Lina Vigren

Is smoking a risk factor for collagenous colitis

Abstract Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohns disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking in microscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. Materials and methods. 116 patients (92 women) with median age of 62 years (interquartile range 55–73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. Results. Of the 116 CC patients, 37% were smokers compared with 17% of controls (p < 0.001, odds ratio (OR) 2.95). In the age group 16–44 years, 75% of CC patients were smokers compared with 15% of controls (p < 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers – at 42 years of age (median) compared with 56 years in non-smokers (p < 0.003). Although the proportion with active disease did not differ between smokers and non-smokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). Conclusions. Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers.

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 5.4/10(5) inhabitants. During the time periods 2001-2005 and 2006-2010, the mean annual incidence rates were 5.4/10(5) 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 6.7/10(5)) 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 (4.6/10(5)) and from Terrassa, Spain during 2004-2008 (2.6/10(5)). Our incidence figures from southern Sweden during 2001-2010 (5.4/10(5)) as well as the incidence figures presented in the studies during the 1990s (Terrassa, Spain during 1993-1997 (2.3/10(5)), Olmsted, United States during 1985-2001 (3.1/10(5)), Örebro, Sweden during 1993-1998 (4.9/10(5)), and Iceland during 1995-1999 (5.2/10(5)) 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.

Long-term effectiveness of vedolizumab in inflammatory bowel disease : a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)

Abstract Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness. Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn’s disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC). Results: Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14–20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96–16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10–4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16–6.48). Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

Celiac disease and other autoimmune diseases in patients with collagenous colitis

Abstract Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patients files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55–73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögrens syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Are collagenous and lymphocytic colitis different aspects of the same disease

Abstract Objective. Collagenous colitis (CC) and lymphocytic colitis (LC) are two subtypes of microscopic colitis (MC). Even though they most often are described as different entities they share many clinical and histological features. The aim of this study was to investigate the occurrence of conversion between CC and LC in a larger cohort of patients. Materials and methods. All 664 patients in our Pathology register with a diagnosis of CC and LC were scrutinized and those where additional endoscopies had been carried out were included, and their biopsies were re-examined. Results. Sixty-five patients (55 women, 10 men, median age 58 years; range 29–86) fulfilled our criteria for inclusion. The primary diagnosis was CC in 47 patients (39 women, 8 men, median age 58 years; range 29–86) and LC in 18 patients (16 women, 2 men, median age 58 years; range 33–74). Conversion occurred in nine of the 65 patients (14%, all women, median age 59 years; range 41–72), three from CC to LC and six from LC to CC. Conclusion. This study has found that patients can show histological features consistent with both CC and LC over time. These patients could represent a subgroup with a true conversion between two separate entities. Alternatively, MC could be a spectral disease where the varying histological features are manifestations of the natural fluctuation. A third possibility could be that the histological changes reflect different manifestations during the disease course and consequently, the diagnostic criteria could be too vague.

Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea

Abstract Objective: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn’s disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. Methods: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. Results: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups. Conclusion: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.

Vitamin D levels in microscopic colitis.

In accordance with many other diseases a northsouth gradient has been proposed in microscopic colitis (MC) [1,2] which could have several explanations [3]. Due to insufficient daylight during winter time, vitamin D deficiency has been suggested to trigger many, especially immune-mediated, disorders. The aim of this study was to investigate whether patients with MC could have vitamin D deficiency to a larger extent than the background population.

Microscopic colitis in patients with ulcerative colitis or Crohn’s disease: a retrospective observational study and review of the literature

Abstract Objectives: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn’s disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature. Methods: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed. Results: We identified 31 patients with onset of MC after a median (range) of 20 (2–52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients. Conclusions: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.

Microscopic colitis in Denmark and Sweden: incidence, putative risk factors, histological assessment and endoscopic activity

Abstract Objective: The significantly higher incidence rates of microscopic colitis (MC) in Denmark compared to Sweden remains unexplained. Methods: Consecutive patients with newly diagnosed MC in the neighbouring regions of Skåne in 2011–2015 and Zealand in 2010–2016 were prospectively identified. Data on large bowel endoscopies and biopsies rates were retrieved. Information on putative factors were obtained from registers and literature. Interobserver agreement between pathologists from both regions on 40 blinded hematoxylin and eosin (H&E)-stained colon biopsies (collagenous colitis (CC), lymphocytic colitis (LC), non-specific inflammation and normal) was evaluated using kappa statistics. Results: The mean annual incidence per 105 inhabitants in Skåne and Zealand 2010–2015 was 5.9 (95% CI 4.6–7.3) versus 16.4 (95% confidence intervals (95% CI) 13.6–19.2) for CC and 2.7 (95% CI 1.0–4.3) versus 11.1 (95% CI 8.8–13.4) for LC, respectively. Number of endoscopies with biopsy per 1000 and the rate of MC per endoscopy with biopsy was higher in Zealand (34–52/1000) than in Skåne (12–21/1000). The kappa value for overall agreement between pathologists was good (0.72; 95% CI 0.64–0.79). Prescription of proton pump inhibitors and selective serotonin reuptake inhibitors was higher in Skåne in the relevant age groups and prescription of non-steroidal anti-inflammatory drugs and smoking rate higher in Zealand. Alcohol consumption was higher in Denmark than in Sweden. Conclusion: The incidence of MC and number of cases per colonic biopsy was higher in Zealand and could not be readily explained by endoscopy or biopsy rates, differences in histological assessment or putative risk factors.

Sclerosing mesenteritis and mesenteric panniculitis - clinical experience and radiological features

BackgroundSclerosing mesenteritis (SM) is sometimes used as an umbrella-term for idiopathic inflammatory conditions in the mesentery. Mesenteric panniculitis (MP) is a radiological finding and its relation to clinical SM is not fully understood. The aims of this study were to determine whether any correlation could be found between the radiological findings and the clinical disease course.MethodsPatients observed due to idiopathic inflammation of the mesentery were identified. If SM could be verified histologically or MP radiologically, the patients were included in this descriptive retro perspective study.ResultsTypical radiological changes were observed in 27 patients. A majority (23/27) of these patients had mild to moderate symptoms. This group with typical radiology was labelled MP. Four patients were included due to histologically verified disease but had uncharacteristic radiology involving multiple compartments of the abdomen. All four had marked systemic inflammation, fever and fluctuating radiologic findings. Three had severe disease with multiple hospitalisations and complications but responded promptly to corticosteroids. This group was denoted SM.ConclusionsWe have identified two subgroups of patients; firstly, MP with stable and characteristic radiologic changes and secondly SM with atypical radiology and a more aggressive clinical course. We propose that the term SM should be reserved for this latter condition.