Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic, relapsing-remitting immune-mediated inflammation of the gut comprising two principal entities — Crohn disease (CD) and ulcerative colitis (UC) — plus a small group labelled IBD-unclassified when features overlap. For NEET PG, the single highest-yield theme is the CD vs UC contrast (transmural skip lesions vs continuous mucosal disease), followed by extraintestinal manifestations, investigations of choice, and the biologics ladder.

Definition & classification

IBD is defined by idiopathic chronic intestinal inflammation with no infectious cause, driven by a dysregulated mucosal immune response to luminal flora in a genetically susceptible host.

• Crohn disease — patchy, transmural inflammation that can affect any part of the GIT from mouth to anus; the terminal ileum + caecum (ileocaecal region) is the commonest site. CD is a Th1/Th17-mediated disease.
• Ulcerative colitis — diffuse, continuous, mucosa + submucosa-limited inflammation always involving the rectum and extending proximally in continuity. UC is Th2-like (atypical, IL-13 driven).

Montreal classification is the examiner's favourite framework:

Axis	Crohn disease	Ulcerative colitis
Age at diagnosis (A)	A1 <17 y, A2 17–40 y, A3 >40 y	—
Location (L)	L1 ileal, L2 colonic, L3 ileocolonic, L4 upper GI	E1 proctitis, E2 left-sided (distal to splenic flexure), E3 extensive/pancolitis
Behaviour (B)	B1 non-stricturing/non-penetrating, B2 stricturing, B3 penetrating; "p" = perianal	—

High-yield: UC is classified by extent (proctitis → left-sided → pancolitis); CD is classified by behaviour (inflammatory → stricturing → penetrating/fistulising). Truelove & Witts criteria grade UC severity.

Epidemiology & risk factors

• Bimodal age peaks: main peak 15–30 y, second 50–70 y.
• Smoking is the great divider: it worsens Crohn disease but is protective in UC (UC is largely a disease of ex-smokers/non-smokers). This is a classic one-liner.
• Appendicectomy is protective against UC.
• NSAIDs can trigger flares of both.
• Strong family history; concordance higher in CD than UC.
• NOD2/CARD15 gene mutations (chromosome 16) — strongest genetic association, especially with ileal/fibrostenotic CD. ATG16L1 and IRGM link CD to defective autophagy.

High-yield: Smoking → bad for Crohn, good for UC. Mnemonic: "Crohn = Cigarettes worsen."

Etiology & pathophysiology

IBD arises from interaction of: (1) genetic susceptibility, (2) dysbiosis of gut microbiota, (3) defective epithelial barrier/innate immunity, and (4) a dysregulated adaptive immune response.

In CD, impaired NOD2-mediated sensing of bacterial muramyl dipeptide and defective autophagy allow persistent bacterial stimulation → granulomatous, transmural Th1/Th17 inflammation with TNF-α, IFN-γ, IL-12/23 as key cytokines. The transmural nature explains strictures, fistulae, abscesses.

In UC, a leaky mucosal barrier and atypical Th2/NKT-cell response with IL-13 drives continuous mucosal inflammation limited to mucosa/submucosa, explaining bleeding and absence of fistulae/strictures.

Morphology — the exam goldmine

Crohn disease

• Skip lesions (discontinuous), transmural inflammation.
• Cobblestone mucosa — linear ulcers + transverse fissures separating oedematous islands.
• Aphthous ulcers → deep "rose-thorn" / fissuring ulcers (seen on barium).
• Creeping fat (mesenteric fat wrapping the bowel) and "string sign of Kantor" on barium (luminal narrowing of terminal ileum).
• Non-caseating granulomas (present in ~30%, but pathognomonic when found).
• Fistulae, strictures, abscesses, perianal disease, fat & vitamin B12 malabsorption (terminal ileum).

Ulcerative colitis

• Continuous disease starting at rectum.
• Mucosa + submucosa only; crypt abscesses (neutrophils in crypts) and crypt distortion.
• Pseudopolyps (regenerating mucosal islands).
• Lead-pipe colon — loss of haustrations on barium (chronic UC).
• Backwash ileitis — mild ileal involvement in pancolitis.
• Toxic megacolon and high colorectal carcinoma risk.

Feature	Crohn disease	Ulcerative colitis
Site	Mouth → anus; terminal ileum commonest	Colon only; rectum always
Distribution	Skip lesions	Continuous
Depth	Transmural	Mucosa + submucosa
Granuloma	Non-caseating (~30%)	Absent
Classic mucosa	Cobblestoning	Pseudopolyps
Ulcers	Aphthous, rose-thorn, deep fissuring	Broad-based, shallow
Bleeding	Less common	Common (bloody diarrhoea)
Fistula/stricture	Common	Rare
Perianal disease	Common	Rare
Barium sign	String sign of Kantor	Lead-pipe colon
Smoking	Worsens	Protective
Cancer risk	Increased (less than UC)	High
Surgery	Not curative (recurs)	Colectomy is curative
p-ANCA / ASCA	ASCA positive	p-ANCA positive

High-yield: ASCA → Crohn, p-ANCA → UC. (ASCA = anti-Saccharomyces cerevisiae.)

High-yield: Colectomy CURES ulcerative colitis but does NOT cure Crohn disease (recurrence at anastomosis is the rule).

Clinical features

Crohn disease: chronic right lower quadrant pain, non-bloody diarrhoea, weight loss, low-grade fever, a palpable RIF mass, perianal fistulae/abscesses/skin tags, oral aphthae, and features of malabsorption (B12, fat, fat-soluble vitamins). Gallstones (bile salt loss) and oxalate renal stones (enteric hyperoxaluria) are typical.

Ulcerative colitis: bloody diarrhoea with mucus, urgency, tenesmus, and lower abdominal cramps relieved by defecation. Severity tracked clinically by stool frequency and systemic signs.

Truelove & Witts criteria (severity of UC) — frequently asked

Parameter	Mild	Severe
Bowel motions/day	<4	≥6 (with blood)
Temperature	Normal	>37.8 °C
Pulse	Normal	>90/min
Haemoglobin	Normal	<10.5 g/dL
ESR	≤30	>30 mm/hr

High-yield: ≥6 bloody stools/day + any systemic sign (fever/tachycardia/anaemia/high ESR) = acute severe UC, an indication for admission and IV steroids.

Extraintestinal manifestations (EIMs)

Roughly classed as related to disease activity (parallel gut flares) vs independent.

• Activity-related: pauci-articular peripheral arthritis (Type 1), erythema nodosum, episcleritis, oral aphthous ulcers.
• Activity-independent: axial arthritis/ankylosing spondylitis & sacroiliitis (HLA-B27), pyoderma gangrenosum, uveitis, primary sclerosing cholangitis (PSC).
• PSC is far more associated with UC than CD; it carries an independent risk of cholangiocarcinoma and colorectal cancer and is screened with MRCP (beaded "string of beads" intra/extrahepatic ducts) and p-ANCA.

High-yield: Pyoderma gangrenosum + erythema nodosum are the two skin lesions; PG is more associated with UC. PSC strongly linked to UC and raises cancer risk independent of colitis duration.

Mnemonic for EIMs — "A PIE SO PUP": Arthritis, Pyoderma, Iritis/uveitis, Erythema nodosum, Sclerosing cholangitis, Osteoporosis, PSC, Uveitis, Episcleritis.

Diagnosis & investigation of choice

Diagnosis is a composite of clinical, laboratory, endoscopic, histological, and radiological findings — no single gold-standard test.

Stepwise approach: Suspect IBD → rule out infection (stool culture, C. difficile toxin, ova/parasites) → bloods (CBC, CRP/ESR, albumin, iron, B12) → faecal calprotectin → ileocolonoscopy with biopsies → cross-sectional imaging for small bowel/complications.

• Investigation of choice for diagnosis & extent: ileocolonoscopy with multiple segmental biopsies (including terminal ileum). It distinguishes continuous (UC) from skip (CD) disease and provides histology.
• Faecal calprotectin — sensitive non-invasive marker of mucosal inflammation; excellent to differentiate IBD from IBS and to monitor activity.
• Small bowel CD assessment: MR enterography (no radiation, preferred in young/repeat imaging) or CT enterography; capsule endoscopy is most sensitive for proximal small-bowel mucosal CD (avoid if stricture suspected — risk of capsule retention).
• Acute severe UC / toxic megacolon: plain abdominal X-ray (colonic dilatation >6 cm, or caecum >9 cm); avoid full colonoscopy (perforation risk) — do a limited flexible sigmoidoscopy.
• Serology: ASCA (CD), p-ANCA (UC) — adjunctive, not diagnostic alone.

High-yield: Faecal calprotectin is the best non-invasive screen and activity monitor; colonoscopy + biopsy is the diagnostic investigation of choice; MR enterography is best for small-bowel Crohn.

Management & drug of choice

Treatment follows a "step-up" or "top-down" strategy aiming for clinical remission + mucosal healing. Therapy = induction then maintenance.

Drug classes

1. 5-Aminosalicylates (mesalazine/sulfasalazine) — mainstay for mild–moderate UC (induction + maintenance). Limited/no role in Crohn. Sulfasalazine helps IBD-associated arthropathy. (Monitor for folate deficiency, oligospermia with sulfasalazine.)
2. Corticosteroids — for flares only (induction); never for maintenance. Budesonide (high first-pass, fewer systemic effects) for ileocaecal CD; IV hydrocortisone/methylprednisolone for acute severe UC.
3. Immunomodulators — azathioprine / 6-mercaptopurine (check TPMT before starting to avoid myelosuppression), methotrexate (effective in CD, not UC).
4. Biologics:
   • Anti-TNF: infliximab, adalimumab — workhorses for moderate–severe CD and UC; infliximab is the drug of choice for fistulising/perianal Crohn disease and for acute severe UC failing IV steroids. Screen for latent TB (Mantoux/IGRA + CXR) and hepatitis B before starting.
   • Anti-integrin: vedolizumab (α4β7, gut-selective, very safe).
   • Anti-IL-12/23: ustekinumab; anti-IL-23: risankizumab.
5. Small-molecule agents: tofacitinib/upadacitinib (JAK inhibitors) and ozanimod (S1P modulator) for UC.
6. Antibiotics (metronidazole/ciprofloxacin) — for perianal CD, fistulae, abscess, pouchitis.

Disease-specific essentials

• Mild–moderate UC: oral/topical 5-ASA (topical mesalazine best for proctitis) → add steroids if no response.
• Acute severe UC: admit, IV corticosteroids; assess at day 3 with Oxford/Travis criteria (CRP >45 mg/L or >8 stools/day predicts colectomy) → rescue infliximab or IV ciclosporin → colectomy if rescue fails.
• Crohn (moderate–severe): steroids/budesonide to induce + azathioprine ± anti-TNF; perianal/fistulising → infliximab + metronidazole/cipro ± seton drainage.
• Surgery: proctocolectomy with ileal pouch–anal anastomosis (IPAA) is curative for UC; in CD surgery is reserved for complications (stricture → stricturoplasty, fistula, abscess) and recurs.

High-yield: Infliximab = DOC for fistulising/perianal Crohn disease and rescue therapy in steroid-refractory acute severe UC. Always screen for latent TB & HBV before any anti-TNF.

High-yield: Test TPMT before azathioprine; budesonide is preferred steroid for ileocaecal Crohn.

Complications

Crohn disease: strictures with subacute intestinal obstruction, enteroenteric/enterovesical/enterocutaneous fistulae, abscess, perforation, malabsorption (B12, fat-soluble vitamins), gallstones, oxalate renal stones, growth failure in children, and small-bowel adenocarcinoma.

Ulcerative colitis:

• Toxic megacolon — transverse colon dilatation >6 cm + systemic toxicity; precipitated by hypokalaemia, opioids, antimotility agents, barium enema. Risk of perforation → surgical emergency.
• Massive haemorrhage, perforation.
• Colorectal carcinoma — the most important long-term risk.

High-yield: Avoid antidiarrhoeals/opioids/anticholinergics in active colitis — they precipitate toxic megacolon.

Cancer surveillance (very high yield)

• CRC risk in UC rises ~8–10 years after diagnosis of extensive colitis; risk factors: extent (pancolitis), duration, PSC, family history.
• Surveillance colonoscopy begins at 8 years of disease (immediately at PSC diagnosis), then periodic with chromoendoscopy + targeted biopsies.
• Cancers in IBD tend to be multifocal, flat, and arise from dysplasia (not adenoma sequence).

High-yield: UC + PSC = highest CRC risk → annual colonoscopy from diagnosis of PSC. Cancer correlates with extent + duration, not severity of symptoms.

Key differentials

• Intestinal tuberculosis vs Crohn (crucial in India): TB favours caseating granulomas, ascites, transverse ulcers, ileocaecal involvement with patulous valve, positive AFB/CBNAAT; CD favours longitudinal ulcers, cobblestoning, non-caseating granulomas, skip lesions, perianal disease. When in doubt, a therapeutic ATT trial is sometimes used.
• Infective colitis (Salmonella, Shigella, Campylobacter, E. histolytica, C. difficile) — exclude before steroids.
• Ischaemic colitis — elderly, splenic flexure ("watershed"), thumbprinting.
• Behçet disease — oral + genital ulcers, ileocaecal ulcers.
• Irritable bowel syndrome — no inflammation, normal calprotectin/CRP.
• Microscopic (collagenous/lymphocytic) colitis — chronic watery diarrhoea, normal endoscopy, abnormal biopsy.

Feature	Crohn disease	Intestinal TB
Ulcers	Longitudinal, aphthous	Transverse, circumferential
Granuloma	Non-caseating, small	Caseating, large, confluent
Ileocaecal valve	Often narrowed	Patulous / fish-mouth
Ascites	Rare	Common
AFB/CBNAAT	Negative	Positive
ASCA	Positive	Negative

Recently asked / exam angle

• CD vs UC table (transmural skip lesions + cobblestoning + non-caseating granuloma vs continuous mucosal + crypt abscess + pseudopolyps) — perennial single-best-answer.
• Smoking protective in UC / harmful in CD — direct one-liner.
• ASCA (Crohn) vs p-ANCA (UC) serology match.
• Infliximab as DOC for fistulising Crohn; mandatory TB screening before anti-TNF.
• Toxic megacolon definition (>6 cm) and precipitants (antimotility drugs, hypokalaemia).
• Faecal calprotectin as the best non-invasive marker; MR enterography for small bowel.
• PSC association with UC and its independent cancer risk; MRCP "beaded ducts."
• Colectomy curative in UC, not in CD.
• String sign of Kantor (CD) vs lead-pipe colon (UC) on barium.
• Image-based: cobblestone mucosa, pseudopolyps, rose-thorn ulcer, creeping fat.

Rapid revision

1. Crohn = mouth-to-anus, skip lesions, transmural, non-caseating granuloma, cobblestoning, fistulae; terminal ileum is the commonest site.
2. UC = colon only, starts at rectum, continuous, mucosal, crypt abscesses, pseudopolyps, bloody diarrhoea.
3. Smoking worsens Crohn, protects against UC; appendicectomy protective in UC.
4. NOD2/CARD15 (chr 16) = strongest CD gene; defective autophagy (ATG16L1).
5. ASCA → Crohn; p-ANCA → UC.
6. Faecal calprotectin = best non-invasive activity marker; colonoscopy + biopsy = diagnostic investigation of choice; MR enterography for small-bowel CD.
7. Truelove–Witts: ≥6 bloody stools + systemic sign = acute severe UC → IV steroids.
8. Infliximab = DOC for fistulising/perianal Crohn & steroid-refractory severe UC; screen TB + HBV first.
9. Check TPMT before azathioprine; budesonide for ileocaecal Crohn; 5-ASA mainly for UC.
10. Colectomy cures UC (IPAA); surgery does not cure Crohn (recurs).
11. Toxic megacolon = transverse colon >6 cm; avoid opioids/antimotility agents.
12. UC + PSC = highest colorectal cancer risk; surveillance colonoscopy from 8 years of disease (from PSC diagnosis if present).