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The role of azathioprine in the management of ulcerative colitis.

The use of azathioprine in ulcerative colitis is unclear. The authors present the details and outcome of 47 patients who received azathioprine for either a) severe, resistant disease otherwise requiring surgery (28 patients) or b) patients with steroid dependence who have been followed up for at least 12 months (19 patients). Duration of treatment ranged from one week to 66 months (median, 12 months). Of the patients in Group I, 13 (46 percent) achieved remission, 11 of whom had not relapsed during a median follow-up of 22 months (range, 12 to 58 months), and 15 underwent surgery one week to 12 months (median, five weeks) after commencing azathioprine. In Group II, steroids were withdrawn or reduced in 12 (63 percent) patients and three patients required colectomy. Side effects necessitating withdrawal of azathioprine occurred in 12 patients (hematologic effects, 6 patients; gastrointestinal effects, 4 patients; other effects, 2 patients). Two patients required a reduced dose of azathioprine because of leukopenia. The authors conclude that azathioprine is a valuable therapeutic option in selected patients with ulcerative colitis.

Adult↗

Mucosal cell proliferation of the rectal stump in ulcerative colitis patients after ileorectal anastomosis.

The proliferative activity and polyamine levels of the rectal epithelium in unoperated ulcerative colitis patients and in ulcerative colitis patients after total colectomy and ileorectal anastomosis were determined and compared with control subjects. Cell proliferation was evaluated in rectal biopsies by in vitro 3H thymidine incorporation by measuring the labeling index and the position of labeled cells along the crypt; polyamines were determined with a chromatographic method. In ulcerative colitis patients the labeling index was significantly increased, and labeled cells were shifted toward the upper part of the crypt when compared with controls. Ileorectal anastomosis patients showed a normalization of the labeling index and a distribution of labeled cells similar to controls. Polyamine levels were also increased in ulcerative colitis patients; in ileorectal anastomosis patients, the level of polyamines was decreased in respect to unoperated patients and return to normal values except for spermine. Because the increased proliferation and higher polyamine levels are related to increased colon cancer risk, our results confirm that ulcerative colitis is a risk factor for the development of carcinoma. Ileorectal anastomosis may reduce this risk through a normalization of mucosal cell proliferative activity and of some polyamine levels.

Adolescent↗

Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis.

BACKGROUND: Epidermal growth factor (EGF) is a potent mitogenic peptide produced by salivary glands. We examined whether EGF enemas are an effective treatment for active left-sided ulcerative colitis and ulceration limited to the rectum (proctitis). METHODS: In a randomized, double-blind clinical trial conducted at Leicester Royal Infirmary, 12 patients with mild-to-moderate left-sided ulcerative colitis received daily enemas of 5 microg of EGF in 100 ml of an inert carrier and 12 received daily enemas with carrier alone for 14 days. All also began to receive 1.2 g of oral mesalamine per day or had their dose increased by 1.2 g per day. Patients were assessed clinically at 0, 2, 4, and 12 weeks and by sigmoidoscopy and biopsy at 0, 2, and 4 weeks. The primary end point was disease remission (defined by a St. Marks score of 4 or less without sigmoidoscopic evidence of inflammation) at two weeks. Secondary end points were clinically significant improvements in disease activity (defined by a decrease of more than 3 points in the St. Marks score or the ulcerative colitis disease-activity index) at two and four weeks. Analyses were performed according to the intention-to-treat principle. RESULTS: After two weeks, 10 of the 12 patients given EGF enemas were in remission, as compared with 1 of 12 in the control group (83 percent vs. 8 percent, P<0.001). At the 2-week assessment, disease-activity scores, sigmoidoscopic score, and histologic scores were all significantly better in the EGF group than in the placebo group (P<0.01 for all comparisons), and this benefit was maintained at 4 weeks and at 12 weeks. CONCLUSIONS: This study provides preliminary data suggesting that EGF enemas are an effective treatment for active left-sided ulcerative colitis.

Administration, Oral↗

Cancer in patients with ulcerative colitis.

A cohort of 5,546 ulcerative colitis patients was identified from the Danish Hospital Discharge Register for 1977-1989. Patients not included in the cohort comprised those with proctitis, those treated in outpatient clinics and those for whom follow-up was less than 1 year. The cohort was linked to the Danish Cancer Registry in order to assess the risks for colorectal and other cancers. The linkage revealed a significant increase in the number of colorectal cancers over that in the general population (RR = 1.8; n = 42; 95% CI = 1.3-2.4) with consistent relative risks during early and late follow-up. The relative risk was considerably higher among younger (20-39 years: RR = 22; n = 8; 95% CI = 9.7-44) than older patients (> or = 60 years: RR = 1.3; n = 25; 95% CI = 0.8-1.9), but the risk difference between patients and the general population was approximately constant across all ages. In addition, we observed a significant increase in the relative risk of hepatobiliary cancers (RR = 2.3; n = 9; 95% = 1.0-4.3) and a slight but significant increase in the relative risk of non-melanoma skin cancer (RR = 1.4; n = 37; 95% CI = 1.0-1.9). In summary, our population-based study confirms the increased risk of colorectal cancer among patients with ulcerative colitis and provides new leads suggesting that hepatobiliary cancer and non-melanoma skin cancer should be considered as possible sites for future patient monitoring.

Adult↗

Superior sagittal sinus thrombosis 10 years after surgery for ulcerative colitis.

Cerebral vein thrombosis is a known complication of active ulcerative colitis. It is generally believed that panproctocolectomy ameliorates the thromboembolic and other systemic complications of ulcerative colitis. We report an unusual patient, 10 years post-panproctocolectomy for ulcerative colitis, who developed a cerebral sinus thrombosis. Physicians should be aware of the possibility of thromboembolic complications of ulcerative colitis long after definitive surgery has been performed.

Adult↗

Evidence of linkage of the inflammatory bowel disease susceptibility locus on chromosome 16 (IBD1) to ulcerative colitis.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) of unknown aetiology which are characterised by chronic inflammation of the gastrointestinal tract. Epidemiological studies suggest the presence of a genetic component in the aetiology of both CD and UC. A susceptibility gene for Crohn's disease has recently been mapped to the pericentromeric region of chromosome 16 (IBD1), and this finding has been replicated in two subsequent studies. Although CD and UC are distinct clinical entities, the fact that both disorders occur in a significant proportion of families with multiple cases of IBD suggests that overlapping sets of susceptibility genes may be involved. We have addressed this question for IBD1 by typing eight microsatellite markers from the locus in 70 kindreds affected with either UC only or with both UC and CD and analysing the data for linkage by both non-parametric and parametric methods. Evidence for linkage was detected in families affected with only UC, with a mean proportion of 0.70 affected sib pairs sharing alleles identical by descent at D16S3136 (p=0.01), and a peak non-parametric linkage score of 2.02 at D16S3120 with the GENEHUNTER program (p=0.02). The estimated sib relative risk attributable to IBD1 in these families was 1.46. Surprisingly, no evidence of linkage was detected in the families affected with both UC and CD (p>0.2). The data suggest that IBD1 may also contribute to susceptibility to ulcerative colitis, and that it is likely to be located in the 12 cM interval between D16S419 and D16S409.

Chromosomes, Human, Pair 16↗

Allergy and mucosal eosinophil infiltrate in ulcerative colitis.

BACKGROUND: Data on allergy in ulcerative colitis (UC) have led to conflicting conclusions without proving any causal association. In this report we have investigated the presence of allergy and its possible relation with chronic colonic inflammation in patients with UC. METHODS: Fifty UC patients underwent clinical, endoscopic, and histologic evaluations. The allergologic study included family/personal history; prick/patch exposition to airborne, food, and contact allergens; total serum IgE; and quantification of eosinophils in peripheral blood and intestinal mucosa. Diagnosis of rhinitis, conjunctivitis, and asthma was confirmed by specific provocation tests. Fifty healthy subjects were studied as control group. RESULTS: A higher prevalence of allergic symptoms was found in patients (56%) and their first-degree relatives (52%) than in controls (18% and 26%) (P < 0.0001; P = 0.008). In patients skin tests showed increased rates of immediate (54%) and delayed-type (20%) hypersensitivity compared with controls (30% and 6%) (P= 0.01; P= 0.03). Diagnosis of allergic IgE-mediated disease was made in 19 cases and 6 controls (P= 0.01), and allergic contact dermatitis in 10 and 3, respectively (P= 0.03). IgE levels were higher in UC patients than in controls (P=0.02). No dose-response relationship was found between degree of colonic tissue eosinophilia and clinical. endoscopic, and histologic disease severity. The degree of colonic tissue eosinophilia was higher in the presence of skin reactivity to food allergens. CONCLUSIONS: UC patients frequently show several markers of allergy. In particular, our data suggest an association between ulcerative colitis, tissue eosinophilia, and type-I allergy.

Adult↗