Interventions for treating collagenous colitis.

BACKGROUND: 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). OBJECTIVES: The primary objective was to assess the benefits and harms of treatments for collagenous colitis. SEARCH METHODS: We searched CENTRAL, the Cochrane IBD Group Specialized Register, MEDLINE and EMBASE from inception to 7 November 2016. SELECTION CRITERIA: We included RCTs comparing a therapy with placebo or active comparator for the treatment of active or quiescent collagenous colitis. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: Twelve RCTs (476 participants) were included. These studies assessed bismuth subsalicylate, Boswellia serrata extract, mesalamine, cholestyramine, probiotics, prednisolone and budesonide therapy. Four studies were low risk of bias. One study assessing mesalamine and cholestyramine was judged to be high risk of bias due to no blinding. The other studies had an unclear risk of bias for random sequence generation (five studies) allocation concealment (six studies), blinding (one study), incomplete outcome data (one study) and selective outcome reporting (one study). Clinical response occurred in 100% (4/4) of patients who received bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks) compared to 0% (0/5) of patients who received placebo (1 study; 9 participants; RR 10.80, 95% CI 0.75 to 155.93; GRADE = very low). Clinical response occurred in 44% (7/16) of patients who received Boswellia serrata extract (three 400 mg/day capsules for 8 weeks) compared to 27% (4/15) of patients who received placebo (1 study; 31 participants; RR 1.64, 95% CI 0.60 to 4.49; GRADE = low). Clinical response occurred in 80% (24/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study; 55 participants; RR 1.82, 95% CI 1.13 to 2.93; GRADE = low). Histological response was observed in 87% (26/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study, 55 participants; RR 1.97, 95% CI 1.24 to 3.13; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 0.69, 95% CI 0.43 to 1.10; GRADE = low), withdrawals due to adverse events (RR 0.09, 95% CI 0.01 to 1.65; GRADE = low) and serious adverse events (RR 0.12, 95% CI 0.01 to 2.21; GRADE = low). Clinical response occurred in 44% (11/25) of mesalamine patients (3 g/day) compared to 59% (22/37) of placebo patients (1 study; 62 participants; RR 0.74, 95% CI 0.44 to 1.24; GRADE = low). Histological response was observed in 44% (11/25) and 51% (19/37) of patients receiving mesalamine and placebo, respectively (1 study; 62 participants; RR 0.86, 95% CI 0.50 to 1.47; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 1.26, 95% CI 0.84 to 1.88; GRADE = low), withdrawals due to adverse events (RR 5.92, 95% CI 0.70 to 49.90; GRADE = low) and serious adverse events (RR 4.44, 95% CI 0.49 to 40.29; GRADE = low). Clinical response occurred in 63% (5/8) of prednisolone (50 mg/day for 2 weeks) patients compared to 0% (0/3) of placebo patients (1 study, 11 participants; RR 4.89, 95% CI 0.35 to 68.83; GRADE = very low). Clinical response occurred in 29% (6/21) of patients who received probiotics (2 capsules containing 0.5 x 1010 CFU each of L. acidophilus LA-5 and B. animalis subsp. lactis strain BB-12 twice daily for 12 weeks) compared to 13% (1/8) of placebo patients (1 study, 29 participants, RR 2.29, 95% CI 0.32 to 16.13; GRADE = very low). Clinical response occurred in 73% (8/11) of patients who received mesalamine (800 mg three times daily) compared to 100% (12/12) of patients who received mesalamine + cholestyramine (4 g daily) (1 study, 23 participants; RR 0.74, 95% CI 0.50 to 1.08; GRADE = very low). Clinical response occurred in 81% (38/47) of patients who received budesonide (9 mg daily in a tapering schedule for 6 to 8 weeks) compared to 17% (8/47) of placebo patients (3 studies; 94 participants; RR 4.56, 95% CI 2.43 to 8.55; GRADE = low). Histological response was higher in budesonide participants (72%, 34/47) compared to placebo (17%, 8/47) (RR 4.15, 95% CI 2.25 to 7.66; GRADE = low). Clinical response was maintained in 68% (57/84) of budesonide patients compared to 20% (18/88) of placebo patients (3 studies, 172 participants, RR 3.30 95% CI 2.13 to 5.09; GRADE = low). Histological response was maintained in 48% (19/40) of budesonide patients compared to 15% (6/40) of placebo patients (2 studies; 80 participants; RR 3.17, 95% CI 1.44 to 6.95; GRADE = very low). No difference was found between budesonide and placebo for adverse events (5 studies; 290 participants; RR 1.18, o95% CI 0.92 to 1.51; GRADE = low), withdrawals due to adverse events (5 studies, 290 participants; RR 0.97, 95% CI 0.43 to 2.17; GRADE = very low) or serious adverse events (4 studies, 175 participants; RR 1.11, 95% CI 0.15 to 8.01; GRADE = very low). Adverse effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Adverse effects reported in the mesalamine studies included nausea and skin rash. Adverse effects in the prednisolone study included abdominal pain, headache, sleep disturbance, mood change and weight gain. AUTHORS' CONCLUSIONS: 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.

Collagenous colitis presenting as spontaneous perforation in an 80 year old woman: Report of a Case.

BACKGROUND: Perforation of the colon occurring during or shortly following colonoscopy or barium enema is a rare complication of collagenous colitis (CC). "Spontaneous" perforation in CC, in which no instigating factor is identified, is even less common, with only five cases reported to date. We report herein an additional case of spontaneous perforation in previously undiagnosed CC and review the clinical and pathological features of previously reported cases. CASE PRESENTATION: An 80 year old woman presented to the emergency department with abdominal pain preceded by approximately one month of frequent non-bloody diarrhea. Abdominal CT showed parietal thickening of the colon at the splenic flexure with pneumatosis and signs of perforation. Segmental resection was performed. Pathologic examination showed the microscopic findings typical of CC complicated by several deep ulcers and perforation. One day following discharge from hospital abdominal pain and frequent non-bloody diarrhea recurred. The patient was managed conservatively and treated with oral budesonide with resulting resolution of symptoms. CONCLUSIONS: Spontaneous perforation is a rare and serious complication of CC. All patients to date have been female. In contrast to procedure-related perforation, which favors the right colon, spontaneous perforation in CC has in all cases involved the left colon. Knowledge of spontaneous perforation as a potential complication of previously undiagnosed CC may be helpful in the evaluation and management of patients presenting with colonic perforation, especially those with risk factors for CC.

Colonic perforation in collagenous colitis: a systematic review of a rare complication and guidance on management.

OBJECTIVE: Collagenous colitis is an increasingly diagnosed clinical and pathological variant of microscopic colitis, mainly affecting middle-aged and elderly women; herein we review the literature for a rare complication (colonic perforation) and the most appropriate management. METHODS: EMBASE, MEDLINE and abstracts from major gastroenterological congresses were searched in addition to hand-searching of electronic journals. Ten case reports and short series were identified as relevant to this study, and full papers of all these articles were obtained. RESULTS: A total of 30 cases were recorded (28 female; age range 37-86 years, median 66 years). Colonic perforation was reported in 21 cases, mainly following colonoscopy (15 cases) or barium enema (4 cases). The site of colonic perforation/tears was predominantly right sided (17 cases). These cases were managed differently in different series, and none of the collagenous colitis-related colonic perforations that were treated conservatively (n = 5), or with diagnostic laparotomy but no colonic resection (n = 2), required further surgical intervention. CONCLUSIONS: Conservative management of collagenous colitis-related perforation seems to be an appropriate initial approach. However, diagnosis of collagenous colitis is usually retrospective in colonic perforations related to endoscopy or barium enema, i.e. when the histology results are available, and it seems difficult to provide a management plan specific to these patients in the clinical setting. Therefore general guidelines for management of all colonoscopy- and barium enema-related perforation are required. When perforation occurs in an otherwise intact colon, diagnostic laparoscopy can be considered as appropriate initial management.

Colonic perforation as a complication of collagenous colitis in a series of 12 patients.

OBJECTIVES: The rare complication of colonic perforation in collagenous colitis following colonoscopy or barium enema is reported in this series of 12 patients. METHODS: Patients with collagenous colitis complicated by perforation were collected from the authors' consultation files between 1992 and 2007. Colectomy and biopsy specimens were reviewed and the corresponding clinical data were analyzed. RESULTS: The patients ranged in age from 44 to 80 yr, with a female-to-male ratio of 11:1. Perforation occurred during colonoscopy in 2 patients, within 0-5 days following colonoscopy in 8 patients, and during barium enema in 2 patients. The most notable colonoscopic findings were bleeding linear ulcers of the right colon in 9 patients, several of which developed under direct visualization during endoscopy. The perforation culminated in right hemicolectomy in 11 patients. Linear fissuring ulcers were identified in the resections of 8 patients along with features of perforation, including pneumatosis in 4 patients and barium extravasation within the muscularis propria in 2 patients. CONCLUSIONS: This is the largest published series to date, and the first to uncover several novel clinicopathologic features of perforation in collagenous colitis, including the right colonic predilection (corresponding to disease severity), the association with not only colonoscopy, but also barium enema, the occurrence of recognizable perforation actually developing during the procedure, and a more detailed information on the marked histologic severity of these patients' collagenous colitis. An awareness of this rare but potentially fatal complication of collagenous colitis may facilitate its diagnosis and management.

Complications of collagenous colitis.

Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease.

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

Colonic perforation in collagenous colitis: an unusual complication.

Collagenous colitis is generally regarded as a benign disease with few serious complications. We report two women with collagenous colitis who presented with colonic perforation, one spontaneously and one 7 days after a barium enema, and a review of the literature. Including the present cases, 13 patients with collagenous colitis and colonic perforation have been reported, in two patients spontaneously and in 11 patients after a colonoscopy or barium enema. All were operated on except one patient who recovered after medical treatment. The pathogenesis of this complication is unknown. We propose that there might be a connection between mucosal tears and colonic perforation in collagenous colitis.