Inflammatory bowel disease Study Guide

📖 Core Concepts Inflammatory Bowel Disease (IBD) – chronic inflammation of the gastrointestinal (GI) tract; two main types: Crohn disease (CD) and ulcerative colitis (UC). Transmural vs. Mucosal – CD can affect any bowel wall layer (transmural); UC inflammation is limited to the mucosa. Genetic Susceptibility – >200 SNPs linked to IBD; NOD2 was the first identified risk gene. Microbiota Dysbiosis – Loss of beneficial microbes (e.g., Faecalibacterium prausnitzii) and over‑growth of harmful species (e.g., Bacteroides fragilis). Barrier Breach & TLR Signaling – Impaired epithelial integrity allows bacterial translocation, triggering chronic immune activation via toll‑like receptors. Extra‑intestinal Manifestations (EIMs) – anemia, arthritis, primary sclerosing cholangitis, skin lesions, and mood disorders are common. Biomarker – Fecal calprotectin: a sensitive, non‑specific marker of intestinal inflammation. Therapeutic Goals – Induce remission, maintain remission, prevent complications, and improve quality of life. --- 📌 Must Remember Location: CD → any GI segment (mouth → anus); UC → colon & rectum only. Histology: Granulomas → suggest CD (not always present). Surgery: UC can be cured by total proctocolectomy + ileal pouch‑anal anastomosis; CD is not curable surgically, recurrence common at anastomosis. First‑line Pediatric CD – Exclusive enteral nutrition (EEN). Medication Hierarchy 5‑ASA (mesalazine) → best for UC. Systemic steroids (prednisone) → acute flares. Immunomodulators (azathioprine, methotrexate, 6‑MP) → steroid‑sparing. Biologics (anti‑TNF, anti‑IL‑12/23, anti‑integrin) → moderate‑to‑severe/refractory disease. Dietary Influence – Mediterranean diet ↓ risk & activity; high processed meat/sugar ↑ flare risk. Micronutrient Replacement – Parenteral iron preferred for anemia; vitamin D supplementation may lower relapse risk. Fecal Calprotectin – >200 µg/g suggests active inflammation; normal does not rule out disease. EIM Frequency – Anemia > arthritis > PSC > skin lesions. --- 🔄 Key Processes Pathogenesis Cascade Genetic susceptibility (e.g., NOD2 variants). Environmental trigger (diet, smoking, antibiotics). Dysbiosis → loss of protective microbes, over‑growth of pathobionts. Barrier disruption → bacterial translocation. TLR activation → cytokine storm (TNF‑α, IL‑23, etc.). Chronic transmural (CD) or mucosal (UC) inflammation. Diagnostic Algorithm Step 1: Clinical suspicion → rule out infections, IBS. Step 2: Non‑invasive tests – CBC, CRP, fecal calprotectin. Step 3: Endoscopy with targeted biopsies (definitive). Step 4: Imaging (MRE/CTE) for extent & complications. Treatment Decision Tree Mild disease → 5‑ASA (UC) or budesonide (ileal CD). Moderate disease → add immunomodulator; consider early biologic if risk factors. Severe/refractory → systemic steroids → biologic (anti‑TNF) → JAK inhibitor / anti‑IL‑23. Complications (stricture, fistula, dysplasia) → surgical referral. --- 🔍 Key Comparisons Crohn disease vs. Ulcerative colitis Location: CD – any GI site; UC – colon/rectum only. Inflammation depth: CD – transmural; UC – mucosal. Granulomas: CD – often present; UC – absent. Fistulas/strictures: Common in CD; rare in UC. Surgical cure: UC – possible; CD – not curable. Oral iron vs. Parenteral iron Oral: Poor absorption when hepcidin ↑ (active inflammation). Parenteral: Bypasses gut, preferred for IBD‑related anemia. 5‑ASA vs. Budesonide 5‑ASA: Topical/colon‑targeted; best for UC. Budesonide: Controlled‑release; effective for mild ileal CD, minimal systemic effect. --- ⚠️ Common Misunderstandings “Normal fecal calprotectin rules out IBD.” – Low levels can occur in mild disease or after treatment; always interpret with clinical context. “All IBD patients need the same diet.” – Diet should be individualized; Mediterranean diet is beneficial, but low‑FODMAP targets symptoms, not inflammation. “Surgery cures Crohn disease.” – Surgery removes diseased segments but does not prevent recurrence; recurrence common at anastomosis. “Biologics are only for severe disease.” – Early use in moderate disease with poor prognostic factors can improve long‑term outcomes. --- 🧠 Mental Models / Intuition “Layer‑Depth Model” – Visualize the bowel wall: mucosa → submucosa → muscularis → serosa. CD punches through all layers (think “full‑thickness wall”); UC stays on the surface (think “paint‑only”). “Genetics + Environment = Fire” – Genes set the stage, environmental triggers (diet, smoking) light the spark, dysbiosis fuels the blaze, and barrier breach spreads the fire. “Treatment Ladder” – Ascend from topical (5‑ASA) → oral steroids → immunomodulators → biologics → surgery; step down only after remission is achieved. --- 🚩 Exceptions & Edge Cases Indeterminate colitis – When features overlap; manage as UC or CD based on predominant pattern. Pregnancy – Aim to keep disease in remission; avoid teratogenic meds (e.g., methotrexate). Pediatric Crohn – Exclusive enteral nutrition is first‑line; biologics used if poor response. Elderly IBD – Higher comorbidity; prefer agents with lower infection risk (e.g., budesonide over systemic steroids). Low‑FODMAP diet – Improves symptoms but does not reduce inflammatory biomarkers. --- 📍 When to Use Which Biologic selection Anti‑TNF (infliximab, adalimumab) – First biologic for moderate‑to‑severe CD/UC, especially with fistulizing CD. Anti‑IL‑23 (guselkumab, risankizumab) – Consider for patients failing anti‑TNF or with predominant UC. Anti‑integrin (vedolizumab) – Preferred when gut‑selective action needed (e.g., extra‑intestinal infection risk). Dietary therapy Mediterranean diet – Routine maintenance for mild‑moderate disease. Low‑FODMAP – Symptom‑focused adjunct when bloating/diarrhea predominate. Exclusive enteral nutrition – Pediatric CD induction or when steroids contraindicated. Surgical indication Refractory disease (no response to optimal medical therapy). Complications – Stricture, fistula, perforation, dysplasia/cancer. --- 👀 Patterns to Recognize Fecal calprotectin spikes → active inflammation; correlate with new symptoms. Transmural thickening on MRE → think CD (possible fistula/abscess). Continuous colonic involvement starting at rectum → classic UC pattern. Perianal disease (fistula, skin tags) → strong clue for CD. Elevated liver enzymes + IBD → consider primary sclerosing cholangitis. --- 🗂️ Exam Traps “Fecal calprotectin is disease‑specific.” – It is sensitive but not specific; infections, celiac, and other conditions raise it. “All patients with IBD should avoid all fiber.” – Fiber restriction is not universal; the Mediterranean diet (high fiber) is protective. “5‑ASA works equally well in CD and UC.” – It is far less effective in CD, especially for small‑bowel disease. “Biologics are contraindicated in pregnancy.” – Anti‑TNF agents are generally considered safe; methotrexate is not. “A normal colonoscopy rules out Crohn disease.” – CD may involve only the small intestine; negative colonoscopy does not exclude CD. ---