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

Abstract

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=8,437) or LC (n=5,865) 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 to 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.

Are Drugs Associated with Microscopic Colitis? A Systematic Review and Meta-Analysis

“…Of these 45 articles, 13 studies fulfilled the selection criteria and were included in the final analysis. Eight studies [ 11 , 13 , 15 , 16 , 17 , 18 , 19 , 20 ] used random control adjusted for age, sex, GP practice, or birth year.…”

“…Nine studies [ 8 , 9 , 12 , 13 , 17 , 18 , 19 , 21 , 22 ] reported the odds of microscopic colitis in patients using proton pump inhibitors. Studies by Masclee et al [ 21 ] and Pascua et al [ 22 ] reported two different Odds ratios based on the control groups (Community random and diarrhea controls).…”

“…Higher pooled odds of MC were observed in patients taking SSRI (OR 2.12(95% CI 1.27–2.96, I 2 96.46%). We included nine different odds ratios from 8 studies [ 8 , 9 , 12 , 17 , 18 , 19 , 21 , 22 ] to calculate the pooled odds ratio because Pascua et al [ 22 ] provided two ratios based on two different control groups. Greater odds of MC were seen in patients taking SSRIs when compared to random health controls (OR 3.23, 95% CI 1.54–4.92, I 2 98.31%), whereas on the contrary, no difference in odds of MC was noted in comparison to the diarrhea control group (OR 0.96, 95% CI 0.49–1.42, I 2 37.89%) ( Figure 3 ).…”

“…Eight studies [ 8 , 9 , 12 , 13 , 17 , 18 , 19 , 21 ] provided the adjusted odds of MC in patients who were currently taking NSAIDs or were on them in the past. Patients taking NSAIDs had greater odds of developing MC (OR 2.02, 95% CI 1.33–2.70, I 2 92.70%).…”

Insights into the underlying mechanisms and clinical management of microscopic colitis in relation to other gastrointestinal disorders

“…Also, environmental factors such as smoking [ 15 ] and alcohol consumption [ 16 ], certain medications such as non-steroidal anti-inflammatory drugs (NSAIDs) [ 17 ], statins [ 18 ], selective serotonin reuptake inhibitors (SSRIs) [ 19 ], and proton-pump inhibitors (PPIs) [ 17 , 20 ] have been shown to be associated with an increased risk of MC. These risk factors may therefore act as a contributing component in the pathogenesis of MC ( Table 1 ).…”