Inflammatory Bowel Disease (IBD) in Adults

SECTION 1: Clinical Overview

1.1 Summary

Inflammatory Bowel Disease (IBD) comprises a group of chronic, immune-mediated inflammatory conditions of the gastrointestinal tract, principally encompassing two distinct phenotypes: Crohn's Disease (CD) and Ulcerative Colitis (UC). These conditions share features of inappropriate mucosal immune activation against commensal gut flora in genetically susceptible individuals but differ fundamentally in their anatomical distribution, depth of inflammation, histopathological characteristics, and clinical behavior. [1,2]

Crohn's disease is characterized by transmural, granulomatous inflammation that can affect any segment of the gastrointestinal tract from mouth to anus, with a predilection for the terminal ileum (40-50% of cases) and right colon. The hallmark pathological features include discontinuous "skip lesions," non-caseating granulomas (present in 40-60% of biopsies), and a natural history progressing from inflammatory to stricturing (B2) or penetrating (B3) phenotypes. Crohn's disease frequently leads to complications including fistulae, abscesses, strictures, and perianal disease. [3,4]

Ulcerative Colitis, in contrast, is limited to the mucosal and submucosal layers of the colon and rectum, presenting with continuous inflammation that invariably involves the rectum and extends proximally without skip lesions. UC is classified by extent: proctitis (E1, 30-40%), left-sided colitis (E2, 30-40%), and extensive/pancolitis (E3, 20-30%). The characteristic histological features include crypt abscesses, crypt architectural distortion, and goblet cell depletion. [5,6]

Globally, IBD affects over 6.8 million individuals, with the highest prevalence in North America (> 0.5%), Northern Europe (> 0.3%), and increasingly in newly industrialized nations undergoing rapid westernization. The condition typically manifests in the second to fourth decades of life, with a bimodal age distribution showing a secondary peak in the sixth decade. The clinical significance of IBD lies in its progressive nature, potential for irreversible structural bowel damage, substantial impact on quality of life, increased colorectal cancer risk, and significant healthcare costs (>$30 billion annually in the United States alone). [7,8]

Contemporary management has evolved from symptom-based control toward a "treat-to-target" paradigm emphasizing endoscopic and histological healing, utilizing advanced biologic therapies and small molecules. Early intervention with disease-modifying therapies in high-risk patients can alter the natural history and prevent progression to complicated disease phenotypes. [9,10]

1.2 Key Facts

1.3 Clinical Pearls

Diagnostic Pearl: "The Rectal Sparing Rule" In Ulcerative Colitis, inflammation almost always involves the rectum. If the rectum is completely spared on endoscopy in an untreated patient, consider Crohn's disease, infectious colitis, or ischemic colitis. However, approximately 5% of UC patients may have relative rectal sparing with topical therapy, and "cecal patch" inflammation can occur in distal UC.

Examination Pearl: "Perianal Inspection is Mandatory" Always perform a thorough perianal examination in patients suspected of IBD. Complex perianal fistulae, multiple skin tags, or off-midline deep anal fissures are highly suggestive of Crohn's disease and may predate intestinal symptoms by years. Approximately 30-50% of CD patients develop perianal disease during their lifetime.

Treatment Pearl: "The Window of Opportunity" Early aggressive therapy ("Top-Down" approach) in high-risk Crohn's patients prevents progression from inflammatory (B1) to stricturing (B2) or penetrating (B3) phenotypes. The SONIC trial demonstrated that combination therapy (Infliximab + Azathioprine) achieves superior remission rates (57% vs 30% monotherapy). [14]

Pitfall Warning: "C. difficile Mimics and Triggers Flares" Never assume an IBD flare is purely immune-mediated without excluding Clostridioides difficile infection. C. diff occurs in 5-10% of hospitalized IBD patients and can mimic or trigger a flare. Treating with steroids alone in this context can lead to toxic megacolon and perforation.

Mnemonic: "CROHNS" C-ompletely transmural, R-egional (skip lesions), O-bstruction/strictures, H-ole (fistulae), N-on-caseating granulomas, S-erpentine ulcers (cobblestoning).

Emergency Pearl: "Toxic Megacolon Warning Signs" In a patient with severe colitis, a sudden disappearance of the urge to defecate or paradoxical decrease in stool frequency despite worsening systemic symptoms (fever > 38.5°C, HR > 120 bpm) indicates impending toxic megacolon. Obtain urgent plain abdominal radiograph; > 6 cm transverse colon diameter is diagnostic.

Exam Pearl: "EIM Activity Correlation" Extraintestinal manifestations follow two patterns:

• Activity-dependent (parallel bowel disease): Erythema nodosum, peripheral arthritis, aphthous ulcers, episcleritis
• Activity-independent (run separate course): Primary Sclerosing Cholangitis, Ankylosing Spondylitis, Pyoderma gangrenosum, Uveitis

Biomarker Pearl: "Calprotectin Interpretation" Fecal calprotectin > 250 μg/g strongly suggests active inflammation (sensitivity 93%, specificity 96% for IBD). Values 50-250 μg/g are indeterminate and require clinical correlation. Values less than 50 μg/g effectively exclude active IBD (negative predictive value > 95%). [15]

1.4 Why This Matters Clinically

Early Diagnosis Impact: Diagnostic delay in Crohn's disease averaging 6-12 months is associated with a significantly higher risk of stricture formation (OR 1.8), need for bowel resection (OR 2.1), and development of penetrating complications. [4]

Healthcare Burden: IBD accounts for over $30 billion in direct costs annually in the United States, primarily driven by hospitalizations (35%), biologic therapies (35%), and surgical interventions (15%). Indirect costs from disability and reduced productivity are similarly substantial.

Medico-Legal Considerations:

• Failure to screen for colorectal cancer in long-standing colitis (> 8-10 years)
• Missing bowel perforation in patients on high-dose corticosteroids (blunted peritoneal signs)
• Failure to provide VTE prophylaxis during hospitalization (3-fold increased risk)
• Missed C. difficile infection leading to inappropriate immunosuppression
• Inadequate tuberculosis screening before initiating anti-TNF therapy

Examination Relevance: IBD represents a masterclass in immunology, chronic disease management, and multi-system medicine. It is heavily tested in MRCP, FRACP, and USMLE examinations, appearing in clinical vivas, data interpretation, and clinical case scenarios.

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SECTION 2: Crohn's Disease vs Ulcerative Colitis - Comprehensive Comparison

2.1 Anatomical and Histological Differences

2.2 Depth of Inflammation

2.3 Endoscopic Appearances

2.4 Histopathological Differences

2.5 Serological Markers

Note: Serological markers should not be used alone for diagnosis but can aid in differentiating indeterminate colitis. [16]

2.6 Complications Comparison

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SECTION 3: Epidemiology

3.1 Incidence and Prevalence

Geographic Patterns:

• North-South gradient exists; higher incidence at northern latitudes (vitamin D hypothesis)
• East-West gradient emerging with Westernization of Asia and South America
• Newly industrialized countries (China, India, Brazil) show rapidly rising incidence
• Urban > Rural (OR 1.4 for CD; OR 1.2 for UC) [7,8]

3.2 Demographics Table

3.3 Risk Factors

Non-Modifiable Risk Factors:

Modifiable Risk Factors:

3.4 Protective Factors

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SECTION 4: Pathophysiology

4.1 Overview: The Four-Hit Model

IBD pathogenesis involves a complex interplay of:

1. Genetic Susceptibility: > 240 risk loci affecting barrier function, immune regulation, and autophagy
2. Environmental Triggers: Diet, smoking, medications, infections
3. Gut Microbiome Dysbiosis: Reduced diversity, loss of protective commensals
4. Immune Dysregulation: Inappropriate activation against commensal flora

4.2 Step 1: Genetic Susceptibility and Barrier Defects

Key Genetic Pathways:

Barrier Dysfunction:

• Paneth Cell Defects: In CD, NOD2 and ATG16L1 mutations impair Paneth cell secretion of α-defensins, antimicrobial peptides that normally control gut bacterial populations
• Tight Junction Failure: TNF-α and IFN-γ downregulate claudin-1, occludin, and ZO-1, increasing paracellular permeability ("leaky gut")
• Mucin Layer Deficiency: UC shows reduced MUC2 production and thinner mucus layer; CD shows altered MUC1 expression

4.3 Step 2: Microbiome Dysbiosis

Characteristics of IBD Dysbiosis:

• Reduced microbial diversity (30-50% reduction in species)
• Loss of protective commensals (Firmicutes, especially Faecalibacterium prausnitzii)
• Expansion of pathobionts (Enterobacteriaceae, adherent-invasive E. coli)
• Reduced short-chain fatty acid (SCFA) production (butyrate, propionate)

Molecular Consequences:

• Adherent-invasive E. coli (AIEC) colonizes ileal mucosa in 40% of CD patients
• Loss of butyrate reduces colonocyte nutrition and anti-inflammatory signaling
• Pathobionts activate pattern recognition receptors (TLR4, TLR5, NOD2)
• Reduced regulatory signals from commensal metabolites

4.4 Step 3: Innate Immune Activation

Antigen Presentation:

• Luminal antigens cross compromised epithelium
• Dendritic cells (DCs) in lamina propria capture antigens
• DCs migrate to mesenteric lymph nodes and present to naive T cells
• In IBD, DCs are hyperactivated and produce excessive IL-12 and IL-23

Macrophage Activation:

• Resident macrophages become pro-inflammatory (M1 phenotype)
• Secrete TNF-α, IL-1β, IL-6, and reactive oxygen species
• TNF-α is central to IBD pathogenesis (validated therapeutic target)
• Tissue-resident memory macrophages perpetuate chronic inflammation

Complement and Neutrophils:

• Alternative complement pathway activation produces C3a and C5a
• Neutrophils recruited via IL-8 and C5a gradients
• Neutrophil elastase and myeloperoxidase cause tissue damage
• Cryptitis and crypt abscesses result from neutrophil infiltration

4.5 Step 4: Adaptive Immune Polarization

Crohn's Disease - Th1/Th17 Dominant:

Ulcerative Colitis - Th2-like/Th9:

Lymphocyte Trafficking:

• Activated gut-homing T cells express α4β7 integrin
• α4β7 binds MAdCAM-1 on intestinal endothelium
• This selective homing is the target of vedolizumab therapy
• Memory T cells recirculate and maintain chronic inflammation

4.6 Step 5: Tissue Damage and Fibrosis

Destructive Phase:

• Matrix metalloproteinases (MMP-2, MMP-9, MMP-13) degrade extracellular matrix
• Fissuring ulcers extend through bowel wall in CD
• Deep ulceration creates tracts for fistula formation

Fibrogenic Phase (Crohn's Disease):

• TGF-β activates intestinal fibroblasts and myofibroblasts
• Excessive collagen I, III, and IV deposition
• Stricture formation (often irreversible, requiring surgical intervention)
• "Creeping fat" (mesenteric adipose hypertrophy unique to CD)

Point of No Return:

• Inflammatory (B1) phenotype → Stricturing (B2) or Penetrating (B3)
• This progression is time-dependent (50% progress within 10 years)
• Early biologic therapy may prevent phenotype progression

4.7 Classification Systems

Montreal Classification for Crohn's Disease:

Montreal Classification for Ulcerative Colitis:

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SECTION 5: Clinical Presentation

5.1 Symptoms

Crohn's Disease:

Ulcerative Colitis:

5.2 Atypical Presentations

5.3 Physical Signs

General Examination:

Abdominal Examination:

Perianal Examination (Mandatory):

Extraintestinal Manifestations:

5.4 Red Flags

[!CAUTION] RED FLAGS - Require Immediate Action:

• Abdominal Rigidity: Board-like abdomen indicates peritonitis/perforation
• High Fever (> 39°C): Intra-abdominal abscess, fulminant colitis
• Inability to Pass Flatus/Feces: Complete mechanical obstruction
• Massive Hematochezia: > 6 units blood/24h, hemodynamic instability
• Altered Mental Status: Sepsis, severe electrolyte disturbance
• Colonic Diameter > 6 cm: Toxic megacolon
• Tachycardia > 120 bpm + Fever: Systemic inflammatory response
• Paradoxical Improvement: Decrease in stool frequency with worsening vital signs (impending megacolon)

5.5 Disease Activity Scoring

Truelove and Witts Criteria (Acute Severe UC):

Severe = ≥6 bloody stools + 1 systemic feature

Mayo Score for UC (0-12):

• Stool frequency (0-3)
• Rectal bleeding (0-3)
• Endoscopic findings (0-3)
• Physician global assessment (0-3)

Crohn's Disease Activity Index (CDAI):

• Complex calculation including liquid stools, abdominal pain, general well-being, complications, antidiarrheal use, abdominal mass, hematocrit, body weight
• less than 150: Remission
• 150-220: Mild disease
• 220-450: Moderate disease

• 450: Severe disease

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SECTION 6: Investigations

6.1 Diagnostic Algorithm

┌──────────────────────────────────────────────────────────────────┐
│              IBD DIAGNOSTIC ALGORITHM                             │
└──────────────────────────────────────────────────────────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │   CLINICAL SUSPICION OF IBD   │
              │   (Chronic diarrhea > 4 weeks  │
              │   ± blood, pain, weight loss) │
              └───────────────────────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │        INITIAL WORKUP         │
              │  • Stool calprotectin         │
              │  • Stool microscopy/culture   │
              │  • C. difficile toxin         │
              │  • FBC, CRP, albumin          │
              │  • Ferritin, B12, folate      │
              └───────────────────────────────┘
                              │
            ┌─────────────────┼─────────────────┐
            │                 │                 │
            ▼                 ▼                 ▼
   ┌────────────────┐ ┌────────────────┐ ┌────────────────┐
   │ Calprotectin   │ │ Calprotectin   │ │ Calprotectin   │
   │    less than 50 μg/g    │ │   50-250 μg/g  │ │   > 250 μg/g    │
   └────────────────┘ └────────────────┘ └────────────────┘
            │                 │                 │
            ▼                 ▼                 ▼
     IBD unlikely       Clinical judgment    Likely IBD
     Consider IBS       Repeat or scope      Proceed to
                                             endoscopy
                              │
                              ▼
              ┌───────────────────────────────┐
              │    ILEOCOLONOSCOPY WITH       │
              │    MULTIPLE SEGMENTAL         │
              │    BIOPSIES (GOLD STANDARD)   │
              │   • ≥2 biopsies from 5 sites  │
              │   • Include terminal ileum    │
              └───────────────────────────────┘
                              │
         ┌────────────────────┼────────────────────┐
         ▼                    ▼                    ▼
  ┌─────────────┐      ┌─────────────┐      ┌─────────────┐
  │   Normal    │      │     UC      │      │     CD      │
  │ Endoscopy   │      │  Features   │      │  Features   │
  └─────────────┘      └─────────────┘      └─────────────┘
         │                    │                    │
         ▼                    ▼                    ▼
   Consider:            Confirm extent       Small bowel
   - Microscopic        with biopsies        imaging:
     colitis                                 MR enterography
   - Small bowel CD                          or CT enterography
   - Other cause

6.2 Bedside and Point-of-Care Tests

6.3 Laboratory Investigations

Inflammatory Markers:

Nutritional/Metabolic:

Pre-Therapy Screening:

Serological Markers (Adjunctive):

6.4 Endoscopy

Ileocolonoscopy (Gold Standard):

• Preparation: Full bowel preparation required
• Technique: Intubation of terminal ileum essential
• Biopsies: Minimum 2 biopsies from 5 sites (ascending, transverse, descending, sigmoid, rectum) + terminal ileum
• Findings to document: Extent, severity, skip lesions, strictures, ulcer pattern

Upper GI Endoscopy:

• Indicated if upper GI symptoms present
• Aphthous ulcers, cobblestoning in stomach/duodenum suggest CD
• ~5-15% of CD has upper GI involvement

Capsule Endoscopy:

• For suspected small bowel CD when conventional imaging negative
• Contraindicated if known stricture (risk of retention)
• Patency capsule first if stricture suspected
• Sensitivity ~90% for small bowel CD lesions

Balloon Enteroscopy:

• For tissue diagnosis of small bowel lesions
• Therapeutic applications (stricture dilation, polypectomy)

6.5 Imaging

Cross-Sectional Imaging:

MR Enterography (MRE) - Preferred for CD:

Plain Abdominal Radiograph:

• First-line for suspected obstruction or toxic megacolon
• Transverse colon > 6 cm = toxic megacolon
• Small bowel dilation with air-fluid levels = obstruction

6.6 Histopathology - Diagnostic Criteria

Crohn's Disease:

• Non-caseating granulomas (40-60%, highly specific)
• Transmural lymphoid aggregates
• Patchy chronic inflammation
• Fissuring ulcers
• Submucosal fibrosis
• Neural hyperplasia

Ulcerative Colitis:

• Diffuse mucosal inflammation
• Crypt architectural distortion (branching, shortening)
• Crypt abscesses (neutrophils in crypt lumen)
• Goblet cell depletion (mucin depletion)
• Basal plasmacytosis
• No granulomas (except mucin granulomas from crypt rupture)

Indeterminate Colitis:

• 5-15% of colonic IBD cannot be definitively classified
• Re-evaluate with time and additional investigations
• May become clearer with disease evolution

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SECTION 7: Management

7.1 Management Algorithm

┌─────────────────────────────────────────────────────────────────┐
│                   IBD MANAGEMENT ALGORITHM                       │
│                (Treat-to-Target Approach)                        │
└─────────────────────────────────────────────────────────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │         CONFIRM DIAGNOSIS      │
              │  • Exclude infection (C. diff) │
              │  • Assess disease extent       │
              │  • Classify by Montreal        │
              │  • Identify risk factors       │
              └───────────────────────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │        RISK STRATIFICATION    │
              │  • Age less than 30 at diagnosis       │
              │  • Extensive disease          │
              │  • Perianal involvement       │
              │  • Deep ulcers on endoscopy   │
              │  • Steroid need at diagnosis  │
              └───────────────────────────────┘
                              │
         ┌────────────────────┼────────────────────┐
         ▼                    ▼                    ▼
  ┌─────────────┐      ┌─────────────┐      ┌─────────────┐
  │  LOW RISK   │      │ MODERATE    │      │  HIGH RISK  │
  │             │      │   RISK      │      │             │
  └─────────────┘      └─────────────┘      └─────────────┘
         │                    │                    │
         ▼                    ▼                    ▼
  ┌─────────────┐      ┌─────────────┐      ┌─────────────┐
  │  STEP-UP    │      │   EARLY     │      │  TOP-DOWN   │
  │  APPROACH   │      │  BIOLOGIC   │      │  APPROACH   │
  │  5-ASA/Bud  │      │ ± Immunomod │      │ Combo Rx    │
  └─────────────┘      └─────────────┘      └─────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │      INDUCTION THERAPY         │
              │                                │
              │  ULCERATIVE COLITIS:           │
              │  • Mild: 5-ASA (oral + topical)│
              │  • Moderate: + oral steroids   │
              │  • Severe: IV steroids         │
              │                                │
              │  CROHN'S DISEASE:              │
              │  • Mild ileal: Budesonide      │
              │  • Moderate-severe: Systemic   │
              │    steroids or biologic        │
              └───────────────────────────────┘
                              │
                              ▼
              ┌───────────────────────────────┐
              │    ASSESS RESPONSE (8-12 wks) │
              │  • Clinical (symptoms)        │
              │  • Biochemical (CRP, FCP)     │
              │  • Endoscopic (if moderate/   │
              │    severe at baseline)        │
              └───────────────────────────────┘
                              │
         ┌────────────────────┼────────────────────┐
         ▼                    ▼                    ▼
    RESPONSE           PARTIAL             NON-RESPONSE
         │             RESPONSE                   │
         │                 │                      │
         ▼                 ▼                      ▼
  ┌─────────────┐   ┌─────────────┐      ┌─────────────┐
  │ MAINTENANCE │   │  OPTIMIZE   │      │  ESCALATE   │
  │   THERAPY   │   │    DOSE     │      │   THERAPY   │
  │             │   │ Check levels│      │             │
  └─────────────┘   └─────────────┘      └─────────────┘
                                                │
                                                ▼
                           ┌─────────────────────────────────┐
                           │       ADVANCED THERAPY          │
                           │                                 │
                           │  1st biologic failure:          │
                           │  • Different mechanism class    │
                           │  • Vedolizumab (gut-selective)  │
                           │  • Ustekinumab (anti-IL-12/23)  │
                           │  • JAK inhibitor (UC)           │
                           │                                 │
                           │  Multiple failures:             │
                           │  • Surgical consultation        │
                           │  • Clinical trial               │
                           └─────────────────────────────────┘

7.2 Emergency and Acute Severe Management

Acute Severe Ulcerative Colitis (ASUC) - Medical Emergency:

Definition: ≥6 bloody stools/day PLUS ≥1 systemic feature (HR > 90, Temp > 37.8°C, Hb less than 10.5 g/dL, ESR > 30)

Day 1-3 Management:

Travis/Oxford Criteria (Day 3 Assessment):

• Stool frequency > 8/day OR
• CRP > 45 mg/L + Stool frequency 3-8/day → 85% will fail IV steroids and require rescue therapy or colectomy

Rescue Therapy Options:

Surgical Consultation:

• Should be involved from Day 1 in all ASUC
• Indications for emergency colectomy:
  • Perforation
  • Massive hemorrhage
  • Failure of rescue therapy
  • Toxic megacolon not responding to 24-72h medical therapy

7.3 Medical Management - Ulcerative Colitis

5-Aminosalicylates (First-Line for Mild-Moderate UC):

Key Point: Combined oral + topical therapy superior to either alone for left-sided disease. [12]

Corticosteroids (Induction Only):

Never use steroids for maintenance - associated with infections, osteoporosis, metabolic complications.

Immunomodulators (Maintenance):

Biologics for UC:

Small Molecules for UC:

7.4 Medical Management - Crohn's Disease

Induction Therapy:

Maintenance Therapy:

Special Situations:

7.5 Biologic Mechanisms of Action

7.6 Therapeutic Drug Monitoring

7.7 Surgical Management

Indications for Surgery in UC:

Surgical Options in UC:

Indications for Surgery in CD:

Surgical Principles in CD:

• Bowel conservation: Minimize resection length to prevent short bowel syndrome
• Strictureplasty: Preferred for jejunal/ileal strictures; avoids resection
• Primary anastomosis: Usually safe unless sepsis, malnutrition, or high-dose steroids
• Recurrence: 50% symptomatic recurrence at 5 years post-surgery; endoscopic recurrence in 70-90%

Surgical Complications:

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SECTION 8: Extraintestinal Manifestations

8.1 Overview

Extraintestinal manifestations (EIMs) occur in 25-40% of IBD patients, can precede intestinal diagnosis by years, and may cause significant morbidity independent of bowel disease. [17]

8.2 Musculoskeletal (Most Common: 20-30%)

Peripheral Arthropathy:

Axial Arthropathy:

Key Point: Axial disease runs independent of bowel activity; anti-TNF agents treat both effectively.

8.3 Dermatological (10-15%)

8.4 Ocular (2-6%)

Warning: Anterior uveitis is an ophthalmologic emergency - delay can cause permanent vision loss.

8.5 Hepatobiliary (5-15%)

PSC-IBD Phenotype:

• UC with PSC has distinct behavior (more often pancolitis, rectal sparing, backwash ileitis)
• Higher colorectal cancer risk (annual surveillance recommended)
• PSC course is independent of bowel disease
• Risk of cholangiocarcinoma: 1.5% per year

8.6 Other Extraintestinal Manifestations

Hematological:

• Anemia (most common: iron deficiency, anemia of chronic disease, B12/folate deficiency)
• Thrombocytosis (reactive)
• Venous thromboembolism (3-fold increased risk during flares)

Renal:

• Nephrolithiasis (oxalate stones in CD with steatorrhea; uric acid stones from dehydration)
• Amyloidosis (rare, secondary AA amyloid)
• Mesalamine-induced interstitial nephritis

Bone:

• Osteopenia/Osteoporosis (corticosteroids, malabsorption, chronic inflammation)
• Screen with DEXA if prolonged steroid use or postmenopausal

Pulmonary (Rare):

• Bronchiectasis
• Organizing pneumonia
• Drug-induced (methotrexate, sulfasalazine)

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SECTION 9: Complications

9.1 Immediate/Acute Complications

9.2 Late Complications

9.3 Colorectal Cancer Surveillance

Risk Factors for IBD-CRC:

• Duration of disease (> 8-10 years)
• Extensive colitis (pancolitis > left-sided > proctitis)
• Primary sclerosing cholangitis (4x additional risk)
• Family history of CRC
• Severe/persistent inflammation
• Pseudopolyps/post-inflammatory polyps

Surveillance Protocol:

Surveillance Technique:

• Chromoendoscopy (dye spray) preferred over white light
• Targeted biopsies of visible lesions
• Random biopsies if chromoendoscopy not available

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SECTION 10: Prognosis and Outcomes

10.1 Natural History

Crohn's Disease:

• Without treatment, progressive from inflammatory (B1) → stricturing (B2) → penetrating (B3)
• 50% progress to complicated phenotype within 10 years
• 40-50% require surgery within 10 years (decreasing with biologics)
• Post-surgical recurrence: 70-90% endoscopic at 1 year; 50% clinical at 5 years

Ulcerative Colitis:

• Relapsing-remitting course in majority
• 10-15% have severe unremitting course
• 10-20% colectomy rate (decreasing with biologics)
• Cure achieved with proctocolectomy (but with functional implications)

10.2 Outcomes with Modern Therapy

10.3 Prognostic Factors

Poor Prognosis in Crohn's Disease:

• Age less than 30 at diagnosis
• Perianal disease at diagnosis
• Deep ulcers on initial colonoscopy
• Need for steroids at first presentation
• Extensive small bowel involvement
• Stricturing or penetrating behavior at diagnosis
• Smoking

Poor Prognosis in Ulcerative Colitis:

• Extensive/pancolitis
• Severe disease at presentation
• Need for steroids at diagnosis
• Young age at onset
• Primary sclerosing cholangitis

10.4 Mortality

Life expectancy is near-normal with optimal management and surveillance.

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SECTION 11: Special Populations

11.1 Pregnancy and IBD

Pre-Conception:

• Optimize disease control before conception (active disease = worse outcomes)
• Continue most medications (except methotrexate - stop 3-6 months before)
• Folic acid supplementation (5mg daily if on sulfasalazine)
• Avoid conception during active flare

Medication Safety in Pregnancy:

Delivery:

• Vaginal delivery preferred unless active perianal disease
• IPAA patients: consider cesarean section to protect pouch function
• Active perianal CD: cesarean section recommended

11.2 Elderly-Onset IBD (≥60 years)

• 10-15% of IBD diagnoses
• More often UC, more often proctitis/left-sided
• Higher surgical rates due to comorbidities and delayed diagnosis
• Lower biologic efficacy observed (but still effective)
• Higher infection risk with immunosuppression (careful monitoring)
• Drug interactions with polypharmacy

11.3 IBD in Specific Scenarios

Post-Surgical Recurrence Prevention (CD):

IBD and Vaccination:

• Avoid live vaccines if on immunosuppression (MMR, varicella, live zoster, yellow fever)
• Inactivated vaccines safe and recommended (influenza, pneumococcal, COVID-19, HPV)
• Zoster vaccination (Shingrix - inactivated) recommended before starting biologics
• Check varicella IgG before immunosuppression

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SECTION 12: Guidelines Summary

12.1 Key International Guidelines

ACG Clinical Guideline: Management of Crohn's Disease in Adults (2018) [13]

• Budesonide for mild-moderate ileal CD (Grade A)
• Anti-TNF ± immunomodulator for moderate-severe CD (Grade A)
• Avoid steroids for maintenance (Grade A)
• Smoking cessation essential (Grade A)

ECCO Guidelines on Therapeutics in Ulcerative Colitis (2022) [12]

• Combined oral + topical 5-ASA for left-sided UC (Grade A)
• IV steroids for acute severe UC; rescue with infliximab or ciclosporin if Day 3 non-response
• Vedolizumab, ustekinumab, and JAK inhibitors for biologic-experienced patients

BSG Guidelines on IBD Management (2019)

• Fecal calprotectin for initial assessment
• TPMT testing before thiopurine initiation
• Annual surveillance colonoscopy in PSC-IBD

AGA Clinical Practice Guidelines on Therapeutic Drug Monitoring (2022)

• Reactive TDM recommended for loss of response
• Proactive TDM may optimize outcomes

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SECTION 13: Evidence and Landmark Trials

13.1 Landmark Trials Summary

13.2 Key Trial Details

SONIC Trial (2010) [14]

• Design: Multicenter RCT, n=508 adult CD patients naive to immunomodulators and biologics
• Arms: Infliximab + Azathioprine vs. Infliximab vs. Azathioprine
• Primary Outcome: Steroid-free remission at week 26
• Results: Combination 56.8% vs. Infliximab 44.4% vs. Azathioprine 30.0%
• Significance: Established combination therapy as gold standard for moderate-severe CD

VARSITY Trial (2019) [18]

• Design: Head-to-head RCT, n=769 moderate-severe UC
• Arms: Vedolizumab vs. Adalimumab
• Primary Outcome: Clinical remission at week 52
• Results: Vedolizumab 31.3% vs. Adalimumab 22.5%
• Significance: First head-to-head trial favoring vedolizumab for UC

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SECTION 14: Viva Preparation

14.1 Opening Statement

"Inflammatory Bowel Disease comprises chronic immune-mediated conditions of the gastrointestinal tract, principally Crohn's disease and ulcerative colitis. They differ fundamentally in distribution—Crohn's affects any part of the GI tract with transmural skip lesions, while UC is continuous mucosal inflammation of the colon starting from the rectum. Diagnosis requires ileocolonoscopy with biopsies. Management follows a treat-to-target approach using biologics and small molecules, aiming for endoscopic remission. Key trials to reference include SONIC for combination therapy and VARSITY comparing vedolizumab to adalimumab."

14.2 Common Viva Questions

Q1: How do you differentiate Crohn's disease from Ulcerative Colitis?

"I differentiate based on several key features. Distribution: Crohn's can affect any part of the GI tract with skip lesions, while UC starts at the rectum and extends proximally continuously. Depth: Crohn's is transmural, causing strictures and fistulae; UC is mucosal only. Histology: Crohn's shows non-caseating granulomas in 40-60%; UC shows crypt abscesses and architectural distortion. Serology can assist: ASCA positivity suggests Crohn's, pANCA suggests UC. Approximately 10% remain as indeterminate colitis."

Q2: A 28-year-old presents with acute severe ulcerative colitis. How do you manage them?

"This is a medical emergency. I would apply the Truelove and Witts criteria—severe disease is defined as greater than 6 bloody stools daily plus systemic features. Management includes IV hydrocortisone 100mg four times daily, IV fluids, electrolyte correction with potassium above 4.0 mmol/L, mandatory VTE prophylaxis with LMWH, C. difficile exclusion, and daily clinical assessment including stool charts, bloods, and abdominal X-ray. I would apply the Travis criteria at day 3—if stool frequency remains above 8 or CRP above 45 with 3-8 stools, rescue therapy with infliximab or ciclosporin is needed. Surgical consultation should be involved from day 1."

Q3: What are the indications for surgery in Crohn's disease?

"Surgical indications in Crohn's include emergency situations—perforation, massive hemorrhage, and abscess not amenable to drainage. Elective indications include symptomatic strictures refractory to medical therapy and endoscopic dilation, fistulizing disease not responding to biologics, medically refractory disease, and dysplasia or malignancy. The principle is bowel conservation—strictureplasty preferred over resection where possible to prevent short bowel syndrome. Post-operative prophylaxis with biologics reduces recurrence rates."

Q4: Discuss the mechanism of action of biologic therapies in IBD.

"Biologics target specific components of the inflammatory cascade. Anti-TNF agents—infliximab, adalimumab—neutralize both soluble and membrane-bound TNF-alpha, inducing T-cell apoptosis and macrophage deactivation. Vedolizumab blocks the α4β7 integrin-MAdCAM-1 interaction, preventing gut-homing lymphocyte trafficking; this provides gut-selective immunosuppression with a lower systemic infection risk. Ustekinumab blocks the p40 subunit shared by IL-12 and IL-23, inhibiting both Th1 and Th17 pathways. Newer IL-23 specific agents like risankizumab target only p19, sparing the Th1 pathway. Choice depends on patient factors, prior exposure, and safety profile."

Q5: What are the extraintestinal manifestations of IBD and how do they relate to disease activity?

"EIMs occur in 25-40% of patients. They are classified as activity-dependent or activity-independent. Activity-dependent EIMs parallel bowel inflammation and include peripheral arthritis type 1, erythema nodosum, oral aphthous ulcers, and episcleritis. These typically improve with control of intestinal disease. Activity-independent EIMs run a course separate from the bowel and include primary sclerosing cholangitis, ankylosing spondylitis, pyoderma gangrenosum, and uveitis. These require specific treatment regardless of bowel disease status. PSC-IBD has a distinct phenotype with higher colorectal cancer risk requiring annual surveillance."

14.3 Common Mistakes (What Fails Candidates)

1. Forgetting to exclude C. difficile infection in every IBD flare
2. Not prescribing VTE prophylaxis in hospitalized IBD patients
3. Using steroids for maintenance therapy
4. Missing tuberculosis screening before anti-TNF initiation
5. Failing to differentiate activity-dependent vs. independent EIMs
6. Not recognizing toxic megacolon warning signs
7. Quoting outdated surgery rates (much lower with biologics)
8. Ignoring perianal examination in suspected IBD

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SECTION 15: Patient Explanation

For Patients (Layperson Language):

"Inflammatory Bowel Disease means there's ongoing inflammation in your digestive system that your body can't properly control. Think of it like a fire alarm that keeps going off even when there's no real fire—your immune system is attacking your own gut lining by mistake.

There are two main types. In Ulcerative Colitis, the inflammation affects just the large bowel (colon) and the lining only. In Crohn's Disease, the inflammation can be anywhere from mouth to bottom and goes through the whole wall of the gut.

We don't know exactly what causes it, but it's a combination of your genes, something in the environment (like diet or infections), and changes in the bacteria that live in your gut. It's not caused by stress or anything you did wrong.

The good news is we have very effective treatments now. We start with medicines that reduce inflammation and calm down your immune system. Some people need stronger medicines called 'biologics' that target specific parts of the immune system very precisely.

Most people with IBD live normal, active lives. You'll need regular check-ups and occasionally cameras tests to make sure everything is healing. The most important things you can do are take your medicines as prescribed, don't smoke, and let us know quickly if you have a flare-up."

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SECTION 16: References

1. Torres J, Mehandru S, Colombel JF, Peyrin-Biroulet L. Crohn's disease. Lancet. 2017;389(10080):1741-1755. doi:10.1016/S0140-6736(16)31711-1

2. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389(10080):1756-1770. doi:10.1016/S0140-6736(16)32126-2

3. Gomollón F, Dignass A, Annese V, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016. J Crohns Colitis. 2017;11(1):3-25. doi:10.1093/ecco-jcc/jjw168

4. Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. The natural history of adult Crohn's disease in population-based cohorts. Am J Gastroenterol. 2010;105(2):289-297. doi:10.1038/ajg.2009.579

5. Magro F, Langner C, Driessen A, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7(10):827-851. doi:10.1016/j.crohns.2013.06.001

6. Fumery M, Singh S, Dulai PS, et al. Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clin Gastroenterol Hepatol. 2018;16(3):343-356.e3. doi:10.1016/j.cgh.2017.06.016

7. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769-2778. doi:10.1016/S0140-6736(17)32448-0

8. Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12(12):720-727. doi:10.1038/nrgastro.2015.150

9. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233

10. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD). Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031

11. Beaugerie L, Itzkowitz SH. Cancers complicating inflammatory bowel disease. N Engl J Med. 2015;372(15):1441-1452. doi:10.1056/NEJMra1403718

12. Raine T, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J Crohns Colitis. 2022;16(1):2-17. doi:10.1093/ecco-jcc/jjab178

13. Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018;113(4):481-517. doi:10.1038/ajg.2018.27

14. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383-1395. doi:10.1056/NEJMoa0904492

15. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341:c3369. doi:10.1136/bmj.c3369

16. Reese GE, Constantinides VA, Simillis C, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006;101(10):2410-2422. doi:10.1111/j.1572-0241.2006.00840.x

17. Vavricka SR, Schoepfer A, Scharl M, et al. Extraintestinal Manifestations of Inflammatory Bowel Disease. Inflamm Bowel Dis. 2015;21(8):1982-1992. doi:10.1097/MIB.0000000000000392

18. Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med. 2019;381(13):1215-1226. doi:10.1056/NEJMoa1905725

19. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541-1549. doi:10.1016/S0140-6736(02)08512-4

20. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699-710. doi:10.1056/NEJMoa1215734

21. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013;369(8):711-721. doi:10.1056/NEJMoa1215739

22. Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016;375(20):1946-1960. doi:10.1056/NEJMoa1602773

23. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017;376(18):1723-1736. doi:10.1056/NEJMoa1606910

24. Turner D, Walsh CM, Steinhart AH, Griffiths AM. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5(1):103-110. doi:10.1016/j.cgh.2006.09.033

25. Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12(4):205-217. doi:10.1038/nrgastro.2015.34

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Last Reviewed: 2026-01-09 | MedVellum Editorial Team

• Clinical Accuracy: 8/8
• Evidence Quality: 8/8
• Exam Relevance: 8/8
• Depth & Completeness: 8/8
• Structure & Clarity: 7/8
• Practical Application: 8/8
• Viva Readiness: 7/8

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