Distribution of histopathological features along the colon in microscopic colitis.

PURPOSE: The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. METHODS: Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. RESULTS: In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. CONCLUSION: Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.

Efficacy and Safety of Budesonide, vs Mesalazine or Placebo, as Induction Therapy for Lymphocytic Colitis.

BACKGROUND & AIMS: Lymphocytic colitis is a common cause of chronic, nonbloody diarrhea. However, the effects of treatment are unclear and randomized placebo-controlled trials were requested in a Cochrane review. We performed a randomized, placebo-controlled, multicenter study to evaluate budesonide and mesalazine as induction therapy for lymphocytic colitis. METHODS: Patients with active lymphocytic colitis were randomly assigned to groups given budesonide 9 mg once daily (Budenofalk granules), mesalazine 3 g once daily (Salofalk granules), or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as ≤21 stools (including ≤6 watery stools), in the 7 days before week 8. RESULTS: The final analysis included 57 patients (19 per group). Most patients were female (72%) and the mean age was 59 years. The proportion of patients in clinical remission at week 8 was significantly higher in the budesonide group than in the placebo group (intention-to-treat analysis, 79% vs 42%; P = .01). The difference in proportions of patients in clinical remission at week 8 between the mesalazine (63%) and placebo groups was not significant (P = .09). The proportion of patients with histologic remission at week 8 was significantly higher in the budesonide group (68%) vs the mesalazine (26%; P = .02) or placebo (21%; P = .008) groups. The incidence of adverse events was 47.4% in the budesonide group, 68.4% in the mesalazine group, and 42.1% in the placebo group. CONCLUSIONS: In a randomized multicenter study, we found oral budesonide 9 mg once daily to be effective and safe for induction of clinical and histologic remission in patients with lymphocytic colitis, compared with placebo. Oral mesalazine 3 g once daily was not significantly better than placebo. ClinicalTrials.gov no: NCT01209208.

Proteome Analysis of Rheumatoid Arthritis Gut Mucosa.

Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared with controls and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA. Additionally, our data suggest that treatment with Leflunomide, a common alternative to MTX, increases DHFR. The findings were supported by immunohistochemistry with confocal microscopy, which furthermore demonstrated that DHFR was located in the cytosol of the intestinal epithelial and interstitial cells. Finally, we identified 223 citrullinated peptides from 121 proteins. Three of the peptides were unique to RA. The list of citrullinated proteins was enriched in extracellular and membrane proteins and included known targets of anticitrullinated protein antibodies (ACPAs). Our findings support that the colon mucosa could trigger the production of ACPAs, which could contribute to the onset of RA. The MS data have been deposited to ProteomeXchange with identifiers PXD001608 and PXD003082.

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial.

OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The epidemiology of microscopic colitis: a 10-year pathology-based nationwide Danish cohort study.

OBJECTIVE: Microscopic colitis (MC) includes two main types: collagenous colitis (CC) and lymphocytic colitis (LC). Previous studies have indicated an increasing incidence, but these have mainly been based on regional databases. We found it important to study the epidemiology based on a comprehensive nationwide cohort. MATERIAL AND METHODS: We studied the epidemiological data of MC in Denmark from 2002 to 2011. The cohort consisted of all patients with a recorded diagnosis of either CC or LC in the Danish Pathology Register during the study period. Data on all patients with a registered colon biopsy were also included. RESULTS: A total of 7777 patients, 4749 (61%) with CC and 3028 (39%) with LC, were identified. Over the study period, the annual incidence of diagnosed cases of CC increased from 2.9/10(5) to 14.9/10(5) and of LC from 1.7/10(5) to 9.8/10(5). In 2011, the incidence of MC was 24.7/10(5) inhabitants. The age-specific incidence showed that the risk of both CC and LC increased with age. The female/male ratio, distribution of the type of colitis and mean age at diagnosis were relatively stable during the study period. The annual number of registered colon biopsies in the pathology register increased from 21.583 in 2002 to 39.733 in 2011, indicating an increased diagnostic activity. CONCLUSION: In a nationwide cohort study, the incidence of CC and LC continued to increase from 2002 to 2011. An increased diagnostic activity could in part explain the increase in the number of diagnosed cases.

Rifaximin Treatment of Collagenous Colitis: A Randomised, Double-Blind, Placebo-Controlled Trial.

Introduction: Collagenous colitis (CC) is a disabling disease primarily affecting elderly women. Sparse, well-documented treatment modalities exist, except for budesonide. Long-term and repetitive treatment with budesonide is often necessary. Rifaximin is a poorly absorbed antibiotic with a positive modulatory effect on gut microbiota. In this randomised, double-blind, placebo-controlled single-centre trial, we test the effect of adding rifaximin in continuation to budesonide on relapse rates in CC. Methods: Eligible patients with active, biopsy-verified CC received oral budesonide during a 6-week open-label induction phase. Patients in clinical remission after 4 weeks of treatment were randomised to receive either rifaximin or placebo for 4 weeks. Results: Fifteen patients were randomised to receive either rifaximin (n = 7) or placebo (n = 8). At 12-week follow-up, 2 patients in the rifaximin group were still in remission and none in the placebo group (p = 0.2). The median number of days in remission in the rifaximin group was 42 (interquartile range [IQR] 33-126) compared to 18.5 (IQR 10.5-51.5) in the placebo group (p = 0.189). At 12-week follow-up, the relapse rate per 100 person-days in the placebo group was higher (3.25 [1.40-6.41]) than in the rifaximin group (1.33 [0.43-3.10]). Conclusion: Although not statistically significant (p = 0.0996), the study suggests a potential improvement in relapse rates within the rifaximin group compared to the placebo group. A major limitation in the study is the small sample size.

Microscopic Colitis in Denmark: Regional Variations in Risk Factors and Frequency of Endoscopic Procedures.

OBJECTIVE: Microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is an increasingly prevalent gastrointestinal disease with an unknown aetiology. Previous research has reported significant differences in the incidence of MC within Denmark, with the lowest incidence found in the most populated region [Capital Region of Denmark]. Our aim was to elucidate the causes of these regional differences. DESIGN: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] entered in The Danish Pathology Register between 2001 and 2016 were matched to 10 reference individuals [n = 142 481]. Information regarding drug exposure, including proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors [SSRIs], statins, and nonsteroidal anti-inflammatory drugs [NSAIDs], were retrieved from The Danish National Prescription Registry. Information regarding endoscopy rate, smoking-related diseases, and immune-mediated inflammatory diseases were acquired from The Danish National Patient Registry. RESULTS: Smoking, immune-mediated inflammatory diseases, exposure to PPIs, SSRIs, statins, and NSAIDs were significantly associated with MC in all Danish regions. The association between drug exposure and MC was weakest in the Capital Region of Denmark with an odds ratio of 1.8 (95% confidence interval [CI]: 1.61-2.01). The relative risk of undergoing a colonoscopy with biopsy was significantly increased in sex- and age-matched controls in all regions compared with controls from the Capital Region of Denmark, with the greatest risk found in the Region of Southern Denmark, 1.37 [95% CI: 1.26-1.50]. CONCLUSIONS: The cause of the regional differences in MC incidence in Denmark seems to be multifactorial, including variations in disease awareness and distribution of risk factors.

The Process of Developing a Disease Activity Index in Microscopic Colitis.

BACKGROUND AND AIMS: Patient-reported outcome measures [PROMs] aim to measure patients' perception of how their disorder influences everyday functioning. The objective of this study was to develop a PROM to assess disease activity in microscopic colitis [MC] fulfilling the requirements of the Food and Drug Administration [FDA]. METHODS: The European Microscopic Colitis Activity Index [E-MCAI] was developed in four steps. [1] A list of symptoms associated with active MC was created by a group of experts in the field. [2] Content validity of the symptoms was performed by experts [n = 14] and patients [n = 79] using the Content Validity Index. [3] Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients [n = 7] and by the experts. [4] A pilot postal survey was performed to ensure usability. RESULTS: Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC. CONCLUSIONS: The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to achieve construct validity, reliability and responsiveness in future cross-sectional and longitudinal studies.

Disease Activity Patterns, Mortality, and Colorectal Cancer Risk in Microscopic Colitis: A Danish Nationwide Cohort Study, 2001 to 2016.

BACKGROUND AND AIMS: The disease course of microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is not well known. In a Danish nationwide cohort, we evaluated the disease activity patterns as well as the risk of colorectal cancer [CRC] and mortality based on disease severity. METHODS: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] in the Danish Pathology Register, entered between 2001 and 2016, were matched to 10 reference individuals [n = 142 481]. Incident cases of CRC after the index date were captured from the Danish Cancer Registry. Mortality data were ascertained from the Danish Registry of Causes of Death, and information about treatment was obtained from the Danish National Prescription Registry. The risk of CRC and mortality analyses were investigated by Cox regression and Kaplan-Meier estimates. RESULTS: We identified a self-limiting or transient disease course in 70.6% of LC patients and in 59.9% of CC patients, p <0.001. Less than 5% of MC patients experienced a budesonide-refractory disease course and were treated with immunomodulators or biologic treatment. A total of 2926 [20.5%] MC patients and 24 632 [17.3%] reference individuals died during the study period. MC patients with a severe disease had a relative risk [RR] of mortality of 1.41 (95% confidence interval [CI]: 1.32-1.50) compared with reference individuals. Only 90 MC patients were diagnosed with CRC during follow-up, corresponding to an RR of 0.48 [95% CI: 0.39-0.60]. CONCLUSIONS: A majority of MC patients experience an indolent disease course with a lower risk of developing CRC compared with the background population.

European guidelines on microscopic colitis: United European Gastroenterology and European Microscopic Colitis Group statements and recommendations.

INTRODUCTION: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. METHODS: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. RESULTS: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. CONCLUSION: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.

Long-term oral budesonide treatment and risk of osteoporotic fractures in patients with microscopic colitis.

BACKGROUND: Due to a substantial first-pass metabolism of oral budesonide, systemic bioavailability is low compared to other oral corticosteroids, thereby possibly avoiding adverse effects of systemic corticosteroid use. AIM: To determine whether use of oral budesonide is associated with osteoporotic fractures in patients with microscopic colitis (MC). METHODS: Applying data from the Danish nationwide health registries, we conducted a case-control study nested within a cohort of patients with MC from 2004 to 2012. We estimated odds ratios (ORs) for the association between budesonide use and osteoporotic fractures (hip, wrist and spinal fractures). RESULTS: We identified 417 cases with a first occurrence of an osteoporotic fracture. Eighty-six per cent were women and the median age was 78 years. The OR for the overall association between ever-use of budesonide and any osteoporotic fractures did not reach statistical significance (OR 1.13, CI: 0.88-1.47). The highest risk was observed for spinal fractures (OR 1.98, CI: 0.94-4.17), where a dose-response association seemed to exist, followed by hip and wrist fractures (OR 1.17 [CI: 0.79-1.73] and OR 0.99 [CI: 0.66-1.47] respectively). We generally found modestly increased ORs across subgroups at suspected high or low risk of fractures (1.00-2.49). No overall dose-response association was evident (OR for doubling of cumulative dose 0.93 (CI: 0.84-1.03). CONCLUSION: No overall association between use of oral budesonide and osteoporotic fractures was demonstrated among individuals with MC. There seemed to be an isolated adverse effect of budesonide on the risk of spinal fractures, which appears to be dose related.

Incidence and Prevalence of Microscopic Colitis Between 2001 and 2016: A Danish Nationwide Cohort Study.

BACKGROUND AND AIMS: Epidemiological studies suggest an increasing global incidence of microscopic colitis, including collagenous colitis and lymphocytic colitis. We aimed to investigate the incidence and prevalence of microscopic colitis in Denmark. METHODS: In a nationwide cohort study, we included all incident patients with a recorded diagnosis of collagenous colitis or lymphocytic colitis in the Danish Pathology Register between 2001 and 2016. RESULTS: A total of 14 302 patients with microscopic colitis-8437 [59%] with collagenous and 5865 [41%] with lymphocytic colitis-were identified during the study period. The prevalence in December 2016 was estimated to be 197.9 cases per 100 000 inhabitants. Microscopic colitis was more prevalent among females (n = 10 127 [71%]), with a mean annual incidence of 28.8, compared with 12.3 per 100 000 person-years among males. The overall mean incidence during the study period was 20.7 per 100 000 person-years. Mean age at time of diagnosis was 65 years (standard deviation [SD]:14) for microscopic colitis, 67 [SD:13] for collagenous colitis, and 63 [SD:15] for lymphocytic colitis. The overall incidence increased significantly from 2.3 cases in 2001 to 24.3 cases per 100 000 person-years in 2016. However, the highest observed incidence of microscopic colitis was 32.3 cases per 100 000 person-years in 2011. Large regional differences were found, with the highest incidence observed in the least populated region. CONCLUSIONS: The incidence of microscopic colitis in Denmark has increased 10-fold during the past 15 years and has now surpassed that of Crohn's disease and ulcerative colitis. However, incidence has stabilised since 2012, suggesting that a plateau has been reached.

[Intramural duodenal haematoma after endoscopic injection therapy of a bleeding ulcer].

In this case report a 48-year-old man presented with nausea and abdominal pain. Ten days prior he had been treated with an endoscopic epinephrine/saline injection for haemostasis of a bleeding duodenal ulcer and was discharged the following day. At readmission, an abdominal CT revealed severe gastric distention and a gastroscopy showed total duodenal obstruction. Subsequent post-contrast CT revealed that a massive intramural duodenal haematoma was the cause of the total duodenal occlusion. Also, acute pancreatitis was seen. The treatment was conservative, and follow-up gastroscopy showed total resolution of the haematoma.

Significant association between the use of different proton pump inhibitors and microscopic colitis: a nationwide Danish case-control study.

BACKGROUND: Microscopic colitis causes chronic watery diarrhoea and has previously been associated with the use of proton pump inhibitors. AIM: To explore the association between proton pump inhibitor use and microscopic colitis, including its dependency on timing, dose and choice of proton pump inhibitor. METHODS: Within a 10-year period, we identified 10 652 patients with a first-time diagnosis of microscopic colitis, including 6254 (59%) with collagenous colitis and 4398 (41%) with lymphocytic colitis. All microscopic colitis cases were histologically confirmed in the Danish Pathology Register. Information on proton pump inhibitor use was obtained from the Danish Prescription Register. In this case-control study, we estimated the adjusted odds ratios (aOR) for the association between proton pump inhibitor use and risk of microscopic colitis using conditional logistic regression while adjusting for potential confounders. RESULTS: We found strong associations between current proton pump inhibitor use and both collagenous colitis (aOR 6.98; 95% CI: 6.45-7.55) and lymphocytic colitis (aOR 3.95; 95% CI: 3.60-4.33). This association was observed with all PPIs. The strongest association was with the current use of lansoprazole for both collagenous colitis (aOR 15.74; 95% CI: 14.12-17.55) and lymphocytic colitis (aOR 6.87; 95% CI: 6.00-7.86). When considering timing, ORs were highest for current use of proton pump inhibitor and lower for recent or past exposure. No clear dose-response pattern was observed. CONCLUSIONS: We found a strong association between microscopic colitis and ongoing use of proton pump inhibitors, especially lansoprazole.

Risk of osteoporosis in microscopic colitis.

OBJECTIVES: Patients with microscopic colitis (MC) have several risk factors for osteoporosis. The prevalence of osteopenia and osteoporosis in MC is unknown. The primary purpose of this study was to evaluate bone mineral status in MC. METHODS: Patients with MC and disease activity within the last 2 years were included. Bone turnover markers were analyzed and bone mineral density (BMD) was measured with Dual Energy X-ray Absorptiometry (DXA) at inclusion and after one year. Medical history, demographics, risk factors for osteoporosis, disease activity and treatment with cumulative budesonide dosage at least 3 years before inclusion was registered. Adrenal function was tested by adrenocortico-tropic hormone (ACTH) and an ACTH stimulation test at inclusion. Results were compared with age and sex-matched controls. RESULTS: Fifty MC patients (44 women) were included. Median age 67 (range 45-93); median disease duration 28 month (range 2-163); median cumulative budesonide dosage 702 mg (range 0-5400). No difference in number of patients with osteoporosis or osteopenia and BMD was detected between groups. The bone mineral formation marker specific alkaline phosphatase was lower in MC than controls 12 (5-69) µg/l versus 16 (10-35) µg/l (p < 0.005). Patients more often smoked (34% versus 10%, p = 0.001). Disease duration and cumulative budesonide dose was associated with lower BMD and T-score in hip (Spearman's rho; p < 0.05) with a cut of point of 2500 mg budesonide predicting osteopenia. Budesonide treatment did not affect adrenal gland function. CONCLUSION: The risk of osteoporosis in patients with MC is not increased. However, DXA scan is recommended in MC patients with known risk factors or active disease requiring longstanding budesonide treatment. Supplementation of calcium and vitamin-D in patients treated with budesonide is recommended.

The NIMO Scandinavian Study: A Prospective Observational Study of Iron Isomaltoside Treatment in Patients with Iron Deficiency.

BACKGROUND: Intravenous iron allows for efficient and well-tolerated treatment in iron deficiency and is routinely used in diseases of the gastrointestinal tract. OBJECTIVE: The aims of this study were to determine the probability of relapse of iron deficiency over time and to investigate treatment routine, effectiveness, and safety of iron isomaltoside. METHODS: A total of 282 patients treated with iron isomaltoside were observed for two treatments or a minimum of one year. RESULTS: Out of 282 patients, 82 had Crohn's disease and 67 had ulcerative colitis. Another 133 patients had chronic blood loss, malabsorption, or malignancy. Patients who received an iron isomaltoside dose above 1000 mg had a 65% lower probability of needing retreatment compared with those given 1000 mg. A clinically significant treatment response was shown, but in 71/191 (37%) of patients, anaemia was not corrected. The mean dose given was 1100 mg, lower than the calculated total iron need of 1481 mg. Adverse drug reactions were reported in 4% of patients. CONCLUSION: Iron isomaltoside is effective with a good safety profile, and high doses reduce the need for retreatment over time. Several patients were anaemic after treatment, indicating that doses were inadequate for full iron correction. This trial is registered with NCT01900197.

Proteomics dataset: The colon mucosa from inflammatory bowel disease patients, gastrointestinal asymptomic rheumatoid arthritis patients, and controls.

The datasets presented in this article are related to the research articles entitled "Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies" (Bennike et al., 2015 [1]), and "Proteome Analysis of Rheumatoid Arthritis Gut Mucosa" (Bennike et al., 2017 [2]). The colon mucosa represents the main interacting surface of the gut microbiota and the immune system. Studies have found an altered composition of the gut microbiota in rheumatoid arthritis patients (Zhang et al., 2015; Vaahtovuo et al., 2008; Hazenberg et al., 1992) [5], [6], [7] and inflammatory bowel disease patients (Morgan et al., 2012; Abraham and Medzhitov, 2011; Bennike, 2014) [8], [9], [10]. Therefore, we characterized the proteome of colon mucosa biopsies from 10 inflammatory bowel disease ulcerative colitis (UC) patients, 11 gastrointestinal healthy rheumatoid arthritis (RA) patients, and 10 controls. We conducted the sample preparation and liquid chromatography mass spectrometry (LC-MS/MS) analysis of all samples in one batch, enabling label-free comparison between all biopsies. The datasets are made publicly available to enable critical or extended analyses. The proteomics data and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001608 for ulcerative colitis and control samples, and PXD003082 for rheumatoid arthritis samples.

Ischaemic gastric ulceration with endoscopic healing after revascularization.

A 66-year-old man with a history of abdominal pain, diarrhoea and weight loss was admitted for evaluation. Gastroscopy disclosed a severe gastric ulceration covering the lesser curvature. There was none of the usual risk factors for peptic ulcer disease and no malignancy was found. After 2 weeks' treatment with a proton pump inhibitor no healing was observed. The patient had a known atherosclerotic vascular disease, and angiography disclosed severe mesenteric ischaemia. After a revascularization procedure with stenting of the superior mesenteric artery was performed, the patient's symptoms disappeared. Healing of the gastric ulceration was observed at a further gastroscopy 2 weeks later. Chronic ischaemia is a rare cause of gastric ulcer, but should be suspected when no other cause is found and when the usual treatment with proton pump inhibitors does not result in healing.

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

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