Inflammatory Bowel Disease

Overview

IBD = 2 idiopathic bowel diseases, similar but DISTINCT morphology:

• Crohn’s disease (regional enteritis) — TRANSMURAL, non-caseating granulomatous inflammation, mostly terminal ileum±colon (any GI segment possible)
• Ulcerative colitis — mucosal+submucosal, chiefly rectum+descending colon (sometimes whole colon)

Both: systemic involvement possible (polyarthritis, uveitis, AS, skin lesions, hepatic disease). Peak 2nd-3rd decade, slight female predominance.

Etiopathogenesis — 3 converging factor groups

1. Genetic: 3-20x ↑1st-degree relative incidence (epithelial barrier defect). MZ twin concordance ~50% overall (Crohn’s ~60%, UC only ~6% — striking asymmetry, Crohn’s more genetic). Loci: 16q,12p,6p,14q,5q. CARD15 (16q) mutation → 50x Crohn’s risk. HLA: UC=DRB1; Crohn’s=DR7/DQ4.

2. Immunologic: Normal CD4+ T cells (IL-10, TGF-β) suppress response to dietary Ag/commensal flora. IBD: this suppression DEFECTIVE → uncontrolled inflammation. Mouse models confirm multiple routes (cytokine deletion, T-cell recognition deletion, barrier disruption).

KEY: 2 CD4+ subtypes drive the 2 diseases differently:

• TH1 (IFN-γ, TNF, via IL-12) → TRANSMURAL granulomatous inflammation = Crohn’s
• TH2 (IL-4, IL-5, IL-13) → SUPERFICIAL mucosal inflammation = UC

This ONE distinction is the mechanistic root of different depth of involvement.

3. Exogenous: microbial candidates unproven (M. paratuberculosis, Salmonella, Shigella, Helicobacter, Clostridia, Bacteroides, E.coli, measles). Psychosocial stress (exacerbates). SMOKING (Crohn’s specifically). OCPs (↑Crohn’s risk, NOT UC).

Consensus: genetically predisposed + host factors → dysregulated mucosal immunity, modified by environment.

Morphology

Crohn’s disease

Mostly 15-25cm terminal ileum, →caecum/ascending colon.

Gross: multiple SEGMENTAL involvement, “SKIP AREAS.” Thick hard wall = “HOSE-PIPE” appearance. Serosal granulomas. Narrowed lumen. SERPIGINOUS ulcers, swollen intervening mucosa = “COBBLESTONE” appearance. Deep fissures possible.

Micro:

1. TRANSMURAL chronic infiltrate (lymphocytes/plasma cells/macrophages) — classic feature
2. NON-CASEATING sarcoid-like granulomas, ALL layers, 60% of cases (± nodes)
3. Patchy ulceration ± deep fissures
4. Submucosal widening (oedema+lymphoid aggregates)
5. Chronic: prominent fibrosis all layers, disrupts muscle coat

Ulcerative colitis

Begins RECTUM, CONTINUOUS extension upward (sigmoid→descending→transverse→whole colon). Backwash ileitis ~10%.

Gross: CONTINUOUS, NO skip areas (key contrast). Linear superficial ulcers, usually not through muscularis. Intact mucosa = pseudopolyps. Muscle thickens (contraction) → shortened/narrowed, lost haustra = “GARDEN-HOSE” appearance.

Micro — alternating active/resolving phases. Active phase:

1. Crypt distortion, cryptitis, CRYPT ABSCESSES
2. Marked capillary congestion/dilatation/haemorrhage
3. SUPERFICIAL ulceration, usually not through muscle (except severe); nonspecific infiltrate
4. ↓↓Goblet cells in active disease
5. Mucosal regeneration+mucin depletion
6. LONGSTANDING: dysplasia (mild→marked) → CIS → frank adenocarcinoma

Comparison

Complications

Crohn’s: malabsorption (fat/B12/protein/electrolytes), FISTULA (internal/external — enterocutaneous, rectal, anal), STRICTURE (fibrosis), malignancy RARER than UC but LYMPHOMA relatively more common than adenocarcinoma.

UC: TOXIC MEGACOLON (thin-walled dilated, perforation/peritonitis risk, deep infiltrate disrupting muscle), rare perianal fistula, CARCINOMA risk after >10yr disease, stricture ALMOST NEVER (contrast Crohn’s).

Clinical relevance

TH1 vs TH2 split = mechanistic fact explaining nearly EVERY morphologic difference — TH1’s transmural granulomatous response → deep fissures/transmural fibrosis/strictures (Crohn’s); TH2’s superficial response → stays crypt-level, no deep scarring (UC). Use as organising principle, not memorise table as unrelated facts. Skip areas vs continuous = most useful bedside/endoscopic discriminator, follows logically from inflammation depth — transmural patchy process (Crohn’s) → discontinuous segments; superficial process starting fixed point (rectum) progressing proximally (UC) → continuous. Complication profile (fistulas/strictures in Crohn’s vs toxic megacolon in UC) traces back to same depth-of-involvement fact — nearly entire clinical picture derivable from ONE anatomic fact. Cancer risk timing differs: UC’s risk well-defined by DURATION (>10yr, drives surveillance protocol); Crohn’s risk rarer/less predictable, lymphoma more notable — direct surveillance strategy implications.

Overview

“Inflammatory bowel disease (IBD)” covers two idiopathic bowel diseases sharing many features but with genuinely distinctive morphology:

• Crohn’s disease (regional enteritis) — idiopathic chronic ulcerative IBD with transmural, non-caseating granulomatous inflammation, most often affecting the terminal ileum and/or colon (any GI segment can be involved).
• Ulcerative colitis — idiopathic acute-and-chronic ulceroinflammatory colitis, primarily mucosal and submucosal, chiefly affecting rectum and descending colon (sometimes the entire colon).

Both may show systemic involvement (polyarthritis, uveitis, ankylosing spondylitis, skin lesions, hepatic disease). Peak onset 2nd–3rd decades; slight female preponderance.

Etiopathogenesis — Three Converging Factor Groups

1. Genetic factors:

• 3–20× higher incidence in first-degree relatives (from a genetic defect diminishing epithelial barrier function).
• Monozygotic twin concordance ~50% overall (Crohn’s ~60%, ulcerative colitis only ~6% — a striking asymmetry suggesting Crohn’s has a stronger genetic component).
• Predisposing loci: chromosomes 16q, 12p, 6p, 14q, 5q. CARD15 (16q) mutation → 50× higher Crohn’s risk.
• HLA associations: ulcerative colitis with HLA-DRB1; Crohn’s with HLA-DR7/DQ4.

2. Immunologic factors:

• Normally, CD4+ T cells secreting anti-inflammatory cytokines (IL-10, TGF-β) suppress the immune response to dietary antigens/commensal flora. In IBD, this suppression mechanism is defective, permitting uncontrolled inflammation.
• Transgenic mouse models confirm multiple routes to IBD-like disease: deleting inhibitory cytokines/receptors, deleting T-cell recognition molecules, or disrupting epithelial barrier function directly.
• Two CD4+ T-cell subtypes drive the two diseases differently: TH1 cells (IFN-γ, TNF, via IL-12) → transmural granulomatous inflammation of Crohn’s; TH2 cells (IL-4, IL-5, IL-13) → superficial mucosal inflammation of ulcerative colitis. This single immunologic distinction is the mechanistic root of the two diseases’ different depth of involvement.

3. Exogenous/environmental factors: microbial candidates without definitive proof (M. paratuberculosis, Salmonella, Shigella, Helicobacter, Clostridia, Bacteroides, E. coli, measles virus); psychosocial stress (exacerbates symptoms, associated with greater functional impairment); smoking (implicated in Crohn’s specifically); oral contraceptives (raised Crohn’s risk with long-term use, no similar link for ulcerative colitis).

Consensus model: in a genetically predisposed individual, exogenous/endogenous host factors dysregulate mucosal immune function, further modified by environmental exposures.

Morphology

Crohn’s Disease

Most commonly affects 15–25 cm of terminal ileum, extending into caecum/ascending colon.

Gross: multiple, well-demarcated segmental involvement with intervening normal “skip areas”; thick, hard bowel wall — “hose-pipe” appearance; serosa studded with minute granulomas; markedly narrowed lumen. Mucosa shows serpiginous ulcers, with swollen intervening surviving mucosa producing a “cobblestone” appearance; deep fissures may penetrate the wall.

Micro:

1. Transmural chronic inflammatory infiltrate (lymphocytes, plasma cells, macrophages) — the classic microscopic feature.
2. Non-caseating, sarcoid-like granulomas in all layers in 60% of cases, sometimes in regional nodes too.
3. Patchy mucosal ulceration, sometimes deep fissures, with lymphoplasmacytic infiltrate.
4. Submucosal widening from oedema and lymphoid aggregates.
5. In chronic disease, prominent fibrosis across all layers, disrupting the muscular coat.

Ulcerative Colitis

Classically begins in the rectum, extending continuously upward through sigmoid, descending, transverse colon, sometimes the entire colon; colonic content backflow into the terminal ileum (“backwash ileitis”) occurs in ~10%.

Gross: continuous involvement, no skip areas (the defining contrast with Crohn’s). Linear, superficial ulcers, usually not penetrating the muscularis; intact intervening mucosa forms inflammatory pseudopolyps. Muscle layer thickens from contraction, shortening/narrowing the colon and losing haustral folds — “garden-hose” appearance.

Micro — alternating “active disease” and “resolving colitis” phases (reflecting remission/exacerbation). Active-phase features:

1. Crypt distortion, cryptitis, crypt abscesses (focal neutrophil accumulation).
2. Marked mucosal capillary congestion/dilatation/haemorrhage.
3. Superficial ulceration, usually not penetrating the muscle coat (except severe cases); nonspecific lymphoplasmacytic/neutrophilic/eosinophilic/mast cell infiltrate in the lamina propria.
4. Markedly diminished goblet cells in active disease.
5. Mucosal regeneration and mucin depletion.
6. Longstanding disease: epithelial dysplasia (mild → marked), sometimes progressing to carcinoma in situ and frank adenocarcinoma.

Crohn’s vs Ulcerative Colitis — Full Comparison

Complications

Crohn’s disease: malabsorption (fat, B12, protein, electrolytes — from diseased small bowel); fistula formation (internal — interloop; external — enterocutaneous, rectal, anal); stricture (chronic fibrosis); malignancy is a rarer late complication than in ulcerative colitis, but when it occurs, lymphoma is relatively more frequent than adenocarcinoma.

Ulcerative colitis: toxic megacolon (fulminant colitis) — thin-walled, dilated colon prone to perforation and faecal peritonitis, with deep inflammatory infiltrate disrupting the muscle layer; rare perianal fistula; carcinoma risk rises after >10 years of disease; stricture formation almost never occurs (a genuine contrast with Crohn’s).

Clinical Relevance

• The TH1-versus-TH2 immunologic split is the single mechanistic fact that explains nearly every morphologic difference between the two diseases — TH1’s transmural granulomatous response naturally produces deep fissures, transmural fibrosis, and strictures (Crohn’s), while TH2’s superficial mucosal response naturally stays confined to crypt-level injury without deep scarring (ulcerative colitis) — this is worth using as the organising principle rather than memorising the comparison table as unrelated facts.
• Skip areas versus continuous involvement is the single most useful gross/endoscopic discriminator at the bedside, and it follows logically from the different depth of inflammation — a transmural, patchy immune process (Crohn’s) naturally produces discontinuous segmental disease, while a superficial process starting at a fixed point (the rectum) and progressing proximally (ulcerative colitis) naturally produces continuous involvement.
• The complication profile split — fistulas/strictures in Crohn’s (transmural, fibrosing) versus toxic megacolon in ulcerative colitis (superficial but capable of sudden severe dilatation) — again traces directly back to depth of bowel wall involvement, reinforcing that nearly the entire clinical picture of both diseases can be derived from that one anatomic fact.
• Cancer risk timing differs meaningfully: ulcerative colitis’s risk is well-defined by disease duration (>10 years), driving a standard surveillance colonoscopy protocol, while Crohn’s malignancy risk is rarer and less predictably timed, with lymphoma being the relatively more notable malignant complication — this distinction has direct implications for surveillance strategy in the two diseases.

• TH1 vs TH2 immune response as the root cause branching into Crohn’s transmural vs UC’s superficial pathology
• Crohn’s disease vs ulcerative colitis: full gross and microscopic comparison side by side

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