====== Inflammatory Bowel Disease (IBD) ======

Inflammatory Bowel Disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract.

Major subtypes:
  * Crohn Disease
  * Ulcerative Colitis

IBD is characterized by inappropriate immune activation against intestinal microbiota in genetically susceptible individuals.

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===== Core Pathophysiology =====

IBD results from:

  * Disrupted epithelial barrier function
  * Dysregulated innate immunity
  * Pathologic T-cell activation
  * Cytokine-driven inflammation

Central inflammatory mediators:

  * TNF-α
  * IL-12
  * IL-23
  * IL-17
  * IL-13 (more prominent in UC)

Chronic inflammation leads to:

  * Ulceration
  * Edema
  * Fibrosis (Crohn)
  * Continuous mucosal injury (UC)

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===== Immunologic Distinction: Crohn vs Ulcerative Colitis =====

Although both are immune-mediated diseases, the dominant pathways differ.

==== Crohn Disease – Th1 / Th17 Dominant ====

Primary drivers:

  * Th1 cells
  * Th17 cells

Key cytokines:
  * TNF-α
  * IFN-γ
  * IL-12
  * IL-23
  * IL-17

Mechanism:

  IL-12 and IL-23 promote Th1/Th17 differentiation →
  Macrophage and neutrophil recruitment →
  Transmural inflammation.

Clinical consequences:
  * Fistulas
  * Abscesses
  * Strictures
  * Deep ulceration

Therapeutic targets:
  * [[immunology:biologics:infliximab|Infliximab]]
  * [[immunology:biologics:adalimumab|Adalimumab]]
  * [[immunology:biologics:ustekinumab|Ustekinumab]]

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==== Ulcerative Colitis – Th2-Like Cytokine Pattern ====

Primary features:

  * Th2-like immune activation
  * IL-5 and IL-13 predominance

Key cytokines:
  * IL-13
  * IL-5
  * TNF-α

Mechanism:

  IL-13-mediated epithelial injury →
  Barrier dysfunction →
  Superficial mucosal inflammation.

Clinical consequences:
  * Continuous lesions
  * Mucosal-only disease
  * Bloody diarrhea

Therapeutic targets:
  * Anti-TNF agents
  * [[immunology:biologics:vedolizumab|Vedolizumab]] (gut-selective)

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===== Crohn vs Ulcerative Colitis Comparison =====

^ Feature ^ Crohn Disease ^ Ulcerative Colitis ^
| Location | Anywhere mouth → anus | Colon only |
| Pattern | Skip lesions | Continuous |
| Depth | Transmural | Mucosal only |
| Fistulas | Common | Rare |
| Strictures | Common | Rare |
| Bloody diarrhea | Less common | Common |
| Cancer risk | Increased | Increased (higher with duration) |

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===== Clinical Presentation =====

Common symptoms:
  * Chronic diarrhea
  * Abdominal pain
  * Weight loss
  * Fatigue

Crohn-specific:
  * Perianal disease
  * Fistulas
  * Obstruction

UC-specific:
  * Bloody diarrhea
  * Tenesmus

Extraintestinal manifestations:
  * Arthritis
  * Uveitis
  * Erythema nodosum
  * Primary sclerosing cholangitis

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===== Treatment Strategy =====

Goals:
  * Induce remission
  * Maintain remission
  * Prevent complications
  * Minimize steroid exposure

Therapy depends on disease severity and phenotype.

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===== Pharmacologic Management =====

==== 1. Mild Disease (Primarily Ulcerative Colitis) ====

Aminosalicylates:

  * [[gastroenterology:drugs:mesalamine|Mesalamine]]
  * [[gastroenterology:drugs:sulfasalazine|Sulfasalazine]]

Mechanism:
  Local suppression of prostaglandins and leukotrienes in colonic mucosa.

Limited efficacy in Crohn disease.

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==== 2. Induction Therapy (Moderate–Severe Flares) ====

Corticosteroids:

  * [[endocrine:drugs:prednisone|Prednisone]]
  * [[endocrine:drugs:methylprednisolone|Methylprednisolone]]
  * [[endocrine:drugs:budesonide|Budesonide]] (GI-targeted)

Mechanism:
  Broad suppression of cytokine transcription.

Not used for maintenance due to:

  * HPA axis suppression
  * Osteoporosis
  * Infection risk

See:
  * [[endocrine:drug_classes:corticosteroids|Corticosteroids]]

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==== 3. Maintenance Therapy ====

Immunomodulators:

  * [[immunology:drugs:azathioprine|Azathioprine]]
  * [[immunology:drugs:mercaptopurine|6-Mercaptopurine]]
  * [[immunology:drugs:methotrexate|Methotrexate]]

Mechanism:
  Suppress lymphocyte proliferation.

Used as:
  * Steroid-sparing agents
  * Maintenance therapy

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==== 4. Biologic Therapy (Moderate–Severe Disease) ====

Anti-TNF agents:
  * [[immunology:biologics:infliximab|Infliximab]]
  * [[immunology:biologics:adalimumab|Adalimumab]]

Anti-IL-12/23:
  * [[immunology:biologics:ustekinumab|Ustekinumab]]

Anti-integrin (gut selective):
  * [[immunology:biologics:vedolizumab|Vedolizumab]]

Mechanisms:

  * TNF blockade reduces inflammatory cascade.
  * IL-12/23 blockade suppresses Th1/Th17 differentiation.
  * Integrin blockade prevents leukocyte trafficking to gut.

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===== Complications =====

Crohn:
  * Fistulas
  * Abscesses
  * Obstruction
  * Malnutrition

Ulcerative Colitis:
  * Toxic megacolon
  * Severe hemorrhage
  * Colorectal cancer (long-standing disease)

Both:
  * Anemia
  * Thromboembolism
  * Osteoporosis (steroid-related)

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===== High-Yield Pearls =====

  * Crohn = Th1/Th17 dominant → transmural inflammation.
  * UC = Th2-like cytokine pattern → mucosal-only disease.
  * TNF-α is central in both diseases.
  * Steroids induce remission but do not maintain it.
  * IL-12/23 pathway is especially important in Crohn.
  * Long-standing UC increases colorectal cancer risk.