microscopic colitis

**Definition:** Chronic inflammatory disease of the colon causing chronic watery diarrhea, with grossly normal (or near-normal) mucosa on colonoscopy and characteristic histologic findings on random colonic biopsies.

**Subtypes (histology = the key board distinction):** - **Collagenous colitis:** Thickened subepithelial collagen band (>10 μm) + increased lamina propria chronic inflammatory cells, with surface epithelial damage. More common in women. - **Lymphocytic colitis:** Increased intraepithelial lymphocytes (>20 per 100 surface epithelial cells), with a normal collagen band. Roughly equal sex distribution. - Both: lamina propria lymphoplasmacytic infiltrate; NO crypt distortion/architectural disarray (unlike IBD), and no granulomas.

**Epidemiology/Risk factors:** - Peak age ~50-70; female predominance (especially collagenous). - Associated with autoimmune disease: celiac disease (especially lymphocytic), autoimmune thyroid disease, type 1 DM, rheumatoid arthritis. - Smoking is a risk factor. - Drugs: NSAIDs, PPIs (esp. lansoprazole), SSRIs (sertraline), ticlopidine, statins, and others.

**Pathophysiology (incompletely understood):** Abnormal mucosal immune response to luminal antigens in genetically susceptible individuals. Diarrhea is mainly secretory (impaired epithelial sodium/chloride absorption, increased permeability) and may have a component of impaired water absorption due to the collagen band.

**Clinical presentation:** - Chronic, watery, non-bloody diarrhea (can be nocturnal), sometimes with urgency, incontinence, abdominal pain, weight loss, fatigue. - NO hematochezia; low risk of complications. - Diarrhea often persists with fasting is NOT typical; stool osmotic gap is low (secretory pattern). Fecal calprotectin may be mildly elevated. - Labs typically normal (no significant anemia or elevated inflammatory markers).

**Diagnosis:** Colonoscopy (or flexible sigmoidoscopy) with **multiple random biopsies** (from right and left colon) even when mucosa looks normal. Exclude infection, celiac disease, medication effect, and bile acid diarrhea.

**Treatment:** 1. Stop offending agents (NSAIDs, PPIs, SSRIs, etc.) and smoking cessation. 2. Antidiarrheals (loperamide) for mild disease. 3. **Budesonide** (locally acting, high first-pass metabolism steroid) – first-line for active disease; high response rate but relapse is common after stopping, so low-dose maintenance may be needed. 4. Refractory: bile acid sequestrants (cholestyramine), mesalamine/bismuth subsalicylate (less evidence), immunomodulators (azathioprine) or anti-TNF/vedolizumab in refractory cases.

**Prognosis:** Benign; NOT associated with increased colorectal cancer risk and does not progress to ulcerative colitis/Crohn disease. Often self-limited or relapsing-remitting.

**High-yield buzzwords/differentials:** - Middle-aged woman + chronic watery diarrhea + normal colonoscopy + biopsy showing thick collagen band = collagenous colitis. - Intraepithelial lymphocytosis + normal collagen = lymphocytic colitis (think celiac association). - Ulcerative colitis: bloody diarrhea, continuous rectal involvement, crypt abscesses. Crohn: skip lesions, transmural, granulomas. - Other normal-colonoscopy diarrhea: celiac disease, IBS, bile acid diarrhea, hyperthyroidism, VIPoma, carcinoid.