Inflammatory Bowel Disease (IBD)

Overview

• IBD includes two phenotypes: Ulcerative Colitis (UC) and Crohn's Disease (CD).
• Main focus: affected bowel parts, pathophysiology, causes, and differentiation factors.

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Crohn's Disease (CD)

Key Characteristics

• Can affect any part of the Gastrointestinal Tract (GIT) from mouth to anus.
• Most common location: Ileum.
• Rectum is typically spared.

Symptoms

• Diarrhea (non-bloody, watery).
• Right lower quadrant pain (common with ileum involvement).
• Relapsing and remitting pattern (flare-ups and healing).

Pathology

• Transmural ulcers (affects all layers of the bowel wall).
• Granulomas (collections of immune cells, common in CD).

Immunological Factors

• Involvement of Th1 cells and Th17 cells.
  • Release cytokines: TNF alpha, Interferon gamma, Interleukin-12, Interleukin-23, Interleukin-17.
• Immune dysregulation as a central concept.

Causes

• Genetic Factors: Family history, NOD2 gene mutation.
• Environmental Factors: Western diet, smoking (increases risk and flare-ups).

Ulcerative Colitis (UC)

Key Characteristics

• Limited to the Colon (large intestine); continuous inflammation starting from rectum.
• Rectum always involved; spreads upwards.

Symptoms

• Bloody diarrhea (hematochezia).
• Left lower quadrant pain.
• Tenesmus: sensation of incomplete bowel evacuation.

Pathology

• Submucosal ulcers (limited to mucosa and submucosa).
• No granulomas.

Immunological Factors

• Predominantly Th2 cells.
  • Release cytokines: TNF alpha, Interleukin-4, Interleukin-5, Interleukin-13.
• Immune dysregulation similar to CD.

Causes

• Genetic Factors: Family history, potential HLA mutations (e.g., DRB1).
• Environmental Factors: Western diet, smoking (decreases flare-ups in UC).

Complications

Crohn's Disease

• Malabsorption: Decreased fat absorption, leading to fat-soluble vitamin deficiencies (A, D, E, K), weight loss.
• Steatorrhea: Greasy, foul-smelling stools.
• Nephrolithiasis: Kidney stones due to increased oxalate absorption.
• Cholelithiasis: Gallstones due to decreased bile acids.
• Fistulas and Abscesses: Enterovesicular, enteroenteric, or enterocutaneous fistulas; perianal abscesses.
• Small Bowel Obstruction (SBO): Due to strictures in ileum.

Ulcerative Colitis

• Toxic Megacolon: Massive colitis leading to dilated colon (>6 cm), possible perforation.
• Colorectal cancer: Increased risk; need regular colonoscopies.

Extraintestinal Manifestations (Both UC and CD)

• Joint Pain: Arthralgia, spondylitis, sacroiliitis.
• Eye Inflammation: Uveitis.
• Skin Conditions: Pyoderma gangrenosum, erythema nodosum.
• Venous Thromboembolism (VTE): Due to hypercoagulability.
• Primary Sclerosing Cholangitis (PSC): Often associated with UC.

Diagnosis

Crohn's Disease

• Initial Assessment: Localize pain (right lower quadrant), look for extraintestinal symptoms, consider complications (fistulas, malabsorption, etc.).
• Diagnostic Tests:
  • Barium Small Bowel Follow Through: Can show string sign, not very specific.
  • Ileocolonoscopy with Biopsy: Skip lesions, cobblestoning, granulomas, and transmural ulcers confirming CD.
• Flare-up Identification:
  • Abdominal X-ray: Check for SBO.
  • Fecal Calprotectin, ESR, CRP: Elevated levels indicate inflammation.
  • Stool Culture, Ova and Parasite, C. diff Assay: Rule out infections.

Ulcerative Colitis

• Initial Assessment: Localize pain (left lower quadrant), look for hematochezia and tenesmus, consider extraintestinal symptoms.
• Diagnostic Tests:
  • Barium Enema: Shows lead pipe sign (avoid if toxic megacolon suspected).
  • Colonoscopy with Biopsy: Continuous lesions from rectum, submucosal ulcers, no granulomas.
• Flare-up Identification:
  • Abdominal X-ray: Rule out toxic megacolon.
  • Fecal Calprotectin, ESR, CRP: Elevated levels indicate inflammation.
  • Stool Culture, Ova and Parasite, C. diff Assay: Rule out infections.

Treatment

Crohn's Disease

• Mild to Moderate:
  • Colonic Involvement: 5-ASA (Mesalamine, Sulfasalazine).
  • Ileal Involvement: Oral budesonide.
• Moderate to Severe:
  • Induction: Oral prednisone.
  • Remission: 6-Mercaptopurine or Azathioprine (consider infliximab).
• Severe/Refractory:
  • Induction: IV Methylprednisolone or Infliximab.
  • Remission: Infliximab (consider Vedalizumab or Ustekinumab).
• Surgical: For fistulas, abscesses, strictures; Colorectal cancer surveillance every 1-3 years after 8 years post-diagnosis.

Ulcerative Colitis

• Mild to Moderate:
  • Treatment: Rectal 5-ASA, Multimatrix Budesonide.
• Moderate to Severe:
  • Induction: Oral prednisone.
  • Remission: 6-Mercaptopurine or Azathioprine (consider infliximab).
• Severe/Refractory:
  • Induction: IV Methylprednisolone or Infliximab.
  • Remission: Infliximab (consider Vedalizumab).
• Surgical: Hemicolectomy for toxic megacolon, cancer, perforations (curative for UC).

Recap

1. Induction Agents (for both CD and UC): 5-ASA, steroids, anti-TNF agents.
2. Maintenance Therapies: 5-ASA, anti-metabolites, anti-TNF agents, anti-integrins, anti-interleukin-1223.

Always monitor and reassess treatment effectiveness and modify as necessary based on patient response and progression.