Therapy of prednisone-refractory collagenous colitis with budesonide

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

Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment

BackgroundControlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal.AimTo evaluate the need for high-dose budesonide (≥6 mg/d) to maintain clinical remission in CC.MethodsAnalysis of a multicentre retrospective cohort of 75 patients with CC (62.3 ± 1.5 years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9 mg/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 (≥6 mg/d) to maintain clinical remission.ResultsBudesonide 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.Treatmentwith thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44–97%), allowing for withdrawal from or a dose decrease of budesonide.ConclusionsOne fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6 mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.     

Enteropathic arthritis in association with collagenous colitis

A 46-year-old man simultaneously developed chronic seronegative non destructive oligoarthritis and chronic watery diarrhoea. Biopsies from the colorectal mucosa showed a thickened subepithelial collagen layer consistent with collagenous colitis. Collagenous colitis should be added to the list of causes of enteropathic arthritis.     

Lansoprazole-associated collagenous colitis： Diffuse mucosal cloudiness mimicking ulcerative colitis

There have only been a few reports on lansoprazole-associated collagenous colitis. Colonic mucosa of collagenous colitis is known to be endoscopically normal. We present a case of collagenous colitis where the mucosa showed diffuse cloudiness mimickin gulcerative colitis. A 70-year-old woman developed watery diarrhea four to nine times a day. She had interstitial pneumonia at 67 and reflux esophagitis at 70 years. Lansoprazole 30 mg/d had been prescribed for reflux esophagitis for nearly 6 mo. Lansoprazole was withdrawn due to its possible side effect of diarrhea. Colonoscopy disclosed diffuse cloudiness of the mucosa which suggested ulcerative colitis.Consequently sulfasalazine 2 g/d was started. The patient＇s diarrhea dramatically disappeared on the following day. However, biopsy specimens showed subepithelial collagenous thickening and infiltration of inflammatory cells in the lamina propria, confirming the diagnosis of collagenous colitis. One month after sulfasalazine therapy was initiated, colonoscopic and histological abnormalities resolved completely. Fivemonths later the diarrhea recurred. The findings on colonoscopy and histology were the same as before, confirming a diagnosis of collagenous colitis relapse. We found that the patient had begun to take lansoprazole again 3 mo ahead of the recent diarrhea.Withdrawal of lansoprazole promptly resolved the diarrhea. Endoscopic and histological abnormalities were also completely resolved, similar to the first episode. Retrospectively, the date of commencement of sulfasalazine and discontinuation of lansoprazole in the first episode was found to be the same. We conclude that this patient had lansoprazole-associated collagenous colitis.     

Colonic mucosal tears in collagenous colitis

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.     

Pitfalls and errors in the diagnosis of collagenous and lymphocytic colitis

The diagnosis of both CC and LC is based on a compatible clinical picture and well-established objective histological criteria. The motivation degree of the involved physicians is essential in the diagnosis of microscopic colitis. The gastroenterologist should refer every patient with chronic watery diarrhea to perform a colonoscopy in spite of the benign course of the disease and the absence of alarm symptoms or signs. The endoscopist should take multiple stepwise biopsy samples of the colonic mucosa despite that the mucosa looked macroscopically normal. Finally, the pathologist should be motivated to use objective histological criteria to make the diagnosis. In this context, it is important to define the terminology as clearly as possible to avoid confusion.     

Mucosa-associated bacteria in two middle-aged women diagnosed with collagenous colitis

AIM: To characterize the colon microbiota in two women histologically diagnosed with collagenous colitis using a culture-independent method.METHODS: Biopsies were taken from the ascending colon and the total DNA was extracted. Universal bacterial primers were used to amplify the bacterial 16S rRNA genes. The amplicons were then cloned into competent Escherichia coli cells. The clones were sequenced and identified by comparison to known sequences.RESULTS: The clones could be divided into 44 different phylotypes. The microbiota was dominated by Firmicutes and Bacteroidetes. Seven phylotypes were found in both patients and constituted 47.5% of the total number of clones. Of these, the most dominating were clones similar to Bacteroides cellulosilyticus, Bacteroides caccae, Bacteroides thetaiotaomicron, Bacteroides uniformis and Bacteroides dorei within Bacteroidetes. Sequences similar to Faecalibacterium prausnitzii and Clostridium citroniae were also found in both patients.CONCLUSION: A predominance of potentially pathogenic Bacteroides spp., and the presence of clones showing similarity to Clostridium clostridioforme were found but the overall colon microbiota showed similarities to a healthy one. Etiologies for collagenous colitis other than an adverse bacterial flora must also be considered.     

Small-bowel permeability in collagenous colitis

Objective. Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability. Material andmethods. Ten patients with CC and chronic diarrhoea participated in the study. Coeliac disease was excluded by small-bowel biopsy and/or serology. Intestinal permeability was assessed as urinary excretion (ratios) 2, 4 and 6 h after ingestion of ¹⁴C-labelled mannitol (¹⁴C-mannitol) and ^99mTc-labelled diethylenetriamine-pentaacetic acid (^99mTc-DTPA). Data were compared with the results from healthy controls. Results. No difference was found between groups in urinary excretion of ¹⁴C-mannitol and ^99mTc-DTPA after 2, 4 or 6 h, respectively. Likewise, no significant differences in the ^99mTc-DTPA/¹⁴C-mannitol ratios between patients and controls were detected after 2 h: 0.030 (0.008–0.130) versus 0.020 (0.007–0.030), p=0.19, after 4 h: 0.040 (0.009–0.180) versus 0.020 (0.008–0.040), p=0.14 or after 6 h: 0.040 (0.012–0.180) versus 0.020 (0.010–0.040), p=0.17. Conclusions. No alterations in intestinal permeability in patients with CC could be demonstrated. Impairment of the integrity of the mucosa of the small bowel and the presence of a general dysfunction of the small intestine in patients with CC seem unlikely.     

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 coUagenous 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.     

溃疡性结肠炎患者生存质量研究现状与展望

溃疡性结肠炎(ulcerative colitis,uc)是炎症性肠病(inflammatory bowel disease,IBD)的一种,其临床表现多样性,病程迁延难愈,患者不仅在生理功能方面受到影响,而且在心理功能、社会关系、情感功能等领域中均有不同程度的下降.对UC患者生存质量(quality of life,...     

An epidemiological study of collagenous colitis in southern Sweden from 2001-2010

AIM: To estimate the incidence of collagenous colitis (CC) in southern Sweden during 2001-2010.METHODS: Cases were identified by searching for CC in the diagnostic registers at the Pathology Departments in the county of Skåne. The catchment area comprised the south-west part of the county (394 307 inhabitants in 2010) and is a mixed urban and rural type with limited migration. CC patients that had undergone colonoscopy during the defined period and were living in this area were included in the study regardless of where in Skåne they had been diagnosed. Medical records were scrutinized and uncertain cases were reassessed to ensure that only newly diagnosed CC cases were included. The diagnosis of CC was based on both clinical and histopathological criteria. The clinical criterion was non-bloody watery diarrhoea. The histopathological criteria were a chronic inflammatory infiltrate in the lamina propria, a thickened subepithelial collagen layer ≥ 10 micrometers (μm) and epithelial damage such as flattening and detachment.RESULTS: During the ten year period from 2001-2010, 198 CC patients in the south-west part of the county of Skåne in southern Sweden were newly diagnosed. Of these, 146 were women and 52 were men, i.e., a female: male ratio of 2.8:1. The median age at diagnosis was 71 years (range 28-95/inter-quartile range 59-81); for women median age was 71 (range 28-95) years and was 73 (range 48-92) years for men. The mean annual incidence was 5.4/10⁵ inhabitants. During the time periods 2001-2005 and 2006-2010, the mean annual incidence rates were 5.4/10⁵ for both periods [95% confidence interval (CI): 4.3-6.5 in 2001-2005 and 4.4-6.4 in 2006-2010, respectively, and 4.7-6.2 for the whole period]. Although the incidence varied over the years (minimum 3.7 to maximum 6.7/10⁵) no increase or decrease in the incidence could be identified. The odds ratio (OR) for CC in women compared to men was estimated to be 2.8 (95% CI: 2.0-3.7). The OR for women 65 years of age or above compared to below 65 years of age was 6.9 (95% CI: 5.0-9.7), and for women 65 years of age or above compared to the whole group the OR was 4.7 (95% CI: 3.6-6.0). The OR for age in general, i.e., above or 65 years of age compared to those younger than 65 was 8.3 (95% CI: 6.2-11.1). During the last decade incidence figures for CC have also been reported from Calgary, Canada during 2002-2004 (4.6/10⁵) and from Terrassa, Spain during 2004-2008 (2.6/10⁵). Our incidence figures from southern Sweden during 2001-2010 (5.4/10⁵) as well as the incidence figures presented in the studies during the 1990s (Terrassa, Spain during 1993-1997 (2.3/10⁵), Olmsted, United States during 1985-2001 (3.1/10⁵), Örebro, Sweden during 1993-1998 (4.9/10⁵), and Iceland during 1995-1999 (5.2/10⁵) are all in line with a north-south gradient, something that has been suggested before both for CC and inflammatory bowel disease.CONCLUSION: The observed incidence of CC is comparable with previous reports from northern Europe and America. The incidence is stable but the female: male ratio seems to be decreasing.     

Diagnosis and management of microscopic colitis

Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscoplc incidence of each disorder examination. The annual is 4-6/100000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented shortterm treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.     

Prevalence of microscopic colitis in patients with diarrhea of unknown etiology in Turkey

AIM： To investigate the prevalence and demography of microscopic colitis in patients with diarrhea of unknown etiology and normal colonoscopy in Turkey. METHODS： Between March, 1998 to July, 2005, 129 patients with chronic non-bloody diarrhea of unexplained etiology who had undergone full colonoscopy with no obvious abnormalities were included in the study. Two biopsies were obtained from all colonic segments and terminal ileum for diagnosis of microscopic colitis. On histopathologic examination, criteria for lymphocytic colitis （intraepithelial lymphocyte ≥ 20 per 100 intercryptal epithelial cells, change in surface epithelium, mononuclear infiltration of the lamina propria） and collagenous colitis （subepithelial collagen band thickness ≥ 10 μm） were explored. RESULTS： Lymphocytic colitis was diagnosed in 12 （9%） patients （Female/Male： 7/5, mean age： 45 year, range： 27-63） and collagenous colitis was diagnosed in only 3 （2.5%） patients （all female, mean age： 60 years, range： 54-65）.CONCLUSION： Biopsy of Turkish patients with the diagnosis of chronic non-bloody diarrhea of unexplained etiology and normal colonoscopic findings will reveal microscopic colitis in approximately 10% of the patients. Lymphocytic colitis is 4 times more frequent than collagenous colitis in these patients.     

Long-term natural history and complications of collagenous colitis

Microscopic forms of colitis have been described, including collagenous colitis, a possibly heterogeneous disorder. Collagenous colitis most often appears to have an entirely benign clinical course that usually responds to limited treatment. Sometimes significant extracolonic disorders, especially arthritis, spondylitis, thyroiditis and skin disorders, such as pyoderma gangrenosum, dominate the clinical course and influence the treatment strategy. However, rare fatalities have been reported and several complications, some severe, have been attributed directly to the colitis. Toxic colitis and toxic megacolon may develop. Concomitant gastric and small intestinal inflammatory disorders have been described including celiac disease and more extensive collagenous inflammatory disease. Colonic ulceration has been associated with the use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn disease, may evolve directly from collagenous colitis. Submucosal ‘dissection’, colonic fractures, or mucosal tears and perforation, possibly from air insufflation during colonoscopy, have been reported. Similar changes may result from increased intraluminal pressures that may occur during radiological imaging of the colon. Neoplastic disorders of the colon may also occur during the course of collagenous colitis, including colon carcinoma and neuroendocrine tumours (ie, carcinoids). Finally, lymphoproliferative disease has been reported.     

Predictors of health-related quality of life in patients with moderate to severely active ulcerative colitis receiving biological therapy

Abstract

Background and aims: Patients with ulcerative colitis have reduced health-related quality of life compared to the general population. Current treatment strategy aims to reduce patients’ symptoms and increase health-related quality of life. We investigated which symptoms of ulcerative colitis correlate to decreased health-related quality of life.

Methods: Among 743 patients with moderate to severely active ulcerative colitis receiving biological therapy in a cross-sectional national study, we determined which disease-related symptoms, as measured by the Simple Clinical Colitis Activity Index, worsened health-related quality of life scores across the Short Health Scale dimensions, while adjusting for treatment, age, and clinical manifestation, and stratifying for sex, by means of multiple linear regression.

Results: Patients with active disease had decreased health-related quality of life compared to those with inactive disease (median 5.8 (range 4.5–7.5) vs. 2 (0.8–3.3)). Both sexes had decreased health-related quality of life in all dimensions for the symptoms: bowel frequency during daytime (0.37–0.86 and 0.46–0.84), urgency of defecation (0.54–0.79 and 0.49–0.65) and blood in stool (0.50–0.75 and 0.36–0.54) for men and women respectively. Women were more often negatively affected by bowel frequency during night-time (4 domains vs. 1) and arthritis (5 domains vs. 3). In non-stratified analysis female sex is an independent predictor of lower health-related quality of life for 3 domains (0.38–0.53).

Conclusions: Health-related quality of life was most prominently associated with bowel frequency during daytime, urgency of defecation, and blood in stool. Other symptoms associated for some health-related quality of life dimensions, and appear to vary between the sexes.     

Fecal stream diversion and mucosal cytokine levels in collagenous colitis:A case report

In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs:loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin(IL)-1β,IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5,IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction,the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.     

布地奈得和氢化可的松灌肠治疗溃疡性结肠炎的对比研究

对比观察布地奈得（ＢＵＤ）和氢化可的松（ＨＤ）灌肠治疗轻、中度远段溃疡性结肠炎的疗效及副作用;建立高效液相色谱仪检测血和结肠粘膜炎ＨＤ浓度的方法。方法随机对照单盲观察ＢＵＤ组１２例,ＨＤ组１９例ＵＣ患者。治疗２经较两组在临床症状,肠镜下,组强及学Ｗｉｌｌｉａｎ疾病活动指数几方面的变化;     

Co-occurrence of psoriatic arthritis with collagenous colitis: clinicopathologic findings of a case

A 58-year-old man developed psoriatic arthritis and, after 6 months, persistent watery diarrhoea. Biopsies from the colorectal mucosa showed thickened subepithelial collagen consistent with collagenous colitis. There also was an inflammatory cell infiltration (mainly lymphocytes and monocytes) in the chorion. These findings and the parallel course of articular and bowel complaints suggest a clinicopathologic correlation between arthritis and colic involvement. Received: 19 July 2001 / Accepted: 2 January 2002     

Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients

INTRODUCTION Collagenous colitis (CC) is characterized by watery diarrhea and an increased subepithelial collagen layer with infiltration of inflammatory cells in the surface epithelium and lamina propria of the colon[1]. The thickened collagen in CC is a…     

A unique case of collagenous colitis presenting as protein-losing enteropathy successfully treated with prednisolone

A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa, and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon, particularly in the ascending portion, was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy （PLE） without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management.