# Lecture 8: Inflammatory Bowel Disease ## Unit 2.2: Gastrointestinal System --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Compare and contrast Crohn's disease and ulcerative colitis 2. Describe the pathophysiology of inflammatory bowel disease 3. Explain the clinical features and diagnosis of IBD 4. Describe the extraintestinal manifestations of IBD 5. Explain the medical and surgical management of IBD 6. Describe IBD complications and cancer surveillance --- ## Lecture Content ### Overview of Inflammatory Bowel Disease Inflammatory bowel disease (IBD) comprises chronic, relapsing-remitting inflammatory disorders of the gastrointestinal tract. The two major forms—Crohn's disease (CD) and ulcerative colitis (UC)—share overlapping features but differ in distribution, depth of involvement, histology, and clinical behavior. In approximately 10-15% of patients with colonic inflammation, the distinction between CD and UC cannot be made definitively; these cases are termed "indeterminate colitis." IBD incidence is increasing worldwide, particularly in newly industrialized nations, suggesting environmental factors play important roles. The peak age of onset is 15-30 years, with a smaller second peak at 50-70 years. Geographic variation is striking: IBD is most common in North America and Northern Europe, with lower but rising rates in Asia, Africa, and South America. Ashkenazi Jewish ethnicity carries increased risk. Interestingly, smoking has opposite effects in the two conditions: smoking protects against UC but worsens CD. The pathophysiology of IBD involves complex interactions between genetic susceptibility, environmental triggers, the gut microbiome, and the immune system. Genetics contribute significantly—first-degree relatives of IBD patients have 5-20 times the risk of developing IBD. Over 200 genetic loci are associated with IBD susceptibility. The NOD2/CARD15 gene is the most strongly associated with Crohn's disease; it encodes an intracellular receptor for bacterial components, and mutations impair innate immune responses to bacteria. IL-23 receptor variants affect both CD and UC. Environmental factors modify genetic risk. Diet (particularly Western diet high in processed foods), infections, antibiotic use, and altered early-life microbial exposure may contribute. The gut microbiome in IBD shows dysbiosis—reduced bacterial diversity, decreased Firmicutes and Bacteroidetes, and increased Proteobacteria. Whether dysbiosis causes or results from inflammation remains debated. The immune mechanisms differ somewhat between CD and UC. Crohn's disease involves predominantly Th1 and Th17 responses, with elevated TNF-α, IL-12, and IL-23. Ulcerative colitis involves a more atypical Th2 response with elevated IL-5 and IL-13. Both involve defects in epithelial barrier function and innate immunity. Panel A: Four interacting components of IBD pathophysiology including genetics with NOD2 and IL-23R loci on chromosome icons, environment with diet, smoking, and infection triggers, microbiome showing dysbiosis with decreased diversity and increased Proteobacteria, and immune system with T cell activation and cytokine release, all connected by bidirectional arrows. Panel B: Immune profile comparison showing Crohn's disease with Th1 and Th17 predominance and elevated TNF-alpha, IL-12, and IL-23 versus ulcerative colitis with atypical Th2 response and elevated IL-5 and IL-13. Panel C: Gut barrier showing normal tight epithelium compared to IBD with disrupted barrier function allowing bacterial translocation and triggering mucosal inflammation. Panel D: Epidemiology including peak age of onset at 15-30 years, geographic gradient with higher rates in developed nations, Ashkenazi Jewish ethnicity with increased risk, and opposite effects of smoking being protective in UC but harmful in CD. --- ### Crohn's Disease vs Ulcerative Colitis Understanding the key differences between Crohn's disease and ulcerative colitis is essential for diagnosis and management. Distribution patterns differ fundamentally. Crohn's disease can affect any portion of the GI tract from mouth to anus, though the terminal ileum is most commonly involved (approximately 30% have isolated ileal disease, 40% have ileocolonic involvement). Importantly, CD produces skip lesions—segments of inflammation separated by normal bowel—and often spares the rectum. Ulcerative colitis involves only the colon and rectum, always involving the rectum and extending proximally in a continuous fashion. Proctitis (rectal involvement only) accounts for 30-40% of cases; left-sided colitis extends to the splenic flexure; extensive colitis or pancolitis extends beyond the splenic flexure. Depth of inflammation is the most important distinction pathologically. Crohn's disease is transmural—inflammation extends through all layers of the bowel wall (mucosa, submucosa, muscularis propria, serosa). This transmural inflammation accounts for characteristic complications: strictures form as chronic inflammation leads to fibrosis; fistulas form as inflammation tracks through the wall to adjacent structures (other bowel loops, bladder, skin); abscesses form when penetrating inflammation encounters closed spaces. Ulcerative colitis is limited to the mucosa and submucosa, sparing the muscularis propria. This superficial inflammation does not produce strictures or fistulas (and if a stricture develops in UC, it should raise concern for cancer). Histologic features assist diagnosis. Crohn's disease shows non-caseating granulomas in 30-50% of cases—aggregates of epithelioid macrophages that, while not pathognomonic, strongly support the diagnosis. Inflammation is focal and may show transmural lymphoid aggregates. Ulcerative colitis shows crypt abscesses (neutrophils within crypt lumens), crypt architectural distortion, and diffuse mucosal inflammation without granulomas. Endoscopic appearances reflect these differences. Crohn's disease shows deep, linear ulcers that intersect to create a "cobblestone" appearance; aphthous ulcers (small, shallow ulcers with surrounding normal mucosa) are early lesions; skip areas with normal intervening mucosa are characteristic. Ulcerative colitis shows continuous erythema, edema, friability (bleeding with light touch), superficial ulceration, and loss of vascular pattern. Pseudopolyps (islands of regenerating mucosa surrounded by denuded areas) indicate chronic disease. Panel A: Distribution patterns showing Crohn's disease affecting any GI tract segment from mouth to anus with patchy involvement, skip lesions, and rectal sparing, compared to ulcerative colitis affecting only the colon with continuous involvement from the rectum extending proximally in three extents of proctitis, left-sided colitis, and pancolitis. Panel B: Depth of inflammation with Crohn's disease showing transmural full-thickness inflammation through all four labeled wall layers leading to fistulas and strictures, versus ulcerative colitis limited to the mucosa and submucosa. Panel C: Histologic features showing Crohn's disease with non-caseating granulomas, focal inflammation, and transmural lymphoid aggregates, compared to ulcerative colitis with crypt abscesses, diffuse mucosal inflammation, and no granulomas. Panel D: Endoscopic appearances with Crohn's disease showing deep linear ulcers and cobblestone pattern with aphthous ulcers and skip areas, versus ulcerative colitis showing continuous erythema, edema, mucosal friability, and pseudopolyps. --- ### Clinical Features of IBD The clinical presentation of Crohn's disease depends on disease location and behavior. Abdominal pain is common, often in the right lower quadrant when the terminal ileum is involved, and may be postprandial in small bowel disease. Diarrhea is usually non-bloody (unlike UC), though colonic involvement may cause bloody stools. Weight loss and malnutrition occur frequently due to reduced intake (eating provokes symptoms), malabsorption (if extensive small bowel involvement), and increased metabolic demands from chronic inflammation. Fatigue is nearly universal. Perianal disease—including fissures, fistulas, abscesses, and skin tags—affects up to 50% of CD patients and may be the presenting feature. Fever suggests abscess formation. Ulcerative colitis presents with the hallmark symptom of bloody diarrhea. The inflammation causes mucosal damage with blood and mucus in the stool. Urgency (the sudden need to defecate) and tenesmus (the sensation of incomplete evacuation) reflect rectal inflammation. Cramping abdominal pain typically localizes to the left lower quadrant but may be diffuse in pancolitis. Fecal incontinence may occur with severe disease. Systemic symptoms (fever, weight loss, fatigue) correlate with disease severity. Disease extent classification for UC uses the Montreal classification: proctitis (rectum only, E1), left-sided colitis (to splenic flexure, E2), and extensive/pancolitis (beyond splenic flexure, E3). Extent influences treatment approach (topical therapies sufficient for distal disease) and cancer surveillance recommendations. Disease behavior classification for CD uses the Montreal classification based on phenotype: B1 (non-stricturing, non-penetrating, purely inflammatory), B2 (stricturing), and B3 (penetrating, with fistulas or abscesses). A perianal modifier (p) is added if perianal disease is present. Behavior evolves over time—most patients begin with inflammatory disease, but many progress to stricturing or penetrating phenotypes, illustrating the importance of achieving disease control early. Panel A: Crohn's disease clinical features including right lower quadrant pain on the abdomen diagram, non-bloody diarrhea, weight loss and malnutrition, perianal disease with fistulas and abscesses affecting up to 50% of patients, and fever suggesting abscess formation. Panel B: Montreal behavior classification for Crohn's disease showing B1 non-stricturing, non-penetrating inflammatory disease as a red inflamed segment, B2 stricturing disease as a narrowed segment, B3 penetrating disease with fistula tracks shown, and the perianal modifier. Panel C: Ulcerative colitis clinical features including bloody diarrhea as the hallmark symptom, urgency and tenesmus reflecting rectal inflammation, left lower quadrant pain, and systemic symptoms correlating with disease severity. Panel D: Montreal extent classification for ulcerative colitis showing E1 proctitis with only the rectum shaded, E2 left-sided colitis extending to the splenic flexure, and E3 extensive colitis or pancolitis extending beyond the splenic flexure, with extent influencing treatment approach and cancer surveillance. --- ### Extraintestinal Manifestations Up to 40% of IBD patients experience extraintestinal manifestations (EIMs), some paralleling intestinal disease activity and others following an independent course. Manifestations that parallel intestinal disease activity generally improve when the underlying IBD is controlled. Erythema nodosum presents as tender, raised, red nodules typically on the anterior shins; it is more common in CD. Type 1 peripheral arthritis (pauciarticular, affecting fewer than 5 large joints) correlates with disease flares. Episcleritis causes red, irritated eyes without vision changes. Aphthous ulcers in the mouth parallel intestinal activity. Manifestations independent of intestinal disease activity require separate treatment. Pyoderma gangrenosum produces deep, painful ulcers with undermined borders, typically on the legs; it may worsen with trauma (pathergy) and does not necessarily improve with IBD treatment. Type 2 peripheral arthritis (polyarticular, affecting smaller joints) follows an independent course. Axial arthropathy (ankylosing spondylitis, sacroiliitis) associates with HLA-B27 and does not correlate with intestinal activity. Uveitis (anterior) causes eye pain, redness, photophobia, and visual changes requiring urgent ophthalmologic evaluation. Primary sclerosing cholangitis (PSC) deserves special attention. This progressive cholestatic liver disease involves inflammation and fibrosis of intrahepatic and extrahepatic bile ducts. Approximately 70-80% of PSC patients have IBD (usually UC with specific features: pancolitis, mild activity, backwash ileitis). Conversely, about 5% of UC patients develop PSC. PSC follows a course independent of IBD activity and may progress despite colectomy. It significantly increases the risk of cholangiocarcinoma and colorectal cancer (even beyond the elevated risk from UC alone). Diagnosis is made by MRCP or ERCP showing multifocal strictures and dilations ("beaded" appearance) of the biliary tree. Treatment is largely supportive, with liver transplantation for end-stage disease. Other associations include thromboembolism (IBD is a hypercoagulable state, particularly during flares), osteoporosis (from corticosteroid use, malabsorption, and inflammation itself), nephrolithiasis (calcium oxalate stones in CD with ileal disease due to increased oxalate absorption), and cholelithiasis (bile acid malabsorption after ileal resection). Panel A: Extraintestinal manifestations paralleling intestinal disease activity including erythema nodosum with tender red nodules on the shins, Type 1 peripheral arthritis affecting fewer than 5 large joints, episcleritis with red eyes without vision loss, and oral aphthous ulcers. Panel B: Extraintestinal manifestations independent of intestinal activity including pyoderma gangrenosum with deep painful ulcers with undermined borders on the legs, Type 2 peripheral arthritis affecting smaller joints, axial arthropathy with ankylosing spondylitis and sacroiliitis associated with HLA-B27, and anterior uveitis with eye pain, photophobia, and vision changes. Panel C: Primary sclerosing cholangitis showing MRCP with beaded bile ducts from multifocal strictures and dilations, 70-80% of PSC patients having IBD usually ulcerative colitis, independent course from IBD activity, and increased risk of cholangiocarcinoma and colorectal cancer. Panel D: Other associations including venous thromboembolism as a hypercoagulable state during flares, osteoporosis from corticosteroids and malabsorption, calcium oxalate kidney stones in Crohn's with ileal disease, and gallstones from bile acid malabsorption after ileal resection. --- ### Diagnosis of IBD The diagnosis of IBD requires integration of clinical, laboratory, endoscopic, histologic, and radiographic findings. No single test is diagnostic. Laboratory studies establish inflammation and exclude other causes. Complete blood count may show anemia (from blood loss or chronic disease), leukocytosis, and thrombocytosis (reactive). Comprehensive metabolic panel reveals hypoalbuminemia (indicating malnutrition or protein-losing enteropathy), electrolyte disturbances, and abnormal liver tests (raising concern for PSC). Inflammatory markers (CRP and ESR) are elevated during active inflammation and useful for monitoring but are not specific for IBD. Fecal calprotectin is a neutrophil-derived protein that correlates with intestinal inflammation; elevated levels (>150-200 μg/g) strongly suggest organic disease and can help distinguish IBD from irritable bowel syndrome. Stool testing for pathogens (Clostridioides difficile, enteric bacteria, parasites) is essential because infections can mimic or trigger IBD flares. Colonoscopy with ileoscopy is the gold standard for diagnosis. It allows direct visualization of mucosal disease, assessment of extent and severity, and biopsy for histologic confirmation. Multiple biopsies should be obtained from involved and uninvolved areas. Upper endoscopy is indicated if upper GI symptoms are present and routinely in some protocols for CD evaluation. Video capsule endoscopy visualizes the small bowel mucosa noninvasively and is useful for detecting small bowel Crohn's disease (after excluding strictures). Deep enteroscopy (balloon-assisted) allows biopsy and therapy in the small bowel. Imaging complements endoscopy, particularly for small bowel evaluation and assessment of transmural disease. CT enterography uses oral and IV contrast to visualize the small bowel; findings in CD include wall thickening, mucosal enhancement, strictures, fistulas, abscesses, and the "comb sign" (engorged vasa recta indicating active inflammation). MR enterography provides similar information without radiation exposure and is preferred for young patients and serial monitoring. MRI of the pelvis is the modality of choice for characterizing perianal fistulas. Ultrasound can detect bowel wall thickening and is increasingly used for monitoring. Serologic markers (ASCA, anti-CBir1 for CD; pANCA for UC) have limited utility for diagnosis but may help in indeterminate cases. A positive ASCA with negative pANCA suggests CD; negative ASCA with positive pANCA suggests UC. Panel A: Laboratory workup including CBC showing anemia and leukocytosis, comprehensive metabolic panel revealing hypoalbuminemia and abnormal liver tests, CRP and ESR elevated in active disease, fecal calprotectin exceeding 150 micrograms per gram suggesting organic disease, and stool pathogen testing to rule out infection. Panel B: Endoscopic evaluation with colonoscopy and ileoscopy as the gold standard, biopsy forceps obtaining samples from involved and uninvolved areas, and video capsule endoscopy for noninvasive small bowel visualization after excluding strictures. Panel C: Imaging with CT enterography showing wall thickening and comb sign indicating active inflammation, MR enterography preferred for young patients and serial monitoring without radiation, and pelvic MRI for characterizing perianal fistulas. Panel D: Serologic markers with ASCA-positive and pANCA-negative suggesting Crohn's disease, ASCA-negative and pANCA-positive suggesting ulcerative colitis, noted as having limited diagnostic utility but potentially helpful in indeterminate cases. --- ### Medical Management Principles The goals of IBD treatment have evolved beyond symptom control to include objective measures. Inducing remission controls active flares. Maintaining remission prevents relapse. Mucosal healing (endoscopically normal-appearing mucosa) correlates with improved long-term outcomes, reduced hospitalizations, fewer surgeries, and decreased cancer risk—it is now a target of therapy. Preventing complications (strictures, fistulas, cancer) requires early and effective disease control. Improving quality of life encompasses all of these goals. Treatment approaches have shifted over time. The traditional step-up approach started with less potent therapies (aminosalicylates) and escalated to more powerful agents only if needed. This is appropriate for mild disease. The top-down approach begins with biologic therapy early, particularly for patients with high-risk features (young age, extensive disease, deep ulcers, perianal disease, prior surgery). This aggressive early approach may modify disease course and prevent complications. Treat-to-target applies objective monitoring (symptoms, biomarkers, endoscopy) and adjusts therapy to achieve defined endpoints rather than accepting symptomatic improvement alone. Disease activity is assessed using validated indices. For Crohn's disease, the Crohn's Disease Activity Index (CDAI) and Harvey-Bradshaw Index (HBI) are clinical scores. For ulcerative colitis, the Mayo score and partial Mayo score are commonly used. Biomarkers (CRP, fecal calprotectin) correlate with inflammation. Endoscopic scores (Simple Endoscopic Score for CD [SES-CD], Mayo endoscopic subscore) assess mucosal disease directly. The goal is achieving both clinical remission (resolution of symptoms) and endoscopic remission (mucosal healing). The therapeutic armamentarium includes several drug classes. Aminosalicylates (5-ASA) act topically on the mucosa. Corticosteroids rapidly suppress inflammation but have significant toxicity with long-term use. Immunomodulators provide steroid-sparing maintenance. Biologics target specific inflammatory pathways. Small molecules offer oral alternatives to injectable biologics. Panel A: Treatment goals as progressive targets from symptom control to clinical remission to mucosal healing to prevention of complications, with mucosal healing now recognized as the key outcome shown by endoscopy images comparing ulcerated versus healed mucosa. Panel B: Treatment approaches including the step-up pyramid with aminosalicylates at the base escalating to biologics, the top-down inverted pyramid starting with biologics early for high-risk patients, and the treat-to-target circular diagram showing repeated cycles of assessment, treatment, and reassessment. Panel C: Disease activity assessment using clinical indices such as CDAI and Mayo scores, biomarkers including CRP and fecal calprotectin trends, and endoscopic scores for direct mucosal evaluation. Panel D: Overview of drug classes including aminosalicylates, corticosteroids, immunomodulators, biologics, and small molecules as distinct therapeutic categories. --- ### Specific Medical Therapies Aminosalicylates (5-ASA compounds) are the mainstay for mild-to-moderate ulcerative colitis. Mesalamine (5-aminosalicylic acid) is available in multiple formulations engineered to release drug at different sites: oral delayed-release (Asacol, Lialda), extended-release (Pentasa), and rectal (suppositories for proctitis, enemas for left-sided disease). Sulfasalazine combines 5-ASA with sulfapyridine (the carrier); it is useful when arthropathy coexists because the sulfapyridine component has anti-inflammatory effects systemically. The mechanism is topical anti-inflammatory action, likely through inhibition of prostaglandin and leukotriene synthesis and scavenging of reactive oxygen species. Aminosalicylates are effective for induction and maintenance in UC but have limited or no role in CD (except possibly for mild colonic CD). Corticosteroids are potent anti-inflammatory agents for inducing remission in moderate-to-severe flares but are not appropriate for maintenance therapy due to significant side effects (osteoporosis, adrenal suppression, hyperglycemia, hypertension, cataracts, infections, mood changes). Prednisone is the typical oral agent, usually starting at 40-60 mg daily with taper over 8-12 weeks. Budesonide is a corticosteroid with high first-pass hepatic metabolism, limiting systemic effects; controlled-release formulations (Entocort) target the ileum and right colon, making it useful for ileal and right-sided CD. IV methylprednisolone is used for severe flares requiring hospitalization. Immunomodulators provide steroid-sparing maintenance therapy. Thiopurines (azathioprine, 6-mercaptopurine) inhibit purine synthesis and suppress lymphocyte proliferation. TPMT enzyme testing should precede initiation because deficiency causes severe myelosuppression. Onset of action is slow (2-3 months). Risks include myelosuppression, hepatotoxicity, pancreatitis, and increased lymphoma risk. Methotrexate (given weekly, usually by injection) is effective for CD maintenance but not UC; it inhibits folate metabolism. Monitoring with CBC and liver tests is required for both classes. Biologics represent a major advance. Anti-TNF agents (infliximab, adalimumab, certolizumab pegol, golimumab) neutralize TNF-α, a key pro-inflammatory cytokine. They are effective for moderate-to-severe CD and UC, both induction and maintenance, and can heal fistulas. Anti-integrin therapy (vedolizumab) blocks α4β7 integrin, preventing lymphocyte trafficking to the gut; it is "gut-selective" with a favorable safety profile. Anti-IL-12/23 agents (ustekinumab) block the shared p40 subunit of IL-12 and IL-23. Anti-IL-23 agents (risankizumab, mirikizumab) specifically target the p19 subunit of IL-23, offering greater specificity. Small molecules offer oral alternatives. JAK inhibitors (tofacitinib, upadacitinib) block Janus kinases that mediate cytokine signaling; they are approved for UC and are effective as induction and maintenance. S1P receptor modulators (ozanimod, etrasimod) prevent lymphocyte egress from lymph nodes, reducing their trafficking to inflamed tissue; they are approved for UC. Panel A: Aminosalicylates showing mesalamine releasing at the colon in oral and rectal formulations, sulfasalazine combining 5-ASA with sulfapyridine, indicated for mild-to-moderate ulcerative colitis with a topical anti-inflammatory mechanism, alongside corticosteroids with prednisone for induction only and not maintenance, budesonide with high first-pass metabolism targeting ileal Crohn's disease, and IV methylprednisolone for severe flares. Panel B: Immunomodulators including azathioprine and 6-mercaptopurine requiring TPMT testing with slow 2-3 month onset, and methotrexate effective for Crohn's disease only given as weekly injection, both requiring CBC and liver function monitoring. Panel C: Biologics including anti-TNF agents infliximab given intravenously and adalimumab given subcutaneously, vedolizumab blocking alpha-4-beta-7 integrin as a gut-selective therapy, ustekinumab targeting the IL-12 and IL-23 shared p40 subunit, and risankizumab specifically targeting the IL-23 p19 subunit. Panel D: Small molecules including JAK inhibitors tofacitinib and upadacitinib as oral agents blocking Janus kinase cytokine signaling, and S1P receptor modulators ozanimod and etrasimod preventing lymphocyte egress from lymph nodes, all approved for ulcerative colitis. --- ### Surgical Management Surgery plays different roles in CD and UC. In Crohn's disease, surgery is not curative—disease recurs in up to 50% of patients at the anastomosis within 5 years. Nonetheless, surgery is frequently necessary. Indications include medically refractory disease that fails to respond to optimized therapy, strictures causing symptomatic obstruction, fistulas (particularly complex perianal fistulas, enterovesical fistulas, or enteroenteric fistulas causing malabsorption), abscesses requiring drainage followed by resection, perforation (emergency surgery), and cancer or dysplasia. Surgical principles in CD emphasize bowel conservation. Resection should be limited to grossly diseased bowel—there is no benefit to wide margins. Strictureplasty widens strictured segments without removing bowel, preserving intestinal length; various techniques (Heineke-Mikulicz, Finney, Jaboulay) are used depending on stricture length. Multiple resections over time create risk of short bowel syndrome, making bowel-preserving techniques important. Perianal disease is managed with setons (draining fistulas), fistula repair procedures, and occasionally proctectomy for severe, refractory cases. In ulcerative colitis, surgery is potentially curative because UC is limited to the colon and rectum. Colectomy removes all diseased tissue. Indications include medically refractory disease, toxic megacolon (medical emergency), perforation, massive hemorrhage, and dysplasia or cancer. The surgical procedure of choice in UC is total proctocolectomy with ileal pouch-anal anastomosis (IPAA), commonly called the "J-pouch." The entire colon and rectum are removed, and a reservoir is constructed from the terminal ileum that is then connected to the anal canal, preserving continence and avoiding a permanent ostomy. This is typically performed in 2-3 stages to allow healing. Pouchitis—inflammation of the ileal pouch—occurs in up to 50% of patients, usually responding to antibiotics (ciprofloxacin, metronidazole). Total proctocolectomy with end ileostomy is an alternative if the anal sphincter is compromised or the patient prefers it. Subtotal colectomy with ileostomy is used in emergency settings, leaving the rectum for future completion or IPAA. Panel A: Crohn's disease surgery showing indications including medically refractory disease, strictures, fistulas, abscesses, perforation, and cancer, with surgical principles of limited resection to grossly diseased bowel and strictureplasty as a bowel-sparing technique, and recurrence rate of 50% at the anastomosis within 5 years. Panel B: Perianal Crohn's disease surgery showing seton placement in fistula tracts for drainage, fistula repair procedures, and proctectomy for severe refractory cases. Panel C: Ulcerative colitis surgery as potentially curative because UC is limited to the colon, with indications including refractory disease, toxic megacolon shown as dilated colon on X-ray, perforation, massive hemorrhage, and dysplasia or cancer. Panel D: J-pouch construction showing total proctocolectomy removing the colon and rectum, ileal reservoir created from the terminal ileum and anastomosed to the anal canal preserving continence, pouchitis occurring in up to 50% of patients treated with antibiotics, and end ileostomy as an alternative with ostomy bag shown. --- ### Complications and Special Situations Complications of Crohn's disease reflect its transmural nature. Strictures cause obstructive symptoms (crampy pain, bloating, nausea, vomiting); management includes balloon dilation, strictureplasty, or resection. Fistulas track between the bowel and other structures: enterocutaneous (to skin, often draining to the abdominal wall), enterovesical (to bladder, causing pneumaturia and recurrent UTIs), rectovaginal (to vagina, causing passage of stool per vagina), and enteroenteric (between bowel loops, causing malabsorption). Treatment includes antibiotics, biologics (particularly infliximab for perianal fistulas), and surgery. Abscesses require drainage (percutaneous or surgical) before definitive treatment. Extensive small bowel disease or multiple resections can cause short bowel syndrome. Complications of ulcerative colitis include toxic megacolon, a life-threatening condition where severe inflammation leads to colonic dilation (transverse colon diameter >6 cm on imaging) with systemic toxicity (fever, tachycardia, leukocytosis). It represents a surgical emergency if there is no improvement with aggressive medical therapy (IV corticosteroids, antibiotics, bowel rest) within 24-72 hours; perforation is imminent. Massive hemorrhage occasionally necessitates emergency colectomy. Strictures in UC are concerning for malignancy and require thorough evaluation with biopsy. Clostridioides difficile infection complicates IBD and should be tested during flares; treatment is vancomycin. IBD in pregnancy requires careful management. Active disease at conception increases the risk of adverse outcomes more than medication exposure. The goal is achieving remission before conception. Most IBD medications are safe during pregnancy: aminosalicylates, corticosteroids (for flares), thiopurines, and anti-TNF agents (though some recommend stopping in the third trimester to reduce neonatal drug exposure; vedolizumab and ustekinumab also appear safe). Methotrexate is absolutely contraindicated due to teratogenicity. Before initiating immunosuppressive or biologic therapy, patients require screening for latent tuberculosis (skin test or interferon-gamma release assay) and hepatitis B (to avoid reactivation). Vaccinations should be updated before immunosuppression, avoiding live vaccines once on therapy. Panel A: Crohn's disease complications including strictures causing obstructive symptoms, fistula types with enterocutaneous fistulas draining to skin, enterovesical fistulas with air in the bladder, and rectovaginal fistulas, abscesses shown on CT as fluid collections requiring drainage, and short bowel syndrome from multiple resection sites. Panel B: Ulcerative colitis complications including toxic megacolon with colonic dilation exceeding 6 cm on X-ray and systemic toxicity as a surgical emergency, strictures raising concern for underlying malignancy, and Clostridioides difficile infection that should be tested during flares and treated with vancomycin. Panel C: IBD in pregnancy showing the goal of achieving remission before conception, safe medications including aminosalicylates, corticosteroids for flares, thiopurines, and anti-TNF agents, and methotrexate as absolutely contraindicated due to teratogenicity. Panel D: Pre-treatment screening before immunosuppressive or biologic therapy including tuberculosis testing with PPD or interferon-gamma release assay, hepatitis B serology to avoid reactivation, and vaccination updates before immunosuppression while avoiding live vaccines once on therapy. --- ### Cancer Surveillance Patients with IBD have an increased risk of colorectal cancer (CRC), particularly those with longstanding extensive colitis. The cumulative risk increases with disease duration: negligible in the first 8-10 years, then approximately 0.5-1% per year thereafter. The risk is higher with greater disease extent (pancolitis > left-sided > proctitis), more severe inflammation, presence of PSC (which dramatically increases risk), family history of CRC, and presence of pseudopolyps or strictures. Surveillance colonoscopy aims to detect dysplasia (premalignant change) before invasive cancer develops. Current guidelines recommend initiating surveillance 8-10 years after diagnosis for patients with extensive colitis (left-sided or pancolitis). For patients with proctitis only, surveillance may begin later or follow average-risk guidelines if disease remains limited. Intervals are risk-stratified: high-risk patients (PSC, prior dysplasia, extensive active inflammation) require annual colonoscopy; intermediate-risk patients every 2-3 years; low-risk patients every 5 years. Patients with PSC should begin annual surveillance from the time of PSC diagnosis, regardless of IBD duration. Technique matters for detecting the often flat or subtle dysplastic lesions in IBD. Chromoendoscopy uses dye spraying (indigo carmine or methylene blue) to highlight mucosal abnormalities and has superior dysplasia detection compared to white-light endoscopy with random biopsies. High-definition white-light endoscopy is also acceptable if chromoendoscopy is not available. Biopsies should be taken from any visible lesions and, in some protocols, randomly from flat mucosa throughout the colon. Management of dysplasia has evolved. Visible dysplastic lesions (polypoid or non-polypoid) that are completely resectable endoscopically should be removed with clear margins, followed by intensified surveillance. Unresectable dysplasia or multifocal dysplasia generally indicates proctocolectomy. High-grade dysplasia is associated with concurrent cancer in a significant proportion and typically warrants colectomy. Low-grade dysplasia management depends on whether it is visible and resectable versus invisible/flat; expert pathology review is essential given interobserver variability. IBD also increases risk of other malignancies: small bowel adenocarcinoma in CD, cholangiocarcinoma in PSC, lymphoma (possibly increased with thiopurines), and skin cancers (increased with thiopurines and biologics—sun protection is recommended). Panel A: Colorectal cancer risk factors in IBD showing disease duration with a graph of cumulative risk increasing after 8-10 years, disease extent with pancolitis carrying the highest risk and proctitis the lowest, PSC dramatically increasing risk, inflammation severity, and family history of CRC. Panel B: Surveillance protocol starting 8-10 years after diagnosis for extensive colitis, with intervals stratified by risk as annual for high-risk patients and those with PSC, every 2-3 years for intermediate risk, and every 5 years for low risk, with PSC surveillance starting from time of PSC diagnosis regardless of IBD duration. Panel C: Surveillance technique showing chromoendoscopy with dye-sprayed colon highlighting subtle and flat dysplastic lesions as superior to white-light endoscopy with random biopsies, with biopsies targeting visible lesions and random samples from flat mucosa. Panel D: Dysplasia management flowchart with visible and resectable lesions undergoing endoscopic resection followed by surveillance, high-grade dysplasia or unresectable lesions warranting colectomy, and flat invisible low-grade dysplasia requiring expert pathology review and intensified surveillance versus colectomy, alongside other cancer risks including small bowel adenocarcinoma in CD, cholangiocarcinoma in PSC, lymphoma, and skin cancers requiring sun protection. --- ## Summary - IBD: CD (transmural, skip, mouth-to-anus) vs UC (mucosal, continuous, colon) - Pathophysiology: Genetic + environmental + microbiome → dysregulated immunity - EIMs: Skin, joints, eyes, liver (PSC); some parallel activity, some independent - Diagnosis: Colonoscopy + biopsy; fecal calprotectin; MR enterography for CD - Treatment: 5-ASA (UC), steroids (induction), immunomodulators, biologics, JAK inhibitors - Surgery: Not curative in CD; proctocolectomy + J-pouch curative in UC - Cancer surveillance: Start after 8-10 years; chromoendoscopy; PSC = annual --- ## Key Terms | Term | Definition | |------|------------| | Crohn's disease | Transmural IBD affecting any GI tract segment | | Ulcerative colitis | Mucosal IBD limited to colon/rectum | | Fecal calprotectin | Stool marker of intestinal inflammation | | Skip lesions | Discontinuous areas of inflammation (CD) | | Toxic megacolon | Life-threatening colonic dilation in severe colitis | | PSC | Primary sclerosing cholangitis; associated with UC | | J-pouch (IPAA) | Ileal pouch-anal anastomosis after proctocolectomy | | Mucosal healing | Endoscopic remission; treatment target | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*