pulmicort and Colitis--Collagenous

Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials.. The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC.. EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo-controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random-effects models. Stratified analyses based on disease- and trial-level characteristics, leave-one-out meta-analysis, and cumulative meta-analysis were performed.. Twelve RCTs enrolling a total of 391 patients (placebo n = 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%-38.4%), I. Approximately one-quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo.

Topics: Adult; Budesonide; Colitis, Collagenous; Colitis, Microscopic; Humans; Randomized Controlled Trials as Topic

Microscopic colitis is a common cause of chronic watery diarrhea with a great impact on patient quality of life. Microscopic colitis includes two histological subtypes: collagenous colitis and lymphocytic colitis. Due to the increasing incidence and awareness of this disease over the last decades, several international guidelines have been recently published. However, there is still significant heterogeneity in the management of these patients, and treatments without solid scientific evidence support are often used in clinical practice. This article reviews the therapeutic role of budesonide in microscopic colitis and summarizes the current evidence regarding other treatments available for this disease, especially for the management of refractory patients. Finally, an updated treatment algorithm is proposed.

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antidiarrheals; Antimetabolites; Azathioprine; Biological Products; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Diarrhea; Humans; Loperamide; Malabsorption Syndromes; Mesalamine; Methotrexate; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Time Factors

Collagenous colitis is a cause of chronic diarrhea. This updated review was performed to identify therapies for collagenous colitis that have been assessed in randomized controlled trials (RCTs).. The primary objective was to assess the benefits and harms of treatments for collagenous colitis.. We searched CENTRAL, the Cochrane IBD Group Specialized Register, MEDLINE and EMBASE from inception to 7 November 2016.. We included RCTs comparing a therapy with placebo or active comparator for the treatment of active or quiescent collagenous colitis.. Data were independently extracted by two authors. The primary outcome was clinical response or maintenance of response as defined by the included studies. Secondary outcome measures included histological response, quality of life and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The Cochrane risk of bias tool was used to assess bias. The overall quality of the evidence was assessed using the GRADE criteria.. Low quality evidence suggests that budesonide may be effective for inducing and maintaining clinical and histological response in patients with collagenous colitis. We are uncertain about the benefits and harms of therapy with bismuth subsalicylate, Boswellia serrata extract, mesalamine with or without cholestramine, prednisolone and probiotics. These agents and other therapies require further study.

Topics: Bismuth; Boswellia; Budesonide; Cholestyramine Resin; Chronic Disease; Colitis, Collagenous; Diarrhea; Glucocorticoids; Humans; Mesalamine; Organometallic Compounds; Plant Extracts; Prednisolone; Probiotics; Randomized Controlled Trials as Topic; Salicylates

Microscopic colitis (MC) is a relatively common cause of chronic watery diarrhea, especially in older persons. Associated symptoms, including abdominal pain and arthralgias, are common. The diagnosis is based upon characteristic histological findings in the presence of diarrhea. The two types of MC, collagenous and lymphocytic colitis, share similar clinical features, with the main difference being the presence or absence of a thickened subepithelial collagen band. There are several treatment options for patients with MC, although only budesonide has been well studied in multiple controlled clinical trials. This review will describe the clinical features, epidemiology, pathophysiology, diagnostic criteria, and treatment of patients with MC.

Topics: Anion Exchange Resins; Anti-Inflammatory Agents, Non-Steroidal; Antidiarrheals; Autoimmunity; Bile Acids and Salts; Budesonide; Cholestyramine Resin; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Collagen; Colon; Genetic Predisposition to Disease; Glucocorticoids; HLA Antigens; Humans; Mesalamine

Microscopic colitis (MC) is a chronic inflammatory bowel disease that has emerged in the last three decades as a leading cause of chronic watery diarrhoea. MC classically includes two main subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Other types of histopathological changes in the colonic mucosa have been described in patients with chronic diarrhoea, without fulfilling the conventional histopathological criteria for MC diagnosis. Whereas those unclassified alterations remained orphan for a long time, the use of the term incomplete MC (MCi) is nowadays universally accepted. However, it is still unresolved whether CC, LC and MCi should be considered as one clinical entity or if they represent three related conditions. In contrast to classical MC, the real epidemiological impact of MCi remains unknown, because only few epidemiological studies and case reports have been described. MCi presents clinical characteristics indistinguishable from complete MC with a good response to budesonide and cholestiramine. Although a number of medical treatments have been assayed in MC patients, currently, there is no causal treatment approach for MC and MCi, and only empirical strategies have been performed. Further studies are needed in order to identify their etiopathogenic mechanisms, and to better classify and treat MC.

Topics: Biopsy; Budesonide; Cholestyramine Resin; Colitis, Collagenous; Colitis, Lymphocytic; Collagen; Colon; Diagnosis, Differential; Diarrhea; Humans; Immunohistochemistry; Inflammatory Bowel Diseases; Intestinal Mucosa; Sex Factors

Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated in the past 40 years reveals increasing incidence and prevalence rates, a wide spectrum of clinical presentations, and several histologic variants. Although several recent randomized clinical trials confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse after a short-duration treatment is common. Despite their common clinical presentations and well-defined histologic diagnostic criteria, there are only few studies on the immunologic abnormalities in colonic tissue. The aim of this review is to (1) familiarize the pathologists in general practice with histomorphology of LC and CC, including the rare histologic variants and the clinical implication associated with these 2 diagnoses, (2) summarize the data from recent randomized clinical trials of oral budesonide, and (3) review immunological studies on colonic tissue. Overall, immunologic abnormalities of colonic tissue seem to explain for the histomorphologic features and the clinical symptomatology of LC and CC. Advances in the understanding of the underlying immunologic abnormalities in the colonic tissue may help develop novel and effective therapies for these 2 diseases.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Humans; Randomized Controlled Trials as Topic

Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities.. To compare pathoanatomical findings, clinical presentations, risk factors, course of diseases and response to treatment in CC and LC to establish whether they could be subtypes of the same disease, microscopic colitis (MC).. The MEDLINE was searched for CC, LC and MC, and clinical studies of >20 patients were included. Pooled results with 95% confidence intervals were calculated based on the number of patients.. An abnormal number of intraepithelial lymphocytes are found in 45% (40-50%) with CC, and an abnormal subepithelial collagen band in 16% (13-20%) with LC suggesting a histological overlap. The incidence of CC and LC has increased in parallel. Mean age (CC 63 years; LC 60 years) and clinical presentation are indistinguishable, and females are predominant in CC (77%; 75-79%) as well as LC (68%; 66-70%). Risk factors such as nonsteroid anti-inflammatory drugs consumption CC 39% (36-42%); LC 32% (29-35%) are similar and prevalence of concomitant autoimmune diseases such as coeliac disease (CC 5%; CI: 4-6% and LC 7%; CI: 6-9%) do not differ. Bile acid diarrhoea is highly prevalent in CC (41%; 37-45%) and LC (29%; 24-34%). The effect of budesonide is identical.. CC and LC could be considered histological subtypes of the same disease, MC. To facilitate recruitment to clinical trials, all MC patients could be included in future trials and stratified for subtypes.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Diagnosis, Differential; Humans

Collagenous colitis belongs to the group of microscopic colitis. The aetiology and pathogenesis are unknown but different pathogenic hypothesis, autoimmune, infectious, alimentary and medicinal being are advanced, the last one being the most frequent aetiology. The collagenous gastritis is a rare entity and its association with collagenous colitis was exceptionally reported, only six cases being published. We report the seventh case of collagenous gastritis, ileitis and colitis in a 75-year-old woman with chronic diarrhea and important weight loss. This thickened subepithelial collagen band was appeared in an autoimmune injury context with antecedent of Hashimoto's thyroiditis and probably chronic atrophic Biermer's gastritis. The clinical and histological evolution was favourable with budesonide.

Topics: Aged; Anti-Inflammatory Agents; Autoimmune Diseases; Budesonide; Colitis, Collagenous; Collagen; Female; Gastric Mucosa; Gastritis; Hashimoto Disease; Humans; Ileitis

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome

Microscopic colitis (MC) causes chronic diarrhea, abdominal cramping, nausea, and weight loss. Colonic mucosa appears normal on endoscopy; however, biopsies show abnormalities such as intraepithelial lymphocytosis in lymphocytic colitis, and a thickened subepithelial collagen band in collagenous colitis. Epidemiologic data demonstrates that MC is a more common cause of diarrhea than previously shown. Although the etiology of this condition is unclear, certain well-defined risk factors exist. Recently there has been more research on the pathophysiology of MC, and studies on treatment have demonstrated budesonide to be most effective, although other treatments also hold promise.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Female; Humans; Incidence; Male; Middle Aged; Prevalence; Treatment Outcome; Young Adult

Chronic diarrhoea is a frequent complaint in clinical practice. Microscopic colitis is the cause of this symptom in 10% of these cases and the prevalence is rising. To exclude microscopic colitis a colonoscopy with multiple biopsies of different regions of the colon is mandatory. A sigmoidoscopy alone is insufficient. Two histopathological types of microscopic colitis can be distinguished: collagenous colitis and lymphocytic colitis. Nowadays, there is sufficient evidence to recommend budesonide as the first-choice treatment. Bismuth can also be recommended, but this drug is not easily available in the Netherlands. Evidence of efficacy of other drugs is scant.

Topics: Adult; Antacids; Anti-Inflammatory Agents; Bismuth; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Female; Humans; Male

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Evidence-Based Medicine; Humans; Meta-Analysis as Topic; Remission Induction

Budesonide is a glucocorticoid with high topical glucocorticoid activity and low systemic availability. Oral pH-modified release budesonide has been investigated for the treatment of various inflammatory intestinal diseases.. To summarise the investigational data of oral pH-modified release budesonide for the treatment of Crohn's disease, ulcerative colitis, collagenous colitis and lymphocytic colitis.. Assessment of all published (full paper or meeting abstract) clinical studies with oral pH-modified release budesonide for the treatment of inflammatory intestinal diseases.. Oral pH-modified release budesonide induces remission in mild-to-moderately active Crohn's disease of the ileum and/or ascending colon. This drug is useful to replace conventional systemic glucocorticoids in patients with ileocoecal Crohn's disease. Open-label studies showed efficacy in ulcerative colitis, but this finding has to be confirmed in controlled trials. Oral pH-modified release budesonide is also effective for the treatment of collagenous colitis and lymphocytic colitis.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Clinical Trials as Topic; Colitis, Collagenous; Colitis, Lymphocytic; Delayed-Action Preparations; Glucocorticoids; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases

Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials.. To determine effective treatments for patients with clinically active collagenous colitis.. Relevant papers published between 1970 and June 2006 were identified via the MEDLINE and PUBMED databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies.. Seven randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), one trial studied Boswellia serrata extract (published in abstract form only), one trial studied probiotics, one trial studied prednisolone, and 3 trials studied budesonide for the therapy of collagenous colitis.. Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition.. There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p = 0.003) and histological (p = 0.003) improvement than those assigned to placebo. Eleven patients were enrolled in the trial studying prednisolone (50 mg daily for 2 weeks). There was a trend towards clinical response in patients on active medication compared to placebo (p = 0.064). The effect of prednisolone on histologic improvement was not studied. Thirty-one patients were enrolled in the Boswellia serrata extract trial. Clinical improvement was noted in 44% of patients who received active treatment compared to 27% of patients who received placebo (p = 0.32). Twenty-nine patients were enrolled in the probiotics trial. Clinical improvement was noted in 29% of patients who received probiotics compared to 13% of patients who received placebo (p = 0.635). A total of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily or in a tapering schedule for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy. Budesonide also appears to improve patients' quality of life.. Budesonide is effective for the treatment of collagenous colitis. The evidence for benefit with bismuth subsalicylate is weaker. The effectiveness of prednisolone, Boswellia serrata extract, probiotics and other therapies for induction or maintenance of remission of collagenous colitis is unknown and requires further study.

Topics: Anti-Inflammatory Agents; Bismuth; Budesonide; Chronic Disease; Colitis, Collagenous; Diarrhea; Humans; Organometallic Compounds; Probiotics; Randomized Controlled Trials as Topic; Salicylates

Collagenous colitis is typified by chronic watery diarrhoea and characteristic histological alterations of the colonic mucosa without endoscopic abnormalities. Budesonide, a corticosteroid with high first-pass metabolism has been examined in collagenous colitis, but studies to date have had small numbers, and relatively low statistical power.. A meta-analysis of existing published trials was undertaken to evaluate the treatment effect of budesonide in collagenous colitis.. All pertinent literature sources were searched for published reports in English of budesonide use in collagenous colitis. MEDLINE and EMBASE databases were reviewed, as well as bibliographies from published articles and available abstracts from relevant meetings. Literature that met prespecified criteria was selected for the meta-analysis.. Three trials were included in the meta-analysis. Budesonide significantly decreased stool frequency (budesonide vs. placebo OR: 20.1, 95% CI: 7.0-57.5, P < 0.0001). In general, budesonide treatment was well-tolerated.. Budesonide is clinically effective short-term in collagenous colitis, and seems to be relatively well-tolerated. Clinicians can consider this drug as a reasonable option for patients with this disorder.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Drug Evaluation; Humans; Randomized Controlled Trials as Topic; Risk Factors

To conduct a systematic review to determine effective treatments for patients with clinically active collagenous colitis.. 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.. 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.. 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.

Topics: Anti-Inflammatory Agents; Bismuth; Budesonide; Chi-Square Distribution; Colitis, Collagenous; Double-Blind Method; Humans; Organometallic Compounds; Prednisolone; Randomized Controlled Trials as Topic; Salicylates

This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.. A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.. Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.. Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.. http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Maintenance Chemotherapy; Male; Middle Aged; Prospective Studies; Treatment Outcome

The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known.. In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model.. Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome.. Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.

Topics: Aged; Budesonide; Colitis, Collagenous; Colon; Female; Gastrointestinal Agents; Humans; Male; Mesalamine; Middle Aged; Prognosis; Remission Induction; Smoking; Treatment Outcome

Topics: Budesonide; Colitis, Collagenous; Dose-Response Relationship, Drug; Double-Blind Method; Long-Term Care; Recurrence; Remission Induction

Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures. Mesalamine has been proposed as a treatment option for collagenous colitis, although its efficacy has never been investigated in placebo-controlled trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis.. Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules (9 mg budesonide once daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily, Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double-dummy fashion. The study was conducted in 31 centers (hospital clinics and private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom. The primary end point was clinical remission at 8 weeks defined as ≤ 3 stools per day. Secondary end points included clinical remission at 8 weeks, according to the Hjortswang-Criteria of disease activity, taking stool consistency into account.. A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group (intention-to-treat analysis, 80.0% vs 59.5%; P = .072; per-protocol analysis, 84.8% vs 60.6%; P = .046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide achieved clinical remission compared with 37.8% of patients given placebo (P = .0006); 44.0% of patients given mesalamine achieved clinical remission, but budesonide was superior to mesalamine (P = .0035). Budesonide significantly improved stool consistency and mucosal histology, and alleviated abdominal pain. The rate of adverse events did not differ among groups.. Oral budesonide (9 mg once daily) is effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily) appears to be ineffective. ClinicalTrials.gov number, NCT00450086.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Budesonide; Capsules; Colitis, Collagenous; Defecation; Delayed-Action Preparations; Double-Blind Method; Europe; Female; Gastrointestinal Agents; Humans; Male; Mesalamine; Middle Aged; Remission Induction; Time Factors; Treatment Outcome; Young Adult

We described three patients with collagenous colitis (CC) who developed side effects or were refractory to both budesonide and methotrexate and were given adalimumab (ADA) as a third-line treatment.. Three patients (two women, mean age 45 years and one man, 74 years old) were included. Mean bowel movements per day per week were calculated and stool weight/24 h registered prior to and following ADA treatment. ADA was given in doses 160 mg s.c. (baseline), 80 mg (week 2) and 40 mg (week 4). Sigmoidoscopies with biopsies were performed at baseline and after 6 weeks to examine changes in histology. The Psychological General Well-Being Index (PGWBI) and Short Health Scale (SHS) were used at baseline and after 6 weeks.. The two female patients tolerated the treatment well. The male patient developed, despite clinical response, side effects (vomiting, abdominal pain) after 80 mg of ADA and the treatment was stopped as side effects reoccurred after rechallenge. The two women were in clinical remission at week 6 and the mean stool frequency per day decreased from mean 11 to 2. Mean stool weight/24 h changed from 600 to 185 g. The quality of life improved drastically in all patients. There were no consistent changes in histology.. ADA seems effective in budesonide and methotrexate refractory CC and can be administrated to selected patients to achieve clinical remission, improve quality of life and possibly avoid colectomy. Further studies for induction and maintenance treatment should be conducted to confirm efficacy and examine safety issues, even in long term.

Topics: Adalimumab; Adult; Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Biopsy; Budesonide; Colitis, Collagenous; Defecation; Drug Resistance; Female; Humans; Male; Methotrexate; Middle Aged; Quality of Life; Sigmoidoscopy; Tumor Necrosis Factor-alpha

Fecal calprotectin (FC) is used as a marker for intestinal inflammation in inflammatory bowel disease (IBD) but there is no reliable marker for collagenous colitis (CC). We have previously demonstrated that the mucosal inflammation in CC is characterized by eosinophil activation, which is restored during budesonide treatment, but there is no enhanced neutrophil activity. The aim of this study was to evaluate the use of fecal eosinophil cationic protein (F-ECP) and eosinophil protein X (F-EPX) compared with the neutrophil-derived myeloperoxidase (F-MPO) and FC in patients treated for active CC.. Patients with active CC (n = 12) were studied before and after 3, 7, 28 and 56 days of budesonide treatment. Clinical symptoms and stool frequency were recorded, fecal samples were collected, and F-ECP, F-EPX, F-MPO and FC were measured at each occasion.. All but one patient achieved remission. On inclusion 92%, 67%, 67% and 75% of the patients had elevated F-ECP, F-EPX, F-MPO and FC levels, respectively. All markers decreased during the treatment, particularly F-ECP and F-EPX, which decreased after only 3 days. At the end of the study 100%, 92%, 83% and 75% of the patients had normal F-ECP, F-EPX, F-MPO and FC values, respectively.. F-ECP demonstrated the best discriminating capacity in detecting active CC. A normalized F-ECP and F-EPX may further be studied as a marker for successful treatment. During budesonide treatment there is a rapid fall in F-ECP and F-EPX, accompanied by clinical improvement, indicating an essential role for the eosinophil participating in the pathophysiology of CC.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anti-Inflammatory Agents; Biomarkers; Budesonide; Colitis, Collagenous; Defecation; Eosinophil Cationic Protein; Eosinophil-Derived Neurotoxin; Feces; Female; Humans; Leukocyte L1 Antigen Complex; Male; Middle Aged; Peroxidase; Pilot Projects; Young Adult

To evaluate the efficacy and safety of long-term budesonide therapy for the maintenance of clinical remission in patients with collagenous colitis.. Randomised, placebo-controlled study with a 24-week, blinded follow-up period without any treatment.. Three gastroenterology clinics in Denmark.. Forty-two patients with histologically confirmed collagenous colitis and diarrhoea (more than three stools/day).. Patients in clinical remission after 6 weeks' open-label therapy with oral budesonide (Entocort CIR capsules, 9 mg/day) received 24 weeks' double-blind maintenance therapy with budesonide 6 mg/day or placebo. Thereafter, patients entered the 24-week, blinded follow-up period.. The proportion of patients in clinical remission (three or fewer stools/day) at the end of maintenance therapy.. A total of 34 patients in remission at week 6 were randomly assigned to budesonide 6 mg/day (n = 17) or placebo (n = 17). After 24 weeks' maintenance treatment, the proportions of patients in clinical remission were 76.5% (13 of 17) with budesonide and 12% (2 of 17) with placebo (p<0.001). At 48 weeks (the end of the follow-up period, without any treatment) these values were 23.5% (4 of 17) and 12% (2 of 17), respectively (p = 0.6). The median times to relapse after stopping active treatment (6 plus 24 weeks in the budesonide group; 6 weeks in the placebo group) were 39 and 38 days, respectively. Long-term treatment with budesonide was well tolerated.. Long-term maintenance therapy with oral budesonide is efficacious and well tolerated for preventing relapse in patients with collagenous colitis. The risk of relapse after 24 weeks' maintenance treatment is similar to that observed after 6 weeks' induction therapy.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Drug Administration Schedule; Epidemiologic Methods; Female; Glucocorticoids; Humans; Male; Middle Aged; Recurrence; Remission Induction; Severity of Illness Index; Treatment Outcome

Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is a high rate of relapse after treatment cessation.. This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of long-term therapy with oral budesonide (Entocort CIR capsules) for maintenance of clinical remission of collagenous colitis. Patients were aged >18 years with histologically proven collagenous colitis and >3 watery/loose stools per day on >or=4 of the prior 7 days. Open-label oral budesonide 9 mg/d was administered to all patients for 6 weeks. Patients in clinical remission (3 stools per day on >or=4 consecutive days (and included patients withdrawn because of adverse events).. Of 48 enrolled patients, 46 (96%) achieved clinical remission at week 6 and were randomized to maintenance budesonide or placebo. There were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events.. Oral budesonide 6 mg/d is efficacious and well tolerated for long-term maintenance of clinical remission in patients with collagenous colitis.

Topics: Administration, Oral; Adult; Aged; Biopsy; Budesonide; Colitis, Collagenous; Colonoscopy; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Glucocorticoids; Humans; Intestinal Mucosa; Male; Middle Aged; Quality of Life; Remission Induction; Retrospective Studies; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colon; Double-Blind Method; Down-Regulation; Female; Gene Expression Regulation, Enzymologic; Glucocorticoids; Humans; Intestinal Mucosa; Male; Nitric Oxide Synthase Type II; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index

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.. 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.. 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).. 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.

Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Quality of Life; Treatment Outcome

Budesonide (Entocort) is effective for the treatment of collagenous colitis.. To assess the long-term outcome of patients after induction of clinical remission by budesonide treatment.. Fifty-one patients with chronic diarrhoea and histologically proven collagenous colitis were enrolled in randomized, placebo-controlled crossover trial using budesonide 9 mg daily for 6 weeks. Patients in clinical remission after either initial or crossover budesonide treatment were followed using standardized questionnaires. Clinical relapse was defined as five or more loose stools/day for at least 4 consecutive days.. A total of 33 patients achieved clinical remission (85% per-protocol). During a median follow-up of 16 months, clinical relapse occurred in 20 patients (61%), after a median time of 2 weeks (range: 1-104, mean: 10 weeks). Patient age <60 years was identified as a significant risk factor for clinical relapse (OR = 7.4, P = 0.048). Budesonide was used for treatment of clinical relapse in 80% of patients achieving clinical response in all of them.. Budesonide is effective in the treatment of collagenous colitis. Clinical relapses may occur in a considerable number of patients, particularly in those <60 years. Treatment of clinical relapse with budesonide appears to be an effective option.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Cross-Over Studies; Diarrhea; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Treatment Outcome

Collagenous colitis (CC) is an inflammatory bowel disease, which usually responds to budesonide treatment. Our aim was to study the immunological background of the disease.. Analyses of peripheral and mucosal MAIT (mucosa associated invariant T cells) and NK (natural killer) cells were performed with flow cytometry. Numbers of mucosal cells were calculated using immunohistochemistry. We studied the same patients with active untreated CC (au-CC) and again while in remission on budesonide treatment. Budesonide refractory patients and healthy controls were also included. The memory marker CD45R0 and activation marker CD154 and CD69 were used to further study the cells. Finally B cells, CD4. The percentages of circulating CD56. Patients with active collagenous colitis have lower percentages of circulating MAIT and NK cells. However, there was no change of these cells in the colonic mucosa. Most mucosal cell populations were increased in budesonide refractory as compared to au-CC patients, particularly the number of MAIT cells. This may indicate that T cell targeting therapy could be an alternative in budesonide refractory CC.

Topics: Budesonide; CD8-Positive T-Lymphocytes; Colitis, Collagenous; Humans; Intestinal Mucosa; Killer Cells, Natural

There is an unmet need in investigating corticosteroid-sparing treatments for induction and maintenance of remission in microscopic colitis (MC). The authors' aim was to evaluate the outcomes of patients with MC treated with bile acid sequestrants (BAS).. MC is a common chronic diarrheal illness. Budesonide is effective induction therapy, but relapses are high after cessation of treatment.. Our cohort consisted of patients enrolled in our institutional MC registry, a biorepository of histology-confirmed diagnoses of MC. Patients receiving BAS for the treatment of MC were reviewed at each clinical visit for efficacy or ability to decrease budesonide maintenance dosing.. The authors included 79 patients (29 collagenous colitis and 50 lymphocytic colitis) with a median follow-up period of 35 months (range, 1 to 120). Most patients were female individuals (78%) and the median age was 69 years (range, 29 to 87). BAS therapy was used in 21 patients who were budesonide-naive, with a response rate of 76% (16/21). In patients treated previously with budesonide, 46 patients were budesonide-dependent and given BAS as maintenance therapy. Of these patients, 23 (50%) were able to decrease their budesonide dosing and 9 (20%) were able to stop budesonide completely. Seven of 46 patients (15%) stopped BAS because of intolerance, perceived lack of benefit, or treatment of concomitant diarrhea illness.. BAS may be an effective corticosteroid-sparing option in the treatment of MC and should be considered after budesonide induction. Larger controlled studies are needed to confirm the efficacy for long-term maintenance and tolerability of BAS in patients with MC.

Topics: Aged; Bile Acids and Salts; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Female; Humans

Microscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce.. To compare clinical characteristics and treatment response by age at diagnosis.. This retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance.. There are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.

Topics: Age Factors; Aged; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Humans; Middle Aged; Retrospective Studies

To study the epidemiological and clinical characteristics, and response to treatment in patients with microscopic colitis.. Epidemiological, clinical, blood test and endoscopic data were retrospectively collected from 113 patients with microscopic colitis. Response to treatment was analyzed in 104 of them. Efficacy and relapse after treatment with budesonide were assessed using survival curves (Kaplan-Meier).. 78% of the patients were women, with a mean age of 65 ± 16 years. In smokers, the mean age was 10 years younger. 48% of them had some concomitant autoimmune disease; 60% suffered a single outbreak of the disease. The clinical presentation was similar in both subtypes, although patients with collagenous colitis had a chronic course more frequently (48% vs. 29%, p = 0.047). The remission rate with budesonide was 93% (95% CI 82-98). The cumulative incidence of relapse, after a median follow-up of 21 months, was 39% (95% CI 26-54%): 19% at one year, 32% at two years, and 46% at three years of follow-up. There were no differences in clinical response to budesonide based on smoking habit or microscopic colitis subtype.. Microscopic colitis is more frequent in elderly women. Smoking was associated with earlier onset of the disease, although it did not influence the clinical course or response to treatment. The majority (> 90%) of patients treated with budesonide achieved remission, although nearly half subsequently relapsed.

Topics: Adult; Aged; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Colonoscopy; Ex-Smokers; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Recurrence; Retrospective Studies; Smokers; Smoking; Treatment Outcome

Increased frequencies of T regulatory (Treg) cells, key players in immune regulation, have been reported in inflammatory bowel diseases, including collagenous colitis (CC). However, traditional Treg identification techniques might have misinterpreted the frequencies of Treg cells in CC. Thus, we investigated the presence of genuine Treg cells in CC.. Treg cells were analyzed in mucosal and peripheral blood samples of CC patients before and during treatment with the corticosteroid drug budesonide and in healthy controls. Samples were analyzed by flow cytometry by classifying CD3+CD4+ cells as activated FoxP3highCD45RA- Treg cells, resting FoxP3dimCD45RA+ Treg cells, and nonsuppressive FoxP3dimCD45RA- T helper cells. Traditional gating strategies that classified Treg cells as CD25highCD127low, FoxP3+CD127low, and CD4+CD25+FoxP3+ were also used to facilitate comparison with previous studies.. Activated and resting Treg cell frequencies did not change in active CC mucosa or peripheral blood and were not affected by budesonide treatment. Instead, nonsuppressive FoxP3dimCD45RA- T helper cells were increased in active CC mucosa, and budesonide helped restore them to normal levels. In contrast, traditional Treg cell gating strategies resulted in increased Treg cell frequencies in active CC mucosa. No alterations were found in peripheral blood samples, independently of patient treatment or gating techniques.. Previously reported increase of Treg cells is a result of incomplete Treg phenotyping, which included nonsuppressive FoxP3dimCD45RA- T helper cells. Because budesonide did not affect Treg percentage, its therapeutic effect in CC might involve alternative mechanisms.

Topics: Budesonide; Case-Control Studies; Colitis, Collagenous; Forkhead Transcription Factors; Humans; Mucous Membrane; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The pathophysiology of the inflammatory bowel disease collagenous colitis (CC) is poorly described. Our aim was to use RNA sequencing of mucosal samples from patients with active CC, CC in remission, refractory CC, ulcerative colitis (UC), and control subjects to gain insight into CC pathophysiology, identify genetic signatures linked to CC, and uncover potentially druggable disease pathways.. We performed whole transcriptome sequencing of CC samples from patients before and during treatment with the corticosteroid drug budesonide, CC steroid-refractory patients, UC patients, and healthy control subjects (n = 9-13). Bulk mucosa and laser-captured microdissected intestinal epithelial cell (IEC) gene expression were analyzed by gene set enrichment and gene set variation analyses to identify significant pathways and cells, respectively, altered in CC. Leading genes and cells were validated using reverse-transcription quantitative polymerase chain reaction or immunohistochemistry.. We identified an activation of the adaptive immune response to bacteria and viruses in active CC that could be mediated by dendritic cells. Moreover, IECs display hyperproliferation and increased antigen presentation in active CC. Further analysis revealed that genes related to the immune response (DUOX2, PLA2G2A, CXCL9), DNA transcription (CTR9), protein processing (JOSD1, URI1), and ion transport (SLC9A3) remained dysregulated even after budesonide-induced remission. Budesonide-refractory CC patients fail to restore normal gene expression, and displayed a transcriptomic profile close to UC.. Our study confirmed the implication of innate and adaptive immune responses in CC, governed by IECs and dendritic cells, respectively, and identified ongoing epithelial damage. Refractory CC could share pathomechanisms with UC.

Topics: Adolescent; Adult; Aged; Budesonide; Cell Proliferation; Colitis, Collagenous; Colitis, Ulcerative; Collagen; Enterocytes; Extracellular Matrix; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunity; Inflammatory Bowel Diseases; Intestinal Mucosa; Male; Middle Aged; Stromal Cells; Transcription, Genetic; Young Adult

Diarrhoea is a common, debilitating symptom of gastrointestinal disorders. Pathomechanisms probably involve defects in trans-epithelial water transport, but the role of aquaporin [AQP] family water channels in diarrhoea-predominant diseases is unknown. We investigated the involvement of AQPs in the pathobiology of collagenous colitis [CC], which features chronic, watery diarrhoea despite overtly normal intestinal epithelial cells [IECs].. We assessed the expression of all AQP family members in mucosal samples of CC patients before and during treatment with the corticosteroid drug budesonide, steroid-refractory CC patients and healthy controls. Samples were analysed by genome-wide mRNA sequencing [RNA-seq] and quantitative real-time PCR [qPCR]. In some patients, we performed tissue microdissection followed by RNA-seq to explore the IEC-specific CC transcriptome. We determined changes in the protein levels of the lead candidates in IEC by confocal microscopy. Finally, we investigated the regulation of AQP expression by corticosteroids in model cell lines.. Using qPCR and RNA-seq, we identified loss of AQP8 expression as a hallmark of active CC, which was reverted by budesonide treatment in steroid-responsive but not refractory patients. Consistently, decreased AQP8 mRNA and protein levels were observed in IECs of patients with active CC, and steroid drugs increased AQP8 expression in model IECs. Moreover, low APQ8 expression was strongly associated with higher stool frequency in CC patients.. Down-regulation of epithelial AQP8 may impair water resorption in active CC, resulting in watery diarrhoea. Our results suggest that AQP8 is a potential drug target for the treatment of diarrhoeal disorders.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Aquaporin 1; Aquaporins; Budesonide; Caco-2 Cells; Colitis, Collagenous; Dexamethasone; Diarrhea; Down-Regulation; Epithelial Cells; Female; Homeostasis; HT29 Cells; Humans; Intestinal Mucosa; Male; Middle Aged; RNA, Messenger; Water

The most commonly reported pattern of anti-PD-1 induced colitis is an active colitis characterized by neutrophilic inflammation and prominent apoptosis. On the other hand, reports of collagenous colitis (which is a microscopic colitis) are exceptional. In this report, we describe an unusual case of anti-PD1-associated collagenous colitis in a 76-year-old man, treated with pembrolizumab for a stage IV cutaneous melanoma. Fourteen months after the start of pembrolizumab, the patient developed a grade 3 diarrhea (up to 9 stools per day) associated with profound hypokalemia. No bacterial, viral or parasitological infectious agents were found from stool analysis. The rectosigmoidoscopy showed colonic diffuse congestion with no ulceration. Systematic biopsies were performed during endoscopy. Histologically, the fragments analyzed revealed a moderately thickened subepithelial collagen layer (20-30μm thick) associated with a mild mixed inflammatory infiltrate within the lamina propria. There were no granuloma lesions, ulcerations or viral inclusion bodies. The patient was initially successfully treated with corticosteroids (prednisone) and temporary interruption of pembrolizumab. However, during corticosteroids tapering, a relapse was observed. The treatment was switched to budesonide, leading to a complete and definitive resolution of diarrhea. To date, budesonide has been stopped and pembrolizumab has not been restarted. Currently, there is a bone progression treated by radiotherapy alone. In case of a more important progression, a systemic treatment will be secondarily discussed.

Topics: Aged; Antibodies, Monoclonal, Humanized; Budesonide; Colitis, Collagenous; Diarrhea; Humans; Hypokalemia; Male; Melanoma; Melanoma, Cutaneous Malignant; Prednisone; Skin Neoplasms

Topics: Budesonide; Colitis, Collagenous; Colitis, Microscopic; Colonoscopy; Enterocolitis, Pseudomembranous; Female; Glucocorticoids; Humans; Middle Aged

Evidence for second-line therapy in patients with microscopic colitis [MC] failing budesonide is scarce, although anti-tumour necrosis factors [anti-TNFs], methotrexate and azathioprine have been reported to be effective in small cohort studies. Vedolizumab, a monoclonal antibody targeting α4β7-integrin, prevents homing of T-cells to the gut. We evaluated clinical remission with vedolizumab in budesonide-refractory MC patients.. We solicited gastroenterologists in Europe and Canada for cases of MC treated with vedolizumab. Vedolizumab 300 mg IV was administered at weeks 0, 2 and 6, and then every 8 weeks. Clinical remission and histological remission were defined as less than three stools per day and normalization of histology, respectively, after induction treatment.. Eleven cases were retrieved (nine females, lymphocytic colitis [LC] n = 5, collagenous colitis [CC] n = 6). Median [interquartile range] disease duration at vedolizumab initiation was 51 [29-70] months. Nine of 11 patients had failed one immunosuppressant and ten of 11 at least one anti-TNF agent. After three infusions of vedolizumab, clinical remission was observed in 5/11 patients [two LC and three CC] of whom three remained well with maintenance therapy [median duration of 13 months]. Biopsies were obtained from 9/11 patients. Histological remission was observed in 3/4 patients with clinical remission [2/3 CC, 1/1 LC] and 0/5 patients without clinical improvement.. In a series of highly refractory MC patients, vedolizumab induced clinical remission in 5/11 subjects, of whom 75% showed normalized histology. Larger randomized trials are needed to assess the efficacy of vedolizumab in patients with MC.

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Budesonide; Canada; Colitis, Collagenous; Colitis, Lymphocytic; Europe; Female; Gastrointestinal Agents; Humans; Maintenance Chemotherapy; Male; Middle Aged; Remission Induction; Retreatment; Retrospective Studies

Topics: Aged; Budesonide; Colitis, Collagenous; Colonoscopy; Female; Glucocorticoids; Humans; Risk Factors; Treatment Outcome

Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal.. To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC.. Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission.. Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis.. with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide.. One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Budesonide; Colitis, Collagenous; Dose-Response Relationship, Drug; Female; Humans; Logistic Models; Maintenance Chemotherapy; Male; Mercaptopurine; Middle Aged; Multivariate Analysis; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Spain

Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments.. To evaluate the outcomes of patients with active MC treated with immune modulators.. All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded.. Seventy-three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7-60) were included. The indications for treatment were budesonide-refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4-63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5-15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3-18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti-TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3-5.5). Complete response occurred in four patients and partial response in four patients.. The majority of patients with active MC responded to thiopurines, methotrexate, or anti-TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC.

Topics: Adult; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Female; Humans; Male; Methotrexate; Middle Aged; Tumor Necrosis Factor-alpha

Topics: Adult; Anti-Inflammatory Agents; Biopsy; Budesonide; Colitis, Collagenous; Collagen; Colon; Diagnosis, Differential; Diarrhea; Drug Substitution; Duodenum; Endoscopy, Gastrointestinal; Enteritis; Female; Humans; Hypoproteinemia; Magnetic Resonance Imaging; Prednisone; Remission Induction; Treatment Outcome

Hypogammaglobulinemia/common variable immunodeficiency (CVID) may lead to disruption of the gut mucosal immune barrier. Collagenous infiltrative disorders of the intestinal tract (colitis, gastritis, sprue) constitute a relatively new spectrum of gastrointestinal disorders. Our aims were (1) to determine the association between immunoglobulin deficiency state like CVID and collagenous infiltrative disorders of the gut and (2) to study the clinic-pathologic characteristics and treatment outcomes in these patients. A retrospective search was conducted to identify cases with concurrence of these two conditions at an academic center from 2007 to 2013. Four such patients were identified from our database: three with collagenous colitis and one with collagenous gastritis. All patients with collagenous colitis had normal colonic mucosa while the patient with collagenous gastritis had nodular gastric mucosa. Only one patient out of four had decreased plasma cells in the submucosa as expected in low immunoglobulin states. All patients had improvement in their symptoms on immunoglobulin therapy with considerable remission on budesonide. Literature search revealed reporting of four similar patients. In conclusion, (1) the association between collagenous infiltrative disorders of the gut and CVID and its prompt response to immunoglobulins with effective maintenance with budesonide are novel findings. Our study also shows that the presence of plasma cells should not rule out the possibility of CVID. (2) In patients with chronic diarrhea, hypogammaglobulinemia and collagenous colitis/sprue should be considered for the available effective treatments such as immunoglobulins and budesonide.

Topics: Adult; Aged; Budesonide; Colitis, Collagenous; Common Variable Immunodeficiency; Female; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Middle Aged; Remission Induction; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Aged; Budesonide; Colitis, Collagenous; Colon; Colonoscopy; Crohn Disease; Humans; Male; Mesalamine; Recurrence

Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory disorders of the colon. There is a paucity of data on differences in etiology, natural history, and treatment response between CC and LC.. Between 2002 and 2013, we identified new diagnoses of CC and LC using the Research Patient Data Registry in a tertiary referral center. We used chi square or Fischer's exact test and Wilcoxon rank-sum tests to compare the differences in clinical characteristics, treatment types, and response rates between LC and CC.. Through 2013, we confirmed 131 patients with a new diagnosis of microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective treatment for both CC and LC (94% and 80%, respectively). However, there were no statistically significant differences in response to various treatments according to the type of MC (all p > 0.10). Older age at the time of diagnosis was associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95% confidence interval: 1.21-2.56 for every 5-year increase) for both CC and LC.. Despite differences in the clinical characteristics, response rates to available treatments appeared to be similar in both LC and CC. Older patients may have a better response to bismuth subsalicylate therapy.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Bismuth; Budesonide; Colitis, Collagenous; Colitis, Lymphocytic; Female; Humans; Logistic Models; Male; Middle Aged; Organometallic Compounds; Salicylates; Tertiary Care Centers; Treatment Outcome

Collagenous colitis (CC) is an inflammatory bowel condition of unknown etiology. Systemic sclerosis (SSc) has been associated with CC in a few cases, but it is not clear whether CC could be considered an unusual manifestation of SSc or an independent condition. Here we present a case of SSc-associated CC and compare routine histology and immunofluorescence studies for allograft inflammatory factor 1 and caveolin 1 expression with other cases of CC and healthy controls. All CC biopsies showed characteristic sublaminal collagen accumulation and a decrease of caveolin 1 expression, this latter finding consistent with and common in any fibrotic reaction. In contrast, the expression of allograft inflammatory factor 1 was increased only in the SSc-CC specimen, suggesting a distinct pathogenesis. A literature review revealed 6 previously reported cases of SSc-CC with common clinical features. These observations suggest that CC should be suspected as a rare gastrointestinal complication of SSc and that clinicians should be aware of the possibility in SSc patients developing watery diarrhea.

Topics: Aged; Biopsy, Needle; Budesonide; Colitis, Collagenous; Colonoscopy; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lansoprazole; Risk Assessment; Scleroderma, Systemic; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome

Collagenous colitis (CC) is a less common colonic disease with variable prevalence and undulating course. Among the available therapies, budesonide was demonstrated to induce a rapid and sustained remission in many cases, but little is known about the comparative efficacy of other treatments, such as mesalamine.. Evaluation of a randomized study assessing the efficacy and safety of budesonide over mesalamine in patients with CC.. Data from the study showed that budesonide was significantly superior to placebo and to mesalamine and further supports the recommendation of the current guidelines on the use of budesonide in CC. However, other forms of mesalamine may further be evaluated for this disease.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Female; Gastrointestinal Agents; Humans; Male; Mesalamine

Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis.

Topics: Aged; Biopsy; Budesonide; Cholestyramine Resin; Colitis, Collagenous; Colon; Colonoscopy; Enterocolitis, Pseudomembranous; Female; Glucocorticoids; Humans; Predictive Value of Tests; Treatment Outcome

Oral budesonide has been proven effective in short- and long-term treatment of collagenous colitis; however, symptom relapse frequently occurs after drug withdrawal. The aim of this study was to identify the risk factors for symptom relapse in patients with collagenous colitis after withdrawal of short-term budesonide therapy.. One hundred twenty-three patients from 4 randomized controlled studies who achieved clinical remission after short-term treatment with budesonide (9 mg/d) were analyzed, including 40 patients receiving subsequent budesonide maintenance therapy (6 mg/d) for 6 months and 83 patients without active maintenance treatment. Variables available for analysis were age, sex, baseline stool frequency, duration of diarrhea, collagenous band thickness, and lamina propria inflammation. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were calculated by Cox proportional hazard model.. The overall symptom relapse rate was 61%. By multivariate analysis, a baseline stool frequency >5 per day (HR, 3.95; 95% CI, 1.08-14.39), history of diarrhea >12 months (HR, 1.77; 95% CI, 1.04-3.03), and the absence of budesonide maintenance therapy (HR, 2.71; 95% CI, 1.37-5.38) were associated with symptom relapse. The time to relapse was shorter in patients with a baseline stool frequency >5 per day (56 versus 199 d, P = 0.024), as in those with history of diarrhea >12 months (56 versus 220 d, P = 0.009). Budesonide maintenance therapy delayed the time to relapse (56 versus 207 d, P = 0.005).. Our data demonstrate that a high stool frequency at baseline and a long duration of diarrhea are risk factors for symptom relapse in collagenous colitis, whereas budesonide maintenance therapy is a protective factor against symptom relapse.

Topics: Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Diarrhea; Female; Follow-Up Studies; Humans; Inflammation; Male; Middle Aged; Prognosis; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Substance Withdrawal Syndrome

"Pseudomembranous collagenous colitis" is a morphologic variant of collagenous colitis in which active inflammation with pseudomembrane formation is prominent and which has been associated with infectious, toxic, and ischemic etiologies. However, extracolonic morphologic findings in patients with pseudomembranous collagenous colitis have not been previously described. Here, we present a case of a patient with pseudomembranous collagenous colitis with abnormal extracolonic findings. These include gastric antral mucosa with histologic features reminiscent of ischemic injury and reactive gastropathy with intraepithelial lymphocytosis and partial villous atrophy in the duodenal and ileal biopsies. The findings in the small intestinal biopsies resemble those seen in enteric mucosa in patients with conventional collagenous colitis. Our pathologic findings as well as the clinical course of the patient further emphasize the clinical and histologic similarities shared by pseudomembranous collagenous colitis and conventional collagenous colitis.

Topics: Aged; Budesonide; Colitis, Collagenous; Colon; Duodenum; Endoscopy, Gastrointestinal; Enterocolitis, Pseudomembranous; Female; Gastric Mucosa; Glucocorticoids; Humans; Ileum; Intestinal Mucosa; Intestine, Small; Pyloric Antrum; Treatment Outcome

Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders.. We report four infant baboons (age 7-12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4-10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment.. Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months).. Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that 1) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; 2) it was associated with the immunocompromised state of the baboons, as two nonimmunosuppressed age-matched baboons in close proximity did not develop the condition; and 3) it may have had an infectious origin, as all four cases developed within a 4-week period of time.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Diarrhea; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Male; Papio; Weight Loss

Patients with collagenous colitis have an impaired mucosal barrier. Moreover, collagenous colitis is associated with bile acid malabsorption. Bile acids can increase bacterial mucosal uptake in humans. Mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA) in Ussing chamber experiments.. To find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients.. The study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), potential difference, trans-epithelial resistance and transmucosal passage of Escherichia coli K12 after adding 100 μmol/L CDCA or DCA.. When adding 100 μmol/L CDCA or DCA, bacterial uptake increased fourfold in biopsies of patients in remission; CDCA 6.5 units [2.5-9.8] and DCA 6.2 units [2.1-22] (median [IQR]), compared with uptake in biopsies without added bile acids 1.6 units [1.1-3] (P=0.004 and P=0.01 respectively). In active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. Confocal microscopy revealed trans-epithelial passage of E. coli K12 within 30 min.. Low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. This allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.

Topics: Adult; Aged; Aged, 80 and over; Bile Acids and Salts; Biological Transport; Biopsy; Budesonide; Case-Control Studies; Chenodeoxycholic Acid; Colitis, Collagenous; Deoxycholic Acid; Escherichia coli K12; Female; Gastrointestinal Agents; Humans; In Vitro Techniques; Male; Microscopy, Confocal; Middle Aged

The aim of this study was to assess the activity of eosinophils, neutrophils, and CD4+ as well as CD8+ T-cells in 11 patients with active collagenous colitis (CC) before and after 8 weeks of budesonide treatment (9 mg once daily) compared to 10 healthy individuals.. Clinical symptoms were recorded and intestinal biopsy samples were taken and analyzed by flow cytometry. Eosinophils with a high surface expression of CD44 and low CD9 expression were classified as activated. Neutrophil activity was assessed by their expression of CD66b, and CD69 was used as an activation marker for T-cells.. All patients responded to the treatment. The eosinophils in active CC showed increased activity compared to controls. The activity was back to control levels after treatment. Neutrophils were not activated in CC patients before or after treatment. CD8+ T-cells from untreated CC patients had a lower activity than controls, and a tendency of lower activity was observed on CD4+ T-cells. After treatment, the activity was increased on both types of T-cells and was not different from controls.. In the present study we demonstrated that the inflammation in CC is characterized by activated eosinophils but there is no neutrophil activity. CD4+ and CD8+ T-cells are increased in numbers in active CC but, surprisingly, they had a lower grade of activity than in control subjects. The major finding of this study is that budesonide treatment restores the normal activation of eosinophils and T-cells, accompanied by clinical remission.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Budesonide; Colitis, Collagenous; Eosinophils; Female; Flow Cytometry; Humans; Immunoenzyme Techniques; Lectins, C-Type; Lymphocyte Activation; Male; Middle Aged; Neutrophil Activation; Neutrophils; T-Lymphocytes; Young Adult

Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC.. Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re-assessed.. All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission.. Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.

Topics: Adult; Aged; Anal Canal; Anti-Inflammatory Agents; Budesonide; Catheterization; Colitis, Collagenous; Female; Humans; Inflammation; Male; Manometry; Middle Aged; Rectum; Sensory Thresholds; Severity of Illness Index; Statistics, Nonparametric; Transducers; Treatment Outcome

Topics: Budesonide; Child, Preschool; Colitis, Collagenous; Female; Glucocorticoids; Humans

Topics: Budesonide; Chromogranin A; Colitis, Collagenous; Female; Glucocorticoids; Humans; Middle Aged; Serotonin

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Psoriatic; Budesonide; Colitis, Collagenous; Diclofenac; Female; Humans; Treatment Outcome

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antidiarrheals; Biopsy; Bismuth; Budesonide; Ciprofloxacin; Colitis, Collagenous; Colonoscopy; Enema; Female; Humans; Intestinal Mucosa; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Treatment Outcome

Collagenous colitis is increasingly recognized as a common diarrheal disorder of inflammatory origin. Intestinal inflammation is generally associated with increased mucosal permeability, but little is known about barrier function in microscopic colitis. Our aim was to investigate the mucosal barrier to nonpathogenic bacteria in collagenous colitis.. The study included 33 individuals, 25 with collagenous colitis (14 in clinical remission, 11 with active disease, and 8 of these again after 6 weeks budesonide treatment) and 8 control patients. Bowel movements were registered for 1 week. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (I(sc)), transepithelial resistance (TER), and transmucosal passage of chemically killed Escherichia coli K12.. Bacterial uptake was increased in patients in remission, 1.6 U (1.1-3.0) and in those with active disease, 4.6 U (2.5-5.8; median (IQR)), compared to controls, 0.7 U (0.1-1.1; P=0.004 and P-0.001, respectively). Active disease also had significant decrease in transepithelial resistance (TER) after 120 min, -9.7 Omega cm(2) ((-13)-(-4.3)), compared to controls, -5.2 Omega cm(2) ((-7.2)-(-3.1)), P-0.03; or patients in remission, -4.8 Omega cm(2) ((-8.0)-(-1.2)), P=0.04. Budesonide decreased median stool frequency to 1.9 (1.3-2.2) compared to 3.8 (3.7-4.2) before treatment (P=0.01), but bacterial uptake was still increased after budesonide 2.9 U (1.5-3.8), (P=0.006 compared to controls), and there were no significant changes in histology.. Collagenous colitis presents with significantly increased uptake and altered mucosal reactivity to nonpathogenic bacteria. Budesonide induces clinical remission and restores mucosal reactivity but does not abolish the increased bacterial uptake. An underlying barrier dysfunction may explain the frequent and rapid relapses in CC.

Topics: Aged; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Electric Impedance; Escherichia coli K12; Female; Humans; In Vitro Techniques; Intestinal Mucosa; Male; Recurrence

The etiology and pathogenesis of collagenous colitis (CC) is poorly understood and probably multifactorial; many potential pathophysiological mechanisms have been described, although none have been conclusively proved. Circumstantial evidence suggests that CC appears as an autoimmune response to a luminal or epithelial antigen of unknown origin. Infections and certain drugs (e.g. NSAID, lansoprazole) may act as triggers for an immune-mediated process. CC is characterized clinically by chronic watery, nonbloody diarrhea with normal endoscopic appearance and without radiological abnormalities, but specific microscopic changes in the colon. Histopathology is featured by the presence of a thickened subepithelial collagen band adjacent to the basal membrane. Up to 40% of patients with CC have associated diseases of autoimmune or inflammatory origin, such as thyroid disease, coeliac disease, rheumatoid arthritis, diabetes mellitus, Sjögren's syndrome, CREST syndrome, scleroderma, pernicious anemia, and sarcoidosis. Prurigo nodularis is a chronic condition characterized by intensely pruritic, lichenified, or excoriated papules and nodules of unknown etiology. It is assumed to represent a cutaneous reaction pattern to repeated scrubbing or scratching caused by pruritus. We report a case of CC and prurigo nodularis. To our knowledge, this association has not been reported earlier.

Topics: Aged; Anti-Inflammatory Agents; Budesonide; Colitis, Collagenous; Diarrhea; Female; Humans; Prurigo; Treatment Outcome

Topics: Adult; Budesonide; Colitis, Collagenous; Common Variable Immunodeficiency; Female; Glucocorticoids; Humans

Collagenous colitis (CC) is an uncommon disease with a favorable prognosis. It is included in the group of chronic watery diarrheas.. To study epidemiological and clinical characteristics of CC, as well as its course and response to the treatment.. This is a descriptive, retrospective study of the endoscopic colon biopsies performed in Hospital de León during 5 years. Those biopsies that fulfilled the histological criteria of CC were selected.. A total of 18 cases with an incidence of 1.25/10(5) inhabitants/year was obtained. Mean age was 66.7 years. There was no difference between both genders. The period of time to diagnosis was long (10 months). A possible association with intake of some drugs, as non-steroidal antiinflammatory drugs (46%) and lansoprazole (42.8%), and smoking (41.6%), as well as autoimmune disease (30.7%) was found. There was a good response to the treatment with mesalazine in 2 of 3 patients who received this treatment. The clinical course was also favorable for the 2 patients treated with budesonide.. It is important to take multiple biopsies of the colon in order to diagnose CC when there is a case of chronic watery diarrhea even when the colonoscopy is normal. Certain drugs and autoimmune diseases may be involved in the etiology.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Budesonide; Colitis, Collagenous; Colon; Colonoscopy; Diarrhea; Female; Glucocorticoids; Humans; Male; Mesalamine; Middle Aged; Retrospective Studies; Time Factors; Treatment Outcome

In general, the colonic mucosa is macroscopically normal in collagenous colitis, although minor, non-specific abnormalities may be found. Significant endoscopic abnormalities, "mucosal tears" representing longitudinal mucosal lacerations, have been reported in a few patients with collagenous colitis. We report the cases of three women with collagenous colitis and mucosal tears detected at the index colonoscopy in order to illustrate the endoscopic characteristics and review the literature. Including the present cases, a total of 12 patients with mucosal tears and collagenous colitis have been reported. In 10 patients, the mucosal lacerations involved the ascending or the transverse colon. Three of the 12 patients had a colonic perforation immediately after the colonoscopy. The colonoscopist should be aware that the risk of perforation is likely to be increased when mucosal tears are present.

Topics: Anti-Inflammatory Agents; Budesonide; Chronic Disease; Colitis, Collagenous; Colon; Colonoscopy; Female; Follow-Up Studies; Humans; Intestinal Mucosa; Intestinal Perforation; Time Factors; Treatment Outcome

Bile acid malabsorption is frequent in collagenous colitis and harmful bile acids may play a pathophysiological role. Glucocorticoids increase ileal bile acid transport. Budesonide have its main effect in the terminal ileum.. To evaluate whether the symptomatic effect of budesonide is linked to increased uptake of bile acids.. Patients with collagenous colitis were treated with budesonide 9 mg daily for 12 weeks. Prior to and after 8 weeks of treatment, the (75)SeHCAT test, an indirect test for the active uptake of bile acid-s, measurements of serum 7alpha-hydroxy-4-cholesten-3-one, an indicator of hepatic bile acid synthesis, and registration of symptoms were performed.. The median (75)SeHCAT retention increased from 18% to 35% (P < 0.001, n = 25) approaching the values of healthy controls (38%). The 7alpha-hydroxy-4-cholesten-3-one values decreased significantly among those with initially high synthesis (from 36 to 23 ng/mL, P = 0.04, n = 9); however, for the whole group the values were not altered (19 ng/mL vs. 13 ng/mL, P = 0.23, N.S., n = 19).. The normalization of the (75)SeHCAT test and the reduction of bile acid synthesis in patients with initially high synthetic rate, suggests that the effect of budesonide in collagenous colitis may be in part due to decreased bile acid load on the colon.

Topics: Adult; Aged; Anti-Inflammatory Agents; Bile Acids and Salts; Budesonide; Colitis, Collagenous; Female; Humans; Intestinal Absorption; Male; Middle Aged

Topics: Anti-Inflammatory Agents; Budesonide; Capsules; Colitis, Collagenous; Cross-Over Studies; Delayed-Action Preparations; Drug Administration Schedule; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome