)CD62L(+) lymphocyte subset derived from conventional housed mice and assumes a lack of T(reg) cells within germ free mice. CONCLUSION: The results indicate that bacterial antigens are crucial for the generation and/or expansion of T(reg) cells in a healthy individual. Therefore, bacterial colonisation is of great importance in maintaining the immunological balance.

Adoptive Transfer↗
PubMed2005

In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy.

BACKGROUND: Mouse models of colitis and cancer are indispensable for our understanding of the pathogenesis of these diseases. In the past, mice had to be sacrificed in order to analyse colitis activity and tumour development. We have developed a safe method for high resolution endoscopic monitoring of living mice. METHODS: Mice developing colitis or colonic tumours were anaesthetised using avertine and repeatedly examined by endoscopy. A novel miniendoscope (1.9 mm outer diameter), denoted Coloview, was introduced via the anus and the colon was carefully insufflated with an air pump before analysis of the colonic mucosa. An extra working channel allowed the introduction of biopsy forceps or injection needles as well as surface staining with methylene blue in order to visualise the surface of the crypts and the pit pattern architecture. RESULTS: Endoscopic pictures obtained were of high quality and allowed monitoring and grading of disease. Scoring of colitis activity as well as tumour size and growth was possible. In addition, pit pattern analysis using chromoendoscopy permitted discrimination between inflammatory and neoplastic changes. Biopsies yielded enough tissue for molecular and histopathological analyses. CONCLUSIONS: In summary, chromoendoscopy in mice allows monitoring of the development of colitis and colon cancer with high resolution. Manipulations such as local injection of reagents or taking biopsies can be performed easily.

Animals↗
PubMed2005

Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice.

BACKGROUND AND AIMS: Interleukin (IL)-15 is a member of the IL-2 family, stimulating dendritic cells, natural killer (NK) cells, NK T cells and memory CD8+ T cells. IL-15 levels were elevated in the intestinal mucosa of inflammatory bowel diseases. Here we investigated the involvement of IL-15 in the pathogenesis of acute and chronic dextran sulphate sodium (DSS) induced colitis. METHODS: IL-15 knockout (KO) mice and control C57BL/6 mice were used to induce colitis with DSS in their drinking water. Survival rate, clinical activity of diseases, extent of tissue damage, leucocyte population, and cytokine production of lamina propria (LP) cells of the large intestines were assessed. RESULTS: IL-15 KO mice exhibited resistance to DSS induced acute colitis, as reflected by lower lethality, weight loss, clinical scores, and histological scores compared with those in control mice (p<0.05). The proportions of CD44(high) CD8+ T cells and NK cells in LP cells and levels of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, and IL-12p40 in culture supernatants of LP cells were reduced in IL-15 KO mice (p<0.05). In vivo depletion of CD8+ T cells and NK cells decreased levels of IFN-gamma, TNF-alpha, and IL-12p40 in culture supernatants of LP cells in C57BL/6 mice (p<0.01). In chronic colitis, weight loss and clinical scores were improved and levels of IFN-gamma, TNF-alpha, and IL-12p40 in culture supernatants of LP cells were also reduced in IL-15 KO mice (p<0.05). CONCLUSIONS: IL-15 plays an important role in the pathogenesis of both acute and chronic colitis induced by DSS in mice.

Acute Disease↗
PubMed2006

Crucial role of the melanocortin receptor MC1R in experimental colitis.

BACKGROUND AND AIMS: alpha-Melanocyte stimulating hormone (alpha MSH) is known to exert anti-inflammatory effects, for example in murine DSS (dextran sodium sulphate induced) colitis. The anti-inflammatory functions of alpha MSH are mediated by the melanocortin1-receptor (MC1R) in an autoregulatory loop. The aim of this study was therefore to determine whether a breakdown of the alpha MSH-MC1R pathway leads to worsening of disease. METHODS: Experimental colitis was induced in mice with a frameshift mutation in the MC1R gene (MC1Re/e), C57BL/6 wild type mice, and MC1Re/e-C57BL/6 bone marrow chimeras. The course of inflammation was monitored by weight loss, histological changes in the colon, and myeloperoxidase activity. In addition, MC1R expression was analysed in intestinal epithelial cells. RESULTS: While the colon of untreated MC1Re/e appeared normal, the course of DSS-colitis in MC1Re/e mice was dramatically aggravated, with a significantly higher weight loss and marked histological changes compared to C57BL/6WT. The inflammation eventually led to death in all MC1Re/e, while all C57BL/6WT survived. Similar observations were detected in a transmissible murine colitis model induced by Citrobacter rodentium. Infected MC1Re/e showed delayed clearance of infection. To determine whether missing haematopoietic cell expressed MC1R was responsible, DSS colitis was induced in MC1Re/e-C57BL/6 bone marrow chimeras. MC1Re/e mice receiving MC1R+ bone marrow showed a similar course of inflammation to non-transplanted MC1Re/e. Likewise, transplantation of MC1R bone marrow into C57BL/6WT mice did not lead to any worsening of disease. CONCLUSIONS: This is the first study to show a functional role of MC1R in intestinal inflammation. The data suggest a pivotal role of non-haematopoietic cell expressed MC1R in the host's response to pathogenic stimuli.

Animals↗
PubMed2006

Pit patterns in rectal mucosa assessed by magnifying colonoscope are predictive of relapse in patients with quiescent ulcerative colitis.

BACKGROUND: Relapse of ulcerative colitis is difficult to predict by routine colonoscopy. A high-resolution video-magnifying colonoscope with chromoscopy enables the observation of colorectal mucosal pit patterns. AIMS: To investigate the association of pit patterns as assessed by magnifying colonoscopy (MCS) with histological inflammation and mucosal chemokine activity in patients with quiescent ulcerative colitis, and to prospectively analyse the prognostic factors that may predict exacerbations. METHODS: MCS was performed in 113 patients with ulcerative colitis in remission. Pit patterns in the rectal mucosa were classified into four MCS grades on the basis of size, shape and arrangement. Mucosal interleukin (IL) 8 activity was measured in biopsy specimens of rectal mucosa and the specimens were assessed for histological disease activity. The patients were then followed until relapse or for a maximum of 12 months. Multivariate survival analysis was carried out to determine the independent predictors of clinical relapse. RESULTS: A positive correlation was identified between MCS grade, histological grade (p = 0.001) and mucosal IL8 activity (p<0.001). Multivariate proportional hazard model analysis showed that MCS grade was a significant predictor of relapse (relative risk 2.06, p = 0.001). Kaplan-Meier estimate of relapse during 12 months of follow-up was found to increase with increasing MCS grade, with values of 0% for grade 1, 21% for grade 2, 43% for grade 3 and 60% for grade 4. CONCLUSION: MCS grading is associated with the degree of histological inflammation and mucosal IL8 activity in patients with quiescent ulcerative colitis, and may predict the probability of subsequent disease relapse in patients with ulcerative colitis in remission.

Adolescent↗
PubMed2006

GITR modulates innate and adaptive mucosal immunity during the development of experimental colitis in mice.

BACKGROUND: Uncontrolled T cell activation and abnormal function of the innate immune system against normal enteric bacterial flora play a critical part in the pathogenesis of inflammatory bowel disease (IBD). Therefore, pharmacological strategies directed to restore the normal responsiveness of the immune system could be efficacious in the treatment of these pathological conditions. Glucocorticoid-induced tumour necrosis factor receptor (GITR)-related gene is a member of the tumour necrosis factor receptor superfamily that is constitutively expressed at high levels on regulatory T cells and at low levels on unstimulated T cells, B cells and macrophages. GITR triggering leads to activation of T effectors and reversal of suppressive function of regulatory T cells. AIM: To investigate the role of GITR in the development of experimental colitis in mice. RESULTS: Using GITR(-/-) mice, GITR deletion protected against 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis by reducing innate immune responses and effector T cell activity. Effector T cells isolated from GITR(-/-) mice were less effective than T cells isolated from GITR(+/+) mice to transfer colitis in immunodeficient mice. Blocking the GITR/ligand for GITR (GITRL) signal by giving soluble GITR prevented TNBS-induced colitis in normal GITR(+/+) and also in lymphocyte-deficient SCID mice. CONCLUSIONS: Collectively, these data suggest that GITR plays a critical part in regulating both acquired and innate mucosal immune responses during the development of experimental colitis in mice. Therefore, targeting the GITR/GITRL system signalling may represent a potential pharmacological tool for the treatment of IBD.

Animals↗
PubMed2006

Ulcerative colitis: no rise in mortality in a European-wide population based cohort 10 years after diagnosis.

BACKGROUND: Population based studies have revealed varying mortality for patients with ulcerative colitis but most have described patients from limited geographical areas who were diagnosed before 1990. AIMS: To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis related mortality across Europe. METHODS: Mortality 10 years after diagnosis was recorded in a prospective European-wide population based cohort of patients with ulcerative colitis diagnosed in 1991-1993 from nine centres in seven European countries. Expected mortality was calculated from the sex, age and country specific mortality in the WHO Mortality Database for 1995-1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: At follow-up, 661 of 775 patients were alive with a median follow-up duration of 123 months (107-144). A total of 73 deaths (median follow-up time 61 months (1-133)) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to 1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a slightly higher risk in older age groups. For disease specific mortality, a higher SMR was found only for pulmonary disease. Mortality by European region was SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45-1.37) for the south. CONCLUSIONS: Higher mortality was not found in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease, and a trend towards an age related rise in SMR, was observed.

Adolescent↗