Clinical meaning
Microscopic colitis is a chronic inflammatory condition of the colon characterized by chronic watery, non-bloody diarrhea with a grossly normal-appearing colonic mucosa on colonoscopy — diagnosis requires histological examination of colonic biopsies, hence the name 'microscopic.' It is classified into two histological subtypes: collagenous colitis, defined by a thickened subepithelial collagen band (greater than 10 micrometers versus normal less than 5 micrometers) with increased intraepithelial lymphocytes and surface epithelial damage; and lymphocytic colitis, characterized by increased intraepithelial lymphocytes (greater than 20 per 100 epithelial cells) without significant collagen band thickening. The pathophysiology involves loss of colonic epithelial barrier integrity and dysregulated mucosal immune response to luminal antigens. In collagenous colitis, the abnormal collagen deposition (primarily type VI collagen) beneath the surface epithelium is produced by activated myofibroblasts and impairs water and electrolyte absorption, contributing to secretory diarrhea. In lymphocytic colitis, CD8+ intraepithelial T lymphocytes infiltrate the epithelium and release pro-inflammatory cytokines (interferon-gamma, TNF-alpha) that increase epithelial permeability and stimulate chloride secretion, producing a net secretory state. Both subtypes share an association with autoimmune conditions (celiac disease, thyroid disease, rheumatoid arthritis), and strong medication associations — particularly NSAIDs, SSRIs, PPIs, and immune checkpoint inhibitors — which may act as antigenic triggers or direct epithelial toxins. Budesonide is the first-line pharmacotherapy based on strong evidence: it is a potent topical corticosteroid with high glucocorticoid receptor affinity that suppresses mucosal inflammation locally in the colon while undergoing extensive (approximately 90%) first-pass hepatic metabolism via CYP3A4, producing low systemic bioavailability (approximately 10%) and significantly fewer systemic steroid side effects than prednisone. However, relapse rates are high (60-80%) upon budesonide discontinuation, often requiring low-dose maintenance therapy (3-6 mg daily) or immunomodulators (cholestyramine, bismuth subsalicylate, thiopurines) for refractory cases. The clinician evaluates medication history for offending agents, ensures random colonic biopsies are obtained even with normal endoscopic appearance (biopsies from both the right and left colon increase diagnostic yield), screens for associated autoimmune conditions and celiac disease, and manages budesonide therapy with attention to adrenal suppression risk during long-term use and drug interactions with CYP3A4 inhibitors.