Microscopic colitis: Etiopathology, diagnosis, and rational management

Abstract

Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.

Keywords: Microscopic colitis; collagenous colitis; etiopathology; lymphocytic colitis; medicine; prognosis; therapy.

Figure 1.. Geographic distribution of microscopic colitis in different parts of the world.

Most recent incidence rates (× 10⁵ inhabitants per year) of both collagenous colitis (CC) and lymphocytic colitis (LC) from Europe and North America where population-based studies have been performed. Moreover, green asterisks indicate countries where microscopic colitis has been described outside Europe and North America but without incidence data. Data retrieved from Miehlke et al., 2021; Davidson et al., 2018.

Figure 2.. Main factors involved in the pathophysiology of microscopic colitis.

Figure 3.. Histological findings of microscopic colitis.

(A) Typical colonic biopsy from a patient with collagenous colitis with a subepithelial collagenous band of more than 10 μM. The surface epithelium is flattened, and mucin depleted, and a mixed inflammatory infiltrate is present in the lamia propria. H&E ×20. (B) Typical colonic biopsy from a patient with lymphocytic colitis with 20 or more intraepithelial lymphocytes per 100 surface epithelial cells. A mixed inflammatory infiltrate is present in the lamia propria. H&E ×20. (C) Lymphocytic colitis, immunohistochemistry stain for CD3 high-lighting lymphocytic infiltration of the epithelium.

Figure 4.. Proposed treatment algorithm for the clinical management of symptomatic microscopic colitis.

Immune checkpoint inhibitors (ICIs). *Loperamide or bismuth subsalicylate in mild cases, cholestyramine mainly if there is associated bile acid malabsorption. **Use the lowest effective dose as maintenance treatment (3–6 mg/day or 3 mg every other day). ***Long-term use of bismuth subsalicylate is not recommended due to potential neurotoxicity. Note: celiac disease should each time be excluded at least with anti-tissue transglutaminase antibody levels, and bile acid diarrhea always kept in mind.