Budesonide in the Treatment of Collagenous Colitis

Delarive, Joakim; Saraga, E.; Dorta, Gian; Blum, André

doi:10.1159/000007516

Cited by 29 publications

(8 citation statements)

References 5 publications

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“…This is in accordance with previous open studies 8 9 and a recently published placebo controlled trial. 10 Collagenous colitis is characterised by watery diarrhoea and in the present study up to 10 bowel movements a day were found.…”

Section: Discussionsupporting

confidence: 93%

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

Bonderup

Hansen²,

Birket-Smith³

et al. 2003

Gut

216

127

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

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Section: Discussionsupporting

confidence: 93%

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

Bonderup

Hansen²,

Birket-Smith³

et al. 2003

Gut

216

127

View full text Add to dashboard Cite

show abstract

“…In many cases, even colonoscopy does not detect any signs of inflammation; therefore, in patients with chronic watery diarrhea, biopsy of even apparently normal mucosa is mandatory. 5,10,14 The findings of Cammarota et al 9 on endoscopic sonography are somewhat different from the findings in our case. First, the predominant finding of watery stool in the large bowel could not be detected on endoscopic sonography because of preparatory bowel cleansing.…”

Section: Discussioncontrasting

confidence: 92%

“…It is characterized by watery diarrhea associated with inflammatory infiltration and subepithelial collagen deposits on colonic biopsies despite a normal or subnormal endoscopic appearance. 10 One suggested pathophysiologic mechanism for diarrhea in collagenous colitis is a reduced permeability of electrolytes and water in the colonic mucosa. 11 Sonography is a very sensitive method for detecting fluid within the bowel.…”

Section: Discussionmentioning

confidence: 99%

Suspicion of microscopic colitis raised by sonographic examination

Hollerweger¹,

Macheiner²,

Brunner

2003

J of Clinical Ultrasound

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This report describes the case of a 57-year-old woman who was incidentally identified as having lymphocytic colitis after she underwent routine transabdominal sonographic examination. She initially reported having no irregularities in her bowel movements. Sonography revealed the following nonspecific findings: watery stool in the entire colon, slight thickening of the hypoechoic mucosal layer and moderate thickening of the hyperechoic submucosal layer of the colon, and no pathologic findings in the small intestine. On additional questioning, the patient said that she had had watery diarrhea for the last 10 years, with as many as 10 bowel movements daily. Endoscopic examination and biopsy were performed. Histopathologic examination of biopsy specimens showed lymphocytic infiltration of the mucosa and some collagen deposits, consistent with a diagnosis of lymphocytic colitis. Treatment was begun with loperamide, sulfasalazine, and budesonide. Within 3 weeks of the start of treatment, the number of bowel movements decreased to 1-2 daily. Follow-up sonography at that time revealed normalization of the bowel contents and disappearance of the thickened submucosal layer of the colon. Nonspecific sonographic findings like those in this case lead to the need to rule out various diseases through further appropriate evaluations to identify the correct diagnosis.

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“…Moreover, budesonide is universally employed to treat asthma, and asthma was recently associated with reduced risk of developing pancreatic ductal adenocarcinoma (30). Furthermore, budesonide is also used to treat the collagenous colitis, a rare inflammatory disorder associated with collagen accumulation in the colorectal mucosa (31,32), and its therapeutic efficacy is ascribed to the anti-inflammatory activity of GCs (33). Thus, our unexpected findings that budesonide blocks mesenchymal transition interfering with collagen accumulation provide novel insights into its therapeutic effects.…”

Section: Discussionmentioning

confidence: 87%

Collagen Prolyl Hydroxylation–Dependent Metabolic Perturbation Governs Epigenetic Remodeling and Mesenchymal Transition in Pluripotent and Cancer Cells

et al. 2019

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Collagen prolyl hydroxylation (CPH), which is catalyzed by prolyl 4-hydroxylase (P4H), is the most prevalent posttranslational modification in humans and requires vitamin C (VitC). Here, we demonstrate that CPH acts as an epigenetic modulator of cell plasticity. Increased CPH induced global DNA/histone methylation in pluripotent stem and tumor cells and promoted cell state transition (CST). Interfering with CPH by either genetic ablation of P4H subunit alpha-2 (P4HA2) or pharmacologic treatment reverted epigenetic changes and antagonized CST. Mechanistically, we suggest that CPH modifies the epigenetic landscape by reducing VitC for DNA and histone demethylases. Repurposed drugs targeting CPH-mediated metabolic perturbation, such as the antiasthmatic budesonide, blocked metastatic dissemination of breast cancer cells in vivo by preventing mesenchymal transition. Our study provides mechanistic insights into how metabolic cues and epigenetic factors integrate to control CST and paves the way for the development of novel antimetastatic strategies. Significance: A phenotype-based high-throughput screening reveals unforeseen metabolic control of cell plasticity and identifies budesonide as a drug candidate for metastatic cancer.

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Budesonide in the Treatment of Collagenous Colitis

Cited by 29 publications

References 5 publications

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

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

Suspicion of microscopic colitis raised by sonographic examination

Collagen Prolyl Hydroxylation–Dependent Metabolic Perturbation Governs Epigenetic Remodeling and Mesenchymal Transition in Pluripotent and Cancer Cells

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