Inflammatory Bowel Disease — Pathology
Pathology · GIT & Liver · lean revision notes
Inflammatory Bowel Disease — Pathology
Inflammatory bowel disease (IBD) is a group of chronic, immune-mediated, relapsing-remitting inflammatory disorders of the gastrointestinal tract comprising Crohn disease (CD) and ulcerative colitis (UC). For NEET PG, the single most heavily examined area is the gross and microscopic distinction between the two — so this set of notes is built around that comparison while still covering aetiopathogenesis, complications, and differentials.
Definition & Classification
IBD results from an inappropriate, sustained mucosal immune response to commensal gut flora in a genetically susceptible host with a defective epithelial barrier. The two principal entities are:
- Crohn disease — transmural, granulomatous inflammation that may affect any part of the GI tract from mouth to anus, classically in a discontinuous ("skip lesion") pattern, with the terminal ileum as the favourite site.
- Ulcerative colitis — a mucosal/submucosal inflammation limited to the colon and rectum, beginning in the rectum and extending proximally in a continuous fashion.
- Indeterminate colitis — used (~10% of colectomy specimens) when features overlap and a confident CD/UC distinction cannot be made.
High-yield: Crohn = "mouth-to-anus, transmural, skip, granuloma." UC = "rectum upward, mucosal, continuous, no granuloma." Almost every NEET PG IBD MCQ hinges on one of these eight words.
Epidemiology & Risk Factors
- Both have a bimodal age distribution; peak incidence in the second to third decade, with a smaller second peak in the 60s.
- More common in Western/developed populations and in people of Ashkenazi Jewish descent.
- Smoking is the key board fact: smoking worsens Crohn disease but is protective in ulcerative colitis (UC is largely a disease of non-smokers/ex-smokers).
- Appendicectomy is protective against UC.
High-yield: Smoking → bad for Crohn, protective for UC. This single-line difference is one of the most repeated PYQs.
Aetiology & Pathophysiology
IBD pathogenesis rests on three interacting pillars: genetics, mucosal immunity, and the gut microbiome/epithelial barrier.
1. Genetics
- NOD2 (CARD15) gene on chromosome 16 — the first and most important susceptibility gene, strongly associated with Crohn disease (especially ileal, fibrostenosing disease). NOD2 senses bacterial muramyl dipeptide; loss of function impairs innate handling of intracellular bacteria.
- ATG16L1 and IRGM — autophagy genes linked to Crohn disease (defective Paneth cell function/bacterial clearance).
- IL23R polymorphisms are associated with both CD and UC.
2. Immune dysregulation
- Crohn disease is classically a Th1 / Th17 mediated process (IFN-γ, IL-12, IL-17, TNF-α), which explains the granuloma formation.
- Ulcerative colitis leans toward a Th2-like / atypical Th2 response (IL-13, IL-5).
- TNF-α is central to both — the rationale for anti-TNF biologics (infliximab, adalimumab).
3. Microbiome & barrier defect
- A defective epithelial tight-junction barrier allows luminal microbial antigens to drive a sustained, dysregulated T-cell response.
Pathogenesis flow: Genetic susceptibility (e.g., NOD2) → defective epithelial barrier / impaired bacterial clearance → abnormal exposure to commensal flora → dysregulated mucosal T-cell response (Th1/Th17 in CD, Th2 in UC) → cytokine-driven chronic inflammation → tissue injury, ulceration, fibrosis.
Gross (Macroscopic) Pathology
This is the highest-yield comparison table — memorise it cold.
| Feature | Crohn disease | Ulcerative colitis |
|---|---|---|
| Site | Anywhere mouth → anus; terminal ileum most common; rectum often spared | Colon + rectum only; rectum always involved |
| Distribution | Skip lesions (discontinuous) | Continuous (no skip areas) |
| Depth | Transmural | Mucosa + submucosa only |
| Mucosa | Cobblestone appearance, aphthous & serpentine (linear) ulcers | Broad-based ulcers, pseudopolyps, friable granular mucosa |
| Wall | Thickened, fibrotic; strictures; "creeping fat" (mesenteric fat wrapping) | Thin wall (no fibrosis); loss of haustra → "lead-pipe" colon |
| Fistulae / sinus | Common (entero-enteric, enterovesical, perianal) | Rare |
| Bowel lumen | Narrowed ("string sign" on barium) | Normal/dilated; risk of toxic megacolon |
High-yield: Creeping (crawling) fat, cobblestoning, string sign, fistulae, and skip lesions = Crohn. Pseudopolyps, lead-pipe colon, loss of haustra, and backwash ileitis = UC.
Microscopic (Histological) Pathology
| Feature | Crohn disease | Ulcerative colitis |
|---|---|---|
| Inflammation depth | Transmural lymphoid aggregates | Confined to mucosa/submucosa |
| Granulomas | Non-caseating granulomas in ~35–50% (pathognomonic when present) | Absent |
| Crypt abscesses | Less prominent | Prominent crypt abscesses (neutrophils in crypt lumen) |
| Crypt architecture | Distortion + chronic injury | Marked crypt distortion, branching, atrophy |
| Paneth cell metaplasia | May be seen | Common in left colon (metaplastic) |
| Goblet cells | Relatively preserved | Goblet cell depletion |
| Fibrosis | Marked (transmural) | Minimal |
| Lymphoid response | Transmural lymphoid aggregates ("Crohn's rosary") | Basal plasmacytosis |
High-yield: Non-caseating granuloma = Crohn (but present in only ~half of cases, so its absence does NOT exclude CD). Crypt abscess is characteristic of UC but is not specific — it can occur in CD and infective colitis too.
Mnemonic for Crohn (CD): "Cobblestones, Creeping fat, Caseating-NO (non-caseating) granuloma, Channels (fistulae), skip lesions and string sign." Mnemonic for UC: "U-C: Ulcers Continuous, Crypt abscess, Curling pseudoPolyps, Cancer risk, lead-pipe Colon."
Clinical Features
| Feature | Crohn disease | Ulcerative colitis |
|---|---|---|
| Diarrhoea | Watery, usually non-bloody | Bloody diarrhoea with mucus (hallmark) |
| Pain | Right lower quadrant (ileal), cramping | Left lower quadrant, tenesmus |
| Mass | Palpable RLQ mass possible | Uncommon |
| Perianal disease | Fistulae, fissures, abscess, tags | Rare |
| Weight loss / malabsorption | Common (ileal disease) | Less prominent |
Extraintestinal manifestations (EIMs) — frequently asked:
- Skin: erythema nodosum (more with CD), pyoderma gangrenosum (more with UC).
- Eyes: uveitis, episcleritis.
- Joints: peripheral arthritis (parallels gut activity), ankylosing spondylitis / sacroiliitis (HLA-B27, independent of gut activity).
- Hepatobiliary: primary sclerosing cholangitis (PSC) — strongly linked to UC; raises cholangiocarcinoma and colorectal cancer risk.
- Others: gallstones and oxalate renal stones (in CD with ileal resection → fat malabsorption → enteric hyperoxaluria), aphthous oral ulcers.
High-yield: PSC + IBD → think UC. PSC patients with UC need more frequent colonoscopic cancer surveillance. "PSC = pANCA-positive, beaded bile ducts, UC association."
Serology
| Marker | Association |
|---|---|
| p-ANCA (atypical/perinuclear) | More positive in ulcerative colitis (~70%) |
| ASCA (anti-Saccharomyces cerevisiae) | More positive in Crohn disease |
High-yield: p-ANCA → UC; ASCA → Crohn. A classic one-mark MCQ pairing.
Diagnosis & Investigation of Choice
Diagnosis is clinicopathological — no single test is definitive; correlation of endoscopy + histology + imaging + serology is required.
Diagnostic approach (stepwise):
- Bloods: anaemia, raised ESR/CRP, hypoalbuminaemia; faecal calprotectin (sensitive marker of intestinal inflammation, useful to differentiate from IBS and to monitor activity).
- Stool studies to exclude infective causes (C. difficile, Entamoeba, Yersinia, TB).
- Ileocolonoscopy with multiple segmental biopsies = investigation of choice for diagnosis and to map distribution; also enables dysplasia surveillance.
- Cross-sectional imaging for small bowel CD: MR enterography / CT enterography (or capsule endoscopy) to assess proximal small-bowel involvement, strictures, fistulae.
- Barium studies (classic radiology pearls): "string sign of Kantor" (terminal ileum) and cobblestoning in CD; lead-pipe colon with loss of haustra in UC.
High-yield: Colonoscopy + biopsy is the diagnostic investigation of choice. For suspected small-bowel Crohn, the imaging of choice is MR enterography (no radiation, best soft-tissue detail). Faecal calprotectin is the best non-invasive marker of mucosal inflammation/activity.
Management / Drug of Choice (pathology-relevant essentials)
- UC (mild–moderate): 5-ASA / mesalamine (sulfasalazine) is first line and the drug of choice for induction & maintenance of mild-moderate UC.
- Crohn disease: 5-ASA is less effective; corticosteroids (budesonide for ileocaecal CD) for acute flares; immunomodulators (azathioprine, 6-MP, methotrexate) for steroid-sparing maintenance.
- Biologics: anti-TNF (infliximab, adalimumab) for moderate-severe disease, fistulising CD; others — vedolizumab (anti-α4β7 integrin), ustekinumab (anti-IL-12/23).
- Surgery: Total proctocolectomy is curative for UC; surgery in Crohn is NOT curative (disease recurs at anastomosis) and is reserved for complications.
High-yield: Surgery cures UC but not Crohn. This reflects the continuous, colon-limited nature of UC versus the pan-gut, recurrent biology of CD.
Complications
Crohn disease
- Fistulae (enterocutaneous, enterovesical, perianal), abscesses.
- Strictures → bowel obstruction.
- Malabsorption, B12 deficiency (terminal ileal disease), bile-salt diarrhoea, gallstones, oxalate renal stones.
- Increased colorectal/small-bowel adenocarcinoma risk.
Ulcerative colitis
- Toxic megacolon (transverse colon dilatation >6 cm) — a surgical emergency; AVOID anti-motility agents and barium enema (precipitate it).
- Massive haemorrhage, perforation.
- Colorectal carcinoma — the most important long-term risk.
Cancer risk — high-yield:
- Risk rises with duration (>8–10 years), extent (pancolitis worst), and co-existing PSC.
- UC-associated cancers tend to be multifocal, flat (not polypoid), and arise from dysplasia in flat mucosa, often mucinous, and can occur in the proximal colon — unlike sporadic cancers, the dysplasia–carcinoma sequence in IBD does not follow the classic adenoma route.
- Surveillance colonoscopy with random biopsies is recommended after ~8 years of disease.
High-yield: Toxic megacolon is more associated with UC; barium enema and anti-diarrhoeals can precipitate it. CRC risk is determined by duration, extent, and PSC — pancolitis of long duration with PSC carries the highest risk.
Key Differentials
- Intestinal tuberculosis — the most important Crohn mimic in India. TB shows caseating (confluent) granulomas, transverse ulcers, and ileocaecal involvement; CD shows non-caseating granulomas and longitudinal ulcers. AFB/culture/GeneXpert help.
- Infective colitis (Shigella, Campylobacter, E. coli, Yersinia, amoebiasis) — preserved crypt architecture, no chronicity.
- Ischaemic colitis — watershed areas (splenic flexure), older patients.
- Behçet disease, NSAID enteropathy, and diversion colitis.
| Feature | Crohn disease | Intestinal TB |
|---|---|---|
| Granuloma | Small, non-caseating, scattered | Large, caseating, confluent |
| Ulcers | Longitudinal, aphthous | Transverse ("girdle") |
| AFB / GeneXpert | Negative | May be positive |
| Response to ATT | None | Improves |
High-yield: Caseating granuloma + transverse ulcers + positive AFB = intestinal TB, not Crohn. In India, always consider TB before labelling ileocaecal disease as Crohn.
Recently asked / exam angle
- Image/description-based MCQs: "Cobblestone mucosa + non-caseating granuloma + transmural inflammation" → Crohn disease. "Continuous mucosal inflammation + crypt abscesses + pseudopolyps + rectum involved" → ulcerative colitis.
- Single-best-fact recalls: NOD2/CARD15 → Crohn; p-ANCA → UC; ASCA → Crohn; PSC → UC; creeping fat → Crohn; lead-pipe colon → UC.
- Smoking questions: protective in UC, harmful in CD.
- Toxic megacolon precipitants (barium enema, anti-motility drugs) and its association with UC.
- "Surgery curative in which IBD?" → UC.
- Investigation of choice: colonoscopy + biopsy for diagnosis; MR enterography for small-bowel Crohn; faecal calprotectin for monitoring.
- CRC risk factors in UC: duration, extent (pancolitis), and PSC.
- Distinguishing Crohn from intestinal TB — a perennial favourite for Indian exams (caseating vs non-caseating, transverse vs longitudinal ulcers).
Rapid revision
- Crohn = mouth-to-anus, transmural, skip lesions, terminal ileum; UC = colon+rectum only, mucosal, continuous, starts in rectum.
- Non-caseating granuloma → Crohn (only ~50%); crypt abscess → UC (not specific).
- Creeping fat, cobblestoning, string sign, fistulae, strictures = Crohn.
- Pseudopolyps, lead-pipe colon, loss of haustra, backwash ileitis = UC.
- NOD2/CARD15 (chr 16) + ATG16L1 → Crohn; Th1/Th17 in CD, Th2 in UC.
- p-ANCA → UC; ASCA → Crohn.
- Smoking worsens Crohn but is protective in UC; appendicectomy protects against UC.
- PSC strongly associated with UC → cholangiocarcinoma + higher CRC risk.
- Bloody diarrhoea = UC; non-bloody diarrhoea + RLQ mass + perianal disease = Crohn.
- Toxic megacolon → UC; avoid barium enema and anti-motility drugs.
- Colectomy cures UC; Crohn recurs after surgery (not curative).
- CRC risk in UC rises with duration (>8–10 yr), extent (pancolitis), and PSC; surveillance colonoscopy after 8 years.