Crohn’s Disease — MD-Level Note (based on Harrison’s Principles of Internal Medicine)

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Video on Chron’s Disease (sensitizer)

Crohn’s disease (CD) is a chronic, relapsing inflammatory bowel disease (IBD) characterized by:

• Transmural inflammation
• Segmental (“skip”) involvement
• Can affect any part of GI tract (mouth → anus), most commonly:
  • Terminal ileum ± colon

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🧬 Etiopathogenesis

1. Genetic Susceptibility

• Strong association with:
  • NOD2 (CARD15) mutation
• Other genes: ATG16L1, IL23R
• Family clustering common

2. Immune Dysregulation

• Predominantly Th1 and Th17 mediated response
• ↑ Cytokines:
  • TNF-α, IL-12, IL-23
• Impaired regulatory T-cell function

3. Microbiome Interaction

• Dysbiosis with abnormal response to gut flora
• Loss of tolerance to commensals

4. Environmental Factors

• Smoking (↑ risk, worse prognosis)
• NSAIDs, infections, diet

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🧠 Pathology

Gross Features

• Skip lesions
• Cobblestone appearance
• Strictures (“string sign”)
• Creeping fat

Microscopy

• Transmural inflammation
• Non-caseating granulomas (not always present)
• Lymphoid aggregates
• Fissuring ulcers → fistula formation

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📍 Distribution Patterns

• Ileocolonic (most common)
• Isolated ileal
• Isolated colonic
• Upper GI involvement (rare but important)

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⚠️ Clinical Features

Intestinal Symptoms

• Chronic diarrhea (may be non-bloody)
• Abdominal pain (RLQ common)
• Weight loss, malnutrition
• Fever during flares

Complications

• Strictures → obstruction
• Fistulas:
  • Enteroenteric
  • Enterocutaneous
  • Perianal (hallmark)
• Abscess formation

Extraintestinal Manifestations

• Joints: peripheral arthritis, ankylosing spondylitis
• Skin: erythema nodosum, pyoderma gangrenosum
• Eyes: uveitis, episcleritis
• Hepatobiliary: PSC (less common than in UC)

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🔎 Diagnosis

1. Endoscopy (Gold Standard)

• Patchy inflammation
• Aphthous ulcers → deep linear ulcers
• Cobblestone mucosa

2. Imaging

• MR enterography preferred
• CT for complications
• Barium:
  • String sign

3. Histology

• Transmural inflammation
• Granulomas (supportive, not mandatory)

4. Laboratory Findings

• ↑ CRP, ESR
• Anemia (iron deficiency, chronic disease)
• Hypoalbuminemia
• Fecal calprotectin ↑

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🧾 Differential Diagnosis

• Ulcerative colitis
• Intestinal tuberculosis (important in Nepal)
• Infectious enterocolitis
• Ischemic colitis

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🧑‍⚕️ Disease Classification

Montreal Classification

• Age at diagnosis (A1–A3)
• Location (L1–L4)
• Behavior:
  • B1: inflammatory
  • B2: stricturing
  • B3: penetrating

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💊 Management (Step-Up vs Top-Down Approach)

1. Induction Therapy

Mild–Moderate

• Budesonide (ileocecal disease)
• 5-ASA (limited role in CD)

Moderate–Severe

• Systemic corticosteroids

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2. Maintenance Therapy

• Thiopurines (azathioprine, 6-MP)
• Methotrexate
• Biologics:
  • Anti-TNF:
    • Infliximab
    • Adalimumab
  • Anti-integrin:
    • Vedolizumab
  • Anti-IL-12/23:
    • Ustekinumab

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3. Surgical Management

• Not curative (unlike UC)
• Indications:
  • Obstruction
  • Fistula
  • Abscess
  • Refractory disease

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🚨 Complications

• Short bowel syndrome
• Malabsorption (B12 deficiency)
• Colorectal cancer (less than UC but still increased risk)
• Osteoporosis (steroid use)

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📊 Prognosis

• Chronic relapsing course
• Majority require surgery at some point
• Smoking cessation improves outcomes significantly

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🧠 High-Yield Harrison Pearls

• Transmural + skip lesions = Crohn’s
• Perianal disease strongly suggests CD
• Granulomas: specific but not sensitive
• Surgery is not curative
• Anti-TNF revolutionized management