Inflammatory Bowel Disease: Crohn's Disease and Ulcerative Colitis

1. Epidemiology

• Ulcerative colitis (UC): incidence ~19/100,000 person-years; prevalence ~280/100,000
• Crohn's disease (CD): incidence ~20/100,000 person-years; prevalence ~320/100,000

• Cigarette smoking: worsens CD but improves UC course
• NSAIDs: associated with new onset and exacerbations of IBD
• Appendectomy (for inflammatory indication): protective against UC
• Western diet (high fat, high sugar, low fiber): ~2-fold increased IBD risk
• Goldman-Cecil Medicine, p. 1480

2. Pathobiology

Genetics

• 5-20% of IBD patients have a first-degree relative with IBD; first-degree relatives have a 10-15-fold increased risk
• NOD2/CARD15 mutations (chromosome 16): strongest genetic association with CD; NOD2 senses bacterial muramyl dipeptide - mutations lead to impaired recognition and dysregulated NF-κB activation
• ATG16L1 and IRGM genes (autophagy pathway): also linked to CD
• IL-23 receptor gene polymorphisms: linked to UC and varied CD risk
• Toll-like receptor-4 gene polymorphisms: linked to both CD and UC
• ADCY7 missense mutation: leads to excessive inflammatory response predisposing to UC
• HLA class II polymorphisms (especially HLA-DR): increased risk for UC

Immunology

• Both CD and UC involve dysregulated innate immunity triggering T cells and humoral response
• Th17 cells are activated in both conditions, stimulated by IL-23 produced by antigen-presenting cells

Microbiome

• Colitis does not develop in animal models in a sterile environment
• The terminal ileum and colon (highest bacterial density, ~10¹² organisms/g) are the preferentially affected sites
• Debaryomyces hansenii (Candida famata) has been implicated in Crohn tissue
• Goldman-Cecil Medicine, p. 1479-1480

3. Key Distinguishing Features

• Goldman-Cecil Medicine, p. 1481

4. Pathology

Crohn's Disease

• Early: acute inflammatory infiltrate in lamina propria, cryptitis, crypt abscesses
• Later: distorted crypt architecture with lymphocytic infiltrate, branching/shortening of crypts
• Pathognomonic (when present): noncaseating granulomas (found in ~15% endoscopic biopsies, up to 70% surgical specimens)
• Surgical specimens: transmural wall inflammation; fat creeping on serosal surface ("creeping fat")

Ulcerative Colitis

• Begins in the rectum, extends proximally in a continuous pattern
• Mild disease: granular, hyperemic, edematous mucosa
• Severe disease: mucosal ulceration extending into lamina propria
• Chronic disease: pseudopolyps (from epithelial regeneration), loss of normal fold pattern, colonic shortening and narrowing
• Histology: epithelial necrosis, acute inflammatory infiltrate, cryptitis/crypt abscesses; with chronicity - lymphocytic infiltrate and crypt architectural distortion

• Goldman-Cecil Medicine, p. 1481

5. Clinical Manifestations

Crohn's Disease

• Terminal ileum affected in ~70% (ileal disease 30%, ileocolonic 40%)
• Symptoms: right lower quadrant pain, diarrhea, hematochezia, fatigue; fever and weight loss with more severe disease
• Obstructive symptoms (pain, distention, nausea) when strictures develop
• Perianal disease (fissures, skin tags, fistulae, abscesses) in up to 30%
• Fistulae in 20-40%: enterocutaneous, rectovaginal, enterovesicular, enteroenteric
• Upper GI involvement in ~5% (esophageal in <2%); gastroduodenal in 0.5-4%

Ulcerative Colitis

• At diagnosis: 44-49% have proctosigmoiditis; 36-41% disease beyond rectum; 14-37% pancolitis
• Symptoms: hematochezia, diarrhea, tenesmus, excess mucus, urgency
• Proctitis/proctosigmoiditis may cause constipation (paradoxically)
• Severe disease: weight loss, fever, nausea/vomiting, anemia, hypoalbuminemia, peripheral edema

Extraintestinal Manifestations

• Crohn's is more frequently associated with: arthritis, aphthous stomatitis, uveitis, erythema nodosum, ankylosing spondyloarthropathy
• UC is most associated with: inflammatory arthropathies and primary sclerosing cholangitis (PSC)
• Both: skin lesions (pyoderma gangrenosum), eye disease, bone disease
• Rosen's Emergency Medicine, p. 1334; Goldman-Cecil Medicine, p. 1481-1482

6. Diagnosis

Laboratory

• Anemia (iron deficiency from blood loss; B12/folate deficiency from terminal ileal disease or resection in CD)
• Elevated ESR, CRP (reflect inflammatory activity)
• Hypoalbuminemia, leukocytosis, thrombocytosis in active disease
• Fecal calprotectin: sensitive marker of gut mucosal inflammation, helpful for monitoring
• ANCA (perinuclear): associated with UC; ASCA (anti-Saccharomyces cerevisiae antibodies): associated with CD

Endoscopy and Biopsy

• Colonoscopy with biopsy is the cornerstone of diagnosis
• For UC: starts in rectum, continuous inflammation; biopsy shows crypt distortion, continuous mucosal inflammation, absence of granulomas, absence of small bowel disease
• For CD: skip pattern of ulceration, discrete ulcers, can involve small bowel or upper GI; noncaseating granulomas confirm CD if present

Radiology

• CT enterography / MRI enterography have replaced barium studies - best for assessing extent, severity, strictures, fistulae, abscesses, and perianal disease in CD
• CT/MRI also essential for detecting intra-abdominal and perianal abscesses

Disease Severity Scoring

• Liquid/soft stools × 7 days (×2)
• Abdominal pain severity × 7 days (×5)
• General well-being × 7 days (×7)
• Complications (×20), antidiarrheal use (×30), abdominal mass (×10), hematocrit deviation (×6), weight deviation (×1)
• Goldman-Cecil Medicine, p. 1482-1485

7. Disease Severity Classification

Ulcerative Colitis

Crohn's Disease

• Rosen's Emergency Medicine, p. 1334

8. Treatment

Medical Therapies Overview

Crohn's Disease Treatment by Severity

• Mild-moderate ileocecal CD: ileal-release budesonide 9 mg PO once daily for 8 weeks (minimal systemic effects due to first-pass metabolism)
• Mild-moderate CD colitis / ileocolonic: 8-week systemic corticosteroid course; prednisone 0.5-0.75 mg/kg/day (typically 40-60 mg/day)
• Esophageal/gastroduodenal CD: proton pump inhibitor only for mild disease
• Extensive small bowel CD: systemic corticosteroids + biologic (anti-TNF)
• Moderate-severe CD responsive to steroids: add azathioprine 1.5-2.5 mg/kg/day PO or 6-mercaptopurine 0.75-1.5 mg/kg/day; methotrexate 25 mg/week SC/IM
• Refractory CD: anti-TNF (infliximab, adalimumab, certolizumab) - equivalent efficacy; vedolizumab for anti-TNF failures
• Aminosalicylates are NOT recommended for CD (meta-analyses show no benefit over placebo)
• Hospitalized patients: methylprednisolone 1 mg/kg/day IV; avoid steroids for long-term maintenance (risk of osteopenia, osteonecrosis, GI mucosal injury)

Ulcerative Colitis Treatment

• 5-ASA drugs are the mainstay (effective in UC but not CD)
• Mesalamine enema (4 g/day) or suppository (1 g/day) for distal/rectal disease
• Oral 5-ASA for more proximal disease
• Corticosteroids for moderate-severe flares
• Immunomodulators and anti-TNF (infliximab) for steroid-refractory/dependent disease
• Tofacitinib and upadacitinib (JAK inhibitors) for moderate-severe UC
• Surgery (colectomy) is curative for UC - unlike CD where surgery does not cure
• Rosen's Emergency Medicine, p. 1334-1335; Goldman-Cecil Medicine, p. 1484

9. Complications

Life-Threatening

• Toxic megacolon: pathologic colonic dilation from transmural inflammation causing smooth muscle paralysis, dilation, and eventual perforation. The hallmark is colonic dilation in a systemically toxic patient. Can occur in both CD and UC.
• Intestinal perforation: from deep ulceration or toxic megacolon
• Fulminant colitis: severe colitis with systemic toxicity, >10 bloody stools/day, requiring urgent hospitalization

CD-Specific

• Intestinal strictures (from chronic fibrosis) leading to small bowel obstruction (SBO)
• Fistulae (enterocutaneous, rectovaginal, enterovesicular, enteroenteric)
• Abscesses (perianal and intra-abdominal)
• Short bowel syndrome (from multiple resections)
• Up to 75% of CD patients will undergo at least one abdominal surgery in their lifetime; 50% require surgery within 10 years, 80% within 20 years; surgery is not curative

Shared

• Colorectal cancer risk is elevated in both - increases with disease duration and extent; ongoing endoscopic surveillance is required
• Thromboembolic disease (DVT/PE) - DVT/PE prophylaxis important in hospitalized patients
• Malabsorption and nutritional deficiencies (iron, B12, folate, fat-soluble vitamins)
• Rosen's Emergency Medicine, p. 1332-1335; Goldman-Cecil Medicine, p. 1482-1484; Sleisenger and Fordtran's GI and Liver Disease, p. 2498

10. Surveillance and Cancer Risk

• Long-standing IBD (especially UC with pancolitis) significantly increases colorectal cancer risk
• Regular colonoscopic surveillance with multiple biopsies is mandated - frequency depends on duration, extent, and activity of disease
• Primary sclerosing cholangitis (common in UC) adds an independent risk for cholangiocarcinoma

Recent Evidence (2024-2025)

• Goldman-Cecil Medicine (26th ed.), Chapter 127 - Inflammatory Bowel Disease, p. 1479-1485
• Rosen's Emergency Medicine (10th ed.), Chapter 81 - Inflammatory Bowel Disease, p. 1332-1336
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease (11th ed.), p. 2498

1. Pull the same topic from Harrison's (22nd ed, 2025) which is the closest equivalent to Manipal in exam-oriented internal medicine content?
2. Check The Washington Manual for a concise clinical summary format (similar to Manipal's style)?
3. Look in Yamada's Gastroenterology for more detailed GI-specific content?