4 New Studies Shed Light on Microscopic Colitis

David A. Johnson, MD


July 18, 2023

Microscopic colitis (MC) is an inflammatory disease of the colon encompassing the two subtypes of lymphocytic colitis and collagenous colitis. MC often causes chronic, watery diarrhea as well as abdominal pain, arthralgias, and weight loss. The epidemiology of MC ranges substantially in the literature, with reports listing its incidence rate anywhere from 1 to 11 per 10,000 person-years. It is known to occur in those who are of older age, who are female, who have underlying autoimmune diseases, and who use certain medications or have lifestyle factors such as smoking.

In surveying the recent literature, my attention was drawn to four new studies of MC. Drawing from diverse datasets, ranging from single-center to large, nationwide analyses, these studies illuminate MC's possible causal role in developing acute pancreatitis and cardiovascular disease as well as its dietary causes and potential treatments.

Here are the top-level summaries of these studies to better guide your treatment of patients with MC.

New Data Linking MC With Acute Pancreatitis

The first study of interest is a matched cohort analysis from Sweden evaluating data from several healthcare registries, including 12,410 patients with biopsy-confirmed MC, 12,781 siblings unaffected by MC, and 57,806 matched reference individuals drawn from the general population. Investigators sought to assess the onset of acute pancreatitis at a minimum of 2 years after the diagnosis of MC.

All participants with a prior dispensation of proton pump inhibitors, nonsteroidal anti-inflammatory drugs, or selective serotonin uptake inhibitors were excluded.

Of note, patients with MC had a 1.6-times increased risk for diagnosis of acute pancreatitis at an incidence rate of 127.8 per 100,000 person-years (95% CI, 109.0-149.9), compared with 85.3 (95% CI, 71.0-102.5) and 80.1 (95% CI, 73.1-85.6) for siblings without MC or the reference population, respectively.

The adjusted hazard ratio (aHR) for men (1.50; 95% CI, 1.07-2.1) and women (1.62; 95% CI, 1.29-2.03) did not increase over the mean follow-up time of 9.9 years.

In terms of duration of disease, the aHR was higher during the time window of 1-3 years, reaching a peak during the first year (1.82; 95% CI, 0.96-3.43), although the elevated aHR also persisted in those who had 10 or more years of follow-up.

There was also an increased aHR associated with the use of budesonide (1.84; 95% CI, 1.37-2.48). Investigators observed an increased aHR for acute pancreatitis unrelated to cholelithiasis but not for cholelithiasis-related acute pancreatitis. Of note, the register analysis was limited by not including data on lifestyle factors, such as alcohol use, smoking, and body mass index.

In summary, clinicians should have a low threshold when evaluating for acute pancreatitis in patients with MC. A potential causality association with budesonide should raise concerns when considering treatment options. Additional acute pancreatitis risk reduction strategies should also be discussed proactively with these patients.

Bile Acid Sequestrants: Investigating a New Treatment Option

A retrospective study from investigators at the Mayo Clinic in Rochester, Minnesota, evaluated the effectiveness of bile salt acid sequestrants (BASs) in MC and the utility of bile acid testing to predict response.

Over a decade-long span (2010-2020), 282 patients treated with BAS for MC were identified. BASs used were cholestyramine (64.9%), 21.6% colesevelam (21.6%), and colestipol (13.5%). Clinical response was defined at 12 ± 4 weeks after BAS initiation by whether diarrhea had complete resolution, partial improvement (≥ 50%), nonresponse (< 50% improvement), or intolerance (side effects causing discontinuation).

After a median follow-up of 4.5 years (range, 0.4-9.1 years), the investigators noted complete response rates of 49.3%, partial response rates of 16.3%, nonresponse rates of 24.8%, and intolerance rates of 9.6%.

Of note, there were no differences when BASs were combined with other medications nor was there an incremental dose response for BASs.

Prior to BAS therapy, 98.6% were treated with another medication or combination for MC, including loperamide (78.4%), budesonide (69.9%), bismuth subsalicylate (41.1%), and mesalamine (11.0%). Of those who previously received budesonide, 64.0% had a complete response, 18.3% a partial response, 11.7% a nonresponse, and 6.1% intolerance. For patients with complete or partial response to budesonide, subsequent initiation of BASs (30.9%) was chosen to avoid corticosteroids.

Fecal bile acid testing was performed in 31.9% of patients (56.7% were positive). However, this did not correlate to response to BAS treatment. Recurrence of diarrhea was 41.6% at a median of 21 weeks (range, 1-172 weeks).

These results highlight that BASs should be considered as a first-line treatment for all patients, including those who are budesonide dependent or nonresponsive, and before escalating to immunosuppressive or biologic therapies.

Patient counseling on the possible adsorbent properties of BAS should address appropriate medication scheduled timing adjustments if needed.

The Possible Impact of Dietary Calcium on MC

A single-center, case-controlled study drew from a cohort of patients referred for an elective outpatient colonoscopy evaluation of diarrhea.

Among the 106 cases of MC and 215 controls, there were significant differences in age (mean, 63 years vs 55 years), race (96% White vs 87% White), cigarette smoking (11% vs 21%), female (86% vs 72%), and body mass index (25.6 vs 29.5), respectively.

A significant risk reduction for MC occurred in patients with the highest vs the lowest reported quartile of dietary calcium intake (adjusted odds ratio, 0.22; 95% CI, 0.07-0.76). Microbiome analysis, conducted via 16S rRNA sequencing, demonstrated that increased dietary calcium intake had significant associations with the abundance of phylum Actinobacteria (maintains gut barrier homeostasis and biotransformation of dietary substances) and Coriobacteriales.

Prior animal studies have shown that diets rich in calcium phosphate favored Firmicutes and increased short-chain fatty acids, which have a protective effect against inflammation, whereas low dietary calcium phosphate promotes mucin-degenerating species, such as Akkermansia and Bacteroides.

There was no association between medications in the MC cohort vs the control cohort.

This study raises the intriguing concept that dietary calcium intake affected MC disease prevalence, possibly related to influences of the intestinal biome. It remains unclear, however, if supplemental calcium ingestion or alteration of dietary calcium amount may be helpful in treatment.

Uncovering an Elevated Risk for Major Cardiovascular Events

Previous studies have demonstrated an increased risk for cardiovascular disease (CVD) in patients with inflammatory bowel disease (both ulcerative colitis and Crohn's disease). Systemic inflammation is predictive of CVD and probably accelerates atherosclerosis.

A nationwide population-based, matched cohort study employed the Swedish Data Registry to evaluate the relative risk for major adverse cardiovascular events (MACEs) in patients with MC.

Over a median 6.6 years of follow-up, incident cases of MACEs were higher in the 2181 patients with MC (19.8%) compared with 6661 control individuals (13.8%), resulting in an aHR of 1.27 (95% CI, 1.21-1.33).

Patients with MC also had increased aHRs associated with ischemic heart disease (1.38; 95% CI, 1.28-1.48), congestive heart failure (1.32; 95% CI, 1.22-1.43), and stroke (1.12; 95% CI, 1.02-1.23) but not cardiovascular mortality (1.07; 95% CI, 0.98-1.18).

Overall, the increased risk for an incident MACE in patients with MC was 27% higher than in control individuals, which was equal to one extra case of MACE for every 13 patients with MC followed for 10 years.

These data highlight the need for an awareness of CVD risk factors among both clinicians and patients. Appropriate attention to other CVD risks should also be addressed in an attempt to lessen other contributory risks.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

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