Etiology
The cause of microscopic colitis is not clear, although it is thought to be the result of a dysregulated immune response to changes in the gut luminal microbiota in genetically susceptible people.[9][21]
Autoimmune diseases including celiac disease, hypothyroidism, rheumatoid arthritis, and hyperthyroidism are commonly associated with microscopic colitis.[9][21] In particular, there is a strong association with celiac disease. Patients with celiac disease have a 50- to 70-fold increased risk of developing microscopic colitis; and 2% to 9% of patients with microscopic colitis are found to have celiac disease.[22][23]
Chronic or frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs), proton-pump inhibitors (PPIs), selective serotonin-reuptake inhibitors (SSRIs), statins, and H2 antagonists has been associated with an increased risk of microscopic colitis.[24][25][26][27][28][29][30] NSAIDs, which are more strongly associated with microscopic colitis, are thought to increase this risk by inhibiting anti-inflammatory prostaglandins and changing epithelial barrier permeability.[31][32] Despite studies suggesting an association, however, this does not imply causation. In addition, there is a lack of convincing pathophysiologic explanations, and results from one multicenter study were conflicting for PPIs and H2 antagonists.[33] It is possible that these drugs do not cause microscopic colitis, but rather worsen diarrhea and bring the diagnosis to attention.[6]
Pathophysiology
The pathogenesis of microscopic colitis remains largely unknown, although several mechanisms have been proposed.[1] One theory is that microscopic colitis may be the result of a reaction to an unidentified toxin or a luminal agent including dietary antigens, bile salts, medications, or bacterial toxins.[34][35][36] In patients with celiac disease, gluten intake may lead to histologic changes resembling lymphocytic colitis.[37][38] Similar histologic changes can be seen in patients with bile acid malabsorption, and bile acid sequestrants may play a role in this subset of patients with microscopic colitis.[39][40] This mechanism would also explain the association of microscopic colitis with several medications and dietary factors. Lastly, infectious agents may lead to changes in gut microbiome, and those infectious agents have been reported to respond to antibiotic therapy.[41] However, no specific organism has been definitively associated with microscopic colitis.
Other postulated mechanisms for the collagenous subtype include abnormal collagen deposition due to exaggerated response to chronic inflammation and primary collagen synthesis abnormality. Both increased collagen deposition and impaired fibrinolysis occur in people with collagenous colitis. Studies have shown upregulation of mediators of fibrosis including vascular endothelial growth factor, transforming growth factor B, and fibroblast growth factor.[42]
Given the small number of pathophysiologic studies with conflicting results, no definite conclusion can be made.[1]
Classification
Subtypes of microscopic colitis
The hallmark of microscopic colitis is intraepithelial lymphocytosis. Based on histological features, microscopic colitis is divided into:
Collagenous colitis
Lymphocytic colitis.
This classification is based on the presence or absence of a thickened subepithelial collagen band, respectively. In the lymphocytic subtype, there is an increased number of intraepithelial cells. Both entities are considered as being on the same disease spectrum and are approached similarly in terms of clinical diagnosis and management.[6][9]
There is a subset of patients who do not meet the above histologic criteria. These patients may be diagnosed as microscopic colitis incomplete or microscopic colitis not otherwise specified. Microscopic colitis incomplete comprises incomplete collagenous colitis (defined by a thickened subepithelial collagenous band >5 micrometers but <10 micrometers) and incomplete lymphocytic colitis (defined by >10 but <20 intraepithelial lymphocytes and a normal collagenous band). Both types show a mild inflammatory infiltrate in the lamina propria.
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