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.

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)

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:

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
Vedolizumab (gut-selective)

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)

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

Treatment Strategy

Goals:

Induce remission
Maintain remission
Prevent complications
Minimize steroid exposure

Therapy depends on disease severity and phenotype.

Pharmacologic Management

1. Mild Disease (Primarily Ulcerative Colitis)

Aminosalicylates:

Mechanism:

Local suppression of prostaglandins and leukotrienes in colonic mucosa.

Limited efficacy in Crohn disease.

2. Induction Therapy (Moderate–Severe Flares)

Corticosteroids:

Mechanism:

Broad suppression of cytokine transcription.

Not used for maintenance due to:

HPA axis suppression
Osteoporosis
Infection risk

See:

Corticosteroids

3. Maintenance Therapy

Immunomodulators:

Mechanism:

Suppress lymphocyte proliferation.

Used as:

Steroid-sparing agents
Maintenance therapy

4. Biologic Therapy (Moderate–Severe Disease)

Anti-TNF agents:

Anti-IL-12/23:

Ustekinumab

Anti-integrin (gut selective):

Vedolizumab

Mechanisms:

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

Complications

Crohn:

Fistulas
Abscesses
Obstruction
Malnutrition

Ulcerative Colitis:

Toxic megacolon
Severe hemorrhage
Colorectal cancer (long-standing disease)

Both:

Anemia
Thromboembolism
Osteoporosis (steroid-related)

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.