Incomplete Remission with Short-Term Prednisolone Treatment in Collagenous Colitis: a Randomized Study

Background: Microscopic colitis is a disease of unknown aetiology characterized by chronic watery diarrhoea and diarrhoea can be eliminated by budesonide but frequently recurs when budesonide is stopped. We studied whether prednisolone could induce remission in patients with disabling, chronic diarrhoea due to microscopic colitis. Methods: A double-blind, randomized (3:1) trial of oral prednisolone 50 &#114 mg daily or placebo for 2 weeks. Remission was defined as stool weight &#104 200 &#114 g/day or frequency &#104 2/day; effect was defined as >50% reduction of either stool frequency or weight. Six centres screened 31 consecutive patients and included 11 with collagenous colitis and 1 with lymphocytic colitis. Median duration of diarrhoea was 9 months. Patients had a normal colonoscopy, and no evidence of coeliac disease, bile acid or lactose malabsorption. Patients with gastrointestinal infection, previous gastrointestinal surgery, abnormal biochemical screening or recent treatment with immunosuppressive agents were excluded. Results: Stool weight (grams) declined in 7 of 9 patients given prednisolone and in 1 of 3 receiving placebo; changes in median weight were from 430 to 278 and from 825 to 489, respectively. Stool frequency (per day) declined from 6 to 3 and from 8 to 5. Remission was obtained in 2 and 0, and effect in 5 and 0, respectively (NS; Fisher exact test). Conclusions: Prednisolone 50 &#114 mg daily for 2 weeks induces incomplete remission in patients with chronic diarrhoea due to collagenous colitis.     

Budesonide treatment of collagenous colitis: a randomised,double blind,placebo controlled trial with morphometric analysis

BACKGROUND: Collagenous colitis is characterised by diarrhoea, lymphocytic inflammation, and a thickened subepithelial collagen layer in the colorectal mucosa. No standard treatment of the disease is established. AIMS: To investigate the clinical and histological effect of oral budesonide (Entocort, AstraZeneca) in the treatment of collagenous colitis. PATIENTS: Twenty patients with collagenous colitis (collagen layer >10 micro m) and diarrhoea (>4 stools/day and/or stool weight >200 g/day). METHODS: A randomised, double blind, placebo controlled trial of budesonide treatment. Patients were randomised to placebo or budesonide for eight weeks. Stool frequency and stool weight were registered before and after treatment. Sigmoidoscopy was performed before and after treatment, and biopsies at fixed locations were obtained for morphometric analysis. RESULTS: Ten patients were randomised to budesonide and 10 to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). In the budesonide group, stool weight was reduced from 574 g/day to 200 g/day and stool frequency was reduced from 6.2/day to 1.9/day (p<0.01). The histological inflammation grade in the sigmoid mucosa and the thickness of the collagen layer were significantly reduced. A correlation between the grade of inflammation as well as collagen layer thickness and stool weight was found. No side effects were reported. Eight of 10 patients had relapse of symptoms within eight weeks after stopping treatment. CONCLUSIONS: Budesonide is a highly effective and well tolerated treatment of collagenous colitis. There is a high risk of relapse after stopping eight weeks of treatment.     

Oral budesonide therapy improves quality of life in patients with collagenous colitis

Introduction Collagenous colitis is an idiopathic microscopic colitis characterised by watery diarrhoea. The impact of collagenous colitis on quality of life has not been assessed. Our aim was to assess quality of life in patients with this condition and compare the effect of treatment with budesonide capsules or placebo on this parameter.Methods Patients with chronic diarrhoea and histologically-proven collagenous colitis were randomised to receive either budesonide controlled-release capsules (Entocort capsules, AstraZeneca, Lund, Sweden), 9 mg/day, or placebo for 6 weeks. Quality of life was measured using the validated Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks. With the GIQLI, scores range from 0 to 144, with higher scores representing better quality of life.Results Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12). At baseline, quality of life was low in patients with collagenous colitis (mean 76). After 6 weeks of treatment, the mean GIQLI score increased significantly in the budesonide group (from 67 to 92, p<0.001), but remained unchanged in the placebo group (86–88). The mean score of the dimensions symptoms (p=0.001), emotional functioning (p=0.003) and physical functioning (p=0.017) increased significantly in the budesonide group compared with the placebo group. A significantly larger proportion of patients in the budesonide group experienced improved stool consistency (p<0.01) and a significant reduction in the mean stool frequency compared with those in the placebo group (p<0.01).Conclusion Quality of life is seriously reduced in patients with collagenous colitis. Six-week treatment with oral budesonide controlled-release capsules significantly improves quality of life and clinical symptoms compared with placebo in these patients.     

Budesonide for the treatment of collagenous colitis: first results of a pilot trial

OBJECTIVE: Collagenous colitis is a chronic watery diarrhea disorder characterized by a subepithelial collagen layer and a lymphoplasmacytic infiltration within the lamina propria. However, no standard treatment has been introduced by controlled clinical trials. Aim of the present pilot trial was to investigate the clinical effects of orally administered budesonide (3 mg t.i.d.) in 7 patients with collagenous colitis. In addition, the histomorphological changes after budesonide treatment were described in a group of 3 patients. METHODS: The study was performed as an open label pilot trial. Study end point was the clinical remission of collagenous colitis defined by stool frequency and stool consistency. RESULTS: The results indicate a rapid and sustained clinical response in all patients. Stool frequency significantly decreased (p < 0.001) from 10.43 +/- 5.56 per day (4-20 per day) to 3.3 +/- 1.2 (1-5 per day) after 10 days and to 1.86 +/- 0.69 per day (1-3 per day) after 10 wk. Moreover stool consistency changed from watery (6 patients) or soft (1 patient) to soft (1 patient) or solid (6 patients). Clinical improvement was achieved within the first 10 days in all patients and maintained after dose reduction. In 3 patients no diarrhea recurred within 7, 12, or 15 months after treatment with budesonide was terminated. In these patients control biopsies were taken and showed a marked regression of both characteristics, the collagen band and the lymphoplasmacytic infiltration. CONCLUSIONS: With respect to the preliminary data from this pilot trial, budesonide with its high topical and low systemic effects seems to be of therapeutic clinical benefit in collagenous colitis. A therapeutic effect could be demonstrated for both therapeutic goals, the clinical response and morphological changes. Further studies on the effects of budesonide on mucosal collagen metabolism and long-term follow-up are warranted.     

Budesonide treatment and expression of inducible nitric oxide synthase mRNA in colonic mucosa in collagenous colitis

OBJECTIVE: In collagenous colitis, the production of nitric oxide in the colon is found to be 50 to 100-fold higher than in healthy controls. The role of nitric oxide in collagenous colitis is debated and it has been suggested that nitric oxide has a causative role in diarrhoea. The aim of this study was to examine the possible effect of budesonide treatment on the level of inducible nitric oxide synthase mRNA. METHODS: In 20 patients with collagenous colitis, clinical activity was assessed by registration of the daily stool frequency and stool weight. Sigmoidoscopy was performed and biopsies for histological examination and one biopsy for determination of inducible nitric oxide synthase mRNA was obtained in 16 patients. RESULTS: Budesonide treatment was followed by a significant reduction of inducible nitric oxide synthase mRNA (P<0.01) whereas no change was observed after placebo treatment. Significant correlations between inducible nitric oxide synthase mRNA and the grade of inflammation (rho=0.47; P<0.01), the daily stool weight (rho=0.51; P<0.005) and the daily stool frequency (rho=0.49; P<0.005) were observed. No significant association was observed between inducible nitric oxide synthase mRNA and the thickness of the collagen layer. CONCLUSIONS: In patients with collagenous colitis, treatment with budesonide results in a reduction of inducible nitric oxide synthase mRNA. The level of inducible nitric oxide synthase mRNA in colonic mucosa correlates with the inflammatory and clinical activity. The results support that nitric oxide is a central factor in the pathogenesis of collagenous colitis.     

Budesonide treatment for collagenous colitis: a randomized,double-blind,placebo-controlled,multicenter trial

BACKGROUND & AIMS: Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial. METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires. RESULTS: Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P < 0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P < 0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects. CONCLUSIONS: Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained.     

Interventions for treating collagenous colitis: a Cochrane Inflammatory Bowel Disease Group systematic review of randomized trials

OBJECTIVES: To conduct a systematic review to determine effective treatments for patients with clinically active collagenous colitis. METHODS: Relevant articles were identified via the MEDLINE, PUBMED, and Cochrane Collaboration databases, manual searches of the references of identified articles, and review articles on collagenous or microscopic colitis, as well as searches of abstracts from major gastroenterological meetings. RESULTS: Five randomized trials assessing treatments for collagenous colitis were identified. One trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 wk) included 9 patients. Patients who received the bismuth preparation were more likely to have clinical (p= 0.003) and histological (p= 0.003) improvement than those who received placebo. In a trial comparing prednisolone (50 mg daily for 2 wk) to a placebo in 11 patients, a trend toward clinical response in patients on prednisone was reported (p= 0.064). The effect of prednisolone on histological improvement was not studied. A total of 94 patients were enrolled in three trials studying budesonide (9 mg daily or in a tapering schedule for 6-8 wk). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI: 5.53-27.46). The NNT (number of patients needed to treat with budesonide to achieve 1 improved patient) was 2 patients. This therapy was well tolerated. There was significant histological improvement with treatment in all three trials studying budesonide therapy. CONCLUSIONS: There is strong evidence that budesonide is effective and well tolerated for the treatment of collagenous colitis. The evidence for benefit with bismuth subsalicylate or prednisolone is weaker. It is not clear that any of these agents produce actual remission, as opposed to clinical and histological improvement of the disease.     

The probiotic E. coli strain Nissle 1917 for the treatment of collagenous colitis: first results of an open-label trial

BACKGROUND: Collagenous colitis is clinically characterized by watery diarrhoea and can histologically be diagnosed by a thickening of the subepithelial collagen layer and an inflammatory infiltrate in the lamina propria. So far, the pathogenesis of collagenous colitis and the role of luminal factors remain unclear. METHODS: This clinical pilot investigation was conducted with an open-label design to monitor the clinical effects of EcN on stool frequency and stool consistency in 14 patients (11 female, 3male; age: 58.1 +/- 9.6 years). Due to the open-label protocol EcN was administered at different doses (1 - 6 capsules/day containing 2.5 - 25 x 10 (9) viable bacteria each). Except for two patients who discontinued treatment, therapy duration was at least 4 weeks. RESULTS: The results indicate a marked clinical response to the oral administration of EcN with a reduction of the stool frequency > or = 50 % in 9/14 (64 %) patients. Stool frequency clearly (p = 0.034) decreased from 7.6 +/- 4.8/day to 3.7 +/- 5.8/day at the end of therapy (between 4 and 18 weeks). Moreover, stool consistency changed in 7/14 patients from watery or slimy to soft (6 pts) and normal (1 pt), respectively. CONCLUSION: With respect to the preliminary data from this trial, the probiotic E. coli strain Nissle 1917 (EcN) seems to be of therapeutic clinical benefit in collagenous colitis. This may be explained with the recently shown antagonistic effect of EcN against Yersinia species, since a relevant number of patients suffering from collagenous colitis showed positive titres of serum IgG and IgA antibodies against Yersinia species. Further studies on the effects of EcN on mucosal collagen metabolism and long-term follow-up are warranted.     

Therapy of prednisone-refractory collagenous colitis with budesonide

Collagenous colitis is a rare cause of chronic watery diarrhea. No effective standard treatment has yet been established. Based upon anecdotal reports some anti-inflammatory and symptomatic drugs seem to have some therapeutic efficacy. Prednisone is widely believed to be the most effective treatment. Here we describe three female patients with histologically confirmed collagenous colitis refractory to therapy with prednisone. Each had received prednisone with a high starting bolus and lower dose maintenance therapy for their disease. However, definite clinical remission could not be achieved. After the administration of 3×3 mg/day controlled ileal release (CIR) capsules of budesonide the symptoms resolved immediately. The mean follow-up after beginning budesonide was 11 months (range 7–18). Two patients are still on budesonide. One had had a quick relapse of diarrhea after stopping her treatment. Budesonide therapy was therefore resumed. She has remained symptom-free on a lower daily dose of 2×3 mg/day budesonide. One patient has been in remission for more than 1 year after a 3-month course of budesonide. Budesonide is a topically acting steroid with rapid absorption, high receptor affinity, and low systemic bioavailability, thus causing almost no side effects. As yet only few case reports have been published on the use of budesonide for collagenous colitis. We present here the first three cases of prednisone refractory collagenous colitis successfully treated with budesonide. Accepted: 23 September 1998     

Collagenous colitis: a prospective trial of prednisolone in six patients

In a prospective study, the clinicopathological effect of prednisolone was evaluated in six patients with collagenous colitis. Prednisolone was associated with a significant decrease in stool frequency. However, the effect was transitory, since the diarrhoea recurred when prednisolone treatment was discontinued. There was a trend toward a diminished inflammatory response in the post-treatment biopsies, but the thickness of the collagen band remained unchanged, except in one patient. Until the results of further studies are available, we recommend that treatment with prednisolone be restricted to periods of acute diarrhoeal episodes.     

Oral budesonide in gastrointestinal and liver disease: A practical guide for the clinician

Oral budesonide is a second‐generation steroid that allows local, selective treatment of the gastrointestinal tract and the liver, minimizing systemic exposure. The results of randomized trials comparing budesonide versus placebo or active comparators have led to expert recommendations that budesonide be used to treat mild or moderate active ileocecal Crohn's disease, microscopic colitis (including both collagenous and lymphocytic colitis), ulcerative colitis, and non‐cirrhotic autoimmune hepatitis. The mechanism of budesonide action obviates the need for dose tapering due to safety reasons after induction therapy. Where low‐dose budesonide is used to maintain remission, usually in microscopic colitis, it does not appear to have adverse safety implications other than slight reductions in cortisol levels on rare occasions. As a gut‐selective and liver‐selective corticosteroid, budesonide offers an appealing alternative to conventional systemic glucocorticoids in diseases of these organs.     

Budesonide versus prednisolone for the treatment of active Crohn's disease in children: a randomized, double-blind, controlled, multicentre trial

OBJECTIVES: Budesonide is a corticosteroid with low systemic bioavailability because of its high first-pass metabolism in the liver. In this paediatric, randomized, double-blind, double-dummy, controlled, multicentre trial, the safety and efficacy of budesonide versus prednisolone were evaluated in children with active Crohn's disease. METHODS: Forty-eight children, aged 6-16 years, with active Crohn's disease (Crohn's Disease Activity Index > 200) involving ileum and/or ascending colon were randomized to receive budesonide (9 mg/day for 8 weeks, 6 mg/day for 4 weeks) or prednisolone (1 mg/kg/day for 4 weeks, tapering for 8 weeks). RESULTS: The groups were comparable for age, sex, pubertal stage, disease activity and disease duration. Mean morning plasma cortisol concentration was significantly higher in the budesonide group (200 nmol/l) than in the prednisolone group (98 nmol/l) after 8 weeks, reflecting less adrenal suppression by budesonide (difference -102 nmol/l; 95% CI -226, -52; P = 0.0028). Glucocorticosteroid side effects such as moon face and acne occurred significantly less frequently in the budesonide group. Remission (Crohn's Disease Activity Index < or = 150) was seen at 8 weeks in 12/22 (55%) patients treated with budesonide and in 17/24 (71%) patients receiving prednisolone (difference -16%; 95% CI -45,13; P = 0.25). CONCLUSIONS: Significantly fewer side effects and less adrenal suppression were observed in the children receiving budesonide. Remission rates were not significantly different in the two groups. However, there was a trend for prednisolone to be more effective for inducing remission.     

Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial

Background and aims The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis. Materials and methods Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency ≤3 soft /solid stools per day on average during the last week). Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks. Results Thirty-one patients were randomized; 26 patients were available for per-protocol-analysis. After 6 weeks, the proportion of patients in clinical remission was higher in the BSE group than in the placebo group (per protocol 63.6%; 95%CI, 30.8–89.1 vs 26.7%, 95%CI, 7.7–55.1; p = 0.04; intention-to-treat 43.8% vs 26.7%, p = 0.25). Compared to placebo, BSE treatment had no effect on histology and quality of life. Five patients discontinued BSE treatment prematurely. Discontinuation was due to adverse events (n = 1), unwillingness to continue (n = 3), or loss to follow-up for unknown reasons (n = 1). Seven patients received open-label BSE therapy, five of whom achieved complete remission. Conclusions Our study suggests that BSE might be clinically effective in patients with collagenous colitis. Larger trials are clearly necessary to establish the clinical efficacy of BSE.     

布地奈德治疗胶原性结肠炎疗效和安全性的荟萃分析

背景:胶原性结肠炎以慢性水样腹泻和结肠黏膜上皮下胶原带增厚为特征,目前尚无标准治疗方案。目的:系统评价口服布地奈德治疗胶原性结肠炎的疗效和安全性。方法:计算机检索Cochrane Central Register of Controlled Trials(1995～2008.1)、MEDLINE/PubMed(1978～2009.12)、Ovid(1978～2009.12)、EMBASE(1978～2009.12)、中国期刊全文数据库(1980～2009.12)和万方数据资源系统(1980～2009.12),纳入所有口服布地奈德治疗胶原性结肠炎的随机对照试验(RCT),按Cochrane协作网推荐的方法进行荟萃分析。结果:共纳入5项RCT,包括179例患者,3项研究评价了诱导缓解治疗,2项评价了维持治疗。在诱导缓解方面,布地奈德的临床和组织学缓解率均优于安慰剂(OR=15.04,95% CI:5.47～41.33,P0.000 01;OR=34.02,95% CI:5.90～196.20,P0.0001)。在维持治疗方面,布地奈德的临床复发率和组织学缓解维持率亦优于安慰剂(OR=0.11.95% CI:0.04～0.31,P0.0001;0R=5.88,95% CI:1.90～18.17,P=-0.002)。布地奈德不良反应轻微,耐受性良好。结论:口服布地奈德能有效诱导并维持胶原性结肠炎的临床和组织学缓解,耐受性良好。由于本荟萃分析纳入研究的样本量较小,故应谨慎对待上述结论,并设计、开展大样本、高质量的RCT作进一步验证。     

Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial.

OBJECTIVE: To investigate the efficacy of azathioprine in treating patients with severe ulcerative colitis. DESIGN: One-year, randomized, placebo-controlled trial. SUBJECTS: 83 patients with severe ulcerative colitis were enrolled. Fifty patients who relapsed within two months on corticosteroid withdrawal were randomized into two groups. The azathioprine group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and oral azathioprine (2 mg/Kg/day). The placebo group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and placebo. Corticosteroids were tapered over 12-16 weeks. RESULTS: Five patients (2 in azathioprine group, 3 in placebo group) dropped out of the study. Three patients in the azathioprine group had side effects. The number of patients going into complete remission and partial remission was not significantly different in the two groups. The proportion of relapses in the azathioprine group was lower than in the placebo group (p < 0.05). CONCLUSIONS: In patients with ulcerative colitis, azathioprine had no effect in achieving remission, when given in combination with prednisolone; however, it lowers the proportion of relapses. Side effects like pancreatitis and hepatitis are mild and respond promptly to drug withdrawal.     

A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS

OBJECTIVE: The aim of this study was to investigate the safety and effectiveness of orally administered SP-303 in patients with AIDS and diarrhea. METHODS: This is a multicenter, phase II, randomized, double blind, placebo-controlled study. HIV-positive subjects with a history of a CD4 count <200 or an AIDS-defining illness were admitted to an inpatient study unit and screened for diarrhea defined as at least three abnormal (i.e., soft or watery) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool samples were studied for routine pathogens. Subjects received 500 mg p.o. of SP-303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights were recorded. Subjects were monitored for symptoms and side effects and were seen 1 wk later in follow-up. RESULTS: A total of 26 subjects received SP-303, and 25 received placebo. There were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 subjects (77%) were receiving at least one protease inhibitor. Stool studies revealed no pathogens in 48 of 51 patients (94%). There were no serious adverse events or laboratory abnormalities. The SP-303 treatment group demonstrated a mean reduction from baseline stool weight of 451 g/24 h versus 150 g/24 h with placebo on day 4 of treatment (p = 0.14), and a mean reduction in abnormal stool frequency of three abnormal stools in 24 h versus two in 24 h in the placebo group (p = 0.30). Daily measures analysis over 4 days of treatment demonstrated that SP-303 subjects had a significant reduction in stool weight (p = 0.008) and abnormal stool frequency (p = 0.04) when compared to placebo-treated subjects. CONCLUSIONS: SP-303 is safe and well tolerated. These results suggest that SP-303 may be effective in reducing stool weight and frequency in patients with AIDS and diarrhea.     

Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial

BACKGROUND: An uncontrolled pilot study demonstrated that daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), might be effective for the treatment of active ulcerative colitis. METHODS: A randomised, double blind, placebo controlled trial was conducted to evaluate the efficacy of daclizumab induction therapy in patients with active ulcerative colitis. A total of 159 patients with moderate ulcerative colitis were randomised to receive induction therapy with daclizumab 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg intravenously at weeks 0, 2, 4, and 6, or placebo. The primary end point was induction of remission at week 8. Remission was defined as a Mayo score of 0 on both endoscopy and rectal bleeding components and a score of 0 or 1 on stool frequency and physician's global assessment components. Response was defined as a decrease from baseline in the Mayo score of at least 3 points. RESULTS: Two per cent of patients receiving daclizumab 1 mg/kg (p = 0.11 v placebo) and 7% of patients receiving 2 mg/kg (p = 0.73) were in remission at week 8, compared with 10% of those who received placebo. Response occurred at week 8 in 25% of patients receiving daclizumab 1 mg/kg (p = 0.04) and in 33% of patients receiving 2 mg/kg (p = 0.30) versus 44% of those receiving placebo. Daclizumab was well tolerated. The most frequently reported adverse events in daclizumab treated patients compared with placebo treated patients were nasopharyngitis (14.6%) and pyrexia (10.7%). CONCLUSION: Patients with moderate ulcerative colitis who are treated with daclizumab are not more likely to be in remission or response at eight weeks than patients treated with placebo.     

Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide.

A 22 year old insulin dependent diabetic with high volume, secretory chronic diarrhoea refractory to standard andiarrhoeal drugs was treated with the somatostatin analogue octreotide, 50 micrograms twice daily by subcutaneous injection. She improved markedly with a decrease in mean stool weight from 1170 g/24 h range 440-2900 g) to 440 g/24 h (range 180-800 g) (p < 0.05). Stool frequency also decreased from six (range two to 12) to one (range one to three) bowel movements per day (p < 0.01). Mouth to caecum transit time increased from 45 minutes to > 210 minutes, although total gut transit time was unchanged and remained rapid at nine hours. Thus octreotide can reduce stool volume and frequency in high volume diabetic diarrhoea when conventional antidiarrhoeal agents have failed. Its therapeutic benefit appeared to be predominantly related to a marked increase in mouth to caecum transit time.     

Treatment responses in collagenous colitis

OBJECTIVE: In the nearly 20 yr since collagenous colitis was first recognized, the results of therapies have not been systematically described in substantial numbers of patients. We have therefore conducted a retrospective analysis of 26 patients treated in this institution during the years 1991-1994. METHODS: Twenty-nine cases of collagenous colitis were obtained by review of biopsy specimens collected between 1991 and 1994 at The Mount Sinai Hospital. Each chart was reviewed for patient demographics, symptoms, coexisting conditions, specific therapies, and therapeutic outcomes. Additional data were obtained from telephone calls to patients when deemed necessary. Three patients were exeluded from the study because of lack of follow-up. Therapeutic outcomes were defined as follows: Complete Remission (CR): normalization of bowel function; Partial Remission (PR): 50% reduction in frequency of bowel movements; Failure: <50% reduction in frequency of bowel movements; or Relapse: return of symptoms after cessation of treatment. Median follow-up was 58 wk from time of diagnosis, with a range of 22-376 wk. RESULTS: The 26 patients (25 women, one man) had a mean age of 62 yr (range, 22-85 yr) at diagnosis. Of 26 patients, 22 responded to some form of therapy and one had spontaneous remission. Six of the responders ultimately remained in CR with no therapy. Twelve are maintained on 5-aminosalicylic acid (5-ASA) and or antidiarrheals to control symptoms. An additional six required prednisone throughout the follow-up period to remain in CR or PR. Two patients failed all therapy. CONCLUSION: Collagenous colitis is a treatable condition in most patients. We recommend initial therapy with antidiarrheals, followed by a trial of 5-ASA agent. A trial of 5-ASA in combination with prednisone should be attempted in patients refractory to 5-ASA alone, with subsequent attempts in the responders to taper prednisone and maintain remission with no therapy, if possible, or with 5-ASA and/or antidiarrheal agents if necessary.     

Association of common variable immunodeficiency with atypical collagenous colitis

Collagenous colitis is a condition characterized by chronic, watery diarrhoea, which is diagnosed histologically as most cases reveal a normal colonoscopic appearance. The aetiology is poorly understood, but nonsteroidal anti-inflammatory drugs or infections may act as triggers for an immune-mediated process. In this report, an unusual case of collagenous colitis associated with pseudomembrane formation is described. Stool assay was negative for Clostridium difficile cytotoxin B. There are only three reports of pseudomembranes in collagenous colitis in the absence of C. difficile infection. In addition, the patient had a deficiency in immunoglobulin production, which may suggest an infective trigger to collagenous colitis. This is the first report of an association between an immunoglobulin deficiency and this unusual variant of collagenous colitis. The implications of these findings are discussed.